Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 (IL-3) multiple mutation polypeptides

Abstract

The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

Description

FIELD OF THE INVENTION

The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted. These hIL-3 multiple mutation polypeptides retain one or more activities of native hIL-3 and may also show improved hematopoietic cell-stimulating activity and/or an improved activity profile which may include reduction of undesirable biological activities associated with native hIL-3. The present invention also relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

BACKGROUND OF THE INVENTION

Colony stimulating factors (CSFs) which stimulate the differentiation and/or proliferation of bone marrow cells have generated much interest because of their therapeutic potential for restoring depressed levels of hematopoietic stem cell-derived cells. CSFs in both human and murine systems have been identified and distinguished according to their activities. For example, granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF) stimulate the in vitro formation of neutrophilic granulocyte and macrophage colonies, respectively while GM-CSF and interleukin-3 (IL-3) have broader activities and stimulate the formation of both macrophage, neutrophilic and eosinophilic granulocyte colonies. IL-3 also stimulates the formation of mast, megakaryocyte and pure and mixed erythroid colonies.

Because of its ability to stimulate the proliferation of a number of different cell types and to support the growth and proliferation of progenitor cells, IL-3 has potential for therapeutic use in restoring hematopoietic cells to normal amounts in those cases where the number of cells has been reduced due to diseases or to therapeutic treatments such as radiation and chemotherapy.

Interleukin-3 (IL-3) is a hematopoietic growth factor which has the property of being able to promote the survival, growth and differentiation of hematopoietic cells. Among the biological properties of IL-3 are the ability (a) to support the growth and differentiation of progenitor cells committed to all, or virtually all, blood cell lineages; (b) to interact with early multipotential stem cells; (c) to sustain the growth of pluripotent precursor cells; (d) to stimulate proliferation of chronic myelogenous leukemia (CML) cells; (e) to stimulate proliferation of mast cells, eosinophils and basophils; (f) to stimulate DNA synthesis by human acute myelogenous leukemia (AML) cells; (g) to prime cells for production of leukotrienes and histamines; (h) to induce leukocyte chemotaxis; and (i) to induce cell surface molecules needed for leukocyte adhesion.

Mature human interleukin-3 (hIL-3) consists of 133 amino acids. It has one disulfide bridge and two potential glycosylation sites (Yang, et al., CELL 47:3, 1986).

Murine IL-3 (mIL-3) was first identified by Ihle, et al., ( J. IMMUNOL . 126:2184, 1981) as a factor which induced expression of a T cell associated enzyme, 20-hydroxysteroid dehydrogenase. The factor was purified to homogeneity and shown to regulate the growth and differentiation of numerous subclasses of early hematopoietic and lymphoid progenitor cells.

In 1984, cDNA clones coding for murine IL-3 were isolated (Fung, et al., NATURE 307:233, 1984; Yokota, et al., PROC. NATL. ACAD. SCI. USA 81:1070, 1984). The murine DNA sequence coded for a polypeptide of 166 amino acids including a putative signal peptide.

The gibbon IL-3 sequence was obtained using a gibbon cDNA expression library. The gibbon IL-3 sequence was then used as a probe against a human genomic library to obtain a human IL-3 sequence.

Gibbon and human genomic DNA homologues of the murine IL-3 sequence were disclosed by Yang, et al., ( CELL 47:3, 1986). The human sequence reported by Yang, et al., included a serine residue at position 8 of the mature protein sequence. Following this finding, others reported isolation of Pro 8 hIL-3 cDNAs having proline at position 8 of the protein sequence. Thus it appears that there may be two allelic forms of hIL-3.

Dorssers, et al., ( GENE 55:115, 1987), found a clone from a human cDNA library which hybridized with mIL-3. This hybridization was the result of the high degree of homology between the 3′ noncoding regions of mIL-3 and hIL-3. This cDNA coded for an hIL-3 (Pro 8 ) sequence.

U.S. Pat. No. 4,877,729 and U.S. Pat. No. 4,959,455 disclose human IL-3 and gibbon IL-3 cDNAs and the protein sequences for which they code. The hIL-3 disclosed has serine rather than proline at position 8 in the protein sequence.

Clark-Lewis, et al., ( SCIENCE 231:134, 1986) performed a functional analysis of murine IL-3 analogues synthesized with an automated peptide synthesizer. The authors concluded that the stable tertiary structure of the complete molecule was required for full activity. A study on the role of the disulfide bridges showed that replacement of all four cysteines by alanine gave a molecule with 1/500th the activity as the native molecule. Replacement of two of the four Cys residues by Ala(Cys 79 , Cys 140 →Ala 79 , Ala 140 ) resulted in an increased activity. The authors concluded that in murine IL-3 a single disulfide bridge is required between cysteines 17 and 80 to get biological activity that approximates physiological levels and that this structure probably stabilizes the tertiary structure of the protein to give a conformation that is optimal for function. (Clark-Lewis, et al., PROC. NATL. ACAD. SCI. USA 85:7897, 1988).

International Patent Application (PCT) WO 88/00598 discloses gibbon- and human-like IL-3. The hIL-3 contains a Ser 8 →Pro 8 replacement. Suggestions are made to replace Cys by Ser, thereby breaking the disulfide bridge, and to replace one or more amino acids at the glycosylation sites.

EP-A-0275598 (WO 88/04691) illustrates that Ala 1 can be deleted while retaining biological activity. Some mutant hIL-3 sequences are provided, e.g., two double mutants, Ala 1 →Asp 1 , Trp 13 →Arg 13 (pGB/IL-302) and Ala 1 →Asp 1 , Met 3 →Thr 3 (pGB/IL-304) and one triple mutant Ala 1 →Asp 1 , Leu 9 →Pro 9 , Trp 13 →Arg 13 (pGB/IL-303).

WO 88/05469 describes how deglycosylation mutants can be obtained and suggests mutants of Arg 54 Arg 55 and Arg 108 Arg 109 Lys 110 might avoid proteolysis upon expression in Saccharomyces cerevisiae by KEX2 protease. No mutated proteins are disclosed. Glycosylation and the KEX2 protease activity are only important, in this context, upon expression in yeast.

WO 88/06161 mentions various mutants which theoretically may be conformationally and antigenically neutral. The only actually performed mutations are Met 2 →Ile 2 and Ile131→Leu 131 . It is not disclosed whether the contemplated neutralities were obtained for these two mutations.

WO 91/00350 discloses nonglycosylated hIL-3 analog proteins, for example, hIL-3 (Pro 8 Asp 15 Asp 70 ), Met 3 rhul-3 (Pro 8 Asp 15 Asp 70 ); Thr 4 rhuL-3 (Pro 8 Asp 15 Asp 70 )and Thr 6 rhuIL-3 (Pro 8 Asp 15 Asp 70 ). It is said that these protein compositions do not exhibit certain adverse side effects associated with native hIL-3 such as urticaria resulting from infiltration of mast cells and lymphocytes into the dermis. The disclosed analog hIL-3 proteins may have N termini at Met 3 , Thr 4 , or Thr 6 .

WO 90/12874 discloses cysteine added variants (CAVs) of IL-3 which have at least one Cys residue substituted for a naturally occurring amino acid residue.

Hematopoietic growth factors, such as hIL-3, have been administered alone, co-administered with other hematopoietic growth factors, or in combination with bone marrow transplants subsequent to high dose chemotherapy to treat the neutropenia and thrombocytopenia which are often the result of such treatment. However the period of severe neutropenia and thrombocytopenia may not be totally eliminated. The myeloid lineage, which is comprised of monocytes (macrophages), granulocytes (including neutrophils) and megakaryocytes, is critical in preventing infections and bleeding which can be life-threatening. Neutropenia and thrombocytopenia may also be the result of disease, genetic disorders, drugs, toxins, radiation and many therapeutic treatments such as conventional oncology therapy.

Bone marrow transplants have been used to treat this patient population. However, several problems are associated with the use of bone marrow to reconstitute a compromised hematopoietic system including: 1) the number of stem cells in bone marrow or other is limited, 2) Graft Versus Host Disease, 3) graft rejection and 4) possible contamination with tumor cells. Stem cells make up a very small percentage of the nucleated cells in the bone marrow, spleen and peripheral blood. It is clear that a dose response exits such that a greater number of stem cells will enhance hematopoietic recovery. Therefore, the use of stem cells, that have been expanded ex-vivo, should enhance hematopoietic recovery and patient survival. Bone marrow from an allogeneic donor has been used to provide bone marrow for transplant. However, Graft Versus Host Disease and graft rejection limit bone marrow transplantation even in recipients with HLA-matched sibling donors. An alternative to allogenic bone marrow transplants is autologous bone marrow transplants. In autologous bone marrow transplants, some of the patient's own marrow is harvested prior to myeloablative therapy, e.g. high dose chemotherapy, and is transplanted back into the patient afterwards. Autologous transplants eliminate the risk of Graft Versus Host Disease and graft rejection. However, autologous bone marrow transplants still present problems in terms of the limited number of stems cells in the marrow and possible contamination with tumor cells.

The limited number of stem cells may be overcome by ex-vivo expansion of the stem cells. In addition, stem cells can be specifically isolated selected based on the presence of specific surface antigen such as CD34+ in order to decrease tumor cell contamination of the marrow graft.

The following patents contain further details on separating stem cells, CD34+ cells, culturing the cells with hematopoietic factors, the use of the cells for the treatment of patients with hematopoietic disorders and the use of hematopoietic factors for cell expansion and gene therapy.

U.S. Pat. No. 5,061,620 relates to compositions comprising human hematopoietic stem cells provided by separating the stem cells from dedicated cells.

U.S. Pat. No. 5,199,942 describes a method for autologous hematopoietic cell transplantation comprising: (1) obtaining hematopoietic progenitor cells from a patient; (2) ex-vivo expansion of cells with a growth factor selected from the group consisting of IL-3, flt3 ligand, c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein and combinations thereof; (3) administering cellular preparation to a patient.

U.S. Pat. No. 5,240,856 relates to a cell separator that includes apparatus for automatically controlling the cell separation process.

U.S. Pat. No. 5,409,813 describes methods of positive and negative selection of a cell population from a mixture of cell populations utilizing a magnetically stabilized fluidized bed.

U.S. Pat. No. 5,409,825 relates to a method of growing hematopoietic stem cells in a liquid culture medium using mast cell growth factor (MGF) and optionally at least one cytokine selected from the group consisting of IL-3, GM-CSF and IL-3/GM-CSF fusion protein.

U.S. Pat. No. 5,459,069 relates to devices for maintaining and growing human stem cells and/or hematopoietic cells in culture.

U.S. Pat. No. 5,541,103 describes peripheral blood progenitor cells obtained by enriching blood progenitors expressing the cd34 antigen and culture the cells in a growth medium consisting of IL-1, IL-3, IL-6, erythropoietin and stem cell growth factor.

U.S. Pat. No. 5,464,753 describes a method of purifying pluripotent hematopoietic stem cells expressing P-glycoprotein from a mixture of blood or bone marrow cells.

U.S. Pat. No. 5,547,687 relates to a method of enriching CD34 cells from a cell mixture by density centrifugation.

U.S. Pat. No. 5,571,686 depicts the use of megapoietin (c-mpl ligand) for the in vitro expansion of stem cells as a source of platelets for transplantation and for increasing the storage life of platelets.

WO 91/16116 describes devices and methods for selectively isolating and separating target cells from a mixture of cells.

WO 91/18972 describes methods for in vitro culturing of bone marrow, by incubating suspension of bone marrow cells, using a hollow fiber bioreactor.

WO 92/18615 relates to a process for maintaining and expanding bone marrow cells, in a culture medium containing specific mixtures of cytokines, for use in transplants.

WO 93/08268 describes a method for selectively expanding stem cells, comprising the steps of (a) separating CD34+stem cells from a mixed population of cells and (b) incubating the separated cells in a selective medium, such that the stem cells are selectively expanded.

WO 93/18136 describes a process for in vitro support of mammalian cells derived from peripheral blood.

WO 93/18648 relates to a composition comprising human neutrophil precursor cells with a high content of myeloblasts and promyelocytes for treating genetic or acquired neutropenia.

WO 94/08039 describes a method of enrichment for human hematopoietic stem cells by selection for cells which express c-kit protein.

WO 94/11493 describes a stem cell population that are CD34+ and small in size, which are isolated using a counterflow elutriation method.

WO 94/27698 relates to a method combining immunoaffinity separation and continuous flow centrifugal separation for the selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture.

WO 94/25848 describes a cell separation apparatus for collection and manipulation of target cells.

The long term culturing of highly enriched CD34+ precursors of hematopoietic progenitor cells from human bone marrow in cultures containing IL-1α, IL-3, IL-6 or GM-CSF is discussed in Brandt et al., J. Clin. Invest . 86:932-941, 1990.

SUMMARY OF THE INVENTION

The present invention relates methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain amino acid substitutions and may also have amino acid deletions at either/or both the N- and C- termini. Preferably, these mutant polypeptides of the present invention contain four or more amino acids which differ from the amino acids found at the corresponding positions in the native hIL-3 polypeptide. The present invention includes mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus and/or from 1 to 15 amino acids have been deleted from the C-terminus, and in which multiple amino acid substitutions have been made.

Preferred muteins of the present invention are those in which amino acids 1 to 14 have been deleted from the N-terminus, amino acids 126 to 133 have been deleted from the C-terminus, and which also contain from about four to about twenty-six amino acid substitutions in the polypeptide sequence.

The present invention is directed to methods for ex vivo expansion of stem cells, comprising the steps of; (a) culturing said stem cells with a selected growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:15);

wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;

Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;

Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;

Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;

Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;

Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;

Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg;

Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;

Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;

Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;

Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;

Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;

Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;

Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;

Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;

Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;

Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;

Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;

Xaa at position 36 is Asp, Leu, or Val;

Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;

Xaa at position 38 is Asn, or Ala;

Xaa at position 40 is Leu, Trp, or Arg;

Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;

Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;

Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;

Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;

Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;

Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;

Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;

Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;

Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;

Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;

Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;

Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;

Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;

Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;

Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;

Xaa at position 57 is Asn or Gly;

Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;

Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;

Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;

Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;

Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;

Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;

Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;

Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;

Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;

Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;

Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;

Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;

Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;

Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;

Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;

Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;

Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;

Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;

Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;

Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;

Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;

Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;

Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;

Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;

Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;

Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;

Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;

Xaa at position 85 is Leu, Asn, Val, or Gln;

Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;

Xaa at position 87 is Leu, Ser, Trp, or Gly;

Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;

Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;

Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;

Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;

Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu;

Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;

Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;

Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;

Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;

Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;

Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;

Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His;

Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;

Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln;

Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;

Xaa at position 103 is Asp, or Ser;

Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;

Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His;

Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;

Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;

Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;

Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp;

Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;

Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;

Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;

Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;

Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;

Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;

Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;

Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;

Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;

Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;

Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;

Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;

Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

wherein from 4 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; wherein from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus of said interleukin-3 mutant polypeptide; and said interleukin-3 mutant polypeptide can additionally be immediately preceded by Methionine −1 , Alanine −1 or Methionine −2 Alanine −1 ; and

(b) harvesting said cultured stem cells.

Additionally, the present invention encompasses methods of ex-vivo expansion of stem cells comprising the steps of (a) separating stem cells from a mixed population of cells; (b) culturing said separated stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide; (c) harvesting said cultured cells.

The present invention includes methods for treatment of a patient having a hematopoietic disorder, comprising the steps of; (a) removing stem cells from said patient or a blood donor; (b) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide; (c) harvesting said cultured cells; and (d) transplanting said cultured cells into said patient.

The present invention also includes methods for treatment of a patient having a hematopoietic disorder, comprising the steps of; (a) removing stem cells from said patient or a blood donor; (b) separating stem cells from a mixed population of cells; (c) culturing said separated stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide; (d) harvesting said cultured cells; and (e) transplanting said cultured cells into said patient.

It is also envisioned that a patient could be given a hematopoietic growth factor, preferably a early acting factor, prior to removing stem cells for ex-vivo expansion to increase the number of early progenitors. It is also envisioned that a portion of the stem cells removed from a patient could be frozen and transplanted with the expanded stem cells to provide more early progenitors.

It is envisioned that the present invention includes methods of human gene therapy, comprising the steps of; (a) removing stem cells from a patient or blood donor; (b) culturing said stem cells with a selected growth medium comprising a human interleukin-3 mutant polypeptide; (c) introducing DNA into said cultured cells; (d) harvesting said transduced cells; and (e) transplanting said transduced cells into said patient.

It is also envisioned that the present invention includes methods of human gene therapy, comprising the steps of; (a) removing stem cells from a patient or blood donor; (b) separating said stem cells from a mixed population of cells; (c) culturing said separated stem cells with a selected growth medium comprising a human interleukin-3 mutant polypeptide; (d) introducing DNA into said cultured cells; (e) harvesting said transduced cells; and (f) transplanting said transduced cells into said patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is the human IL-3 gene for E. coli expression (pMON5873), encoding the polypeptide sequence of natural (wild type) human IL-3 [SEQ ID NO:128], plus an initiator methionine, as expressed in E. coli , with the amino acids numbered from the N-terminus of the natural hIL-3.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the use of muteins of human interleukin-3 (hIL-3) in which amino acid substitutions have been made at four or more positions in amino acid sequence of the polypeptide and to muteins which have substantially the same structure and substantially the same biological activity for the ex-vivo expansion of hematopoietic cells. Preferred muteins of the present invention are (15-125)hIL-3 deletion mutants which have deletions of amino acids 1 to 14 at the N-terminus and 126 to 133 at the C-terminus and which also have four or more amino acid substitutions in the polypeptide and muteins having substantially the same structure and substantially the same biological activity. Among the preferred muteins are those having twenty-six amino acid substitutions. As used herein human interleukin-3 corresponds to the amino acid sequence (1-133) as depicted in FIG. 1 and (15-125) hIL-3 corresponds to the 15 to 125 amino acid sequence of the hIL-3 polypeptide. Naturally occurring variants of hIL-3 polypeptide amino acids are also included in the present invention (for example, the allele in which proline rather than serine is at position 8 in the hIL-3 polypeptide sequence) as are variant hIL-3 molecules which are modified post-translationally (e.g. glycosylation).

Hematopoiesis requires a complex series of cellular events in which stem cells generate continuously into large populations of maturing cells in all major lineages. There are currently at least 20 known regulators with hematopoietic proliferative activity. Most of these proliferative regulators can stimulate one or another type of colony formation in vitro, the precise pattern of colony formation stimulated by each regulator is quite distinctive. No two regulators stimulate exactly the same pattern of colony formation, as evaluated by colony numbers or, more importantly, by the lineage and maturation pattern of the cells making up the developing colonies. Proliferative responses can most readily be analyzed in simplified in vitro culture systems. Three quite different parameters can be distinguished: alteration in colony size, alteration in colony numbers and cell lineage.

The mutant hIL-3 polypeptides of the present invention may also have methionine, alanine, or methionine-alanine residues inserted at the N-terminus.

“Mutant amino acid sequence,” “mutant protein” or “mutant polypeptide” refers to a polypeptide having an amino acid sequence which varies from a native sequence or is encoded by a nucleotide sequence intentionally made variant from a native sequence. “Mutant protein,” “variant protein” or “mutein” means a protein comprising a mutant amino acid sequence and includes polypeptides which differ from the amino acid sequence of native hIL-3 due to amino acid deletions, substitutions, or both. “Native sequence” refers to an amino acid or nucleic acid sequence which is identical to a wild-type or native form of a gene or protein.

Human IL-3 can be characterized by its ability to stimulate colony formation by human hematopoietic progenitor cells. The colonies formed include erythroid, granulocyte, megakaryocyte, granulocytic macrophages and mixtures thereof. Human IL-3 has demonstrated an ability to restore bone marrow function and peripheral blood cell populations to therapeutically beneficial levels in studies performed initially in primates and subsequently in humans (Gillio, A. P., et al., J. Clin. Invest . 85:1560 (1990); Ganser, A., et al., Blood 76: 666 (1990); Falk, S., et al., Hematopathology 95:355 (1991). Additional activities of hIL-3 include the ability to stimulate leukocyte migration and chemotaxis; the ability to prime human leukocytes to produce high levels of inflammatory mediators like leukotrienes and histamine; the ability to induce cell surface expression of molecules needed for leukocyte adhesion; and the ability to trigger dermal inflammatory responses and fever. Other IL-3-like properties are the interaction with early multipotential stem cells, the sustaining of the growth of pluripotent precursor cells, the ability to stimulate chronic myelogenous leukemia (CML) cell proliferation, the stimulation of proliferation of mast cells, the ability to support the growth of various factor-dependent cell lines, and the ability to trigger immature bone marrow cell progenitors. Other biological properties of IL-3 have been disclosed in the art. Many or all of these biological activities of hIL-3 involve signal transduction and high affinity receptor binding.

Biological activity of hIL-3 and hIL-3 varinats of the present invention is determined by DNA synthesis by human acute myelogenous leukemia cells (AML). The factor-dependent cell line AML 193 was adapted for use in testing biological activity. The biological activity of hIL-3 and hIL-3 chimera proteins of the present invention is also determined by counting the colony forming units in a bone marrow assay.

Other in vitro cell based assays may also be useful to determine the activity of the chimera molecules depending on the hematopoietic growth factors that comprise the chimera. The following are examples of other useful assays. TF-1 proliferation assay: The TF-1 cell line was derived from bone marrow of a patient with erythroleukemia (Kitamura et al., J. Cell Physiol . 140:323-334, 1989). TF-1 cells respond to IL-3, GM-CSF, EPO and IL-5.

Compounds of this invention are preferably made by genetic engineering techniques now standard in the art U.S. Pat. No. 4,935,233 and Sambrook et al., “Molecular Cloning. A Laboratory Manual”, Cold Spring Harbor Laboratory, 1989. One method of creating the preferred hIL-3 (15-125) mutant genes is cassette mutagenesis (Wells, et al., Gene , 34:315-323, 1985) in which a portion of the coding sequence of hIL-3 in a plasmid is replaced with synthetic oligonucleotides that encode the desired amino acid substitutions in a portion of the gene between two restriction sites. In a similar manner amino acid substitutions could be made in the full-length hIL-3 gene, or genes encoding variants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus and/or from 1 to 15 amino acids have been deleted from the C-terminus. When properly assembled these oligonucleotides would encode hIL-3 variants with the desired amino acid substitutions and/or deletions from the N-terminus and/or C-terminus. These and other mutations could be created by those skilled in the art by other mutagenesis methods including; oligonucleotide-directed mutagenesis (Zoller and Smith, Nucleic Acid Research , 10:6487-6500, 1982; Zoller and Smith, Methods in Enzymology , 100:468-500, 1983; Zoller and Smith, DNA, 3: 479, 1984 Smith M., Ann. Rev. Genet ., 19:423-462, 1985; Kunkel, Proc. Natl. Acad. Sci. USA , 82:488-492, 1985, Taylor, et al., Nucl. Acids Res . 13:8764-8785 (1985), Deng and Nickoloff, Anal-Biochem 200:81-88, 1992) or polymerase chain reaction (PCR) techniques (Saiki, Science 230:1350-1354, 1985).

Additional details about recombinant techniques for construction of DNA sequences that encode the IL-3 variants, plasmid DNA vectors for use in the expression of these novel chimera molecules, methods for producing the IL-3 variants in bacterial cells, mammalian cells, or insect cells can be found in WO 94/12638. It is understood that the IL-3 variants of the present invention, used for the ex-vivo expansion of hematopoietic cells, can be made by other methods known to those skilled in the art.

Interpretation of Activity of Single Amino Acid Mutants in IL-3 (15-125)

As illustrated in Tables 6 and 9 of WO 94/12638, there are certain positions in the IL-3 (15-125) molecule which are intolerant of substitutions, in that most or all substitutions at these positions resulted in a considerable decrease in bioactivity. There are two likely classes of such “down-mutations”: mutations that affect overall protein structure, and mutations that interfere directly with the interaction between the IL-3 molecule and its receptor. Mutations affecting the three-dimensional structure of the protein will generally lie in the interior of the protein, while mutations affecting receptor binding will generally lie on the surface of the protein. Although the three-dimensional structure of IL-3 is unknown, there are simple algorithms which can aid in the prediction of the structure. One such algorithm is the use of “helical wheels” (Kaiser, E. T. & Kezdy, F. J., Science 223:249-255, 1984). In this method, the presence of alpha helical protein structures can be predicted by virtue of their amphipathic nature. Helices in globular proteins commonly have an exposed hydrophilic side and a buried hydrophobic side. As a broad generalization, in globular proteins, hydrophobic residues are present in the interior of the protein, and hydrophilic residues are present on the surface. By displaying the amino acid sequence of a protein on such a “helical wheel” it is possible to derive a model for which amino acids in alpha helices are exposed and which are buried in the core of the protein. Such an analysis of the IL-3 (15-125) molecule predicts that the following helical residues are buried in the core:

M19, I20, I23, I24, L27, L58, F61, A64, L68, A71, I74, I77, L78, L81, W104, F107, L111, Y114, L115, L118.

In addition, cysteine residues at positions 16 and 84 are linked by a disulfide bond, which is important for the overall structure or “folding” of the protein. Finally, mutations which result in a major disruption of the protein structure may be expressed at low level in the secretion system used in our study, for a variety of reasons: either because the mis-folded protein is poorly recognized by the secretion machinery of the cell; because mis-folding of the protein results in aggregation, and hence the protein cannot be readily extracted from the cells; or because the mis-folded protein is more susceptible to degradation by cellular proteases. Hence, a block in secretion may indicate which positions in the IL-3 molecule which are important for maintenance of correct protein structure.

In order to retain the activity of a variant of IL-3, it is necessary to retain both the structural integrity of the protein, and retain the specific residues important for receptor contact. Hence it is possible to define specific amino acid residues in IL-3 (15-125) which must be retained in order to preserve biological activity.

Residues predicted to be important for interaction with the receptor: D21, E22, E43, D44, L48, R54, R94, D103, K110, F113.

Residues predicted to be structurally important: C16, L58, F61, A64, I74, L78, L81, C84, P86, P92, P96, F107, L111, L115, L118.

One aspect of the present invention provides a novel hematopoietic factors for selective ex-vivo expansion of stem cells. The term “stem cell” refers to the totipiotent hematopoietic stem cells as well as early precursors and progenitor cells which can be isolated from bone marrow, spleen or peripheral blood. The term “expanding” refers to the differentiation and proliferation of the cells. The present invention provides a method for selective ex-vivo expansion of stem cells, comprising the steps of; (a) separating stem cells from a mixed population of cells, (b) culturing said separated stem cells with a selected media which contains a mutant interleukin-3 polypeptide and (c) harvesting said cultured stems cells.

Stem cells as well as committed progenitor cells destined to become neutrophils, erythrocytes, platelets. etc., may be distinguished from most other cells by the presence or absence of particular progenitor marker antigens, such as CD34, that are present on the surface of these cells and/or by morphological characteristics. The phenotype for a highly enriched human stem cell fraction is reported as CD34+, Thy-1+ and lin−, but it is to be understood that the present invention is not limited to the expansion of this stem cell population. The CD34+ enriched human stem cell fraction can be separated by a number of reported methods, including affinity columns or beads, magnetic beads or flow cytometry using antibodies directed to surface antigens such as the CD34+. Further, physical separation methods such as counterflow elutriation may be used to enrich hematopoietic progenitors. The CD34+ progenitors are heterogeneous, and may be divided into several subpopulations characterized by the presence or absence of coexpression of different lineage associated cell surface associated molecules. The most immature progenitor cells do not express any known lineageassociated markers, such as HLA-DR or CD38, but they may express CD90(thy-1). Other surface antigens such as CD33, CD38, CD41, CD71, HLA-DR or c-kit can also be used to selectively isolate hematopoietic progenitors. The separated cells can be incubated in selected medium in a culture flask, sterile bag or in hollow fibers. Various hematopoietic growth factors may be utilized in order to selectively expand cells. Representative factors that have been utilized for ex-vivo expansion of bone marrow include, c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6, IL-11, flt-3 ligand or combinations thereof. The proliferation of the stem cells can be monitored by enumerating the number of stem cells and other cells, by standard techniques (e.g. hemacytometer, CFU, LTCIC) or by flow cytometry prior and subsequent to incubation.

Several methods for ex-vivo expansion of stem cells have been reported utilizing a number of selection methods and expansion using various hematopoietic growth factors including c-kit ligand (Brandt et al., Blood 83:1507-1514 (1994), McKenna et al., Blood 86:3413-3420 (1995), IL-3 (Brandt et al., Blood 83:1507-1514 (1994), Sato et al., Blood 82:3600-3609 (1993), G-CSF (Sato et al., Blood 82:3600-3609 (1993), GM-CSF (Sato et al., Blood 82:3600-3609 (1993), IL-1 (Muench et al., Blood 81:3463-3473 (1993), IL-6 (Sato et al., Blood 82:3600-3609 (1993), IL-11 (Lemoli et al., Exp. Hem . 21:1668-1672 (1993), Sato et al., Blood 82:3600-3609 (1993), flt-3 ligand (McKenna et al., Blood 86:3413-3420 (1995) and/or combinations thereof (Brandt et al., Blood 83:1507-1514 (1994), Haylock et al., Blood 80:1405-1412 (1992), Koller et al., Biotechnology 11:358-363 (1993), (Lemoli et al., Exp. Hem . 21:1668-1672 (1993), McKenna et al., Blood 86:3413-3420 (1995), Muench et al., Blood 81:3463-3473 (1993), Patchen et al., Biotherapy 7:13-26 (1994), Sato et al., Blood 82:3600-3609 (1993), Smith et al., Exp. Hem . 21:870-877 (1993), Steen et al., Stem Cells 12:214-224 (1994), Tsujino et al., Exp. Hem . 21:1379-1386 (1993). Among the individual hematopoietic growth factors, hIL-3 has been shown to be one of the most potent in expanding peripheral blood CD34+ cells (Sato et al., Blood 82:3600-3609 (1993), Kobayashi et al., Blood 73:1836-1841 (1989). However, no single factor has been shown to be as effective as the combination of multiple factors. The present invention provides methods for ex vivo expansion that utilize molecules that are more effective than IL-3 alone.

Another projected clinical use of growth factors has been in the in vitro activation of hematopoietic progenitors and stem cells for gene therapy. Due to the long life-span of hematopoietic progenitor cells and the distribution of their daughter cells throughout the entire body, hematopoietic progenitor cells are good candidates for ex vivo gene transfection. In order to have the gene of interest incorporated into the genome of the hematopoietic progenitor or stem cell one needs to stimulate cell division and DNA replication. Hematopoietic stem cells cycle at a very low frequency which means that growth factors may be useful to promote gene transduction and thereby enhance the clinical prospects for gene therapy. Potential applications of gene therapy (review Crystal, Science 270:404-410 (1995) include; 1) the treatment of many congenital metabolic disorders and immunodifiencies (Kay and Woo, Trends Genet . 10:253-257 (1994), 2) neurological disorders (Freedmann, Trends Genet . 10:210-214 (1994), 3) cancer (Culver and Blaese, Trends Genet . 10:174-178 (1994) and 4) infectious diseases (Gilboa and Smith, Trends Genet . 10:139-144 (1994). Due to the long life-span of hematopoietic progenitor cells and the distribution of their daughter cells throughout the entire body, hematopoietic progenitor cells are good candidates for ex vivo gene transfection include the treatment of many congenital metabolic disorders and immunodifiencies (Kay and Woo, Trends Genet . 10:253-257 (1994) neurological disorders (Freedmann, Trends Genet . 10:210-214 (1994), cancer (Culver and Blaese, Trends Genet . 10:174-178 (1994) and infectious diseases (Gilboa and Smith, Trends Genet . 10:139-144 (1994).

There are a variety of methods, known to those with skill in the art, for introducing genetic material into a host cell. A number of vectors, both viral and non-viral have been developed for transferring therapeutic genes into primary cells. Viral based vectors include; 1) replication-deficient recombinant retrovirus (Boris-Lawrie and Temin, Curr. Opin. Genet. Dev . 3:102-109 (1993), Boris-Lawrie and Temin, Annal. New York Acad. Sci . 716:59-71 (1994), Miller, Current Top. Microbiol. Immunol . 158:1-24 (1992) and replication-deficient recombinant adenovirus (Berkner, BioTechniques 6:616-629 (1988), Berkner, Current Top. Microbiol. Immunol . 158:39-66 (1992), Brody and Crystal, Annal. New York Acad. Sci . 716:90-103 (1994). Non-viral based vectors include protein/DNA complexes (Cristiano et al., PNAS USA . 90:2122-2126 (1993), Curiel et al., PNAS USA 88:8850-8854 (1991), Curiel, Annal. New York Acad. Sci . 716:36-58 (1994), electroporation and liposome mediated delivery such as cationic liposomes (Farhood et al., Annal. New York Acad. Sci . 716:23-35 (1994).

Hematopoietic cells that have been expanded ex-vivo using hIL-3 variants of the present invention may be useful in the treatment of diseases characterized by a decreased levels of either myeloid, erythroid, lymphoid, or megakaryocyte cells of the hematopoietic system or combinations thereof. In addition, they may be used to activate mature myeloid and/or lymphoid cells. Among conditions susceptible to treatment with the hematopoietic cells that have been expanded ex-vivo using hIL-3 variants of the present invention is leukopenia, a reduction in the number of circulating leukocytes (white cells) in the peripheral blood. Leukopenia may be induced by exposure to certain viruses or to radiation. It is often a side effect of various forms of cancer therapy, e.g., exposure to chemotherapeutic drugs and of infection or hemorrhage. Therapeutic treatment of leukopenia with these expanded hematopoietic cells may avoid undesirable side effects caused by treatment with current drugs.

The expanded hematopoietic cells of the present invention may be useful in the treatment of neutropenia and, for example, in the treatment of such conditions as aplastic anemia, cyclic neutropenia, idiopathic neutropenia, Chediak-Higashi syndrome, systemic lupus erythematosus (SLE), leukemia, myelodysplastic syndrome and myelofibrosis.

Many drugs may cause bone marrow suppression or hematopoietic deficiencies. Examples of such drugs are AZT, DDI, alkylating agents and anti-metabolites used in chemotherapy, antibiotics such as chloramphenicol, penicillin and sulfa drugs, phenothiazones, tranquilizers such as meprobamate, and diuretics. The expanded hematopoietic cells of the present invention may be useful in preventing or treating the bone marrow suppression or hematopoietic deficiencies which often occur in patients treated with these drugs.

Hematopoietic deficiencies may also occur as a result of viral, microbial or parasitic infections and as a result of treatment for renal disease or renal failure, e.g., dialysis. The expanded hematopoietic cells of the present invention may be useful in treating such hematopoietic deficiency.

Various immunodeficiencies e.g., in T and/or B lymphocytes, or immune disorders, e.g., rheumatoid arthritis, may also be beneficially affected by expanded hematopoietic cells of the present invention. Immunodeficiencies may be the result of viral infections e.g. HTLVI, HTLVII, HTLVIII, severe exposure to radiation, cancer therapy or the result of other medical treatment. The expanded hematopoietic cells of the present invention may also be employedn in the treatment of other blood cell deficiencies, including thrombocytopenia or anemia.

The dosage regimen involved in ex-vivo expansion of hematopoietic cells and methods for treating the above-described conditions will be determined by the attending physician considering various factors which modify the action of drugs, e.g. the condition, body weight, sex and diet of the patient, the severity of any infection, time of administration and other clinical factors. Generally, a daily regimen may be in the range of 1 ng/ml to 100 ng/mL of non-glycosylated IL-3 protein per mL of culture medium. This dosage regimen is referenced to a standard level of biological activity which recognizes that native IL-3 generally possesses an EC 50 at or about 10 picoMolar to 100 picoMolar in the AML proliferation assay described herein. Therefore, dosages would be adjusted relative to the activity of a given mutein vs. the activity of native (reference) IL-3 and it would not be unreasonable to note that dosage regimens may include doses as low as 0.1 ng and as high as 1 milligram per mL of culture medium. In addition, there may exist specific circumstances where dosages of IL-3 mutein would be adjusted higher or lower These include co-administration with other hematopoietic growth factors; co-administration with chemotherapeutic drugs and/or radiation; the use of glycosylated IL-3 mutein; and various patient-related issues mentioned earlier in this section.

EXAMPLE 1

AML Proliferation Assay for Bioactive Human Interleukin-3

hIL-3 SANDWICH ELISA

IL-3 protein concentrations can be determined using a sandwich ELISA based on an affinity purified polyclonal goat anti-rhIL-3. Microtiter plates (Dynatech Immulon II) were coated with 150 μl goat-anti-rhIL-3 at a concentration of approximately 1 μg/ml in 100 mM NaHCO3, pH 8.2. Plates were incubated overnight at room temperature in a chamber maintaining 100% humidity. Wells were emptied and the remaining reactive sites on the plate were blocked with 200 μl of solution containing 10 mM PBS, 3% BSA and 0.05% Tween 20, pH 7.4 for 1 hour at 37° C. and 100% humidity. Wells were emptied and washed 4× with 150 mM NaCl containing 0.05% Tween 20 (wash buffer). Each well then received 150 μl of dilution buffer (10 mM PBS containing 0.1% BSA, 0.01% Tween 20, pH 7.4), containing rhIL-3 standard, control, sample or dilution buffer alone. A standard curve was prepared with concentrations ranging from 0.125 ng/ml to 5 ng/ml using a stock solution of rhIL-3 (concentration determined by amino acid composition analysis). Plates were incubated 2.5 hours at 37° C. and 100% humidity. Wells were emptied and each plate was washed 4× with wash buffer. Each well then received 150 μl of an optimal dilution (as determined in a checkerboard assay format) of goat anti-rhIL-3 conjugated to horseradish peroxidase. Plates were incubated 1.5 hours at 37° C. and 100% humidity. Wells were emptied and each plate was washed 4× with wash buffer. Each well then received 150 ul of ABTS substrate solution (Kirkegaard and Perry). Plates were incubated at room temperature until the color of the standard wells containing 5 ng/ml rhIL-3 had developed enough to yield an absorbance between 0.5-1.0 when read at a test wavelength of 410 nm and a reference wavelength of 570 nm on a Dynatech microtiter plate reader. Concentrations of immunoreactive rhIL-3 in unknown samples were calculated from the standard curve using software supplied with the plate reader.

AML Proliferation Assay for Bioactive Human Interleukin-3

The factor-dependent cell line AML 193 was obtained from the American Type Culture Collection (ATCC, Rockville, Md.). This cell line, established from a patient with acute myelogenous leukemia, is a growth factor dependent cell line which displayed enhanced growth in GM/CSF supplemented medium (Lange, B., et al., Blood 70:192, 1987; Valtieri, M., et al., J. Immunol 138:4042, 1987). The ability of AML 193 cells to proliferate in the presence of human IL-3 has also been documented. (Santoli, D., et al., J. Immunol 139:348, 1987). A cell line variant was used, AML 193 1.3, which was adapted for long term growth in IL-3 by washing out the growth factors and starving the cytokine dependent AML 193 cells for growth factors for 24 hours. The cells were then replated at 1×10 5 cells/well in a 24 well plate in media containing 100 U/ml IL-3. It took approximately 2 months for the cells to grow rapidly in IL-3. These cells were maintained as AML 193 1.3 thereafter by supplementing tissue culture medium (see below) with human IL-3.

AML 193 1.3 cells were washed 6 times in cold Hanks balanced salt solution (HBSS, Gibco, Grand Island, N.Y.) by centrifuging cell suspensions at 250×g for 10 minutes followed by decantation of supernatant. Pelleted cells were resuspended in HBSS and the procedure was repeated until six wash cycles were completed. Cells washed six times by this procedure were resuspended in tissue culture medium at a density ranging from 2×10 5 to 5×10 5 viable cells/ml. This medium was prepared by supplementing Iscovels modified Dulbecco's Medium (IMDM, Hazleton, Lenexa, Kans.) with albumin, transferrin, lipids and 2-mercaptoethanol. Bovine albumin (Boehringer-Mannheim, Indianapolis, Ind.) was added at 500 μg/ml; human transferrin (Boehringer-Mannheim, Indianapolis, IN) was added at 100 μg/ml; soybean lipid (Boehringer-Mannheim, Indianapolis, Ind.) was added at 50 μg/ml; and 2-mercaptoethanol (Sigma, St. Louis, Mo.) was added at 5×10 −5 M.

Serial dilutions of human interleukin-3 or human interleukin-3 variant protein (hIL-3 mutein) were made in triplicate series in tissue culture medium supplemented as stated above in 96 well Costar 3596 tissue culture plates. Each well contained 50 μl of medium containing interleukin-3 or interleukin-3 variant protein once serial dilutions were completed. Control wells contained tissue culture medium alone (negative control). AML 193 1.3 cell suspensions prepared as above were added to each well by pipetting 50 μl (2.5×10 4 cells) into each well. Tissue culture plates were incubated at 37° C. with 5% CO 2 in humidified air for 3 days. On day 3, 0.5 μCi 3 H-thymidine (2 Ci/mM, New England Nuclear, Boston, Mass.) was added in 50 μl of tissue culture medium. Cultures were incubated at 37° C. with 5% CO 2 in humidified air for 18-24 hours. Cellular DNA was harvested onto glass filter mats (Pharmacia LKB, Gaithersburg, Md.) using a TOMTEC cell harvester (TOMTEC, Orange, Conn.) which utilized a water wash cycle followed by a 70% ethanol wash cycle. Filter mats were allowed to air dry and then placed into sample bags to which scintillation fluid (Scintiverse II, Fisher Scientific, St. Louis, Mo. or BetaPlate Scintillation Fluid, Pharmacia LKB, Gaithersburg, Md.) was added. Beta emissions of samples from individual tissue culture wells were counted in a LKB Betaplate model 1205 scintillation counter (Pharmacia LKB, Gaithersburg, Md.) and data was expressed as counts per minute of 3 H-thymidine incorporated into cells from each tissue culture well. Activity of each human interleukin-3 preparation or human interleukin-3 variant preparation was quantitated by measuring cell proliferation ( 3 H-thymidine incorporation) induced by graded concentrations of interleukin-3 or interleukin-3 variant. Typically, concentration ranges from 0.05 pM-105 pM are quantitated in these assays. Activity is determined by measuring the dose of interleukin-3 or interleukin-3 variant which provides 50% of maximal proliferation [EC 50 =0.5× (maximum average counts per minute of 3 H-thymidine incorporated per well among triplicate cultures of all concentrations of interleukin-3 tested—background proliferation measured by 3 H-thymidine incorporation observed in triplicate cultures lacking interleukin-3]. This EC 50 value is also equivalent to 1 unit of bioactivity. Every assay was performed with native interleukin-3 as a reference standard so that relative activity levels could be assigned.

Relative biological activities of IL-3 muteins of the present invention are shown in Table 1. The Relative Biological Activity of IL-3 mutants is calculated by dividing the EC 50 of (1-133) hIL-3 by the EC 50 of the mutant. The Relative Biological Activity may be the average of replicate assays. by 3 H-thymidine incorporation observed in triplicate cultures lacking interleukin-3]. This EC 50 value is also equivalent to 1 unit of bioactivity. Every assay was performed with native interleukin-3 as a reference standard so that relative activity levels could be assigned.

Relative biological activities of IL-3 muteins of the present invention are shown in Table 1. The Relative Biological Activity of IL-3 mutants is calculated by dividing the EC50 of (1-133) hIL-3 by the EC 50 of the mutant. The Relative Biological Activity may be the average of replicate assays.

TABLE 1
BIOLOGICAL ACTIVITY OF IL-3 MUTEINS
			Relative*
	Plasmid	Polypeptide	Biological
	Code	Structure	Activity
	Reference (1-133)hIL-3		1
	pMON13298	SEQ ID NO. 82	3
	pMON13299	SEQ ID NO. 83	2
	pMON13300	SEQ ID NO. 84	3
	pMON13301	SEQ ID NO. 85	2
	pMON13302	SEQ ID NO. 86	1.2
	pMON13303	SEQ ID NO. 87	0.6
	pMON13287	SEQ ID NO. 88	26
	pMON13288	SEQ ID NO. 89	24
	pMON13289	SEQ ID NO. 90	13
	pMON13290	SEQ ID NO. 91	20
	pMON13292	SEQ ID NO. 92	6
	pMON13294	SEQ ID NO. 93	3
	pMON13295	SEQ ID NO. 94	3
	pMON13312	SEQ ID NO. 95	4
	pMON13313	SEQ ID NO. 96	8
	pMON13285	SEQ ID NO. 259	32
	pMON13286	SEQ ID NO. 260	8
	pMON13325	SEQ ID NO. 261	8
	pMON13326	SEQ ID NO. 262	25
	pMON13330	SEQ ID NO. 263	19
	pMON13329	SEQ ID NO. 406	10
	pMON13364	SEQ ID NO. 117	13
	pMON13475	SEQ ID NO. 280	7
	pMON13366	SEQ ID NO. 281	38
	pMON13367	SEQ ID NO. 282	36
	pMON13368	SEQ ID NO. 278	1.6
	pMON13369	SEQ ID NO. 283	10
	pMON13370	SEQ ID NO. 284	6
	pMON13373	SEQ ID NO. 285	12
	pMON13374	SEQ ID NO. 286	6
	pMON13375	SEQ ID NO. 287	14
	pMON13376	SEQ ID NO. 288	0.4
	pMON13377	SEQ ID NO. 289	0.4
	pMON13379	SEQ ID NO. 291	0.9
	pMON13380	SEQ ID NO. 279	0.05
	pMON13381	SEQ ID NO. 293	10
	pMON13382	SEQ ID NO. 313	38
	pMON13383	SEQ ID NO. 294	0.5
	pMON13384	SEQ ID NO. 295	0.25
	pMON13385	SEQ ID NO. 292	1
	pMON13387	SEQ ID NO. 308	32
	pMON13388	SEQ ID NO. 296	23
	pMON13389	SEQ ID NO. 297	10
	pMON13391	SEQ ID NO. 298	30
	pMON13392	SEQ ID NO. 299	17
	pMON13393	SEQ ID NO. 300	32
	pMON13394	SEQ ID NO. 301	20
	pMON13395	SEQ ID NO. 302	11
	pMON13396	SEQ ID NO. 303	20
	pMON13397	SEQ ID NO. 304	16
	pMON13398	SEQ ID NO. 305	36
	pMON13399	SEQ ID NO. 306	18
	pMON13404	SEQ ID NO. 307	1.3
	pMON13417	SEQ ID NO. 310	24
	pMON13420	SEQ ID NO. 311	19
	pMON13421	SEQ ID NO. 312	0.5
	pMON13432	SEQ ID NO. 313	10
	pMON13400	SEQ ID NO. 317	0.09
	pMON13402	SEQ ID NO. 318	20
	pMON13403	SEQ ID NO. 321	0.03
	pMON13405	SEQ ID NO. 267	9
	pMON13406	SEQ ID NO. 264	5
	pMON13407	SEQ ID NO. 266	16
	pMON13408	SEQ ID NO. 269	7
	pMON13409	SEQ ID NO. 270	15
	pMON13410	SEQ ID NO. 271	0.4
	pMON13411	SEQ ID NO. 322	1.2
	pMON13412	SEQ ID NO. 323	0.5
	pMON13413	SEQ ID NO. 324	0.6
	pMON13414	SEQ ID NO. 265	4
	pMON13415	SEQ ID NO. 268	4
	pMON13418	SEQ ID NO. 326	0.5
	pMON13419	SEQ ID NO. 325	0.015
	pMON13422	SEQ ID NO. 272	0.4
	pMON13423	SEQ ID NO. 273	0.4
	pMON13424	SEQ ID NO. 274	3
	pMON13425	SEQ ID NO. 275	6
	pMON13426	SEQ ID NO. 276	>0.0003
	pMON13429	SEQ ID NO. 277	>0.0002
	pMON13440	SEQ ID NO. 319	9
	pMON13451	SEQ ID NO. 320	0.1
	pMON13459	SEQ ID NO. 328	0.003
	pMON13416	SEQ ID NO. 309	19.9
	pMON13428	SEQ ID NO. 327	0.008
	pMON13467	SEQ ID NO. 329	0.16
	pMON13446	SEQ ID NO. 315	21.5
	pMON13390	SEQ ID NO. 316	20
	*The Relative Biological Activity of IL-3 mutants is calculated by dividing the EC 50 of (1-133) hIL-3 by the EC 50 of the mutant.

EXAMPLE 2

Determination of Bioactivity of IL-3 Variants and other Hematopoietic Growth Factors in the Methylcellulose Assay

Methylcellulose Assay

This assay provides a reasonable approximation of the growth activity of colony stimulating factors to stimulate normal bone marrow cells to produce different types of hematopoietic colonies in vitro (Bradley et al., Aust. Exp. Biol. Med. Sci . 44:287-300 1966; Pluznik et al., J Cell-Comp Physiol 66:319-324 1965).

Methods

Approximately 30 ml of fresh, normal, healthy bone marrow aspirate are obtained from individuals. Under sterile conditions samples are diluted 1:5 with a 1× PBS (#14040.059 Life Technologies, Gaithersburg, Md.) solution in a 50 ml conical tube (#25339-50 Corning, Corning Md). Ficoll (Histopaque-1077 Sigma H-8889) is layered under the diluted sample and centrifuged, 300×g for 30 min. The mononuclear cell band is removed and washed two times in 1× PBS and once with 1% BSA PBS (CellPro Co., Bothel, Wash.). Mononuclear cells are counted and CD34+ cells are selected using the Ceprate LC (CD34) Kit (CellPro Co., Bothel, Wash.) column. This fractionation is performed since all stem and progenitor cells within the bone marrow display CD34 surface antigen. Alternatively whole bone marrow or peripheral blood may be used.

Cultures are set up in triplicate wells with a final volume of 0.1 ml in 48 well tissue culture plates (#3548 CoStar, Cambridge, Mass.). Culture medium is purchased from Terry Fox Labs. (HCC-4330 medium (Terry Fox Labs, Vancouver, B.C., Canada)). 600-1000 CD34+ cells are added per well. Native IL-3 and IL-3 variants are added to give final concentrations ranging from 0.01 nM-10 nM. G-CSF and GM-CSF and C-Kit ligand are added at a final concentration of 0.1 nM. Native IL-3 and IL-3 variants are supplied in house. C-Kit Ligand (#255-CS), G-CSF (#214-CS) and GM-CSF (#215-GM) are purchased from R&D Systems (Minneapolis, Minn.).

Cultures are resuspended using an Eppendorf repeater and 0.1 ml is dispensed per well. Control (baseline response) cultures received no colony stimulating factors. Positive control cultures received conditioned media (PHA stimulated human cells:Terry Fox Lab. H2400). Cultures are incubated at 37° C., 5% CO2 in humidified air.

Hematopoietic colonies which are defined as greater than 50 cells are counted on the day of peak response (days 10-11) using a Nikon inverted phase microscope with a 40× objective combination. Groups of cells containing fewer than 50 cells are referred to as clusters. Alternatively colonies can be identified by spreading the colonies on a slide and stained or they can be picked, resuspended and spun onto cytospin slides for staining.

EXAMPLE 3

Ex vivo Expansion of CD34+ Cells from Peripheral Blood Using Chimera Molecules pMON13416 Compared with Human IL-3

Flow Cytometry Evaluation

The percentage of CD34+ cells in the thawed peripheral blood cell population was determined by flow cytometry. Cells were removed from the selected cell population and placed into two centrifuge tube and washed once in 9/1% albumin Phosphate buffer (PAB). Twenty microliters of anti-CD34 monoclonal antibody (8G12-FITC) or mouse monoclonal antibody IgG-FITC control was added to the tube. The tubes were incubated for 15 minutes on ice. The cells were washed once with PAB and resuspended in approximately 0.5 mL PAB. Propidium iodide (2 ug/mL) was added to each tube just prior to the analysis on the FACSort or FACScan. Selected cells that contain greater than 80% CD34+ cells were used to initiate the cultures.

On day 12, cultures were harvested and evaluated with CD41A-FITC (a megakaryocyte marker), CD15-FITC and CD11b-PE (early to late neutrophil marker) and CD34 by flow cytometry, using the same processes of preparation and analysis as described above.

Colony Assay Evaluation

Colony assay evaluation was performed on day 0 with 500-1000 selected CD34+ cells per dish and again on day 12 of culture with 5,000-10,000 cultured cells per dish. The cells were added to a colony assay culture tube containing 3 mL of Terry Fox Iscove's based methylcellulose and the following growth factors: 20 ng/mL SCF, 10 U/mL EPO, 300 U/mL GM-CSF, 300 U/mL G-CSF, 30 U/mL IL3, 50 ng/mL of IL-3 variants and 40 ng/mL IL6. Two 35 mm tissue culture dishes containing 1 mL were set up. All dishes were incubated at 37° C., 5% carbon dioxide, 5% oxygen and high humidity for 13-15 days. The dishes were scored for myeloid (CFU-GM), erythroid (BFU-E) or mixed myeloid and erythroid colonies (CFU-mix) using a Nikon SMZU stereoscope.

Cell Morphology Evaluation

On day 12 of culture cells were analyzed for cell morphology after Wright-Giemsa staining. Cultured cells were cytocentrifuged onto slides at 1000 rpm for 4 minutes. Each slide contained approximately 10000-20000 cells. Slides were allowed to air dry before staining with 0.5 mL Wright-Giemsa for 1 minutes and 0.5 mL tap water for 1-2 minutes. Slides were cover-slipped and evaluated using a Microstar light microscope. A differential cell count of neutrophils, megakaryocytes and other blood cells was performed.

RESULTS

CD34+ Selection

Studies were performed on CD34+ cells selected using the Isolex™ 300 magnetic Cell Separator from apheresis products from normal donors mobilized with G-CSF. The selected cells were stored in X-VIVO 10+12.5% HSA containing 10% DMSO in liquid nitrogen until required. Cultures were initiated as described in the methods section.

Proliferation Index Of Cultures At Day 12

The proliferation index of cultures was calculated by diving the cell concentration at day 5-7 by 5×10 4 and then multiplying it by the cell concentration at day 12 divided by 1×10 5 . A summary of the proliferation index obtained from these CD34+ cell cultures is shown in Table 5.

Flow Cytometry Evaluation of Neutrophil Precursors

The percentage of neutrophil precursors in the CD34+ cell cultures at day 12 was assessed by flow cytometry using the CD15 marker for early to late neutrophil precursors and the CD11b marker found on late neutrophil precursors determined is shown in Table 2.

Flow Cytometry Evaluation of Megakaryocytes

The percentage of Mks in the CD34+ cell cultures was assessed by flow cytometry using the CD41a marker for megakaryocytes. The percentage of Mks observed in the CD34+ cell cultures is shown in Table 2.

Flow Cytometry Evaluation Of CD34+ Cells

The percentage of CD34+cells present in the cultures at day 12 was determined by flow cytometry. The percentage of CD34+ cells still remaining in the cultures at day 12 ranged from 0.103-19.3%, with no significant difference or patterns observed with the different growth factor combinations.

Total Number Of Megakaryocytes Generated In Culture

The total number of megakaryocytes present in each culture is calculated by multiplying the total number of cells at day 12 by the percentage of CD15+ cells and is shown in Table 2.

Colony Forming Unit Granulocyte-Macrophage (CFU-GM) Index

CFU-GM index is calculate by dividing the total number of GM-colonies obtained at day 12 by the number of GM-colonies obtained at day 0. A CFU-GM index of 1 indicates that the number of colonies at day 12 is equivalent to the number of colonies at the start of the culture. A summary of the CFU-GM index for these cultures is shown in Table 2.

Colony Forming Unit (CFU) Index

CFU index is calculated by dividing the total number of colonies (CFU-GM, BFU-E and mixed) obtained at day 12 by the total number of colonies obtained at day 0. A CFU index of 1 indicates that the number of colonies at day 12 is equivalent to the number of colonies at the start of the culture. A summary of the CFU index for these cultures is shown in Table 2.

TABLE 2
Ex-vivo Expansion
		Do-	Do-	Do-	Do-	Do-
	Growth	nor	nor	nor	nor	nor
Assay	Factor	*1	*2	*3	*4	*5
Proliferation Index	pMON13416	31.2	44.4	13.9	18.3	5
of CD34+ Cell	native	9	4.1	3.4	10.7	1.4
Cultures at Day 12	hIL-3
Percentage CD15+	pMON13416	44	42.4	72.2	48.8	54.5
Cells at Day 12 of	native	25.6	10.5	43.3	26	18.2
CD34+ Cultures	hIL-3
Percentage CD41+	pMON13416	9.2	13.7	2.3	1.4	3.1
Cells at Day 12 of	native	18.9	14.1	13.7	4.2	5.5
CD34+ Cultures	hIL-3
Total Number of	pMON13416	11	24	1.3	1	0.6
Megakaryoctes (E +	native	6.8	2.3	5.9	0.2	0.3
05) In Day 10-12	hIL-3
Cultures
Colony Forming Unit	pMON13416	1.1	2.5	0.06	1	0.1
Granulocyte	native	0.2	0.06	0.03	0.03	0.03
Macrophage	hIL-3
(CFU-GM) Index
Colony Forming	pMON13416	1.6	3.7	0.1	0.8	0.2
Unit-Index	native	0.2	0.08	0.03	0.03	0.04
	hIL-3

Additional details may be found in co-pending U.S. patent application Ser. No. 08/411,795 which is hereby incorporated by reference in its entirety as if written herein.

All references, patents or applications cited herein are incorporated by reference in their entirety as if written herein.

Various other examples will be apparent to the person skilled in the art after reading the present disclosure without departing from the spirit and scope of the invention. It is intended that all such other examples be included within the scope of the appended claims.

415 23 base pairs nucleic acid single linear DNA (synthetic) 1CTAGCGATCT TTTAATAAGC TTG 23 23 base pairs nucleic acid single linear DNA (synthetic) 2GATCCAAGCT TATTAAAAGA TCG 23 69 base pairs nucleic acid single linear DNA (synthetic) 3GGCAACAATT TCTACAAAAC ACTTGATACT GTATGAGCAT ACAGTATAAT TGCTTCAACA 60GAACAGATC 69 67 base pairs nucleic acid single linear DNA (synthetic) 4TGTTCTGTTG AAGCAATTAT ACTGTATGCT CATACAGTAT CAAGTGTTTT GTAGAAATTG 60TTGCCGC 67 23 base pairs nucleic acid single linear DNA (synthetic) 5CCATTGCTGC CGGCATCGTG GTC 23 46 base pairs nucleic acid single linear DNA (synthetic) 6CATGGCTCCA ATGACTCAGA CTACTTCTCT TAAGACTTCT TGGGTT 46 42 base pairs nucleic acid single linear DNA (synthetic) 7AACCCAAGAA GTCTTAAGAG AAGTAGTCTG AGTCATTGGA GC 42 64 base pairs nucleic acid single linear DNA (synthetic) 8AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT 60AATA 64 64 base pairs nucleic acid single linear DNA (synthetic) 9AGCTTATTAC TGTTGAGCCT GCGCGTTCTC CAAGGTTTTC AGATAGAAGG TCAGTTTACG 60ACGG 64 126 amino acids amino acid linear peptide 10Met Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro 20 25 30Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile 35 40 45Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg 50 55 60Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys65 70 75 80Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His 85 90 95Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu 100 105 110Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 115 120 125 24 base pairs nucleic acid single linear DNA (synthetic) 11CATGGCTAAC TGCTCTAACA TGAT 24 22 base pairs nucleic acid single linear DNA (synthetic) 12CGATCATGTT AGAGCAGTTA GC 22 113 amino acids amino acid linear peptide 13Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 27 amino acids amino acid linear peptide 14Met Met Ile Thr Leu Arg Lys Leu Pro Leu Ala Val Ala Val Ala Ala1 5 10 15Gly Val Met Ser Ala Gln Ala Met Ala Asn Cys 20 25 133 amino acids amino acid linear peptide Modified-site /note= “Met- may or may not precede the amino acid in position 1” Modified-site 17 /note= “Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg” Modified-site 18 /note= “Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln” Modified-site 19 /note= “Xaa at positiion 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys” Modified-site 20 /note= “Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala” Modified-site 21 /note= “Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser, or Val” Modified-site 22 /note= “Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly” Modified-site 23 /note= “Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg” Modified-site 24 /note= “Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu” Modified-site 25 /note= “Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala” Modified-site 26 /note= “Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp” Modified-site 27 /note= “Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala” Modified-site 28 /note= “Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val, or Trp” Modified-site 29 /note= “Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val” Modified-site 30 /note= “Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys” Modified-site 31 /note= “Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln” Modified-site 32 /note= “Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu” Modified-site 33 /note= “Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu” Modified-site 34 /note= “Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile, or Met” Modified-site 35 /note= “Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val” Modified-site 36 /note= “Xaa at position 36 is Asp, Leu, or Val” Modified-site 37 /note= “Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile” Modified-site 38 /note= “Xaa at position 38 is Asn, or Ala” Modified-site 40 /note= “Xaa at position 40 is Leu, Trp, or Arg” Modified-site 41 /note= “Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro” Modified-site 42 /note= “Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met, or Ala” Modified-site 43 /note= “Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly, or Ser” Modified-site 44 /note= “Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala, or Pro” Modified-site 45 /note= “Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu, or His” Modified-site 46 /note= “Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val, or Gly” Modified-site 47 /note= “Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His” Modified-site 48 /note= “Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val, or Asn” Modified-site 49 /note= “Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp” Modified-site 50 /note= “Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met, or Gln” Modified-site 51 /note= “Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 52 /note= “Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr” Modified-site 53 /note= “Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met” Modified-site 54 /note= “Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala, or Leu” Modified-site 55 /note= “Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly” Modified-site 56 /note= “Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val, or Lys” Modified-site 57 /note= “Xaa at position 57 is Asn or Gly” Modified-site 58 /note= “Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys” Modified-site 59 /note= “Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg” Modified-site 60 /note= “Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr” Modified-site 61 /note= “Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser” Modified-site 62 /note= “Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile” Modified-site 63 /note= “Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val” Modified-site 64 /note= “Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys” Modified-site 65 /note= “Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser” Modified-site 66 /note= “Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser” Modified-site 67 /note= “Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His” Modified-site 68 /note= “Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His” Modified-site 69 /note= “Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu” Modified-site 70 /note= “Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala” Modified-site 71 /note= “Xaa at position 71 is Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp,or Asn” Modified-site 72 /note= “Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp” Modified-site 73 /note= “Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg” Modified-site 74 /note= “Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, or Ala” Modified-site 75 /note= “Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu” Modified-site 76 /note= “Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp” Modified-site 77 /note= “Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu” Modified-site 78 /note= “Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg” Modified-site 79 /note= “Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp” Modified-site 80 /note= “Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg” Modified-site 81 /note= “Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys” Modified-site 82 /note= “Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met, or Val” Modified-site 83 /note= “Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met” Modified-site 84 /note= “Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val” Modified-site 85 /note= “Xaa at position 85 is Leu, Asn, Val, or Gln” Modified-site 86 /note= “Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys” Modified-site 87 /note= “Xaa at position 87 is Leu, Ser, Trp, or Gly” Modified-site 88 /note= “Xaa at position 88 is Ala, Lys, Arg, Val, or Trp” Modified-site 89 /note= “Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser” Modified-site 90 /note= “Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met” Modified-site 91 /note= “Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His” Modified-site 92 /note= “Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile, or Leu” Modified-site 93 /note= “Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg” Modified-site 94 /note= “Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro” Modified-site 95 /note= “Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr” Modified-site 96 /note= “Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr” Modified-site 97 /note= “Xaa at position 97 is Ile, Val, Lys, Ala, or Asn” Modified-site 98 /note= “Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr, or Pro” Modified-site 99 /note= “Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His” Modified-site 100 /note= “Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro” Modified-site 101 /note= “Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln” Modified-site 102 /note= “Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro” Modified-site 103 /note= “Xaa at position 103 is Asp, or Ser” Modified-site 104 /note= “Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly” Modified-site 105 /note= “Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His” Modified-site 106 /note= “Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro” Modified-site 108 /note= “Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro” Modified-site 109 /note= “Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly” Modified-site 110 /note= “Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp” Modified-site 111 /note= “Xaa at position 111 is Leu, Ile, Arg, Asp, or Met” Modified-site 112 /note= “Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe” Modified-site 113 /note= “Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val, or Asn” Modified-site 114 /note= “Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu” Modified-site 115 /note= “Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met” Modified-site 116 /note= “Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Glu, or Ile” Modified-site 117 /note= “Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro” Modified-site 118 /note= “Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr” Modified-site 119 /note= “Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg” Modified-site 120 /note= “Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln” Modified-site 121 /note= “Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly” Modified-site 122 /note= “Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 123 /note= “Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 15Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 85 90 95Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa 100 105 110Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu 115 120 125Ser Leu Ala Ile Phe 130 133 amino acids amino acid linear peptide Modified-site /note= “Met- may or may not precede the amino acid in position 1” Modified-site 17 /note= “Xaa at position 17 is Ser, Gly, Asp, Met, or Gln” Modified-site 18 /note= “Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln” Modified-site 19 /note= “Xaa at position 19 is Met, Phe, Ile, Arg, or Ala” Modified-site 20 /note= “Xaa at position 20 is Ile or Pro” Modified-site 21 /note; “Xaa at position 21 is Asp or Glu” Modified-site 23 /note= “Xaa at position 23 is Ile, Val, Ala, Leu, or Gly” Modified-site 24 /note= “Xaa at position 24 is Ile, Val, Phe, or Leu” Modified-site 25 /note= “Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala” Modified-site 26 /note= “Xaa at position 26 is His, Phe, Gly, Arg, or Ala” Modified-site 28 /note= “Xaa at position 28 is Lys, Leu, Gln, Gly, Pro, or Val” Modified-site 29 /note= “Xaa at position 29 is Gln, Asn, Leu, Arg, or Val” Modified-site 30 /note= “Xaa at position 30 is Pro, His, Thr, Gly, or Gln” Modified-site 31 /note= “Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln” Modified-site 32 /note= “Xaa at position 32 Leu, Arg, Gln, Asn, Gly, Ala, or Glu” Modified-site 33 /note= “Xaa at position 33 is Pro, Leu, Gln, Ala, or Glu” Modified-site 34 /note= “Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met” Modified-site 35 /note= “Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, or Val” Modified-site 36 /note= “Xaa at position 36 is Asp or Leu” Modified-site 37 /note= “Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile” Modified-site 38 /note= “Xaa at position 38 is Asn or Ala” Modified-site 41 /note= “Xaa at position 41 is Asn, Cys, Arg, His, Met, or Pro” Modified-site 42 /note= “Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr, Val, or Arg” Modified-site 44 /note=“Xaa at position 44 is Asp or Glu” Modified-site 45 /note= “Xaa at position 45 is Gln, Val, Met, Leu, Thr, Lys, Ala, Asn, Glu, Ser, or Trp” Modified-site 46 /note= “Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Ala, Asn, Gln, Glu, His, Ile, Lys, Tyr, Val, or Gly” Modified-site 47 /note= “Xaa at position 47 is Ile, Val, or His” Modified-site 49 /note= “Xaa at position 49 is Met, Asn, or Asp” Modified-site 50 /note= “Xaa at position 50 is Glu, Thr, Ala, Asn, Ser, or Asp” Modified-site 51 /note= “Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 52 /note= “Xaa at position 52 is Asn or Gly” Modified-site 53 /note= “Xaa at position 53 is Leu, Met, or Phe” Modified-site 54 /note= “Xaa at position 54 is Arg Ala, or Ser” Modified-site 55 /note= “Xaa at position 55 is Arg, Thr, Val, Leu, or Gly” Modified-site 56 /note= “Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Ala, Arg, Asn, Glu, His, Leu, Thr, Val, or Lys” Modified-site 59 /note= “Xaa at position 59 is Glu, Tyr, His, Leu, or Arg” Modified-site 60 /note= “Xaa at position 60 is Ala, Ser, Asn, or Thr” Modified-site 61 /note= “Xaa at position 61 is Phe or Ser” Modified-site 62 /note= “Xaa at position 62 is Asn, Val, Pro, Thr, or Ile” Modified-site 63 /note= “Xaa at position 63 is Arg, Tyr, Lys, Ser, His, or Val” Modified-site 64 /note= “Xaa at position 64 is Ala or Asn” Modified-site 65 /note= “Xaa at position 65 is Val, Thr, Leu, or Ser” Modified-site 66 /note= “Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser” Modified-site 67 /note= “Xaa at position 67 is Ser, Phe, Val, Gly, Asn, Ile, or His” Modified-site 68 /note= “Xaa at position 68 is Leu, Val, Ile, Phe, or His” Modified-site 69 /note= “Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly” Modified-site 70 /note= “Xaa at position 70 is Asn or Pro” Modified-site 71 /note= “Xaa at position 71 is Ala, Met, Pro, Arg, Glu, Thr, or Gln” Modified-site 72 /note= “Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp” Modified-site 73 /note= “Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, Arg, or Pro” Modified-site 74 /note= “Xaa at position 74 is Ile or Met” Modified-site 75 /note= “Xaa at position 75 is Glu, Gly, Asp, Ser, or Gln” Modified-site 76 /note= “Xaa at position 76 is Ser, Val, Ala, Asn, Glu, Pro, Gly, or Asp” Modified-site 77 /note= “Xaa at position 77 is Ile, Ser, or Leu” Modified-site 79 /note= “Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp” Modified-site 80 /note= “Xaa at position 80 is Asn, Val, Gly, Thr, Leu, Glu, or Arg” Modified-site 81 /note= “Xaa at position 81 is Leu or Val” Modified-site 82 /note= “Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 83 /note= “Xaa at position 83 is Pro, Ala, Thr, Trp, or Met” Modified-site 85 /note= “Xaa at position 85 is Leu or Val” Modified-site 87 /note= “Xaa at position 87 is Leu or Ser” Modified-site 88 /note= “Xaa at position 88 is Ala, Arg, or Trp” Modified-site 89 /note= “Xaa at position 89 is Thr, Asp, Glu, His, Asn, or Ser” Modified-site 90 /note= “Xaa at position 90 is Ala, Asp, or Met” Modified-site 91 /note= “Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, or Asp” Modified-site 92 /note= “Xaa at position 92 is Pro or Ser” Modified-site 93 /note= “Xaa at position 93 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg” Modified-site 95 /note= “Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly, Asn, Ile, Phe, Ser, or Thr” Modified-site 96 /note= “Xaa at position 96 is Pro or Tyr” Modified-site 97 /note= “Xaa at position 97 is Ile, Val, or Ala” Modified-site 98 /note= “Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Arg, Gln, Glu, Lys, Met, Ser, Tyr, Val, or Pro” Modified-site 99 /note= “Xaa at position 99 is Ile, Leu, Val, or Phe” Modified-site 100 /note= “Xaa at position 100 is Lys, Leu, His, Arg, Ile, Gln, Pro, or Ser” Modified-site 101 /note= “Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Asn, Ile, Leu, or Tyr” Modified-site 102 /note= “Xaa at position 102 is Gly, Glu, Lys, or Ser” Modified-site 104 /note= “Xaa at position 104 is Trp, Val, Tyr, Met, or Leu” Modified-site 105 /note= “Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp or His” Modified-site 106 /note= “Xaa at position 106 is Glu, Ser, Ala, or Gly” Modified-site 108 /note= “Xaa at position 108 is Arg, Ala, Gln, Ser, or Lys” Modified-site 109 /note= “Xaa at position 109 is Arg, Thr, Glu, Leu, Ser, or Gly” Modified-site 112 /note= “Xaa at position 112 is Thr, Val, Gln, Glu, His, or Ser” Modified-site 114 /note= “Xaa at position 114 is Tyr or Trp” Modified-site 115 /note= “Xaa at position 115 is Leu or Ala” Modified-site 116 /note= “Xaa at position 116 is Lys, Thr, Met, Val, Trp, Ser, Leu, Ala, Asn, Gln, His, Phe, Tyr, or Ile” Modified-site 117 /note= “Xaa at position 117 is Thr, Ser, or Asn” Modified-site 119 /note= “Xaa at position 119 is Glu, Ser, Pro, Leu, Thr, or Tyr” Modified-site 120 /note= “Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 121 /note= “Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly” Modified-site 122 /note= “Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 123 /note= “Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 16Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Xaa Xaa Xaa Glu Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa 20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Glu Xaa Xaa Xaa Xaa Leu 35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa65 70 75 80Xaa Xaa Xaa Cys Xaa Pro Xaa Xaa Xaa Xaa Xaa Xaa Xaa Arg Xaa Xaa 85 90 95Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Xaa Phe Xaa Xaa Lys Leu Xaa 100 105 110Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu 115 120 125Ser Leu Ala Ile Phe 130 133 amino acids amino acid linear peptide Modified-site /note= “Met- may or may not precede the amino acid in position 1” Modified-site 17 /note= “Xaa at position 17 is Ser, Gly, Asp, Met, or Gln” Modified-site 18 /note= “Xaa at position 18 is Asn, His, or Ile” Modified-site 19 /note= “Xaa at position 19 is Met or Ile” Modified-site 21 /note= “Xaa at position 21 is Asp or Glu” Modified-site 23 /note= “Xaa at position 23 is Ile, Ala, Leu, or Gly” Modified-site 24 /note= “Xaa at position 24 is Ile, Val, or Leu” Modified-site 25 /note= “Xaa at position 25 is Thr, His, Gln, or Ala” Modified-site 26 /note= “Xaa at position 26 is His or Ala” Modified-site 29 /note= “Xaa at position 29 is Gln, Asn, or Val” Modified-site 30 /note= “Xaa at position 30 is Pro, Gly, or Gln” Modified-site 31 /note= “Xaa at position 31 is Pro, Asp, Gly, or Gln” Modified-site 32 /note= “Xaa at position 32 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu” Modified-site 33 /note= “Xaa at position 33 is Pro or Glu” Modified-site 34 /note= “Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe Thr, or Met” Modified-site 35 /note= “Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, or Val” Modified-site 37 /note= “Xaa at position 37 is Phe, Ser, Pro, or Trp” Modified-site 38 /note= “Xaa at position 38 is Asn or Ala” Modified-site 42 /note= “Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg” Modified-site 44 /note= “Xaa at position 44 is Asp or Glu” Modified-site 45 /note= “Xaa at position 45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser, or Lys” Modified-site 46 /note= “Xaa at position 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys, Tyr, Val, or Cys” Modified-site 50 /note= “Xaa at position 50 is Glu, Ala, Asn, Ser, or Asp” Modified-site 51 /note= “Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 54 /note= “Xaa at position 54 is Arg or Ala” Modified-site 55 /note= “Xaa at position 55 is Arg, Thr, Val, Leu, or Gly” Modified-site 56 /note= “Xaa at position 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val, or Lys” Modified-site 60 /note= “Xaa at position 60 is Ala or Ser” Modified-site 62 /note= “Xaa at position 62 is Asn, Pro, Thr, or Ile” Modified-site 63 /note= “Xaa at position 63 is Arg or Lys” Modified-site 64 /note= “Xaa at position 64 is Ala or Asn” Modified-site 65 /note= “Xaa at position 65 is Val or Thr” Modified-site 66 /note= “Xaa at position 66 is Lys or Arg” Modified-site 67 /note= “Xaa at position 67 is Ser Phe or His” Modified-site 68 /note= “Xaa at position 68 is Leu, Ile, Phe, or His” Modified-site 69 /note= “Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly” Modified-site 71 /note= “Xaa at position 71 is Ala, Pro, or Arg” Modified-site 72 /note= “Xaa at position 72 is Ser, Glu, Arg, or Asp” Modified-site 73 /note= “Xaa at position 73 is Ala or Leu” Modified-site 76 /note= “Xaa at position 76 is Ser, Val, Ala, Asn, Glu, Pro, or Gly” Modified-site 77 /note= “Xaa at position 77 is Ile or Leu” Modified-site 79 /note= “Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp” Modified-site 80 /note= “Xaa at position 80 is Asn, Gly, Glu, or Arg” Modified-site 82 /note= “Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 83 /note= “Xaa at position 83 is Pro or Thr” Modified-site 85 /note= “Xaa at position 85 is Leu or Val” Modified-site 87 /note= “Xaa at position 87 is Leu or Ser” Modified-site 88 /note= “Xaa at position 88 is Ala or Trp” Modified-site 91 /note= “Xaa at position 91 is Ala or Pro” Modified-site 93 /note= “Xaa at position 93 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg” Modified-site 95 /note= “Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser, or Thr” Modified-site 96 /note= “Xaa at position 96 is Pro or Tyr” Modified-site 97 /note= “Xaa at position 97 is Ile or Val” Modified-site 98 /note= “Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val, or Pro” Modified-site 99 /note= “Xaa at position 99 is Ile, Leu, or Val” Modified-site 100 /note= “Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser” Modified-site 101 /note= “Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Pro, Asn, Ile, Leu, or Tyr” Modified-site 104 /note= “Xaa at position 104 is Trp or Leu” Modified-site 105 /note= “Xaa at position 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His” Modified-site 106 /note= “Xaa at position 106 is Glu or Gly” Modified-site 109 /note= “Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser” Modified-site 112 /note= “Xaa at position 112 is Thr, Val, or Gln” Modified-site 114 /note= “Xaa at position 114 is Tyr or Trp” Modified-site 115 /note= “Xaa at position 115 is Leu or Ala” Modified-site 116 /note= “Xaa at position 116 is Lys, Thr, Val, Trp, Ser, Ala, His, Met, Phe, Tyr, or Ile” Modified-site 117 /note= “Xaa at position 117 is Thr or Ser” Modified-site 120 /note= “Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 121 /note= “Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly” Modified-site 122 /note= “Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 123 /note= “Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 17Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa Xaa Xaa 20 25 30Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa Xaa Ile Leu 35 40 45Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa Phe Xaa Xaa Xaa 50 55 60Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu Xaa Xaa Leu Xaa Xaa65 70 75 80Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Xaa 85 90 95Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa Xaa Phe Xaa Xaa Lys Leu Xaa 100 105 110Phe Xaa Xaa Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu 115 120 125Ser Leu Ala Ile Phe 130 133 amino acids amino acid linear peptide Modified-site /note= “Met- may or may not precede the amino acid in position 1” Modified-site 17 /note= “Xaa at position 17 is Ser, Gly, Asp, or Gln” Modified-site 18 /note= “Xaa at position 18 is Asn, His, or Ile” Modified-site 23 /note= “Xaa at position 23 is Ile, Ala, Leu, or Gly” Modified-site 25 /note= “Xaa at position 25 is Thr, His, or Gln” Modified-site 26 /note= “Xaa at position 26 is His or Ala” Modified-site 29 /note=“Xaa at position 29 is Gln or Asn” Modified-site 30 /note= “Xaa at position 30 is Pro or Gly” Modified-site 32 /note= “Xaa at position 32 is Leu, Arg, Asn, or Ala” Modified-site 34 /note= “Xaa at position 34 is Leu, Val, Ser, Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met” Modified-site 35 /note= “Xaa at position 35 is Leu, Ala, Asn, or Pro” Modified-site 38 /note= “Xaa at position 38 is Asn or Ala” Modified-site 42 /note= “Xaa at position 42 is Gly, Asp, Ser, Ala, Asn, Ile, Leu, Met, Tyr, or Arg” Modified-site 45 /note= “Xaa at position 45 is Gln, Val, Met, Leu, Ala, Asn, Glu, or Lys” Modified-site 46 /note= “Xaa at position 46 is Asp, Phe, Ser, Gln, Glu, His, Val, or Thr” Modified-site 50 /note= “Xaa at position 50 is Glu, Asn, Ser, or Asp” Modified-site 51 /note= “Xaa at position 51 is Asn, Arg, Pro, Thr, or His” Modified-site 55 /note= “Xaa at position 55 is Arg, Leu, or Gly” Modified-site 56 /note= “Xaa at position 56 is Pro, Gly, Ser, Ala, Asn, Val, Leu, or Gln” Modified-site 62 /note= “Xaa at position 62 is Asn, Pro, or Thr” Modified-site 64 /note= “Xaa at position 64 is Ala or Asn” Modified-site 65 /note= “Xaa at position 65 is Val or Thr” Modified-site 67 /note= “Xaa at position 67 is Ser or Phe” Modified-site 68 /note= “Xaa at position 68 is Leu or Phe” Modified-site 69 /note= “Xaa at position 69 is Gln, Ala, Glu, or Arg” Modified-site 76 /note= “Xaa at position 76 is Ser, Val, Asn, Pro, or Gly” Modified-site 77 /note= “Xaa at position 77 is Ile or Leu” Modified-site 79 /note= “Xaa at position 79 is Lys, Asn, Met, Arg, Ile, or Gly” Modified-site 80 /note= “Xaa at position 80 is Asn, Gly, Glu, or Arg” Modified-site 82 /note= “Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Asn, Glu, His, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 87 /note= “Xaa at position 87 is Leu or Ser” Modified-site 88 /note= “Xaa at position 88 is Ala or Trp” Modified-site 91 /note= “Xaa at position 91 is Ala or Pro” Modified-site 93 /note= “Xaa at position 93 is Thr, Asp, or Ala” Modified-site 95 /note= “Xaa at position 95 is His, Pro, Arg, Val, Gly, Asn, Ser, or Thr” Modified-site 98 /note= “Xaa at position 98 is His, Ile, Asn, Ala, Thr, Arg, Gln, Glu, Lys, Met, Ser, Tyr, Val, or Leu” Modified-site 99 /note= “Xaa at position 99 is Ile or Leu” Modified-site 100 /note= “Xaa at position 100 is Lys or Arg” Modified-site 101 /note= “Xaa at position 101 is Asp, Pro, Met, Lys, Thr, His, Pro, Asn, Ile, Leu, or Tyr” Modified-site 105 /note= “Xaa at position 105 is Asn, Pro, Ser, Ile, or Asp” Modified-site 108 /note= “Xaa at position 108 is Arg, Ala, or Ser” Modified-site 109 /note= “Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser” Modified-site 112 /note= “Xaa at position 112 is Thr or Gln” Modified-site 116 /note= “Xaa at position 116 is Lys, Val, Trp, Ala, His, Phe, Tyr, or Ile” Modified-site 117 /note= “Xaa at position 117 is Thr or Ser” Modified-site 120 /note= “Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 121 /note= “Xaa at position 121 is Ala, Ser, Ile, Pro, or Asp” s Modified-site 122 /note= “Xaa at position 122 is Gln, Met, Trp, Phe, Pro, His, Ile, or Tyr” Modified-site 123 /note= “Xaa at position 123 is Ala, Met, Glu, Ser, or Leu” 18Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa Pro Xaa 20 25 30Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu 35 40 45Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala Phe Xaa Arg Xaa 50 55 60Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu Xaa Xaa Leu Xaa Xaa65 70 75 80Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Pro 85 90 95Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa Glu Phe Xaa Xaa Lys Leu Xaa 100 105 110Phe Tyr Leu Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu 115 120 125Ser Leu Ala Ile Phe 130 111 amino acids amino acid linear peptide Modified-site /note= “Met- or Met-Ala- may or may not precede the amino acid in position 1” Modified-site /note= “Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg” Modified-site /note= “Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln” Modified-site /note= “Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys” Modified-site /note= “Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala” Modified-site /note= “Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser, or Val” Modified-site /note= “Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly” Modified-site /note= “Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser or Arg” Modified-site 10 /note= “Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu” Modified-site 11 /note= “Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala” Modified-site 12 /note= “Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp” Modified-site 13 /note= “Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala” Modified-site 14 /note= “Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val, or Trp” Modified-site 15 /note= “Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val” Modified-site 16 /note= “Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys” Modified-site 17 /note= “Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln” Modified-site 18 /note= “Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu” Modified-site 19 /note= “Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu” Modified-site 20 /note= “Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile, or Met” Modified-site 21 /note= “Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val” Modified-site 22 /note= “Xaa at position 22 is Asp, Leu, or Val” Modified-site 23 /note= “Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile” Modified-site 24 /note= “Xaa at position 24 is Asn or Ala” Modified-site 26 /note= “Xaa at position 26 is Leu, Trp, or Arg” Modified-site 27 /note= “Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, or Pro” Modified-site 28 /note= “Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile, or Met” Modified-site 29 /note= “Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly, or Ser” Modified-site 30 /note= “Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala, or Pro” Modified-site 31 /note= “Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His, or Trp” Modified-site 32 /note= “Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val, or Gly” Modified-site 33 /note= “Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His” Modified-site 34 /note= “Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val, or Asn” Modified-site 35 /note= “Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp” Modified-site 36 /note= “Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met, or Gln” Modified-site 37 /note= “Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 38 /note= “Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr” Modified-site 39 /note= “Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met” Modified-site 40 /note= “Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala, or Leu” Modified-site 41 /note= “Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly” Modified-site 42 /note= “Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val, or Lys” Modified-site 43 /note= “Xaa at position 43 is Asn or Gly” Modified-site 44 /note= “Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys” Modified-site 45 /note= “Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg” Modified-site 46 /note= “Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr” Modified-site 47 /note= “Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser” Modified-site 48 /note= “Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile” Modified-site 49 /note= “Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val” Modified-site 50 /note= “Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys” Modified-site 51 /note= “Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser” Modified-site 52 /note= “Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser” Modified-site 53 /note= “Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His” Modified-site 54 /note= “Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His” Modified-site 55 /note= “Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu” Modified-site 56 /note= “Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala” Modified-site 57 /note= “Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn” Modified-site 58 /note= “Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp” Modified-site 59 /note= “Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg” Modified-site 60 /note= “Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala” Modified-site 61 /note= “Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu” Modified-site 62 /note= “Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp” Modified-site 63 /note= “Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu” Modified-site 64 /note= “Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg” Modified-site 65 /note= “Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp” Modified-site 66 /note= “Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg” Modified-site 67 /note= “Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys” Modified-site 68 /note= “Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met, or Val” Modified-site 69 /note= “Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met” Modified-site 70 /note= “Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val” Modified-site 71 /note= “Xaa at position 71 is Leu, Asn, Val, or Gln” Modified-site 72 /note= “Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys” Modified-site 73 /note= “Xaa at position 73 is Leu, Ser, Trp, or Gly” Modified-site 74 /note= “Xaa at position 74 is Ala, Lys, Arg, Val, or Trp” Modified-site 75 /note= “Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser” Modified-site 76 /note= “Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met” Modified-site 77 /note= “Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His” Modified-site 78 /note= “Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile, or Leu” Modified-site 79 /note= “Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg” Modified-site 80 /note= “Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro” Modified-site 81 /note= “Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr” Modified-site 82 /note= “Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr” Modified-site 83 /note= “Xaa at position 83 is Ile, Val, Lys, Ala, or Asn” Modified-site 84 /note= “Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr, or Pro” Modified-site 85 /note= “Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His” Modified-site 86 /note= “Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro” Modified-site 87 /note= “Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln” Modified-site 88 /note= “Xaa at position 88 Gly, Leu, Glu, Lys, Ser, Tyr, or Pro” Modified-site 89 /note= “Xaa at position 89 is Asp or Ser” Modified-site 90 /note= “Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly” Modified-site 91 /note= “Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His” Modified-site 92 /note= “Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro” Modified-site 94 /note= “Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro” Modified-site 95 /note= “Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly” Modified-site 96 /note= “Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala, or Trp” Modified-site 97 /note= “Xaa at position 97 is Leu, Ile, Arg, Asp, or Met” Modified-site 98 /note= “Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe” Modified-site 99 /note= “Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val, or Asn” Modified-site 100 /note= “Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu” Modified-site 101 /note= “Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met” Modified-site 102 /note= “Xaa at position 102 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile” Modified-site 103 /note= “Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro” Modified-site 104 /note= “Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr” Modified-site 105 /note= “Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg” Modified-site 106 /note= “Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val or Gln” Modified-site 107 /note= “Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly” Modified-site 108 /note= “Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 109 /note= “Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 19 Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5 10 15 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 80 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa 85 90 95 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Gln 100 105 110 111 amino acids amino acid linear peptide Modified-site /note= “Met- or Met-Ala- may or may not precede the amino acid in position 1” Modified-site /note= “Xaa at position 3 is Ser, Gly, Asp, Met, or Gln” Modified-site /note= “Xaa at position 4 is Asn, His, Leu,Ile, Phe, Arg, or Gln” Modified-site /note= “Xaa at position 5 is Met, Phe, Ile, Arg, or Ala” Modified-site /note= “Xaa at position 6 is Ile or Pro” Modified-site /note= “Xaa at position 7 is Asp or Glu” Modified-site /note= “Xaa at position 9 is Ile, Val, Ala, Leu, or Gly” Modified-site 10 /note= “Xaa at position 10 is Ile, Val, Phe, or Leu” Modified-site 11 /note= “Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala” Modified-site 12 /note= “Xaa at position 12 is His, Phe, Gly, Arg, or Ala” Modified-site 14 /note= “Xaa at position 14 is Lys, Leu, Gln, Gly, Pro, or Val” Modified-site 15 /note= “Xaa at position 15 is Gln, Asn, Leu, Arg, or Val” Modified-site 16 /note= “Xaa at position 16 is Pro, His, Thr, Gly, or Gln” Modified-site 17 /note= “Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln” Modified-site 18 /note= “Xaa at position 18 is Leu, Arg, Gln, Asn, Gly, Ala or Glu” Modified-site 19 /note= “Xaa at poisiton 19 is Pro, Leu, Gln, Ala, or Glu” Modified-site 20 /note= “Xaa at positon 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met” Modified-site 21 /note= “Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, or Val” Modified-site 22 /note= “Xaa at position 22 is Asp or Leu” Modified-site 23 /note= “Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile” Modified-site 24 /note= “Xaa at position 24 is Asn or Ala” Modified-site 27 /note= “Xaa at position 27 is Asn, Cys, Arg, His, Met, or Pro” Modified-site 28 /note= “Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg” Modified-site 30 /note= “Xaa at position 30 is Asp or Glu” Modified-site 31 /note= “Xaa at position 31 is Gln, Val, Met, Leu, Thr, Lys, Ala, Asn, Glu, Ser, or Trp” Modified-site 32 /note= “Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Ala, Asn, Gln, Glu, His, Ile, Lys, Tyr, Val, or Gly” Modified-site 33 /note= “Xaa at position 33 is Ile, Val, or His” Modified-site 35 /note= “Xaa at position 35 is Met, Asn, or Asp” Modified-site 36 /note= “Xaa at position 36 is Glu, Thr, Ala, Asn, Ser, or Asp” Modified-site 37 /note= “Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 38 /note= “Xaa at position 38 is Asn or Gly” Modified-site 39 /note= “Xaa at position 39 is Leu, Met, or Phe” Modified-site 40 /note= “Xaa at position 40 is Arg, Ala, or Ser” Modified-site 41 /note= “Xaa at position 41 is Arg, Thr, Val, Leu, or Gly” Modified-site 42 /note= “Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Ala, Arg, Asn, Glu, His, Leu, Thr, Val, or Lys” Modified-site 45 /note= “Xaa at position 45 is Glu, Tyr, His, Leu, or Arg” Modified-site 46 /note= “Xaa at position 46 is Ala, Ser, Asn, or Thr” Modified-site 47 /note= “Xaa at position 47 is Phe or Ser” Modified-site 48 /note= “Xaa at position 48 is Asn, Val, Pro, Thr, or Ile” Modified-site 49 /note= “Xaa at position 49 is Arg, Tyr, Lys, Ser, His, or Val” Modified-site 50 /note= “Xaa at position 50 is Ala or Asn” Modified-site 51 /note= “Xaa at position 51 is Val, Thr, Leu, or Ser” Modified-site 52 /note= “Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser” Modified-site 53 /note= “Xaa at position 53 is Ser, Phe, Val, Gly, Asn, Ile, or His” Modified-site 54 /note= “Xaa at position 54 is Leu, Val, Ile, Phe, or His” Modified-site 55 /note= “Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly” Modified-site 56 /note= “Xaa at position 56 is Asn or Pro” Modified-site 57 /note= “Xaa at position 57 is Ala, Met, Pro, Arg, Glu, Thr, or Gln” Modified-site 58 /note= “Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp” Modified-site 59 /note= “Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, Arg, or Pro” Modified-site 60 /note= “Xaa at position 60 is Ile or Met” Modified-site 61 /note= “Xaa at position 61 is Glu, Gly, Asp, Ser, or Gln” Modified-site 62 /note= “Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, Gly, or Asp” Modified-site 63 /note= “Xaa at position 63 is Ile, Ser, or Leu” Modified-site 65 /note= “Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp” Modified-site 66 /note= “Xaa at position 66 is Asn, Val, Gly, Thr, Leu, Glu, or Arg” Modified-site 67 /note= “Xaa at position 67 is Leu or Val” Modified-site 68 /note= “Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 69 /note= “Xaa at position 69 is Pro, Ala, Thr, Trp, or Met” Modified-site 71 /note= “Xaa at position 71 is Leu or Val” Modified-site 73 /note= “Xaa at position 73 is Leu or Ser” Modified-site 74 /note= “Xaa at position 74 is Ala, Arg, or Trp” Modified-site 75 /note= “Xaa at position 75 is Thr, Asp, Glu, His, Asn, or Ser” Modified-site 76 /note= “Xaa at position 76 is Ala, Asp, or Met” Modified-site 77 /note= “Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, or Asp” Modified-site 78 /note= “Xaa at position 78 is Pro or Ser” Modified-site 79 /note= “Xaa at position 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg” Modified-site 81 /note= “Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly, Asn, Ile, Phe, Ser, or Thr” Modified-site 82 /note= “Xaa at position 82 is Pro or Tyr” Modified-site 83 /note= “Xaa at position 83 is Ile, Val, or Ala” Modified-site 84 /note= “Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Arg, Gln, Glu, Lys, Met, Ser, Tyr, Val, or Pro” Modified-site 85 /note= “Xaa at position 85 is Ile, Leu, Val, or Phe” Modified-site 86 /note= “Xaa at position 86 is Lys, Leu, His, Arg, Ile, Gln, Pro, or Ser” Modified-site 87 /note= “Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Asn, Ile, Leu, or Tyr” Modified-site 88 /note= “Xaa at position 88 is Gly, Glu, Lys, or Ser” Modified-site 90 /note= “Xaa at position 90 is Trp, Val, Tyr, Met, or Leu” Modified-site 91 /note= “Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His” Modified-site 92 /note= “Xaa at position 92 is Glu, Ser, Ala, or Gly” Modified-site 94 /note= “Xaa at position 94 is Arg, Ala, Gln, Ser, or Lys” Modified-site 95 /note= “Xaa at position 95 Arg, Thr, Glu, Leu, Ser, or Gly” Modified-site 98 /note= “Xaa at position 98 is Thr, Val, Gln, Glu, His, or Ser” Modified-site 100 /note= “Xaa at position 100 is Tyr or Trp” Modified-site 101 /note= “Xaa at position 101 is Leu or Ala” Modified-site 102 /note= “Xaa at position 102 is Lys, Thr, Met, Val, Trp, Ser, Leu, Ala, Asn, Gln, His, Phe, Tyr, or Ile” Modified-site 103 /note= “Xaa at position 103 is Thr, Ser, or Asn” Modified-site 105 /note= “Xaa at position 105 is Glu, Ser, Pro, Leu, Thr, or Tyr” Modified-site 106 /note= “Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 107 /note= “Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly” Modified-site 108 /note= “Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 109 /note= “Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 20Asn Cys Xaa Xaa Xaa Xaa Xaa Glu Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Glu Xaa Xaa Xaa 20 25 30Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Xaa Xaa 35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu 50 55 60Xaa Xaa Xaa Xaa Xaa Cys Xaa Pro Xaa Xaa Xaa Xaa Xaa Xaa Xaa Arg65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Xaa Phe Xaa Xaa Lys 85 90 95Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Gln Gln 100 105 110 111 amino acids amino acid linear peptide Modified-site /note= “Met- or Met-Ala- may or may not precede the amino acid in position 1” Modified-site /note= “Xaa at position 3 is Ser, Gly, Asp, Met, or Gln” Modified-site /note= “Xaa at position 4 is Asn, His, or Ile” Modified-site /note= “Xaa at position 5 is Met or Ile” Modified-site /note= “Xaa at position 7 is Asp or Glu” Modified-site /note= “Xaa at position 9 is Ile, Ala, Leu, or Gly” Modified-site 10 /note= “Xaa at position 10 is Ile, Val, or Leu” Modified-site 11 /note= “Xaa at position 11 is Thr, His, Gln, or Ala” Modified-site 12 /note= “Xaa at position 12 is His or Ala” Modified-site 15 /note= “Xaa at position 15 is Gln, Asn, or Val” Modified-site 16 /note= “Xaa at position 16 is Pro, Gly, or Gln” Modified-site 17 /note= “Xaa at position 17 is Pro, Asp, Gly, or Gln” Modified-site 18 /note= “Xaa at position 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu” Modified-site 19 /note= “Xaa at position 19 is Pro or Glu” Modified-site 20 /note= “Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met” Modified-site 21 /note= “Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, or Val” Modified-site 23 /note= “Xaa at position 23 is Phe, Ser, Pro, or Trp” Modified-site 24 /note= “Xaa at position 24 is Asn or Ala” Modified-site 28 /note= “Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg” Modified-site 30 /note= “Xaa at position 30 is Asp or Glu” Modified-site 31 /note= “Xaa at position 31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser, or Lys” Modified-site 32 /note= “Xaa at position 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys, Tyr, Val, or Cys” Modified-site 36 /note= “Xaa at position 36 is Glu, Ala, Asn, Ser, or Asp” Modified-site 37 /note= “Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His” Modified-site 40 /note= “Xaa at position 40 is Arg or Ala” Modified-site 41 /note= “Xaa at position 41 is Arg, Thr, Val, Leu, or Gly” Modified-site 42 /note= “Xaa at position 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val, or Lys” Modified-site 46 /note= “Xaa at position 46 is Ala or Ser” Modified-site 48 /note= “Xaa at position 48 is Asn, Pro, Thr, or Ile” Modified-site 49 /note= “Xaa at position 49 is Arg or Lys” Modified-site 50 /note= “Xaa at position 50 is Ala or Asn” Modified-site 51 /note= “Xaa at position 51 is Val or Thr” Modified-site 52 /note= “Xaa at position 52 is Lys or Arg” Modified-site 53 /note= “Xaa at position 53 is Ser, Phe, or His” Modified-site 54 /note= “Xaa at position 54 is Leu, Ile, Phe, or His” Modified-site 55 /note= “Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly” Modified-site 57 /note= “Xaa at position 57 is Ala, Pro, or Arg” Modified-site 58 /note= “Xaa at position 58 is Ser, Glu, Arg, or Asp” Modified-site 59 /note= “Xaa at position 59 is Ala or Leu” Modified-site 62 /note= “Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, or Gly” Modified-site 63 /note= “Xaa at position 63 is Ile or Leu” Modified-site 65 /note= “Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp” Modified-site 66 /note= “Xaa at position 66 is Asn, Gly, Glu, or Arg” Modified-site 68 /note= “Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 69 /note= “Xaa at position 69 is Pro or Thr” Modified-site 71 /note= “Xaa at position 71 is Leu or Val” Modified-site 73 /note= “Xaa at position 73 is Leu or Ser” Modified-site 74 /note= “Xaa at position 74 is Ala or Trp” Modified-site 77 /note= “Xaa at position 77 is Ala or Pro” Modified-site 79 /note= “Xaa at position 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg” Modified-site 81 /note= “Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser, or Thr” Modified-site 82 /note= “Xaa at position 82 is Pro or Tyr” Modified-site 83 /note= “Xaa at position 83 is Ile or Val” Modified-site 84 /note= “Xaa at position 84 is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val, or Pro” Modified-site 85 /note= “Xaa at position 85 is Ile, Leu, or Val” Modified-site 86 /note= “Xaa at position 86 is Lys, Arg, Ile, Gln, Pro, or Ser” Modified-site 87 /note= “Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Asn, Ile, Leu, or Tyr” Modified-site 90 /note= “Xaa at position 90 is Trp or Leu” Modified-site 91 /note=“Xaa at position 91 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His” Modified-site 92 /note= “Xaa at position 92 is Glu or Gly” Modified-site 94 /note= “Xaa at position 94 is Arg, Ala, or Ser” Modified-site 95 /note= “Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser” Modified-site 98 /note= “Xaa at position 98 is Thr, Val, or Gln” Modified-site 100 /note= “Xaa at position 100 is Tyr or Trp” Modified-site 101 /note= “Xaa at position 101 is Leu or Ala” Modified-site 102 /note= “Xaa at position 102 is Lys, Thr, Val, Trp, Ser, Ala, His, Met, Phe, Tyr, or Ile” Modified-site 103 /note= “Xaa at position 103 is Thr or Ser” Modified-site 106 /note= “Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 107 /note= “Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly” Modified-site 108 /note= “Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys” Modified-site 109 /note= “Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu” 21Asn Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa Xaa 20 25 30Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa Phe Xaa 35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu Xaa Xaa Leu 50 55 60Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa Xaa Phe Xaa Xaa Lys 85 90 95Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln 100 105 110 111 amino acids amino acid linear peptide Modified-site /note= “Met- or Met-Ala- may or may not precede the amino acid in position 1” Modified-site /note= “Xaa at position 3 is Ser, Gly, Asp, or Gln” Modified-site /note= “Xaa at position 4 is Asn, His, or Ile” Modified-site /note= “Xaa at position 9 is Ile, Ala, Leu, or Gly” Modified-site 11 /note= “Xaa at position 11 is Thr, His, or Gln” Modified-site 12 /note= “Xaa at position 12 is His or Ala” Modified-site 15 /note= “Xaa at position 15 is Gln or Asn” Modified-site 16 /note= “Xaa at position 16 is Pro or Gly” Modified-site 18 /note= “Xaa at position 18 is Leu, Arg, Asn, or Ala” Modified-site 20 /note= “Xaa at position 20 is Leu, Val, Ser, Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met” Modified-site 21 /note= “Xaa at position 21 is Leu, Ala, Asn, or Pro” Modified-site 24 /note= “Xaa at position 24 is Asn or Ala” Modified-site 28 /note= “Xaa at position 28 is Gly, Asp, Ser, Ala, Asn, Ile, Leu, Met, Tyr, or Arg” Modified-site 31 /note= “Xaa at position 31 is Gln, Val, Met, Leu, Ala, Asn, Glu, or Lys” Modified-site 32 /note= “Xaa at position 32 is Asp, Phe, Ser, Ala, Gln, Glu, His, Val, or Thr” Modified-site 36 /note= “Xaa at position 36 is Glu, Asn, Ser, or Asp” Modified-site 37 /note= “Xaa at position 37 is Asn, Arg, Pro, Thr, or His” Modified-site 41 /note= “Xaa at position 41 is Arg, Leu, or Gly” Modified-site 42 /note= “Xaa at position 42 is Pro, Gly, Ser, Ala, Asn, Val, Leu, or Gln” Modified-site 48 /note= “Xaa at position 48 is Asn, Pro, or Thr” Modified-site 50 /note= “Xaa at position 50 is Ala or Asn” Modified-site 51 /note= “Xaa at position 51 is Val or Thr” Modified-site 53 /note= “Xaa at position 53 is Ser or Phe” Modified-site 54 /note= “Xaa at position 54 is Leu or Phe” Modified-site 55 /note= “Xaa at position 55 is Gln, Ala, Glu, or Arg” Modified-site 62 /note= “Xaa at position 62 is Ser, Val, Asn, Pro, or Gly” Modified-site 63 /note= “Xaa at position 63 is Ile or Leu” Modified-site 65 /note= “Xaa at position 65 is Lys, Asn, Met, Arg, Ile, or Gly” Modified-site 66 /note= “Xaa at position 66 is Asn, Gly, Glu, or Arg” Modified-site 68 /note= “Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Asn, Glu, His, Met, Phe, Ser, Thr, Tyr, or Val” Modified-site 73 /note= “Xaa at position 73 is Leu or Ser” Modified-site 74 /note= “Xaa at position 74 is Ala or Trp” Modified-site 77 /note= “Xaa at position 77 is Ala or Pro” Modified-site 79 /note= “Xaa at position 79 is Thr, Asp, or Ala” Modified-site 81 /note= “Xaa at position 81 is His, Pro, Arg, Val, Gly, Asn, Ser, or Thr” Modified-site 84 /note= “Xaa at position 84 is His, Ile, Asn, Ala, Thr, Arg, Gln, Glu, Lys, Met, Ser, Tyr, Val, or Leu” Modified-site 85 /note= “Xaa at position 85 is Ile or Leu” Modified-site 86 /note= “Xaa at position 86 is Lys or Arg” Modified-site 87 /note= “Xaa at position 87 is Asp, Pro, Met, Lys, His, Pro, Asn, Ile, Leu, or Tyr” Modified-site 91 /note= “Xaa at position 91 is Asn, Pro, Ser, Ile, or Asp” Modified-site 94 /note= “Xaa at position 94 is Arg, Ala, or Ser” Modified-site 95 /note= “Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser” Modified-site 98 /note= “Xaa at position 98 is Thr or Gln” Modified-site 102 /note= “Xaa at position 102 is Lys, Val, Trp, or Ile” Modified-site 103 /note= “Xaa at position 103 is Thr, Ala, His, Phe, Tyr, or Ser” Modified-site 106 /note= “Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln” Modified-site 107 /note= “Xaa at position 107 is Ala, Ser, Ile, Pro, or Asp” Modified-site 108 /note= “Xaa at position 108 is Gln, Met, Trp, Phe, Pro, His, Ile, or Tyr” Modified-site 109 /note= “Xaa at position 109 is Ala, Met, Glu, Ser, or Leu” 22Asn Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa1 5 10 15Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa 20 25 30Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala Phe Xaa 35 40 45Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu Xaa Xaa Leu 50 55 60Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa Glu Phe Xaa Xaa Lys 85 90 95Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln 100 105 110 27 base pairs nucleic acid single linear DNA (synthetic) 23AACAACCTCA ATGCTGAAGA CGTTGAT 27 18 base pairs nucleic acid single linear DNA (synthetic) 24ATCAACGTCT TCAGCATT 18 27 base pairs nucleic acid single linear DNA (synthetic) 25AACAACCTCA ATTCTGAAGA CATGGAT 27 18 base pairs nucleic acid single linear DNA (synthetic) 26ATCCATGTCT TCAGAATT 18 22 base pairs nucleic acid single linear DNA (synthetic) 27CATGGGAACC ATATGTCAGG AT 22 18 base pairs nucleic acid single linear DNA (synthetic) 28ATCCTGACAT ATGGTTCC 18 16 base pairs nucleic acid single linear DNA (synthetic) 29TGAACCATAT GTCAGG 16 24 base pairs nucleic acid single linear DNA (synthetic) 30AATTCCTGAC ATATGGTTCA TGCA 24 20 base pairs nucleic acid single linear DNA (synthetic) 31AATTCGAACC ATATGTCAGA 20 20 base pairs nucleic acid single linear DNA (synthetic) 32AGCTTCTGAC ATATGGTTCG 20 22 base pairs nucleic acid single linear DNA (synthetic) 33ATCGAACCAT ATGTCAGATG CA 22 18 base pairs nucleic acid single linear DNA (synthetic) 34TCTGACATAT GGTTCGAT 18 36 base pairs nucleic acid single linear DNA (synthetic) 35ATCCTGATGG AACGAAACCT TCGACTTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 36AAGTCGAAGG TTTCGTTCCA TCAGGAT 27 36 base pairs nucleic acid single linear DNA (synthetic) 37ATCCTGATGG AACGAAACCT TCGAACTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 38AGTTCGAAGG TTTCGTTCCA TCAGGAT 27 24 base pairs nucleic acid single linear DNA (synthetic) 39CTCGCATTCG TAAGGGCTGT CAAG 24 24 base pairs nucleic acid single linear DNA (synthetic) 40CCTTACGAAT GCGAGCAGGT TTGG 24 24 base pairs nucleic acid single linear DNA (synthetic) 41GAGAGCTTCG TAAGGGCTGT CAAG 24 24 base pairs nucleic acid single linear DNA (synthetic) 42CCTTACGAAG CTCTCCAGGT TTGG 24 15 base pairs nucleic acid single linear DNA (synthetic) 43CACTTAGAAA ATGCA 15 20 base pairs nucleic acid single linear DNA (synthetic) 44TTTTCTAAGT GCTTGACAGC 20 15 base pairs nucleic acid single linear DNA (synthetic) 45AACTTAGAAA ATGCA 15 20 base pairs nucleic acid single linear DNA (synthetic) 46TTTTCTAAGT TCTTGACAGC 20 48 base pairs nucleic acid single linear DNA (synthetic) 47GGTGATTGGA TGTCGAGAGG GTGCGGCCGT GGCAGAGGGC AGACATGG 48 48 base pairs nucleic acid single linear DNA (synthetic) 48CTGCCCTCTG CCACGGCCGC ACCCTCTCGA CATCCAATCA CCATCAAG 48 48 base pairs nucleic acid single linear DNA (synthetic) 49GATGATTGGA TGTCGAGAGG GTGCGGCCGT GGCAGAGGGC AGACATGG 48 48 base pairs nucleic acid single linear DNA (synthetic) 50CTGCCCTCTG CCACGGCCGC ACCCTCTCGA CATCCAATCA TCATCAAG 48 18 base pairs nucleic acid single linear DNA (synthetic) 51TACGAGATTA CGAAGAAT 18 18 base pairs nucleic acid single linear DNA (synthetic) 52CGTAATCTCG TACCATGT 18 18 base pairs nucleic acid single linear DNA (synthetic) 53TTGGAGATTA CGAAGAAT 18 18 base pairs nucleic acid single linear DNA (synthetic) 54CGTAATCTCC AACCATGT 18 19 base pairs nucleic acid single linear DNA (synthetic) 55TGCCTCAATA CCTGATGCA 19 21 base pairs nucleic acid single linear DNA (synthetic) 56TCAGGTATTG AGGCAATTCT T 21 26 base pairs nucleic acid single linear DNA (synthetic) 57AATTCTTGCC AGTCACCTGC CTTGAT 26 16 base pairs nucleic acid single linear DNA (synthetic) 58GCAGGTGACT GGCAAG 16 32 base pairs nucleic acid single linear DNA (synthetic) 59AATTCCGGGA AAAACTGACG TTCTATCTGG TT 32 37 base pairs nucleic acid single linear DNA (synthetic) 60CTCAAGGGAA ACCAGATAGA ACGTCAGTTT TTCCCGG 37 32 base pairs nucleic acid single linear DNA (synthetic) 61ACCCTTGAGC ACGCGCAGGA ACAACAGTAA TA 32 27 base pairs nucleic acid single linear DNA (synthetic) 62AGCTTATTAC TGTTGTTCCT GCGCGTG 27 32 base pairs nucleic acid single linear DNA (synthetic) 63ACCCTTGAGC AAGCGCAGGA ACAACAGTAA TA 32 27 base pairs nucleic acid single linear DNA (synthetic) 64AGCTTATTAC TGTTGTTCCT GCGCTTG 27 111 amino acids amino acid linear peptide 65Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 66Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 67Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 68Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro1 5 10 15Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 69Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val 35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 70Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 71Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val 35 40 45Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 72Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu 50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 73Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu 50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 74Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys 85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln 100 105 110 111 amino acids amino acid linear peptide 75Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys 85 90 95Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln 100 105 110 111 amino acids amino acid linear peptide 76Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu 50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys 85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln 100 105 110 111 amino acids amino acid linear peptide 77Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu 50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys 85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln 100 105 110 111 amino acids amino acid linear peptide 78Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu 50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys 85 90 95Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln 100 105 110 111 amino acids amino acid linear peptide 79Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 80Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val 35 40 45Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 111 amino acids amino acid linear peptide 81Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro1 5 10 15Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp 20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val 35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 113 amino acids amino acid linear peptide 82Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 83Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 84Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 85Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 86Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 87Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 88Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 89Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 90Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 91Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 92Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 93Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 94Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 95Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 96Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln 100 105 110Gln 339 base pairs nucleic acid double linear DNA (genomic) 97ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 98ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 99ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTTCCCTTGA GCACGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 100ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 101ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 102ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTTCCCTTGA GCACGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 103ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 104ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 105ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTTCCCTTGA GCACGCGCAG GAACAACAG 339 333 base pairs nucleic acid double linear DNA (genomic) 106AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGAGACCACC TGCACCTTTG 60CTGGACCCGA ACAACCTCAA TGCTGAAGAC GTCGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 107AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGAGACCACC TAACCCTTTG 60CTGGACCCGA ACAACCTCAA TTCTGAAGAC ATGGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 108AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGGTTCCACC TGCACCTTTG 60CTGGACAGTA ACAACCTCAA TTCCGAAGAC ATGGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 109AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAACG AAACCTTCGA 120CTTCCAAACC TGCTCGCATT CGTAAGGGCT GTCAAGAACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 110AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAACG AAACCTTCGA 120CTTCCAAACC TGGAGAGCTT CGTAAGGGCT GTCAAGAACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 111AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAACG AAACCTTCGA 120ACTCCAAACC TGCTCGCATT CGTAAGGGCT GTCAAGCACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 112AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGGTATT 180GAGGCAATTC TTCGTAATCT CCAACCATGT CTGCCCTCTG CCACGGCCGC ACCCTCTCGA 240CATCCAATCA TCATCAAGGC AGGTGACTGG CAAGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 113AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGGTATT 180GAGGCAATTC TTCGTAATCT CGTACCATGT CTGCCCTCTG CCACGGCCGC ACCCTCTCGA 240CATCCAATCA CCATCAAGGC AGGTGACTGG CAAGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 114AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GGGAAAAACT GACGTTCTAT 300CTGGTTACCC TTGAGCAAGC GCAGGAACAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 115AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GGGAAAAACT GACGTTCTAT 300CTGGTTTCCC TTGAGCACGC GCAGGAACAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 116AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGAGACCACC TGCACCTTTG 60CTGGACCCGA ACAACCTCAA TGCTGAAGAC GTCGATATCC TGATGGAACG AAACCTTCGA 120CTTCCAAACC TGGAGAGCTT CGTAAGGGCT GTCAAGAACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 117AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGAGACCACC TAACCCTTTG 60CTGGACCCGA ACAACCTCAA TTCTGAAGAC ATGGATATCC TGATGGAACG AAACCTTCGA 120ACTCCAAACC TGCTCGCATT CGTAAGGGCT GTCAAGCACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 118AACTGCTCTA TAATGATCGA TGAAATTATA CATCACTTAA AGGTTCCACC TGCACCTTTG 60CTGGACAGTA ACAACCTCAA TTCCGAAGAC ATGGATATCC TGATGGAACG AAACCTTCGA 120CTTCCAAACC TGCTCGCATT CGTAAGGGCT GTCAAGAACT TAGAAAATGC ATCAGCAATT 180GAGAGCATTC TTAAAAATCT CCTGCCATGT CTGCCCCTGG CCACGGCCGC ACCCACGCGA 240CATCCAATCC ATATCAAGGA CGGTGACTGG AATGAATTCC GTCGTAAACT GACCTTCTAT 300CTGAAAACCT TGGAGAACGC GCAGGCTCAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 119AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGGTATT 180GAGGCAATTC TTCGTAATCT CCAACCATGT CTGCCCTCTG CCACGGCCGC ACCCTCTCGA 240CATCCAATCA TCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GACGTTCTAT 300CTGGTTACCC TTGAGCAAGC GCAGGAACAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 120AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGGTATT 180GAGGCAATTC TTCGTAATCT CGTACCATGT CTGCCCTCTG CCACGGCCGC ACCCTCTCGA 240CATCCAATCA CCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GACGTTCTAT 300CTGGTTACCC TTGAGCAAGC GCAGGAACAA CAG 333 333 base pairs nucleic acid double linear DNA (genomic) 121AACTGCTCTA ACATGATCGA TGAAATCATC ACCCACCTGA AGCAGCCACC GCTGCCGCTG 60CTGGACTTCA ACAACCTCAA TGGTGAAGAC CAAGATATCC TGATGGAAAA TAACCTTCGT 120CGTCCAAACC TCGAGGCATT CAACCGTGCT GTCAAGTCTC TGCAGAATGC ATCAGGTATT 180GAGGCAATTC TTCGTAATCT CGTACCATGT CTGCCCTCTG CCACGGCCGC ACCCTCTCGA 240CATCCAATCA CCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GACGTTCTAT 300CTGGTTTCCC TTGAGCACGC GCAGGAACAA CAG 333 339 base pairs nucleic acid double linear DNA (genomic) 122ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 123ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 124ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 125ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC 120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 126ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC 120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 127ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC 120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCGTA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCACCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTTCCCTTGA GCACGCGCAG GAACAACAG 339 134 amino acids amino acid linear peptide 128Met Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro 20 25 30Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile 35 40 45Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg 50 55 60Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys65 70 75 80Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His 85 90 95Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu 100 105 110Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln Thr Thr 115 120 125Leu Ser Leu Ala Ile Phe 130 133 amino acids amino acid linear peptide Modified-site /note= “Met- may or may not precede the amino acid in position 1” Modified-site 18 /note= “Xaa at position 18 is Asn or Ile” Modified-site 19 /note= “Xaa at position 19 is Met, Ala, or Ile” Modified-site 20 /note= “Xaa at position 20 is Ile, Pro, or Leu” Modified-site 23 /note= “Xaa at position 23 is Ile, Ala, or Leu” Modified-site 25 /note= “Xaa at position 25 is Thr or His” Modified-site 29 /note= “Xaa at position 29 is Gln, Arg, Val, or Leu” Modified-site 32 /note= “Xaa at position 32 is Leu, Ala, Asn, or Arg” Modified-site 34 /note= “Xaa at position 34 is Leu or Ser” Modified-site 37 /note= “Xaa at position 37 is Phe, Pro, or Ser” Modified-site ; 38 /note= “Xaa at position 38 is Asn or Ala” Modified-site 42 /note= “Xaa at position 42 is Gly, Ala, Ser, Asp, or Asn” Modified-site 45 /note= “Xaa at position 45 is Gln, Val, or Met” Modified-site 46 /note= “Xaa at position 46 is Asp or Ser” Modified-site 49 /note= “Xaa at position 49 is Met, Ile, Leu, or Asp” Modified-site 50 /note= “Xaa at position 50 is Glu or Asp” Modified-site 51 /note= “Xaa at position 51 is Asn, Arg, or Ser” Modified-site 55 /note= “Xaa at position 55 is Arg, Leu, or Thr” Modified-site 56 /note= “Xaa at position 56 is Pro or Ser” Modified-site 59 /note= “Xaa at position 59 is Glu or Leu” Modified-site 60 /note= “Xaa at position 60 is Ala or Ser” Modified-site 62 /note= “Xaa at position 62 is Asn Val, or Pro” Modified-site 63 /note= “Xaa at position 63 is Arg or His” Modified-site 65 /note= “Xaa at position 65 is Val or Ser” Modified-site 67 /note= “Xaa at position 67 is Ser, Asn, His, or Gly” Modified-site 69 /note= “Xaa at position 69 is Gln or Glu” Modified-site 73 /note= “Xaa at position 73 is Ala or Gly” Modified-site 76 /note= “Xaa at position 76 is Ser, Ala, or Pro” Modified-site 79 /note= “Xaa at position 79 is Lys, Arg, or Ser” Modified-site 82 /note= “Xaa at position 82 is Leu, Glu, Val, or Trp” Modified-site 85 /note= “Xaa at position 85 is Leu or Val” Modified-site 87 /note= “Xaa at position 87 is Leu, Ser, or Trp” Modified-site 88 /note= “Xaa at position 88 is Ala or Trp” Modified-site 91 /note= “Xaa at position 91 is Ala or Pro” Modified-site 93 /note= “Xaa at position 93 is Pro or Ser” Modified-site 95 /note= “Xaa at position 95 is His or Thr” Modified-site 98 /note= “Xaa at position 98 is His, Ile, or Thr” Modified-site 100 /note= “Xaa at position 100 is Lys or Arg” Modified-site 101 /note= “Xaa at position 101 is Asp, Ala, or Met” Modified-site 105 /note= “Xaa at position 105 is Asn or Gln” Modified-site 109 /note= “Xaa at position 109 is Arg, Glu, or Leu” Modified-site 112 /note= “Xaa at position 112 is Thr or Gln” Modified-site 116 /note= “Xaa at position 116 is Lys, Val, Trp, or Ser” Modified-site 117 /note= “Xaa at position 117 is Thr or Ser” Modified-site 120 /note= “Xaa at position 120 is Asn, Gln, or His” Modified-site 123 /note= “Xaa at position 123 is Ala or Glu” 129Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Ser Xaa Xaa Xaa Asp Glu Xaa Ile Xaa His Leu Lys Xaa Pro Pro Xaa 20 25 30Pro Xaa Leu Asp Xaa Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu 35 40 45Xaa Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa Ala 50 55 60Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa Ile Leu Xaa Asn65 70 75 80Leu Xaa Pro Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Pro 85 90 95Ile Xaa Ile Xaa Xaa Gly Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa 100 105 110Phe Tyr Leu Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln Thr Thr Leu 115 120 125Ser Leu Ala Ile Phe 130 111 amino acids amino acid linear peptide Modified-site /note= “Met- or Met-Ala may or may not precede the amino acid in position 1” Modified-site /note= “Xaa at position 4 is Asn or Ile” Modified-site /note= “Xaa at position 5 is Met, Ala, or Ile” Modified-site /note= “Xaa at position 6 is Ile, Pro, or Leu” Modified-site /note= “Xaa at position 9 is Ile, Ala, or Leu” Modified-site 11 /note= “Xaa at position 11 is Thr or His” Modified-site 15 /note= “Xaa at position 15 is Gln, Arg, Val, or Leu” Modified-site 18 /note= “Xaa at position 18 is Leu, Ala, Asn, or Arg” Modified-site 20 /note= “Xaa at position 20 is Leu or Ser” Modified-site 23 /note= “Xaa at position 23 is Phe, Pro, or Ser” Modified-site 24 /note= “Xaa at position 24 is Asn or Ala” Modified-site 28 /note= “Xaa at position 28 is Gly, Ala, Ser, Asp, or Asn” Modified-site 31 /note= “Xaa at position 31 is Gln, Val, or Met” Modified-site 32 /note= “Xaa at position 32 is Asp or Ser” Modified-site 35 /note= “Xaa at position 35 is Met, Ile, Leu, or Asp” Modified-site 36 /note= “Xaa at position 36 is Glu or Asp” Modified-site 37 /note= “Xaa at position 37 is Asn, Arg, or Ser” Modified-site 41 /note= “Xaa at position 41 is Arg, Leu, or Thr” Modified-site 42 /note= “Xaa at position 42 is Pro or Ser” Modified-site 45 /note= “Xaa at position 45 is Glu or Leu” Modified-site 46 /note= “Xaa at position 46 is Ala or Ser” Modified-site 48 /note= “Xaa at position 48 is Asn, Val, or Pro” Modified-site 49 /note= “Xaa at position 49 is Arg or His” Modified-site 51 /note= “Xaa at position 51 is Val or Ser” Modified-site 53 /note= “Xaa at position 53 is Ser, Asn, His, or Gly” Modified-site 55 /note= “Xaa at position 55 is Gln or Glu” Modified-site 59 /note= “Xaa at position 59 is Ala or Gly” Modified-site 62 /note= “Xaa at position 62 is Ser, Ala, or Pro” Modified-site 65 /note= “Xaa at position 65 is Lys, Arg, or Ser” Modified-site 67 /note= “Xaa at position 67 is Leu, Glu, or Val” Modified-site 68 /note= “Xaa at position 68 is Leu, Glu, Val, or Trp” Modified-site 71 /note= “Xaa at position 71 is Leu or Val” Modified-site 73 /note= “Xaa at position 73 is Leu, Ser, or Trp” Modified-site 74 /note= “Xaa at position 74 is Ala or Trp” Modified-site 77 /note= “Xaa at position 77 is Ala or Pro” Modified-site 79 /note= “Xaa at position 79 is Pro or Ser” Modified-site 81 /note= “Xaa at position 81 is His or Thr” Modified-site 84 /note= “Xaa at position 84 is His, Ile, or Thr” Modified-site 86 /note= “Xaa at position 86 is Lys or Arg” Modified-site 87 /note= “Xaa at position 87 is Asp, Ala, or Met” Modified-site 91 /note= “Xaa at position 91 is Asn or Glu” Modified-site 95 /note= “Xaa at position 95 is Arg, Glu, or Leu” Modified-site 98 /note= “Xaa at position 98 is Thr or Gln” Modified-site 102 /note= “Xaa at position 102 is Lys, Val, Trp, or Ser” Modified-site 103 /note= “Xaa at position 103 is Thr or Ser” Modified-site 106 /note= “Xaa at position 106 is Asn, Gln, or His” Modified-site 109 /note= “Xaa at position 109 is Ala or Glu” 130Asn Cys Ser Xaa Xaa Xaa Asp Glu Xaa Ile Xaa His Leu Lys Xaa Pro1 5 10 15Pro Xaa Pro Xaa Leu Asp Xaa Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa 20 25 30Ile Leu Xaa Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa 35 40 45Xaa Ala Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa Ile Leu 50 55 60Xaa Asn Xaa Xaa Pro Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Pro Ile Xaa Ile Xaa Xaa Gly Asp Trp Xaa Glu Phe Arg Xaa Lys 85 90 95Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln 100 105 110 58 base pairs nucleic acid single linear DNA (synthetic) 131CTAGCCACGG CCGCACCCAC GCGACATCCA ATCCATATCA AGGACGGTGA CTGGAATG 58 58 base pairs nucleic acid single linear DNA (synthetic) 132TTAACATTCC AGTCACCGTC CTTGATATGG ATTGGATGTC GCGTGGGTGC GGCCGTGG 58 29 base pairs nucleic acid double linear DNA (genomic) 133AAGGAGATAT ATCCATGAAC TGCTCTAAC 29 5 amino acids amino acid linear peptide 134Met Asn Cys Ser Asn1 5 120 amino acids amino acid linear peptide 135Met Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln1 5 10 15Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln 20 25 30Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe 35 40 45Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile 50 55 60Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr65 70 75 80Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg 85 90 95Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110Thr Thr Leu Arg Leu Ala Ile Phe 115 120 71 base pairs nucleic acid single linear DNA (synthetic) 136AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGA 60CCACTCTGTC G 71 71 base pairs nucleic acid single linear DNA (synthetic) 137CTAGCGACAG AGTGGTCTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TAGAAGGTCA 60GTTTACGACG G 71 112 amino acids amino acid linear peptide 138Met Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln1 5 10 15Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln 20 25 30Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe 35 40 45Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile 50 55 60Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr65 70 75 80Arg His Pro Ile His Ile Lys Ala Gly Asp Trp Asn Glu Phe Arg Arg 85 90 95Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 75 amino acids amino acid linear peptide 139Met Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln1 5 10 15Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln 20 25 30Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe 35 40 45Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile 50 55 60Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala65 70 75 58 base pairs nucleic acid single linear DNA (synthetic) 140CTAGCCACGG CCGCACCCAC GCGACATCCA ATCCATATCA AGGCTGGTGA CTGGAATG 58 58 base pairs nucleic acid single linear DNA (synthetic) 141AATTCATTCC AGTCACCAGC CTTGATATGG ATTGGATGTC GCGTGGGTGC GGCCGTGG 58 64 base pairs nucleic acid single linear DNA (synthetic) 142AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT 60AATA 64 64 base pairs nucleic acid single linear DNA (synthetic) 143AGCTTATTAC TGTTGAGCCT GCGCGTTCTC CAAGGTTTTC AGATAGAAGG TCAGTTTACG 60ACGG 64 408 base pairs nucleic acid double linear DNA (genomic) 144ATGGCTCCAA TGACTCAGAC TACTTCTCTT AAGACTTCTT GGGTTAACTG CTCTAACATG 60ATCGATGAAA TTATAACACA CTTAAAGCAG CCACCTTTGC CTTTGCTGGA CTTCAACAAC 120CTCAATGGGG AAGACCAAGA CATTCTGATG GAAAATAACC TTCGAAGGCC AAACCTGGAG 180GCATTCAACA GGGCTGTCAA GAGTTTACAG AATGCATCAG CAATTGAGAG CATTCTTAAA 240AATCTCCTGC CATGTCTGCC CCTGGCCACG GCCGCACCCA CGCGACATCC AATCCATATC 300AAGGACGGTG ACTGGAATGA ATTCCGTCGT AAACTGACCT TCTATCTGAA AACCTTGGAG 360AACGCGCAGG CTCAACAGAC CACTCTGTCG CTAGCGATCT TTTAATAA 408 157 base pairs nucleic acid double linear DNA (genomic) CDS 1..156 145ATC GAT GAA ATC ATC ACC CAC CTG AAG CAG CCA CCG CTG CCG CTG CTG 48Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu 1 5 10 15GAC TTC AAC AAC CTC AAT GGT GAA GAC CAA GAT ATC CTG ATG GAA AAT 96Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn 20 25 30AAC CTT CGT CGT CCA AAC CTC GAG GCA TTC AAC CGT GCT GTC AAG TCT 144Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser 35 40 45CTG CAG AAT GCA T 157Leu Gln Asn Ala 50 52 amino acids amino acid linear protein 146Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu 1 5 10 15Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn 20 25 30Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser 35 40 45Leu Gln Asn Ala 50 414 base pairs nucleic acid double linear DNA (genomic) 147CCATGGCTCC AATGACTCAG ACTACTTCTC TTAAGACTTC TTGGGTTAAC TGCTCTAACA 60TGATCGATGA AATTATAACA CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTCAACA 120ACCTCAATGG GGAAGACCAA GACATTCTGA TGGAAAATAA CCTTCGAAGG CCAAACCTGG 180AGGCATTCAA CAGGGCTGTC AAGAGTTTAC AGAATGCATC AGCAATTGAG AGCATTCTTA 240AAAATCTCCT GCCATGTCTG CCCCTGGCCA CGGCCGCACC CACGCGACAT CCAATCCATA 300TCAAGGACGG TGACTGGAAT GAATTCCGTC GTAAACTGAC CTTCTATCTG AAAACCTTGG 360AGAACGCGCA GGCTCAACAG ACCACTCTGT CGCTAGCGAT CTTTTAATAA GCTT 414 414 base pairs nucleic acid double linear DNA (genomic) 148AAGCTTATTA AAAGATCGCT AGCGACAGAG TGGTCTGTTG AGCCTGCGCG TTCTCCAAGG 60TTTTCAGATA GAAGGTCAGT TTACGACGGA ATTCATTCCA GTCACCGTCC TTGATATGGA 120TTGGATGTCG CGTGGGTGCG GCCGTGGCCA GGGGCAGACA TGGCAGGAGA TTTTTAAGAA 180TGCTCTCAAT TGCTGATGCA TTCTGTAAAC TCTTGACAGC CCTGTTGAAT GCCTCCAGGT 240TTGGCCTTCG AAGGTTATTT TCCATCAGAA TGTCTTGGTC TTCCCCATTG AGGTTGTTGA 300AGTCCAGCAA AGGCAAAGGT GGCTGCTTTA AGTGTGTTAT AATTTCATCG ATCATGTTAG 360AGCAGTTAAC CCAAGAAGTC TTAAGAGAAG TAGTCTGAGT CATTGGAGCC ATGG 414 81 base pairs nucleic acid double linear DNA (genomic) 149ATGATGATTA CTCTGCGCAA ACTTCCTCTG GCGGTTGCCG TCGCAGCGGG CGTAATGTCT 60GCTCAGGCCA TGGCTAACTG C 81 81 base pairs nucleic acid double linear DNA (genomic) 150GCAGTTAGCC ATGGCCTGAG CAGACATTAC GCCCGCTGCG ACGGCAACCG CCAGAGGAAG 60TTTGCGCAGA GTAATCATCA T 81 24 base pairs nucleic acid single linear DNA (synthetic) 151CATGGCTAAC TGCTCTAACA TGAT 24 22 base pairs nucleic acid single linear DNA (synthetic) 152CGATCATGTT AGAGCAGTTA GC 22 12 base pairs nucleic acid double linear DNA (genomic) 153ATGGCTAACT GC 12 4 amino acids amino acid linear peptide 154Met Ala Asn Cys1 34 base pairs nucleic acid single linear DNA (synthetic) 155GCCGATACCG CGGCATACTC CCACCATTCA GAGA 34 33 base pairs nucleic acid single linear DNA (synthetic) 156GCCGATAAGA TCTAAAACGG GTATGGAGAA ACA 33 30 base pairs nucleic acid single linear DNA (synthetic) 157ATAGTCTTCC CCAGATATCT AACGCTTGAG 30 24 base pairs nucleic acid single linear DNA (synthetic) 158CAATACCTGA TGCGTTTTCT AAGT 24 33 base pairs nucleic acid single linear DNA (synthetic) 159GGTTTCGTTC CATCAGAATG TCCATGTCTT CAG 33 339 base pairs nucleic acid double linear DNA (genomic) 160ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAACGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 338 base pairs nucleic acid double linear DNA (genomic) 161ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ACATTTGATG GAACGAAACC 120TTCGAACTCC AAACCTGCTC GCATTCGTAA GGGCTGTCAA GCACTTAGAA AACGCATCAG 180GTATTGAGGC AATTCTTCGT AATCTCCAAC CATGTCTGCC CTCTGCCACG GCCGCACCCT 240CTCGACATCC AATCATCATC AAGGCAGGTG ACTGGCAAGA ATTCCGGGAA AAACTGACGT 300TCTATCTGGT TACCCTTGAG CAAGCGCAGG AACAACAG 338 40 base pairs nucleic acid single linear DNA (synthetic) 162CATGGCTAAC TGCTCTAACA TGATCGATGA AATTATAACA 40 45 base pairs nucleic acid single linear DNA (synthetic) 163CTTTAAGTGT GTTATAATTT CATCGATCAT GTTAGAGCAG TTAGC 45 36 base pairs nucleic acid single linear DNA (synthetic) 164CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTC 36 36 base pairs nucleic acid single linear DNA (synthetic) 165GAGGTTGTTG AAGTCCAGCA AAGGCAAAGG TGGCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 166AACAACCTCA ATGACGAAGA CATGTCT 27 18 base pairs nucleic acid single linear DNA (synthetic) 167AGACATGTCT TCGTCATT 18 16 base pairs nucleic acid single linear DNA (synthetic) 168TGAACCATAT GTCAGG 16 24 base pairs nucleic acid single linear DNA (synthetic) 169AATTCCTGAC ATATGGTTCA TGCA 24 40 base pairs nucleic acid single linear DNA (synthetic) 170CATGGCAAAC TGCTCTATAG CTATCGATGA AATTATACAT 40 45 base pairs nucleic acid single linear DNA (synthetic) 171CTTTAAGTGA TGTATAATTT CATCGATAGC TATAGAGCAG TTTGC 45 40 base pairs nucleic acid single linear DNA (synthetic) 172CATGGCAAAC TGCTCTATAA TCATCGATGA AATTATACAT 40 45 base pairs nucleic acid single linear DNA (synthetic) 173CTTTAAGTGA TGTATAATTT CATCGATGAT TATAGAGCAG TTTGC 45 36 base pairs nucleic acid single linear DNA (synthetic) 174ATCCTGGACG AACGAAACCT TCGAACTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 175AGTTCGAAGG TTTCGTTCGT CCAGGAT 27 36 base pairs nucleic acid single linear DNA (synthetic) 176ATCCTGATCG AACGAAACCT TCGAACTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 177AGTTCGAAGG TTTCGTTCGA TCAGGAT 27 36 base pairs nucleic acid single linear DNA (synthetic) 178ATCCTGCTGG AACGAAACCT TCGAACTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 179AGTTCGAAGG TTTCGTTCCA GCAGGAT 27 27 base pairs nucleic acid single linear DNA (synthetic) 180AACAACCTCA ATTCTGAAGA CGTTGAT 27 18 base pairs nucleic acid single linear DNA (synthetic) 181ATCAACGTCT TCAGAATT 18 51 base pairs nucleic acid single linear DNA (synthetic) 182CGCGCCATGG CTAACTGCTC TATAATGATC GATGAAGCAA TACATCACTT A 51 18 base pairs nucleic acid single linear DNA (synthetic) 183CGCGTCGATA AGCTTATT 18 18 base pairs nucleic acid single linear DNA (synthetic) 184GGAGATATAT CCATGGCT 18 42 base pairs nucleic acid single linear DNA (synthetic) 185TCGGTCCATC AGAATAGACA TGTCTTCAGC ATTGAGGTTG TT 42 42 base pairs nucleic acid single linear DNA (synthetic) 186TCGGTCCATC AGAATAGAAA CGTCTTCAGC ATTGAGGTTG TT 42 42 base pairs nucleic acid single linear DNA (synthetic) 187TCGGTCCATC AGAATAGACA TGTCTTCGTC ATTGAGGTTG TT 42 42 base pairs nucleic acid single linear DNA (synthetic) 188TCGGTCCATC AGAATAGAAA CGTCTTCGTC ATTGAGGTTG TT 42 42 base pairs nucleic acid single linear DNA (synthetic) 189TCGGTCCATC AGAATAGACA TGTCTTCAGA ATTGAGGTTG TT 42 42 base pairs nucleic acid single linear DNA (synthetic) 190TCGGTCCATC AGAATAGAAA CGTCTTCAGA ATTGAGGTTG TT 42 48 base pairs nucleic acid single linear DNA (synthetic) 191CTGCCCTCTG CCACGGCCGC ACCCTCTCGA CATCCAATCA TCATCCGT 48 26 base pairs nucleic acid single linear DNA (synthetic) 192AATTCTTGCC AGTCACCTGC ACGGAT 26 16 base pairs nucleic acid single linear DNA (synthetic) 193ATGGGTGACT GGCAAG 16 26 base pairs nucleic acid single linear DNA (synthetic) 194AATTCTTGCC AGTCACCCAT ACGGAT 26 40 base pairs nucleic acid single linear DNA (synthetic) 195CATGGCTAAC TGCTCTATTA TGATCGATGA AGCAATACAT 40 45 base pairs nucleic acid single linear DNA (synthetic) 196CTTTAAGTGA TGTATTGCTT CATCGATCAT AATAGAGCAG TTAGC 45 36 base pairs nucleic acid single linear DNA (synthetic) 197CACTTAAAGG TACCACCTCG CCCTTCCCTG GACCCG 36 36 base pairs nucleic acid single linear DNA (synthetic) 198GAGGTTGTTC GGGTCCAGGG AAGGGCGAGG TGGTAC 36 36 base pairs nucleic acid single linear DNA (synthetic) 199CACTTAAAGA GACCACCTGC ACCTTCCCTG GACCCG 36 36 base pairs nucleic acid single linear DNA (synthetic) 200GAGGTTGTTC GGGTCCAGGG AAGGTGCAGG TGGTCT 36 27 base pairs nucleic acid single linear DNA (synthetic) 201AACAACCTCA ATGACGAAGA CATGGAT 27 18 base pairs nucleic acid single linear DNA (synthetic) 202ATCCATGTCT TCGTCATT 18 27 base pairs nucleic acid single linear DNA (synthetic) 203AACAACCTCA ATGACGAAGA CGTCGAT 27 18 base pairs nucleic acid single linear DNA (synthetic) 204ATCGACGTCT TCGTCATT 18 27 base pairs nucleic acid single linear DNA (synthetic) 205AACAACCTCA ATGACGAAGA CATGTCT 27 18 base pairs nucleic acid single linear DNA (synthetic) 206AGACATGTCT TCGTCATT 18 27 base pairs nucleic acid single linear DNA (synthetic) 207AACAACCTCA ATGACGAAGA CGTCTCT 27 18 base pairs nucleic acid single linear DNA (synthetic) 208AGAGACGTCT TCGTCATT 18 36 base pairs nucleic acid single linear DNA (synthetic) 209ATCCTGATGG ACCGAAACCT TCGACTTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 210AAGTCGAAGG TTTCGGTCCA TCAGGAT 27 36 base pairs nucleic acid single linear DNA (synthetic) 211ATCCTGATGG ACCGAAACCT TCGACTTAGC AACCTG 36 24 base pairs nucleic acid single linear DNA (synthetic) 212CCTTACGAAG CTCTCCAGGT TGCT 24 18 base pairs nucleic acid single linear DNA (synthetic) 213CGTAATCTCT GGCCATGT 18 18 base pairs nucleic acid single linear DNA (synthetic) 214CCAGAGATTA CGAAGAAT 18 32 base pairs nucleic acid single linear DNA (synthetic) 215AATTCCGGGA AAAACTGCAA TTCTATCTGT GG 32 37 base pairs nucleic acid single linear DNA (synthetic) 216CTCAAGGGTC CACAGATAGA ATTGCAGTTT TTCCCGG 37 32 base pairs nucleic acid single linear DNA (synthetic) 217AATTCCGGGA AAAACTGCAA TTCTATCTGG TT 32 37 base pairs nucleic acid single linear DNA (synthetic) 218CTCAAGGGTA ACCAGATAGA ATTGCAGTTT TTCCCGG 37 23 base pairs nucleic acid single linear DNA (synthetic) 219AATTCCGGGA AAAACTGACG TTC 23 28 base pairs nucleic acid single linear DNA (synthetic) 220AACCAGATAG AACGTCAGTT TTTCCCGG 28 23 base pairs nucleic acid single linear DNA (synthetic) 221TATCTGGTTA CCCTTGAGTA ATA 23 19 base pairs nucleic acid single linear DNA (synthetic) 222AGCTTATTAC TTCAAGGGT 19 23 base pairs nucleic acid single linear DNA (synthetic) 223AATTCCGGGA AAAACTGCAA TTC 23 28 base pairs nucleic acid single linear DNA (synthetic) 224AACCAGATAG AATTGCAGTT TTTCCCGG 28 61 base pairs nucleic acid single linear DNA (synthetic) 225CGATCATTAT AGAGCAGTTA GCCTTGTCAT CGTCGTCCTT GTAATCAGTT TCTGGATATG 60C 61 63 base pairs nucleic acid single linear DNA (synthetic) 226CATGGCATAT CCAGAAACTG ATTACAAGGA CGACGATGAC AAGGCTAACT GCTCTATAAT 60GAT 63 32 base pairs nucleic acid single linear DNA (synthetic) 227AATTCCGGCT TAAACTGCAA TTCTATCTGT CT 32 37 base pairs nucleic acid single linear DNA (synthetic) 228CTCAAGGGTA GACAGATAGA ATTGCAGTTT AAGCCGG 37 32 base pairs nucleic acid single linear DNA (synthetic) 229TCTCTTGAGC AAGCGCAGGA ACAACAGTAA TA 32 40 base pairs nucleic acid single linear DNA (synthetic) 230CATGGCAAAC TGCTCTATAA TACTCGATGA AGCAATACAT 40 45 base pairs nucleic acid single linear DNA (synthetic) 231CTTTAAGTGA TGTATTGCTT CATCGAGTAT TATAGAGCAG TTTGC 45 40 base pairs nucleic acid single linear DNA (synthetic) 232CATGGCAAAC TGCTCTATAA TGCCAGATGA AGCAATACAT 40 45 base pairs nucleic acid single linear DNA (synthetic) 233CTTTAAGTGA TGTATTGCTT CATCTGGCAT TATAGAGCAG TTTGC 45 41 base pairs nucleic acid single linear DNA (synthetic) 234CATGGCAAAC TGCTCTATAA TGATCGATGA AACTGATACA T 41 45 base pairs nucleic acid single linear DNA (synthetic) 235CTTTAAGTGA TGTATCAGTT CATCGATCAT TATAGAGCAG TTTGC 45 36 base pairs nucleic acid single linear DNA (synthetic) 236CACTTAAAGA TACCACCTAA CCCTAGCCTG GACAGT 36 36 base pairs nucleic acid single linear DNA (synthetic) 237GAGGTTAGCA CTGTCCAGGC TAGGGTTAGG TGGTAT 36 27 base pairs nucleic acid single linear DNA (synthetic) 238GCTAACCTCA ATTCCGAAGA CGTCTCT 27 18 base pairs nucleic acid single linear DNA (synthetic) 239AGAGACGTCT TCGGAATT 18 36 base pairs nucleic acid single linear DNA (synthetic) 240ATCCTGATGG ACTCCAACCT TCGAACTCCA AACCTG 36 27 base pairs nucleic acid single linear DNA (synthetic) 241AGTTCGAAGG TTGGAGTCCA TCAGGAT 27 48 base pairs nucleic acid single linear DNA (synthetic) 242GTTCCCTATT GGACGGCCCC TCCCTCTCGA ACACCAATCA CGATCAAG 48 48 base pairs nucleic acid single linear DNA (synthetic) 243CGTGATTGGT GTTCGAGAGG GAGGGGCCGT CCAATAGGGA ACACATGG 48 24 base pairs nucleic acid single linear DNA (synthetic) 244CTCGCATTCC CACATGCTTC TAAG 24 24 base pairs nucleic acid single linear DNA (synthetic) 245CTCGCATTCC CACATGCTGT CAAG 24 24 base pairs nucleic acid single linear DNA (synthetic) 246ATGTGGGAAT GCGAGCAGGT TTGG 24 20 base pairs nucleic acid single linear DNA (synthetic) 247TTTTCTAATT GCTTAGAAGC 20 15 base pairs nucleic acid single linear DNA (synthetic) 248CAATTAGAAA ATGCA 15 20 base pairs nucleic acid single linear DNA (synthetic) 249TTTTCTAATT GCTTGACAGC 20 21 base pairs nucleic acid single linear DNA (synthetic) 250TCAGGTATTG AGCCAATTCT T 21 19 base pairs nucleic acid single linear DNA (synthetic) 251TGGCTCAATA CCTGATGCA 19 18 base pairs nucleic acid single linear DNA (synthetic) 252TCTAATCTCC AACCATGT 18 18 base pairs nucleic acid single linear DNA (synthetic) 253TTGGAGATTA GAAAGAAT 18 37 base pairs nucleic acid single linear DNA (synthetic) 254CTCAAGAGAA GACAGATAGA ATTGCAGTTT AAGCCGG 37 40 base pairs nucleic acid single linear DNA (synthetic) 255CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT 40 43 base pairs nucleic acid single linear DNA (synthetic) 256AATTCCGGCT TAAACTGCAA TTCTATCTGT CTACCCTTTA ATA 43 43 base pairs nucleic acid single linear DNA (synthetic) 257AGCTTATTAA AGGGTAGACA GATAGAATTG CAGTTTAAGC CGG 43 43 base pairs nucleic acid single linear DNA (synthetic) 258AATTCCGGCT TAAACTGCAA TTCTATCTGT CTACCCTTTA ATA 43 113 amino acids amino acid linear peptide 259Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 260Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 261Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Trp Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 262Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Trp Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 263Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg Arg Pro Ile Ile Ile Arg Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Trp Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 113 amino acids amino acid linear peptide 264Met Ala Asn Cys Ser Ile Ala Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 265Met Ala Asn Cys Ser Ile Ile Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 266Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 267Met Ala Asn Cys Ser Ile Ala Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 268Met Ala Asn Cys Ser Ile Ile Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 269Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Ile Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 270Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Leu Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 271Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Asp Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 272Met Ala Asn Cys Ser Ile Ala Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Ile Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 273Met Ala Asn Cys Ser Ile Ile Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Ile Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 274Met Ala Asn Cys Ser Ile Ala Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Leu Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 275Met Ala Asn Cys Ser Ile Ile Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Leu Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 276Met Ala Asn Cys Ser Ile Ala Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Asp Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 277Met Ala Asn Cys Ser Ile Ile Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Val Asp Ile Leu Asp Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 278Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 279Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 280Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 281Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asn Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 282Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 283Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 284Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Met Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 285Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 286Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 107 amino acids amino acid linear peptide 287Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu 100 105 107 amino acids amino acid linear peptide 288Met Asp Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu 100 105 113 amino acids amino acid linear peptide 289Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 107 amino acids amino acid linear peptide 290Met Asp Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu 100 105 113 amino acids amino acid linear peptide 291Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 292Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Arg Pro Ser Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 293Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Trp Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 294Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 295Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 296Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 297Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 298Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 299Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 300Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 301Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 302Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Val Pro Pro Arg Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 303Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Arg Met Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 304Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Trp Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Arg Met Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 305Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 306Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Val Pro Pro Arg Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 107 amino acids amino acid linear peptide 307Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Val Thr Leu Glu 100 105 113 amino acids amino acid linear peptide 308Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 309Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 310Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 311Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 312Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 313Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Gln Phe Tyr Leu Trp Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 314Met Asp Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp 20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 125 amino acids amino acid linear peptide 315Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys1 5 10 15Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala 20 25 30Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu 35 40 45Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala 50 55 60Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn65 70 75 80Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro 85 90 95Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr 100 105 110Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln 115 120 125 125 amino acids amino acid linear peptide 316Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys1 5 10 15Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn 20 25 30Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu 35 40 45Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala 50 55 60Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn65 70 75 80Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro 85 90 95Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr 100 105 110Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln 115 120 125 113 amino acids amino acid linear peptide 317Met Ala Asn Cys Ser Ile Met Pro Asp Glu Ala Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 318Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 319Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg Thr Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 320Met Ala Asn Cys Ser Ile Ile Leu Asp Glu Ala Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg Thr Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 321Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Asp Ser Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Pro His Ala Ser Lys Gln Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 322Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 106 amino acids amino acid linear peptide 323Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Thr Leu 100 105 113 amino acids amino acid linear peptide 324Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Ser Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 325Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Asp Ser Asn Leu Leu Thr Pro Asn Leu Leu Ala 35 40 45Phe Pro His Ala Ser Lys Gln Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Ser Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 326Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Ser Asn Leu Gln Pro Cys Val Pro Tyr Trp Thr Ala Pro Pro65 70 75 80Ser Arg Thr Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 327Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp 20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Ser Asn Leu Gln Pro Cys Val Pro Tyr Trp Thr Ala Pro Pro65 70 75 80Ser Arg Thr Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 328Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Ser Asn Leu Gln Pro Cys Val Pro Tyr Trp Thr Ala Pro Pro65 70 75 80Ser Arg Thr Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 329Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Leu Lys Leu Gln Phe Tyr Leu Ser Ser Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 330Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp 20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala 35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Pro 50 55 60Ile Leu Ser Asn Leu Gln Pro Cys Val Pro Tyr Trp Thr Ala Pro Pro65 70 75 80Ser Arg Thr Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 113 amino acids amino acid linear peptide 331Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser 35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala 50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg 85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln 100 105 110Gln 339 base pairs nucleic acid double linear DNA (genomic) 332ATGGCAAACT GCTCTATAGC TATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 333ATGGCAAACT GCTCTATAAT CATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 334ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 335ATGGCAAACT GCTCTATAGC TATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 336ATGGCAAACT GCTCTATAAT GATCCATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 337ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 338ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGCT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 339ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGGA CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 340ATGGCAAACT GCTCTATAGC TATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGAT CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 341ATGGCAAACT GCTCTATAAT CATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGAT CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 342ATGGCAAACT GCTCTATAGC TATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGCT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 343ATGGCAAACT GCTCTATAAT CATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGCT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 344ATGGCAAACT GCTCTATAGC TATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGGA CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 345ATGGCAAACT GCTCTATAAT CATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACGTTG ATATCCTGGA CGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 346ATGGCTAACT GCTCTATTAT GATCGATGAA GCAATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 347ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGGT TCCACCTGCA 60CCTTTGCTGG ACAGTAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 348ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTTT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 349ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATAAC GAAGACGTTT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 350ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTTT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 351ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTTT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 352ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACATGT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 353ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACATGT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 354ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 321 base pairs nucleic acid double linear DNA (genomic) 355ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA G 321 321 base pairs nucleic acid double linear DNA (genomic) 356ATGGATAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA G 321 321 base pairs nucleic acid double linear DNA (genomic) 357ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA G 321 321 base pairs nucleic acid double linear DNA (genomic) 358ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA G 321 339 base pairs nucleic acid double linear DNA (genomic) 359ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTTT CTATCCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 360ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGGT ACCACCTCGC 60CCTTCCCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 361ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCTGG CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 362ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTTT CTATTCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 363ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 364ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGACCGAAAC 120CTTCGACTTA GCAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 365ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 366ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTCCCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 367ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 368ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 369ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 370ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGGT ACCACCTCGC 60CCTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 371ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CCGTATGGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 372ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCTGG CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CCGTATGGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 373ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 374ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGGT ACCACCTCGC 60CCTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 321 base pairs nucleic acid double linear DNA (genomic) 375ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGG TTACCCTTGA G 321 339 base pairs nucleic acid double linear DNA (genomic) 376ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 377ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCG ATTCTCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 378ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCA TGTCTCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 379ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGAC 60CTTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120CTTCGACTTA GCAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 380ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGACCGAAAC 120CTTCGACTTA GCAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 381ATGGCTAACT GCTCTATAAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTCCCTGG ACCCGAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGACCGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 382ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGCAA 300TTCTATCTGT GGACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 383ATGGATAACT GCTCTATTAT GATCGATGAA GCAATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGCT GAAGACGTCG ATATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 384ATGGCTAACT GCTCTATAAT GCCAGATGAA GCAATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 385ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 386ATGGCTAACT GCTCTATTAT GATCGATGAA GCAATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 387ATGGCTAACT GCTCTATAAT ACTCGATGAA GCAATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 388ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGACTCCAAC 120CTTCGAACTC CAAACCTGCT CGCATTCCCA CATGCTGTCA AGCAATTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 389ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGACTCCAAC 120CTTCGAACTC CAAACCTGCT CGCATTCCCA CATGCTTCTA AGCAATTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 390ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTACCCTTGA GCAAGCGCAG GAACAACAG 339 318 base pairs nucleic acid double linear DNA (genomic) 391ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTACCCTT 318 339 base pairs nucleic acid double linear DNA (genomic) 392ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTTCTCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 393ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGC CAATTCTTTC TAATCTCCAA CCATGTGTTC CCTATTGGAC GGCCCCTCCC 240TCTCGAACAC CAATCACGAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 394ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCC GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGC CAATTCTTTC TAATCTCCAA CCATGTGTTC CCTATTGGAC GGCCCCTCCC 240TCTCGAACAC CAATCACGAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 395ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGC CAATTCTTTC TAATCTCCAA CCATGTGTTC CCTATTGGAC GGCCCCTCCC 240TCTCGAACAC CAATCACGAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 396ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGCT TAAACTGCAA 300TTCTATCTGT CTTCTCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 397ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAT ACCACCTAAC 60CCTAGCCTGG ACAGTGCTAA CCTCAATTCC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGC CAATTCTTTC TAATCTCCAA CCATGTGTTC CCTATTGGAC GGCCCCTCCC 240TCTCGAACAC CAATCACGAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 398ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGACAATAAC 120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG 339 339 base pairs nucleic acid double linear DNA (genomic) 399ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GGAAAATAAC 120CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG 339 29 base pairs nucleic acid double linear DNA (genomic) 400AAGGAGATAT ATCCATGAAC TGCTCTAAC 29 5 amino acids amino acid linear peptide 401Met Asn Cys Ser Asn1 5 120 amino acids amino acid linear peptide 402Met Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln1 5 10 15Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln 20 25 30Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe 35 40 45Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile 50 55 60Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr65 70 75 80Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg 85 90 95Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110Thr Thr Leu Arg Leu Ala Ile Phe 115 120 14 amino acids amino acid linear peptide 403Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys1 5 10 378 base pairs nucleic acid double linear DNA (genomic) 404ATGGCATATC CAGAAACTGA TTACAAGGAC GACGATGACA AGGCTAACTG CTCTATAATG 60ATCGATGAAA TTATACATCA CTTAAAGAGA CCACCTGCAC CTTTGCTGGA CCCGAACAAC 120CTCAATGCTG AAGACGTCGA TATCCTGATG GAACGAAACC TTCGACTTCC AAACCTGGAG 180AGCTTCGTAA GGGCTGTCAA GAACTTAGAA AATGCATCAG GTATTGAGGC AATTCTTCGT 240AATCTCCAAC CATGTCTGCC CTCTGCCACG GCCGCACCCT CTCGACATCC AATCATCATC 300AAGGCAGGTG ACTGGCAAGA ATTCCGGGAA AAACTGACGT TCTATCTGGT TACCCTTGAG 360CAAGCGCAGG AACAACAG 378 378 base pairs nucleic acid double linear DNA (genomic) 405ATGGCATATC CAGAAACTGA TTACAAGGAC GACGATGACA AGGCTAACTG CTCTATAATG 60ATCGATGAAA TTATACATCA CTTAAAGAGA CCACCTAACC CTTTGCTGGA CCCGAACAAC 120CTCAATTCCG AAGACATGGA TATCCTGATG GAACGAAACC TTCGAACTCC AAACCTGCTC 180GCATTCGTAA GGGCTGTCAA GCACTTAGAA AATGCATCAG GTATTGAGGC AATTCTTCGT 240AATCTCCAAC CATGTCTGCC CTCTGCCACG GCCGCACCCT CTCGACATCC AATCATCATC 300AAGGCAGGTG ACTGGCAAGA ATTCCGGGAA AAACTGACGT TCTATCTGGT TACCCTTGAG 360CAAGCGCAGG AACAACAG 378 113 amino acids amino acid linear peptide 406Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp Glu Asp 20 25 30Met Ser Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser 50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile Ile Ile Arg Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95Arg Lys Leu Thr Phe Tyr Leu Trp Thr Leu Glu Asn Ala Gln Ala Gln 100 105 110Gln 111 amino acids amino acid linear peptide 407Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp 20 25 30Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn 35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu 50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys 85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln 100 105 110 340 base pairs nucleic acid double linear DNA (genomic) 408ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAACAATAA 120CCTTCGTCGT CCAAACCTCG AGGCATTCAA CCGTGCTGTC AACTCTCTGC AGAATGCATC 180AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCATGTCTG CCCCTGGCCA CGGCCGCACC 240CACGCGACAT CCAATCCATA TCAAGGACGG TGACTGGAAT GAATTCCGTC GTAAACTGAC 300CTTCTATCTG AAAACCTTGG AGAACGCGCA GGCTCAACAG 340 45 base pairs nucleic acid single linear DNA (synthetic) 409CTTTAAGTGA TGTATAATTT CATCGATCAT TATAGAGCAG TTAGC 45 36 base pairs nucleic acid single linear DNA (synthetic) 410CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCG 36 36 base pairs nucleic acid single linear DNA (synthetic) 411GAGGTTGTTC GGGTCCAGCA AAGGTGCAGG TGGTCT 36 36 base pairs nucleic acid single linear DNA (synthetic) 412CACTTAAAGA GACCACCTAA CCCTTTGCTG GACCCG 36 36 base pairs nucleic acid single linear DNA (synthetic) 413GAGGTTGTTC GGGTCCAGCA AAGGGTTAGG TGGTCT 36 36 base pairs nucleic acid single linear DNA (synthetic) 414CACTTAAAGG TTCCACCTGC ACCTTTGCTG GACAGT 36 36 base pairs nucleic acid single linear DNA (synthetic) 415GAGGTTGTTA CTGTCCAGCA AAGGTGCAGG TGGAAC 36

Claims

1. A method for ex vivo expansion of stem cells, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of (SEQ ID NO:15); wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, .Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, [i], Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than on of the amino acids at positions 63, 82, 87, 98, 112 and 121 are different from the corresponding amino acids in native han interleukin-3; wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said interleukin-3 mutant polypeptide; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the aroud consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); and (b) harvesting said cultured stem cells.

2. A method for ex vivo expansion of stem cells, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of; wherein Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn, or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp; Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, Met, or; Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr, Trp, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaa at position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Ala, Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro; Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu or Gln; Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser; Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 is Leu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than one of the amino acids at positions 49, 68, 73, 84, 98 and 107 are different from the corresponding amino acids in native human interleukin-3; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); and (b) harvesting said cultured stem cells.

3. A method for ex vivo expansion of stem cells, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:129); wherein; Xaa at position 18 is Asn or Ile; Xaa at position 19 is Met, Ala or Ile; Xaa at position 20 is Ile, Pro or Leu; Xaa at position 23 is Ile, Ala or Leu; Xaa at position 25 is Thr or His; Xaa at position 29 is Gln, Arg, Val or Leu; Xaa at position 32 is Leu, Ala, Asn or Arg; Xaa at position 34 is Leu or Ser; Xaa at position 37 is Phe, Pro, or Ser; Xaa at position 38 is Asn or Ala; Xaa at position 42 is Gly, Ala, Ser, Asp or Asn; Xaa at position 45 is Gln, Val, or Met; Xaa at position 46 is Asp or Ser; Xaa at position 49 is Met, Ile, Leu or Asp; Xaa at position 50 is Glu or Asp; Xaa at position 51 is Asn Arg or Ser; Xaa at position 55 is Arg, Leu, or Thr; Xaa at position 56 is Pro or Ser; Xaa at position 59 is Glu or Leu; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Val or Pro; Xaa at position 63 is Arg or His; Xaa at position 65 is Val or Ser; Xaa at position 67 is Ser, Asn, His or Gly; Xaa at position 69 is Gln or Glu; Xaa at position 73 is Ala or Gly; Xaa at position 76 is Ser, Ala or Pro; Xaa at position 79 is Lys, Arg or Ser; Xaa at position 82 is Leu, Glu, Val or Trp; Xaa at position 85 is Leu or Val; Xaa at position 87 is Leu, Ser, or Trp; Xaa at position 88 is Ala or Trp; Xaa at position 91 is Ala or Pro; Xaa at position 93 is Pro or Ser; Xaa at position 95 is His or Thr; Xaa at position 98 is His, Ile, or Thr; Xaa at position 100 is Lys or Arg; Xaa at position 101 is Asp, Ala or Met; Xaa at position 105 is Asn or Gln; Xaa at position 109 is Arg, Glu or Leu; Xaa at position 112 is Thr or Gln; Xaa at position 116 is Lys, Val, Trp or Ser; Xaa at position 117 is Thr or Ser; and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and (b) harvesting said cultured stem cells.

4. A method for ex vivo expansion of stem cells, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:130); wherein; Xaa at position 4 is Asn or Ile; Xaa at position 5 is Met, Ala or Ile; Xaa at position 6 is Ile, Pro or Leu; Xaa at position 9 is Ile, Ala or Leu; Xaa at position 11 is Thr or His; Xaa at position 15 is Gln, Arg, Val or Leu; Xaa at position 18 is Leu, Ala, Asn or Arg; Xaa at position 20 is Leu or Ser; Xaa at position 23 is Phe, Pro, or Ser; Xaa at position 24 is Asn or Ala; Xaa at position 28 is Gly, Ala, Ser, Asp or Asn; Xaa at position 31 is Gln, Val, or Met; Xaa at position 32 is Asp or Ser; Xaa at position 35 is Met, Ile, Leu or Asp; Xaa at position 36 is Glu or Asp; Xaa at position 37 is Asn, Arg or Ser; Xaa at position 41 is Arg, Leu, or Thr; Xaa at position 42 is Pro or Ser; Xaa at position 45 is Glu or Leu; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Val or Pro; Xaa at position 49 is Arg or His; Xaa at position 51 is Val or Ser; Xaa at position 53 is Ser, Asn, His or Gly; Xaa at position 55 is Gln or Glu; Xaa at position 59 is Ala or Gly; Xaa at position 62 is Ser, Ala or Pro; Xaa at position 65 is Lys, Arg or Ser; Xaa at position 67 is Leu, Glu, or Val; Xaa at position 68 is Leu, Glu, Val or Trp; Xaa at position 71 is Leu or Val; Xaa at position 73 is Leu, Ser or Trp; Xaa at position 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa at position 79 is Pro or Ser; Xaa at position 81 is His or Thr; Xaa at position 84 is His, Ile, or Thr; Xaa at position 86 is Lys or Arg; Xaa at position 87 is Asp, Ala or Met; Xaa at position 91 is Asn or Gln; Xaa at position 95 is Arg, Glu, Leu; Xaa at position 98 Thr or Gin; Xaa at position 102 is Lys, Val, Trp or Ser; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Gin, or His; Xaa at position 109 is Ala or Glu; with the proviso that from four to about forty-four of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(b) harvesting said cultured stem cells.

5. The method according to claim 2 wherein said interleukin-3 mutant polypeptide is selected from the group consisting of:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:66); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:67); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:68); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:69); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:70); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:71); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:72); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:73); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:74); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:75); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:76); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:77); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:78); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:79); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:80); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:81); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:82); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:83); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:84); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:85); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:86); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:87); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:88); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:89); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:90); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:91); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:92); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:93); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:94); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:95); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:96); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:296); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:300); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:301); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:308); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:309); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:310); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:315); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:316); and Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:318).

6. The method of claim 1 wherein said mutant human interleukin-3 polypeptide has at least three times greater activity than native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

7. The method of claim 1 further comprising the step of separating the stem cells from a mixed population of cells prior to culturing the stem cells.

8. The method of claim 7 wherein said stem cells are separated from a mixed population of cells based on the stem cells having CD34 surface antigen.

9. A method of enhancing the efficiency of the transduction of cultured stem cells by a heterologous gene, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of (SEQ ID NO:15); wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser. Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu,.Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than one of the amino acids at positions 63, 82, 87, 98, 112 and 121 are different from the corresponding amino acids in native human interleukin-3; wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said interleukin-3 mutant polypeptide; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); and (b) transducing DNA into said cultured cells; and (c) harvesting said transduced cells.

10. A method of enhancing the efficiency of the transduction of cultured stem cells by a heterologous gene, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of SEQ ID NO:19; wherein Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn, or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp; Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, Met, or; Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr, Trp, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position.56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaa at position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro; Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu or Gln; Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser; Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gin, Lys, Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 is Leu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than one of the amino acids at positions 49, 68, 73, 84, 98 and 107 are different from the corresponding amino acids in native human interleukin-3; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); and (b) transducing DNA into said cultured cells; and (c) harvesting said transduced cells.

11. A method of enhancing the efficiency of the transduction of cultured stem cells by a heterologous gene, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:129); wherein Xaa at position 18 is Asn or Ile; Xaa at position 19 is Met, Ala or Ile; Xaa at position 20 is Ile, Pro or Leu; Xaa at position 23 is Ile, Ala or Leu; Xaa at position 25 is Thr or His; Xaa at position 29 is Gln, Arg, Val or Leu; Xaa at position 32 is Leu, Ala, Asn or Arg; Xaa at position 34 is Leu or Ser; Xaa at position 37 is Phe, Pro, or Ser; Xaa at position 38 is Asn or Ala; Xaa at position 42 is Gly, Ala, Ser, Asp or Asn; Xaa at position 45 is Gln, Val, or Met; Xaa at position 46 is Asp or Ser; Xaa at position 49 is Met, Ile, Leu or Asp; Xaa at position 50 is Glu or Asp; Xaa at position 51 is Asn Arg or Ser; Xaa at position 55 is Arg, Leu, or Thr; Xaa at position 56 is Pro or Ser; Xaa at position 59 is Glu or Leu; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Val or Pro; Xaa at position 63 is Arg or His; Xaa at position 65 is Val or Ser; Xaa at position 67 is Ser, Asn, His or Gly; Xaa at position 69 is Gln or Glu; Xaa at position 73 is Ala or Gly; Xaa at position 76 is Ser, Ala or Pro; Xaa at position 79 is Lys, Arg or Ser; Xaa at position 82 is Leu, Glu, Val or Trp; Xaa at position 85 is Leu or Val; Xaa at position 87 is Leu, Ser, or Trp; Xaa at position 88 is Ala or Trp; Xaa at position 91 is Ala or Pro; Xaa at position 93 is Pro or Ser; Xaa at position 95 is His or Thr; Xaa at position 98 is His, Ile, or Thr; Xaa at position 100 is Lys or Arg; Xaa at position 101 is Asp, Ala or Met; Xaa at position 105 is Asn or Gln; Xaa at position 109 is Arg, Glu or Leu; Xaa at position 112 is Thr or Gln; Xaa at position 116 is Lys, Val, Trp or Ser; Xaa at position 117 is Thr or Ser; Xaa at position 120 is Asn, Gln, or His; Xaa at position 123 is Ala or Glu; with the proviso that from four to about forty-four of the amino acids designated by Xaa are different from the corresponding amino acids of native human interleukin-3 and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and (b) transducing DNA into said cultured cells; and (c) harvesting said transduced cells.

12. A method of enhancing the efficiency of the transduction of cultured stem cells by a heterologous gene, comprising the steps of;(a) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:130); wherein; Xaa at position 4 is Asn or Ile; Xaa at position 5 is Met, Ala or Ile; Xaa at position 6 is Ile, Pro or Leu; Xaa at position 9 is Ile, Ala or Leu; Xaa at position 11 is Thr or His; Xaa at position 15 is Gln, Arg, Val or Leu; Xaa at position 18 is Leu, Ala, Asn or Arg; Xaa at position 20 is Leu or Ser; Xaa at position 23 is Phe, Pro, or Ser; Xaa at position 24 is Asn or Ala; Xaa at position 28 is Gly, Ala, Ser, Asp or Asn; Xaa at position 31 is Gln, Val, or Met; Xaa at position 32 is Asp or Ser; Xaa at position 35 is Met, Ile, Leu or Asp; Xaa at position 36 is Glu or Asp; Xaa at position 37 is Asn, Arg or Ser; Xaa at position 41 is Arg, Leu, or Thr; Xaa at position 42 is Pro or Ser; Xaa at position 45 is Glu or Leu; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Val or Pro; Xaa at position 49 is Arg or His; Xaa at position 51 is Val or Ser; Xaa at position 53 is Ser, Asn, His or Gly; Xaa at position 55 is Gin or Glu; Xaa at position 59 is Ala or Gly; Xaa at position 62 is Ser, Ala or Pro; Xaa at position 65 is Lys, Arg or Ser; Xaa at position 67 is Leu, Glu, or Val; Xaa at position 68 is Leu, Glu, Val or Trp; Xaa at position 71 is Leu or Val; Xaa at position 73 is Leu, Ser or Trp; Xaa at position 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa at position 79 is Pro or Ser; Xaa at position 81 is His or Thr; Xaa at position 84 is His, Ile, or Thr; Xaa at position 86 is Lys or Arg; Xaa at position 87 is Asp, Ala or Met; Xaa at position 91 is Asn or Gln; Xaa at position 95 is Arg, Glu, Leu; Xaa at position 98 Thr or Gln; Xaa at position 102 is Lys, Val, Trp or Ser; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Gln, or His; Xaa at position 109 is Ala or Glu; with the proviso that from four to about forty-four of the amino acids designated by Xaa are different from the corresponding amino acids of native (15-125)human interleukin-3 and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and (b) transducing DNA into said cultured cells; and (c) harvesting said transduced cells.

13. The method according to claim 10 wherein said interleukin-3 mutant polypeptide is selected from the group consisting of:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:66); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:67); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:68); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:69); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:70); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:71); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:72); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:73); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:74); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:75); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:76); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:77); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:78); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:79); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:80); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:81); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:82); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:83); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:84); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:85); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:86); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:87); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:88); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:89); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:90); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:91); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:92); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:93); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:94); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:95); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:96); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:296); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:300); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:301); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:308); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:309); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:310); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:315); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:316); and Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:318).

14. The method of claim 9 wherein said mutant human interleukin-3 polypeptide has at least three times greater activity than native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

15. The method of claim 9 further comprising the step of separating the stem cells from a mixed population of cells prior to culturing the stem cells.

16. The method of claim 15 wherein said stem cells are separated from a mixed population of cells based on the stem cells having CD34 surface antigen.

17. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;(a) removing stem cells from said patient or a blood donor; (b) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of (SEQ ID NO:15); wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser. Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than one of the amino acids at positions 63, 82, 87, 98, 112 and 121 are different from the corresponding amino acids in native human interleukin-3; wherein from 1 to 14 amino acids are optionally deleted from the N-terminus and/or from 1 to 15 amino acids are optionally deleted from the C-terminus of said interleukin-3 mutant polypeptide; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell Proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); (c) harvesting said cultured stem cells; and (d) transplanting said cultured stem cells into said patient.

18. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;(a) removing stem cells from said patient or a blood donor; (b) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide selected from the group consisting of: (i) a human interleukin-3 mutant polypeptide of (SEQ ID NO:19); wherein Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn, or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp; Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, Met, or; Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 45 is-Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr, Trp, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaa at position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro; Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu or Gln; Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser; Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 is Leu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 4 to about 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; with the proviso that no more than one of the amino acids at positions 49, 68, 73, 84, 98 and 107 are different from the corresponding amino acids in native human interleukin-3; and wherein said interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay; and(ii) a polypeptide comprising an N-terminal methionine residue, alanine residue or methionine-alanine di-peptide immediately preceding said sequence according to (i); (c) harvesting said cultured stem cells; and (d) transplanting said cultured stem cells into said patient.

19. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;(a) removing stem cells from said patient or a blood donor; (b) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:129); wherein; Xaa at position 18 is Asn or Ile; Xaa at position 19 is Met, Ala or Ile; Xaa at position 20 is Ile, Pro or Leu; Xaa at position 23 is Ile, Ala or Leu; Xaa at position 25 is Thr or His; Xaa at position 29 is Gln, Arg, Val or Leu; Xaa at position 32 is Leu, Ala, Asn or Arg; Xaa at position 34 is Leu or Ser; Xaa at position 37 is Phe, Pro, or Ser; Xaa at position 38 is Asn or Ala; Xaa at position 42 is Gly, Ala, Ser, Asp or Asn; Xaa at position 45 is Gln, Val, or Met; Xaa at position 46 is Asp or Ser; Xaa at position 49 is Met, Ile, Leu or Asp; Xaa at position 50 is Glu or Asp; Xaa at position 51 is Asn Arg or Ser; Xaa at position 55 is Arg, Leu, or Thr; Xaa at position 56 is Pro or Ser; Xaa at position 59 is Glu or Leu; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Val or Pro; Xaa at position 63 is Arg or His; Xaa at position 65 is Val or Ser; Xaa at position 67 is Ser, Asn, His or Gly; Xaa at position 69 is Gln or Glu; Xaa at position 73 is Ala or Gly; Xaa at position 76 is Ser, Ala or Pro; Xaa at position 79 is Lys, Arg or Ser; Xaa at position 82 is Leu, Glu, Val or Trp; Xaa at position 85 is Leu or Val; Xaa at position 87 is Leu, Ser, or Trp; Xaa at position 88 is Ala or Trp; Xaa at position 91 is Ala or Pro; Xaa at position 93 is Pro or Ser; Xaa at position 95 is: His or Thr; Xaa at position 98 is His, Ile, or Thr; Xaa at position 100 is Lys or Arg; Xaa at position 101 is Asp, Ala or Met; Xaa at position 105 is Asn or Gln; Xaa at position 109 is Arg, Glu or Leu; Xaa at position 112 is Thr or Gln; Xaa at position 116 is Lys, Val, Trp or Ser; Xaa at position 117 is Thr or Ser; Xaa at position 12o is Asn, Gln, or His; Xaa at position 123 is Ala or Glu; with the proviso that from four to about forty-four of the amino acids designated by Xaa are different from the corresponding amino acids of native human interleukin-3 and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation an4 Methylcellulose assay; (c) harvesting said cultured stem cells; and (d) transplanting said cultured stem cells into said patient.

20. A method for treatment of a patient having a hematopoietic disorder, comprising the steps of;(a) removing stem cells from said patient or a blood donor; (b) culturing said stem cells with a growth medium comprising a human interleukin-3 mutant polypeptide of (SEQ ID NO:130); wherein; Xaa at position 4 is Asn or Ile; Xaa at position 5 is Met, Ala or Ile; Xaa at position 6 is Ile, Pro or Leu; Xaa at position 9 is Ile, Ala or Leu; Xaa at position 11 is Thr or His; Xaa at position 15 is Gln, Arg, Val or Leu; Xaa at position 18 is Leu, Ala, Asn or Arg; Xaa at position 20 is Leu or Ser; Xaa at position 23 is Phe, Pro, or Ser; Xaa at position 24 is Asn or Ala; Xaa at position 28 is Gly, Ala, Ser, Asp or Asn; Xaa at position 31 is Gln, Val, or Met; Xaa at position 32 is Asp or Ser; Xaa at position 35 is Met, Ile, Leu or Asp; Xaa at position 36 is Glu or Asp; Xaa at position 37 is Asn, Arg or Ser; Xaa at position 41 is Arg, Leu, or Thr; Xaa at position 42 is Pro or Ser; Xaa at position 45 is Glu or Leu; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Val or Pro; Xaa at position 49 is Arg or His; Xaa at position 51 is Val or Ser; Xaa at position 53 is Ser, Asn, His or Gly; Xaa at position 55 is Gln or Glu; Xaa at position 59 is Ala or Gly; Xaa at position 62 is Ser, Ala or Pro; Xaa at position 65 is Lys, Arg or Ser; Xaa at position 67 is Leu, Glu, or Val; Xaa at position 68 is Leu, Glu, Val or Trp; Xaa at position 71 is Leu or Val; Xaa at position 73 is Leu, Ser or Trp; Xaa at position 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa at position 79 is Pro or Ser; Xaa at position 81 is His or Thr; Xaa at position 84 is His, Ile, or Thr; Xaa at position 86 is Lys or Arg; Xaa at position 87 is Asp, Ala or Met; Xaa at position 91 is Asn or Gln; Xaa at position 95 is Arg, Glu, Leu; Xaa at position 98 Thr or Gln; Xaa at position 102 is Lys, Val, Trp or Ser; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Gln, or His; Xaa at position 109 is Ala or Glu; with the proviso that from four to about forty-four of the amino acids designated by Xaa are different from the corresponding amino acids of native (15-125)human interleukin-3 and wherein said human interleukin-3 mutant polypeptide has increased activity relative to native human interleukin-3, in at least one assay selected from the group consisting of: ADL cell proliferation, TF-1 cell proliferation and Methylcelluloue assay; (c) harvesting said cultured stem cells; and (d) transplanting said cultured stem cells into said patient.

21. The method according to claim 18 wherein said interleukin-3 mutant polypeptide is selected from the group consisting of:Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:66); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:67); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:68); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:69); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:70); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:71); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:72); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:73); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:74); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:75); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:76); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:77); Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:78); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:79); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:80); Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:81); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:82); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:83); Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:84); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:85); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:86); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln (SEQ ID NO:87); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:88); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:89); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:90); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:91); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:92); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:93); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:94); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:95); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln (SEQ ID NO:96); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:296); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:300); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:301); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:308); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:309); Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:310); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:315); Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:316); and Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln (SEQ ID NO:318).

22. The method of claim 17 wherein said mutant human interleukin-3 polypeptide has at least three times greater activity than native human interleukin-3, in at least one assay selected from the group consisting of: AML cell proliferation, TF-1 cell proliferation and Methylcellulose assay.

23. The method of claim 17 further comprising the step of separating the stem cells from a mixed population of cells prior to culturing the stem cells.

24. The method of claim 23 wherein said stem cells are separated from a mixed population of cells based on the stem cells having CD34 surface antigen.