HUMAN ANALOGS OF MURINE DEUBIQUITINATING PROTEASE

Information

  • Patent Application
  • 20070166297
  • Publication Number
    20070166297
  • Date Filed
    March 14, 2007
    17 years ago
  • Date Published
    July 19, 2007
    17 years ago
Abstract
The present invention is directed to human analogs of murine hematopoetic-specific, cytokine-inducible deubiquinating proteases (“DUBs”) clustered on chromosomes 4 and 8 and their respective regulatory regions. The nucleotides or proteins encoded thereby my be used in assays to identify inhibitors of human DUBs.
Description
BACKGROUND OF THE INVENTION

The role of ubiquitin in protein degradation was discovered and the main enzymatic reactions of this system elucidated in biochemical studies in a cell-free system from reticulocytes. In this system, proteins are targeted for degradation by covalent ligation to ubiquitin, a 76-amino-acid-residue protein. Briefly, ubiquitin-protein ligation requires the sequential action of three enzymes. The C-terminal Gly residue of ubiquitin is activated in an ATP-requiring step by a specific activating enzyme, E1 (Step 1). This step consists of an intermediate formation of ubiquitin adenylate, with the release of PPi, followed by the binding of ubiquitin to a Cys residue of E1 in a thiolester linkage, with the release of AMP. Activated ubiquitin is next transferred to an active site Cys residue of a ubiquitin-carrier protein, E2 (Step 2). In the third step catalyzed by a ubiquitin-protein ligase or E3 enzyme, ubiquitin is linked by its C-terminus in an amide isopeptide linkage to an -amino group of the substrate protein's Lys residues (Step 3).


Proteins ligated to polyubiquitin chains are usually degraded by the 26S proteasome complex that requires ATP hydrolysis for its action. The 26S proteasome is formed by an ATP-dependent assembly of a 20S proteasome, a complex that contains the protease catalytic sites, with 19S “cap” or regulatory complexes. The 19S complexes contain several ATPase subunits and other subunits that are presumably involved in the specific action of the 26S proteasome on ubiquitinylated proteins. The roles of ATP in the assembly of the 26S proteasome complex and in its proteolytic action are not understood. The action of the 26S proteasome presumably generates several types of products: free peptides, short peptides still linked to ubiquitin via their Lys residues, and polyubiquitin chains (Step 4). The latter two products are converted to free and reusable ubiquitin by the action of ubiquitin-C-terminal hydrolases or isopeptidases (Steps 5 and 6). Some isopeptidases may also disassemble certain ubiquitin-protein conjugates (Step 7) and thus prevent their proteolysis by the 26S proteasome. The latter type of isopeptidase action may have a correction function to salvage incorrectly ubiquitinylated proteins or may have a regulatory role. Short peptides formed by the above processes can be further degraded to free amino acids by cytosolic peptidases (Step 8).


Ubiquitin-mediated degradation of protein is involved in various biological processes. The selective and programmed degradation of cell-cycle regulatory proteins, such as cyclins, inhibitors of cyclin-dependent kinases, and anaphase inhibitors are essential events in cell-cycle progression. Cell growth and proliferation are further controlled by ubiquitin-mediated degradation of tumor suppressors, protooncogenes, and components of signal transduction systems. The rapid degradation of numerous transcriptional regulators is involved in a variety of signal transduction processes and responses to environmental cues. The ubiquitin system is clearly involved in endocytosis and down-regulation of receptors and transporters, as well as in the degradation of resident or abnormal proteins in the endoplasmic reticulum. There are strong indications for roles of the ubiquitin system in development and apoptosis, although the target proteins involved in these cases have not been identified. Dysfunction in several ubiquitin-mediated processes causes pathological conditions, including malignant transformation.


Our knowledge of different signals in proteins that mark them for ubiquitinylation is also limited. Recent reports indicate that many proteins are targeted for degradation by phosphorylation. It was observed previously that many rapidly degraded proteins contain PEST elements, regions enriched in Pro, Glu, Ser, and Thr residues. More recently, it was pointed out that PEST elements are rich in S/TP sequences, which are minimum consensus phosphorylation sites for Cdks and some other protein kinases. Indeed, it now appears that in several (though certainly not all) instances, PEST elements contain phosphorylation sites necessary for degradation. Thus multiple phosphorylations within PEST elements are required for the ubiquitinylation and degradation of the yeast G1 cyclins Cln3 and Cln2, as well as the Gcn4 transcriptional activator. Other proteins, such as the mammalian G1 regulators cyclin E and cyclin D1, are targeted for ubiquitinylation by phosphorylation at specific, single sites. In the case of the IkBα inhibitor of the NF-kB transcriptional regulator, phosphorylation at two specific sites, Ser-32 and Ser-36, is required for ubiquitin ligation. β-cateinin, which is targeted for ubiquitin-mediated degradation by phosphorylation, has a sequence motif similar to that of IkBα around these phosphorylation sites. However, the homology in phosphorylation patterns of these two proteins is not complete, because phosphorylation of other sites of β-cateinin is also required for its degradation. Other proteins targeted for degradation by phosphorylation include the Cdk inhibitor Siclp and the STAT1 transcription factor. Though different patterns of phosphorylation target different proteins for degradation, a common feature appears to be that the initial regulatory event is carried out by a protein kinase, while the role of a ubiquitin ligase would be to recognize the phosphorylated form of the protein substrate. It further appears that different ubiquitin ligases recognize different phosphorylation patterns as well as additional motifs in the various protein substrates. However, the identity of such E3s is unknown, except for some PULC-type ubiquitin ligases that act on some phosphorylated cell-cycle regulators in the budding yeast. The multiplicity of signals that target proteins for ubiquitin-mediated degradation (and of ligases that have to recognize such signals) is underscored by observations that the phosphorylation of some proteins actually prevents their degradation. Thus the phosphorylation of the c-Mos protooncogene on Ser3 and the multiple phosphorylations of c-Fos and c-Jun protooncogenes at multiple sites by MAP kinases suppress their ubiquitinylation and degradation.


In addition to the families of enzymes involved in conjugation of ubiquitin, a very large family of deubiquitinating enzymes has recently been identified from various organisms. These enzymes have several possible functions. First, they may have peptidase activity and cleave the products of ubiquitin genes. Ubiquitin is encoded by two distinct classes of genes. One is a polyubiquitin gene, which encodes a linear polymer of ubiquitins linked through peptide bonds between the C-terminal Gly and N-terminal Met of contiguous ubiquitin molecules. Each copy of ubiquitin must be released by precise cleavage of the peptide bond between Gly-76-Met-1 of successive ubiquitin moieties. The other class of ubiquitin genes encodes ubiquitin C-terminal extension proteins, which are peptide bond fusions between the C-terminal Gly of ubiquitin and N-terminal Met of the extension protein. To date, the extensions described are ribosomal proteins consisting of 52 or 76-80 amino acids. These ubiquitin fusion proteins are processed to yield ubiquitin and the corresponding C-terminal extension proteins. Second, deubiquitinating enzymes may have isopeptidase activities. When a target protein is degraded, deubiquitinating enzymes can cleave the polyubiquitin chain from the target protein or its remnants. The polyubiquitin chain must also be disassembled by deubiquitinating enzymes during or after proteolysis by the 26 S proteasome, regenerating free monomeric ubiquitin. In this way, deubiquitinating enzymes can facilitate the ability of the 26 S proteasome to degrade ubiquitinated proteins. Third, deubiquitinating enzymes may hydrolyze ester, thiolester, and amide linkages to the carboxyl group of Gly-76 of ubiquitin. Such nonfunctional linkages may arise from reactions between small intracellular compounds such as glutathione and the E1-, E2-, or E3-ubiquitin thiolester intermediates. Fourth, deubiquitinating enzymes may compete with the conjugating system by removing ubiquitin from protein substrates, thereby rescuing them from degradation or any other function mediated by ubiquitination. Thus generation of ubiquitin by deubiquitinating enzymes from the linear polyubiquitin and ubiquitin fusion proteins and from the branched polyubiquitin ligated to proteins should be essential for maintaining a sufficient pool of free ubiquitin. Many deubiquitinating enzymes exist, suggesting that these deubiquitinating enzymes recognize distinct substrates and are therefore involved in specific cellular processes. Although there is recent evidence to support such specificity of these deubiquitinating enzymes, the structure-function relationships of these enzymes remain poorly studied.


Deubiquitinating enzymes can be divided broadly on the basis of sequence homology into two classes, the ubiquitin-specific processing protease (UBP or USP, also known as type 2 ubiquitin C-terminal hydrolase (type 2 UCH)) and the UCH, also known as type 1 UCH). UCH (type 1 UCH) enzymes hydrolyze primarily C-terminal esters and amides of ubiquitin but may also cleave ubiquitin gene products and disassemble polyubiquitin chains. They have in common a 210-amino acid catalytic domain, with four highly conserved blocks of sequences that identify these enzymes. They contain two very conserved motifs, the CYS and HIS boxes. Mutagenesis studies revealed that the two boxes play important roles in catalysis. Some UCH enzymes have significant C-terminal extensions. The functions of the C-terminal extensions are still unknown but appear to be involved in proper localization of the enzyme. The active site of these UCH enzymes contains a catalytic triad consisting of cysteine, histidine, and aspartate and utilizes a chemical mechanism similar to that of papain. The crystal structure of one of these, UCH-L3, has been solved at 1.8 Å resolution. The enzyme comprises a central antiparallel β-sheet flanked on both sides by helices. The β-sheet and one of the helices are similar to those observed in the thiol protease cathepsin B. The similarity includes the three amino acid residues that comprise the active site, Cys95, His169, and Asp184. The active site appears to fit the binding of ubiquitin that may anchor also at an additional site. The catalytic site in the free enzyme is masked by two different segments of the molecule that limit nonspecific hydrolysis and must undergo conformational rearrangement after substrate binding.


UBP (type 2 UCH) enzymes are capable of cleaving the ubiquitin gene products and disassembling polyubiquitin chains after hydrolysis. It appears that there is a core region of about 450 amino acids delimited by CYS and HIS boxes. Many of these isoforms have N-terminal extensions and a few have C-terminal extensions. In addition, there are variable sequences in the core region of many of the isoforms. The functions of these divergent sequences remain poorly characterized. Another interesting function of specific UBPs is the regulation of cell proliferation. It was observed that cytokines induced in T-cells specific de-ubiquitinating enzymes (DUBs), termed DUB-1 and DUB-2. DUB-1 is induced by stimulation of the cytokine receptors for IL-3, IL-5, and GM-CSF, suggesting a role in its induction for the β-common (betac) subunit of the interleukin receptors. Overexpression of a dominant negative mutant of JAK2 inhibits cytokine induction of DUB-1, suggesting that the regulation of the enzyme is part of the cell response to the JAK/STAT signal transduction pathway. Continued expression of DUB-1 arrests cells at G1; therefore, the enzyme appears to regulate cellular growth via control of the G0-G1 transition. The catalytic conserved Cys residue of the enzyme is required for its activity. DUB-2 is induced by IL-2 as an immediate early (IE) gene that is down-regulated shortly after the initiation of stimulation. The function of this enzyme is also obscure. It may stimulate or inhibit the degradation of a critical cell-cycle regulator.


Cytokines, such as interleukin-2 (IL-2), activate intracellular signaling pathways via rapid tyrosine phosphorylation of their receptors, resulting in the activation of many genes involved in cell growth and survival. The deubiquitinating enzyme DUB-2 is induced in response to IL-2 and is expressed in human T-cell lymphotropic virus-I (HTLV-1)-transformed T cells that exhibit constitutive activation of the IL-2 JAK/STAT (signal transducers and activators of transcription) pathway, and when expressed in Ba/F3 cells DUB-2 markedly prolonged IL-2-induced STAT5 phosphorylation. Although DUB-2 does not enhance IL-2-mediated proliferation, when withdrawn from growth factor, cells expressing DUB-2 had sustained STAT5 phosphorylation and enhanced expression of IL-2-induced genes cis and c-myc. DUB-2 expression markedly inhibited apoptosis induced by cytokine withdrawal allowing cells to survive. Therefore, DUB-2 has a role in enhancing signaling through the JAK/STAT pathway, prolonging lymphocyte survival, and, when constitutively expressed, may contribute to the activation of the JAK/STAT pathway observed in some transformed cells. (Migone, T.-S., et al., Blood. 2001; 98:1935-1941).


Protein ubiquitination is an important regulator of cytokine-activated signal transduction pathways and hematopoietic cell growth. Protein ubiquitination is controlled by the coordinate action of ubiquitin-conjugating enzymes and deubiquitinating enzymes. Recently a novel family of genes encoding growth-regulatory deubiquitinating enzymes (DUB-1 and DUB-2) has been identified. DUBs are immediate-early genes and are induced rapidly and transiently in response to cytokine stimuli. By means of polymerase chain reaction amplification with degenerate primers for the DUB-2 complementary DNA, 3 murine bacterial artificial chromosome (BAC) clones that contain DUB gene sequences were isolated. One BAC contained a novel DUB gene (DUB-2A) with extensive homology to DUB-2. Like DUB-1 and DUB-2, the DUB-2A gene consists of 2 exons. The predicted DUB-2A protein is highly related to other DUBs throughout the primary amino acid sequence, with a hypervariable region at its C-terminus. In vitro, DUB-2A had functional deubiquitinating activity; mutation of its conserved amino acid residues abolished this activity. The 5′ flanking sequence of the DUB-2A gene has a hematopoietic-specific functional enhancer sequence. It is proposed that there are at least 3 members of the DUB subfamily (DUB-1, DUB-2, and DUB-2A) and that different hematopoietic cytokines induce specific DUB genes, thereby initiating a cytokine-specific growth response. (Baek, K.-H., et al, Blood. 2001; 98:636-642).


Protein ubiquitination also serves regulatory functions in the cell that do not involve proteasome-mediated degradation. For example, Hicke and Riezman have recently demonstrated ligand-inducible ubiquitination of the Ste2 receptor in yeast. Ubiquitination of the Ste2 receptor triggers receptor endocytosis and receptor targeting to vacuoles, not proteasomes. Also, Chen et al. have demonstrated that activation of the IB kinase requires a rapid, inducible ubiquitination event. This ubiquitination event is a prerequisite for the specific phosphorylation of IB and does not result in subsequent proteolysis of the kinase complex. The ubiquitination of Ste2 and IB kinase appears reversible, perhaps resulting from the action of a specific deubiquitinating enzyme.


A large superfamily of genes encoding deubiquitinating enzymes, or UBPs, has recently been identified. UBPs are ubiquitin-specific thiol-proteases that cleave either linear ubiquitin precursor proteins or post-translationally modified proteins containing isopeptide ubiquitin conjugates. The large number of UBPs suggests that protein ubiquitination, like protein phosphorylation, is a highly reversible process that is regulated in the cell.


Interestingly, UBPs vary greatly in length and structural complexity, suggesting functional diversity. While there is little amino acid sequence similarity throughout their coding region, sequence comparison reveals two conserved domains. The Cys domain contains a cysteine residue that serves as the active enzymatic nucleophile. The His domain contains a histidine residue that contributes to the enzyme's active site. More recent evidence demonstrates six homology domains contained by all members of the ubp superfamily. Mutagenesis of conserved residues in the Cys and His domains has identified several residues that are essential for UBP activity.


Recently, a growth regulatory deubiquitinating enzyme, DUB-1, that is rapidly induced in response to cytokine receptor stimulation was identified. DUB-1 is specifically induced by the receptors for IL-3, granulocyte macrophage-colony-stimulating factor, and IL-5, suggesting a specific role for the c subunit shared by these receptors. In the process of cloning the DUB-1 gene, a family of related, cross-hybridizing DUB genes was identified. From this, other DUB genes might be induced by different growth factors. Using this approach, an IL-2-inducible DUB enzyme, DUB-2 and closely related DUB-2a were identified. DUB-1 and DUB-2 are more related to each other than to other members of the ubp superfamily and thereby define a novel subfamily of deubiquitinating enzymes.


Hematopoietic-specific, cytokine induced DUBs in murine system have shown to prolong cytokine receptor, see Migone, T. S., et al. (2001). The deubiquitinating enzyme DUB-2 prolongs cytokine-induced signal transducers and activators of transcription activation and suppresses apoptosis following cytokine withdrawal, Blood 98, 1935-41; Zhu, Y., et al., (1997). DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes, J Biol Chem 272, 51-7 and Zhu, Y., et al., (1996). The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor, Mol Cell Biol 16, 4808-17.). These effects are likely due to the deubiquitination of receptors or other signaling intermediates by DUB-1 or DUB-2, murine analogs of hDUBs. Inhibition of hDUBs may achieve downregulation of specific cytokine receptor signaling, thus modulating specific immune responses.


Cytokines regulate cell growth by inducing the expression of specific target genes. A recently identified a cytokine-inducible, immediate-early gene, DUB-1, encodes a deubiquitinating enzyme with growth regulatory activity. In addition, a highly related gene, DUB-2, that is induced by interleukin-2 was identified. The DUB-2 mRNA was induced in T cells as an immediate-early gene and was rapidly down-regulated. Like DUB-1, the DUB-2 protein had deubiquitinating activity in vitro. When a conserved cysteine residue of DUB-2, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. DUB-1 and DUB-2 proteins are highly related throughout their primary amino acid sequence except for a hypervariable region at their COOH terminus. Moreover, the DUB genes co-localize to a region of mouse chromosome 7, suggesting that they arose by a tandem duplication of an ancestral DUB gene. Additional DUB genes co-localize to this region, suggesting a larger family of cytokine-inducible DUB enzymes. We propose that different cytokines induce specific DUB genes. Each induced DUB enzyme thereby regulates the degradation or the ubiquitination state of an unknown growth regulatory factor, resulting in a cytokine-specific growth response.


On the basis of these structural criteria, additional members of the DUB subfamily can be identified in the GenBank™. The highest degree of homologyis in the Cys and His domains. Additionally, this putative human DUB protein contains a Lys domain (amino acids 400-410) and a hypervariable region (amino acids 413-442).


Murine DUB (mDUB) subfamily members differ from other UBPs by functional criteria as well. mDUB subfamily members are cytokine-inducible, immediate-early genes and may therefore play regulatory roles in cellular growth or differentiation. Also, DUB proteins are unstable and are rapidly degraded by ubiquitin-mediated proteolysis shortly after their induction.


mDUB reports demonstrate that specific cytokines, such as IL-2 and IL-3, induce specific deubiquitinating enzymes (DUBs). The DUB proteins may modify the ubiquitin-proteolytic pathway and thereby mediate specific cell growth or differentiation signals. These modifications are temporally regulated. The DUB-2 protein, for instance, is rapidly but transiently induced by IL-2. Interference of DUB enzymes with specific isopeptidase inhibitors may block specific cytokine signaling events.


Defensins constitute a major family of antimicrobial peptides in mammals. Depending on the distribution of the cysteines and the linkages of the disulfide bonds, human defensins can be divided into two categories: α-defensins, which can be found in granulocytes and in epithelial cells of the small intestine, and β-defensins, which are expressed by epithelial cells and leukocytes including macrophages. Some defensins are expressed constitutive manner in granulocytes and epithelial cells where as others are induces by either exposure to microbial pathogens or pro-inflammatory cytokines such as IL-1β, TNF-α and interferon-γ. The genes coding for human defensins are clustered within 1 Mb segment on chromosome 8P23, and it has been suggested that β-defensins may predate the a-defensin family during recent gene amplification since α-defensin cannot be detected even in many mammalians including cow. Cow has at least 13 β-defensins but no α-defensin. β-defensins contribute to early host defense against several bacterial and fungal pathogens, as an important mechanism of innate immune response. Beside this antimicrobial activity, a chemoattractant activity on both immature dentritic cells and memory T cells, as well as monocytes, has been recently described, demonstrating that β-defensins may promote both innate and adaptive immune response.




BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1: Proposed enzyme reaction mechanism of DUB-




SUMMARY OF THE INVENTION

The present invention is directed to analogs of murine DUBs, hematopoietic-specific, cytokine-inducible deubiquitinating proteases found as a cluster of genes on chromosomes 4 and 8 and respective regulatory regions. Eleven novel human DUBs and four potential genes that express truncated form of DUBs not previously reported in public databases were identified by searching human genome database using murine DUB-1 and DUB-2 sequences. These genes share open reading frames (ORFs) that are 88 to 99% amino acid identity to each other, when gaps caused by deletion and N-terminal and/or C-terminal extension was not counted as mismatch, and exhibit approximately 50% identity to murine DUBs. Eight of eleven ORFs generate a protein of 530 amino acids. Two ORFs (hDUB8.3 and hDUB8.11) have internal in-frame deletions such that the genes are capable of generating 497 and 417 amino acid long polypeptides, respectively. One ORF (hDUB4.5) exhibits extension at both 5′ and 3′ end of the ORF so that the gene is capable of expressing 574 amino acid long polypeptide. Surprisingly, this 5′ extension results in specific pro-polypeptide sequence that can direct polypeptide targeting to the mitochondria. Furthermore, the respective regulatory regions, putative promoters, of these genes also share close to 90% identity each other suggesting that their expression is coordinated. In addition, we found that two of these genes can be expressed under the control of separate promoters that can be controlled independently and expressing potentially distinctive protein products.


Manipulation of these gene products by small molecular compounds can (1) reduce inflammation by regulating proinflammatory cytokine signaling, (2) modulate autoimmune diseases by regulating cytokine receptor signaling that are critical for lymphocytes proliferation, and (3) immune over-reaction during infection using above mechanisms.


Two of cluster genes (hDUB4.1 and hDUB4.2) possesses two distinctive promoter domains in front of their ORFs such that they can be regulated independently in their transcription potential. The longer transcripts of these ORFs (called hDUB4.1a and hDUB4.2a) has 12 and 4 exons respectively and capable of generating 1016 and 1021 amino acid long polypeptides, respectively. These polypeptides share C-terminal 530 amino acids with their shorter form that can be expressed separately from independent promoters (called hDUB4.1b and hDUB4.2b, respectively). In addition, two other ORFs are capable of generating longer than 530 amino acid polypeptides (hDUB4.10 and hDUB4.11). Remarkably, these two deduced polypeptides shares significant homology within portion of N-terminal portions (I added alignment file of these at the end of sequence file). Three of the ORFs (hDUB4.5, 4.8, and 8.2) has N-terminal insertion that is typical for mitochondria targeting sequence. An alignment of these sequences is provide in the Tables. The promoter sequences defined as upstream of initiation ATG of the ORF exhibit remarkable level of homology each other except that of hDUB4.1a. The sequence identity among all promoter sequences except that of hDUB4.1a is approximately 90% in 2000 base pair span upstream of initiation ATG. Two of the promoter sequences (hDUB8.3 and 8.11) have 334 nucleotides insertion at approximately 1000 base pair upstream of initiation ATG. Interestingly, hDUB8.3 and hDUB8.11 are the only ones with shorter ORFs due to the internal deletions. In addition to these ORFs, there are 5 ORFs that are capable of expressing polypeptides (hDUB4.4, hDUB4.9, hDUB8.2, hDUB8.9, and hDUB8.10) that share initiation codon with other 530 amino acid long polypeptides but terminate prematurely due to the in frame termination sequences. These also shares significant homology upstream of ATG initiation codon suggesting they may expressed as truncated proteins, potential regulatory functions. All 11 hDUB8 genes are clustered with the defensin clusters within 2 Mb region in 8P23, implying that both acquisition and amplification are relatively recent event, perhaps during mammalian evolution. It is of interest that hDUB4 gene cluster is also in highly amplified cluster region of chromosome 4P16 that is yet to be assigned in chromosome location. These data suggest that hDUB4s and hDUB8s are within very dynamic region of the human chromosomes (both 4p 16 and 8p23) that are undergoing volatile amplifications. The data also suggest that expression of hDUB8 may also be coordinated in conjunction with defensins that are critical components of innate immune response and inflammation.


Search Methods for Identifying Human Analogs of mDUBs:


In order to identify human analogs of mDUB1, -2, -2A, mDUB1 (U41636), mDUB2 (NM010089), and mDUB2A (AF393637) DNA sequences were used to search against Ensembl entire “golden path” (as contigs) using Ensembl blast search engine (http://www.ensembl.org/perl/blastview). All three mDUBs have significant alignments with contig AC083981, AF252831, AF228730, AF252830, AC068974 on chromosome 8 with the high score above 2000 and the probability less than e-87. In order to find all the homolog genes in the genome, exhaust search was performed using genomic aligned sequence to search against the “golden path” contigs. Two more contigs were found to have significant alignment that has probability less than e-100: one is AC074340 on chromosome 8 and the other is AC022770 on chromosome 4.


DNA sequences for contig AC083981, AF252831, AF228730, AF252830, AC068974, AC074340 and AC022770 were downloaded from Ensembl and gene annotation for each contig was performed using GenScan gene annotation program. Genes having homolog with mDUBs were named in sequence based on their locations on chromosomes.


For example, hDUB8.1 was derived from AF228730, 8.2, 8.3 were derived from AF252830, 8.5 were derived from AC074340, 8.6 were derived from AF252831, 8.7, 8.8 and 8.9 were derived from AC083981, and 8.10 and 8.11 were derived from AC068974. hDUB4.1, 4.2, 4.3, 4.4, 4.5 were derived from AC022770 on chromosome 4.


Using these hDUB4s and hDUB8s, both Ensemble and NCBI blast search was performed. Further contig NT028165 that covers chromosome 4 was identified. From this and already assembled chromosome 4p16.1 region, further annotation was performed using GenScan gene annotation program. From this we identified hDUB4.6, 4.7, 4.8, 4.9, 4.10, and 4.11.


Analysis of the hDUB gene clusters in chromosome 4 reveals that at least five ORFs in an unmapped cOntig (AC022770) were identified by nucleotide homology search with murine DUB1 and 2. At least four out of five ORFs share core 530 amino acid sequences. Two ORFs (hDUB4.1 and hDUB4.2) are multi-exon ORFs that extend N-terminal part of polypeptides that shares minimal sequence identity. However, there is a conserved putative promoter sequences that encompass over 2,000 bases in the intron region proximal to the last exon that is conserved among all 5 genes. Three of the ORFs (hDUB4.5, 4.8, and 8.2) has N-terminal insertion that is typical for mitochondria targeting sequence. The hDUB genes cluster in 4P16 of the human chromosome, which is an unmapped part of the human chromosome.


Analysis of the hDUB gene clusters in chromosome 8 reveals that at least eleven ORFs in six different contigs (AC068974, AC074340, AC083981, AF228730, AF252830, and AF252831) were identified by nucleotide homology search with murine DUB1 and 2. At least seven out of eleven ORFs share significant identities with similar length. There are conserved putative promoter sequences that encompass over 2,000 bases in all 11 genes. The hDUB genes cluster in 8P23.1 of the human chromosome and clustered with defensin molecules (at lease 9 defensins are clustered with hDUB8s) and the whole domain belongs the olfactory GPCR cluster.


Analysis of the deduced amino acid sequences of the hDUBs reveals polypeptides consistent with mDUBs, which contain highly conserved Cys and His domains that are likely to form the enzyme's active site. The putative active site nucleophile of mDUB-2 is a cysteine residue (Cys−60) in the Cys domain. Both mDUB-1 and mDUB-2 have a lysine rich region (Lys domain; amino acids 374-384 of mDUB-2) and a short hypervariable region (amino acids 385-451 of mDUB-2), in which the mDUB-1 and mDUB-2 sequences diverge considerably. The hypervariable (HV) region of mDUB-2 contains a duplication of the eight-amino acid sequence: PQEQNHQK (Seq ID No. 55).


The protein and nucleotide sequences named in this invention and their corresponding Sequence ID No are set forth as following:


Nucleotide Sequence for hDUB4.1a: Seq ID No. 3


hDUB4.1a deduced polypeptide sequence: Seq ID No. 4


Nucleotide Sequence for hDUB4.1b: Seq ID No. 5


hDUB4.1b deduced polypeptide sequence: Seq ID No. 6


Nucleotide Sequence for hDUB4.2a: Seq ID No. 7


hDUB4.2a deduced polypeptide sequence: Seq ID No. 8


Nucleotide Sequence for hDUB4.2b: Seq ID No. 9


hDUB4.2b deduced polypeptide sequence: Seq ID No. 10


Nucleotide Sequence for hDUB4.3: Seq ID No. 11


hDUB4.3 deduced polypeptide sequence: Seq ID No. 12


Nucleotide Sequence for hDUB4.5: Seq ID No. 13


hDUB4.5 deduced polypeptide sequence: Seq ID No. 14


Nucleotide Sequence for hDUB4.6: Seq ID No. 15


hDUB4.6 deduced polypeptide sequence: Seq ID No. 16


Nucleotide Sequence for hDUB4.7: Seq ID No. 17


hDUB4.7 deduced polypeptide sequence: Seq ID No. 18


Nucleotide Sequence for hDUB4.8: Seq ID No. 19


hDUB4.8 deduced polypeptide sequence: Seq ID No. 20


Nucleotide Sequence for hDUB4.10: Seq ID No. 21


hDUB4.10 deduced polypeptide sequence: Seq ID No. 22


Nucleotide Sequence for hDUB4.11: Seq ID No. 23


hDUB4.11 deduced polypeptide sequence: Seq ID No. 24


Nucleotide Sequence for hDUB8.1: Seq ID No. 25


hDUB8.1 deduced polypeptide sequence: Seq ID No. 26


Nucleotide Sequence for hDUB8.3: Seq ID No. 27


hDUB8.3 deduced polypeptide sequence: Seq ID No. 28


Nucleotide Sequence for hDUB8.5: Seq ID No. 29


hDUB8.5 deduced polypeptide sequence: Seq ID No. 30


Nucleotide Sequence for hDUB8.6: Seq ID No. 31


hDUB8.6 deduced polypeptide sequence: Seq ID No. 32


Nucleotide Sequence for hDUB8.7: Seq ID No. 33


hDUB8.7 deduced polypeptide sequence: Seq ID No. 34


Nucleotide Sequence for hDUB8.8: Seq ID No. 35


hDUB8.8 deduced polypeptide sequence: Seq ID No. 36


Nucleotide Sequence for hDUB8.11: Seq ID No. 37


hDUB8.11 deduced polypeptide sequence: Seq ID No. 38


Nucleotide Sequence for hDUB4.4: Seq ID No. 39


hDUB4.4 deduced polypeptide sequence: Seq ID No. 40


Nucleotide Sequence for hDUB4.9: Seq ID No. 41


hDUB4.9 deduced polypeptide sequence: Seq ID No. 42


Nucleotide Sequence for hDUB8.2: Seq ID No. 43


hDUB8.2 deduced polypeptide sequence: Seq ID No. 44


Nucleotide Sequence for hDUB8.9: Seq ID No. 45


hDUB8.9 deduced polypeptide sequence: Seq ID No. 46


Nucleotide Sequence for hDUB8.10: Seq ID No. 47


hDUB8.10 deduced polypeptide sequence: Seq ID No. 48


Promoter sequence for hDUB4.6: Seq ID No. 49


Promoter sequence for hDUB4.7: Seq ID No. 50


Promoter sequence for hDUB4.8: Seq ID No. 51


Promoter sequence for hDUB4.9: Seq ID No. 52


Promoter sequence for hDUB4.10: Seq ID No. 53


Promoter sequence for hDUB4.11: Seq ID No. 54


TaqMan Real Time PCR Analysis of Expression of hDUB4s and hDUB8s in Human Immunocytes Upon Various Stimulation


Protocol of reverse transcription (RT) from total cellular RNA using random hexamer as primer (using TaqMan Reverse Transcription Reagents Cat# N808-0234)


1 ug of total RNA preparation in 100 ul of 1×TaqMan RT Buffer Mix, 5.5 mM MgCl2, 0.5 mM dNTPs, 2.5 uM Random Hexamers, 40 U RNAse inhibitor, 125U Multiscribe Reverse Transcriptase. Mix by pipeting up and down. Incubate 25° C. for 10 minutes (annealing step), 48° C. for 30 minutes (reverse transcription), and 95° C. for 5 minutes (heat killing of the enzyme). The samples can be left at the machine at 4° C., or alternatively, can be stored at −20° C. Yield of cDNA synthesis can be measured by incorporation of small portion of radioactive dATP (or dCTP). Average efficiency for this protocol is between 60-80% of conversion of RNA to cDNA.


Protocol of TaqMan Real-Time Quantitative PCR


1 ul of TaqMan RT product in 12.5 ul of 1× master Mix (Applied Biosystems Cat# 4304437) containing all necessary reaction components except primers and probes, 0.9 uM forward primer, 0.9 uM reverse primer, 0.2 uM probe. Mix by pipetting up and down. Samples containing GADPH primer pair and probe were also prepared as control. Thermal cycling and detection of the real-time amplification were performed using the ABI PRISM 7900HT Sequence Detection System. The quantity of target gene is given relative to the GADPH control based on Ct values determined during the exponential phase of PCR.


Primer-Probe Sets Used and their Specificities:


Primer 4.1 is unique for hDUB 4.1


Primer 4.2 covers hDUB 4.2, 4.3, 4.5 and 8.1


Primer 8.3 covers hDUB 8.3 and 8.11


Primer 8.5 is unique for hDUB 8.5


Primer 8.6 covers hDUB 8.6, 8.7 and 8.8

TABLE 1Expression of hDUBs in PBMC stimulated with LPS (100 ng/ml) andPHA (5 μg/ml) for 7 hours.Donor 1Fold-Donor 2UpregulationRelativeFold-UpregulationRelativePrimerupon stimulationexpressionupon stimulationexpression4.12.213.814.22.0210002.0164008.31.855601.855008.52.1803.13108.62.6192003.023000









TABLE 2










Expression of hDUBS in PBMC stimulated with LPS


(100 ng/ml) for 1.5, 7 and 24 hours (DONOR 4)











1.5 hours
7 hours
24 hours














Fold-

Fold-

Fold-




Upregulation

Upregulation

Upregulation



upon
Relative
upon
Relative
upon
Relative


Primer
stimulation
expression
stimulation
expression
stimulation
expression
















4.2
2.4
64
336
35.2
1.8
12.5


8.3
0.4
1
13.1
1
1.7
1


8.5
1.6
11
65.9
4.8
1.5
1.8
















TABLE 3










Expression of DUBs in PBMC stimulated with LPS (100 ng/ml)


and/or PHA (5 ug/ml) for 1.5, 7, 24 hours (donor 4)











1.5 hours
7 hours
24 hours














Fold-

Fold-

Fold-




Upregulation

Upregulation

Upregulation



upon
Relative
upon
Relative
upon
Relative


Stimuli
stimulation
expression
stimulation
expression
stimulation
expression

















LPS
4.2
0.4
39
2.5
54
1.6
48



8.3
0.5
5
1.6
6
1.1
7



8.5
0.9
1
1.5
1.7
1.4
2



8.6
0.6
26
1.7
57
1.0
21


PHA
4.2
3.5
367
4.4
94
0.9
26



8.3
1.5
13
1.7
6
0.7
5



8.5
1.9
2
0.9
1
0.7
1



8.6
2.3
103
2.5
23
0.8
17


LPS + PHA
4.2
1.2
129
3.4
73
0.8
23



8.3
1.0
9
2.2
8
0.7
5



8.5
1.0
1
0.9
1.3
0.9
1.2



8.6
1.3
56
2.5
33
0.8
18









There is no increase of expression in T lymphocytes (donor 5) and B lymphocytes (donor 6) when stimulated with anti-CD4/CD28 and anti-CD40/IL-4, respectively.

TABLE 4Expression of hDUB 4.2, 4.3, 4.5 and 8.1 examined by primer 4.2 indifferent human organ panel by TaqMan analysis.β2Tissue TypeMeanMean∂∂ CtExpressionAdrenal Gland29.7220.0010.080.92Bone marrow34.0220.4913.890.07Brain26.9222.734.5442.84Colon32.0319.9712.420.18Fetal Brain27.5924.233.7176.15Fetal Liver33.2222.5810.990.49Heart33.0921.6011.850.27Kidney29.9321.978.323.13Lung32.1019.3113.150.11Mammary Gland30.0021.748.612.56Pancreas34.8324.0711.110.45Placenta36.6023.7713.190.00Prostate29.1420.938.552.66Salivary Gland32.1121.3911.070.46Skeletal Muscle28.2720.448.183.45Small Intestine34.3321.0013.690.08Spinal Cord27.0421.915.4722.48Spleen32.4519.0213.780.07Stomach32.1521.6610.840.55Testis28.5723.075.8717.16Thymus31.0120.6810.690.61Thyroid28.8420.808.392.97Trachea31.3919.6312.110.23Uterus30.3721.099.641.25PBMC/Control33.9818.8215.520.02PBMC/PMA33.6218.8115.170.03PBMC/PHA34.2018.7715.780.02PBMC/HDM34.2317.8116.770.01A549 Cells31.9821.5710.770.57THP-135.4820.7515.090.00Ovary31.8421.5510.650.62(+ve) Positive Control29.6121.868.113.62









TABLE 5










Expression of hDUB 4.2, 4.3, 4.5 and 8.1 examined by primer 4.2


in human immunocytes panel:











Cell Type and stimulation

β2




condition
Mean
Mean
∂∂ Ct
Expression














Granulocyte resting
34.18
17.22
17.50
0.005


Granulocyte TNF-custom character4/24 hr
32.39
17.16
15.76
0.018


CD19 (tonsillar - CD40L)
28.7
19.92
9.32
1.565


CD19 (tonsillar - LPS)
31.14
20.67
11.00
0.488


FLS-REST
34.67
20.43
14.78
0.036


FLS-IL1 4/24 hr
34.26
20.41
14.38
0.047


FLS-TNF-custom character4/24 hr
34.91
20.15
15.31
0.025


Monocyte resting (pool 1.5, 7,
33.63
18.29
15.89
0.017


24 hr)


Monocyte LPS (pool 1.5, 7, 24 hr)
34.55
18.03
17.06
0.007


Monocyte INF-g (pool 1.5, 7,
34.62
17.27
17.88
0.004


24 hr)


Monocyte LPS & IFN-custom character(pool
34.87
17.38
18.03
0.004


1.5, 7, 24 hr)


DCs progenitors (CD14+)
35.87
19.73
16.67
0.000


DCs immature
35.48
18.18
17.84
0.000


DCs mature
37.46
17.92
20.07
0.000


TH0 resting
31.11
17.63
14.02
0.060


TH0 activated
31.29
18.23
13.60
0.081


Th1 resting
33.88
18.27
16.15
0.014


Th1 CD28/CD3
32.15
19.31
13.38
0.094


Th2 resting
33.94
18.07
16.40
0.012


Th2 CD28/CD3
33.27
18.78
15.02
0.030


BSMC
35.33
21.64
14.22
0.000


BSMC IL-4 + TNF-custom character24 hr
36.44
21.52
15.45
0.000


BSMC IL-13 + TNF-custom character24 hr
35.94
21.41
15.07
0.000


BSMC IL-4 + IL-13
36.28
22.09
14.73
0.000


NHBE d0
36.63
22.24
14.92
0.000


NHBE IL-4 + TNF-custom characterd0
35.72
21.42
14.83
0.000


NHBE IL-13 + TNF-custom characterd0
36.35
21.37
15.52
0.000


NHBE resting d7 + d14
34.89
22.41
13.01
0.121


NHBE IL-4 + TNF-custom characterd7 + d14
38.59
22.02
17.11
0.000


NHBE IL-13 + TNF-custom characterd7 + d14
37.62
21.93
16.23
0.000


CD8 T cell O hour
30.15
19.52
11.16
0.437


CD8 T cell a-CD3/CD28 4 hour
32.08
19.6
13.01
0.121


CD8 T cell a-CD3/CD28 24
30.94
18.64
12.84
0.137


hour


HMVEC resting
35.09
20.25
15.38
0.000


HMVEC TNF-custom character+ IL-4 24 hr
35.91
20.86
15.59
0.000


HMVEC TNF-custom character24 hr
35.57
21.06
15.05
0.000


HMVEC TNF-custom character+ IL-13 24 hr
36.38
20.61
16.31
0.000


Normal synovium pool
34.92
21.16
14.3
0.050


RA synovium pool
33.65
20.88
13.3
0.099


Normal colon
32.5
21.68
11.36
0.381


Colitis Colon
33.17
21.32
12.39
0.187


Crohns colon pooled
32.91
22.06
11.39
0.374


Normal Lung
31.01
20.5
11.05
0.472


COPD Lung
35.09
22.14
13.49
0.000


Positive control
28.4
22.29
6.64
9.992










Cloning of hDUB4, 8s by PCR


Following primer set was used to clone 530 amino acid open reading frame portion of single exon hDUB4s and 8s from human genomic DNA:

N-terminal primer:5′-atggaggacgactcactct-3′ (19 mer, Seq ID No.1)C-terminal primer:5′-ctggcacacaagcaga-3′ (19 mer, Seq ID No.2)


Underlined triplet nucleotides in each primer represent translational initiation and termination codon. This primer set can amplify most of hDUB4s and hDUB8s as well as potentially yet to be identified hDUBs that are similar enough to hDUB4s and hDUB8s due to the high homology in nucleotide sequences in this part of the ORF. 1593 base pair fragment was successfully amplified from genomic DNA from two healthy human subjects and cloned into pCR2.1 vector and transformed into TOP10 strain of E. coli. Over 300 independent clones with appropriate size insert were obtained and sequences are obtained by ABI automated DNA sequencers.


Deubiqititination Assay


Confirmation that the DUB is a deubiquitinating enzyme may be shown using previously identified deubiquitination assay of ubiquitin—galactosidase fusion proteins, as described previously in the literature. Briefly, a fragment of the DUB, of approximately 1,500 nucleotides, based on the wild-type DUB cDNA (corresponding to amino acids 1 to about 500) and a cDNA containing a missense mutation are generated by PCR and inserted, in frame, into pGEX (Pharmacia), downstream of the glutathione S-transferase (GST) coding element. Ub-Met—gal is expressed from a pACYC184-based plasmid. Plasmids are co-transformed as indicated into MC 1061 Escherichia coli. Plasmid-bearing E. coli MC 1061 cells are lysed and analyzed by immunoblotting with a rabbit anti—gal antiserum (Cappel), arabbit anti-GST antiserum (Santa Cruz), and the ECL system (Amersham Corp.). in vitro deubiquitinating enzyme activity may be shown from purified hDUB fusion protein using commercial polyubiquitinated protein as substrate.


HDUB4s and hDUB8s are Potential Inflammatory Cytokines Specific Immediate-Early Genes


mDUB-1 was originally cloned as an IL-3-inducible immediate-early gene. Similarly, in DUB-2 was cloned as an IL-2-inducible immediate-early gene. We examined inducibility as well as cell-type specific expression of these genes using multiple TaqMan analysis from human organ RNA samples and human immunocytes RNA samples. Our data suggest that expression of hDUBs are not apparent in lymphocytes and granulocytes but high in fresh human PBMC from several donor. This strongly suggest that expression may be limited to the monocytes/macrophages and potentially NK cells. hDUB4s and hDUB8s are upregulated in PBMC stimulated with stimuli (LPS and/or PHA) that is known to upregulate various inflammatory cytokines such as TNF-alpha, IL-1 beta etc. This increase of expression is almost completely disappeared 20 to 24 hours after stimulation suggesting this is an early gene. The fact that there is only weak expression upregulation at 1.5 hours after stimulation suggests that stimuli by themselves may not upregulate hDUB4s and hDUB8s, but cytokines that are upregulated within couple of hours after stimulation may be responsible for upregulation of the hDUB4s and hDUB8s.


The DUB Subfamily of the ubp Superfamily


From these data we propose that hDUB4s and hDUB8s are members of a discrete subfamily of deubiquitinating enzymes that shows the strongest similarity to mDUB subfamily including mDUB1, mDUB2, and mDUB2A, called the DUB subfamily. DUB subfamily members contain distinct structural features that distinguish them from other ubps. First, DUB subfamily members are comparatively small enzymes of approximately 500-550 amino acids. Second, DUB subfamily members share amino acid similarity not only in the Cys and His domains but also throughout their primary amino acid sequence. For instance, DUB proteins contain a lysine-rich region (Lys domain) and a HV domain near their carboxyl terminus.


The regulatory regions, or promoter regions, of each of the DUBs was analyzed for putative transcription factor binding motifs using TRANSFACFind, a dynamic programming method, see Heinemeyer, T., et al., “Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms” Nucleic Acids Res. 27, 318-322, (1999). The Transfac database provides eukaryotic cis- and trans-acting regulatory elements.

TABLE 6putative transcription factor binding motifs within the DUB regulatory or promoter,region of hDUB 4.1a. The position is indicated by nucleotides.TransfacPosition(Score)NameDescriptionM00271729 . . . 724(100)AML-1arunt-factor AML-1M00148296 . . . 302(100)SRYsex-determining region Y gene product1016 . . . 1010(96)958 . . . 964(94)474 . . . 480(94)1982 . . . 1988(92)129 . . . 123(90)857 . . . 863(90)776 . . . 782(90)1919 . . . 1913(90)1227 . . . 1233(90)276 . . . 282(90)1741 . . . 1735(90)193 . . . 199(90)105 . . . 111(90)M002401600 . . . 1606(100)Nkx-2.5homeo domain factor Nkx-2.5/Csx, tinmanhomolog700 . . . 694(100)M00083892 . . . 899(100)MZF1MZF1M00101162 . . . 156(100)CdxACdxA1008 . . . 1002(100)423 . . . 429(100)153 . . . 147(99)359 . . . 353(98)1388 . . . 1394(98)1644 . . . 1650(97)1702 . . . 1696(97)250 . . . 256(97)231 . . . 237(97)617 . . . 611(94)509 . . . 503(93)432 . . . 426(92)307 . . . 313(92)153 . . . 159(92)1832 . . . 1838(92)1366 . . . 1372(92)494 . . . 500(92)1450 . . . 1456(91)1456 . . . 1450(91)722 . . . 716(90)991 . . . 985(90)986 . . . 992(90)1646 . . . 1640(90)M002531142 . . . 1149(97)capcap signal for transcription initiation1344 . . . 1351(96)639 . . . 632(95)1313 . . . 1320(94)1872 . . . 1879(93)269 . . . 262(92)257 . . . 250(91)1103 . . . 1110(91)745 . . . 752(91)1589 . . . 1596(90)M00099978 . . . 993(96)S8S81637 . . . 1652(94)995 . . . 980(93)M00100162 . . . 156(96)CdxACdxA1008 . . . 1002(96)423 . . . 429(96)1774 . . . 1768(96)415 . . . 421(92)860 . . . 854(91)1026 . . . 1020(91)494 . . . 500(91)94 . . . 100(91)M00285725 . . . 713(95)TCF11TCF11/KCR-F1/Nrf1 homodimers982 . . . 970(92)M00347531 . . . 522(95)GATA-1GATA-binding factor 1M001351642 . . . 1660(95)Oct-1octamer factor 1M00075217 . . . 226(94)GATA-1GATA-binding factor 1M00278530 . . . 522(94)Lmo2complex of Lmo2 bound to Tal-1, E2A proteins,and GATA-1, half-site 2900 . . . 908(90)M00157990 . . . 978(94)RORalpha2RAR-related orphan receptor alpha2M00127533 . . . 520(93)GATA-1GATA-binding factor 1M001091933 . . . 1920(93)C/EBPbetaCCAAT/enhancer binding protein betaM001901656 . . . 1643(93)C/EBPCCAAT/enhancer binding factorM001371193 . . . 1205(93)Oct-1octamer factor 1248 . . . 260(90)1652 . . . 1640(90)M003021501 . . . 1512(92)NF-ATNuclear factor of activated T-cellsM00077900 . . . 908(91)GATA-3GATA-binding factor 3530 . . . 522(90)M00126533 . . . 520(91)GATA-1GATA-binding factor 1M001591231 . . . 1219(91)C/EBPCCAAT/enhancer binding proteinM000741280 . . . 1292(91)c-Ets-1(p54)c-Ets-1(p54)M00042192 . . . 201(91)Sox-5Sox-5M002411650 . . . 1643(91)Nkx-2.5homeo domain factor Nkx-2.5/Csx, tinmanhomologM00116138 . . . 125(91)C/EBPalphaCCAAT/enhancer binding protein alphaM001381640 . . . 1662(91)Oct-1octamer factor 1M00128532 . . . 520(90)GATA-1GATA-binding factor 1M002481645 . . . 1656(90)Oct-1octamer factor 1M002891009 . . . 1021(90)HFH-3HNF-3/Fkh Homolog 3 (=Freac-6)









TABLE 7










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.1b. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00254
1831 . . . 1820(99)
CCAAT
cellular and viral CCAAT box


M00101
832 . . . 826(98)
CdxA
CdxA



727 . . . 721(92)



70 . . . 64(92)



570 . . . 564(92)



523 . . . 529(92)



425 . . . 431(92)



1682 . . . 1688(91)



1409 . . . 1415(91)



1415 . . . 1409(91)



1688 . . . 1682(91)


M00054
470 . . . 461(97)
NF-kappaB
NF-kappaB



643 . . . 634(95)


MM00148
946 . . . 940(96)
SRY
sex-determining region Y gene product



1564 . . . 1570(92)



1528 . . . 1534(92)



1092 . . . 1098(92)



1048 . . . 1054(90)



708 . . . 714(90)



655 . . . 661(90)



1360 . . . 1354(90)



1824 . . . 1818(90)



396 . . . 390(90)



749 . . . 743(90)



1016 . . . 1010(90)



302 . . . 308(90)


M00053
470 . . . 461(95)
c-Rel
c-Rel



643 . . . 634(94)


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1111 . . . 1123(91)



17 . . . 5(90)


M00052
470 . . . 461(95)
NF-kappaB
NF-kappaB (p65)



643 . . . 634(94)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00253
485 . . . 492(95)
cap
cap signal for transcription initiation



1893 . . . 1886(95)



749 . . . 756(94)



834 . . . 841(93)



1484 . . . 1477(92)



511 . . . 504(92)



1194 . . . 1201(91)



163 . . . 170(91)



321 . . . 328(91)



340 . . . 347(91)



1815 . . . 1808(90)



563 . . . 570(90)


M00096
652 . . . 660(95)
Pbx-1
Pbx-1


M00194
472 . . . 459(95)
NF-kappaB
NF-kappaB


M00209
1818 . . . 1831(94)
NF-Y
NF-Y binding site


M00116
1238 . . . 1225(94)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00203
1699 . . . 1689(94)
GATA-X
GATA binding site



1227 . . . 1217(90)


M00241
535 . . . 542(94)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog


M00033
759 . . . 746(94)
p300
p300



333 . . . 320(90)


M00127
1703 . . . 1690(93)
GATA-1
GATA-binding factor 1


M00158
323 . . . 310(93)
COUP-TF
COUP/HNF-4 heterodimer


M00075
1889 . . . 1898(93)
GATA-1
GATA-binding factor 1



142 . . . 133(90)



1736 . . . 1745(90)


M00286
963 . . . 976(93)
GKLF
gut-enriched Krueppel-like factor


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins,





and GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



983 . . . 992(92)


M00208
471 . . . 460(93)
NF-kappaB
NF-kappaB binding site


M00185
1829 . . . 1819(92)
NF-Y
nuclear factor Y (Y-box binding factor)


M00302
232 . . . 243(92)
NF-AT
Nuclear factor of activated T-cells


M00348
98 . . . 107(92)
GATA-2
GATA-binding factor 2


M00134
308 . . . 326(92)
HNF-4
hepatic nuclear factor 4


M00223
548 . . . 540(92)
STATx
signal transducers and activators of transcription


M00039
1046 . . . 1039(92)
CREB
cAMP-responsive element binding protein


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00074
231 . . . 243(91)
c-Ets-1(p54)
c-Ets-1(p54)



252 . . . 264(91)


M00289
385 . . . 397(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00199
1722 . . . 1714(91)
AP-1
AP-1 binding site


M00032
254 . . . 263(91)
c-Ets-1(p54)
c-Ets-1(p54)


M00147
782 . . . 773(91)
HSF2
heat shock factor 2


M00100
1101 . . . 1095(91)
CdxA
CdxA


M00042
650 . . . 659(90)
Sox-5
Sox-5


M00183
1026 . . . 1035(90)
c-Myb
c-Myb


M00240
963 . . . 957(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog



1272 . . . 1266(90)


M00190
1238 . . . 1225(90)
C/EBP
CCAAT/enhancer binding factor


M00083
49 . . . 42(90)
MZF1
MZF1


M00184
275 . . . 284(90)
MyoD
myoblast determining factor


M00087
980 . . . 991(90)
Ik-2
Ikaros 2


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00137
1388 . . . 1376(90)
Oct-1
octamer factor 1
















TABLE 8










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.2a. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
992 . . . 986(100)
SRY
sex-determining region Y gene product



942 . . . 948(100)



919 . . . 913(96)



1544 . . . 1550(92)



1505 . . . 1511(92)



815 . . . 809(90)



1068 . . . 1074(90)



1196 . . . 1190(90)



1337 . . . 1331(90)



680 . . . 686(90)



1697 . . . 1691(90)



1802 . . . 1796(90)



368 . . . 362(90)



721 . . . 715(90)



274 . . . 280(90)


M00100
1077 . . . 1071(100)
CdxA
CdxA


M00271
1933 . . . 1938(100)
AML-1a
runt-factor AML-1



2204 . . . 2209(92)


M00101
1077 . . . 1071(99)
CdxA
CdxA



805 . . . 799(98)



699 . . . 693(92)



1384 . . . 1390(92)



936 . . . 942(92)



495 . . . 501(92)



1660 . . . 1666(91)



1666 . . . 1660(91)


M00076
716 . . . 707(98)
GATA-2
GATA-binding factor 2



1910 . . . 1919(95)



959 . . . 968(92)



1679 . . . 1670(91)


M00285
1712 . . . 1724(96)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1087 . . . 1099(91)


M00272
1242 . . . 1251(96)
p53
tumor suppressor p53


M00253
135 . . . 142(96)
cap
cap signal for transcription initiation



457 . . . 464(95)



1871 . . . 1864(95)



721 . . . 728(94)



1461 . . . 1454(92)



312 . . . 319(92)



1989 . . . 1996(92)



1855 . . . 1848(91)



770 . . . 777(90)



1793 . . . 1786(90)



295 . . . 302(90)



1274 . . . 1281(90)


M00106
627 . . . 636(95)
CDP
cut-like homeodomain protein



634 . . . 625(93)


M00116
1215 . . . 1202(95)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00254
1809 . . . 1798(95)
CCAAT
cellular and viral CCAAT box


M00249
1117 . . . 1105(95)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00054
442 . . . 433(95)
NF-kappaB
NF-kappaB


M00147
2182 . . . 2173(94)
HSF2
heat shock factor 2



2173 . . . 2182(92)



754 . . . 745(91)



141 . . . 132(90)


M00104
634 . . . 625(94)
CDP
cut-like homeodomain protein



2 . . . 11(92)


M00134
280 . . . 298(94)
HNF-4
hepatic nuclear factor 4


M00052
442 . . . 433(94)
NF-kappaB
NF-kappaB (p65)


M00053
442 . . . 433(94)
c-Rel
c-Rel



785 . . . 794(90)


M00033
731 . . . 718(94)
p300
p300


M00158
295 . . . 282(93)
COUP-TF
COUP/HNF-4 heterodimer


M00032
225 . . . 216(93)
c-Ets-1(p54)
c-Ets-1(p54)



226 . . . 235(93)


M00172
1851 . . . 1861(92)
AP-1
activator protein 1


M00223
520 . . . 512(92)
STATx
signal transducers and activators of transcription


M00075
1679 . . . 1670(92)
GATA-1
GATA-binding factor 1



1867 . . . 1876(91)



716 . . . 707(91)



316 . . . 307(90)


M00184
1463 . . . 1472(91)
MyoD
myoblast determining factor



1472 . . . 1463(91)



247 . . . 256(90)



2057 . . . 2048(90)


M00289
357 . . . 369(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00109
1202 . . . 1215(91)
C/EBPbeta
CCAAT/enhancer binding protein beta



2036 . . . 2023(90)


M00268
937 . . . 950(91)
XFD-2
Xenopus fork head domain factor 2


M00208
443 . . . 432(90)
NF-kappaB
NF-kappaB binding site


M00173
1851 . . . 1861(90)
AP-1
activator protein 1


M00183
1002 . . . 1011(90)
c-Myb
c-Myb



2020 . . . 2011(90)


M00240
217 . . . 211(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00188
1851 . . . 1861(90)
AP-1
activator protein 1


M00099
1086 . . . 1101(90)
S8
S8


M00302
813 . . . 802(90)
NF-AT
Nuclear factor of activated T-cells


M00083
21 . . . 14(90)
MZF1
MZF1


M00190
1215 . . . 1202(90)
C/EBP
CCAAT/enhancer binding factor


M00221
1838 . . . 1828(90)
SREBP-1
sterol regulatory element-binding protein 1


M00294
949 . . . 937(90)
HFH-8
HNF-3/Fkh Homolog-8


M00137
1365 . . . 1353(90)
Oct-1
octamer factor 1


M00077
1911 . . . 1919(90)
GATA-3
GATA-binding factor 3


M00194
444 . . . 431(90)
NF-kappaB
NF-kappaB
















TABLE 9










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.2b. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00100
1102 . . . 1096(100)
CdxA
CdxA


M00148
1017 . . . 1011(100)
SRY
sex-determining region Y gene product



967 . . . 973(100)



944 . . . 938(96)



1566 . . . 1572(92)



1530 . . . 1536(92)



840 . . . 834(90)



1093 . . . 1099(90)



705 . . . 711(90)



1362 . . . 1356(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



393 . . . 387(90)



746 . . . 740(90)



299 . . . 305(90)


M00253
1120 . . . 1127(99)
cap
cap signal for transcription initiation



160 . . . 167(96)



482 . . . 489(95)



1893 . . . 1886(95)



746 . . . 753(94)



1486 . . . 1479(92)



337 . . . 344(92)



1877 . . . 1870(91)



795 . . . 802(90)



1815 . . . 1808(90)



320 . . . 327(90)



1299 . . . 1306(90)


M00101
1102 . . . 1096(99)
CdxA
CdxA



830 . . . 824(98)



1231 . . . 1225(98)



1409 . . . 1415(92)



724 . . . 718(92)



520 . . . 526(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00076
741 . . . 732(98)
GATA-2
GATA-binding factor 2



1932 . . . 1941(95)



984 . . . 993(92)



1701 . . . 1692(91)


M00285
1734 . . . 1746(96)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1112 . . . 1124(91)


M00272
1267 . . . 1276(96)
p53
tumor suppressor p53


M00106
652 . . . 661(95)
CDP
cut-like homeodomain protein



659 . . . 650(93)


M00116
1240 . . . 1227(95)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00254
1831 . . . 1820(95)
CCAAT
cellular and viral CCAAT box


M00249
1142 . . . 1130(95)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00054
467 . . . 458(95)
NF-kappaB
NF-kappaB


M00104
659 . . . 650(94)
CDP
cut-like homeodomain protein



27 . . . 36(92)


M00134
305 . . . 323(94)
HNF-4
hepatic nuclear factor 4


M00052
467 . . . 458(94)
NF-kappaB
NF-kappaB (p65)


M00053
467 . . . 458(94)
c-Rel
c-Rel


M00033
756 . . . 743(94)
p300
p300


M00158
320 . . . 307(93)
COUP-TF
COUP/HNF-4 heterodimer


M00075
1889 . . . 1898(93)
GATA-1
GATA-binding factor 1



1701 . . . 1692(92)



741 . . . 732(91)



341 . . . 332(90)



641 . . . 632(90)


M00160
965 . . . 976(93)
SRY
sex-determining region Y gene product


M00032
250 . . . 241(93)
c-Ets-
c-Ets-1(p54)




1(p54)



251 . . . 260(93)


M00172
1873 . . . 1883(92)
AP-1
activator protein 1


M00223
545 . . . 537(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00184
1488 . . . 1497(91)
MyoD
myoblast determining factor



1497 . . . 1488(91)



272 . . . 281(90)


M00289
382 . . . 394(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00109
1227 . . . 1240(91)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00147
779 . . . 770(91)
HSF2
heat shock factor 2



166 . . . 157(90)


M00208
468 . . . 457(90)
NF-kappaB
NF-kappaB binding site


M00183
1027 . . . 1036(90)
c-Myb
c-Myb


M00173
1873 . . . 1883(90)
AP-1
activator protein 1


M00240
242 . . . 236(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog


M00188
1873 . . . 1883(90)
AP-1
activator protein 1


M00302
838 . . . 827(90)
NF-AT
Nuclear factor of activated T-cells


M00083
46 . . . 39(90)
MZF1
MZF1


M00190
1240 . . . 1227(90)
C/EBP
CCAAT/enhancer binding factor


M00096
1115 . . . 1123(90)
Pbx-1
Pbx-1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
469 . . . 456(90)
NF-kappaB
NF-kappaB


M00077
1933 . . . 1941(90)
GATA-3
GATA-binding factor 3
















TABLE 10










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.3. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
1015 . . . 1009(100)
SRY
sex-determining region Y gene product



965 . . . 971(100)



942 . . . 936(96)



1566 . . . 1572(92)



1528 . . . 1534(92)



838 . . . 832(90)



1091 . . . 1097(90)



1219 . . . 1213(90)



703 . . . 709(90)



1360 . . . 1354(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



391 . . . 385(90)



744 . . . 738(90)



297 . . . 303(90)


M00100
1100 . . . 1094(100)
CdxA
CdxA


M00101
1100 . . . 1094(99)
CdxA
CdxA



828 . . . 822(98)



1407 . . . 1413(92)



722 . . . 716(92)



959 . . . 965(92)



518 . . . 524(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00076
739 . . . 730(98)
GATA-2
GATA-binding factor 2



1932 . . . 1941(95)



982 . . . 991(92)



1701 . . . 1692(91)


M00285
1734 . . . 1746(96)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1110 . . . 1122(91)


M00272
1265 . . . 1274(96)
p53
tumor suppressor p53


M00253
158 . . . 165(96)
cap
cap signal for transcription initiation



480 . . . 487(95)



1893 . . . 1886(95)



744 . . . 751(94)



1484 . . . 1477(92)



335 . . . 342(92)



1877 . . . 1870(91)



793 . . . 800(90)



318 . . . 325(90)



1297 . . . 1304(90)


M00106
650 . . . 659(95)
CDP
cut-like homeodomain protein



657 . . . 648(93)


M00116
1238 . . . 1225(95)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00254
1831 . . . 1820(95)
CCAAT
cellular and viral CCAAT box


M00249
1140 . . . 1128(95)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00054
465 . . . 456(95)
NF-kappaB
NF-kappaB


M00104
657 . . . 648(94)
CDP
cut-like homeodomain protein



25 . . . 34(92)


M00134
303 . . . 321(94)
HNF-4
hepatic nuclear factor 4


M00052
465 . . . 456(94)
NF-kappaB
NF-kappaB (p65)


M00053
465 . . . 456(94)
c-Rel
c-Rel


M00033
754 . . . 741(94)
p300
p300


M00158
318 . . . 305(93)
COUP-TF
COUP/HNF-4 heterodimer


M00075
1889 . . . 1898(93)
GATA-1
GATA-binding factor 1



1701 . . . 1692(92)



739 . . . 730(91)



339 . . . 330(90)


M00160
963 . . . 974(93)
SRY
sex-determining region Y gene product


M00032
248 . . . 239(93)
c-Ets-
c-Ets-1(p54)



249 . . . 258(93)
1(p54)


M00172
1873 . . . 1883(92)
AP-1
activator protein 1


M00223
543 . . . 535(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00173
1873 . . . 1883(91)
AP-1
activator protein 1


M00184
1486 . . . 1495(91)
MyoD
myoblast detennining factor



1495 . . . 1486(91)



270 . . . 279(90)


M00289
380 . . . 392(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00109
1225 . . . 1238(91)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00147
777 . . . 768(91)
HSF2
heat shock factor 2



164 . . . 155(90)


M00208
466 . . . 455(90)
NF-kappaB
NF-kappaB binding site


M00183
1025 . . . 1034(90)
c-Myb
c-Myb


M00240
240 . . . 234(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog


M00099
1109 . . . 1124(90)
S8
S8


M00302
836 . . . 825(90)
NF-AT
Nuclear factor of activated T-cells


M00083
44 . . . 37(90)
MZF1
MZF1


M00190
1238 . . . 1225(90)
C/EBP
CCAAT/enhancer binding factor


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00174
1873 . . . 1883(90)
AP-1
activator protein 1


M00077
1933 . . . 1941(90)
GATA-3
GATA-binding factor 3


M00194
467 . . . 454(90)
NF-kappaB
NF-kappaB
















TABLE 11










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.4. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00100
1101 . . . 1095(100)
CdxA
CdxA


M00148
1016 . . . 1010(100)
SRY
sex-determining region Y gene product



966 . . . 972(100)



944 . . . 938(96)



1566 . . . 1572(92)



1529 . . . 1535(92)



840 . . . 834(90)



1092 . . . 1098(90)



705 . . . 711(90)



1361 . . . 1355(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



393 . . . 387(90)



746 . . . 740(90)



299 . . . 305(90)


M00101
1101 . . . 1095(99)
CdxA
CdxA



830 . . . 824(98)



1230 . . . 1224(98)



1408 . . . 1414(92)



724 . . . 718(92)



520 . . . 526(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00076
741 . . . 732(98)
GATA-2
GATA-binding factor 2



1932 . . . 1941(95)



983 . . . 992(92)



1701 . . . 1692(91)


M00350
876 . . . 867(96)
GATA-3
GATA-binding factor 3


M00285
1734 . . . 1746(96)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1111 . . . 1123(91)


M00272
1266 . . . 1275(96)
p53
tumor suppressor p53


M00253
160 . . . 167(96)
cap
cap signal for transcription initiation



482 . . . 489(95)



1893 . . . 1886(95)



746 . . . 753(94)



1485 . . . 1478(92)



337 . . . 344(92)



1877 . . . 1870(91)



795 . . . 802(90)



1815 . . . 1808(90)



320 . . . 327(90)



1298 . . . 1305(90)


M00106
652 . . . 661(95)
CDP
cut-like homeodomain protein



659 . . . 650(93)


M00116
1239 . . . 1226(95)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00254
1831 . . . 1820(95)
CCAAT
cellular and viral CCAAT box


M00249
1141 . . . 1129(95)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00349
876 . . . 867(95)
GATA-2
GATA-binding factor 2


M00054
467 . . . 458(95)
NF-kappaB
NF-kappaB


M00104
659 . . . 650(94)
CDP
cut-like homeodomain protein



27 . . . 36(92)


M00134
305 . . . 323(94)
HNF-4
hepatic nuclear factor 4


M00052
467 . . . 458(94)
NF-kappaB
NF-kappaB (p65)


M00053
467 . . . 458(94)
c-Rel
c-Rel


M00033
756 . . . 743(94)
p300
p300


M00348
876 . . . 867(93)
GATA-2
GATA-binding factor 2


M00158
320 . . . 307(93)
COUP-TF
COUP/HNF-4 heterodimer


M00075
1889 . . . 1898(93)
GATA-1
GATA-binding factor 1



1701 . . . 1692(92)



741 . . . 732(91)



341 . . . 332(90)


M00160
964 . . . 975(93)
SRY
sex-determining region Y gene product


M00347
876 . . . 867(93)
GATA-1
GATA-binding factor 1


M00032
250 . . . 241(93)
c-Ets-1(p54)
c-Ets-1(p54)



251 . . . 260(93)


M00172
1873 . . . 1883(92)
AP-1
activator protein 1


M00223
545 . . . 537(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00184
1487 . . . 1496(91)
MyoD
myoblast determining factor



1496 . . . 1487(91)



272 . . . 281(90)


M00289
382 . . . 394(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00109
1226 . . . 1239(91)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00208
468 . . . 457(90)
NF-kappaB
NF-kappaB binding site


M00183
1026 . . . 1035(90)
c-Myb
c-Myb


M00173
1873 . . . 1883(90)
AP-1
activator protein 1


M00240
242 . . . 236(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog


M00188
1873 . . . 1883(90)
AP-1
activator protein 1


M00099
1110 . . . 1125(90)
S8
S8


M00302
838 . . . 827(90)
NF-AT
Nuclear factor of activated T-cells


M00083
46 . . . 39(90)
MZF1
MZF1


M00190
1239 . . . 1226(90)
C/EBP
CCAAT/enhancer binding factor


M00147
166 . . . 157(90)
HSF2
heat shock factor 2


M00080
874 . . . 864(90)
Evi-1
ectopic viral integration site 1 encoded factor


M00082
874 . . . 864(90)
Evi-1
ectopic viral integration site 1 encoded factor


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
469 . . . 456(90)
NF-kappaB
NF-kappaB


M00077
1933 . . . 1941(90)
GATA-3
GATA-binding factor 3
















TABLE 12










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 4.5. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
963 . . . 969(100)
SRY
sex-determining region Y gene product



1013 . . . 1007(100)



940 . . . 934(96)



1526 . . . 1532(92)



1089 . . . 1095(90)



836 . . . 830(90)



701 . . . 707(90)



1358 . . . 1352(90)



1720 . . . 1714(90)



1825 . . . 1819(90)



389 . . . 383(90)



742 . . . 736(90)



295 . . . 301(90)


M00100
1098 . . . 1092(100)
CdxA
CdxA


M00101
1098 . . . 1092(99)
CdxA
CdxA



826 . . . 820(98)



1405 . . . 1411(92)



720 . . . 714(92)



957 . . . 963(92)



516 . . . 522(92)



1683 . . . 1689(91)



1689 . . . 1683(91)


M00076
737 . . . 728(98)
GATA-2
GATA-binding factor 2



980 . . . 989(92)



1702 . . . 1693(91)



1299 . . . 1308(90)


M00285
1735 . . . 1747(96)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1108 . . . 1120(91)


M00272
1263 . . . 1272(96)
p53
tumor suppressor p53


M00253
156 . . . 163(96)
cap
cap signal for transcription initiation



478 . . . 485(95)



742 . . . 749(94)



1482 . . . 1475(92)



333 . . . 340(92)



791 . . . 798(90)



1816 . . . 1809(90)



316 . . . 323(90)


M00106
648 . . . 657(95)
CDP
cut-like homeodomain protein



655 . . . 646(93)


M00116
1236 . . . 1223(95)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00254
1832 . . . 1821(95)
CCAAT
cellular and viral CCAAT box


M00249
1138 . . . 1126(95)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00054
463 . . . 454(95)
NF-kappaB
NF-kappaB


M00183
1493 . . . 1484(94)
c-Myb
c-Myb



1023 . . . 1032(90)


M00104
655 . . . 646(94)
CDP
cut-like homeodomain protein



23 . . . 32(92)


M00134
301 . . . 319(94)
HNF-4
hepatic nuclear factor 4


M00052
463 . . . 454(94)
NF-kappaB
NF-kappaB (p65)


M00053
463 . . . 454(94)
c-Rel
c-Rel



806 . . . 815(90)


M00033
752 . . . 739(94)
p300
p300


M00158
316 . . . 303(93)
COUP-TF
COUP/HNF-4 heterodimer


M00032
246 . . . 237(93)
c-Ets-
c-Ets-1(p54)



247 . . . 256(93)
1(p54)


M00278
1300 . . . 1308(92)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00223
541 . . . 533(92)
STATx
signal transducers and activators of transcription


M00075
1702 . . . 1693(92)
GATA-1
GATA-binding factor 1



737 . . . 728(91)



337 . . . 328(90)


M00077
1300 . . . 1308(91)
GATA-3
GATA-binding factor 3


M00289
378 . . . 390(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00109
1223 . . . 1236(91)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00268
958 . . . 971(91)
XFD-2
Xenopus fork head domain factor 2


M00147
775 . . . 766(91)
HSF2
heat shock factor 2



162 . . . 153(90)


M00208
464 . . . 453(90)
NF-kappaB
NF-kappaB binding site


M00240
238 . . . 232(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00099
1107 . . . 1122(90)
S8
S8


M00302
834 . . . 823(90)
NF-AT
Nuclear factor of activated T-cells


M00083
42 . . . 35(90)
MZF1
MZF1


M00184
268 . . . 277(90)
MyoD
myoblast determining factor


M00190
1236 . . . 1223(90)
C/EBP
CCAAT/enhancer binding factor


M00221
1861 . . . 1851(90)
SREBP-1
sterol regulatory element-binding protein 1


M00294
970 . . . 958(90)
HFH-8
HNF-3/Fkh Homolog-8


M00137
1386 . . . 1374(90)
Oct-1
octamer factor 1


M00194
465 . . . 452(90)
NF-kappaB
NF-kappaB
















TABLE 13










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 8.1. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
1015 . . . 1009(100)
SRY
sex-determining region Y gene product



965 . . . 971(100)



942 . . . 936(96)



1544 . . . 1550(92)



838 . . . 832(90)



702 . . . 708(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



390 . . . 384(90)



1384 . . . 1390(90)



1356 . . . 1350(90)



296 . . . 302(90)



63 . . . 69(90)


M00100
1100 . . . 1094(100)
CdxA
CdxA



724 . . . 730(96)



1547 . . . 1541(91)


M00349
93 . . . 102(100)
GATA-2
GATA-binding factor 2


M00350
93 . . . 102(100)
GATA-3
GATA-binding factor 3


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00348
93 . . . 102(100)
GATA-2
GATA-binding factor 2


M00101
1100 . . . 1094(99)
CdxA
CdxA



828 . . . 822(98)



1229 . . . 1223(98)



1203 . . . 1209(94)



721 . . . 715(92)



959 . . . 965(92)



1386 . . . 1380(92)



65 . . . 59(92)



517 . . . 523(92)



419 . . . 425(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00203
95 . . . 105(98)
GATA-X
GATA binding site


M00347
93 . . . 102(97)
GATA-1
GATA-binding factor 1


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1701 . . . 1692(95)



137 . . . 128(92)



1483 . . . 1492(92)



1889 . . . 1898(91)



1736 . . . 1745(90)


M00158
317 . . . 304(96)
COUP-
COUP/HNF-4 heterodimer




TF


M00253
158 . . . 165(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



479 . . . 486(95)



1297 . . . 1304(93)



337 . . . 344(93)



48 . . . 55(93)



1484 . . . 1477(92)



1324 . . . 1317(91)



557 . . . 564(91)



1893 . . . 1886(91)



1877 . . . 1870(91)



793 . . . 800(90)



1356 . . . 1363(90)



1815 . . . 1808(90)



317 . . . 324(90)


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1110 . . . 1122(91)



13 . . . 1(90)


M00134
302 . . . 320(95)
HNF-4
hepatic nuclear factor 4


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00096
1827 . . . 1819(95)
Pbx-1
Pbx-1


M00141
451 . . . 459(94)
Lyf-1
LyF-1


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00076
1483 . . . 1492(93)
GATA-2
GATA-binding factor 2



1932 . . . 1941(93)



1701 . . . 1692(92)



982 . . . 991(92)


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00099
1813 . . . 1798(92)
S8
S8



1109 . . . 1124(90)


M00294
1551 . . . 1539(92)
HFH-8
HNF-3/Fkh Homolog-8


M00223
542 . . . 534(92)
STATx
signal transducers and activators of transcription


M00073
36 . . . 46(92)
deltaEF1
deltaEF1


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1



132 . . . 127(92)


M00137
335 . . . 323(91)
Oct-1
octamer factor 1


M00042
644 . . . 653(91)
Sox-5
Sox-5



1829 . . . 1820(90)


M00289
379 . . . 391(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00183
1025 . . . 1034(90)
c-Myb
c-Myb


M00240
239 . . . 233(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00302
836 . . . 825(90)
NF-AT
Nuclear factor of activated T-cells


M00128
92 . . . 104(90)
GATA-1
GATA-binding factor 1


M00184
269 . . . 278(90)
MyoD
myoblast determining factor


M00147
164 . . . 155(90)
HSF2
heat shock factor 2


M00087
979 . . . 990(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1
















TABLE 14










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.2. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00241
1804 . . . 1811(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00240
556 . . . 562(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



1354 . . . 1360(90)



301 . . . 307(90)


M00096
1342 . . . 1350(100)
Pbx-1
Pbx-1



1831 . . . 1823(96)


M00271
702 . . . 707(100)
AML-1a
runt-factor AML-1



1955 . . . 1960(92)



170 . . . 175(92)


M00050
104 . . . 111(100)
E2F
E2F


M00148
1271 . . . 1277(100)
SRY
sex-determining region Y gene product



1572 . . . 1578(92)



1345 . . . 1351(90)



1719 . . . 1713(90)



1828 . . . 1822(90)



1634 . . . 1628(90)


M00272
472 . . . 463(97)
p53
tumor suppressor p53



463 . . . 472(97)



295 . . . 286(91)


M00075
1842 . . . 1851(97)
GATA-1
GATA-binding factor 1



1893 . . . 1902(93)



1380 . . . 1371(92)



1740 . . . 1749(90)


M00253
1072 . . . 1065(96)
cap
cap signal for transcription initiation



1798 . . . 1805(95)



1897 . . . 1890(95)



769 . . . 776(92)



1701 . . . 1708(92)



1881 . . . 1874(91)



497 . . . 504(90)



1819 . . . 1812(90)



21 . . . 28(90)


M00285
1738 . . . 1750(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



366 . . . 378(93)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00147
148 . . . 139(94)
HSF2
heat shock factor 2



139 . . . 148(92)


M00199
1801 . . . 1793(94)
AP-1
AP-1 binding site



1037 . . . 1029(94)



1793 . . . 1801(91)



1029 . . . 1037(90)


M00174
1792 . . . 1802(94)
AP-1
activator protein 1



1038 . . . 1028(92)


M00074
1247 . . . 1259(93)
c-Ets-
c-Ets-1(p54)




1(p54)


M00211
702 . . . 710(93)
Poly
Retroviral Poly A downstream element



1531 . . . 1539(91)


M00124
1339 . . . 1353(93)
Pbx1b
homeo domain factor Pbx-1


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00052
1261 . . . 1252(93)
NF-
NF-kappaB (p65)




kappaB


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



837 . . . 828(90)


M00099
1817 . . . 1802(92)
S8
S8


M00101
987 . . . 981(92)
CdxA
CdxA


M00042
1635 . . . 1626(92)
Sox-5
Sox-5


M00254
1835 . . . 1824(91)
CCAAT
cellular and viral CCAAT box


M00008
252 . . . 243(91)
Sp1
stimulating protein 1



1323 . . . 1314(91)


M00227
933 . . . 941(90)
v-Myb
v-Myb


M00141
1328 . . . 1320(90)
Lyf-1
LyF-1


M00183
1033 . . . 1042(90)
c-Myb
c-Myb


M00001
654 . . . 665(90)
MyoD
myoblast determination gene product


M00188
1792 . . . 1802(90)
AP-1
activator protein 1


M00184
23 . . . 14(90)
MyoD
myoblast determining factor


M00172
1792 . . . 1802(90)
AP-1
activator protein 1


M00221
1864 . . . 1854(90)
SREBP-1
sterol regulatory element-binding protein 1


M00037
871 . . . 861(90)
NF-E2
NF-E2 p45


M00053
1261 . . . 1252(90)
c-Rel
c-Rel


M00249
823 . . . 835(90)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00302
1248 . . . 1259(90)
NF-AT
Nuclear factor of activated T-cells
















TABLE 15










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.3. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00348
71 . . . 80(100)
GATA-2
GATA-binding factor 2


M00349
71 . . . 80(100)
GATA-2
GATA-binding factor 2


M00148
990 . . . 984(100)
SRY
sex-determining region Y gene product



1654 . . . 1648(100)



813 . . . 807(96)



917 . . . 911(96)



1848 . . . 1854(92)



1840 . . . 1846(92)



1826 . . . 1832(92)



1504 . . . 1498(92)



1391 . . . 1397(90)



680 . . . 686(90)



2094 . . . 2088(90)



368 . . . 362(90)



721 . . . 715(90)



1002 . . . 996(90)



1900 . . . 1894(90)



274 . . . 280(90)


M00350
71 . . . 80(100)
GATA-3
GATA-binding factor 3


M00100
595 . . . 589(100)
CdxA
CdxA



1400 . . . 1394(100)


M00101
595 . . . 589(99)
CdxA
CdxA



1400 . . . 1394(99)



803 . . . 797(98)



1527 . . . 1521(98)



1705 . . . 1711(92)



699 . . . 693(92)



934 . . . 940(92)



43 . . . 37(92)



495 . . . 501(92)



397 . . . 403(92)


M00141
1274 . . . 1266(98)
Lyf-1
LyF-1


M00347
71 . . . 80(97)
GATA-1
GATA-binding factor 1


M00272
1563 . . . 1572(96)
p53
tumor suppressor p53


M00253
1128 . . . 1135(96)
cap
cap signal for transcription initiation



136 . . . 143(96)



2064 . . . 2071(95)



457 . . . 464(95)



2163 . . . 2156(95)



721 . . . 728(94)



660 . . . 653(94)



1782 . . . 1775(92)



312 . . . 319(92)



1622 . . . 1615(91)



535 . . . 542(91)



2085 . . . 2078(91)



2147 . . . 2140(91)



1350 . . . 1357(91)



768 . . . 775(90)



295 . . . 302(90)


M00285
2004 . . . 2016(95)
TCF11
TCF11/KCR-F1/Nrfl homodimers



1410 . . . 1422(91)


M00254
2101 . . . 2090(95)
CCAAT
cellular and viral CCAAT box


M00130
1647 . . . 1658(95)
HFH-2
HNF-3/Fkh Homolog 2


M00054
442 . . . 433(95)
NF-kappaB
NF-kappaB


M00077
2203 . . . 2211(95)
GATA-3
GATA-binding factor 3


M00052
442 . . . 433(94)
NF-kappaB
NF-kappaB (p65)


M00203
73 . . . 83(94)
GATA-X
GATA binding site


M00199
2067 . . . 2059(94)
AP-1
AP-1 binding site



2059 . . . 2067(91)



1984 . . . 1992(90)


M00174
2058 . . . 2068(94)
AP-1
activator protein 1


M00075
895 . . . 886(94)
GATA-1
GATA-binding factor 1



2159 . . . 2168(93)



1082 . . . 1073(93)



1971 . . . 1962(92)



2006 . . . 2015(90)


M00053
442 . . . 433(94)
c-Rel
c-Rel


M00241
2070 . . . 2077(94)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00076
716 . . . 707(94)
GATA-2
GATA-binding factor 2



1599 . . . 1608(92)



957 . . . 966(92)



895 . . . 886(91)



1971 . . . 1962(91)


M00106
627 . . . 636(94)
CDP
cut-like homeodomain protein


M00033
731 . . . 718(94)
p300
p300


M00227
2139 . . . 2131(94)
v-Myb
v-Myb


M00158
295 . . . 282(93)
COUP-TF
COUP/HNF-4 heterodimer


M00162
2070 . . . 2083(93)
Oct-1
octamer-binding factor 1


M00134
280 . . . 298(93)
HNF-4
hepatic nuclear factor 4


M00032
226 . . . 235(93)
c-Ets-1(p54)
c-Ets-1(p54)


M00117
1080 . . . 1067(92)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00223
520 . . . 512(92)
STATx
signal transducers and activators of transcription


M00042
1901 . . . 1892(92)
Sox-5
Sox-5



622 . . . 631(91)


M00073
13 . . . 23(92)
deltaEF1
deltaEF1


M00099
2083 . . . 2068(91)
S8
S8



2066 . . . 2081(90)



1409 . . . 1424(90)


M00289
1647 . . . 1659(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)



357 . . . 369(91)


M00147
752 . . . 743(91)
HSF2
heat shock factor 2



142 . . . 133(90)


M00208
443 . . . 432(90)
NF-kappaB
NF-kappaB binding site


M00217
115 . . . 108(90)
USF
USF binding site


M00183
1325 . . . 1334(90)
c-Myb
c-Myb


M00240
217 . . . 211(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00188
2058 . . . 2068(90)
AP-1
activator protein 1


M00184
1955 . . . 1964(90)
MyoD
myoblast determining factor



247 . . . 256(90)


M00087
954 . . . 965(90)
Ik-2
Ikaros 2


M00128
70 . . . 82(90)
GATA-1
GATA-binding factor 1


M00172
2058 . . . 2068(90)
AP-1
activator protein 1


M00145
1339 . . . 1354(90)
Brn-2
POU factor Brn-2


M00062
1217 . . . 1205(90)
IRF-1
interferon regulatory factor 1


M00194
444 . . . 431(90)
NF-kappaB
NF-kappaB
















TABLE 16










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.4. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00100
1105 . . . 1099(100)
CdxA
CdxA


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00148
1020 . . . 1014(100)
SRY
sex-determining region Y gene product



970 . . . 976(100)



947 . . . 941(96)



1550 . . . 1556(92)



843 . . . 837(90)



707 . . . 713(90)



1362 . . . 1356(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



395 . . . 389(90)



748 . . . 742(90)



300 . . . 306(90)


M00101
1105 . . . 1099(99)
CdxA
CdxA



833 . . . 827(98)



1385 . . . 1379(98)



1409 . . . 1415(92)



964 . . . 970(92)



726 . . . 720(92)



424 . . . 430(92)


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1889 . . . 1898(93)



925 . . . 916(93)



1736 . . . 1745(90)


M00272
1267 . . . 1276(96)
p53
tumor suppressor p53


M00253
161 . . . 168(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



484 . . . 491(95)



1893 . . . 1886(95)



1452 . . . 1459(94)



798 . . . 805(94)



748 . . . 755(94)



957 . . . 964(94)



1486 . . . 1479(92)



338 . . . 345(92)



1697 . . . 1704(92)



562 . . . 569(91)



1877 . . . 1870(91)



1815 . . . 1808(90)



321 . . . 328(90)



1326 . . . 1319(90)



1299 . . . 1306(90)


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrfl homodimers



1115 . . . 1127(91)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00054
469 . . . 460(95)
NF-kappaB
NF-kappaB


M00141
456 . . . 464(94)
Lyf-1
LyF-1


M00134
306 . . . 324(94)
HNF-4
hepatic nuclear factor 4


M00052
469 . . . 460(94)
NF-kappaB
NF-kappaB (p65)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00053
469 . . . 460(94)
c-Rel
c-Rel


M00033
758 . . . 745(94)
p300
p300



808 . . . 795(92)


M00158
321 . . . 308(93)
COUP-TF
COUP/HNF-4 heterodimer


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



1303 . . . 1312(92)



743 . . . 734(92)



987 . . . 996(92)



925 . . . 916(90)


M00099
1813 . . . 1798(92)
S8
S8



1114 . . . 1129(90)


M00104
28 . . . 37(92)
CDP
cut-like homeodomain protein


M00223
547 . . . 539(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00042
649 . . . 658(91)
Sox-5
Sox-5


M00289
384 . . . 396(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00302
1384 . . . 1395(91)
NF-AT
Nuclear factor of activated T-cells



841 . . . 830(90)


M00155
367 . . . 382(91)
ARP-1
apolipoprotein AI regulatory protein 1


M00208
470 . . . 459(90)
NF-kappaB
NF-kappaB binding site


M00183
1030 . . . 1039(90)
c-Myb
c-Myb


M00240
243 . . . 237(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



1454 . . . 1448(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00083
47 . . . 40(90)
MZF1
MZF1


M00184
273 . . . 282(90)
MyoD
myoblast determining factor


M00147
167 . . . 158(90)
HSF2
heat shock factor 2


M00087
984 . . . 995(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
471 . . . 458(90)
NF-kappaB
NF-kappaB
















TABLE 17










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.5. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00100
1105 . . . 1099(100)
CdxA
CdxA


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00271
27 . . . 32(100)
AML-1a
runt-factor AML-1



1955 . . . 1960(92)


M00148
1020 . . . 1014(100)
SRY
sex-determining region Y gene product



970 . . . 976(100)



947 . . . 941(96)



1553 . . . 1559(92)



100 . . . 106(92)



141 . . . 135(90)



843 . . . 837(90)



1365 . . . 1359(90)



1719 . . . 1713(90)



1824 . . . 1818(90)


M00101
1105 . . . 1099(99)
CdxA
CdxA



833 . . . 827(98)



1234 . . . 1228(98)



1388 . . . 1382(98)



1300 . . . 1294(93)



1412 . . . 1418(92)



964 . . . 970(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00278
618 . . . 610(98)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2



1933 . . . 1941(93)


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



619 . . . 610(97)



1701 . . . 1692(95)



1889 . . . 1898(93)



903 . . . 894(91)



1736 . . . 1745(90)


M00054
442 . . . 451(96)
NF-
NF-kappaB



451 . . . 442(91)
kappaB


M00253
175 . . . 168(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



1893 . . . 1886(95)



1455 . . . 1462(94)



798 . . . 805(94)



629 . . . 636(94)



1489 . . . 1482(92)



433 . . . 426(92)



1329 . . . 1322(91)



1877 . . . 1870(91)



921 . . . 928(91)



957 . . . 964(90)



1815 . . . 1808(90)



1302 . . . 1309(90)


M00272
1270 . . . 1279(96)
p53
tumor suppressor p53


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1115 . . . 1127(91)



1490 . . . 1478(91)


M00076
619 . . . 610(95)
GATA-2
GATA-binding factor 2



1932 . . . 1941(93)



1701 . . . 1692(92)



1306 . . . 1315(92)



987 . . . 996(92)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3



618 . . . 610(92)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00083
566 . . . 559(93)
MZF1
MZF1


M00099
1813 . . . 1798(92)
S8
S8



1114 . . . 1129(90)


M00208
441 . . . 452(92)
NF-
NF-kappaB binding site




kappaB


M00033
808 . . . 795(92)
p300
p300


M00227
1677 . . . 1669(91)
v-Myb
v-Myb


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00183
166 . . . 157(91)
c-Myb
c-Myb



1030 . . . 1039(90)


M00267
102 . . . 89(91)
XFD-1
Xenopus fork head domain factor 1


M00240
1457 . . . 1451(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



296 . . . 302(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00302
841 . . . 830(90)
NF-AT
Nuclear factor of activated T-cells


M00087
984 . . . 995(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00003
965 . . . 956(90)
v-Myb
v-Myb


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00053
441 . . . 450(90)
c-Rel
c-Rel
















TABLE 18










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.6. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00100
1105 . . . 1099(100)
CdxA
CdxA


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog


M00148
1020 . . . 1014(100)
SRY
sex-determining region Y gene product



970 . . . 976(100)



947 . . . 941(96)



1550 . . . 1556(92)



843 . . . 837(90)



707 . . . 713(90)



1362 . . . 1356(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



395 . . . 389(90)



748 . . . 742(90)



300 . . . 306(90)


M00101
1105 . . . 1099(99)
CdxA
CdxA



833 . . . 827(98)



1385 . . . 1379(98)



1409 . . . 1415(92)



964 . . . 970(92)



726 . . . 720(92)



424 . . . 430(92)


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1889 . . . 1898(93)



925 . . . 916(93)



1736 . . . 1745(90)


M00272
1267 . . . 1276(96)
p53
tumor suppressor p53


M00253
161 . . . 168(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



484 . . . 491(95)



1893 . . . 1886(95)



1452 . . . 1459(94)



798 . . . 805(94)



748 . . . 755(94)



957 . . . 964(94)



1486 . . . 1479(92)



338 . . . 345(92)



1697 . . . 1704(92)



562 . . . 569(91)



1877 . . . 1870(91)



1815 . . . 1808(90)



321 . . . 328(90)



1326 . . . 1319(90)



1299 . . . 1306(90)


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1115 . . . 1127(91)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00054
469 . . . 460(95)
NF-kappaB
NF-kappaB


M00141
456 . . . 464(94)
Lyf-1
LyF-1


M00134
306 . . . 324(94)
HNF-4
hepatic nuclear factor 4


M00052
469 . . . 460(94)
NF-kappaB
NF-kappaB (p65)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00053
469 . . . 460(94)
c-Rel
c-Rel


M00033
758 . . . 745(94)
p300
p300



808 . . . 795(92)


M00158
321 . . . 308(93)
COUP-TF
COUP/HNF-4 heterodimer


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins,





and GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



1303 . . . 1312(92)



743 . . . 734(92)



987 . . . 996(92)



925 . . . 916(90)


M00099
1813 . . . 1798(92)
S8
S8



1114 . . . 1129(90)


M00104
28 . . . 37(92)
CDP
cut-like homeodomain protein


M00223
547 . . . 539(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00042
649 . . . 658(91)
Sox-5
Sox-5


M00289
384 . . . 396(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00302
1384 . . . 1395(91)
NF-AT
Nuclear factor of activated T-cells



841 . . . 830(90)


M00155
367 . . . 382(91)
ARP-1
apolipoprotein AI regulatory protein 1


M00208
470 . . . 459(90)
NF-kappaB
NF-kappaB binding site


M00183
1030 . . . 1039(90)
c-Myb
c-Myb


M00240
243 . . . 237(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman





homolog



1454 . . . 1448(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00083
47 . . . 40(90)
MZF1
MZF1


M00184
273 . . . 282(90)
MyoD
myoblast determining factor


M00147
167 . . . 158(90)
HSF2
heat shock factor 2


M00087
984 . . . 995(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
471 . . . 458(90)
NF-kappaB
NF-kappaB
















TABLE 19










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.7. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00349
94 . . . 103(100)
GATA-2
GATA-binding factor 2


M00348
94 . . . 103(100)
GATA-2
GATA-binding factor 2


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00100
1102 . . . 1096(100)
CdxA
CdxA


M00148
1017 . . . 1011(100)
SRY
sex-determining region Y gene product



967 . . . 973(100)



704 . . . 710(100)



944 . . . 938(96)



1550 . . . 1556(92)



840 . . . 834(90)



1362 . . . 1356(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



392 . . . 386(90)



745 . . . 739(90)



298 . . . 304(90)


M00350
94 . . . 103(100)
GATA-3
GATA-binding factor 3


M00101
1102 . . . 1096(99)
CdxA
CdxA



830 . . . 824(98)



1231 . . . 1225(98)



1385 . . . 1379(98)



1297 . . . 1291(93)



1409 . . . 1415(92)



723 . . . 717(92)



961 . . . 967(92)



66 . . . 60(92)



421 . . . 427(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00203
96 . . . 106(98)
GATA-X
GATA binding site


M00347
94 . . . 103(97)
GATA-1
GATA-binding factor 1


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1701 . . . 1692(95)



1889 . . . 1898(93)



900 . . . 891(91)



138 . . . 129(90)



1736 . . . 1745(90)


M00158
319 . . . 306(96)
COUP-TF
COUP/HNF-4 heterodimer


M00272
1267 . . . 1276(96)
p53
tumor suppressor p53


M00134
304 . . . 322(96)
HNF-4
hepatic nuclear factor 4


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1112 . . . 1124(91)



1487 . . . 1475(91)



13 . . . 1(90)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00253
1794 . . . 1801(95)
cap
cap signal for transcription initiation



481 . . . 488(95)



1893 . . . 1886(95)



1452 . . . 1459(94)



795 . . . 802(94)



656 . . . 649(93)



1486 . . . 1479(92)



1326 . . . 1319(91)



559 . . . 566(91)



1877 . . . 1870(91)



745 . . . 752(91)



918 . . . 925(91)



954 . . . 961(90)



1815 . . . 1808(90)



1299 . . . 1306(90)


M00054
466 . . . 457(95)
NF-kappaB
NF-kappaB


M00146
165 . . . 156(94)
HSF1
heat shock factor 1


M00147
165 . . . 156(94)
HSF2
heat shock factor 2



156 . . . 165(94)


M00141
453 . . . 461(94)
Lyf-1
LyF-1


M00052
466 . . . 457(94)
NF-kappaB
NF-kappaB (p65)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00053
466 . . . 457(94)
c-Rel
c-Rel


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



1701 . . . 1692(92)



1303 . . . 1312(92)



984 . . . 993(92)


M00099
1813 . . . 1798(92)
S8
S8



1111 . . . 1126(90)


M00184
271 . . . 280(92)
MyoD
myoblast determining factor


M00223
544 . . . 536(92)
STATx
signal transducers and activators of transcription


M00073
36 . . . 46(92)
deltaEF1
deltaEF1


M00033
805 . . . 792(92)
p300
p300


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00277
281 . . . 270(91)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 1


M00289
381 . . . 393(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00208
467 . . . 456(90)
NF-kappaB
NF-kappaB binding site


M00183
1027 . . . 1036(90)
c-Myb
c-Myb


M00240
241 . . . 235(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



1454 . . . 1448(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00302
838 . . . 827(90)
NF-AT
Nuclear factor of activated T-cells


M00128
93 . . . 105(90)
GATA-1
GATA-binding factor 1


M00087
981 . . . 992(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00042
69 . . . 78(90)
Sox-5
Sox-5


M00003
962 . . . 953(90)
v-Myb
v-Myb


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
468 . . . 455(90)
NF-kappaB
NF-kappaB
















TABLE 20










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.8. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
1020 . . . 1014(100)
SRY
sex-determining region Y gene product



970 . . . 976(100)



947 . . . 941(96)



1550 . . . 1556(92)



843 . . . 837(90)



707 . . . 713(90)



1362 . . . 1356(90)



1719 . . . 1713(90)



1824 . . . 1818(90)



395 . . . 389(90)



748 . . . 742(90)



300 . . . 306(90)


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00100
1105 . . . 1099(100)
CdxA
CdxA


M00101
1105 . . . 1099(99)
CdxA
CdxA



833 . . . 827(98)



1385 . . . 1379(98)



1409 . . . 1415(92)



964 . . . 970(92)



726 . . . 720(92)



424 . . . 430(92)


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1889 . . . 1898(93)



925 . . . 916(93)



1736 . . . 1745(90)


M00272
1267 . . . 1276(96)
p53
tumor suppressor p53


M00253
161 . . . 168(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



484 . . . 491(95)



1893 . . . 1886(95)



1452 . . . 1459(94)



798 . . . 805(94)



748 . . . 755(94)



957 . . . 964(94)



1486 . . . 1479(92)



338 . . . 345(92)



1697 . . . 1704(92)



562 . . . 569(91)



1877 . . . 1870(91)



1815 . . . 1808(90)



321 . . . 328(90)



1326 . . . 1319(90)



1299 . . . 1306(90)


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1115 . . . 1127(91)


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00054
469 . . . 460(95)
NF-kappaB
NF-kappaB


M00141
456 . . . 464(94)
Lyf-1
LyF-1


M00134
306 . . . 324(94)
HNF-4
hepatic nuclear factor 4


M00052
469 . . . 460(94)
NF-kappaB
NF-kappaB (p65)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00053
469 . . . 460(94)
c-Rel
c-Rel


M00033
758 . . . 745(94)
p300
p300



808 . . . 795(92)


M00158
321 . . . 308(93)
COUP-TF
COUP/HNF-4 heterodimer


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



1303 . . . 1312(92)



743 . . . 734(92)



925 . . . 916(90)


M00099
1813 . . . 1798(92)
S8
S8



1114 . . . 1129(90)


M00104
28 . . . 37(92)
CDP
cut-like homeodomain protein


M00223
547 . . . 539(92)
STATx
signal transducers and activators of transcription


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00042
649 . . . 658(91)
Sox-5
Sox-5


M00289
384 . . . 396(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00302
1384 . . . 1395(91)
NF-AT
Nuclear factor of activated T-cells



841 . . . 830(90)


M00155
367 . . . 382(91)
ARP-1
apolipoprotein AI regulatory protein 1


M00208
470 . . . 459(90)
NF-kappaB
NF-kappaB binding site


M00183
1030 . . . 1039(90)
c-Myb
c-Myb


M00240
243 . . . 237(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



1454 . . . 1448(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00083
47 . . . 40(90)
MZF1
MZF1


M00184
273 . . . 282(90)
MyoD
myoblast determining factor


M00147
167 . . . 158(90)
HSF2
heat shock factor 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00194
471 . . . 458(90)
NF-kappaB
NF-kappaB
















TABLE 21










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.9. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
991 . . . 997(100)
SRY
sex-determining region Y gene product



1040 . . . 1034(100)



967 . . . 961(96)



1576 . . . 1582(92)



1550 . . . 1556(92)



1385 . . . 1379(90)



1824 . . . 1818(90)



13 . . . 19(90)



415 . . . 409(90)



727 . . . 733(90)


M00101
1125 . . . 1119(100)
CdxA
CdxA



1254 . . . 1248(98)



1167 . . . 1161(97)



542 . . . 548(97)



884 . . . 878(94)



1432 . . . 1438(93)



743 . . . 737(92)



89 . . . 83(92)



592 . . . 586(92)



1280 . . . 1286(92)



444 . . . 450(92)



1682 . . . 1688(91)



1688 . . . 1682(91)


M00083
779 . . . 772(100)
MZF1
MZF1



68 . . . 61(90)


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00272
1290 . . . 1299(96)
p53
tumor suppressor p53


M00253
182 . . . 189(96)
cap
cap signal for transcription initiation



1794 . . . 1801(95)



1893 . . . 1886(95)



1475 . . . 1482(94)



768 . . . 775(94)



1506 . . . 1499(93)



1349 . . . 1342(91)



582 . . . 589(91)



351 . . . 358(90)



1815 . . . 1808(90)



342 . . . 349(90)



1877 . . . 1870(90)



504 . . . 511(90)



1322 . . . 1329(90)


M00100
1125 . . . 1119(96)
CdxA
CdxA


M00042
742 . . . 751(96)
Sox-5
Sox-5



669 . . . 678(92)



726 . . . 735(92)


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00077
1933 . . . 1941(95)
GATA-3
GATA-binding factor 3


M00045
1877 . . . 1888(95)
E4BP4
E4BP4


M00054
489 . . . 480(95)
NF-kappaB
NF-kappaB


M00141
476 . . . 484(94)
Lyf-1
LyF-1


M00052
489 . . . 480(94)
NF-kappaB
NF-kappaB (p65)


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00053
489 . . . 480(94)
c-Rel
c-Rel


M00278
1933 . . . 1941(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00076
1932 . . . 1941(93)
GATA-2
GATA-binding factor 2



1007 . . . 1016(92)



1701 . . . 1692(91)


M00285
1734 . . . 1746(92)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1135 . . . 1147(91)


M00099
1813 . . . 1798(92)
S8
S8



1134 . . . 1149(90)


M00104
49 . . . 58(92)
CDP
cut-like homeodomain protein


M00223
567 . . . 559(92)
STATx
signal transducers and activators of transcription


M00075
1701 . . . 1692(92)
GATA-1
GATA-binding factor 1



161 . . . 152(90)



1736 . . . 1745(90)


M00348
316 . . . 325(92)
GATA-2
GATA-binding factor 2


M00109
873 . . . 886(91)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00203
318 . . . 328(91)
GATA-X
GATA binding site


M00350
316 . . . 325(91)
GATA-3
GATA-binding factor 3


M00289
404 . . . 416(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00113
833 . . . 822(90)
CREB
cAMP-responsive element binding protein


M00249
1165 . . . 1153(90)
CHOP-
heterodimers of CHOP and C/EBPalpha




C/EBPalpha


M00208
490 . . . 479(90)
NF-kappaB
NF-kappaB binding site


M00190
1263 . . . 1250(90)
C/EBP
CCAAT/enhancer binding factor


M00349
316 . . . 325(90)
GATA-2
GATA-binding factor 2


M00116
1263 . . . 1250(90)
C/EBPalpha
CCAAT/enhancer binding protein alpha


M00183
1050 . . . 1059(90)
c-Myb
c-Myb


M00240
263 . . . 257(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



1477 . . . 1471(90)


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00302
1407 . . . 1418(90)
NF-AT
Nuclear factor of activated T-cells


M00184
293 . . . 302(90)
MyoD
myoblast determining factor


M00147
188 . . . 179(90)
HSF2
heat shock factor 2


M00087
1004 . . . 1015(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1


M00033
778 . . . 765(90)
p300
p300


M00194
491 . . . 478(90)
NF-kappaB
NF-kappaB
















TABLE 22










putative transcription factor binding motifs within the DUB regulatory or


promoter, region of hDUB 8.10. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00148
1038 . . . 1032(100)
SRY
sex-determining region Y gene product



965 . . . 959(96)



1550 . . . 1556(92)



725 . . . 731(90)



1382 . . . 1376(90)



310 . . . 316(90)



1715 . . . 1709(90)



1824 . . . 1818(90)



12 . . . 18(90)



413 . . . 407(90)



1630 . . . 1624(90)



319 . . . 325(90)


M00241
1800 . . . 1807(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00100
1123 . . . 1117(100)
CdxA
CdxA


M00240
1240 . . . 1234(100)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog



262 . . . 256(90)


M00141
474 . . . 482(100)
Lyf-1
LyF-1


M00101
1123 . . . 1117(99)
CdxA
CdxA



540 . . . 546(97)



1429 . . . 1435(94)



982 . . . 988(92)



88 . . . 82(92)



741 . . . 735(92)



442 . . . 448(92)


M00075
1838 . . . 1847(97)
GATA-1
GATA-binding factor 1



1889 . . . 1898(93)



1736 . . . 1745(90)


M00253
766 . . . 773(96)
cap
cap signal for transcription initiation



181 . . . 188(96)



1794 . . . 1801(95)



1893 . . . 1886(95)



1210 . . . 1217(94)



816 . . . 823(94)



1506 . . . 1499(92)



357 . . . 364(92)



1697 . . . 1704(92)



1090 . . . 1097(91)



1346 . . . 1339(91)



1877 . . . 1870(91)



71 . . . 78(90)



580 . . . 587(90)



1815 . . . 1808(90)



340 . . . 347(90)



502 . . . 509(90)



1319 . . . 1326(90)


M00096
1827 . . . 1819(96)
Pbx-1
Pbx-1


M00285
1734 . . . 1746(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1133 . . . 1145(91)



35 . . . 23(91)



1089 . . . 1101(90)


M00134
325 . . . 343(94)
HNF-4
hepatic nuclear factor 4


M00199
1797 . . . 1789(94)
AP-1
AP-1 binding site



1789 . . . 1797(91)


M00174
1788 . . . 1798(94)
AP-1
activator protein 1


M00042
740 . . . 749(94)
Sox-5
Sox-5



1631 . . . 1622(92)



667 . . . 676(91)


M00106
672 . . . 681(94)
CDP
cut-like homeodomain protein


M00158
340 . . . 327(93)
COUP-TF
COUP/HNF-4 heterodimer


M00076
761 . . . 752(93)
GATA-2
GATA-binding factor 2



1323 . . . 1332(92)



1005 . . . 1014(92)


M00099
1813 . . . 1798(92)
S8
S8



1132 . . . 1147(90)


M00104
48 . . . 57(92)
CDP
cut-like homeodomain protein


M00223
565 . . . 557(92)
STATx
signal transducers and activators of transcription


M00033
826 . . . 813(92)
p300
p300


M00271
1955 . . . 1960(92)
AML-1a
runt-factor AML-1


M00254
1831 . . . 1820(91)
CCAAT
cellular and viral CCAAT box


M00289
402 . . . 414(91)
HFH-3
HNF-3/Fkh Homolog 3 (=Freac-6)


M00217
160 . . . 153(90)
USF
USF binding site


M00183
1048 . . . 1057(90)
c-Myb
c-Myb


M00188
1788 . . . 1798(90)
AP-1
activator protein 1


M00083
67 . . . 60(90)
MZF1
MZF1


M00184
292 . . . 301(90)
MyoD
myoblast determining factor


M00147
187 . . . 178(90)
HSF2
heat shock factor 2


M00087
1002 . . . 1013(90)
Ik-2
Ikaros 2


M00172
1788 . . . 1798(90)
AP-1
activator protein 1


M00221
1860 . . . 1850(90)
SREBP-1
sterol regulatory element-binding protein 1
















TABLE 23










putative transcription factor binding motifs within the DUB regulatory or promoter,


region of hDUB 8.11. The position is indicated by nucleotides.










Transfac
Position(Score)
Name
Description





M00348
71 . . . 80(100)
GATA-2
GATA-binding factor 2


M00350
71 . . . 80(100)
GATA-3
GATA-binding factor 3


M00349
71 . . . 80(100)
GATA-2
GATA-binding factor 2


M00148
990 . . . 984(100)
SRY
sex-determining region Y gene product



1664 . . . 1658(100)



813 . . . 807(96)



917 . . . 911(96)



1858 . . . 1864(92)



1850 . . . 1856(92)



1836 . . . 1842(92)



1399 . . . 1405(90)



1514 . . . 1508(90)



680 . . . 686(90)



2104 . . . 2098(90)



368 . . . 362(90)



721 . . . 715(90)



1002 . . . 996(90)



1910 . . . 1904(90)



274 . . . 280(90)


M00100
595 . . . 589(100)
CdxA
CdxA



1408 . . . 1402(100)



1474 . . . 1480(96)


M00101
595 . . . 589(99)
CdxA
CdxA



1408 . . . 1402(99)



803 . . . 797(98)



1537 . . . 1531(98)



1715 . . . 1721(92)



699 . . . 693(92)



934 . . . 940(92)



43 . . . 37(92)



495 . . . 501(92)


M00141
1282 . . . 1274(98)
Lyf-1
LyF-1


M00347
71 . . . 80(97)
GATA-1
GATA-binding factor 1


M00272
1573 . . . 1582(96)
p53
tumor suppressor p53


M00253
1137 . . . 1144(96)
cap
cap signal for transcription initiation



136 . . . 143(96)



2074 . . . 2081(95)



457 . . . 464(95)



2173 . . . 2166(95)



721 . . . 728(94)



1444 . . . 1437(94)



660 . . . 653(94)



1792 . . . 1785(92)



312 . . . 319(92)



1632 . . . 1625(91)



535 . . . 542(91)



2095 . . . 2088(91)



1358 . . . 1365(91)



768 . . . 775(90)



295 . . . 302(90)



2157 . . . 2150(90)


M00096
2107 . . . 2099(96)
Pbx-1
Pbx-1


M00285
2014 . . . 2026(95)
TCF11
TCF11/KCR-F1/Nrf1 homodimers



1418 . . . 1430(91)


M00130
1657 . . . 1668(95)
HFH-2
HNF-3/Fkh Homolog 2


M00077
2213 . . . 2221(95)
GATA-3
GATA-binding factor 3


M00054
442 . . . 433(95)
NF-kappaB
NF-kappaB


M00052
442 . . . 433(94)
NF-kappaB
NF-kappaB (p65)


M00203
73 . . . 83(94)
GATA-X
GATA binding site


M00199
2077 . . . 2069(94)
AP-1
AP-1 binding site



2069 . . . 2077(91)



1994 . . . 2002(90)


M00174
2068 . . . 2078(94)
AP-1
activator protein 1



1436 . . . 1446(90)


M00075
895 . . . 886(94)
GATA-1
GATA-binding factor 1



2169 . . . 2178(93)



1091 . . . 1082(93)



1981 . . . 1972(92)



2016 . . . 2025(90)


M00053
442 . . . 433(94)
c-Rel
c-Rel


M00241
2080 . . . 2087(94)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00076
716 . . . 707(94)
GATA-2
GATA-binding factor 2



2212 . . . 2221(93)



1609 . . . 1618(92)



957 . . . 966(92)



895 . . . 886(91)



1981 . . . 1972(91)


M00106
627 . . . 636(94)
CDP
cut-like homeodomain protein


M00033
731 . . . 718(94)
p300
p300


M00227
2149 . . . 2141(94)
v-Myb
v-Myb


M00158
295 . . . 282(93)
COUP-TF
COUP/HNF-4 heterodimer


M00162
2080 . . . 2093(93)
Oct-1
octamer-binding factor 1


M00278
2213 . . . 2221(93)
Lmo2
complex of Lmo2 bound to Tal-1, E2A proteins, and





GATA-1, half-site 2


M00134
280 . . . 298(93)
HNF-4
hepatic nuclear factor 4


M00032
226 . . . 235(93)
c-Ets-1(p54)
c-Ets-1(p54)


M00172
1436 . . . 1446(92)
AP-1
activator protein 1



2068 . . . 2078(90)


M00117
1089 . . . 1076(92)
C/EBPbeta
CCAAT/enhancer binding protein beta


M00223
520 . . . 512(92)
STATx
signal transducers and activators of transcription


M00042
1911 . . . 1902(92)
Sox-5
Sox-5



622 . . . 631(91)


M00073
13 . . . 23(92)
deltaEF1
deltaEF1


M00188
1436 . . . 1446(91)
AP-1
activator protein 1



2068 . . . 2078(90)


M00254
2111 . . . 2100(91)
CCAAT
cellular and viral CCAAT box


M00099
2093 . . . 2078(91)
S8
S8



2076 . . . 2091(90)



1417 . . . 1432(90)


M00289
1657 . . . 1669(91)
HFH-3
HNF-3/Fkh Homolog 3 (= Freac-6)



357 . . . 369(91)


M00147
752 . . . 743(91)
HSF2
heat shock factor 2



142 . . . 133(90)


M00208
443 . . . 432(90)
NF-kappaB
NF-kappaB binding site


M00217
115 . . . 108(90)
USF
USF binding site


M00183
1333 . . . 1342(90)
c-Myb
c-Myb


M00173
1436 . . . 1446(90)
AP-1
activator protein 1


M00240
217 . . . 211(90)
Nkx-2.5
homeo domain factor Nkx-2.5/Csx, tinman homolog


M00184
1965 . . . 1974(90)
MyoD
myoblast determining factor



247 . . . 256(90)


M00087
954 . . . 965(90)
Ik-2
Ikaros 2


M00128
70 . . . 82(90)
GATA-1
GATA-binding factor 1


M00145
1347 . . . 1362(90)
Brn-2
POU factor Brn-2


M00194
444 . . . 431(90)
NF-kappaB
NF-kappaB









REFERENCES



  • 1. Baek, K. H., Mondoux, M. A., Jaster, R., Fire-Levin, E., and D'Andrea, A. D. (2001). DUB-2A, a new member of the DUB subfamily of hematopoietic deubiquitinating enzymes, Blood 98, 636-42.

  • 2. Jaster, R., Baek, K. H., and D'Andrea, A. D. (1999). Analysis of cis-acting sequences and trans-acting factors regulating the interleukin-3 response element of the DUB-1 gene, Biochim Biophys Acta 1446, 308-16.

  • 3. Jaster, R., Zhu, Y., Pless, M., Bhattacharya, S., Mathey-Prevot, B., and D'Andrea, A. D. (1997). JAK2 is required for induction of the murine DUB-1 gene, Mol Cell Biol 17, 3364-72.

  • 4. Migone, T. S., Humbert, M., Rascle, A., Sanden, D., D'Andrea, A., Johnston, J. A., Baek, K. H., Mondoux, M. A., Jaster, R., Fire-Levin, E., et al. (2001). The deubiquitinating enzyme DUB-2 prolongs cytokine-induced signal transducers and activators of transcription activation and suppresses apoptosis following cytokine withdrawal, Blood 98, 1935-41.

  • 5. Zhu, Y., Carroll, M., Papa, F. R., Hochstrasser, M., and D'Andrea, A. D. (1996a). DUB-1, a deubiquitinating enzyme with growth-suppressing activity, Proc Natl Acad Sci USA 93, 3275-9.

  • 6. Zhu, Y., Lambert, K., Corless, C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., and D'Andrea, A. D. (1997). DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes, J Biol Chem 272, 51-7.



7. Zhu, Y., Pless, M., Inhom, R., Mathey-Prevot, B., and D'Andrea, A. D. (1996b). The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor, Mol Cell Biol 16, 4808-17.

Nucleotide sequence for hDUB4.1aatgaccctgcaacagagcatgcccttctgcattgagcatgcaatcatgaatcacaggcggaggaactgcgagagtgcctacgttagcccaaggcctgacccgacgatcccagggaccctcgacctaactggccccgcctcccgggccccaaacccggactcggcccccccgaagctccggatcctggggcccgcccctggccccgcgtcggaagaccatgggctcgctcctgggccttcctcaaaccctccgcagtccaggcccggcttcctccaggtctccaggcaacgctgcggctccgcccacgtcatggcgcccgaggagaacgcggggacagaactctggctgcagggtttcgagcgccgcttcctggcggcgcgctcactgcgctccttcccctggcagagcttagaggcaaagttaagagactcatcagattctgagctgctgcgggatattttgcagaagactgtgaagcatcccgtgtgtgtgaagcacccgccatcagtcaagtatgcccggtgctttctctcagaactcatcaaaaagggtgcatctgtggtcaccagcagcacgagggctgtccacacggagcctttggacgagctgtacgaggtgctggcggagactctgatggccaaggagtccacccagggccaccggagctatttgctgccctcgggaggctcgttcacactttccgagatcacagccatcatctcccatggtactacaggcctggtcacatgggacgccaccctctaccttgcagaatgggccatcgagaacccagcagccttcactaacaggggtgtcctagagcttggcagtggcgctggcctcacaggcctggccatctgcaagatgtgtcgcccccaggcatacatcttcagcgactgtcacagccgggtcctcgagcagctccgagggaatgtccttctcaatggcctctcattagaggcagacatcactgccaacttagacgccccaggagaccacaggagaaaaacaaccacttctgggacgaggacagggcccttgagaaaaggtggtgtttggctgggccaccgaaaacccctcacccctgccagcacactcagtcccctctctggtggaacagagctctgcctgtggccctgggtcccagccctgaaacccacaggtccagcggtggccagggacacaggcccacccctgcaagccagcagaccaaacggcagacacctgaaacaagaagttcacgacgtgctgtattgcccagaagccatcgtgtcactggtcggggtcctgcggaggctggctgcctgccgggagcacaagcaggctcctgaggtctacctggcctttaccgtccgcaacccagagacgtgccagctgttcaccaccgagctagagatagcgtctttctgcaacctgcggtcccagcagaaaaaccttgtgatccttgttccagtcgacatggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcttttgctgaaatccagcgtacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcctcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccctgcagtgcctgacatacaaaccgccacttgccaactacatgctgttccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtactatgcaagctcacatcacaagggccctccacattcctggccatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgagaaaggcatgccttcccgggcacaagcaggtagatcgtcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggtgtttgtctccagagggcgccggcctccaagacgttaactttacacaactctgccaaggtcctcatccttgtattgaagagattccccgatgtcacaggcaacaaaattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctctcgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattactcctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgcctctagcatcacttctgtcctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgtagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaagagtcgaaggtacggtgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtcggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgaccccgacagatcaggagtccatgaacactggcacactcgcttccctacgagggaggaccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB4.1a deduced polypeptide sequenceMTLQQSMPFCIEHAIMNHRRRNCESAYVSPRPDPTIPGTLDLTGPASRAPNPDSAPPKLRILGPAPGPASEDHGLAPGPSSNPPQSRPGFLQVSRQRCGSAHVMAPEENAGTELWLQGFERRFLAARSLRSFPWQSLEAKLRDSSDSELLRDILQKTVKHPVCVKHPPSVKYARCFLSELIKKGASVVTSSTRAVHTEPLDELYEVLAETLMAKESTQGHRSYLLPSGGSFTLSEITAIISHGTTGLVTWDATLYLAEWAIENPAAFTNRGVLELGSGAGLTGLAICKMCRPQAYIFSDCHSRVLEQLRGNVLLNGLSLEADITANLDAPGDHRRKTTTSGTRTGPLRKGGVWLGHRKPLTPASTLSPLSGGTELCLWPWVPALKPTGPAVARDTGPPLQASRPNGRHLKQEVHDVLYCPEAIVSLVGVLRRLAACREHKQAPEVYLAFTVRNPETCQLFTTELEIASFCNLRSQQKNLVILVPVDMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKPPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYKPPLANYMLFREHSQTCHRHKGCMLCTMQAHITRALHIPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMRKACLPGHKQVDRHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHNSAKVLILVLKRFPDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYSSYVKAQEGQWYKMDDAEVTASSITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGVEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRRVEGTVPPDVLVIHQSKYKCRMKNHHPEQQSSLLNLSSTTPTDQESMNTGTLASLRGRTRRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.1batggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcttttgctgaaatccagcgtacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcctcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccctgcagtgcctgacatacaaaccgccacttgccaactacatgctgttccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtactatgcaagctcacatcacaagggccctccacattcctggccatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgagaaaggcatgccttcccgggcacaagcaggtagatcgtcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggtgtttgtctccagagggcgccggcctccaagacgttaactttacacaactctgccaaggtcctcatccttgtattgaagagattccccgatgtcacaggcaacaaaattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctctcgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattactcctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgcctctagcatcacttctgtcctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgtagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaagagtcgaaggtacggtgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtcggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgaccccgacagatcaggagtccatgaacactggcacactcgcttccctacgagggaggaccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB4.1b deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKPPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYKPPLANYMLFREHSQTCHRHKGCMLCTMQAHITRALHIPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMRKACLPGHKQVDRHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHNSAKVLILVLKRFPDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYSSYVKAQEGQWYKMDDAEVTASSITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGVEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRRVEGTVPPDVLVIHQSKYKCRMKNHHPEQQSSLLNLSSTTPTDQESMNTGTLASLRGRTRRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.2aatgggaaatacctgctacgtgaacgcttccttgcagtgcctgacatacacaccgccccttgccaactacatgctgtcccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtactatgcaagctcacatcacacgggccctccacaatcctggccacgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccaggcacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggtgtttgtctccagagggcgccggcctccaagacgttaactttacacacctctgccaaggtcctcatccttgtattgaagagattctccgatgtcacaggcaacaagattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgagtggagttgtcacaacggacattacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgccgctagcatcacttctgtcctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacatagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgcagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcaaaggtacagtgatcaaagttgaccagccccagaggaaagctgcccagggcacaactcagggctccgtagaaccacagaatcttgggcgcaaccctgctcaagcacccaaatgtgcatacgaacagggtctccgtgtgacggaacatgtccactttcggcagcattacaattttggcaccaaatgtgctaactgcaattccaccatacaatgcgtaactggaaatggaggcaacatcgccgatcctgaacgatcgatgcgagaatccaggatatgcacggcttattttggccttttcccactgaaacaagggccagtattaaaaatgcagaaaaaccttgtgatcctcgttccagtcgacatggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggcccgatgcagcttttgctgaaatccagcggacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccttgcagtgcctgacatacacaacgccccttgccaactacatgctgtcccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtactatgcaagctcacatcacacgggccctccacaatcctggccacgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccgggcacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctagatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattctggtgtttgtctccagagggcgccggcctccaagacgttaactttacacacctctgccaaggtcctcatccttgtattgaagagattctccgatgtcacaggcaacaagattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgccgctagcatcacttctgccctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcacagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtgggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgtcgaccccgacacatcaggagtccatgaacactggcacactcgcttccctgcgagggagggccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB4.2a deduced polypeptide sequenceMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPRHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAEWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVKGTVIKVDQPQRKAAQGTTQGSVEPQNLGRNPAQAPKCAYEQGLRVTEHVHFRQHYNFGTKCANCNSTIQCVTGNGGNIADPERSMRESRICTAYFGLFPLKQGPVLKMQKNLVILVPVDMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTTPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHSGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASITSALSQQAYVLFYIQKSEWERHSESVSRGREPRALGTEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.2batggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggcccgatgcagcttttgctgaaatccagcggacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccttgcagtgcctgacatacacaacgccccttgccaactacatgctgtcccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtactatgcaagctcacatcacacgggccctccacaatcctggccacgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccgggcacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctagatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattctggtgtttgtctccagagggcgccggcctccaagacgttaactttacacacctctgccaaggtcctcatccttgtattgaagagattctccgatgtcacaggcaacaagattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgccgctagcatcacttctgccctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcacagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtgggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgtcgaccccgacacatcaggagtccatgaacactggcacactcgcttccctgcgagggagggccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB4.2b deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTTPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHSGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASITSALSQQAYVLFYIQKSEWERHSESVSRGREPRALGTEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.3atggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggcccgatgcagcttttgctgaaatccagcggacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccttgcagtgcctgacatacacaccgccccttgccaactacatgctgtcccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtacgatgcaagctcacatcacacgggccctccacaatcctggccacgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccgggcacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggtgtttgtctccagagggcgccggcctccaagacgttaactttacacacctctgccaaggtcctcatccttgtattgaagagattctccgatgtgacaggcaacaagattgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattacttctcttatgtcaaagctcaagaaggccaatggtataaaatggatgatgccgaggtcaccgccgctagcatcacttctgtcctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgcagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccgctggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtgggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgtcgaccccgacacatcaggagtccatgaacactggcacactcgcttccctgcgagggagggccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB4.3 deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDRWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.5atgcgccagagagctcgtcatttgaagactctctcggaagggatagcgtctttctgcaacctgcggtcccagcagaaaaaccttgtgatccttgttccagtcgacatggaggaagactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggcccgatgcagcttttgctgaaatccagcggacttctctccctgagaagtcaccactctcatgtgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaagcttcctctgagtaacaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttccttgcagtgcctgacatacacaccgccccttgccaactacatgctgtcccgggagcactctcaaacgtgtcatcgtcacaagggctgcatgctctgtacgatgcaagctcacatcacacgggccctccacaatcctggccacgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccgggcacaagcaggtggatcatcactctaaggacaccaccctcatccaccaaatatttggaggctactggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtccagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggtgtttgtctccagagggcgccggcctccaagacgttaactttacacacctctgccaaggtcctcatccttgtattgaagagattctccgatgtcacaggcaacaagattgacaagaatgtgcaatatcctgagtgccttgacatgaagctatacatgtctcagacgaactcaggacctctcgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacattacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcaccgcctctagcatcacttctgtcctgagtcaacaggcctacgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgcagaagacacagacaggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcccccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattccttcaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccgacgtacttgtgattcatcaatcaaaatacaagtgtgggatgaagaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgaccccgacacatcaggagtccatgaacactggcacactcgcttccctgcgagggagggccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtggtctcagtggaagtaccgacccacahDUB4.5 deduced polypeptide sequenceMRQRARHLKTLSEGIASFCNLRSQQKNLVILVPVDMEEDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSNRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIDKNVQYPECLDMKLYMSQTNSGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASSITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQWSQWKYRPTNucleotide sequence for hDUB4.6atggaggacg actcactcta cttgggaggt gagtggcagttcaaccactt ttcaaaactc acatcttctc ggcccgatgcagcttttgct gaaatccagc ggacttctct ccctgagaagtcaccactct catgtgagac ccgtgtcgac ctctgtgatgatttggctcc tgtggcaaga cagcttgctc ccagggagaagcttcctctg agtagcagga gacctgctgc ggtgggggctgggctccaga atatgggaaa tacctgctac gtgaacgcttccttgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc cgggagcact ctcaaacgtg tcatcgtcacaagggctgta tgctctgtac gatgcaagct cacatcacacgggccctcca caatcctggc cacgtcatcc agccctcacaggcattggct gctggcttcc atagaggcaa gcaggaagatgcccatgaat ttctcatgtt cactgtggat gccatgaaaaaggcatgcct tcccgggcac aagcaggtgg atcatcactctaaggacacc accctcatcc accaaatatt tggaggctactggagatctc aaatcaagtg tctccactgc cacggcatttcagacacttt tgacccttac ctggacatcg ccctggatatccaggcagct cagagtgtcc agcaagcttt ggaacagttggtgaagcccg aagaactcaa tggagagaat gcctatcattgtggtgtttg tctccagagg gcgccggcct ccaagacgttaactttacac acctctgcca aggtcctcat ccttgtattgaagagattct ccgatgtcac aggcaacaag attgccaagaatgtgcaata tcctgagtgc cttgacatgc agccatacatgtctcagacg aacacaggac ctctcgtcta tgtcctctatgctgtgctgg tccacgctgg gtggagttgt cacaacggacattacttctc ttatgtcaaa gctcaagaag gccagtggtataaaatggat gatgccgagg tcaccgcctc tagcatcacttctgtcctga gtcaacaggc ctacgtcctc ttttacatccagaagagtga atgggaaaga cacagtgaga gtgtgtcaagaggcagggaa ccaagagccc ttggcgcaga agacacagacaggcgagcaa cgcaaggaga gctcaagaga gaccacccctgcctccaggc ccccgagttg gacgagcact tggtggaaagagccactcag gaaagcacct tagaccactg gaaattccttcaagagcaaa acaaaacgaa gcctgagttc aacgtcagaaaagtcgaagg taccctgcct cccgacgtac ttgtgattcatcaatcaaaa tacaagtgtg ggatgaagaa ccatcatcctgaacagcaaa gctccctgct aaacctctct tcgacgaccccgacacatca ggagtccatg aacactggca cactcgcttccctgcgaggg agggccagga gatccaaagg gaagaacaaacacagcaaga gggctctgct tgtgtgccag tgahDUB4.6 deduced polypeptide sequenceMEDDSLYLGG EWQFNHFSKL TSSRPDAAFA EIQRTSLPEKSPLSCETRVD LCDDLAPVAR QLAPREKLPL SSRRPAAVGAGLQNMGNTCY VNASLQCLTY TPPLANYMLS REHSQTCHRHKGCMLCTMQA HITRALHNPG HVIQPSQALA AGFHRGKQEDAHEFLMFTVD AMKKACLPGH KQVDHHSKDT TLIHQIFGGYWRSQIKCLHC HGISDTFDPY LDIALDIQAA QSVQQALEQLVKPEELNGEN AYHCGVCLQR APASKTLTLH TSAKVLILVLKRFSDVTGNK IAKNVQYPEC LDMQPYMSQT NTGPLVYVLYAVLVHAGWSC HNGHYFSYVK AQEGQWYKMD DAEVTASSITSVLSQQAYVL FYIQKSEWER HSESVSRGRE PRALGAEDTDRRATQGELKR DHPCLQAPEL DEHLVERATQ ESTLDHWKFLQEQNKTKPEF NVRKVEGTLP PDVLVIHQSK YKCGMKNHHPEQQSSLLNLS STTPTHQESM NTGTLASLRG RARRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.7atggaggacg actcactcta cttgggtggt gagtggcagttcaaccactt ttcaaaactc acatcttctc ggcccgatgcagcttttgct gaaatccagc ggacttctct ccctgagaagtcaccactct catgtgagac ccgtgtcgac ctctgtgatgatttggctcc tgtggcaaga cagcttgctc ccagggagaagcttcctctg agtagcagga gacctgctgc ggtgggggctgggctccaga atatgggaaa tacctgctac gtgaacgcttccttgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc cgggagcact ctcaaacgtg tcatcgtcacaagggctgca tgctctgtac tatgcaagct cacatcacacgggccctcca caatcctggc cacgtcatcc agccctcacaggcattggct gctggcttcc atagaggcaa gcaggaagatgcccatgaat ttctcatgtt cactgtggat gccatgaaaaaggcatgcct tcccgggcac aagcaggtag atcatcactctaaggacacc accctcatcc accaaatatt tggaggctactggagatctc aaatcaactg tctccactgc cacggcatttcagacacttt tgacccttac ctggacatcg ccctggatatccaggcagct cagagtgtcc agcaagcttt ggaacagttggtgaagcccg aagaactcaa tggagagaat gcctatcattgtggtgtttg tctccagagg gcgccggcct ccaagacgttaactttacac acctctgcca aggtcctcat ccttgtattgaagagattct ccgatgtcac aggcaacaag attgccaagaatgtgcaata tcctgagtgc cttgacatgc agccatacatgtctcagcag aacacaggac ctcttgtcta tgtcctctatgctgtgctgg tccacgctgg gtggagttgt cacaacggacattacttctc ttatgtcaaa gctcaagaag gccagtggtataaaatggat gatgccgagg tcaccgccgc tagcatcacttctgtcctga gtcaacaggc ctacgtcctc ttttacatccagaagagtga atgggaaaga cacagtgaga gtgtgtcaagaggcagggaa ccaagagccc ttggcgcaga agacacagacaggcgagcaa cgcaaggaga gctcaagaga gaccacccctgcctccaggc ccccgagttg gacgagcact tggtggaaagagccactcag gaaagcacct tagaccactg gaaattccttcaagagcaaa acaaaacgaa gcctgagttc aacgtcagaaaagtcgaagg taccctgcct cccgacgtac ttgtgattcatcaatcaaaa tacaagtgtg ggatgaagaa ccatcatcctgaacagcaaa gctccctgct aaacctctct tcgtcgaccccgacacatca ggaggccatg aacactggca cactcgcttccctgcgaggg aggaccagga gatccaaagg gaagaacaaacacagcaaga gggctctgct tgtgtgccag tgahDUB4.7 deduced polypeptide sequenceMEDDSLYLGG EWQFNHFSKL TSSRPDAAFA EIQRTSLPEKSPLSCETRVD LCDDLAPVAR QLAPREKLPL SSRRPAAVGAGLQNMGNTCY VNASLQCLTY TPPLANYMLS REHSQTCHRHKGCMLCTMQA HITRALHNPG HVIQPSQALA AGFHRGKQEDAHEFLMFTVD ANKKACLPGH KQVDHHSKDT TLIHQIFGGYWRSQINCLHC HGISDTFDPY LDIALDIQAA QSVQQALEQLVKPEELNGEN AYHCGVCLQR APASKTLTLH TSAKVLILVLKRFSDVTGNK IAKNVQYPEC LDMQPYNSQQ NTGPLVYVLYAVLVHAGWSC HNGHYFSYVK AQEGQWYKMD DAEVTAASITSVLSQQAYVL FYIQKSEWER HSESVSRGRE PRALGAEDTDRRATQGELKR DHPCLQAPEL DEHLVERATQ ESTLDHWKFLQEQNKTKPEF NVRKVEGTLP PDVLVIHQSK YKCGMKNHHPEQQSSLLNLS SSTPTHQEAM NTGTLASLRG RTRRSKGKNKHSKRALLVCQNucleotide sequence for hDUB4.8atgcgccaga gagctcgtca tttgaagact ctctcggaagggatagcgtc ttgctgcaaa ctgcggtccc agcagaaaaaccttgtgatc cttgttccag tcgacatgga ggacgactcactctacttgg gaggtgagtg gcagttcaac cacttttcaaaactcacatc ttctcggccc gatgcagctt ttgctgaaatccagcggact tctctccctg agaagtcacc actctcatgtgagacccgtg tcgacctctg tgatgatttg gctcctgtggcaagacagct tgctcccagg gagaagcttc ctctgagtagcaggagacct gctgcggtgg gggctgggct ccagaatatgggaaatacct gctacgtgaa cgcttccttg cagtgcctgacatacacacc gccccttgcc aactacatgc tgtcccgggagcactctcaa acgtgtcatc gtcacaaggg ctgcatgctctgtacgatgc aagctcacat cacacgggcc ctccacaatcctggccacgt catccagccc tcacaggcat tggctgctggcttccataga ggcaagcagg aagatgccca tgaatttctcatgttcactg tggatgccat gaaaaaggca tgccttcccgggcacaagca ggtagatcat cactctaagg acaccaccctcatccaccaa atatttggag gctactggag atctcaaatcaagtgtctcc actgccacgg catttcagac acttttgacccttacctgga catcgccctg gatatccagg cagctcagagtgtccagcaa gctttggaac agttggtgaa gcccgaagaactcaatggag agaatgccta tcattgtggt gtttgtctccagagggcgcc ggcctccaag acgttaactt tacacacctctgccaaggtc ctcatccttg tattgaagag attctccgatgtgacaggca acaagattgc caagaatgtg caatatcctgagtgccttga catgcagcca tacatgtctc agcagaacacaggacctctt gtctatgtcc tctatgctgt gctggtccacgctgggtgga gttgtcacaa cggacattac ttctcttatgtcaaagctca agaaggccaa tggtataaaa tggatgatgccgaggtcacc gccgctagca tcacttctgt cctgagtcaacaggcctacg tcctctttta catccagaag agtgaatgggaaagacacag tgagagtgtg tcaagaggca gggaaccaagagcccttggc gcagaagaca cagacaggcg agcaacgcaaggagagctca agagagacca cccctgcctc caggcccccgagttggacga gcacttggtg gaaagagcca ctcaggaaagcaccttagac cactggaaat tccttcaaga gcaaaacaaaacgaagcctg agttcaacgt cagaaaagtc gaaggtaccctgcctcccga cgtacttgtg attcatcaat caaaatacaagtgtgggatg aagaaccatc atcctgaaca gcaaagctccctgctaaacc tctcttcgtc gaccccgaca catcaggagtccatgaacac tggcacactc gcttccctgc gagggagggccaggagatcc aaagggaaga acaaacacag caagagggctctgcttgtgt gccagtgahDUB4.8 deduced polypeptide sequenceMRQRARHLKT LSEGIASCCK LRSQQKNLVI LVPVDMEDDSLYLGGEWQFN HFSKLTSSRP DAAFAEIQRT SLPEKSPLSCETRVDLCDDL APVARQLAPR EKLPLSSRRP AAVGAGLQNMGNTCYVNASL QCLTYTPPLA NYMLSREHSQ TCHRHKGCMLCTMQAHITRA LHNPGHVIQP SQALAAGFHR GKQEDAHEFLMFTVDANKKA CLPGHKQVDH HSKDTTLIHQ IFGGYWRSQIKCLHCHGISD TFDPYLDIAL DIQAAQSVQQ ALEQLVKPEELNGENAYHCG VCLQRAPASK TLTLHTSAKV LILVLKRFSDVTGNKIAKNV QYPSCLDMQP YNSQQNTGPL VYVLYAVLVHAGWSCHNGHY FSYVKAQEGQ WYKMDDAEVT AASITSVLSQQAYVLFYIQK SEWERHSESV SRGREPRALG AEDTDRRATQGELKRDHPCL QAPELDEHLV ERATQESTLD HWKFLQEQNKTKPEFNVRKV EGTLPPDVLV IHQSKYKCGM KNHHPEQQSSLLNLSSSTPT HQESMNTGTL ASLRGRARRS KGKNKHSKRALLVCQNucleotide sequence for hDUB4.10atgtgcatac gaacagggtc tccgtgtgac gtgtgtgaaaactacagtgt gatgagcatg actggcagac agcttatcgattgggctccc ctcaaaatcg gttatgagca ttcaagcacaccgatgccca gggaacatgt ccactttcgg cagcattacaattttggcac caaatgtgct aactgcaatt ccaccatacaatgcgtaact ggaaatggag gcaacatcgc cgatcctgaacgatcgatgc gagaatccag gatatgcacg gcttattttggccttttccc actgaaacaa gggccagtat taaaaatggtaatttcactc ggacagagaa tcaataggct caacgtggaaaggttatcgc tggaagggaa gaaaatacgc tgtgctaaatactatacttc attgactatt ctcaggtcag aaagcgcactttcgacttct tgtccttccg tcgctgagag gatgatggcagctgccaaaa ggatagcgtc tttctgcaac ctgcggtcccagcagaaaaa ccttgtgatc ctcgttccag tcgacatggaggacgactca ctctacttgg gaggtgagtg gcagttcaaccacttttcaa aactcacatc ttctcggccc gatgcagcttttgctgaaat ccagcggact tctctccctg agaagtcaccactctcatgt gagacccgtg tcgacctctg tgatgatttggctcctgtgg caagacagct tgctcccagg gagaagcttcctctgagtag caggagacct gctgcggtgg gggctgggctccagaatatg ggaaatacct gctacgtgaa cgcttccttgcagtgcctga catacacaac gccccttgcc aactacatgctgtcccggga gcactctcaa acgtgtcatc gtcacaagggctgcatgctc tgtactatgc aagctcacat cacacgggccctccacaatc ctggccacgt catccagccc tcacaggcattggctgctgg cttccataga ggcaagcagg aagatgcccatgaatttctc atgttcactg tggatgccat gaaaaaggcatgccttcccg ggcacaagca ggtagatcat cactctaaggacaccaccct catccaccaa atatttggag gctactggagatctcaaatc aagtgtctcc actgccacgg catttcagacacttttgacc cttacctgga catcgcccta gatatccaggcagctcagag tgtccagcaa gctttggaac agttggtgaagcccgaagaa ctcaatggag agaatgccta tcattctggtgtttgtctcc agagggcgcc ggcctccaag acgttaactttacacacctc tgccaaggtc ctcatccttg tattgaagagattctccgat gtcacaggca acaagattgc caagaatgtgcaatatcctg agtgccttga catgcagcca tacatgtctcagcagaacac aggacctctt gtctatgtcc tctatgctgtgctggtccac gctgggtgga gttgtcacaa cggacattacttctcttatg tcaaagctca agaaggccag tggtataaaatggatgatgc cgaggtcacc gccgctagca tcacttctgccctgagtcaa caggcctacg tcctctttta catccagaagagtgaatggg aaagacacag tgagagtgtg tcaagaggcagggaaccaag agcccttggc acagaagaca cagacaggcgagcaacgcaa ggagagctca agagagacca cccctgcctccaggcccccg agttggacga gcacttggtg gaaagagccactcaggaaag caccttagac cactggaaat tccttcaagagcaaaacaaa acgaagcctg agttcaacgt cagaaaagtcgaaggtaccc tgcctcccga cgtacttgtg attcatcaatcaaaatacaa gtgtgggatg aagaaccatc atcctgaacagcaaagctcc ctgctaaacc tctcttcgtc gaccccgacacatcaggagt ccatgaacac tggcacactc gcttccctgcgagggagggc caggagatcc aaagggaaga acaaacacagcaagagggct ctgcttgtgt gccagtgahDUB4.10 deduced polypeptide sequenceMCIRTGSPCD VCENYSVMSM TGRQLIDWAP LKIGYEHSSTPNPRSHVHFR QHYNFGTKCA NCNSTIQCVT GNGGNIADPERSMRESRICT AYFGLFPLKQ GPVLKMVISL GQRINRLNVERLSLEGKKIR CAKYYTSLTI LRSESALSTS CPSVAERMMAAAKRIASFCN LRSQQKNLVI LVPVDMEDDS LYLGGEWQFNHFSKLTSSRP DAAFAEIQRT SLPEKSPLSC ETRVDLCDDLAPVARQLAPR EKLPLSSRRP AAVGAGLQNM GNTCYVNASLQCLTYTTPLA NYMLSREHSQ TCHRHKGCML CTMQAHITRALHNPGHVIQP SQALAAGFHR GKQEDAHEFL NFTVDANKKACLPGHKQVDH HSKDTTLIHQ IFGGYWRSQI KCLHCHGISDTFDPYLDIAL DIQAAQSVQQ ALEQLVKPEE LNGENAYHSGVCLQRAPASK TLTLHTSAKV LILVLKRFSD VTGNKIAKNVQYPECLDMQP YMSQQNTGPL VYVLYAVLVH AGWSCHNGHYFSYVKAQEGQ WYKMDDAEVT AASITSALSQ QAYVLFYIQKSEWERHSESV SRGREPRALG TEDTDRRATQ GELKRDHPCLQAPELDEHLV ERATQESTLD HWKFLQEQNK TKPEFNVRKVEGTLPPDVLV IHQSKYKCGM KNHHPEQQSS LLNLSSSTPTHQESMNTGTL ASLRGRARRS KGKNKHSKRA LLVCQNucleotide sequence for hDUB4.11atgtgcatac gaacagggtc tccgtgtgac gtgtgtgaaaactacagtgt gatgagcatg actggcagac agcttatcgattgggctccc ctcaaaatcg gttatgagca ttcaagcacaccgatgccca ggacacttta catccggcac aggaagccttctgatggagc acacctggcc catgaaaaga caagggaaagaaacggggcc aaagggaaga aaatacgctg tgctaaatactatacttcat tgactattct caggtcagaa agcgcactttcgtcttcttg tccttccgtc gcggagagga tgatggcagctgccaaaatc gacatggagg acgactcact ctacttgggaggtgagtggc agttcaacca cttttcaaaa ctcacatcttctcggccaga tgcagctttt gctgaaatcc agcggacttctctccctgag aagtcaccac tctcatatga tttggctcctgtggcaagac agcttgctcc cagggagaag cttcctctgagtagcaggag acctgctgcg gtgggggctg ggctccagaatatgggaaat acctgctacg tgaacgcttc cttgcagtgcctgacataca caccgcccct tgccaactac atgctgtcccgggagcactc tcaaacgtgt catcgtcaca agggctgcatgctctgtact atgcaagctc acatcacacg ggccctccacaatcctggcc acgtcatcca gccctcacag gcattggctgctggcttcca tagaggcaag caggaagatg cccatgaatttctcatgttc actgtggatg ccatgaaaaa ggcatgccttcccaggcaca agcaggtaga tcatcactct aaggacaccaccctcatcca ccaaatattt ggaggctact ggagatctcaaatcaagtgt ctccactgcc acggcatttc agacacttttgacccttacc tggacatcgc cctggatatc caggcagctcagagtgtcca gcaagctttg gaacagttgg tgaagcccgaagaactcaat ggagagaatg cctatcattg tggtgtttgtctccagaggg cgccggcctc caagacgtta actttacacacctctgccaa ggtcctcatc cttgtattga agagattctccgatgtcaca ggcaacaaga ttgccaagaa tgtgcaatatcctgagtgcc ttgacatgca gccatacatg tctcagcagaacacaggacc tcttgtctat gtcctctatg ctgtgctggtccacgctgag tggagttgtc acaacggaca ttacttctcttatgtcaaag ctcaagaagg ccagtggtat aaaatggatgatgccgaggt caccgccgct agcatcactt ctgtcctgagtcaacaggcc tacgtcctct tttacatcca gaagagtgaatgggaaagac atagtgagag tgtgtcaaga ggcagggaaccaagagccct tggcgcagaa gacacagaca ggcgagcaacgcaaggagag ctcaagagag accacccctg cctccaggcccccgagttgg acgagcactt ggtggaaaga gccactcaggaaagcacctt agaccactgg aaattccttc aagagcaaaacaaaacgaag cctgagttca acgtcagaaa agtcaaaggtaccctgcctc ccgacgtact tgtgattcat caatcaaaatacaagtgtgg gatgaagaac catcatcctg aacagcaaagctccctgcta aacctctctt cgtcgacccc gacacatcaggagtccatga acactggcac actcgcttcc ctgcgagggagggccaggag atccaaaggg aagaacaaac acagcaagagggctctgctt gtgtgccagt gahDUB4.11 deduced polypeptide sequenceMCIRTGSPCD VCENYSVMSM TGRQLIDWAP LKIGYEHSSTPMPRTLYIRH RKPSDGAHLA HEKTRERNGA KGKKIRCAKYYTSLTILRSE SALSSSCPSV AERMMAAAKI DMEDDSLYLGGEWQFNHFSK LTSSRPDAAF AEIQRTSLPE KSPLSYDLAPVARQLAPREK LPLSSRRPAA VGAGLQNMGN TCYVNASLQCLTYTPPLANY MLSREHSQTC HRHKGCNLCT MQAHITRALHNPGHVIQPSQ ALAAGFHRGK QEDAHEFLMF TVDAMKKACLPRHKQVDHHS KDTTLIHQIF GGYWRSQIKC LHCHGISDTFDPYLDIALDI QAAQSVQQAL EQLVKPEELN GENAYHCGVCLQRAPASKTL TLHTSAKVLI LVLKRFSDVT GNKIAKNVQYPECLDMQPYN SQQNTGPLVY VLYAVLVHAE WSCHNGHYFSYVKAQEGQWY KMDDAEVTAA SITSVLSQQA YVLFYIQKSEWERHSESVSR GREPRALGAE DTDRRATQGE LKRDHPCLQAPELDEHLVER ATQESTLDHW KFLQEQNKTK PEFNVRKVKGTLPPDVLVIH QSKYKCGMKN HHPEQQSSLL NLSSSTPTHQESMNTGTLAS LRGRARRSKG KNKHSKRALL VCQNucleotide sequence for hDUB8.1atgggggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcttttgctgaaatccagcggacttctctccctgagaagtcaccactctcatctgagacccgtgtcgacctctgtgatgatttggctcctgtggcaagacagctcgctcccagggagaagcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgagaacgcttccctgcagtgcctgacatacacactgccccttgccaactacatgctgtcccgggagcactctcaaacatgtcagcgtcccaagtgctgcatgctctgtactatgcaagctcacatcacatgggccctccacagtcctggccatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgtccatgaatttctcatgttcactgtggatgccatgaaaaaggcatgccttcccggccacaagcaggtagatcatcactgcaaggacaccaccctcatccaccaaatatttggaggctgctggagatctcaaatcaagtgtctccactgccacgggatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtcaagcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgcggtctttgtctccagagggcgccggcctccaacacgttaactttacacacttctgccaaggtcctcatccttgtcttgaagagattctccgatgtcgcaggcaacaaacttgccaagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacgacggacattacttctcctatgtcaaagctcaagaagtccagtggtataaaatggatgatgccgaggtcactgtctgtagcatcatttctgtcctgagtcaacaggcctatgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagccctcggcgctgaagacacagacaggcgagcaaagcaaggagagctcaagagagaccacccctgcctccaggcacccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattcctgcaagagcaaaacaaaacgaagcctgagttcaacgtcggaaaagtcgaaggtaccctgcctcccaacgcacttgtgattcatcaatcaaaatacaagtgtgggatgaaaaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgacccggacagatcaggagtccatgaacactggcacactcgcttctctgcaagggaggaccaggagagccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgahDUB8.1 deduced polypeptide sequenceMGDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSETRVDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTLPLANYMLSREHSQTCQRPKCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDVHEFLMFTVDAMKKACLPGHKQVDHHCKDTTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQLVKPEELNGENAYHCGLCLQRAPASNTLTLHTSAKVLILVLKRFSDVAGNKLAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEVQWYKMDDAEVTVCSIISVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRAKQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVGKVEGTLPPNALVIHQSKYKCGMKNHHPEQQSSLLNLSSTTRTDQESMNTGTLASLQGRTRRAKGKNKHSKRALLVCQNucleotide sequence for HDUB8.3AtggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcctttgctgaaatccagcGgacttctctccctgagaagtcacaactctcaactgagacccgcgtcgacttctgcgatgatttggcgcctgtggcaagacagcttgctcccagggagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttcccagcagtgtctgacatacAcaccgccccttgccaactacatgctgtcccgggagcactctcaaacatgtcatcgtcacaagtgctgcatgctctgtaccatggaagctcacatcacatGgcccctccacattcctggccatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagctgcccttgaatttctcatgttCactgtggatgccatgaaaaaggcatgccttcccgggcacaagcaggtagatcatcactccaaggacaccaccctcatccaccaaatatttggagggtacTggagatctcaaatcaagtgtctccactgccacggcatttcagacacttttggcccttacctggacatcgccctggatatccaggaagctcagagtgtcaAgcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgtggcaacaaaattgccaagaatgtgcaatatcctgagtgCcttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgccgggtggagttgtcacaacggaCattacttctcttatgtcaaagttcaagaaggccagtggtataaaatggatgatgccgaggtcactgcctctggcatcacctctgtcctgagtcaacaggCctatgtcctcttttacatccacaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagccctcggcgctgaagacacagaCaggcgagcaacgcaaggagagctcaagagagactacccctgcctccaggtacccgagttggacgagcacttggtggaaagagccactcaggaaagcaccTtagaccactggaaattcctccaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaacttgaaggtaccctgcctcccaacgtacttgtgattcAtcaatcaaaatacaagtgtgggatgaaaaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgaacccgacagatcaggagtccatGaacactggcacactcgcttctctgcaagggaggaccaggagagccaaagggaagaacaaacactgcaagagggctctgcttgtgtgccagtgaHDUB8.3 deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSQLSTETRVDFCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASQQCLTYTPPLANYMLSREHSQTCHRHKCCMLCTMEAHITWPLHIPGHVIQPSQALAAGFHRGKQEAALEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFGPYLDIALDIQEAQSVKQALEQLVKPEELNGENAYHCGNKIAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKVQEGQWYKMDDAEVTASGITSVLSQQAYVLFYIHKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDYPCLQVPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKLEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTNPTDQESMNTGTLASLQGRTRRAKGKNKHCKRALLVCQNucleotide sequence for HDUB8.5AtggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcttttgctgaaatccagcGgacttctctccctgagaagtcaccactctcatctgaggcccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccaggaagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgagaacgcttccctgcagtgcctgacatacAcaccgccccttgccaactacatgctgtcccgggagcactctcaaacatgtcagcgtcccaagtgctgcatgctctgtactatgcaagctcacatcacatGggccctccacagtcctggtcatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttCactgtggatgccatgaaaaaggcatgccttcccggccacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctgcTggagatctcaaatcaagtgtctccactgccacgggatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtcaAgcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgcggtctttgtcttcagagggcgccagtctccaagacgttAactttacacacttttgccaaggaacgcatacttgaaacgcagagaccatgggtggtcacacgccacaaactagccaagagtgtgcaatatgctgagagcCttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacgatggacAttacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccaaggtcactgcctgtagcatcacttctgtcctgagtcaacaggcCtatgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagccctcggcgctgaagacacagacAggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcacccgagttggacgagcgcttggtggaaagagccactcaggaaagcacctTagaccactggagattcccccaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccaacgtacttgtgattcaTcaatcgaaatacaagtgtgggatgaaaaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgacccggacagatcaggagtccgtgaacactggcaccctcgcttctctgcaagggaggaccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgaHDUB8.5 deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVARQLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRPKCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQLVKPEELNGENAYHCGLCLQRAPVSKTLTLHTFAKERILETQRPWVVTRHKLAKSVQYAESLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEGQWYKMDDAKVTACSITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDERLVERATQESTLDHWRFPQEQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKGKNKHSKRALLVCQNucleotide sequence for HDUB8.6AtggaagacgactcactctatttgggaggtgactggcagttcaatcacttttcaaaactcacatcttctcggctagatgcagcttttgctgaaatccagcGgacttctctctctgaaaagtcaccactctcatctgagacccgtttcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaagataggaaataccttctatgtgaacgtttccctgcagtgcctgacatacAcactgccgctttccaactacatgctgtcccgggaggactctcaaacgtgtcatcttcacaagtgctgcatgttctgtactatgcaagctcacatcacatGggccctctaccgtcctggccatgtcatccagccctcacaggtattggctgctggcttccatagaggtgagcaggaggatgcccatgaatttctcatgttTactgtggatgccatgaaaaaggcatgccttcccgggcacaagcagctagatcatcactccaaggacaccaccctcatccaccaaatatttggagcgtatTggagatctcaaatcaagtatctccactgccacggcatttcagacacctttgacccttacctggacatcgccctggatatccaggcagctcagagtgtcaAgcaagctttggaacagttggtgaagcccaaagaactcaatggagagaatgcctatcattgtggtctttgtctccagaaggcgcctgcctccaagacgttAactttacccacttctgccaaggtcctcattcttgtattgaagagattctccgatgtcacaggcaacaaacttgccaagaatgtgcaatatcctaagtgcCgtgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacAttacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcactgcctctggcatcacctctgtcctgagtcaacaggcCtatgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggtgctgaagacacagacAggccagcaacgcaaggagagctcaagagagaccacccttgcctccaggtacccgagttggacgagcacttggtggaaagagccactcaggaaagcacctTagaccactggaaattcccccaaaagcaaaacaaaacgaagcctgagttcaacgtcagaaaagttgaaggtaccctgcctcccaacgtacttgtgattcaTcaatcaaaatacaagtgtggtatgaaaaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgaaaccgacagatcaggagtccatgAacactggcacactcgcttctctgcaagggagcaccaggagatccaaagggaataacaaacacagcaagagatctctgcttgtgtgccagtgaHDUB8.6 deduced polypeptide sequenceMEDDSLYLGGDWQFNHFSKLTSSRLDAAFAEIQRTSLSEKSPLSSETRFDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQKIGNTFYVNVSLQCLTYTLPLSNYMLSREDSQTCHLHKCCMFCTMQAHITWALYRPGHVIQPSQVLAAGFHRGEQEDAHEFLMFTVDAMKKACLPGHKQLDHHSKDTTLIHQIFGAYWRSQIKYLHCHGISDTFDPYLDIALDIQAAQSVKQALEQLVKPKELNGENAYHCGLCLQKAPASKTLTLPTSAKVLIIKLKRFSDVTGNKLAKNVQYPKCRDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASGITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRPATQGELKRDHPCLQVPELDEHLVERATQESTLDHWKFPQKQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTKPTDQESMNTGTLASLQGSTRRSKGNNKHSKRSLLVCQNucleotide sequence for HDUB8.7AtggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcttttgctgaaatccagcGgacttctctccctgagaagtcaccactctcatctgaggcccgtgtcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccaggaagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgagaacgcttccctgcagtgcctgacatacAcaccgccccttgccaactacatgctgtcccgggagcactctcaaacatgtcagcgtcccaagtgctgcatgctctgtactatgcaagctcacatcacatGggccctccacagtcctggtcatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagatgcccatgaatttctcatgttCactgtggatgccatgaaaaaggcatgccttcccggccacaagcaggtagatcatcactctaaggacaccaccctcatccaccaaatatttggaggctgcTggagatctcaaatcaagtgtctccactgccacgggatttcagacacttttgacccttacctggacatcgccctggatatccaggcagctcagagtgtcaAgcaagctttggaacagttggtgaagcccgaagaactcaatggagagaatgcctatcattgcggtctttgtctccagagggcgccagcctccaagacgttAactttacacacttctgccaaggtcctcatccttgtcttgaagagattctccgatgtcacaggcaacaaacttgccaagaatgtgcaatatcctgagtgcCttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacgatggacAttacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccaaggtcactgcctgtagcatcacttctgtcctgagtcaacaggcCtatgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagccctcggcgctgaagacacagacAggcgagcaacgcaaggagagctcaagagagaccacccctgcctccaggcacccgagttggacgagcgcttggtggaaagagccactcaggaaagcacctTagaccactggagattcccccaagagcaaaacaaaacgaagcctgagttcaacgtcagaaaagtcgaaggtaccctgcctcccaacgtacttgtgattcaTcaatcgaaatacaagtgtgggatgaaaaaccatcatcctgaacagcaaagctccctgctaaacctctcttcgacgacccggacagatcaggagtccgtgaacactggcaccctcgcttctctgcaagggaggaccaggagatccaaagggaagaacaaacacagcaagagggctctgcttgtgtgccagtgaHDUB8.7 deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVARQLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRPKCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGCWRSQIKCLHCHGISDTVDPYLDIALDIQAAQSVKQALEQLVKPEELNGENAYHCGLCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKLAKNVQYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEGQWYKMDDAKVTACSITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDERLVERATQESTLDHWRFPQEQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKGKNKHSKRALLVCQNucleotide sequence for HDUB8.8AtggaagacgactcactctatttgggaggtgactggcagttcaatcacttttcaaaactcacatcttctcggctagatgcagcttttgctgaaatccagcGgacttctctctctgaaaagtcaccactctcatctgagacccgtttcgacctctgtgatgatttggctcctgtggcaagacagcttgctcccagggagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaagataggaaataccttctatgtgaacgtttccctgcagtgcctgacatacAcactgccgctttccaactacatgctgtcccgggaggactctcaaacgtgtcatcttcacaagtgctgcatgttctgtactatgcaagctcacatcacatGggccctctaccgtcctggccatgtcatccagccctcacaggtattggctgctggcttccatagaggtgagcaggaggatgcccatgaatttctcatgttTactgtggatgccatgaaaaaggcatgccttcccgggcacaagcagctagatcatcactccaaggacaccaccctcatccaccaaatatttggagcgtatTggagatctcaaatcaagtatctccactgccacggcatttcagacacctttgacccttacctggacatcgccctggatatccaggcagctcagagtgtcaAgcaagctttggaacagttggtgaagcccaaagaactcaatggagagaatgcctatcattgtggtctttgtctccagaaggcgcctgcctccaagacgttAactttacccacttctgccaaggtcctcattcttgtattgaagagattctccgatgtcacaggcaacaaacttgccaagaatgtgcaatatcctaagtgcCgtgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgctgggtggagttgtcacaacggacAttacttctcttatgtcaaagctcaagaaggccagtggtataaaatggatgatgccgaggtcactgcctctggcatcacctctgtcctgagtcaacaggcCtatgtcctcttttacatccagaagagtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaaccaagagcccttggtgctgaagacacagacAggccagcaacgcaaggagagctcaagagagaccacccttgcctccaggtacccgagttggacgagcacttggtggaaagagccactcaggaaagcacctTagaccactggaaattcccccaaaagcaaaacaaaacgaagcctgagttcaacgtcagaaaagttgaaggtaccctgcctcccaacgtacttgtgattcaTcaatcaaaatacaagtgtggtatgaaaaaccatcatcctgaacagcaaagctccgtgctaaacctctcttcgacgaaaccgacagatcaggagtccatgaacactggcacactcgcttctctgcaagggagcaccaggagatccaaagggaataacaaacacagcaagagatctctgcttgtgtgccagtgaHDUB8.8 deduced polypeptide sequenceMEDDSLYLGGDWQFNHFSKLTSSRLDAAFAEIQRTSLSEKSPLSSETRFDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQKIGNTFYVNVSLQCLTYTLPLSNYMLSREDSQTCHLHKCCMFCTMQAHITWALYRPGHVIQPSQVLAAGFHRGEQEDAHEFLNFTVDAMKKACLPGHKQLDHHSKDTThIHQIFGAYWRSQIKYLHCHGISDTFDPYLDIALDIQAAQSVKQALEQLVKPKELNGENAYHCGLCLQKAPASKTLTLPTSAKVLILVLKRFSDVTGNKLAKNVQYPKCRDMQPYMSQQNTGPLVYTLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASGITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRPATQGELKRDHPCLQVPELDEHLVERATQESTLDHWKFPQKQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSVLNLSSTKPTDQESMNTGTLASLQGSTRRSKGNNKHSKRSLLVCQNucleotide sequence for HDUB8.11AtggaggacgactcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggccagatgcagcctttgctgaaatccagcGgacttctctccctgagaagtcacaactctcaactgagacccgcgtcgacttctgcgatgatttggccgctgtggcaagacagctcgctcccagggagaaGcttcctctgagtagcaggagacctgctgcggtgggggctgggctccagaatatgggaaatacctgctacgtgaacgcttcccagcagtgtctgacatacAtaccgccccttgccaactacatgctgtcccgggagcactctcaaacatgtcatcgtcacaagtgctgcatgctctgtaccatggaagctcacatcacatGgcccctccacattcctggccatgtcatccagccctcacaggcattggctgctggcttccatagaggcaagcaggaagctgcccttgaatttctcatgttCactgtggatgccatgaaaaaggcatgccttcccgggcacaagcagatcctcatcctcgtatggaagagattctccgatgtcacaggcaacaaaattgccAagaatgtgcaatatcctgagtgccttgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccacgCcgggtggagttgtcacaacggacattacttctcttatgtcaaagttcaagaaggccagtggtataaaatggatgatgccgagaagagtgaatgggaaagAcacagtgagagtgtgtcaagaggcagggaaccaagagccctcggcgctgaagacacagacaggcgagcaacgcaaggagagctcaagagagactaccccTgcctccaggtacccgagttggacgagcacttggtggaaagagccactcaggaaagcaccttagaccactggaaattcctccaagagcaaaacaaaacgaAgcctgagttcaacgtcagaaaacttgaaggtaccctgcctcccaacgtacttgtgattcatcaatcaaaatacaagtgtgggatgaaaaaccatcatccTgaacagcaaagctccctgctaaacctctcttcgacgaacccgacagatcaggagtccatgaacactggcacactcgcttctctgcaagggaggaccaggagatccaaagggaagaacaaacactgcaagagggctctgcttgtgtgccagtgaHDUB8.11 deduced polypeptide sequenceMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSQLSTETRVDFCDDLAAVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASQQCLTYIPPLANYMLSREHSQTCHRHKCCMLCTNEAHITWPLHIPGHVIQPSQALAAGFHRGKQEAALEFLMFTVDAMKKACLPGHKQILILVWKRFSDVTGNKIAKNVQYPECLDMQPYNSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKVQEGQWYKMDDAEKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDYPCLQVPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKLEGTLPPNVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTNPTDQESMNTGTLASLQGRTRRSKGKNKHCKRALLVCQNucleotide sequence for HDUB4.4 sequenceatggaggagg actcactcta cttgggtggt gagtggcagttcaaccactt ttcaaaactc acatcttctc ggctcgatgcagcttttgct gaaatccagc ggacttctct ccctgagaagtcaccactct catgtgagac ccgtgtcgac ctctgtgatgatttggttcc tgaggcaaga cagcttgctc ccagggagaagcttcctctg agtagcagga gacctgctgc ggtgggggctgggctccaga atatgggaaa tacctgctac gtgaacgcttccttgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc cgggagcact ctcaaacgtg tcatcgtcacaagggctgca tgctctgtac tatgcaagct cacatcacacgggccctcca caatcctggc cacgtcatcc agccctcacaggcattggct gctggcttcc atagaggcaa gcaggaagatgcccatgaat ttctcatgtt cactgtggat gccatgaaaaaggcatgcct tcccgggcac aagcaggtag atcatccctctaaggacacc accctcatcc accaaatatt tggaggctactggagatctc aaatcaagtg tctccactgc cacggcatttcagacacttt tgacccttac ctggacatcg ccctggatatccaggcagct cagagtgtcc agcaagcttt ggaacagttggtgaagcccg aagaactcaa tggagagaat gcctatcattgtggtgtttg tctccagagg gcgccggcct ccaagacgttaactttacac acttctgcca aggtcctcat ccttgtattgaagagattct ccgatgtcac aggcaacaag attgccaagaatgtgcaata tcctgagtgc cttgacatgc agccatacatgtctcagcag aacacaggac ctcttgtcta tgtcctctatgctgtgctgg tccatgctgg gtggagttgt cacaacggacattacttctc ttatgtcaaa gctcaagaag gccagtggtataaaatggat gatgccgagg tcaccgcctc ttagcatcacatctgtcctg agtcaacagg cctacgtcct cttttacatccagaagagtg aatgggaaag acacagtgag agtgtgtcaagaggcaggga accaagagcc cttggcgcag aagacacagacaggcgagta acgcaaggag agctcaagag agaccacccctgactccagg cccccgagtt ggacgagcac ttggtggaaagagccactca ggaaagcacc ttagaccact ggaaattccttcaagagcaa aacaaaacga agcctgagtt caacgtcagaaaagtcgaag gtaccctgcc tcccgacgta cttgtgattcatcaatcaaa atacaagtgt gggatgaaga accatcatcctgaacagcaa agctccctgc taaacctctc ttcgacgaccccgacacatc agcagtccat gaacaatggc acactcgcttccctgcgagg gagggccagg agatccaaag ggaagaacaaacacagcaag agggctctgc ttgtgtgcca gtgahDUB4.4 Deduced polypeptide sequenceMEEDSLYLGG EWQFNHFSKL TSSRLDAAFA EIQRTSLPEKSPLSCETRVD LCDDLVPEAR QLAPREKLPL SSRRPAAVGAGLQNMGNTCY VNASLQCLTY TPPLANYMLS REHSQTCHRHKGCMLCTMQA HITRALHNPG HVIQPSQALA AGFHRGKQEDAHEFLMFTVD ANKKACLPGH KQVDHPSKDT TLIHQIFGGYWRSQIKCLHC HGISDTFDPY LDIALDIQAA QSVQQALEQLVKPEELNGEN AYHCGVCLQR APASKTLTLH TSAKVLILVLKRFSDVTGNK IAKNVQYPEC LDMQPYNSQQ NTGPLVYVLYAVLVHAGWSC HNGHYFSYVK AQEGQWYKMD DAEVTASNucleotide sequence for hDUB4.9atggaggacg actcactcta cttgggaggt gagtggcagttcaaccactt ttcaaaactc acatctcctc ggcccgatgcagcttttgct gaaatccagc ggacttctct ccctgagaagtcaccactct catgtgagac ccgtgtcgac ctctgtgattatttggctcc tgtggcaaga cagcttgctc ccagggagaagcttcctctg agtagcagga gacctgctgc ggtgggggctgggctccaga atatgggaaa tacctgctac gtgaacgcttccttgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc cgggagcact ctcaaacgtg tcatcgtcacaagggctgca tgctctgtac tatgcaagct cacatcacacgggccctcca caatcctggc cacgtcatcc agccctcacaggcattggct gctggcttcc atagaggcaa gcaggaagatgcccatgaat ttctcatgtt cactgtggat gccatgaaaaaggcatgcct tcccgggcac aagcaggtgg atcatcactctaaggacacc accctcatcc accaaatatt tggaggctactggagatctc aaatcaagtg tctccactgc cacggcatttcagacacttt tgacccttac ctggacatcg ccctggatatccaggcagct cagagtgtcc agcaagcttt ggaacagttggtgaagcccg aagaactcaa tggagagaat gcctatcattgtggtgtttg tctccagagg gcgccggcct ccaagacgttaactttacac acctctgcca aggtcctcat ccttgtattgaagagattct ccgatgtcac aggcaacaag attgccaagaatgtgcaata tcctgagtgc cttgacatgc agccatacatgtctcagcag aacacaggac ctcttgtcta tgtcctctatgctgtgctgg tccacgctgg gtggagttgt cacaacggacattacttctc ttatgtcaaa gctcaagaag gccagtggtataaaattgat gatgccgagg tcaccgcctc tagcatcacttctgtcctga ctcaacaggc ctacgtcctc ttttacatccagaagagtga atgggaaaga cacagtgaga gtgtgtcaagaggcagggaa ccaagagccc ttggctctga agactaahDUB4.9 deduced polypeptide sequenceMEDDSLYLGG EWQFNHFSKL TSPRPDAAFA EIQRTSLPEKSPLSCETRVD LCDYLAPVAR QLAPREKLPL SSRRPAAVGAGLQNMGNTCY VNASLQCLTY TPPLANYMLS REHSQTCHRHKGCMLCTMQA HITRALHNPG HVIQPSQALA AGFHRGKQEDAHEFLMFTVD AMKKACLPGH KQVDHHSKDT TLIHQIFGGYWRSQIKCLHC HGISDTFDPY LDIALDIQAA QSVQQALEQLVKPEELNGEN AYHCGVCLQR APASKTLTLH TSAKVLILVLKRFSDVTGNK IAKNVQYPEC LDMQPYNSQQ NTGPLVYVLYAVLVHAGWSC HNGHYFSYVK AQEGQWYKID DAEVTASSITSVLTQQAYVL FYIQKSEWER HSESVSRGRE PRALGSEDNucleotide sequence for hDUB8.2 sequenceatgcggccag agagcccgtc atttgaagac tcggaagagatagcgtcttt ctgcaacctg cggtcccagc cgaaaaaccttgtgatcctt gttccgggcg acatggagga cgactcactctacttgggag gtgagtggca gttcaaccac ttttcaaaactcacatcttc tcggccagat gcagcttttg ctgaaatccagcggacttct ctctctgaga agtcatcact ctcatctgagacccgcgtcg acctctgtga tgatttggct cctgtggcaagacagctcgc tcccagggag aagcttcctc tgagtagcaggagacctgct gcggtggggg ctgggctcca gaatatgggaaatacctgct acgtgaacgc ttccctgcag tgcctgacatacacaccgcc ccttgccaac tacatgctgt cccgggagcactctcaaacg tgtcatcgtc acaagtgctg catgctctgtactatgcaag ctcacatcac atggcccctc cacagtcctggccatgtcat ccagccctca caggtgttgg ctgctggcttccatagaggc gagcaggaag atgcccatga atttctcatgttcactgtgg atgccatgaa aaaggcattc cttcccgggcacaagcattt agataatcac tctaaggaca ccaccctcatccaccaaata tttggagggt actggagatc tcacatcaactgtttccact gccacgggat ttcagacacc tttgacccttacctggacat cgccctggat atccaggcag ctcagagtgtcaagcaagct ttgtaacagt tggtgaagcc cgaagaactcaatggataaa atgcctatca ttgtggtctt tgtctccagaaggcgcctgc ctccaggacg ttaactttac acacttctgccaaggtcctc atccttgtat tgaagagatt ctctgaggtcacaggcaaca aacttgccaa gaatgtgcaa tatcctgagtgccttgacat gcagccatac atgtctcagc agaacacaggacctcttgtc tatgtcctct atgctgtgct ggtccacgctgggtggagtt gtcacaacgg acattactta tcttatgtcaaactcaagaa ggccattggt ataaaatgga tgatgccgaggtcactgcct ccggtatcac ttctgtcctg agtcaacaggcctatgtcct cttttacatc cagaagaatg aatttggaagacccagttac agtgtgtcca taggcaggga accaagagctctttgcgtga aggcaagtga attgtgtgtg aaataaaatgtcatgaataa atcttgcagt ggagtattta tttgtctcactttgtaatca gtgaatgagc tttaaccaat atcaatgcctagtgcctacc ccccagagat aagaacttcc actctcttatgtgtaaccat ggcctctgga ttgcttatga ctctgaagataattctcctt tcccccaacg tttcagaatc acttcaggtggtggtaacag ataacacatc agtccctttc tctctcttttctcttcactc aggaaaactc tcactgagac aaaggaaaatcctatggttt actggggagg aagaattccc tcaggagtgaaattggtggc tccttcctcc ctgtcaagtc tcttcctcaggattgcccct ttgtctcttc aggacthDUB8.2 dedeuced polypeptide sequenceMRPESPSFED SEEIASFCNL RSQPKNLVIL VPGDMEDDSLYLGGEWQFNH FSKLTSSRPD AAFAEIQRTS LSEKSSLSSETRVDLCDDLA PVARQLAPRE KLPLSSRRPA AVGAGLQNMGNTCYVNASLQ CLTYTPPLAN YMLSREHSQT CHRHKCCMLCTMQAHITWPL HSPGHVIQPS QVLAAGFHRG EQEDAHEFLMFTVDANKKAF LPGHKHLDNH SKDTTLIHQI FGGYWRSHINCFHCHGISDT FDPYLDTALD IQAAQSVKQA LNucleotide sequence for hDUB8.9atggaggaag actcactcta cttgggaggt gagtggcagttcaaccactt ttcaaaactc acatcttctc agccagatgcagcttttcct gaaatccagc ggacttctct ccctgagaagtcaccactct catcggagac ccgtgtcgac ctctgtgacgatttggctcc tgtgacaaga cagcttgctc ccagggagaagcttcctccg agtagcagga gacctgctgc ggtgggagctggtctccaga atatgggaaa tacctgccac ttgaatgcttccctgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc tgggagctct ctcaaatgtg tcatcgtcccaagtgctgca tgctctgtat tatggaagct cacagcacacgggcacctcc accgtcctgg ccatgtcatc cagccctcacaggcattggc tgctgacttc catagagaca agcaggaagatgcccatgaa tttctcatat tcactgtgga tgccattagaaaggcatgcc ttcccgggca caagcagcta gatcatcactgcaaggacac catcctcatc caccaaatat ttggagggtactagagatct caaatcaagt gtctctactt ccacggcatttcagacacct tcgaccctta cctggatatc gccctggatatccaggcagc tcagagtgtc aagcaagctt tggaacagttggtgaagccc gaagaactca atggagagaa tgcctatcattgtggtcttt gtctccagaa ggcgcctgcc gccaagacgttaactttacc cacttctgcc aaggtcctca tccttgtcttgaagagattc tccgatgtca caggcaacaa acttgccaagaatctgcaat atcctgagtg cgttgacatg cagccatacatgtctcagca gaacacagga cctcttttct atgtcctctatgctgttctc gtcatcaccg ggtggagttg tcacaacggacattacttct cttgtgtcaa actcaagaag gccagtggtataaaatggat gatgccgagg tcactgcctc tggtatcacttctccttaga gtcaacaggc ctatgtcctc ttttacatccagaagaatga atttggaaga cccagttaca gggtgtccgcaggcagagaa ccaagagctc tttgtgctga agacaattgaattgtggtga aataatatgt catgaataaa tcttgcagcagatttatttg tctcactttg taatcagtga atgagctttaacgaatatca atgcctagtg cctacccccc agagataagaacttccagtt tctcatgtgt aatcatggca tctggattgctcatgattct gaagataatt ctcctgtccc ccaaagtttcagaatcactt caggtggtag aaacagataa cacatcagtccctttctctc tcttttctct tcahDUB8.9 Deduced polypeptide sequenceMEDDSLYLGG EWQFNHFSKL TSSRPDAAFA EIQRTSLSEKSSLSSETRVD LCDDLAPVAR QLAPREKLPL SSRRPAAVGAGLQNMGNTCY VNASLQCLTY TPPLANYNLS REHSQTCHRHKCCMLCTMQA HITWPLHSPG HVIQPSQVLA AGFHRGEQEDAHEFLNFTVD AMKKAFLPGH KHLDNHSKDT TLIHQIFGGYWRSHINCFHC HGISDTFDPY LDIALDIQAA QSVKQALEQLVKPEELNGNucleotide sequence for hDUB8.10atggaggacg actcactcta cttgggaggt gagtggcagttcaaccactt ttcaaaactc acatcttctc ggccagatgcagcttttgct gaaatccagc ggacttctct ctctgagaagtcatcactct catctgagac ccgcgtcgac ctctgtgatgatttggctcc tgtggcaaga cagctcgctc ccagggagaagcttcctctg agtagcagga gacctgctgc ggtgggggctgggctccaga atatgggaaa tacctgctac gtgaacgcttccctgcagtg cctgacatac acaccgcccc ttgccaactacatgctgtcc cgggagcact ctcaaacgtg tcatcgtcacaagtgctgca tgctctgtac tatgcaagct cacatcacatggcccctcca cagtcctggc catgtcatcc agccttcacaggtgttggct gctggcttcc atagaggcga gcaggaagatgcccatgaat ttctcatgtt cactgtggat gccatgaaaaaagcattcct tcccgggcac aagcatttag ataatcactctaaggacacc accctcatcc accaaatatt tggagggtactggagatctc acatcaactg tttccactgc catgggatttcagacacctt tgacccttac ctggacatcg ccctggatatccaggcagct cagagtgtca agcaagcttt ggaacagttggtgaagcccg aagaactcaa tggataaaat gcctatcattgtggtctttg tctccagaag gcgcctacct ccaggacgttaactttacac acttctgcca aggtcctcat ccttgtattgaagagattct ctgatgtcac aggcaacaaa cttgccaagaatgtgcaata tcctgagtgc cttgacatgc agccatacatgtctcagcag aacacaggac ctcttgtcta tgtcctctatgctgtgctgg tccacgctgg gtggagttgt cacaacggacattacttatc ttatgtcaaa ctcaagaagg ccattggtataaaatggatg atgccgaggt cactgcctcc ggtatcacttctgtcctgag tcaacaggcc tatgtcctct tttacatccagaagaatgaa tttggaagac ccagttacag tgtgtccataggcagggaac cgagagctct ttgcgtgaag gcaagtgaattgtgtgtgaa ataaaatgtc atgaataaat cttgcagtggagtatttatt tgtctcactt tgtaatcagt gaatgagctttaaccaatat caatgcctag tgcctacccc ccagagataagaacttccac tctcttatgt gtaaccatgg cctctggattgcttatgact ctgaagataa ttctcctttc ccccaacgtttcagaatcac ttcaggtggt ggtaacagat aacacatcagtccctttctc tctcttttct cttcactcag gaaaactctcactgagacaa aggaaaatcc tatggtttac tggggaggaagaattccctc aggagtgaaa ttggtggctc cttcctccctgtcaagtctc ttcctcagga ttgccccttt gtctcttcaggactctgctc atcaggcccg agatgccccc tggttgtgcatacctggcct gtgaagaaat ahDUB8.10 Deduced polypeptide sequenceMEEDSLYLGG EWQFNHFSKL TSSQPDAAFP EIQRTSLPEKSPLSSETRVD LCDDLAPVTR QLAPREKLPP SSRRPAAVGAGLQNMGNTCH LNASLQCLTY TPPLANYMLS WELSQMCHRPKCCMLCIMEA HSTRAPPPSW PCHPALTGILG C










TABLE 24








Deduced Amino acid alignment of hDUB4.10 (Seq ID NO.22) and



hDUB4.11 (Seq ID NO.24).

















hDUB4.10
MCIRTGSPCDVCENYSVMSMTGRQLIDWAPLKIGYEHSSTPMPREHVHFRQHYNFGTKCA  60



hDUB4.11
MCIRTGSPCDVCENYSVMSMTGRQLIDWAPLKIGYEHSSTPMPRT-LYIRHRK-------  52



********************************************  :::*::





hDUB4.10
NCNSTIQCVTGNGGNIADPERSMRESRICTAYFGLFPLKQGPVLKMVISLGQRINRLNVE 120


hDUB4.11
---------PSDGAHLAHEK-------------------------------------TRE  66



         ..:*.::*. :                                     . *





hDUB4.10
RLSLEGKKIRCAKYYTSLTILRSESALSTSCPSVAERMMAAAKRIASFCNLRSQQKNLVI 180


hDUB4.11
RNGAKGKKIRCAKYYTSLTILRSESALSSSCPSVAERMMAAAK----------------- 109



* . :***********************:**************





hDUB4.10
LVPVDMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDL 240


hDUB4.11
---IDMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLS--------YDL 158



:********************************************* **         **





hDUB4.10
APVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQ 300


hDUB4.11
APVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQ 218



**********************************************.*************





hDUB4.10
TCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKA 360


hDUB4.11
TCHRHKGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKA 278



************************************************************





hDUB4.10
CLPGHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQ 420


hDUB4.11
CLPRHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQ 338



*** ********************************************************





hDUB4.10
ALEQLVKPEELNGENAYHSGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNV 480


hDUB4.11
ALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNV 398



******************.*****************************************





hDUB4.10
QYPECLDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVT 540


hDUB4.11
QYPECLDMQPYMSQQNTGPLVYVLYAVLVHAEWSCHNGHYFSYVKAQEGQWYKMDDAEVT 458



******************************* ****************************





hDUB4.10
AASITSALSQQAYVLFYIQKSEWERHSESVSRGREPRALGTEDTDRRATQGELKRDHPCL 600


hDUB4.11
AASITSVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCL 518



******.*********************************:*******************





hDUB4.10
QAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGM 660


hDUB4.11
QAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVKGTLPPDVLVIHQSKYKCGM 578



****************************************:*******************





hDUB4.10
KNHHPEQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQ      715


hDUB4.11
KNHHPEQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVC-      632



******************************************************

















TABLE 25








Nucleotide sequence alignment of hDUB4.5 (Seq ID NO.13), hDUB4.8



(Seq ID NO.19) and hDUB8.2 (Seq ID NO.43).

















hDUB4.5
ATGCG-CCAGAGACCTCGTCATTTGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAA   59



hDUB4.8
ATGCG-CCAGAGAGCTCGTCATTTGAAGACTCTCTCGGAAGGGATAGCGTCTTGCTGCAA   59


hDUB8.2
ATGCGGCCAGAGAGCCCGTCATTTGAAGA----CTCGGAAGAGATAGCGTCTTTCTGCAA   56



***** ********* *************    ******** *********** ******





hDUB4.5
CCTGCGGTCCCAGCAGAAAAACCTTGTGATCCTTGTTCCAGTCGACATGGAGGAAGACTC  119


hDUB4.8
ACTGCGGTCCCAGCAGAAAAACCTTGTGATCCTTGTTCCAGTCGACATGGAGGACGACTC  119


hDUB8.2
CCTGCGGTCCCAGCCGAAAAACCTTGTGATCCTTGTTCCGGGCGACATGGAGGACGACTC  116



 ************* ************************ * ************ *****





hDUB4.5
ACTCTACTTGGGAGGTGAGTGGCAGTTCAACCACTTTTCAAAACTCACATCTTCTCGGCC  179


hDUB4.8
ACTCTACTTGGGAGGTGAGTGGCAGTTCAACCACTTTTCAAAACTCACATCTTCTCGGCC  179


hDUB8.2
ACTCTACTTGGGAGGTGAGTGGCAGTTCAACCACTTTTCAAAACTCACATCTTCTCGGCC  176



************************************************************





hDUB4.5
CGATGCAGCTTTTGCTGAAATCCAGCGGACTTCTCTCCCTGAGAAGTCACCACTCTCATG  239


hDUB4.8
CGATGCAGCTTTTGCTGAAATCCAGCGGACTTCTCTCCCTGAGAAGTCACCACTCTCATG  239


hDUB8.2
AGATGCAGCTTTTGCTGAAATCCAGCGGACTTCTCTCTCTGAGAAGTCATCACTCTCATC  236



 ************************************ *********** *********





hDUB4.5
TGAGACCCGTGTCGACCTCTGTGATGATTTGGCTCCTGTGGCAAGACAGCTTGCTCCCAG  299


hDUB4.8
TGAGACCCGTGTCGACCTCTGTGATGATTTGGCTCCTGTGGCAAGACAGCTTGCTCCCAG  299


hDUB8.2
TGAGACCCGCGTCGACCTCTGTGATGATTTGGCTCCTGTGGCAAGACAGCTCGCTCCCAG  296



********* ***************************************** ********





hDUB4.5
GGAGAAGCTTCCTCTGAGTAACAGGAGACCTGCTGCGGTGGGGGCTGGGCTCCAGAATAT  359


hDUB4.8
GGAGAAGCTTCCTCTGAGTAGCAGGAGACCTGCTGCGGTGGGGGCTGGGCTCCAGAATAT  359


hDUB8.2
GGAGAAGCTTCCTCTGAGTAGCAGGAGACCTGCTGCGGTGGGGGCTGGGCTCCAGAATAT  356



******************** ***************************************





hDUB4.5
GGGAAATACCTGCTACGTGAACGCTTCCTTGCAGTGCCTGACATACACACCGCCCCTTGC  419


hDUB4.8
GGGAAATACCTGCTACGTGAACGCTTCCTTGCAGTGCCTGACATACACACCGCCCCTTGC  419


hDUB8.2
GGGAAATACCTGCTACGTGAACGCTTCCCTGCAGTGCCTGACATACACACCGCCCCTTGC  416



**************************** *******************************





hDUB4.5
CAACTACATGCTGTCCCGGGAGCACTCTCAAACGTGTCATCGTCACAAGGGCTGCATGCT  479


hDUB4.8
CAACTACATGCTGTCCCGGGAGCACTCTCAAACGTGTCATCGTCACAAGGGCTGCATGCT  479


hDUB8.2
CAACTACATGCTGTCCCGGGAGCACTCTCAAACGTGTCATCGTCACAAGTGCTGCATGCT  476



************************************************* **********





hDUB4.5
CTGTACGATGCAAGCTCACATCACACGGGCCCTCCACAATCCTGGCCACGTCATCCAGCC  539


hDUB4.8
CTGTACGATGCAAGCTCACATCACACGGGCCCTCCACAATCCTGGCCACGTCATCCAGCC  539


hDUB8.2
CTGTACTATGCAAGCTCACATCACATGGCCCCTCCACAGTCCTGGCCATGTCATCCAGCC  536



****** ****************** ** ********* ********* ***********





hDUB4.5
CTCACAGGCATTGGCTGCTGGCTTCCATAGAGGCAAGCAGGAAGATGCCCATGAATTTCT  599


hDUB4.8
CTCACAGGCATTGGCTGCTGGCTTCCATAGAGGCAAGCAGGAAGATGCCCATGAATTTCT  599


hDUB8.2
CTCACAGGTGTTGGCTGCTGGCTTCCATAGAGGCGAGCAGGAAGATGCCCATGAATTTCT  596



******** ************************ *************************





hDUB4.5
CATGTTCACTGTGGATGCCATGAAAAAGGCATGCCTTCCCGGGCACAAGCAGGTGGATCA  659


hDUB4.8
CATGTTCACTGTGGATGCCATGAAAAAGGCATGCCTTCCCGGGCACAAGCAGGTAGATCA  659


hDUB8.2
CATGTTCACTGTGGATGCCATGAAAAAGGCATTCCTTCCCGGGCACAAGCATTTAGATAA  656



******************************** ******************  * *** *





hDUB4.5
TCACTCTAAGGACACCACCCTCATCCACCAAATATTTGGAGGCTACTGGAGATCTCAAAT  719


hDUB4.8
TCACTCTAAGGACACCACCCTCATCCACCAAATATTTGGAGGCTACTGGAGATCTCAAAT  719


hDUB8.2
TCACTCTAAGGACACCACCCTCATCCACCAAATATTTGGAGGGTACTGGAGATCTCACAT  716



****************************************** ************** **





hDUB4.5
CAAGTGTCTCCACTGCCACGGCATTTCAGACACTTTTGACCCTTACCTGGACATCGCCCT  779


hDUB4.8
CAAGTGTCTCCACTGCCACGGCATTTCAGACACTTTTGACCCTTACCTGGACATCGCCCT  779


hDUB8.2
CAACTGTTTCCACTGCCACGGGATTTCAGACACCTTTGACCCTTACCTGGACATCGCCCT  776



*** *** ************* *********** **************************





hDUB4.5
GGATATCCAGGCAGCTCAGAGTGTCCAGCAAGCTTTGGAACAGTTGGTGAAGCCCGAAGA  839


hDUB4.8
GGATATCCAGGCAGCTCAGAGTGTCCAGCAAGCTTTGGAACAGTTGGTGAAGCCCGAAGA  839


hDUB8.2
GGATATCCAGGCAGCTCAGAGTGTCAAGCAAGCTTTGTAACAGTTGGTGAAGCCCGAAGA  836



************************* *********** **********************





hDUB4.5
ACTCAATGGAGAGAATGCCTATCATTGTGGTGTTTGTCTCCAGAGGGCGCCGGCCTCCAA  899


hDUB4.8
ACTCAATGGAGAGAATGCCTATCATTGTGGTGTTTGTCTCCAGAGGGCGCCGGCCTCCAA  899


hDUB8.2
ACTCAATGGATAAAATGCCTATCATTGTGGTCTTTGTCTCCAGAAGGCGCCTGCCTCCAA  896



********** * ****************** ************ ****** *******





hDUB4.5
GACGTTAACTTTACACACCTCTGCCAAGGTCCTCATCCTTGTATTGAAGAGATTCTCCGA  959


hDUB4.8
GACGTTAACTTTACACACCTCTGCCAAGGTCCTCATCCTTGTATTGAAGAGATTCTCCGA  959


hDUB8.2
GACGTTAACTTTACACACTTCTGCCAAGGTCCTCATCCTTGTATTGAAGAGATTCTCTGA  959



****************** ************************************** **





hDUB4.5
TGTCACAGGCAACAAGATTGACAAGAATGTGCAATATCCTGAGTGCCTTGACATGAAGCT 1019


hDUB4.8
TGTGACAGGCAACAAGATTGCCAAGAATGTGCAATATCCTGAGTGCCTTGACATGCAGCC 1019


hDUB8.2
GGTCACAGGCAACAAACTTGCCAAGAATGTGCAATATCCTGAGTGCCTTGACATGCAGCC 1016



 ** ***********  *** ********************************** ***





hDUB4.5
ATACATGTCTCAGACGAACTCAGGACCTCTCGTCTATGTCCTCTATGCTGTGCTGGTCCA 1079


hDUB4.8
ATACATGTCTCAGCAGAACACAGGACCTCTTGTCTATGTCCTCTATGCTGTGCTGGTCCA 1079


hDUB8.2
ATACATGTCTCAGCAGAACACAGGACCTCTTGTCTATGTCCTCTATGCTGTGCTGGTCCA 1076



*************  **** ********** *****************************





hDUB4.5
CGCTGGGTGGAGTTGTCACAACGGACATTACTTCTCTTATGTCAAAGCTCAAGAAGGCCA 1139


hDUB4.8
CGCTGGGTGGAGTTGTCACAACGGACATTACTTCTCTTATGTCAAAGCTCAAGAAGGCCA 1139


hDUB8.2
CGCTGGGTGGAGTTGTCACAACGGACATTACTTATCTTATGTCAAA-CTCAAGAAGGCCA 1135



********************************* ************ *************





hDUB4.5
GTGGTATAAAATGGATGATGCCGAGGTCACCGCCTCTAGCATCACTTCTGTCCTGAGTCA 1199


hDUB4.8
ATGGTATAAAATGGATGATGCCGAGGTCACCGCCGCTAGCATCACTTCTGTCCTGAGTCA 1199


hDUB8.2
TTGGTATAAAATGGATGATGCCGAGGTCACTGCCTCCGGTATCACTTCTGTCCTGAGTCA 1195



 ***************************** *** * * ********************





hDUB4.5
ACAGGCCTACGTCCTCTTTTACATCCAGAAGAGTGAATGGGAAAGACACAGTGAGAGTGT 1259


hDUB4.8
ACAGGCCTACGTCCTCTTTTACATCCAGAAGAGTGAATGGGAAAGACACAGTGAGAGTGT 1259


hDUB8.2
ACAGGCCTATGTCCTCTTTTACATCCAGAAGAATGAATTTGGAAGACCCAGTTACAGTGT 1259



********* ********************** *****  * ***** **** * *****





hDUB4.5
GTCAAGAGGCAGGGAAACCAAGAGCCCTTGGCGCAGAAGACACAGACAGGCGAGCAACGCA 1319


hDUB4.8
GTCAAGAGGCAGGGAAACCAAGAGCCCTTGGCGCAGAAGACACAGACAGGCGAGCAACGCA 1319


hDUB8.2
GTCCATAGGCAGGGAAACCAAGAGCTCTTTGCGTGAAGGCAAGTGAATTGTGTGTGAAATA 1315



*** * ******************* *** ***   * *  *  **   * * *  *   *





hDUB4.5
AGGAGAGCTCAAGAGAGACCACCCCTGCCTCCAGGCCCCCGAGTTGGACGAGCACTTGGT 1379


hDUB4.8
AGGAGAGCTCAAGAGAGACCACCCCTGCCTCCAGGCCCCCGAGTTGGACGAGCACTTGGT 1379


hDUB8.2
AAATG---TCATGA---ATAAATCTTGCAGTGGAGTATTT-ATTTGTCTCACTTTGTAAT 1368



*   *   *** **   *  *  * ***      *      * ***    *     *  *





hDUB4.5
GGAAAGAGCCACTCAGGAAAGCACCTTAGACCACTGGAAATTCCTTCAAGAGCAAAACAA 1439


hDUB4.8
GGAAAGAGCCACTCAGGAAAGCACCTTAGACCACTGGAAATTCCTTCAAGAGCAAAACAA 1439


hDUB8.2
CAGTGAATGAGCTTTAACCAATATCAATGCCTAGTGCCTACCCCCCAGAGATAAGAACTT 1428



      *    **      *  * *   * * * **   *  **    ***  * ***





hDUB4.5
AACGAAGCCTGAGTTCAACGTCAGAAAAGTCGAAGGTACCCTGCCTCCCGACGTACTTGT 1499


hDUB4.8
AACGAAGCCTGAGTTCAACGTCAGAAAAGTCGAAGGTACCCTGCCTCCCGACGTACTTGT 1499


hDUB8.2
CCACTCTCTTATGTGTAAC--CATGGCCTCTGGATTGCTTATGACTCTGAAGATAATTCT 1486



       * *  **  ***  **        * *       ** ***   *  ** ** *





hDUB4.5
GATTCATCAATCAAAATACAAGTGTGGGATGAAGAACCATCATCCTG-AACAGCAAAGCT 1558


hDUB4.8
GATTCATCAATCAAAATACAAGTGTGGGATGAAGAACCATCATCCTG-AACAGCAAAGCT 1558


hDUB8.2
CCTT--TCCCCCAACGTTTCAGAATCACTTCAGGTGGTGGTAACAGATAACACATCAGTC 1544



  **  **   ***  *   **  *    * * *       * *    ****    **





hDUB4.5
CCCTGCTAAACCTCTCTTCGACGACCCCGACACATCAGGAGTCCATGAACACTGGCACAC 1618


hDUB4.8
CCCTGCTAAACCTCTCTTCGACGACCCCGACACATCAGGAGTCCATGAACACTGGCACAC 1618


hDUB8.2
CCTTTCTCTCTCTTTTCTCTTCACTCAGGAAAACTCTCACTGAGACAAAGGAAAATCCTA 1604



** * **    ** *  **  *   *  ** *  **        *  **        *





hDUB4.5
TCGCTTCCCTGCGAGGGAGGGC-----CAGGAGATCCAAAGGGAAGAACAAACACAGCAA 1673


hDUB4.8
TCGCTTCCCTGCGAGGGAGGGC-----CAGGAGATCCAAAGGGAAGAACAAACACAGCAA 1673


hDUB8.2
TGGTTTACTGGGGAGGAAGAATTCCCTCAGGAGTGAAATTGGTGGCTCCTTCCTCCCTGT 1664



* * ** *  * **** **        ******    *  **      *   * *





hDUB4.5
GAGGGCTCTGCTTGTGTG----CCAGTGGTCTCAGTGGAAGTACCGACCCACA        1722


hDUB4.8
GAGGGCTCTGCTTGTGTG----CCAGTGA------------------------        1698


hDUB8.2
CAAGTCTCTTCCTCAGGATTGCCCCTTTGTCTCTTCAGGACT-----------        1706



 * * **** * *  *      **  *







In frame termination codons in hDUB8.2 are underlined















TABLE 26








Deduced amino acid alignment of hDUB4.5 (Seq ID NO.14), hDUB4.8



(Seq ID NO.20) and hDUB8.2 (Seq ID NO.44).

















hDUB4.5

MRQRARHLKTLSEGIASFCNLRSQQKNLVILVPVDMEEDSLYLGGEWQFNHFSKLTSSRP  60




hDUB4.8

MRQRARHLKTLSEGIASCCKLRSQQKNLVILVPVDMEDDSLYLGGEWQFNHFSKLTSSRP  60



hDUB8.2

MRPESPSFED-SEEIASFCNLRSQPKNLVILVPGDMEDDSLYLGGEWQFNHFSKLTSSRP  59




** .:  ::  ** *** *:**** ******** ***:**********************





hDUB4.5
DAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSNRRPAAVGAGLQNM 120


hDUB4.8
DAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVARQLAPREKLPLSNRRPAAVGAGLQNM 120


hDUB8.2
DAAFAEIQRTSLSEKSSLSSETRVDLCDDLAPVARQLAPREKLPLSSRRPAAVGAGLQNM 119



************.***.**.**************************.*************





hDUB4.5
GNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQP 180


hDUB4.8
GNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQAHITRALHNPGHVIQP 180


hDUB8.2
GNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKCCMLCTMQAHITWPLHSPGHVIQP 179



************************************ *********** .**.*******





hDUB4.5
SQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQI 240


hDUB4.8
SQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGHKQVDHHSKDTTLIHQIFGGYWRSQI 240


hDUB8.2
SQVLAAGFHRGEQEDAHEFLMFTVDAMKKAFLPGHKHLDNHSKDTTLIHQIFGGYWRSHI 239



**.********:****************** *****::*:******************:*





hDUB4.5
KCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASK 300


hDUB4.8
KCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASK 300


hDUB8.2
NCFHCHGISDTFDPYLDIALDIQAAQSVKQAL---------------------------- 271



:*:*************************:***





hDUB4.5
TLTLHTSAKVLILVLKRFSDVTGNKIDKNVQYPECLDMKLYMSQTNSGPLVYVLYAVLVH 360


hDUB4.8
TLTLHTSAKVLILVLKRFSDVTGNKIDKNVQYPECLDMKLYMSQTNSGPLVYVLYAVLVH 360


hDUB8.2
------------------------------------------------------------





hDUB4.5
AGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASSITSVLSQQAYVLFYIQKSEWERHSESV 420


hDUB4.8
AGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASSITSVLSQQAYVLFYIQKSEWERHSESV 420


hDUB8.2
------------------------------------------------------------





hDUB4.5
SRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNK 480


hDUB4.8
SRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDEHLVERATQESTLDHWKFLQEQNK 480


hDUB8.2
------------------------------------------------------------





hDUB4.5
TKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTTPTHQESMNTGTL 540


hDUB4.8
TKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHPEQQSSLLNLSSTTPTHQESMNTGTL 540


hDUB8.2
------------------------------------------------------------





hDUB4.5
ASLRGRARRSKGKNKHSKRALLVCQWSQWKYRPT                           574


hDUB4.8
ASLRGRARRSKGKNKHSKRALLVCQ---------                           565


hDUB8.2
----------------------------------







N-terminal potential mitochondrial targeting sequences are underlined.















TABLE 27








Upstream of initiation codon nucleotide sequence (putative



promoter region) alignment of hDUB4.5 (Seq ID NO.13), hDUB4.8


(Seq ID NO.19) and hDUB8.2 (Seq ID NO.43). Numbering is


initiated from initiation ATG.

















hDUB4.5
CACACGAACACAATCACACACACACACTCACACGGTTTCCTACGTAAAGATTTCTTCCCT −276



hDUB4.8
CACACGAACACAATCACACACACACACTCACACGGTTTCCTACGTAAAGATTTCTTCCCT −276


hDUB8.2
GGGAGAAAAACACACACACACACACACACACACGGTTTCATAGGTAAAGATTTCTTCCCT −276



   *  ** ***  ************* *********** ** *****************





hDUB4.5
GCCATTGCTTTACCTAAAATAAGGCAACTGTGTGGCCACTGTCCCAACCCGGTTACACTC −216


hDUB4.8
GCCATTGCTTTACCTAAAATAAGGCAACTGTGTGGCCACTGTCCCAACCCGGTTACACTC −216


hDUB8.2
GACATTGTTTTACCTAAAATAAGGCAACTGTGTGGCCACTGTCCCAACCCGGTTACACTC −216



* ***** ****************************************************





hDUB4.5
CTATTATATGTGCCTATCATCCTGAGGAGTAATTTGATTCAGGTGTTCTGGAAGTCATGC −156


hDUB4.8
CTATTATATGTGCCTATCATCCTGAGGAGTAATTTGATTCAGGTGTTCTGGAAGTCATGC −156


hDUB8.2
ATATTACATGTGTCTATCAGCCTGAGGAGTAGTTTGATTCAGGTGTTCTAGAAGTCATGA −156



 ***** ***** ****** ************ ***************** ********





hDUB4.5
TGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTCCTTCC  −96


hDUB4.8
TGTGGGCTGTGTCTGTTGAATACCCAGCGATGCAAGGGGACACACCCTGTGACTCCTTCC  −96


hDUB8.2
TGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTCATTCC  −96



********************* ********************************* ****





hDUB4.5
TGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGGTGTTC  −36


hDUB4.8
TGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGGTGTTC  −36


hDUB8.2
TTAATTGAGTGCTGATATTTGATTGGTTTATCGCGCACCTGATGGGTGGGTGGGGTGTTC  −36



* ************************ ***************** ***************





hDUB4.5
GCGGTTGGTGGGGTTGACTTACAGAAGGGCTGATG                             0


hDUB4.8
GCGGTTGGTGGGGGTGACTTACAGAAGGGCTGATG                             0


hDUB8.2
GCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATG                             0



************* *** *** * ***********

















TABLE 28








CLUSTAL W (1.81) multiple sequence alignment of core amino



acids of hDUBs (8.5: Seq ID NO.30; 8.7: Seq ID NO.34; 8.1:


Seq ID NO.26; 4.2: Seq ID NO.10; 4.3: Seq ID NO.12; 4.5:


Seq ID NO.14; 4.1: Seq ID NO.6; 8.3: Seq ID NO.28; 8.11:


Seq ID NO.38; 8.8: Seq ID NO.36; 8.6: Seq ID NO.32)

















8.5
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVAR  60



8.7
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVAR  60


8.1
MGDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSETRVDLCDDLAPVAR  60


4.2
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR  60


4.3
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR  60


4.5
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR  60


4.1
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR  60


8.3
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSQLSTETRVDFCDDLAPVAR  60


8.11
MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSQLSTETRVDFCDDLAPVAR  60


8.8
MEDDSLYLGGDWQFNHFSKLTSSRLDAAFAEIQRTSLSEKSPLSSETRFDLCDDLAPVAR  60


8.6
MEDDSLYLGGDWQFNHFSKLTSSRLDAAFAEIQRTSLSEKSPLSSETRFDLCDDLAPVAR  60



* :*******:************* ************.*** ** *:*.*:*****.***





8.5
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRP 120


8.7
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRP 120


8.1
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRP 120


4.2
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRH 120


4.3
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRH 120


4.5
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRH 120


4.1
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRH 120


8.3
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASQQCLTYTPPLANYMLSREHSQTCHRH 120


8.11
QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYVNASQQCLTYIPPLANYMLSREHSQTCHRH 120


8.8
QLAPRKKLPLSSRRPAAVGAGLQKIGNTFYVNVSLQCLTYTLPLSNYMLSREDSQTCHLH 120


8.6
QLAPRKKLPLSSRRPAAVGAGLQKIGNTFYVNVSLQCLTYTLPLSNYMLSREDSQTCHLH 120



*****:* ***.***********::*** * *.* *****  **:**** **.****:





8.5
KCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180


8.7
KCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180


8.1
KCCMLCTMQAHITWALHSPGHVIQPSQALAAGFHRGKQEDVHEFLMFTVDAMKKACLPGH 180


4.2
KGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180


4.3
KGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180


4.5
KGCMLCTMQAHITRALHNPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180


4.1
KGCMLCTMQAHITRALHIPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMRKACLPGH 180


8.3
KCCMLCTMEAHITWPLHIPGHVIQPSQALAAGFHRGKQEAALEFLMFTVDAMKKACLPGH 180


8.11
KCCMLCTMEAHITWPLHIPGHVIQPSQALAAGFHRGKQEAALEFLMFTVDAMKKACLPGH 180


8.8
KCCMFCTMQAHITWALYRPGHVIQPSQVLAAGFHRGEQEDAHEFLMFTVDAMKKACLPGH 180


8.6
KCCMFCTMQAHITWALYRPGHVIQPSQVLAAGFHRGEQEDAHEFLMFTVDAMKKACLPGH 180



* **:***:**** .*: *********.********:** . **********:*******





8.5
KQVDHHSKDTTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240


8.7
KQVDHHSKDTTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240


8.1
KQVDHHCKDTTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240


4.2
KQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQL 240


4.3
KQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQL 240


4.5
KQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQL 240


4.1
KQVDRHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQALEQL 240


8.3
KQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFGPYLDIALDIQEAQSVKQALEQL 240


8.11
K----------------------QILILVWKRFSDVTG---------------------- 196


8.8
KQLDHHSKDTTLIHQIFGAYWRSQIKYLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240


8.6
KQLDHHSKDTTLIHQIFGAYWRSQIKYLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240



*                      **  *  : :**. .





8.5
VKPEELNGENAYHCGLCLQRAPVSKTLTLHTFAKERILETQRPWVVTRHKLAKSVQYAES 300


8.7
VKPEELNGENAYHCGLCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKLAKNVQYPEC 300


8.1
VKPEELNGENAYHCGLCLQRAPASNTLTLHTSAKVLILVLKRFSDVAGNKLAKNVQYPEC 300


4.2
VKPEELNGENAYHSGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPEC 300


4.3
VKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIAKNVQYPEC 300


4.5
VKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKVLILVLKRFSDVTGNKIDKNVQYPEC 300


4.1
VKPEELNGENAYHCGVCLQRAPASKTLTLHNSAKVLILVLKRFPDVTGNKIAKNVQYPEC 300


8.3
VKPEELNGENAYHC---------------------------------GNKIAKNVQYPEC 267


8.11
------------------------------------------------NKIAKNVQYPEC 208


8.8
VKPKELNGENAYHCGLCLQKAPASKTLTLPTSAKVLILVLKRFSDVTGNKLAKNVQYPKC 300


8.6
VKPKELNGENAYHCGLCLQKAPASKTLTLPTSAKVLILVLKRFSDVTGNKLAKNVQYPKC 300



                                                :*: *.***.:.





8.5
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEGQWYKMDDAKVTACSIT 360


8.7
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEGQWYKMDDAKVTACSIT 360


8.1
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSYVKAQEVQWYKMDDAEVTVCSII 360


4.2
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASIT 360


4.3
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTAASIT 360


4.5
LDMKLYMSQTNSGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASSIT 360


4.1
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYSSYVKAQEGQWYKMDDAEVTASSIT 360


8.3
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKVQEGQWYKMDDAEVTASGIT 327


8.11
LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKVQEGQWYKMDDAE------- 261


8.8
RDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASGIT 360


8.6
RDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHNGHYFSYVKAQEGQWYKMDDAEVTASGIT 360



 **: **** *:*******************:*** ****.** ********:





8.5
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPEL 420


8.7
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPEL 420


8.1
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRAKQGELKRDHPCLQAPEL 420


4.2
SALSQQAYVLFYIQKSEWERHSESVSRGREPRALGTEDTDRRATQGELKRDHPCLQAPEL 420


4.3
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPEL 420


4.5
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPEL 420


4.1
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGVEDTDRRATQGELKRDHPCLQAPEL 420


8.3
SVLSQQAYVLFYIHKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDYPCLQVPEL 387


8.11
--------------KSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDYPCLQVPEL 307


8.8
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRPATQGELKRDHPCLQVPEL 420


8.6
SVLSQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRPATQGELKRDHPCLQVPEL 420



              *********************.***** *.*******:****.***





8.5
DERLVERATQESTLDHWRFPQEQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHP 480


8.7
DERLVERATQESTLDHWRFPQEQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHP 480


8.1
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVGKVEGTLPPNALVIHQSKYKCGMKNHHP 480


4.2
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHP 480


4.3
DEHLVERATQESTLDRWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHP 480


4.5
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQSKYKCGMKNHHP 480


4.1
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVRRVEGTVPPDVLVIHQSKYKCRMKNHHP 480


8.3
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKLEGTLPPNVLVIHQSKYKCGMKNHHP 447


8.11
DEHLVERATQESTLDHWKFLQEQNKTKPEFNVRKLEGTLPPNVLVIHQSKYKCGMKNHHP 367


8.8
DEHLVERATQESTLDHWKFPQKQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHP 480


8.6
DEHLVERATQESTLDHWKFPQKQNKTKPEFNVRKVEGTLPPNVLVIHQSKYKCGMKNHHP 480



**:************:*:* *:********** ::***:**:.********** ******





8.5
EQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKGKNKHSKRALLVCQ           530


8.7
EQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKGKNKHSKRALLVCQ           530


8.1
EQQSSLLNLSSTTRTDQESMNTGTLASLQGRTRRAKGKNKHSKRALLVCQ           530


4.2
EQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQ           530


4.3
EQQSSLLNLSSSTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQ           530


4.5
EQQSSLLNLSSTTPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQ           530


4.1
EQQSSLLNLSSTTPTDQESMNTGTLASLRGRTRRSKGKNKHSKRALLVCQ           530


8.3
EQQSSLLNLSSTNPTDQESMNTGTLASLQGRTRRAKGKNKHCKRALLVCQ           497


8.11
EQQSSLLNLSSTNPTDQESMNTGTLASLQGRTRRSKGKNKHCKRALLVCQ           417


8.8
EQQSSVLNLSSTKPTDQESMNTGTLASLQGSTRRSKGNNKHSKRSLLVCQ           530


8.6
EQQSSLLNLSSTKPTDQESMNTGTLASLQGSTRRSKGNNKHSKRSLLVCQ           530



*****:*****:. *.***:********:* :**:**:***.**:*****

















TABLE 29








CLUSTAL W (1.81) multiple sequence alignment of putative promoter



sequences of hDUBs (upstream of ATG initiation codon)


















8.9
TGACGTGTGTGAAAACTACAGTGTGATGAGCATGACTTGCAGACAGGTTATCGATTGGGC
60



8.10
-GACGTGTGTGAAAACTACAGTGTGACGAGCATGACTCGCAGACAGGTTATCGATTGGGC
59


8.3
----------------------------------------------GATATCAATACGGC
14


8.11
----------------------------------------------GATATCAATACGGC
14


4.2_a
-----------------------------------------------TTATCGATTGGGC
13


4.5
--------------------------TGAGCATGACTGGCAGACAGCTTATCGATTGGGC
34


4.3
------------------------GATGAGCATGACTGGCAGACAGCTTATCGATTGGGC
36


4.2_b
----------------------GTGATGAGCATGACTGGCAGACAGCTTATCGATTGGGC
38


4.4
----------------------GTGATGAGCATGACTGGCAGACAGCTTATCGATTGGGC
38


4.1_b
-------------------AGTGCAATGAGCATGACACGCAGGCAGGATATCAATTCGGC
41


8.1
-----------------------CAATGAGCATGACACGAAGACAGAATATCAATTCGGC
37


8.7
-----------------------CAATGAGCATGACACGAAGACAGAATATCAATTCGGC
37


8.6
---------------------TGTGATGAGCATGACTCGCAGACAGGTTATCGATTGGGC
39


8.8
---------------------TGTGATGAGCATGACTCGCAGACAGGTTATCGATTGGGC
39


8.5
-----------------TCTCTGTCAGAACCATGGTACTCTGTTGTGGTGTGAAAGTAGC
43


8.2
---------TCACATCTTCTCGGCCAGATGCAGCCTTTGCTGAAATCCAGCGGACTTCTC
51


4.1_a
----------------------------AGTATAGCAGAGCAGAGAGCTG-GAAGGGACC
31



                                                     *     *





8.9
T-CCCCTCAAAAT-TAGTTATGAGCATTAAAGGACACCGATGCCC---AGGTCCCGGCTG
115


8.10
T-CCCCTCAAAAT-CAGTTATGAGCATTAAAGCACACCGATCCCC---AGGTCCCGGCTC
114


8.3
T-CACCTCAAAAG-CAGTTATGAGCATTAAAGGACACCCATGCCT---AGGTCCCGCTTA
69


8.11
T-CACCTCAAAAG-CAGTTATGAGCATTAAAGGACACCCATGCCT---AGGTCCCGGTTA
69


4.2_a
T-CCCCTCAAAAT-CGGTTATGAGCATTCAAGCACACCGATGCCC---AGGTCCCGGCTG
68


4.5
T-CCCCTCAAAAT-CGGTTATGAGCATTCAAGCACACCGATGCCC---AGGTCCCGGCTG
89


4.3
T-CCCCTCAAAAT-CGGTTATGAGCATTCAAGCACACCGATGCCC---AGGTCCCGGCTG
91


4.2_b
T-CCCCTCAAAAT-CGGTTATGAGCATTCAAGCACACCGATGCCC---AGGTCCCGGCTG
93


4.4
T-CCCCTCAAAAT-CGGTTATGAGTATTCAAGCACACCGATGCCC---AGGTCCCGGCTG
93


4.1_b
T-CCCCTCAAAAG-CTGTTATGAGCATTAAAGGACACCAATGCCT---AGTTCCCGGTTA
96


8.1
T-CACCTCAAAT--CAGTTGTGAGCATTAAAGAAAACCAATTCCT---AGGTCCCGCTTA
91


8.7
T-CACCTCAAAAG-CAGTTATGAGCATTAAAGGACAACAATTCCT---AGGTCCCGCTTA
92


8.6
T-CCCCTCAAAAT-CAGTTAGGAACATGAAAGCACACCGATGCCC---AGGTCCTGGCTG
94


8.8
T-CCCCTCAAAAT-CAGTTAGGAACATGAAAGCACACCGATGCCC---AGGTCCTGGCTG
94


8.5
CACAGATCATCTG-TAGAT-TAAGGGGTGTGGCTTTGTTCCAACA---AAGCTTTATTTA
98


8.2
TCCCTGAGAAGTCACAACTCTCAACTGAGACCCGCGTCGACTTCTGCGATGATTTGGCGC
111


4.1_a
TGCATCCCTAAT----GATATAAGAAAGTATCTGTACTAGCCCTGA--ATGGTATAACTA
85



  *               *   *                         *





8.9
CAGGAATAAGAC-CCTCCGACGTCTTGTGTGAAGCCACGGC--ATCTGGATTGCTCATGC
172


8.10
CAGGAATAAGAC-CCTCCAGCGTCTTGTGTGAAGCCACGGC--ATGTGGATTGCTCATGC
171


8.3
AAGAGATAAGAC-TCTCCCACACCCTGTGTGAAGCCACGGC--ATGTGGATTGCTCATGC
126


8.11
AAGAGATAAGAC-TCTCCCACACCCTGTGTGAAGCCACGGC--ATGTGGATTGCTCATGC
126


4.2_a
CAGGAATAAGAC-CCTCCAGGGTCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC
125


4.5
CAGGAATAAGAC-CCTCCAGGGTCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC
146


4.3
CAGGAATAAGAC-CCTCCAGGGTCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC
148


4.2_b
CAGGAATAAGAC-CCTCCAGGGTCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC
150


4.4
CAGGAATAAGAC-CCTCCAGGGTCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC
150


4.1_b
AAACGATAAGAC-TCTCGCACACCCTGTGGGAAGCCACGGC--ATCTGGATTGCTCATGC
153


8.1
AAGAGATAAGAC-CATCCAACAACCTGTGTGAAGCCACCGC--ATCTGGCTTGCTCATGA
148


8.7
AAGAGATAAGAC-CATCCAACACCCTGTGTGAAGCCACGGC--ATCTGGATTGCTCATGT
149


8.6
CAGGAATAAGAT-CCTCCGACGTCTTGTGTGAAGCCACGAC--ATCTGCATTGCTCATGC
151


8.8
CAGGAATAAGAT-CCTCCGACGTCTTGTGTGAAGCCACGAC--ATCTGCATTGCTCATGC
151


8.5
CAAACACAGGCTGTGGGCTGGATTTGGCCTGCAGCTGTAGT--TTGTG----ATCCTTGA
152


8.2
CTGTGGCAAGAC--AGCTTGCTCCCAGGGAGAAGCTTCCTCTGAGTAGCAGGAGACCTGC
169


4.1_a
CAG-GTTAAATT---TACGTGAAAAAGAAATCAACTTCTGCCTTGTTTAAGCAAACTTA-
140



       *                  *     * *                    * *





8.9
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTCCTGCCTGTGGAGCACCTCT
228


8.10
TTCTG-G-CGATCATTCTCCTGAAAACG--GTGGCTCCTTTCTCCCTGTGGAGCACCTTT
227


8.3
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCACTGTGGAGCATCTTT
182


8.11
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCACTGTGGAGCATCTTT
182


4.2_a
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCCCTGTGGACCATCTTT
181


4.5
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCCCTGTGGAGCATCTTT
202


4.3
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCCCTGTGGAGCATCTTT
204


4.2_b
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCCCTGTGGAGCATCTTT
206


4.4
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTCCTTTCTCCCTGTGGAGCATCTTT
206


4.1_b
TTCTG-G-GGATCATTTTCCTGAAAATC--GTGGCTGCTTTCTCCCTGTGTAGCATCTTT
209


8.1
TTCTG-G-GGATCATTCTCCAGAAAATG--GTGGCTCCTTTCTCCCTGTGGAGCATCTTT
204


8.7
TTCTG-G-GGAACATTCTTCTGAAAATG--GCGGCTCCTTTCTCCCTGTGGAGCATCTTT
205


8.6
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTTCTTTCTCCCTGTGGAGCATCTTT
207


8.8
TTCTG-G-GGATCATTCTCCTGAAAATG--GTGGCTTCTTTCTCCCTGTGGAGCATCTTT
207


8.5
TTCAG-ACAGTTTAGCAAGGCTGAAAAG--AACACCCACACCCCCTTGTTACCCACAGAT
209


8.2
TGCGGTGGGGGCTGGGCTCCAGAATATG--GGAAATACCTGCTACGTG---AACGCTTCC
224


4.1_a
TTCAG---GCATTAATTTTATAAATATGTAGAGAATACATACTCCTTAT-GAGCAGA---
193



* * *                  * *               *    *      *





8.9
CTA-AGCA-GTGC-CCTTTCTTCACCCAGGACACTTTACATCAGGCACAGAAAGCCTTCT
285


8.10
CTA-AGCA-GTGC-CCTTTCTTCACCCAGGACACTTTACATCAGGCACAGAAAGCCTTCT
284


8.3
GTA-AGCA-GTGT-CCTTTCTTCCCCCAGGACACTTTACTTCAGGCACAGGAAGCCTTCT
239


8.11
CTA-AGCA-GTGT-CCTTTCTTCCCCCAGGACACTTTACTTCAGGCACAGGAAGCCTTCT
239


4.2_a
CTA-AGCA-GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT
239


4.5
CTA-AGCA-GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT
260


4.3
CTA-AGCA-GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT
262


4.2_b
CTA-AGCA-GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT
264


4.4
CTA-AGCA-GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT
264


4.1_b
CTA-AGCA-GTGCTCCTTTCTTCCCACAGGAAACTTTACATCAGGCACAGGAAGCTTTCT
267


8.1
CTA-AGCA-GTGC-CCTTTCTTCCCCCAGGACACTTTACATGAGGTGCAGGAAGCCTTCT
261


8.7
CTA-AGCA-GTGCTCCTTTCTTCCCCCAGGACACTTTACATCAGGCATAGGAAGCCTTCT
263


8.6
CTA-AGCA-GTGCTCCTTTCTTCCCCCAGGACACTTTACATCAGGCGCACGAAGCCTTCT
265


8.8
CTA-AGCA-GTGCTCCTTTCTTCCCCCAGGACACTTTACATCAGGCGCACGAAGCCTTCT
265


8.5
GGGTGGGA-CTGTGTTGGCCAGAGACCGAGAGACGGGTGCTCACAGGGGAACGTACAGCA
268


8.2
CAGCAGTGTCTGACATACACACCGCCCCTTGCCAACTACATGCTGTCCCGGGAGCACTCT
284


4.1_a
-AACAATGTTTGCGCCATATGGTCCATGATGGGTGTTCAATAATGTGTGATGATGATAAT
252



          **                            *





8.9
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGATAAGAAACGGGGCCAAACATCACAG
345


8.10
GATGGAGCACACCTGGCCCATGAAAAAACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
343


8.3
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAG
298


8.11
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAG
298


4.2_a
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
298


4.5
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
319


4.3
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
321


4.2_b
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
323


4.4
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
323


4.1_b
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAC
326


8.1
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAAAAGGGCCAAAGGTCACAG
320


8.7
GATGAAGTACACCTGGCCCATGAAAAGACAAAGGA-AAGAAACAGGGCCAAAGGTCACAG
322


8.6
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
324


8.8
GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG
324


8.5
TGTAGAGGCCGGAAGGTGCTCCAGGGCACAAGTGT-GGGAAAGTGGGACATACGGGGAAG
327


8.2
CAAACATGTCATC--GTCACAAGTGCTGCATGCTCTGTACCATGGAAGCTCACATCACAT
342


4.1_a
AATGAAGACAATAGTGACAAATAAAAGAAAATAAA-AAGCAGTGAAACAAAGTGGTTTAA
311



     *         *             *                            *





8.9
TCCTCTCATTCCACCGTCCTCCTTAAAATCATCCTAATTTCATGGGCTCT-GCGGCCACG
404


8.10
TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAGGCCACG
402


8.3
TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
357


8.11
TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAGGCCACG
357


4.2_a
TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
357


4.5
TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
378


4.3
TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
380


4.2_b
TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
382


4.4
TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT-GAAGCCAGG
382


4.1_b
TCCTCTCATTCCATCATACTCCTTAAAATCATCCTAATTTCATGGGTCCT-GAAGCCAGG
385


8.1
TCCTCTCATTACATCATCATCCTTAAAATCATCCTAATTTCATGAGCCCT-GAAGACAGG
379


8.7
CCCACTCATTTCATCACCATCCTTAAAATCATCCTAATTTCATGGGCCAT-GAAGCCAGG
381


8.6
TCCTCTCATTCCATCATCCTCCTTAAAATCATCCGAATTTCATGAGCCCTTGAAGCCAGG
384


8.8
TCCTCTCATTCCATCATCCTCCTTAAAATCATCCGAATTTCATGAGCCCTTGAAGCCAGG
384


8.5
TTTCCAGAAAGCATGATGTCAAGTTGGAG-GTGGAGCGCTGCTGGGCTTGTGAAGGGTCT
386


8.2
GGCCCC---TCCA-CATTCCTGGCCATGTCATCCAGCCCTCACAGGCATT---------G
389


4.1_a
TAGCTATACATAGTTATT-TTGTTGAAAGATTCTGCTGCTAATATTATTCAATATTTTTG
370



                               *       *





8.9
GCTGTTTCTTTACACCTCGAGACCTTGGCGCCAGGCCTCAATTCTGCCCCGGTGCTTACT
464


8.10
GCTGTTTCTTTACACCTCGAGACCTTGGCGCCGGGCCTCAATTCTGCTCCAGTGCTTACT
462


8.3
GCTGTTTCTTTAAAACTAGAGGCCTTGGCGCCGTGCCTCAATTCTGCCCTGTTCCTTACT
417


8.11
GCTGTTTCTTTAAAACTAGAGGCCTTGGCGCCGGGCCTCAATTTTGCCCTGTTCCTTACT
417


4.2_a
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC
417


4.5
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC
438


4.3
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC
440


4.2_b
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC
442


4.4
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC
442


4.1_b
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTGCTTACT
445


8.1
GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT
439


8.7
GCTGTTTCTTTACACCCAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT
441


8.6
GCTGTTTCTTTACACCCAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT
444


8.8
GCTGTTTCTTTACACCCAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT
444


8.5
CGAGTCCAAGTGAGGGCGGGTTGTGAAGGGTCTCCTCTCAAAGCTGACCGACTTCGGGAC
446


8.2
GCTGCTGGCTTCCATAGAGGCAAGCAGGAAGCTGCCCTTGAATTTCTCATGTTCACTGTG
449


4.1_a
TATGCTGGC--GCAAATAAGGAAATTTACATCGTCTAATAAAAATTATTTATCAATTTAT
428



   *                           *        *





8.9
GTCTAAGACATTTTGGGAAAATCCCTAGAGC-CTGGATCTTCAATCCTGGTAAGCCAGAG
523


8.10
GTCTAAGACATTTTGGGAGAATCCCTAGAGC-CTAGATCTTCAATCCTGGTAAGCCAGAG
521


8.3
GTCTAAGAAAGGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGGTAAGCCAGAG
476


8.11
GTCTAACAAAGGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGGTAAGCCAGAG
476


4.2_a
GTCTAAGACATGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGCTAAGCCAGAC
476


4.5
GTCTAAGACATGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGCTAAGCCAGAC
497


4.3
GTCTAAGACATGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGCTAAGCCAGAC
499


4.2_b
GTCTAAGACATGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGCTAAGCCAGAC
501


4.4
GTCTAAGACATGTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGCTAAGCCAGAC
501


4.1_b
CTCTAAGACATGTTGGGAAAGTCCCAAGAGC-CAGGATCTTCATTCCTGGTAAGGCAGAC
504


8.1
GTCTAAGACATTTTGGGAAAATCACTAGAGC-CAGGACCTTCATTCCTGGTAAGCCAGAG
498


8.7
GTCTAAGACATTTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGGTAAGCCAGAG
500


8.6
GTCTAAGACATTTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGGTAAGCCAGAG
503


8.8
GTCTAAGACATTTTGGGAAAATCCCTAGAGC-CAGGATCTTCATTCCTGGTAAGCCAGAG
503


8.5
TTCCCAGGGATTGTTGTTGAGTCCACGGCTCACGTCGTCCACACTC-TGAGGTCCCATGG
505


8.2
GATGCCATGAAAAAGGCATGCCTTCCCGGGCACAAGCAGGTAGATC--ATCACTCCAAGG
507


4.1_a
AAAACAGTAAAAATTTCATAG--AATGGGGCTAAGAATCTGCACTGCAAACTAACTCTTT
486



         *                 *  *             *





8.9
AGCCTGGAGACACACCCAAATTATGTCCCTCTTAGTTCAGGGAACATGTCCATTTTCGTC
583


8.10
AGCCTGAAGACACACCCAAATTATGTCCCTCTTAGTTCAGGGAACATGTCCATTTTCGTC
581


8.3
AGCCTGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGTC
536


8.11
AGCCTGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGTC
536


4.2_a
AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC
536


4.5
AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC
557


4.3
AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC
559


4.2_b
AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC
561


4.4
AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC
561


4.1_b
AGAATGAAGACACACCAAAATTCTGTCCCTCTTAATTCAGGGAACGTGTCCACTTTCGTC
564


8.1
AGCCGAAAGACACACCCAAATTCTGTCCCTCTTAGTTCAGGGAACAGGTCTACTTTCGTC
558


8.7
AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC
560


8.6
AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC
563


8.8
AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC
563


8.5
ATTCGCCACCCACATTCATCTACTCTCCTCTCTCTCTTCCTTACCTCCTTTGATCCCCTC
565


8.2
ACACCACCCTCATCCACCAAATATTTGGAGGGTACTGGAGATCTCAAATCAAGTGTCTCC
567


4.1_a
CAGTTGATTTTATGCACAGAAATTATTGAGAATCCCCTTATCTAGATCCAACAGATCTGG
546



           *            * *     *                       *





8.9
AGCATTAAAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAACTG
643


8.10
AGCACTAAAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATGCAATGCGTAACTG
641


8.3
AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAAATG
596


8.11
AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAAATG
596


4.2_a
AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG
596


4.5
AGCATTACAATCTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG
617


4.3
AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG
619


4.2_b
AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG
621


4.4
AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG
621


4.1_b
AGAATTAAAATTTTTGCACCAAATGTGCTAACTGGAATTCCACCATACAATGCATAACTG
624


8.1
AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAACTG
618


8.7
AGCATTACAATTTTTGCACCAAATGTACTAACTGCAATTCCACCATACAATGCATAACTG
620


8.6
AGCATTACAATTTTTGCACCAAATGTACTAACTGCAATTCCACCATACAATGCATAACTG
623


8.8
AGCATTACAATTTTTGCACCAAATGTACTAACTGCAATTCCACCATACAATGCATAACTG
623


8.5
CCCA-TATGCTACCCCCCGCTACCAAACCTCTGCCAAGCATACCACCCTATCGGCAGCTA
624


8.2
ACTGCCACGGCATTTCAGACACTTTTGGCCCTTACCTGGACATCGCCCTGGATATCCAGG
627


4.1_a
GCTTACATAGGTGCTATCAAGACTTAAGGAAGAAAATTTTCCTGACTCTATCCATACCTC
606



      *                                        *





8.9
GAAATAGAGGCAACATCTCATATCCTGAACAATTCATGTG------AGAATCTAGGAGAC
697


8.10
TAAATGGAGGCAACATCTCAGATCCTGAACAATCGATGCG------AGAATCCAGGAGAC
695


8.3
GAAATGGAGGGAACATCTCAGATCCTGAACAATCGATGCG------AGAATCCAGGAGAT
650


8.11
GAAATGGAGGGAACATCTCAGATCCTGAACAATCGATGCG------AGAATCCAGGAGAT
650


4.2_a
GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG------AGAATCCAGGATAT
650


4.5
GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG------AGAATCCAGGATAT
671


4.3
GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG------AGAATCCAGGATAT
673


4.2_b
GAAATGGAGGCAACATCGCCGATCCTGAACGATCGATGCG------AGAATCCAGGATAT
675


4.4
GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG------AGAATCCAGGATAT
675


4.1_b
GAAATGGAGGGAAAATCCCAGATCATGAACAATCAAAGCG------AGAATCCAGGAGAC
678


8.1
GAAATGGAGGGAACATCTCAGATCATGAACAATCGATGAG------AGAATCCAGGAGAT
672


8.7
GAAATGGAGGGAACATCTCAGAGCATGAACAACTGATGCG------AGAATCCAGGAGAT
674


8.6
GAAATGGAGGGAACATCTCAGACCATGAACAATCGATGAG------AGAATCCAGGAGAC
677


8.8
GAAATGGAGGGAACATCTCAGACCATGAACAATCGATGAG------AGAATCCAGGAGAC
677


8.5
CTCTTCACTCCCA-ACTACATCGGCCGCATCNNNNNNNNN------NNNNNNNNNNNNNN
677


8.2
AAGCTCAGAGTGTCAAGCAAGCTTTGGAACAGTTGGTGAAGCCCGAAGAACTCAATGGAG
687


4.1_a
CAATTAGTAATAGATCTAGAGATTTAAAACTGAAATCCAGACCTC-CTGCTTCCATGTGC
665



    *                       *





8.9
ACACCGCTTATTTTTGCCTTTTCCCACTGAAACAATGGCTAGTATTAACAATGTTATGCT
757


8.10
ACACGGCTTATTTTTGCCTTTTCCCACTGAAACAAGGGCCAGTATTAACAATCTTATGCT
755


8.3
ACACGGCTGATTTTTGCGTTTTCCCTGTGAAACAAGGGCCAGTATTAAAAATGGTATGCT
710


8.11
ACACGGCTGATTTTTGCGTTTTCCCTGTCAAACAAGGGCCAGTATTAAAAATGGTATGCT
710


4.2_a
GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCCAGTATTAAAAATGGCACGCT
710


4.5
GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCCAGTATTAAAAATGGCACGCT
731


4.3
GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCCAGTATTAAAAATGGCACGCT
733


4.2_b
GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCCAGTATTAAAAATGGTACGCT
735


4.4
GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCCAGTATTAAAAATGGCACGCT
735


4.1_b
ACACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGACCAGTATTAAAAATGGTATGCT
738


8.1
ACACGGCTTATTTTTGCCTTTTCCCTGTGAAACAAGGGCAAGTATTAAAAACTTTATGCT
732


8.7
ACACGGTTTATTTTTGCCATTTCCCAGTGAAACAAAAGCCAGTATTAAAAAGGTTATGCT
734


8.6
ACACGGCTTATTTTTGCCTTTTCCCTGTGAAACAAGGGCCAGCATTAAAAAGGTTATGCT
737


8.8
ACACGGCTTATTTTTGCCTTTTCCCTGTGAAACAAGGGCCAGCATTAAAAAGGTTATGCT
737


8.5
NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN
737


8.2
AGAATGCCTATCATTGTGGTCTTTGTCTCCAGAGGGCGCCGGCCTCCAAGACGTAAACTT
747


4.1_a
AGTGTCCTTTCACTGTCCTGTTTTGCTTCACTTGATGAAGAGGATTTGAGAATAAATGAC
725





8.9
ATCCTTGGTTTCACTCCCCACTTTTAAATCTCTCGGATGTTTACTTCT-TGAGACAGG--
814


8.10
ATCCTGGGTTTCACTCTCTGCTTTTAAATCTCTCCAATGTTTTCTTCT-TGAGACAGG--
812


8.3
ATCCTCTGTTTCACTCCCTGCTTTTAAGTCTCC--GATGTTT-CTTCT-TAAGACAGG--
764


8.11
ATCCTCTGTTTCACTCCCTGCTTTTAAGTCTCC--GATGTTT-CTTCT-TAAGACAGG--
764


4.2_a
ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTCCC-TGAGACAGG--
766


4.5
ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTCCC-TGAGACAGG--
787


4.3
ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTCCC-TGAGACAGG--
789


4.2_b
ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTCCC-TGAGACAGG--
791


4.4
ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCTGATGT-TTCTCCC-TGAGACAGG--
791


4.1_b
ATACTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTTCT-TGAGACAGG--
794


8.1
GTCTTCTATTTCACTGCCTGCTTTTAAACGTCTCCGATGTATTCTTCT-TGAGAAAGG--
789


8.7
ACCCTCTGTTTCACTCACTGCTTTTAAACGTCTCCGATGTTTTCTTCT-TCAGACAGG--
791


8.6
ATCTTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGTTTTCTTCT-TCAGACAGG--
794


8.8
ATCTTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGTTTTCTTCT-TCAGACAGG--
794


8.5
NNNNNNNNNNNNNNNNNCTGCTTTTAAACGTCTCCGATGTTTTCTTCT-TCAGACAGG--
794


8.2
TACACACTTCTGCCAAGATCCTCATCCTCGTATTGAAGAGATTCTCCGATGTCACAGGCA
807


4.1_a
CACATGATTCAACTCCTCCTCAGCTCTGAGCAAT-ATAGCCCTGTCCTGGCAAACAAGAA
784



                    *   *                   * *      * * *





8.9
GCGTC-ACTGCCGTCACCCACGCTTTTCTACGGT------GTAATTTTTGTTGTTCGCTT
867


8.10
GCCTC-ACTCCCGTCACCAGGGCTTTTCTACGGT------GCAATTTTCGGTGTTTGCTT
865


8.3
GCCTC-ACTTCCTTCCCCCTGACTTTTCTACGGT------ATAATTTTCGTTGTTTGCTT
817


8.11
GCCTC-ACTTCCTTCCCCCTGACTTTTCTACGGT------ATAATTTTCGTTGTTTGCTT
817


4.2_a
GCCTC-ACTTCCGTCAGCCGGGCTTTTCCACGGT------ATAATTTTCCTTGTTTGCTT
819


4.5
GCCTC-ACTTCCGTCAGCCGGGCTTTTCCACGGT------ATAATTTTCCTTGTTTGCTT
840


4.3
GCCTC-ACTTCCGTCAGCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
842


4.2_b
GCCTC-ACTTCCGTCAGCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
844


4.4
GCCTC-ACTTCCGTCAGCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
844


4.1_b
GCCTC-ACTGCCGTCCGCCGGGCTAT-CTAGAGT------ATAATTTTCAGTGTTTGCTT
846


8.1
GCCTC-ACTACTGTCACCTGGGCTTTTCTAAGGT------ATAATTTTCCTTGTTTGCTT
842


8.7
GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
844


8.6
GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
847


8.8
GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
847


8.5
GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT------ATAATTTTCCTTGTTTGCTT
847


8.2
ACAAA-ATTGCCAAGAATGTGCAATATCCTGAGTGCCTTGACATGCAGCCATACATGTCT
866


4.1_a
GCTCCTGCAGTAGTAGAGGAGGCAAATATACGTT----CACTAATCTAACATACAAG---
837



 *                               *        *        *       *





8.9
TTGTCAAATTTAGAAATTTTCATTTCA--TCTCTATCAAATGTTGCTCCATT----ATCA
921


8.10
TTGTCAAATTTAGAACTTTTCATTTCA--TCTCTATCAAATGTTGATCCATT----ATCA
919


8.3
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGATCCATT----ATCA
871


8.11
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGATCCATT----ATCA
871


4.2_a
TTGTCCAAATTAGAACTTTTTATTTCA--CCTCTAGGAAACGTTGATCCATT----ATCA
873


4.5
TTGTCCAAATTAGAACTTTTTATTTCA--CCTCTAGGAAACGTTGATCCATT----ATCA
894


4.3
TTGTCCAAATTAGAACTTTTTATTTCA--TCTCTAGGAAACGTTGATCCATT----ATCA
896


4.2_b
TTGTCCAAATTAGAACTTTTTATTTCA--TCTCTAGGAAACGTTGATCCATT----ATCA
898


4.4
TTGTCCAAATTAGAACTTTTTATTTTA--TCTCTAGGAAACGTTGATCCATT----ATCA
898


4.1_b
TTGTCAACCTTAGAACATTTTATTTCG--TCTCTATGAAATGTTGATCCATT----ATCA
900


8.1
TTGTCAAAATTAGAACATTTTATTTCA--TATCTATGAAATGTTGATCCATT----ATCA
896


8.7
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGATCCATT----ATCA
898


8.6
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGAGCCATT----ATCA
901


8.8
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGAGCCATT----ATCA
901


8.5
TTGTCAAAATTAGAACTTTTTATTTCA--TCTCTATGAAATGTTGATCCATT----ATCA
901


8.2
CAGCAGAACACAGGACCTCTTGTCTATGTCCTCTATGCTGTGCTGGTCCACGCCGGGTGG
926


4.1_a
--GCAGTAGGCACTGTACCATAAACAAG-ACACTGTGGGGGTTCAGACCAGG---GGCAA
891



  *        *                    **             ***





8.9
CATACGTATGA-AAATATTATCACGCGTGCTGTGAGATACGTTGTTTTTATTTTCATCAA
980


8.10
CATACGTATGA-AAATATTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
978


8.3
CATACGTATGG-AAAGACTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
930


8.11
CATACGTATGG-AAAGACTATCACCCATGATGTGAGATACGTTGTTTTTATTTTCATCAA
930


4.2_a
CATACGTATGG-AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
932


4.5
CATACGTATGG-AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
953


4.3
CATACGTATGG-AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
955


4.2_b
CATACGTATGG-AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
957


4.4
CATACGTATGG-AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA
957


4.1_b
CATACACATGG-AAATATTATCACCCACGGTGTCAGATACGTTGTTTTTATTTTCATCAC
959


8.1
CATACGTATGG-AAATAGTATCACCAATGCTGTGAGATAAGTTGTTTTTATTTTGGTCAA
955


8.7
CGTAAGTATGG-AAATAGTATCAGCCACGCTGTGAGATACGTTGTTTTTATTTTCATCAG
957


8.6
CATACGTATGG-AAACAGTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAG
960


8.8
CATACGTATGG-AAACAGTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAG
960


8.5
CGTAAGTATGG-AAATAGTATCAGCCACGCTGTGAGATACGTTGTTTTTATTTTCATCAG
960


8.2
AGTTGTCACAACGGACATTACTTCTCTTATGTCAAAGTTCAAGAAGGCCAGTGGTATAAA
986


4.1_a
AGTGGGGATTG---ATAGGGCTAGTAAAGTCTAGGAAGTGTTCACTAACAAAATGTCTAA
948



  *    *      * *                                *        *





8.9
TTCTTTTGTAAAACAAAGGTTATAGTTGGGATACCTTCTGATTTCTCAAGTTTTTTGTTT
1040


8.10
TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCTGATTTCTCAAGTTTTTTGTTT
1038


8.3
TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCCGATTTCTCTAGTTTTTTGTTT
990


8.11
TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCCGATTTCTCTAGTTTTTTGTTT
990


4.2_a
TTCTTTAATAAACAAACGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT
992


4.5
TTCTTTAATAAACAAACGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT
1013


4.3
TTCTTTAATAAACAAAAGGGTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT
1015


4.2_b
TTCCTTAATAAACAAAAGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT
1017


4.4
TTC-TTAATAAACAAAAGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT
1016


4.1_b
TTC---AAGAAAAAAAAGGGTATAGTTGGGATACCTTCTGATTTCTCAAGATTTTTCTTT
1016


8.1
TTCTTTAATAAACAAAAGCTTATAGTTGGGATACCTTCTGATTTCTCAAGGTTTTTGTTT
1015


8.7
TTATTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCAAGTTTTTTGTTT
1017


8.6
TTCTTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCAAGTTTTTTGTTT
1020


8.8
TTCTTTAATAAACAAAAGCTTATAGTTTGGATACCTTTGGATTTCTCAAGTTTTTTGTTT
1020


8.5
TTATTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCAAGTTTTTTGTTT
1020


8.2
ATGGATGATGCCGAGGTCACTGCCTCTGGCATCACCTCTG---TCCTGAGTCAACAGGCC
1043


4.1_a
TTATTAACTAAACTAAATGGTTTC-TCAACATGACCTAATTAATTGTAACTTACTATAAA
1007



 *                  *         **  * *      *    *





8.9
CATGTTTTCTT-------------------------------------------------
1051


8.10
CAGGTTTTCTT-------------------------------------------------
1049


8.3
CATGTTTTCTTTCTTTTTTTTTTTTTTTTTTTT---------GAGACGGGGTCTCGCTCT
1041


8.11
CATGTTTTCTTTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACGGGGTCTCGCTCT
1050


4.2_a
CGTGTTTTCTT-------------------------------------------------
1003


4.5
CGTGTTTTCTT-------------------------------------------------
1024


4.3
CGTGTTTTCTT-------------------------------------------------
1026


4.2_b
CGTGTTTTCTT-------------------------------------------------
1028


4.4
CCTGTTTTCTT-------------------------------------------------
1027


4.1_b
CATATTTTCTT-------------------------------------------------
1027


8.1
CATGTTTTCTT-------------------------------------------------
1026


8.7
CAAGTTTTCTT-------------------------------------------------
1028


8.6
CATGTTTTCTT-------------------------------------------------
1031


8.8
CATGTTTTCTT-------------------------------------------------
1031


8.5
CAAGTTTTCTT-------------------------------------------------
1031


8.2
TATGTCCTCTTTTACATCC-----------------------------------------
1062


4.1_a
TGGTTGTTTGTTCA----------------------------------------------
1021



    *  *  *





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
GTCGCCCAGGCCGGACTGCGGACTGCAGTGGCGCAATCTCGGCTCACTGCAAGCTCCGCT
1101


8.11
GTCGCCCAGGCCGGACTGCGGACTGCAGTGGCGCAATCTCGGCTCACTGCAAGCTCCGCT
1110


4.2_a
------------------------------------------------------------


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
TCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCC
1161


8.11
TCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCC
1170


4.2_a
------------------------------------------------------------


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
---A--------------------------------------------------------
1052


8.10
---A--------------------------------------------------------
1050


8.3
GCCACCGCGCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACTTTGTTAGC
1221


8.11
GC-ACGCGCCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCTTGTTAGC
1229


4.2_a
------------------------------------------------------------


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
CAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG
1281


8.11
CAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG
1289


4.2_a
------------------------------------------------------------


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
----------------------------------------------AACTGCCGTCGCAC
1066


8.10
----------------------------------------------AACTGCCGTCGCAC
1064


8.3
GATTACAGGCGTGAGCCACCGCGCCCGGCCGTTTCATGTTTTCTTAAACTGCCATCGCAC
1341


8.11
GATTACAGGCGTGAGCCACCGCGCCCGGCCGTTTCATGTTTTCTTAAACTGCCATCGCAC
1349


4.2_a
----------------------------------------------AACTGCCGTCGCAC
1018


4.5
----------------------------------------------AACTGCCGTCGCAC
1039


4.3
----------------------------------------------AACTGCCGTCGCAC
1041


4.2_b
----------------------------------------------AACTGCCGTCGCAC
1043


4.4
----------------------------------------------AACTGCCGTCGCAC
1042


4.1_b
----------------------------------------------AACTGCCGTCGGAC
1042


8.1
----------------------------------------------AACTGCCGCCGCAC
1041


8.7
----------------------------------------------AACTGCCGCCGCAC
1043


8.6
----------------------------------------------AACTGCCGCCGCAC
1046


8.8
----------------------------------------------AACTGCCGCCGCAC
1046


8.5
----------------------------------------------AACTGCCGCCGCAC
1046


8.2
-------------------------------------ACAAGAGTGAATGGGAAAGACAC
1085


4.1_a
--------------------------------------------TAAACCTTAATCTTTT
1037



                                              **





8.9
GTCCAAAACCACTCGCTATGCAATGTCTTG-ACCATCTCTCTTTTCTGGCAAATATAAAT
1125


8.10
GTCCGAAACCATTCACTATACAATGTCATT-TTCATCTCTCTTTTCTGGCACACATAAAT
1123


8.3
ATCCGAAATCATTCACTATACAATGTCATG-ACCATCTCTCTTTCCTGGCAAACATAAAT
1400


8.11
ATCCGAAATCATTCACTATACAATGTCATG-ACCATCTCTCTTTTCTGGCAAACATAAAT
1408


4.2_a
GTCCGAAACCGCTCACTATGCAGTGTCATG-ACCGTCTCTCTTTTCTGGCAAACATAAAT
1077


4.5
GTCCGAAACCGCTCACTATGCAGTCTCATG-ACCGTCTCTCTTTTCTGGCAAACATAAAT
1098


4.3
GTCCGAAACCGCTCACTATGCAGTGTCATG-ACCGTCTCTCTTTTCTGGCAAACATAAAT
1100


4.2_b
GTCCGAAACCGCTCACTATGCAGTGTCATG-ACCGTCTCTCTTTTCTGGCAAACATAAAT
1102


4.4
GTCCGAAACCGCTCACTATGCAGTGTCATG-ACCGTCTCTCTTTTCTGGCAAACATAAAT
1101


4.1_b
GTCAGAAACTACTCACTATACAATGTCGTG-ACAATCTACATTTTCGGGCAAACACAAAT
1101


8.1
GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGCACACATAAAT
1100


8.7
GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGCACACATAAAT
1102


8.6
GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGTACACATAAAT
1105


8.8
GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGTACACATAAAT
1105


8.5
GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGCACACATAAAT
1105


8.2
AGTGAGAGTGTGTCAAGAGGCAGGGA-ACC-AAGAGCCCTCGGCGCTGA-AGACACAGAC
1142


4.1_a
GCCAAAATATTTGTAGCTTATGTTCCCATTTAACAAGGTTTTCTGGTCAAAACTGTGCAC
1097



      *                                           *       *





8.9
TTTCGGAATGTCATCAATTAGTCTCTCGGTGATTGCATTATTTCCCCAAAGTCTTTTACA
1185


8.10
TTGCGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTACACA
1183


8.3
TTGGGGATTGTCATCAATTAGTCTCTCAGTGACTGCATGATTTCCACAAAGTCTTTCACA
1460


8.11
TTGGGGATTGTCATCAATTAGTCTCTCGGTGACTGAATGATTTCCACAAAGTCTTTCACA
1468


4.2_a
TTGGGGATTGTCATCAATTAGTCTCTCGGGGATTGCATGATTTCCCCAAAGGCTTTCACA
1137


4.5
TTGGGGATTGTCATCAATTAGTCTCTCGGGGATTGCATGATTTCCCCAAAGGCTTTCACA
1158


4.3
TTGGGGATTCTCATCAATTAGTCTCTCGGGGATTGCATGATTTCCCCAAAGGCTTTCACA
1160


4.2_b
TTGGGGATTGTCATCAATCAGTCTCTCGGGGATTGCATGATTTCCCCAAAGGCTTTCACA
1162


4.4
TTGGGGATTGTCATCAATTAGTCTCTCGGGGATTGCATGATTTCCCCAAAGGCTTTCACT
1161


4.1_b
TTGGGGAATGTCATCAAATAGTCTCCCGCTGATTGCATGATT-CCACAAAGTCCTACACA
1160


8.1
TTGGGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTTCACA
1160


8.7
TTGGGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTTCACA
1162


8.6
TTGGGGAAAGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTTCACA
1165


8.8
TTGGGGAAAGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTTCACA
1165


8.5
TTGGGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAAAGTCTTTCACA
1165


8.2
A-GGCGAGCAACG-CAAGGAGAGCTCAAGAGAGACTACCCCTGCCTCCAGG--TACCCGA
1198


4.1_a
CCACATCATTCTAATGAACTTAGTGTCCAATAAAACATGGACTCTCAGTCGTCCCACGGA
1157



                *              *    *      *      *





8.9
GTCTAGTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACGACTTAATGC
1245


8.10
CTCTACATTGTGCACTGAGTATCTCTTCAGACTTTAGTGCATGTTTCTACCACTTGATGC
1243


8.3
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGT--GTTTCTACCATATGATGC
1518


8.11
GTCTACTTTATGCACTGAGTATCTCTTCAAACTTCAGTGTATGTTTCTACCATTTGATGC
1528


4.2_a
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTGATTC
1197


4.5
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTCATGC
1218


4.3
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTGATTC
1220


4.2_b
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTGATGC
1222


4.4
GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTGATGC
1221


4.1_b
GTCTACATTGTGCACTGAGTATCTCTTCAAACTTCAGTGCTTCTTTCTACCATATGATGC
1220


8.1
GTCTACTTTGTGCAATGAGTATCTCTTCAAACTTCAGTGCATATTTCTACCATTTGATGC
1220


8.7
GCCTACTTTGTGCACTGAGTATCTCTTCAAACTTTAGTGCATGTTTCTACCATTTGATGC
1222


8.6
GTCTACTTTGTGCACTGAGTAACTCTCCAAACTTCAGTGCATGTTTCIACCATTTGATGC
1225


8.8
GTCTACTTTGTGCACTGAGTAACTCTCCAAACTTCAGTGCATGTTTCTACCATTTGATGC
1225


8.5
GCCTACTTTGTGCACTGAGTATCTCTTCAAACTTTAGTGCATGTTTCTACCATTTGATGC
1225


8.2
GTTGGACGAGCACTTGGTGGAAAGAGCCACTCAGGAAAGCAC-CTTAGACCACTGGAAAT
1257


4.1_a
AGTTATTTTGTGTGCATAGTACATCTCTGTGAATATGCCTAATGAGGTATGGAAGGACAC
1217



                  * *                           *       *





8.9
TTTATTATTCAGCAATCTAGCTTCCACAAGAGCATTTAATGTAAAGACTTGTCT-TTTTC
1304


8.10
TTTATTACTT-GCCATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTCTCT-TGTTC
1301


8.3
TTTATTATTTGGCAACCTAGCTTCCAAAAGAGCATTTCATGCAAAGACTTGTCT-TGTTA
1577


8.11
TTTATTATTTGGCAACCTAGCTTCCAAAAGAGCATTTCATGCAAAGACTTGTCT-TGTTA
1587


4.2_a
TTTCTTATTTGGCAATCTAGCTTCCACAAGAGCATTTCACGCAAAGACTTGTCT-TGTTC
1256


4.5
TTTCTTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TGTTC
1277


4.3
TTTCTTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TGTTC
1279


4.2_b
TTTATTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TGTTC
1281


4.4
TTTATTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TCTTC
1280


4.1_b
TTTATCATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAACACTTGTCT-TGTTG
1279


8.1
TTTATTATTTGGCAACCTAGCTTCCACAAGAGCATGTCAGGCAAAGAGTTCTCT-TGTTC
1279


8.7
TTTATTATTTGGCAGCCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TGTTC
1281


8.6
TTTATT---TGGCAGCCTAGCTTCCACAAGAGTATTTCATGCAAAGACTTGTCT-TGTTC
1281


8.8
TTTATT---TGGCAGCCTAGCTTCCACAAGAGTATTTCATGCAAAGACTTGTCT-TGTTC
1281


8.5
TTTATTATTTGGCAGCCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT-TGTTC
1284


8.2
TCCTCCAAGAGCAAAACAAAACGAAGCCTGAGTTCAACGTCAGAAAACTTGAAGGTACCC
1317


4.1_a
TT-ATTATCCAAACAGAGACATTCCACTGGTGCTAGAGAGCCACAGAC--GGAAGTTTTC
1274



*                 *          * *            * *        *





8.9
TCCACTGGCAGGTAATTTCACTCGGATATAGAATCATTAGGCTGAACATGGAAAGGTTAT
1364


8.10
TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGGCTGAACGTGGAAAGGTTAT
1361


8.3
TCCACTGGCAGCTAATTTCATTCGGATAGAGAATCAATAGGCTGAACGTGGAAAGCTTAT
1637


8.11
TCCACTGGCAGCTAATTTCATTCGGATAGAGAATCAATAGGCTGAACGTGGAAAGCTTAT
1647


4.2_a
TCCACTGGCAGGTAATTTCACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGCTTAT
1316


4.5
TCCACTGGCAGGTAATTTCACTCAGATAGAGAATCAATAGGCTCAACGTGGAAAGCTTAT
1337


4.3
TCCCCTGGCAGGTAATTTCACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT
1339


4.2_b
TCCACTGGCAGGTAATTTCACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT
1341


4.4
TCCACTGGCAGGTAATTTCACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT
1340


4.1_b
TCCACTGGCAAGTAATTCAACACGGATAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT
1339


8.1
TCCACTGGAAGGTAATTTCATTCGCACAGAGAATCAATAGGCTGAACGTAGAAAGGTTAT
1339


8.7
TCCACTGGCCAGTAATTTCACTCGGATAGAGAGTCAATAGGCTGAACGTGGAAAGGTTAT
1341


8.6
TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGTCTGAACGTGGAAAGGTTAT
1341


8.8
TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGTCTGAACGTGGAAAGGTTAT
1341


8.5
TCCACTGGCCAGTAATTTCACTCGGATAGAGAGTCAATAGGCTGAACGTGGAAAGGTTAT
1344


8.2
TGCCTCCCAACGTACTTGTGATTCATCAATCAAAATACAAGTGTGGGATGAAAAA-CCAT
1376


4.1_a
TCTGCCTACTGGAAATAAAGC-----CAAGCTTTCTTCTTTCCTCAGCCGTGAGGATTGC
1329



*            * *           *                        *





8.9
CGCTGGGAGGTCTGTTTGATTCCACGGATCTCTCCTTTTTTATTGAGGAAAAAAATATGC
1424


8.10
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTTATTAAGGAAAAAGATACAC
1421


8.3
CGCTGGAAGGTTTGTTTGTTTCCACGGATCTCTCCTTTCTTATTAGGGAAAAAAATACGC
1697


8.11
CGCTGGAAGGTTTGTTTGTTTCCACGGATCTCTCCTTTCTTATTAGGGAAAAAAATACGC
1707


4.2_a
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCATTAGGGAAGAAAATACGC
1376


4.5
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCATTAGGGAAGAAAATACGC
1397


4.3
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCACTAGGGAAGAAAATACGC
1399


4.2_b
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCACTAGGGAAGAAAATACGC
1401


4.4
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCACTAGGGAAGAAAATACGC
1400


4.1_b
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCATTAGGGAAGAAAATACGC
1399


8.1
CGCTGGAAGCTCTGTTTCATTCCACGGATCTCTCCTTTCTTATTAAAGAAAAAAATACGC
1399


8.7
CCCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAGAAAATACGC
1401


8.6
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAAAATATACGC
1401


8.8
CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAAAATATACGC
1401


8.5
CCCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAGAAAATACGC
1404


8.2
CATCCTGAA--CAGCAAAGCTCCCTGCTAAACCTCTCTTCGACGAACCCGACAGATCAGG
1434


4.1_a
TGACCTCC--TCTTTATCATTCTCTCTCTCTCTTTTTTTTTAATGAGCCAAGCTCCACCA
1387



                    **         *   * *   *





8.9
TGTGCTAATTACTGTACTTCATTGCCTATTCTCAGGTCAGAAAG-----CGCACTTCAGA
1479


8.10
TGCGCTAATTACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTCCGA
1476


8.3
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTCCGA
1752


8.11
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTCCGA
1762


4.2_a
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTTCGT
1431


4.5
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTTCGA
1452


4.3
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTTCGA
1454


4.2_b
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTTCGA
1456


4.4
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTTCGA
1455


4.1_b
TGTGCTAAATATTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CACACTTCCGA
1454


8.1
TGTGCTAAATACCATACTTCATTGACTAATCTCAGGTCAGAAAG-----CACACTTCCGA
1454


8.7
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTCAGA
1456


8.6
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----TGCACTTCAGA
1456


8.8
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----TGCACTTCAGA
1456


8.5
TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAAAG-----CGCACTTCAGA
1459


8.2
AGT-CCATGAACACTGGCACACTCGCTTCTCT---GCAAGGGAG-----GAC-CAGGAGA
1484


4.1_a
AATAATAAGATAAACTTTGTGCAAGACTTGGTAAGAGTAGAGTGTCTGACACCTTATGGT
1447



      *                        *      **   *       *      *





8.9
CTTCT---CCTTCTATCGCTGAAAGGAT-GATGGTATCTGCCAAAAGCACATAC-TCGGA
1534


8.10
CTTCTTGTCCTTCCATCGCTGAGAGGAT-GATGGTATCTGCCAAAAGCACATAT-TTGGA
1534


8.3
CTTCTTCTCTTTCCGTCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGCACATAC-TTGGA
1810


8.11
CTTCTTCTCTTTCCGTCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGCACATAC-TTGGA
1820


4.2_a
CTTCTTGTCCTTCCGTCGCGGAGAGGAT-GATGGCAGCTGCCAAAAGTACATAC-TTGGA
1489


4.5
CTTCTTGTCTTTCCGTCGCTGAGAGGAT-GATGGCAGTTGCCAAAAGTACATAC-TTGGA
1510


4.3
CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAAAGTACCTAC-TTGGA
1512


4.2_b
CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAAAGTACCTAC-TTGGA
1514


4.4
CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAAAGTAACTAC-TTGGA
1513


4.1_b
ATTCTTGTCCTTCGGTCACTGAGAGGAT-GATGGTAGCTGCCAAAAGTACATAC-TTGGA
1512


8.1
TTTCTTGTCCTTCTGTCGCTGAGAGGAT-GATGATAGCTGCCAAAAGTACATAC-TTGGA
1512


8.7
CTTCTTGTCCTTCCGTTGATGAGAGGAT-GACGGTAGCTGCCAAAAGTACATAC-TTGGA
1514


8.6
CTTCTTGTGCTTCCATCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGTACATAC-TTGGA
1514


8.8
CTTCTTGTGCTTCCATCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGTACATAC-TTGGA
1514


8.5
CTTCTTGTCCTTCCGTTGATGAGAGGAT-GACGGTAGCTGCCAAAAGTACATAC-TTGGA
1517


8.2
--------------GCCAAAGGGAAGA---ACAAACACTGCAAGAGGGCTCTGC-TTGTG
1526


4.1_a
GCTATAATACTCAAAGCAAAAGCAAAATCGCCTAGGACCAGAAAAGGGAGTCACATAGGA
1507



                       *  *               * * *        * *





8.8
AGT---ACATCCCAGCACAAACACACACACACACA---------------CACGCACACA
1576


8.10
AGT---ACATCCCGGCACAAACACACACACACACA---------------CACACACACA
1576


8.3
GGT---TCATCCCAGCACAAACACACACACACAAA---------------CACACAAACA
1852


8.11
GGT---TCATCCCAGCACAAACACACACACACAAA---------------CACACAAACA
1862


4.2_a
AGT---TCATCCCAGCACAAACACACACACACACGC--CCCCCCCACACACACACACACA
1544


4.5
AGT---TCATCCCAGCACAAACACACACACACACGCGCCCCCCCCACACACACACACACG
1567


4.3
GGT---TCATCCCAGCACAAACACACACACACACACGCCCCCCCC---CACACACACACA
1566


4.2_b
GGT---TCATCCCAGCACAAACACACACACACACACGCCCCCCCC-----CACACACACA
1566


4.4
GGT---TCATCCCAGCACAAACACACACACACACATGCCCCCCCC----ACACACACACA
1566


4.1_b
AGT---TCATCCCAGCACAAACACACATACACACACGCCCCCCCC-----CACACACACA
1564


8.1
AGT---TCATCCCAGCACGAGCACACACACACATAAACACACACA-----CACACACACA
1564


8.7
AGT---TCATCCCAGCACAAGCACACACACACACA--CACAAACA-----CACACACACA
1564


8.6
AGT---TCATCCCAGCACAAGCACACACACACACA--CACAAACA-----CACACACACA
1564


8.8
AGT---TCATCCCAGCACAAGCACACACACACACA--CACAAACA-----CACACACACA
1564


8.5
AGT---TCATCCCAGCACAAGCACACACACACACA--CACAAACA-----CACACACACA
1567


8.2
TGCCAGTGATCTCAGTGGAAGTGCCGACCCACACGTAGGGGAGAA------AAACACACA
1580


4.1_a
AATCTAGAAGACCTATTGGCTGAGAGACCTGCAGCCTCATAGTTCATTAGCTCTC-CATA
1566



        *   *             *    **                     *  *





8.9
AACACACATACTCACAC------------GGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.10
CACACACACACACACAC------------GGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.3
CACACACA------CAC------------GGCTTCA--TAGGTAAAGATTTCTTCCCTGA
1892


8.11
CACACACA------CAC------------GGCTTCA--TAGGTAAAGATTTCTTCCCTGA
1902


4.2_a
AACACACTCACACACACACACGCACAC--GGTTTCC--TAGGTAAAGATTTCTTCCCTGC
1600


4.5
AACACAATCACACACACACACTCACAC--GGTTTCC--TACGTAAAGATTTCTTCCCTGC
1623


4.3
AACACACTCACACACACACACCCACAC--GGTTTCC--TAGGTAAAGATTTCTTCCCTGC
1622


4.2_b
AACACACTCACACACACACACGCACAC--GGTTTCC--TAGGTAAAGATTTCTTCCCTGC
1622


4.4
AACACACTCACACACACACACGCACAC--GGTTTCC--TAGGTAAAGATTTCTTCCCTGC
1622


4.1_b
AACACACTCACACACACACACACACACACGGTTTCC--AAGGTAAAGATTTCTTCCCTGC
1622


8.1
CACACACACACACACACAGACACACACAGGGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.7
CACACACACACAGAGAGAGATACACACACGGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.6
CACACACACACACACACAGACACACACACGGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.8
CACACACACACACACACAGACACACACACGGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1622


8.S
CACACACACACAGAGAGAGATACACACACGGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1625


8.2
CACACACACACACACAC------------GGTTTCA--TAGGTAAAGATTTCTTCCCTGA
1626


4.1_a
GCAACTCTCACATGAAATGAAGTCAGTGGTGTTTCAAGTGCTTGAAACCCTCTTTACT-C
1625



   **          *              * ***       * **    ****  **





8.9
CATTCTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACCAT
1679


8.10
CATTGTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1679


8.3
CATTGTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCTGGTTACACT
1949


8.11
CATTGTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCTGGTTACACT
1959


4.2_a
CATTGCTTTACCTAAAATAAG---GCAAGTGTGAGGCCACTGTCCCAACCCGGTTACACT
1657


4.5
CATTGCTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1680


4.3
CATTGCTTTACCTAAAATAAG---GCAACTGTGAGGCCACTGTCCCAACCCGGTTACACT
1679


4.2_b
CATTGCTTTACCTAAAATAAG---GCAACTGTGAGTCCACTGTCCCAACCCGGTTACACT
1679


4.4
CATTGCTTTACCTAAAATAAG---GCAACTGTGAGGCCACTGTCCCAACCCGGTTACACT
1679


4.1_b
CATTGCTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1679


8.1
CATTCTTTTACCTAAAATAAG---GCAACTGTGCGGCCACTGCCCAAACCCGGTTACACT
1679


8.7
CATTCTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1679


8.6
CATTCTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1679


8.8
CATTCTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1679


8.5
CATT-CTGTACCTAAAATAAG---GCAACTGTGTG-CCACTGTCCCAACCCG-TTACACT
1679


8.2
CATTGTTTTACCTAAAATAAG---GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT
1683


4.1_a
TACTTCTAAATGTGAATTAATTATGCAAATTTACTAGCAGTTGCTAGACCT--CAAAAGC
1683



 * *  *  *  * ** ***    **** * *     ** *  *   ***     *





8.9
CATATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATGAAGGTGTTTTAGAAGT
1735


8.10
CATATTACATGTGTCTATCAGCCTGAGGAGTAGTTT----GATTCAGGTGTTCTAGAAGT
1735


8.3
CATATTACATCTGCCTATCATCCTGAGGAGTAATGT----GATTCAGGTGTTCTAGAAGT
2005


8.11
CATATTACATCTGCCTATCATCCTGAGGAGTAATGT----GATTCAGGTGTTCTAGAAGT
2015


4.2_a
CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATTCAGGTGTTCTGGAAGT
1713


4.5
CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATTCAGGTGTTCTGGAAGT
1736


4.3
CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATTCAGGTGTTCTGGAAGT
1735


4.2_b
CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATTCAGGTGTTCTGGAAGT
1735


4.4
CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT----GATTCAGGTGTTCTGGAAGT
1735


4.1_b
CCTATTATATGTGCTTATCATCCTGAGGAGTAATCT----GATTCAGGTGTTCTGGAAGT
1735


8.1
CATATTATATGTGCCTATCACCCTGAGGAGTAATTT----GATTCAGGTGTTCTAGAAGT
1735


8.7
CATATTATATGTGCCTATCACCCTGAGGAGTAATTT----GATTCAGGTGTTCTAGAAGT
1735


8.6
CATATTACATGTGTCTATCAGCCTGAGGAGTAATTT----GATTCAGGTGTTCTAGAAGT
1735


8.8
CATATTACATGTGTCTATCAGCCTGAGGAGTAATTT----GATTCAGGTGTTCTAGAAGT
1735


8.5
CATATTATATGTGCCTATCACCCTGAGGAGTAATTT----GATTCAGGTGTTCTAGAAGT
1735


8.2
CATATTACATGTGTCTATCAGCCTGAGGAGTAGTTT----GATTCAGGTGTTCTAGAAGT
1739


4.1_a
AAAATAATCAGGCATTATTCTACTAAGTATTGGTCTCCATAACTCCTCTATTTTCTTTAG
1743



   ** *        ***    ** ** * *  * *     *      * ** *





8.9
CATGATGTGGACTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.10
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.3
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
2065


8.11
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
2075


4.2_a
CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGGGACACACCCTGTGACTC
1773


4.5
CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1796


4.3
CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGGGACACACCCTGTGACTC
1795


4.2_b
CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGGGACACACCCTGTGACTC
1795


4.4
CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGGGACACACCCTGTGACTC
1795


4.1_b
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.1
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.7
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.6
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.8
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.5
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1795


8.2
CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC
1799


4.1_a
GAAAAGTTAGTCTAAGACATTTGGCATAAAGGCTATGCCAAAGCTTTGGTGGGGTCAGCC
1803



 *     * * **  * *  ***   *    ** **** *  *          ** *  *





8.9
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATTGCCCACCTTATGTGCGGGTGGGG
1855


8.10
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCGCACCTGATGGGTGGGTGGGG
1855


8.3
ATTCCTTAATTAAATGCTGACATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGAGG
2125


8.11
ATTCCTTAATTAAATGCTGATATTTGATTGGTTTATCGCGCACCTGATGAGTGGGTGAGG
2135


4.2_a
CTTCCTGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTAGGTGGGG
1833


4.5
CTTCCTGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGG
1856


4.3
CTTCCTGAATTGAGTGCTGTTATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGG
1855


4.2_b
CTTCCTGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGG
1855


4.4
CTTCCTGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGG
1855


4.1_b
CTTCCTGAATTGAGTGCTGATATTTGATTGGCTAATCGCGCACCTGATGAGTGGGTGGGG
1855


8.1
ATTCCTTAATTGAGTGCTGATATTTGATTGTTTTATCGCGCACCTGATGGGTGGGTGGGG
1855


8.7
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCACACCTGATGGGTGGGTGGGG
1855


8.6
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCACACCTGATGGGTGGGTGGGG
1855


8.8
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCACACCTGATGGGTGGGTGGGG
1855


8.5
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCACACCTGATGGGTGGGTGGGG
1855


8.2
ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTATCGCGCACCTGATGGGTGGGTGGGG
1859


4.1_a
AGGAAGGATTCGTGGGGGTCTCCTTGAAAATACTGCAATA-ATCTAAGAAATCTTCAACC
1862



       * *     *       ****              * ** *





8.9
TGTTCGCTCTTGGTGCGGGTGAGTTATGTAAGGGCTGATTTGGCCAGAGAACTCGTTATT
1915


8.10
TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


8.3
TGTTCGCCGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
2185


8.11
TGTTCGCCGTTGGTGCGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
2195


4.2_a
TGTTCGCGGTTGGTGGGGGTGACTTACAGAAGGGCTGATGTGGCCAGAGAGCTCGTCATT
1893


4.5
TGTTCGCGGTTGGTGGGGTTGACTTACAGAAGGGCTGATGCG-CCAGAGAGCTCGTCATT
1915


4.3
TGTTCGCGGTTCGTGGGGGTGACTTATAGAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


4.2_b
TGTTCGCTGTTGGTGGGGGTGACTTACAGAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


4.4
TGTTCGCGGTTCGTGGGGGTGACTTACAGAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


4.1_b
TGTTCGCGGTTGGTGTGGGTGAGTTATAGAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


8.1
TGTTCGCGGTTGGTGGGGGTGAGTTCTATAAGGGATGATGCGGCCAGAGAGCTCGTCATT
1915


8.7
TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


8.6
TGTTCGCGGTTGGAGGGGGTGAGTTATATAAGGCCTGATGCGGCCAGAGAGCTGGTCATT
1915


8.8
TGTTCGCGGTTGGAGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTGGTCATT
1915


8.5
TGTTCGCCGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT
1915


8.2
TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCCCGTCATT
1919


4.1_a
TATTGCCCCTCAGTACTGTTG-GTCCCCTGTACTTGACTTTTCCCCTTAAGTTTG--ATT
1919



* **  *  *  *    * **  *              *    **    *    *  ***





8.9
TGAAGACTCTCTCGGAAGAGATAGCGTTTTTCTGCAACCTACGGTCCCAGCAGAAAAACC
1975


8.10
TGAAGACTCTCTCGGAAGAGATAGCATCTTTCTGCAACCTGCGGTCCCAGCCGAAAAACC
1975


8.3
TGAAGACTCTCTCGGAAGAGATAGAGTCTTTCTGCAACATAAGGTCCCAGCCGAAAAACC
2245


8.11
TGAAGACTCTCTCGGAAGAGATAGCGTCTTTCTGCAACATAAGGTCCCAGCCGAAAAACC
2255


4.2_a
TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGTGGTCCCAGCAGACAAACC
1953


4.5
TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


4.3
TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


4.2_b
TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


4.4
TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGACAAACC
1975


4.1_b
TGAAGACTCTCTCGGAAGAGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


8.1
TGAAGACTCTCTCGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


8.7
TGAAGACTCTCTTGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCACAAAAACC
1975


8.6
TGAAGACTCTCTCGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


8.8
TGAAGACTCTCTCGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


8.5
TGAAGACTCTCTTGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC
1975


8.2
TGAAGACTC----GGAAGAGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCCGAAAAACC
1975


4.1_a
CCATTTCCTAATATTATCCTTCCCTCTTCCTCCTCAGCAACTAGTCTTCTAAATTAGAAC
1979



  *   *        *          *    *  ** *     ***         * * *





8.9
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.10
CTGTGATCCTTGTTCCGGGCGACATG----------------------------------
2001


8.3
TTGTGATCCTTGTTCCGGGCGACATG----------------------------------
2271


8.11
TTGTGATCCTTGTTCCGGGCGACATG----------------------------------
2281


4.2_a
TTGTGATCCTTGTTCCAGTCGACATGGAGGACGACTCACTCTACTTGGGAGGTGAGTGGC
2013


4.5
TTGTGATCCTTGTTCCAGTCGACATG----------------------------------
2001


4.3
TTGTGATCCTCGTTCCAGTCGACATG----------------------------------
2001


4.2_b
TTGTGATCCTCGTTCCAGTCGACATG----------------------------------
2001


4.4
TTGTGATCCTTGTTCCAGTCGACATG----------------------------------
2001


4.1_b
TTGTGATCCTTGTTCCAGTCGACATG----------------------------------
2001


8.1
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.7
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.6
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.8
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.5
TTGTGATCCTTGTTGCGGGCGACATG----------------------------------
2001


8.2
TTGTGATCCTTGTTCCGGGCGACATG----------------------------------
2001


4.1_a
TTAAACACAATG----AGCAGATATG----------------------------------
2001



 *     *   *     *  ** ***





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
------------------------------------------------------------


8.11
------------------------------------------------------------


4.2_a
AGTTCAACCACTTTTCAAAACTCACATCTTCTCGGCCAGATGCAGCTTTTGCTGAAATCC
2073


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
------------------------------------------------------------


8.11
------------------------------------------------------------


4.2_a
AGCGGACTTCTCTCCCTGAGAAGTCACCACTCTCATGTGAGACCCGTGTCGACCTCTGAG
2133


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
------------------------------------------------------------


8.10
------------------------------------------------------------


8.3
------------------------------------------------------------


8.11
------------------------------------------------------------


4.2_a
ATGATTTGGCTCCTGTGGCAAGACAGCTTGCTCCCAGGGAGAAGCTTCCTCTGAGTAGCA
2193


4.5
------------------------------------------------------------


4.3
------------------------------------------------------------


4.2_b
------------------------------------------------------------


4.4
------------------------------------------------------------


4.1_b
------------------------------------------------------------


8.1
------------------------------------------------------------


8.7
------------------------------------------------------------


8.6
------------------------------------------------------------


8.8
------------------------------------------------------------


8.5
------------------------------------------------------------


8.2
------------------------------------------------------------


4.1_a
------------------------------------------------------------





8.9
--------------------------------------


8.10
--------------------------------------


8.3
--------------------------------------


8.11
--------------------------------------


4.2_a
GGAGACCTGCTGCGGTGGGGGCTGGGCTCCAGAATATG
2231


4.5
--------------------------------------


4.3
--------------------------------------


4.2_b
--------------------------------------


4.4
--------------------------------------


4.1_b
--------------------------------------


8.1
--------------------------------------


8.7
--------------------------------------


8.6
--------------------------------------


8.8
--------------------------------------


8.5
--------------------------------------


8.2
--------------------------------------


4.1_a
--------------------------------------























HDUB4.6 putative promoter sequence upstream of




initiation ATG



gcatgactgg cagacagctt atcgattggg ctcccctcaa







aatcggttat gagcattcaa gcacaccgat gcccaggtcc







cggctgcagg aataagaccc tccagggtct tgtgtgaagc







ctcggcatct gcattgctca tgcttctggg gatcattctc







ctgaaaatgg tggctccttt ctccctgtgg agcatctttc







taagcagtgc tcttttcttc ccccaggaca ctttacatcc







ggcacaggaa gccttctgat ggagcacacc tggcccatga







aaagacaagg gaaagaaacg gggccaaagg tcacagtcct







ctcatcccat catcctcctt aaaatcatcc taatttcatg







ggccctgaag ccagggctgt ttctttacac ctagaggcct







tggcgccggg cctcaattcc gccctgttcc ttaccgtcta







agacatgttg ggaaaatccc tagagccagg atcttcattc







ctgctaagcc agacagccgg aagacacacc caaattctgt







ccctcttact tcagggaaca tgtccacttt cggcagcatt







acaattttgg caccaaatgt gctaactgca attccaccat







acaatgcgta actggaaatg gaggcaacat ctccgatcct







gaacgatcga tgcgagaatc caggatatgc acggcttatt







ttggcctttt cccactgaaa caagggccag tattaaaaat







ggcacgctat cctctgtttc actccctgct tttaaacgtc







tccgatgttt ctccctgaga cagggcctca cttccgtcag







ccgggctttt ccacggtata attttccttg tttgcttttg







tccaaattag aactttttat ttcacctcta ggaaacgttg







atccattatc acatacgtat ggaaatatta tcacacatgc







tgtgagatac gttgttttta ttttcatcaa ttctttaata







aacaaacggt tatagctggg ataccttctg agttctcaag







ttttttgttt cgtgttttct taaactgccg tcgcacgtcc







gaaaccgctc actatgcagt gtcatgaccg tctctctttt







ctggcaaaca taaatttggg gattgtcatc aattagtctc







tcggggattg catgatttcc ccaaaggctt tcacagtcta







ctttgtgcac tgagtatctc ttcaaacttc agtgcatgtt







tctaccattt catgctttct tatttggcaa tctagcttcc







acaagagcat ttcatgcaaa gacttgtctt gttctccact







ggcaggtaat ttcactcaga tagagaatca ataggctcaa







cgtggaaagg ttatcgctgg aaggtctgtt tgattccacg







gatctctcct ttctcattag ggaagaaaat acgctgtgct







aaatactata cttcattgac tattctcagg tcagaaagcg







cactttcgac ttcttgtctt tccgtcgctg agaggatgat







ggcagctgcc aaaagtacat acttggaagt tcatcgcaga







aaaaacacac acacacacgc gcccccccca cacacacaca







cacgaacaca atcacacaca cacacactca cacggtttcc







tacgtaaaga tttcttccct gccattgctt tacctaaaat







aaggcaactg tgtggccact gtcccaaccc ggttacactc







ctattatatg tgcctatcat cctgaggagt aatttgattc







aggtgttctg gaagtcatgc tgtgggctgt gtctgttgaa







ttcccagcga tgcaagggga cacaccctgt gactccttcc







tgaattgagt gctgatattt gattggctta tcgcgcacct







gatgagtggg tgtggtgttc gcggttggag ggggtgactt







acagaagggc tgatgcggcc agagagctcg tcatttgaag







actctctcgg aagggatagc gtctttctgc aacctgcggt







cccagcagaa aaaccttgtg atccttgttc cagtcgacat







g







HDUB4.7 putative promoter sequence upstream of



initiation ATG



tcctcagcgt cggtttttag gcctggcata agctgtttga







aacccaggaa cgtaccccac ccatcatctt tggcctagtt







aacacctccc ctccgtgtgt ggtggtttgg agaacctgct







ttttcctcat cccactgatc ccaaacccag gacaccctac







agctgctgac caggattaaa cctaatggag atttaatgcc







attaaatcag aagaaattct gattctcagg gactgacatt







cattcactta catacttgca gagtcggcca ggtgtgttgg







ctcacacctg taatcccagc actttgggaa gccgaggtgg







gtggatcacg aggtcaagaa ttcgagacca tcctggccaa







catggtgaaa ccccgtctct actaaaaata caaaaattaa







ctggtgtagc tgtgcgtgcc tgtaatccca gctactcagg







aggctgaggc aggcgatttg cttgaacctg ggaggtggag







gttgcagtga gccaagatta tgccattgca ctccagcctg







ggcaacagag cgagactctc agaaaacaaa aaacccaaaa







acttgcagag tgaatttagg aaaccatgaa gtacacagtt







tgatccaatg ccttcctttt tctctttctc aaatattttg







agccaggtac tatcctagac tgtcttgtga tatttacaat







ctaggagaag gcaggagaga gaactaagaa cagagagcat







gttctgagat gtctgctgtg tttgcaggta ccttccctca







atttccctac tcactggcca tgctggaaag caggtcttgg







cgctatattt ataccatggt acttcccctc cctatactca







attggttggc cagaagccca attgtcactc tctctctctg







tctccctctc gctccctccc tccctccctc cctccctccc







tctccaagat atccagtaac tgactgatca gctgggggtg







ggctctgctg gctgccaaga tgggccacca gcaaaaaggg







aaaattggtt gtgagtgaga agaagagata agaaattcca







cagggctgat aagaaagacc atgggcttcc aggcgcggtg







tttcacgcct gtaatcccag cacttgggag gccaggatgg







tcggatttgg caatctagct tccacaagag catttcacgc







aaagacttgt cttgttctcc actggcaggt aatttcactc







ggatagagaa tcaataggct caacgtggaa aggttatcgc







tggaaggtct gtttaattcc acggatctct cctttctcat







tagggaagaa aatacgctgt gctaaatact atacttcatt







gactattctc aggtcagaaa gcgcactttc gacttcttgt







ccttccgtcg ctgagaggat gatggcagct gccaaaagta







catacttgga agttcatccc agcacaaaca cacacacaca







cacgcccccc cacacacaca cacacaaaca cactcacaca







cacacacgca cacggtttcc taggtaaaga tttcttccct







gccattgctt tacctaaaat aaggcaactg tgaggccact







gtcccaaccc ggttacgctc ctattatatg tgcctatcat







cctgaggagt aatttgattc aggtgttctg gaagtcatgt







tgtgggctgt gtctgttgaa ttcccagcga tgccagggga







cacaccctgt gactccttcc tgaattgagt gctgatattt







gattggctta tcgcgcacct gatgagtggg tggggtgttc







gcggttggtg ggggtgactt acagaagggc tgatgcggcc







agagagctcg tcatttgaag actctctcgg aagggatagc







gtccttctgc aacctgcggt cccagcagac aaaccttgtg







atccttgttc cagtcgacat g







HDUB4.8 putative promoter sequence upstream of



initiation ATG



CAGGGCTCCG TAGAACCACA GAATCTTGGG CGCAACCCTG







CTCAAGCACC CAAATGTGCA TACGAACAGG GTCTCCGTGT







GACGTGTGTG AAAACTACAG TGTGATGAGC ATGACTGGCA







GACAGCTTAT CGATTGGGCT CCCCTCAAAA TCGGTTATGA







GCATTCAAGC ACACCGATGC CCAGGTCCCG GCTGCAGGAA







TAAGACCCTC CAGGGTCTTG TGTGAAGCCT CGGCATCTGC







ATTGCTCATG CTTCTGGGGA TCATTCTCCT GAAAATGGTG







GCTCCTTTCT CCCTGTGGAG CATCTTTCTA AGCAGTGCTC







TTTTCTTCCC CCAGGACACT TTACATCCGG CACAGGAAGC







CTTCTGATGG AGCACACCTG GCCCATGAAA AGACAAGGGA







AAGAAACGGG GCCAAAGGTC ACAGTCCTCT CATCCCATCA







TCCTCCTTAA AATCATCCTA ATTTCATGGG CCCTGAAGCC







AGGGCTGTTT CTTTACACCT AGAGGCCTTG GCGCCGGGCC







TCAATTCCGC CCTGTTCCTT ACCGTCTAAG ACATGTTGGG







AAAATCCCTA GAGCCAGGAT CTTCATTCCT GCTAAGCCAG







ACAGCCGGAA GACACACCCA AATTCTGTCC CTCTTACTTC







AGGGAACATG TCCACTTTCG GCAGCATTAC AATTTTGGCA







CCAAATGTGC TAACTGCAAT TCCACCATAC AATGCGTAAC







TGGAAATGGA GGCAACATCT CCGATCCTGA ACGATCGATG







CGAGAATCCA GGATATGCAC GGCTTATTTT GGCCTTTTCC







CACTGAAACA AGGGCCAGTA TTAAAAATGG CACGCTATCC







TCTGTTTCAC TCCCTGCTTT TAAACGTCTC CGATGTTTCT







CCCTGAGACA GGGCCTCACT TCCGTCAGCC GGGCTTTTCT







ACGGTATAAT TTTCCTTGTT TGCTTTTGTC CAAATTAGAA







CTTTTTATTT CACCTCTAGG AAACGTTGAT CCATTATCAC







ATACGTATGG AAATATTATC ACACATGCTG TGAGATACGT







TGTTTTTATT TTCATCAATT CTTTAATAAA CAAACGGTTA







TAGCTGGGAT ACCTTCTGAG TTCTCAAGTT TTTTGTTTCG







TGTTTTCTTA AACTGCCGTC GCACGTCCGA AACCGCTCAC







TATGCAGTGT CATGACCGTC TCTCTTTTCT GGCAAACATA







AATTTGGGGA TTGTCATCAA TTAGTCTCTC GGGGATTGCA







TGATTTCCCC AAAGGCTTTC ACAGTCTACT TTGTGCACTG







AGTATCTCTT CAAACTTCAG TGCATGTTTC TACCATTTGA







TGCTTTATTA TTTGGCAATC TAGCTTCCAC AAGAGCATTT







CATGCAAAGA CTTGTCTTCT TCTCCACTGG CAGGTAATTT







CACTTGGACA GAGAATCAAT AGGCTCAACG TGGAAAGGTT







ATCGCTGGAA GGTCTGTTTG ATTCCACGGA TCTCTCCTTT







CTCATTAGGG AAGAAAATAC GCTGTGCTAA ATACTATACT







TCATTGACTA TTCTCAGGTC AGAAAGCGCA CTTTCGACTT







CTTGTCCTTC CGTCGCTGAG AGGATGATGG CAGCTGCCAA







AAGTACATAC TTGGAGGTTC ATCCCAGCAC AAACACACAC







ACACACGCGC CCCCCCCACA CACACACACA CGAACACAAT







CACACACACA CACTCACACG GTTTCCTACG TAAAGATTTC







TTCCCTGCCA TTGCTTTACC TAAAATAAGG CAACTGTGTG







GCCACTGTCC CAACCCGGTT ACACTCCTAT TATATGTGCC







TATCATCCTG AGGAGTAATT TGATTCAGGT GTTCTGGAAG







TCATGCTGTG GGCTGTGTCT GTTGAATACC CAGCGATGCA







AGGGGACACA CCCTGTGACT CCTTCCTGAA TTGAGTGCTG







ATATTTGATT GGCTTATCGC GCACCTGATG AGTGGGTGGG







GTGTTCGCGG TTGGTGGGGG TGACTTACAG AAGGGCTGAT







G







HDUB4.9 putative promoter sequence upstream of



initiation ATG



gcatctttct agtcagcgct cttttcttcg cccaggacac







tttacatccg gcacacgaag ccttctgatg gagcacacct







ggcccatgaa aagccaaggg aaagaaacgg ggccaaaggt







cacagtcctc tcctcccatc atcctcctta aaatcatcct







aatttcctgg ccctgaagcc agggctgttt ctttacacct







agaggccttg gcgccgggcc tcaattccgc cctgttcctt







accgtctaag acatgttggg aaaatcccta gagccaggat







cttcattcct gctaagccag acagccggaa gacacaccca







aattctgtcc ctcttacttc agggaacatg tccactttcg







gcagcattac aattttggca ccaaatgtgc taactgcaat







tccaccatac aatgcctaac tggaaatgga ggcaacatct







ccgatcctga acgatcgatg cgagaatcca ggatatgcac







ggcttatttt ggccttttcc cactgaaaca agggccagta







ttaaaaatgg cacgctatcc tctgtttcac tccctgcttt







taaacgtctc cgatgttgct ccctgagaca ggacctcact







tccgtcagcc gggcttttct acggtataat tttccttgtt







tgcttttgtc caaattagaa ctttttattt catctctagg







aaacgttgat ccattatcac atacgtatgg aaatattatc







acacatgctg tgagatacgt tgtttttatt ttcatcaatt







ctttaataaa caaaaggtta tagctgggat accttctgag







ttctcaagtt ttttgtttcg tgttttctta aactgccgtc







gcacgtccga aaccgctcac tatgcagtgt catgaccgtc







tctcttttct ggcaaacata aatttgggga ttgtcatcaa







ttagtctctc ggggattgca tgatttcccc aaaggctttc







acagtctact ttgtgcactg agtatctctt caaacttcag







tgcatgtttc tacaatttga tgctttatta tttggcaatc







tagcttccac aagagcattt catgcaaaga cttgtcttgt







tctccactgg caggtacttt cactcggaca gagaatcaat







aggctcaacg tggaaaggtt ttcgctggaa ggtctgtttg







attccacgga tctctccttt ctcattaggg aagaaaatac







actgtgctaa atactatact tcattgacta ttctcaggtc







agaaagcgca ctttcgactt cttgtccttc cgtcgctgag







aggatgatgg cagctgccaa aagtacatac ttggaagttc







atcccagcac aaacacacac acacgcgccc ccccacacac







acacacaaac acaatcacac acacacacaa tcacacggtt







tcctaggtaa agatttcttc cctgccatgg ctttacctaa







aataaggcaa ctgtgtgacc actgtcccaa cccggttaca







ctcctattat atgtgcctat catcctgagg agtaatttga







ttcaggtgtt ctggaagtca tgctgtggga tgtgtctgtt







gaattcccag cgatgccagg gggacacacc ctgtgactcc







ttcctgaatt gagtgctgat atttgattgg cttatcgcgc







acctgatgag tgggtggggt gttcgcggtt ggtgggggtg







acttacagaa gggctgatgc ggccagagag ctcgtcattt







gaagactctc tcggaaggga tagcgtcttt ctgcaacctg







cggtcccagc agaaaaacct tgtgatcctt gttccagtcg







acatg







HDUB4.10 putative promoter sequence upstream of



initiation ATG



agcaagcttt ggaacagttg gtgaagcccg aagaactcaa







tggagagaat gcctatcatt gtggtgtttg tctccagagg







gcgccggcct ccaagacgtt aactttacac acctctgcca







aggtcctcat ccttgtattg aagagattct ccgatgtcac







aggcaacaag attgccaaga atgtgcaata tcctgagtgc







cttgacatgc agccatacat gtctcagcag aacacaggac







ctcttgtcta tgtcctctat gctgtgctgg tccacgctga







gtggagttgt cacaacggac attacttctc ttatgtcaaa







gctcaagaag gccagtggta taaaatggat gatgccgagg







tcaccgccgc tagcatcact tctgtcctga gtcaacaggc







ctacgtcctc ttttacatcc agaagagtga atgggaaaga







catagtgaga gtgtgtcaag aggcagggaa ccaagagccc







ttggcgcaga agacacagac aggcgagcaa cgcaaggaga







gctcaagaga gaccacccct gcctccaggc ccccgagttg







gacgagcact tggtggaaag agccactcag gaaagcacct







tagaccactg gaaattcctt caagagcaaa acaaaacgaa







gcctgagttc aacgtcagaa aagtcaaagg taccctgcct







cccgacgtac ttgtgattca tcaatcaaaa tacaagtgtg







ggatgaagaa ccatcatcct gaacagcaaa gctccctgct







aaacctctct tcgtcgaccc cgacacatca ggagtccatg







aacactggca cactcgcttc cctgcgaggg agggccagga







gatccaaagg gaagaacaaa cacagcaaga gggctctgct







tgtgtgccag tgatctcagt ggaagtaccg acccacacgt







aggggtgcac acacacacgc acacacacag acacacacat







aactacaccc agaagcgcgc acgcaaacac acacacaccc







acacaaacac gaacaccgtc aatcctacat aaactaatga







ggagcccaag tttctgtctc tacaacaggg acaactggat







agtgatggct acatctcagg atgagcccgc atatgggaaa







catcaagttt tggggtcgtg agtcttccga acctctggag







ggactgtctg agtgtttgtg ttcatgatag gtgacattca







gtgtgtattt ctgaatatga cctaccgacg tgtaggtttg







cgtgtgaggt aattgcaggg gactcggttt cgtattttct







cttggggtgt gtttcattcg tcagttgttg gtcggcatga







gaaggtgaaa tgtggctcat gtgggacatc cgtggatcat







tctcgccacc ttgaatagtg gaaactggaa tgcatttgga







agagaagaac ggtgctcttc tttcttcccc gggctcgccg







tttttacact ggttcctgaa tggacctcag gcgccctggg







acttgtgctc ttgctggaac ccacataacg ccggaagcgg







acagaccgac ttgcctgttt cacggtgccc gcttcccatg







agtccaaacg gaaaattttc ccacgggcat gtaagtcatc







tggaagtaag ctgtattgat aataaaggaa agcaaacaca







ggagtgtgtg tattcaactg aaataaattc agaaagccct







gaaatcaatc tcactgggtg tgtttaaaaa tggcatttgg







ggaatttctg ggtcatttgt ccagctgcga aagctgcatc







tctgaagcac agtccctgtc ccgcagtgag acttattgat







ccgacgtggt gtttccgtgg aaatgattgt gggaaatggc







cccttccttt tctctatttg ctgattagac ttcatggtcc







ctttctcgtc aggtacagtg atcaaagttg accagcccca







gaggaaagct gcccagggca caactcaggg ctccgtagaa







ccacagaatc ttgggcgcaa ccctgctcaa gcacccaaat







g







HDUB4.11 putative promoter sequence upstream of



initiation ATG



cagcaagctt tggaacagtt ggtgaagccc gaagaactca







atggagagaa tgcctatcat tgtggtgttt gtctccagag







ggcgccggcc tccaagacgt taactttaca caactctgcc







aaggtcctca tccttgtatt gaagagattc cccgatgtca







caggcaacaa aattgccaag aatgtgcaat atcctgagtg







ccttgacatg cagccataca tgtctcagca gaacacagga







cctctcgtct atgtcctcta tgctgtgctg gtccacgctg







ggtggagttg tcacaacgga cattactcct cttatgtcaa







agctcaagaa ggccagtggt ataaaatgga tgatgccgag







gtcaccgcct ctagcatcac ttctgtcctg agtcaacagg







cctacgtcct cttttacatc cagaagagtg aatgggaaag







acacagtgag agtgtgtcaa gaggcaggga accaagagcc







cttggcgtag aagacacaga caggcgagca acgcaaggag







agctcaagag agaccacccc tgcctccagg cccccgagtt







ggacgagcac ttggtggaaa gagccactca ggaaagcacc







ttagaccact ggaaattcct tcaagagcaa aacaaaacga







agcctgagtt caacgtcaga agagtcgaag gtacggtgcc







tcccgacgta cttgtgattc atcaatcaaa atacaagtgt







cggatgaaga accatcatcc tgaacagcaa agctccctgc







taaacctctc ttcgacgacc ccgacagatc aggagtccat







gaacactggc acactcgctt ccctacgagg gaggaccagg







agatccaaag ggaagaacaa acacagcaag agggctctgc







ttgtgtgcca gtgatctcag tggaagtacc gacccacacg







taggggtgca tacacacaca cacacacaca cacacacaca







taactacacc cagaagcgcg cacgcaaaca cacacacacc







cacacaaaca cgaacaccgt caatcctaca taaactaatg







aggagcccaa gtttctgtct gtacaacagg gacaactgga







tagagatggc tacatctcag gatgagcccg catatgggaa







acatcaagtt ttggggtcgt gagtcttccg aacctctgga







gggactgtct gagtgtttgt gttcatgata ggtgacattc







agtgtgtatt tatgaatatg acctaccgac gtgtaggttt







gcgtgtgagg taattgcagg ggactcggtt tcgtattttc







tcttggggtg tgtttcattc gacagttgtt ggtcggcacg







agaaggtgaa atttggctca tgtgggacat ccgtggatca







ttctcgccac cttgaatagt ggaaactgga atgcatttgg







aagagaagaa cggtgctctt ctttcttccc cgggctcgcc







gtttttacac tagttcctga atggacctca ggcgccctgg







gacttgtgct cttgctggaa cccacataac gccggaagca







gacagaccga cttgcctgtt tcacggtgcc cgcttcccat







gagtccaaac ggaaaatttt cccacgggca tgtaagtcat







ctggaagtaa gctgtattga taataaagga aagcaaacac







aggagtgtgt gtattcaaca gaaataaatt cagaaagccc







tgaaatcaat ctcactgggt gtgtttaaaa atggcatttg







gggaatttct gggtcatttg tccagctgcg aaagctgcat







ctctgaagca cagtccctgt cccgcagtga gacttattta







tccgacgtgg tgtttccgtg gaaatgattg tgggaaatgg







ccccttcctt ttctctattt gctgactaga cttcatggtc







cctttctcgt caggtacagt gatcaaagtt gaccaacccc







agaggaaagc tgcccagggc acaactcagg gctccataga







accacagaat cttgggagca accctgctca agcacccaaa







tg






Claims
  • 1. An isolated polynucleotide encoding a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.1b, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11.
  • 2. An isolated polypeptide comprising a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11.
  • 3. A method of using a polynucleotide according to claim 1, wherein the polynucleotide is used in an assay to identify an inhibitor of a hDUB of claim 1.
  • 4. A method of using a polypeptide according to claim 2, wherein the polypeptide is used in an assay to identify an inhibitor of a hDUB of claim 2.
  • 5. A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of inhibiting a polypeptide according to claim 2.
  • 6. A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of inhibiting a polypeptide according to claim 2.
  • 7. A method of modulating an immune reaction during infection, by administering a compound capable of inhibiting a polypeptide according to claim 2.
  • 8. A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of altering regulation of transcription of a polynucleotide of claim 1.
  • 9. A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of altering regulation of transcription of a polynucleotide of claim 1.
  • 10. A method of modulating an immune reaction during infection, by administering a compound capable of altering regulation of transcription of a polynucleotide of claim 1.
  • 11. A method of identifying a modulator of a human deubiquitinating protease, wherein a compound is added to the reporter assay comprising a polynucleotide immediately 5′ to a human deubiquitinating protease selected from the group consisting of hDUB 4.1a, hDUB 4.1b, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11 operatively linked to a reporter gene, and the effect of the compound is determined.
Priority Claims (1)
Number Date Country Kind
GB0208404.4 Apr 2002 GB national
CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 10/371,905, filed on Feb. 20, 2003 which claims the benefit of U.S. Provisional No. 60/358,873, filed on Feb. 22, 2002 and U.S. Provisional No. 60/358,875, filed on Feb. 22, 2002 and U.S. Provisional No. 60/363,020, filed on Mar. 8, 2002 and claims priority to GB0208404.4, filed Apr. 12, 2002, which are hereby incorporated by reference herein in their entireties.

Provisional Applications (3)
Number Date Country
60358873 Feb 2002 US
60358875 Feb 2002 US
60363020 Mar 2002 US
Divisions (1)
Number Date Country
Parent 10371905 Feb 2003 US
Child 11685860 Mar 2007 US