STREPTOCOCCUS PNEUMONIAE POLYNUCLEOTIDES AND SEQUENCES

Abstract
The present invention provides polynucleotide sequences of the genome of Streptococcus pneumoniae, polypeptide sequences encoded by the polynucleotide sequences, corresponding polynucleotides and polypeptides, vectors and hosts comprising the polynucleotides, and assays and other uses thereof. The present invention further provides polynucleotide and polypeptide sequence information stored on computer readable media, and computer-based systems and methods which facilitate its use.
Description


FIELD OF THE INVENTION

[0001] The present invention relates to the field of molecular biology. In particular, it relates to, among other things, nucleotide sequences of Streptococcus pneumoniae, contigs, ORFs, fragments, probes, primers and related polynucleotides thereof, peptides and polypeptides encoded by the sequences, and uses of the polynucleotides and sequences thereof, such as in fermentation, polypeptide production, assays and pharmaceutical development, among others.


[0002] This application claims benefit of 35 U.S.C. section 119(e) based on copending U.S. Provisional Application Serial No. 60/029,960, filed Oct. 31, 1996.



BACKGROUND OF THE INVENTION

[0003]

Streptococcus pneumoniae
has been one of the most extensively studied microorganisms since its first isolation in 1881. It was the object of many investigations that led to important scientific discoveries. In 1928, Griffith observed that when heat-killed encapsulated pneumococci and live strains constitutively lacking any capsule were concomitantly injected into mice, the nonencapsulated could be converted into encapsulated pneumococci with the same capsular type as the heat-killed strain. Years later, the nature of this “transforming principle,” or carrier of genetic information, was shown to be DNA. (Avery, O. T., et al., J. Exp. Med., 79:137-157 (1944)).


[0004] In spite of the vast number of publications on S. pneumoniae many questions about its virulence are still unanswered, and this pathogen remains a major causative agent of serious human disease, especially community-acquired pneumonia. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991)). In addition, in developing countries, the pneumococcus is responsible for the death of a large number of children under the age of 5 years from pneumococcal pneumonia. The incidence of pneumococcal disease is highest in infants under 2 years of age and in people over 60 years of age. Pneumococci are the second most frequent cause (after Haemophilus influenzae type b) of bacterial meningitis and otitis media in children. With the recent introduction of conjugate vaccines for H. influenzae type b, pneumococcal meningitis is likely to become increasingly prominent. S. pneumoniae is the most important etiologic agent of community-acquired pneumonia in adults and is the second most common cause of bacterial meningitis behind Neisseria meningitidis.


[0005] The antibiotic generally prescribed to treat S. pneumoniae is benzylpenicillin, although resistance to this and to other antibiotics is found occasionally. Pneumococcal resistance to penicillin results from mutations in its penicillin-binding proteins. In uncomplicated pneumococcal pneumonia caused by a sensitive strain, treatment with penicillin is usually successful unless started too late. Erythromycin or clindamycin can be used to treat pneumonia in patients hypersensitive to penicillin, but resistant strains to these drugs exist. Broad spectrum antibiotics (e.g., the tetracyclines) may also be effective, although tetracycline-resistant strains are not rare. In spite of the availability of antibiotics, the mortality of pneumococcal bacteremia in the last four decades has remained stable between 25 and 29%. (Gillespie, S. H., et al., J. Med. Microbiol. 28:237-248 (1989).


[0006]

S. pneumoniae
is carried in the upper respiratory tract by many healthy individuals. It has been suggested that attachment of pneumococci is mediated by a disaccharide receptor on fibronectin, present on human pharyngeal epithelial cells. (Anderson, B. J., et al., J. Immunol. 142:2464-2468 (1989). The mechanisms by which pneumococci translocate from the nasopharynx to the lung, thereby causing pneumonia, or migrate to the blood, giving rise to bacteremia or septicemia, are poorly understood. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991).


[0007] Various proteins have been suggested to be involved in the pathogenicity of S. pneumoniae, however, only a few of them have actually been confirmed as virulence factors. Pneumococci produce an IgA1 protease that might interfere with host defense at mucosal surfaces. (Kornfield, S. J., et al., Rev. Inf. Dis. 3:521-534 (1981). S. pneumoniae also produces neuraminidase, an enzyme that may facilitate attachment to epithelial cells by cleaving sialic acid from the host glycolipids and gangliosides. Partially purified neuraminidase was observed to induce meningitis-like symptoms in mice; however, the reliability of this finding has been questioned because the neuraminidase preparations used were probably contaminated with cell wall products. Other pneumococcal proteins besides neuraminidase are involved in the adhesion of pneumococci to epithelial and endothelial cells. These pneumococcal proteins have as yet not been identified. Recently, Cundell et al., reported that peptide permeases can modulate pneumococcal adherence to epithelial and endothelial cells. It was, however, unclear whether these permeases function directly as adhesions or whether they enhance adherence by modulating the expression of pneumococcal adhesions. (DeVelasco, E. A., et al., Micro. Rev. 59:591-603 (1995). A better understanding of the virulence factors determining its pathogenicity will need to be developed to cope with the devastating effects of pneumococcal disease in humans.


[0008] Ironically, despite the prominent role of S. pneumoniae in the discovery of DNA, little is known about the molecular genetics of the organism. The S. pneumoniae genome consists of one circular, covalently closed, double-stranded DNA and a collection of so-called variable accessory elements, such as prophages, plasmids, transposons and the like. Most physical characteristics and almost all of the genes of S. pneumoniae are unknown. Among the few that have been identified, most have not been physically mapped or characterized in detail. Only a few genes of this organism have been sequenced. (See, for instance current versions of GENBANK and other nucleic acid databases, and references that relate to the genome of S. pneumoniae such as those set out elsewhere herein.)


[0009] It is clear that the etiology of diseases mediated or exacerbated by S. pneumoniae, infection involves the programmed expression of S. pneumoniae genes, and that characterizing the genes and their patterns of expression would add dramatically to our understanding of the organism and its host interactions. Knowledge of S. pneumoniae genes and genomic organization would improve our understanding of disease etiology and lead to improved and new ways of preventing, ameliorating, arresting and reversing diseases. Moreover, characterized genes and genomic fragments of S. pneumoniae would provide reagents for, among other things, detecting, characterizing and controlling S. pneumoniae infections. There is a need to characterize the genome of S. pneumoniae and for polynucleotides of this organism.



SUMMARY OF THE INVENTION

[0010] The present invention is based on the sequencing of fragments of the Streptococcus pneumoniae genome. The primary nucleotide sequences which were generated are provided in SEQ ID NOS:1-391.


[0011] The present invention provides the nucleotide sequence of several hundred contigs of the Streptococcus pneumoniae genome, which are listed in tables below and set out in the Sequence Listing submitted herewith, and representative fragments thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan. In one embodiment, the present invention is provided as contiguous strings of primary sequence information corresponding to the nucleotide sequences depicted in SEQ ID NOS:1-391.


[0012] The present invention further provides nucleotide sequences which are at least 95% identical to the nucleotide sequences of SEQ ID NOS: 1-391.


[0013] The nucleotide sequence of SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NOS:1-391 may be provided in a variety of mediums to facilitate its use. In one application of this embodiment, the sequences of the present invention are recorded on computer readable media. Such media includes, but is not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.


[0014] The present invention further provides systems, particularly computer-based systems which contain the sequence information herein described stored in a data storage means. Such systems are designed to identify commercially important fragments of the Streptococcus pneumoniae genome.


[0015] Another embodiment of the present invention is directed to fragments of the Streptococcus pneumoniae genome having particular structural or functional attributes. Such fragments of the Streptococcus pneumoniae genome of the present invention include, but are not limited to, fragments which encode peptides, hereinafter referred to as open reading frames or ORFs, fragments which modulate the expression of an operably linked ORF, hereinafter referred to as expression modulating fragments or EMFs, and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in a sample, hereinafter referred to as diagnostic fragments or DFs.


[0016] Each of the ORFs in fragments of the Streptococcus pneumoniae genome disclosed in Tables 1-3, and the EMFs found 5′ to the ORFs, can be used in numerous ways as polynucleotide reagents. For instance, the sequences can be used as diagnostic probes or amplification primers for detecting or determining the presence of a specific microbe in a sample, to selectively control gene expression in a host and in the production of polypeptides, such as polypeptides encoded by ORFs of the present invention, particular those polypeptides that have a pharmacological activity.


[0017] The present invention further includes recombinant constructs comprising one or more fragments of the Streptococcus pneumoniae genome of the present invention. The recombinant constructs of the present invention comprise vectors, such as a plasmid or viral vector, into which a fragment of the Streptococcus pneumoniae has been inserted.


[0018] The present invention further provides host cells containing any of the isolated fragments of the Streptococcus pneumoniae genome of the present invention. The host cells can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic cell, such as a yeast cell, or a procaryotic cell such as a bacterial cell.


[0019] The present invention is further directed to isolated polypeptides and proteins encoded by ORFs of the present invention. A variety of methods, well known to those of skill in the art, routinely may be utilized to obtain any of the polypeptides and proteins of the present invention. For instance, polypeptides and proteins of the present invention having relatively short, simple amino acid sequences readily can be synthesized using commercially available automated peptide synthesizers. Polypeptides and proteins of the present invention also may be purified from bacterial cells which naturally produce the protein. Yet another alternative is to purify polypeptide and proteins of the present invention from cells which have been altered to express them.


[0020] The invention further provides methods of obtaining homologs of the fragments of the Streptococcus pneumoniae genome of the present invention and homologs of the proteins encoded by the ORFs of the present invention. Specifically, by using the nucleotide and amino acid sequences disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.


[0021] The invention further provides antibodies which selectively bind polypeptides and proteins of the present invention. Such antibodies include both monoclonal and polyclonal antibodies.


[0022] The invention further provides hybridomas which produce the above-described antibodies. A hybridoma is an immortalized cell line which is capable of secreting a specific monoclonal antibody.


[0023] The present invention further provides methods of identifying test samples derived from cells which express one of the ORFs of the present invention, or a homolog thereof. Such methods comprise incubating a test sample with one or more of the antibodies of the present invention, or one or more of the DFs of the present invention, under conditions which allow a skilled artisan to determine if the sample contains the ORF or product produced therefrom.


[0024] In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the above-described assays.


[0025] Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the antibodies, or one of the DFs of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of bound antibodies or hybridized DFs.


[0026] Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents capable of binding to a polypeptide or protein encoded by one of the ORFs of the present invention. Specifically, such agents include, as further described below, antibodies, peptides, carbohydrates, pharmaceutical agents and the like. Such methods comprise steps of: (a) contacting an agent with an isolated protein encoded by one of the ORFs of the present invention; and (b) determining whether the agent binds to said protein.


[0027] The present genomic sequences of Streptococcus pneumoniae will be of great value to all laboratories working with this organism and for a variety of commercial purposes. Many fragments of the Streptococcus pneumoniae genome will be immediately identified by similarity searches against GenBank or protein databases and will be of immediate value to Streptococcus pneumoniae researchers and for immediate commercial value for the production of proteins or to control gene expression.


[0028] The methodology and technology for elucidating extensive genomic sequences of bacterial and other genomes has and will greatly enhance the ability to analyze and understand chromosomal organization. In particular, sequenced contigs and genomes will provide the models for developing tools for the analysis of chromosome structure and function, including the ability to identify genes within large segments of genomic DNA, the structure, position, and spacing of regulatory elements, the identification of genes with potential industrial applications, and the ability to do comparative genomic and molecular phylogeny.







DESCRIPTION OF THE FIGURES

[0029]
FIG. 1 is a block diagram of a computer system (102) that can be used to implement computer-based systems of present invention.


[0030]
FIG. 2 is a schematic diagram depicting the data flow and computer programs used to collect, assemble, edit and annotate the contigs of the Streptococcus pneumoniae genome of the present invention. Both Macintosh and Unix platforms are used to handle the AB 373 and 377 sequence data files, largely as described in Kerlavage et al., Proceedings of the Twenty-Sixth Annual Hawaii International Conference on System Sciences, 585, IEEE Computer Society Press, Washington, D.C. (1993). Factura (AB) is a Macintosh program designed for automatic vector sequence removal and end-trimming of sequence files. The program Loadis runs on a Macintosh platform and parses the feature data extracted from the sequence files by Factura to the Unix based Streptococcus pneumoniae relational database. Assembly of contigs (and whole genome sequences) is accomplished by retrieving a specific set of sequence files and their associated features using Extrseq, a Unix utility for retrieving sequences from an SQL database. The resulting sequence file is processed by seq_filter to trim portions of the sequences with more than 2% ambiguous nucleotides. The sequence files were assembled using TIGR Assembler, an assembly engine designed at The Institute for Genomic Research (TIGR) for rapid and accurate assembly of thousands of sequence fragments. The collection of contigs generated by the assembly step is loaded into the database with the lassie program. Identification of open reading frames (ORFs) is accomplished by processing contigs with zorf or GenMark. The ORFs are searched against S. pneumoniae sequences from GenBank and against all protein sequences using the BLASTN and BLASTP programs, described in Altschul et al., J. Mol. Biol. 215: 403-410 (1990)). Results of the ORF determination and similarity searching steps were loaded into the database. As described below, some results of the determination and the searches are set out in Tables 1-3.







DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0031] The present invention is based on the sequencing of fragments of the Streptococcus pneumoniae genome and analysis of the sequences. The primary nucleotide sequences generated by sequencing the fragments are provided in SEQ ID NOS:1-391. (As used herein, the “primary sequence” refers to the nucleotide sequence represented by the IUPAC nomenclature system.)


[0032] In addition to the aforementioned Streptococcus pneunoniae polynucleotide and polynucleotide sequences, the present invention provides the nucleotide sequences of SEQ ID NOS:1-391, or representative fragments thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan.


[0033] As used herein, a “representative fragment of the nucleotide sequence depicted in SEQ ID NOS:1-391” refers to any portion of the SEQ ID NOS:1-391 which is not presently represented within a publicly available database. Preferred representative fragments of the present invention are Streptococcus pneumoniae open reading frames (ORFs), expression modulating fragment (EMFs) and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in sample (DFs). A non-limiting identification of preferred representative fragments is provided in Tables 1-3. As discussed in detail below, the information provided in SEQ ID NOS: 1-391 and in Tables 1-3 together with routine cloning, synthesis, sequencing and assay methods will enable those skilled in the art to clone and sequence all “representative fragments” of interest, including open reading frames encoding a large variety of Streptococcus pneunoniae proteins.


[0034] While the presently disclosed sequences of SEQ ID NOS: 1-391 are highly accurate, sequencing techniques are not perfect and, in relatively rare instances, further investigation of a fragment or sequence of the invention may reveal a nucleotide sequence error present in a nucleotide sequence disclosed in SEQ ID NOS:1-391. However, once the present invention is made available (i.e., once the information in SEQ ID NOS:1-391 and Tables 1-3 has been made available), resolving a rare sequencing error in SEQ ID NOS: 1-391 will be well within the skill of the art. The present disclosure makes available sufficient sequence information to allow any of the described contigs or portions thereof to be obtained readily by straightforward application of routine techniques. Further sequencing of such polynucleotide may proceed in like manner using manual and automated sequencing methods which are employed ubiquitous in the art. Nucleotide sequence editing software is publicly available. For example, Applied Biosystem's (AB) AutoAssembler can be used as an aid during visual inspection of nucleotide sequences. By employing such routine techniques potential errors readily may be identified and the correct sequence then may be ascertained by targeting further sequencing effort, also of a routine nature, to the region containing the potential error.


[0035] Even if all of the very rare sequencing errors in SEQ ID NOS:1-391 were corrected, the resulting nucleotide sequences would still be at least 95% identical, nearly all would be at least 99% identical, and the great majority would be at least 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391.


[0036] As discussed elsewhere herein, polynucleotides of the present invention readily may be obtained by routine application of well known and standard procedures for cloning and sequencing DNA. Detailed methods for obtaining libraries and for sequencing are provided below, for instance. A wide variety of Streptococcus pneumoniae strains that can be used to prepare S. pneumoniae genomic DNA for cloning and for obtaining polynucleotides of the present invention are available to the public from recognized depository institutions, such as the American Type Culture Collection (ATCC). While the present invention is enabled by the sequences and other information herein disclosed, the S. pneumoniae strain that provided the DNA of the present Sequence Listing, Strain 7/87 14.8.91, has been deposited in the ATCC, as a convenience to those of skill in the art. As a further convenience, a library of S. pneumoniae genomic DNA, derived from the same strain, also has been deposited in the ATCC. The S. pneumoniae strain was deposited on Oct. 10, 1996, and was given Deposit No. 55840, and the cDNA library was deposited on Oct. 11, 1996 and was given Deposit No. 97755. The genomic fragments in the library are 15 to 20 kb fragments generated by partial Sau3A1 digestion and they are inserted into the BamHI site in the well-known lambda-derived vector lambda DASH II (Stratagene, La Jolla, Calif.). The provision of the deposits is not a waiver of any rights of the inventors or their assignees in the present subject matter.


[0037] The nucleotide sequences of the genomes from different strains of Streptococcus pneumoniae differ somewhat. However, the nucleotide sequences of the genomes of all Streptococcus pneumoniae strains will be at least 95% identical, in corresponding part, to the nucleotide sequences provided in SEQ ID NOS:1-391. Nearly all will be at least 99% identical and the great majority will be 99.9% identical.


[0038] Thus, the present invention further provides nucleotide sequences which are at least 95%, preferably 99% and most preferably 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391, in a form which can be readily used, analyzed and interpreted by the skilled artisan.


[0039] Methods for determining whether a nucleotide sequence is at least 95%, at least 99% or at least 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391 are routine and readily available to the skilled artisan. For example, the well known fasta algorithm described in Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85: 2444 (1988) can be used to generate the percent identity of nucleotide sequences. The BLASTN program also can be used to generate an identity score of polynucleotides compared to one another.



Computer Related Embodiments

[0040] The nucleotide sequences provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a polynucleotide sequence of SEQ ID NOS:1-391 may be “provided” in a variety of mediums to facilitate use thereof. As used herein, provided refers to a manufacture, other than an isolated nucleic acid molecule, which contains a nucleotide sequence of the present invention; i.e., a nucleotide sequence provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a polynucleotide of SEQ ID NOS:1-391. Such a manufacture provides a large portion of the Streptococcus pneumoniae genome and parts thereof (e.g., a Streptococcus pneumoniae open reading frame (ORF)) in a form which allows a skilled artisan to examine the manufacture using means not directly applicable to examining the Streptococcus pneumoniae genome or a subset thereof as it exists in nature or in purified form.


[0041] In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, “computer readable media” refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories, such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the present invention. Likewise, it will be clear to those of skill how additional computer readable media that may be developed also can be used to create analogous manufactures having recorded thereon a nucleotide sequence of the present invention.


[0042] As used herein, “recorded” refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently know methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information of the present invention. A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and MicroSoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data-processor structuring formats (e.g., text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention.


[0043] Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. Thus, by providing in computer readable form the nucleotide sequences of SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a sequence of SEQ ID NOS:1-391 the present invention enables the skilled artisan routinely to access the provided sequence information for a wide variety of purposes.


[0044] The examples which follow demonstrate how software which implements the BLAST (Altschul et al., J. Mol. Biol. 215:403-410 (1990)) and BLAZE (Brutlag et al., Comp. Chem. 17:203-207 (1993)) search algorithms on a Sybase system was used to identify open reading frames (ORFs) within the Streptococcus pneumoniae genome which contain homology to ORFs or proteins from both Streptococcus pneumoniae and from other organisms. Among the ORFs discussed herein are protein encoding fragments of the Streptococcus pneumoniae genome useful in producing commercially important proteins, such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.


[0045] The present invention further provides systems, particularly computer-based systems, which contain the sequence information described herein. Such systems are designed to identify, among other things, commercially important fragments of the Streptococcus pneumoniae genome.


[0046] As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based systems are suitable for use in the present invention.


[0047] As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means.


[0048] As used herein, “data storage means” refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.


[0049] As used herein, “search means” refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of the present genomic sequences which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. Examples of such software includes, but is not limited to, MacPattern (EMBL), BLASTN and BLASTX (NCBIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems.


[0050] As used herein, a “target sequence” can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length.


[0051] As used herein, “a target structural motif,” or “target motif,” refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzymic active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).


[0052] A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. A preferred format for an output means ranks fragments of the Streptococcus pneumoniae genomic sequences possessing varying degrees of homology to the target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences which contain various amounts of the target sequence or target motif and identifies the degree of homology contained in the identified fragment.


[0053] A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the Streptococcus pneumoniae genome. In the present examples, implementing software which implement the BLAST and BLAZE algorithms, described in Altschul et al., J. Mol. Biol. 215: 403-410 (1990), is used to identify open reading frames within the Streptococcus pneumoniae genome. A skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer-based systems of the present invention. Of course, suitable proprietary systems that may be known to those of skill also may be employed in this regard.


[0054]
FIG. 1 provides a block diagram of a computer system illustrative of embodiments of this aspect of present invention. The computer system 102 includes a processor 106 connected to a bus 104. Also connected to the bus 104 are a main memory 108 (preferably implemented as random access memory, RAM) and a variety of secondary storage devices 110, such as a hard drive 112 and a removable medium storage device 114. The removable medium storage device 114 may represent, for example, a floppy disk drive, a CD-ROM drive, a magnetic tape drive, etc. A removable storage medium 116 (such as a floppy disk, a compact disk, a magnetic tape, etc.) containing control logic and/or data recorded therein may be inserted into the removable medium storage device 114. The computer system 102 includes appropriate software for reading the control logic and/or the data from the removable medium storage device 114, once it is inserted into the removable medium storage device 114.


[0055] A nucleotide sequence of the present invention may be stored in a well known manner in the main memory 108, any of the secondary storage devices 110, and/or a removable storage medium 116. During execution, software for accessing and processing the genomic sequence (such as search tools, comparing tools, etc.) reside in main memory 108, in accordance with the requirements and operating parameters of the operating system, the hardware system and the software program or programs.



Biochemical Embodiments

[0056] Other embodiments of the present invention are directed to isolated fragments of the Streptococcus pneumoniae genome. The fragments of the Streptococcus pneumoniae genome of the present invention include, but are not limited to fragments which encode peptides and polypeptides, hereinafter open reading frames (ORFs), fragments which modulate the expression of an operably linked ORF, hereinafter expression modulating fragments (EMFs) and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in a sample, hereinafter diagnostic fragments (DFs).


[0057] As used herein, an “isolated nucleic acid molecule” or an “isolated fragment of the Streptococcus pneumoniae genome” refers to a nucleic acid molecule possessing a specific nucleotide sequence which has been subjected to purification means to reduce, from the composition, the number of compounds which are normally associated with the composition. Particularly, the term refers to the nucleic acid molecules having the sequences set out in SEQ ID NOS:1-391, to representative fragments thereof as described above, to polynucleotides at least 95%, preferably at least 99% and especially preferably at least 99.9% identical in sequence thereto, also as set out above.


[0058] A variety of purification means can be used to generate the isolated fragments of the present invention. These include, but are not limited to methods which separate constituents of a solution based on charge, solubility, or size.


[0059] In one embodiment, Streptococcus pneumoniae DNA can be enzymatically sheared to produce fragments of 15-20 kb in length. These fragments can then be used to generate a Streptococcus pneumoniae library by inserting them into lambda clones as described in the Examples below. Primers flanking, for example, an ORF, such as those enumerated in Tables 1-3 can then be generated using nucleotide sequence information provided in SEQ ID NOS:1-391. Well known and routine techniques of PCR cloning then can be used to isolate the ORF from the lambda DNA library or Streptococcus pneumoniae genomic DNA. Thus, given the availability of SEQ ID NOS:1-391, the information in Tables 1, 2 and 3, and the information that may be obtained readily by analysis of the sequences of SEQ ID NOS:1-391 using methods set out above, those of skill will be enabled by the present disclosure to isolate any ORF-containing or other nucleic acid fragment of the present invention.


[0060] The isolated nucleic acid molecules of the present invention include, but are not limited to single stranded and double stranded DNA, and single stranded RNA.


[0061] As used herein, an “open reading frame,” ORF, means a series of triplets coding for amino acids without any termination codons and is a sequence translatable into protein.


[0062] Tables 1, 2, and 3 list ORFs in the Streptococcus pneumoniae genomic contigs of the present invention that were identified as putative coding regions by the GeneMark software using organism-specific second-order Markov probability transition matrices. It will be appreciated that other criteria can be used, in accordance with well known analytical methods, such as those discussed herein, to generate more inclusive, more restrictive, or more selective lists.


[0063] Table 1 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that over a continuous region of at least 50 bases are 95% or more identical (by BLAST analysis) to a nucleotide sequence available through GenBank in October, 1997.


[0064] Table 2 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that are not in Table 1 and match, with a BLASTP probability score of 0.01 or less, a polypeptide sequence available through GenBank in October, 1997.


[0065] Table 3 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that do not match significantly, by BLASTP analysis, a polypeptide sequence available through GenBank in October, 1997.


[0066] In each table, the first and second columns identify the ORF by, respectively, contig number and ORF number within the contig; the third column indicates the first nucleotide of the ORF (actually the first nucleotide of the stop codon immediately preceeding the ORF), counting from the 5′ end of the contig strand; and the fourth column, “stop (nt)” indicates the last nucleotide of the stop codon defining the 3′end of the ORF.


[0067] In Tables 1 and 2, column five, lists the Reference for the closest matching sequence available through GenBank. These reference numbers are the databases entry numbers commonly used by those of skill in the art, who will be familiar with their denominators. Descriptions of the nomenclature are available from the National Center for Biotechnology Information. Column six in Tables 1 and 2 provides the gene name of the matching sequence; column seven provides the BLAST identity score and column eight the BLAST similarity score from the comparison of the ORF and the homologous gene; and column nine indicates the length in nucleotides of the highest scoring segment pair identified by the BLAST identity analysis.


[0068] Each ORF described in the tables is defined by “start (nt)” (5′) and “stop (nt)” (3′) nucleotide position numbers. These position numbers refer to the boundaries of each ORF and provide orientation with respect to whether the forward or reverse strand is the coding strand and which reading frame the coding sequence is contained. The “start” position is the first nucleotide of the triplet encoding a stop codon just 5′ to the ORF and the “stop” position is the last nucleotide of the triplet encoding the next in-frame stop codon (i.e., the stop codon at the 3′ end of the ORF). Those of ordinary skill in the art appreciate that preferred fragments within each ORF described in the table include fragments of each ORF which include the entire sequence from the delineated “start” and “stop” positions excepting the first and last three nucleotides since these encode stop codons. Thus, polynucleotides set out as ORFs in the tables but lacking the three (3) 5′ nucleotides and the three (3) 3′ nucleotides are encompassed by the present invention. Those of skill also appreciate that particularly preferred are fragments within each ORF that are polynucleotide fragments comprising polypeptide coding sequence. As defined herein, “coding sequence” includes the fragment within an ORF beginning at the first in-frame ATG (triplet encoding methionine) and ending with the last nucleotide prior to the triplet encoding the 3′ stop codon. Preferred are fragments comprising the entire coding sequence and fragments comprising the entire coding sequence, excepting the coding sequence for the N-terminal methionine. Those of skill appreciate that the N-terminal methionine is often removed during post-translational processing and that polynucleotides lacking the ATG can be used to facilitate production of N-termainal fusion proteins which may be benefical in the production or use of genetically engineered proteins. Of course, due to the degeneracy of the genetic code many polynucleotides can encode a given polypeptide. Thus, the invention further includes polynucleotides comprising a nucleotide sequence encoding a polypeptide sequence itself encoded by the coding sequence within an ORF described in Tables 1-3 herein. Further, polynucleotides at least 95%, preferably at least 99% and especially preferably at least 99.9% identical in sequence to the foregoing polynucleotides, are contemplated by the present invention.


[0069] Polypeptides encoded by polynucleotides described above and elsewhere herein are also provided by the present invention as are polypeptide comprising a an amino acid sequence at least about 95%, preferably at least 97% and even more preferably 99% identical to the amino acid sequence of a polypeptide encoded by an ORF shown in Tables 1-3. These polypeptides may or may not comprise an N-terminal methionine.


[0070] The concepts of percent identity and percent similarity of two polypeptide sequences is well understood in the art. For example, two polypeptides 10 amino acids in length which differ at three amino acid positions (e.g., at positions 1, 3 and 5) are said to have a percent identity of 70%. However, the same two polypeptides would be deemed to have a percent similarity of 80% if, for example at position 5, the amino acids moieties, although not identical, were “similar” (i.e., possessed similar biochemical characteristics). Many programs for analysis of nucleotide or amino acid sequence similarity, such as fasta and BLAST specifically list percent identity of a matching region as an output parameter. Thus, for instance, Tables 1 and 2 herein enumerate the percent identity of the highest scoring segment pair in each ORF and its listed relative. Further details concerning the algorithms and criteria used for homology searches are provided below and are described in the pertinent literature highlighted by the citations provided below.


[0071] It will be appreciated that other criteria can be used to generate more inclusive and more exclusive listings of the types set out in the tables. As those of skill will appreciate, narrow and broad searches both are useful. Thus, a skilled artisan can readily identify ORFs in contigs of the Streptococcus pneumoniae genome other than those listed in Tables 1-3, such as ORFs which are overlapping or encoded by the opposite strand of an identified ORF in addition to those ascertainable using the computer-based systems of the present invention.


[0072] As used herein, an “expression modulating fragment,” EMF, means a series of nucleotide molecules which modulates the expression of an operably linked ORF or EMF.


[0073] As used herein, a sequence is said to “modulate the expression of an operably linked sequence” when the expression of the sequence is altered by the presence of the EMF. EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are fragments which induce the expression or an operably linked ORF in response to a specific regulatory factor or physiological event.


[0074] EMF sequences can be identified within the contigs of the Streptococcus pneumoniae genome by their proximity to the ORFs provided in Tables 1-3. An intergenic segment, or a fragment of the intergenic segment, from about 10 to 200 nucleotides in length, taken from any one of the ORFs of Tables 1-3 will modulate the expression of an operably linked ORF in a fashion similar to that found with the naturally linked ORF sequence. As used herein, an “intergenic segment” refers to fragments of the Streptococcus pneumoniae genome which are between two ORF(s) herein described. EMFs also can be identified using known EMFs as a target sequence or target motif in the computer-based systems of the present invention. Further, the two methods can be combined and used together.


[0075] The presence and activity of an EMF can be confirmed using an EMF trap vector. An EMF trap vector contains a cloning site linked to a marker sequence. A marker sequence encodes an identifiable phenotype, such as antibiotic resistance or a complementing nutrition auxotrophic factor, which can be identified or assayed when the EMF trap vector is placed within an appropriate host under appropriate conditions. As described above, a EMF will modulate the expression of an operably linked marker sequence. A more detailed discussion of various marker sequences is provided below. A sequence which is suspected as being an EMF is cloned in all three reading frames in one or more restriction sites upstream from the marker sequence in the EMF trap vector. The vector is then transformed into an appropriate host using known procedures and the phenotype of the transformed host in examined under appropriate conditions. As described above, an EMF will modulate the expression of an operably linked marker sequence.


[0076] As used herein, a “diagnostic fragment,” DF, means a series of nucleotide molecules which selectively hybridize to Streptococcus pneumoniae sequences. DFs can be readily identified by identifying unique sequences within contigs of the Streptococcus pneumoniae genome, such as by using well-known computer analysis software, and by generating and testing probes or amplification primers consisting of the DF sequence in an appropriate diagnostic format which determines amplification or hybridization selectivity.


[0077] The sequences falling within the scope of the present invention are not limited to the specific sequences herein described, but also include allelic and species variations thereof. Allelic and species variations can be routinely determined by comparing the sequences provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferrably at least 99% and most at least preferably 99.9% identical to SEQ ID NOS:1-391, with a sequence from another isolate of the same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon for another which encodes the same amino acid is expressly contemplated. Any specific sequence disclosed herein can be readily screened for errors by resequencing a particular fragment, such as an ORF, in both directions (i.e., sequence both strands). Alternatively, error screening can be performed by sequencing corresponding polynucleotides of Streptococcus pneumoniae origin isolated by using part or all of the fragments in question as a probe or primer.


[0078] Preferred DFs of the present invention comprise at least about 17, preferrably at least about 20, and more preferrably at least about 50 contiguous nucleotides within an ORF set out in Tables 1-3. Most highly preferred DFs specifically hybridize to a polynucleotide containing the sequence of the ORF from which they are derived. Specific hybridization occurs even under stringent conditions defined elsewhere herein.


[0079] Each of the ORFs of the Streptococcus pneumoniae genome disclosed in Tables 1, 2 and 3, and the EMFs found 5′ to the ORFs, can be used as polynucleotide reagents in numerous ways. For example, the sequences can be used as diagnostic probes or diagnostic amplification primers to detect the presence of a specific microbe in a sample, particularly Streptococcus pneumoniae. Especially preferred in this regard are ORFs such as those of Table 3, which do not match previously characterized sequences from other organisms and thus are most likely to be highly selective for Streptococcus pneumoniae. Also particularly preferred are ORFs that can be used to distinguish between strains of Streptococcus pneumoniae, particularly those that distinguish medically important strain, such as drug-resistant strains.


[0080] In addition, the fragments of the present invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA. Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Information from the sequences of the present invention can be used to design antisense and triple helix-forming oligonucleotides. Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription, for triple-helix formation, or to the mRNA itself, for antisense inhibition. Both techniques have been demonstrated to be effective in model systems, and the requisite techniques are well known and involve routine procedures. Triple helix techniques are discussed in, for example, Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991). Antisense techniques in general are discussed in, for instance, Okano, J. Neurochem. 56:560 (1991) and Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)).


[0081] The present invention further provides recombinant constructs comprising one or more fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention. Certain preferred recombinant constructs of the present invention comprise a vector, such as a plasmid or viral vector, into which a fragment of the Streptococcus pneumoniae genome has been inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs of the present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. For vectors comprising the EMFs of the present invention, the vector may further comprise a marker sequence or heterologous ORF operably linked to the EMF.


[0082] Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs of the present invention. The following vectors are provided by way of example. Useful bacterial vectors include phagescript, PsiX174, pBluescript SK, pBS KS, pNH8a, pNH16a, pNH18a, pNH46a (available from Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (available from Pharmacia). Useful eukaryotic vectors include pWLneo, pSV2cat, pOG44, pXT1, pSG (available from Stratagene) pSVK3, pBPV, pMSG, pSVL (available from Pharmacia).


[0083] Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lacI, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein- I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.


[0084] The present invention further provides host cells containing any one of the isolated fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention, wherein the fragment has been introduced into the host cell using known methods. The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or a procaryotic cell, such as a bacterial cell.


[0085] A polynucleotide of the present invention, such as a recombinant construct comprising an ORF of the present invention, may be introduced into the host by a variety of well established techniques that are standard in the art, such as calcium phosphate transfection, DEAE, dextran mediated transfection and electroporation, which are described in, for instance, Davis, L. et al., BASIC METHODS IN MOLECULAR BIOLOGY (1986).


[0086] A host cell containing one of the fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to produce a heterologous protein under the control of the EMF. The present invention further provides isolated polypeptides encoded by the nucleic acid fragments of the present invention or by degenerate variants of the nucleic acid fragments of the present invention. By “degenerate variant” is intended nucleotide fragments which differ from a nucleic acid fragment of the present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy of the Genetic Code, encode an identical polypeptide sequence.


[0087] Preferred nucleic acid fragments of the present invention are the ORFs and subfragments thereof depicted in Tables 2 and 3 which encode proteins.


[0088] A variety of methodologies known in the art can be utilized to obtain any one of the isolated polypeptides or proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. Such short fragments as may be obtained most readily by synthesis are useful, for example, in generating antibodies against the native polypeptide, as discussed further below.


[0089] In an alternative method, the polypeptide or protein is purified from bacterial cells which naturally produce the polypeptide or protein. One skilled in the art can readily employ well-known methods for isolating polypeptides and proteins to isolate and purify polypeptides or proteins of the present invention produced naturally by a bacterial strain, or by other methods. Methods for isolation and purification that can be employed in this regard include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography.


[0090] The polypeptides and proteins of the present invention also can be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. Those skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one of the polypeptides or proteins of the present invention.


[0091] Any host/vector system can be used to express one or more of the ORFs of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, CV-1 cell, COS cells, and Sf9 cells, as well as prokaryotic host such as E. coli and B. subtilis. The most preferred cells are those which do not normally express the particular polypeptide or protein or which expresses the polypeptide or protein at low natural level.


[0092] “Recombinant,” as used herein, means that a polypeptide or protein is derived from recombinant (e.g., microbial or mammalian) expression systems. “Microbial” refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, “recombinant microbial” defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g., E. coli, will be free of glycosylation modifications; polypeptides or proteins expressed in yeast will have a glycosylation pattern different from that expressed in mammalian cells.


[0093] “Nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. Generally, DNA segments encoding the polypeptides and proteins provided by this invention are assembled from fragments of the Streptococcus pneumoniae genome and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.


[0094] Recombinant expression vehicle or vector” refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. The expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic regulatory elements necessary for gene expression in the host, including elements required to initiate and maintain transcription at a level sufficient for suitable expression of the desired polypeptide, including, for example, promoters and, where necessary, an enhancer and a polyadenylation signal; (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate signals to initiate translation at the beginning of the desired coding region and terminate translation at its end. Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an N-terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.


[0095] “Recombinant expression system” means host cells which have stably integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extra chromosomally. The cells can be prokaryotic or eukaryotic. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction of the regulatory elements linked to the DNA segment or synthetic gene to be expressed.


[0096] Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described in Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), the disclosure of which is hereby incorporated by reference in its entirety.


[0097] Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coli and S. cerevisiae TRP1 gene, and a promoter derived from a highly expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), alpha-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product.


[0098] Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector and, when desirable, provide amplification within the host.


[0099] Suitable prokaryotic hosts for transformation include strains of E. coli, B. subtilis, Salmonella typhimurium and various species within the genera Pseudomonas and Streptomyces. Others may, also be employed as a matter of choice.


[0100] As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pKK223-3 (available form Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (available from Promega Biotec, Madison, Wis., USA). These pBR322 “backbone” sections are combined with an appropriate promoter and the structural sequence to be expressed.


[0101] Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter, where it is inducible, is derepressed or induced by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period to provide for expression of the induced gene product. Thereafter cells are typically harvested, generally by centrifugation, disrupted to release expressed protein, generally by physical or chemical means, and the resulting crude extract is retained for further purification.


[0102] Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described in Gluzman, Cell 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines.


[0103] Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.


[0104] Recombinant polypeptides and proteins produced in bacterial culture is usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps.


[0105] The present invention further includes isolated polypeptides, proteins and nucleic acid molecules which are substantially equivalent to those herein described. As used herein, substantially equivalent can refer both to nucleic acid and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between reference and subject sequences. For purposes of the present invention, sequences having equivalent biological activity, and equivalent expression characteristics are considered substantially equivalent. For purposes of determining equivalence, truncation of the mature sequence should be disregarded.


[0106] The invention further provides methods of obtaining homologs from other strains of Streptococcus pneumoniae, of the fragments of the Streptococcus pneumoniae genome of the present invention and homologs of the proteins encoded by the ORFs of the present invention. As used herein, a sequence or protein of Streptococcus pneumoniae is defined as a homolog of a fragment of the Streptococcus pneumoniae fragments or contigs or a protein encoded by one of the ORFs of the present invention, if it shares significant homology to one of the fragments of the Streptococcus pneumoniae genome of the present invention or a protein encoded by one of the ORFs of the present invention. Specifically, by using the sequence disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.


[0107] As used herein, two nucleic acid molecules or proteins are said to “share significant homology” if the two contain regions which possess greater than 85% sequence (amino acid or nucleic acid) homology. Preferred homologs in this regard are those with more than 90% homology. Especially preferred are those with 93% or more homology. Among especially preferred homologs those with 95% or more homology are particularly preferred. Very particularly preferred among these are those with 97% and even more particularly preferred among those are homologs with 99% or more homology. The most preferred homologs among these are those with 99.9% homology or more. It will be understood that, among measures of homology, identity is particularly preferred in this regard.


[0108] Region specific primers or probes derived from the nucleotide sequence provided in SEQ ID NOS:1-391 or from a nucleotide sequence at least 95%, particularly at least 99%, especially at least 99.5% identical to a sequence of SEQ ID NOS:1-391 can be used to prime DNA synthesis and PCR amplification, as well as to identify colonies containing cloned DNA encoding a homolog. Methods suitable to this aspect of the present invention are well known and have been described in great detail in many publications such as, for example, Innis et al., PCR Protocols, Academic Press, San Diego, Calif. (1990)).


[0109] When using primers derived from SEQ ID NOS:1-391 or from a nucleotide sequence having an aforementioned identity to a sequence of SEQ ID NOS: 1-391, one skilled in the art will recognize that by employing high stringency conditions (e.g., annealing at 50-60° C. in 6× SSPC and 50% formamide, and washing at 50-65° C. in 0.5× SSPC) only sequences which are greater than 75% homologous to the primer will be amplified. By employing lower stringency conditions (e.g., hybridizing at 35-37° C. in 5× SSPC and 40-45% formamide, and washing at 42° C. in 0.5× SSPC), sequences which are greater than 40-50% homologous to the primer will also be amplified.


[0110] When using DNA probes derived from SEQ ID NOS:1-391, or from a nucleotide sequence having an aforementioned identity to a sequence of SEQ ID NOS:1-391, for colony/plaque hybridization, one skilled in the art will recognize that by employing high stringency conditions (e.g., hybridizing at 50-65° C. in 5×SSPC and 50% formamide, and washing at 50-65° C. in 0.5× SSPC), sequences having regions which are greater than 90% homologous to the probe can be obtained, and that by employing lower stringency conditions (e.g., hybridizing at 35-37° C. in 5× SSPC and 40-45% formamide, and washing at 42° C. in 0.5×SSPC), sequences having regions which are greater than 35-45% homologous to the probe will be obtained.


[0111] Any organism can be used as the source for homologs of the present invention so long as the organism naturally expresses such a protein or contains genes encoding the same. The most preferred organism for isolating homologs are bacteria which are closely related to Streptococcus pneumoniae.



Illustrative Uses of Compositions of the Invention

[0112] Each ORF provided in Tables 1 and 2 is identified with a function by homology to a known gene or polypeptide. As a result, one skilled in the art can use the polypeptides of the present invention for commercial, therapeutic and industrial purposes consistent with the type of putative identification of the polypeptide. Such identifications permit one skilled in the art to use the Streptococcus pneumoniae ORFs in a manner similar to the known type of sequences for which the identification is made; for example, to ferment a particular sugar source or to produce a particular metabolite. A variety of reviews illustrative of this aspect of the invention are available, including the following reviews on the industrial use of enzymes, for example, BIOCHEMICAL ENGINEERING AND BIOTECHNOLOGY HANDBOOK, 2nd Ed., MacMillan Publications, Ltd. NY (1991) and BIOCATALYSTS IN ORGANIC SYNTHESES, Tramper et al., Eds., Elsevier Science Publishers, Amsterdam, The Netherlands (1985). A variety of exemplary uses that illustrate this and similar aspects of the present invention are discussed below.


[0113] 1. Biosynthetic Enzymes


[0114] Open reading frames encoding proteins involved in mediating the catalytic reactions involved in intermediary and macromolecular metabolism, the biosynthesis of small molecules, cellular processes and other functions includes enzymes involved in the degradation of the intermediary products of metabolism, enzymes involved in central intermediary metabolism, enzymes involved in respiration, both aerobic and anaerobic, enzymes involved in fermentation, enzymes involved in ATP proton motor force conversion, enzymes involved in broad regulatory function, enzymes involved in amino acid synthesis, enzymes involved in nucleotide synthesis, enzymes involved in cofactor and vitamin synthesis, can be used for industrial biosynthesis.


[0115] The various metabolic pathways present in Streptococcus pneumoniae can be identified based on absolute nutritional requirements as well as by examining the various enzymes identified in Table 1-3 and SEQ ID NOS:1-391.


[0116] Of particular interest are polypeptides involved in the degradation of intermediary metabolites as well as non-macromolecular metabolism. Such enzymes include amylases, glucose oxidases, and catalase.


[0117] Proteolytic enzymes are another class of commercially important enzymes. Proteolytic enzymes find use in a number of industrial processes including the processing of flax and other vegetable fibers, in the extraction, clarification and depectinization of fruit juices, in the extraction of vegetables' oil and in the maceration of fruits and vegetables to give unicellular fruits. A detailed review of the proteolytic enzymes used in the food industry is provided in Rombouts et al., Symbiosis 21:79 (1986) and Voragen et al. in Biocatalysts In Agricultural Biotechnology, Whitaker et al., Eds., American Chemical Society Symposium Series 389:93 (1989).


[0118] The metabolism of sugars is an important aspect of the primary metabolism of Streptococcus pneumoniae. Enzymes involved in the degradation of sugars, such as, particularly, glucose, galactose, fructose and xylose, can be used in industrial fermentation. Some of the important sugar transforming enzymes, from a commercial viewpoint, include sugar isomerases such as glucose isomerase. Other metabolic enzymes have found commercial use such as glucose oxidases which produces ketogulonic acid (KGA). KGA is an intermediate in the commercial production of ascorbic acid using the Reichstein's procedure, as described in Krueger et al., Biotechnology 6(A), Rhine et al., Eds., Verlag Press, Weinheim, Germany (1984).


[0119] Glucose oxidase (GOD) is commercially available and has been used in purified form as well as in an immobilized form for the deoxygenation of beer. See, for instance, Hartmeir et al., Biotechnology Letters 1:21 (1979). The most important application of GOD is the industrial scale fermentation of gluconic acid. Market for gluconic acids which are used in the detergent, textile, leather, photographic, pharmaceutical, food, feed and concrete industry, as described, for example, in Bigelis et al., beginning on page 357 in GENE MANIPULATIONS AND FUNGI; Benett et al., Eds., Academic Press, New York (1985). In addition to industrial applications, GOD has found applications in medicine for quantitative determination of glucose in body fluids recently in biotechnology for analyzing syrups from starch and cellulose hydrosylates. This application is described in Owusu et al., Biochem. et Biophysica. Acta. 872:83 (1986), for instance.


[0120] The main sweetener used in the world today is sugar which comes from sugar beets and sugar cane. In the field of industrial enzymes, the glucose isomerase process shows the largest expansion in the market today. Initially, soluble enzymes were used and later immobilized enzymes were developed (Krueger et al., Biotechnology, The Textbook of Industrial Microbiology, Sinauer Associated Incorporated, Sunderland, Mass. (1990)). Today, the use of glucose-produced high fructose syrups is by far the largest industrial business using immobilized enzymes. A review of the industrial use of these enzymes is provided by Jorgensen, Starch 40:307 (1988).


[0121] Proteinases, such as alkaline serine proteinases, are used as detergent additives and thus represent one of the largest volumes of microbial enzymes used in the industrial sector. Because of their industrial importance, there is a large body of published and unpublished information regarding the use of these enzymes in industrial processes. (See Faultman et al., Acid Proteases Structure Function and Biology, Tang, J., ed., Plenum Press, New York (1977) and Godfrey et al., Industrial Enzymes, MacMillan Publishers, Surrey, UK (1983) and Hepner et al., Report Industrial Enzymes by 1990, Hel Hepner & Associates, London (1986)).


[0122] Another class of commercially usable proteins of the present invention are the microbial lipases, described by, for instance, Macrae et al., Philosophical Transactions of the Chiral Society of London 310:227 (1985) and Poserke, Journal of the American Oil Chemist Society 61:1758 (1984). A major use of lipases is in the fat and oil industry for the production of neutral glycerides using lipase catalyzed inter-esterification of readily available triglycerides. Application of lipases include the use as a detergent additive to facilitate the removal of fats from fabrics in the course of the washing procedures.


[0123] The use of enzymes, and in particular microbial enzymes, as catalyst for key steps in the synthesis of complex organic molecules is gaining popularity at a great rate. One area of great interest is the preparation of chiral intermediates. Preparation of chiral intermediates is of interest to a wide range of synthetic chemists particularly those scientists involved with the preparation of new pharmaceuticals, agrochemicals, fragrances and flavors. (See Davies et al., Recent Advances in the Generation of Chiral Intermediates Using Enzymes, CRC Press, Boca Raton, Fla. (1990)). The following reactions catalyzed by enzymes are of interest to organic chemists: hydrolysis of carboxylic acid esters, phosphate esters, amides and nitrites, esterification reactions, trans-esterification reactions, synthesis of amides, reduction of alkanones and oxoalkanates, oxidation of alcohols to carbonyl compounds, oxidation of sulfides to sulfoxides, and carbon bond forming reactions such as the aldol reaction.


[0124] When considering the use of an enzyme encoded by one of the ORFs of the present invention for biotransformation and organic synthesis it is sometimes necessary to consider the respective advantages and disadvantages of using a microorganism as opposed to an isolated enzyme. Pros and cons of using a whole cell system on the one hand or an isolated partially purified enzyme on the other hand, has been described in detail by Bud et al., Chemistry in Britain (1987), p. 127.


[0125] Amino transferases, enzymes involved in the biosynthesis and metabolism of amino acids, are useful in the catalytic production of amino acids. The advantages of using microbial based enzyme systems is that the amino transferase enzymes catalyze the stereo-selective synthesis of only L-amino acids and generally possess uniformly high catalytic rates. A description of the use of amino transferases for amino acid production is provided by Roselle-David, Methods of Enzymology 136:479 (1987).


[0126] Another category of useful proteins encoded by the ORFs of the present invention include enzymes involved in nucleic acid synthesis, repair, and recombination.


[0127] 2. Generation of Antibodies


[0128] As described here, the proteins of the present invention, as well as homologs thereof, can be used in a variety of procedures and methods known in the art which are currently applied to other proteins. The proteins of the present invention can further be used to generate an antibody which selectively binds the protein. Such antibodies can be either monoclonal or polyclonal antibodies, as well fragments of these antibodies, and humanized forms.


[0129] The invention further provides antibodies which selectively bind to one of the proteins of the present invention and hybridomas which produce these antibodies. A hybridoma is an immortalized cell line which is capable of secreting a specific monoclonal antibody.


[0130] In general, techniques for preparing polyclonal and monoclonal antibodies as well as hybridomas capable of producing the desired antibody are well known in the art (Campbell, A. M., Monoclonal Antibody Technology: Laboratory Techniques In Biochemistry And Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984); St. Groth et al., J. Immunol. Methods 35: 1-21 (1980), Kohler and Milstein, Nature 256:495-497 (1975)), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today 4:72 (1983), pgs. 77-96 of Cole et al., in Monoclonal Antibodies And Cancer Therapy, Alan R. Liss, Inc. (1985)). Any animal (mouse, rabbit, etc.) which is known to produce antibodies can be immunized with the pseudogene polypeptide. Methods for immunization are well known in the art. Such methods include subcutaneous or interperitoneal injection of the polypeptide. One skilled in the art will recognize that the amount of the protein encoded by the ORF of the present invention used for immunization will vary based on the animal which is immunized, the antigenicity of the peptide and the site of injection.


[0131] The protein which is used as an immunogen may be modified or administered in an adjuvant in order to increase the protein's antigenicity. Methods of increasing the antigenicity of a protein are well known in the art and include, but are not limited to coupling the antigen with a heterologous protein (such as globulin or galactosidase) or through the inclusion of an adjuvant during immunization.


[0132] For monoclonal antibodies, spleen cells from the immunized animals are removed, fused with myeloma cells, such as SP2/0-Ag14 myeloma cells, and allowed to become monoclonal antibody producing hybridoma cells.


[0133] Any one of a number of methods well known in the art can be used to identify the hybridoma cell which produces an antibody with the desired characteristics. These include screening the hybridomas with an ELISA assay, western blot analysis, or radioimmunoassay (Lutz et al., Exp. Cell Res. 175:109-124 (1988)).


[0134] Hybridomas secreting the desired antibodies are cloned and the class and subclass is determined using procedures known in the art (Campbell, A. M., Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984)).


[0135] Techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778) can be adapted to produce single chain antibodies to proteins of the present invention.


[0136] For polyclonal antibodies, antibody containing antisera is isolated from the immunized animal and is screened for the presence of antibodies with the desired specificity using one of the above-described procedures.


[0137] The present invention further provides the above- described antibodies in detectably labelled form. Antibodies can be detectably labelled through the use of radioisotopes, affinity labels (such as biotin, avidin, etc.), enzymatic labels (such as horseradish peroxidase, alkaline phosphatase, etc.) fluorescent labels (such as FITC or rhodamine, etc.), paramagnetic atoms, etc. Procedures for accomplishing such labeling are well-known in the art, for example see Sternberger et al., J. Histochem. Cytochem. 18:315 (1970); Bayer, E. A. et al., Meth. Enzym. 62:308 (1979); Engval, E. et al., Immunol. 109:129 (1972); Goding, J. W., J. Immunol. Meth. 13:215 (1976)).


[0138] The labeled antibodies of the present invention can be used for in vitro, in vivo, and in situ assays to identify cells or tissues in which a fragment of the Streptococcus pneumoniae genome is expressed.


[0139] The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and sepharose, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D. M. et al., “Handbook of Experimental Immunology” 4th Ed., Blackwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W. D. et al., Meth. Enzym. 34 Academic Press, N.Y. (1974)). The immobilized antibodies of the present invention can be used for in vitro, in vivo, and in situ assays as well as for immunoaffinity purification of the proteins of the present invention.


[0140] 3. Diagnostic Assays and Kits


[0141] The present invention further provides methods to identify the expression of one of the ORFs of the present invention, or homolog thereof, in a test sample, using one of the DFs or antibodies of the present invention.


[0142] In detail, such methods comprise incubating a test sample with one or more of the antibodies or one or more of the DFs of the present invention and assaying for binding of the DFs or antibodies to components within the test sample.


[0143] Conditions for incubating a DF or antibody with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the DF or antibody used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the DFs or antibodies of the present invention. Examples of such assays can be found in Chard, T., An Introduction to Radioimmunoassay and Related Techniques, Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G. R. et al., Techniques in Immunocytochemistry, Academic Press, Orlando, Fla. Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of Enzyme Immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1985).


[0144] The test samples of the present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized.


[0145] In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention.


[0146] Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the DFs or antibodies of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound DF or antibody.


[0147] In detail, a compartmentalized kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or DF.


[0148] Types of detection reagents include labelled nucleic acid probes, labelled secondary antibodies, or in the alternative, if the primary antibody is labelled, the enzymatic, or antibody binding reagents which are capable of reacting with the labelled antibody. One skilled in the art will readily recognize that the disclosed DFs and antibodies of the present invention can be readily incorporated into one of the established kit formats which are well known in the art.


[0149] 4. Screening Assay for Binding Agents


[0150] Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents which bind to a protein encoded by one of the ORFs of the present invention or to one of the fragments and the Streptococcus pneumoniae fragment and contigs herein described.


[0151] In general, such methods comprise steps of:


[0152] (a) contacting an agent with an isolated protein encoded by one of the ORFs of the present invention, or an isolated fragment of the Streptococcus pneumoniae genome; and


[0153] (b) determining whether the agent binds to said protein or said fragment.


[0154] The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques.


[0155] For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF of the present invention.


[0156] Alternatively, agents may be rationally selected or designed. As used herein, an agent is said to be “rationally selected or designed” when the agent is chosen based on the configuration of the particular protein. For example, one skilled in the art can readily adapt currently available procedures to generate peptides, pharmaceutical agents and the like capable of binding to a specific peptide sequence in order to generate rationally designed antipeptide peptides, for example see Hurby et al., “Application of Synthetic Peptides: Antisense Peptides,” in Synthetic Peptides, A User's Guide, W. H. Freeman, NY (1992), pp. 289-307, and Kaspczak et al., Biochemistry 28:9230-8 (1989), or pharmaceutical agents, or the like.


[0157] In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one of the ORFs or EMFs of the present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control.


[0158] One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulfhydryl or polymeric derivatives which have base attachment capacity.


[0159] Agents suitable for use in these methods usually contain 20 to 40 bases and are designed to be complementary to a region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991)) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)). Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention can be used to design antisense and triple helix-forming oligonucleotides, and other DNA binding agents.


[0160] 5. Pharmaceutical Compositions and Vaccines


[0161] The present invention further provides pharmaceutical agents which can be used to modulate the growth or pathogenicity of Streptococcus pneumoniae, or another related organism, in vivo or in vitro. As used herein, a “pharmaceutical agent” is defined as a composition of matter which can be formulated using known techniques to provide a pharmaceutical compositions. As used herein, the “pharmaceutical agents of the present invention” refers the pharmaceutical agents which are derived from the proteins encoded by the ORFs of the present invention or are agents which are identified using the herein described assays.


[0162] As used herein, a pharmaceutical agent is said to “modulate the growth pathogenicity of Streptococcus pneumoniae or a related organism, in vivo or in vitro,” when the agent reduces the rate of growth, rate of division, or viability of the organism in question. The pharmaceutical agents of the present invention can modulate the growth or pathogenicity of an organism in many fashions, although an understanding of the underlying mechanism of action is not needed to practice the use of the pharmaceutical agents of the present invention. Some agents will modulate the growth by binding to an important protein thus blocking the biological activity of the protein, while other agents may bind to a component of the outer surface of the organism blocking attachment or rendering the organism more prone to act the bodies nature immune system. Alternatively, the agent may comprise a protein encoded by one of the ORFs of the present invention and serve as a vaccine. The development and use of a vaccine based on outer membrane components are well known in the art.


[0163] As used herein, a “related organism” is a broad term which refers to any organism whose growth can be modulated by one of the pharmaceutical agents of the present invention. In general, such an organism will contain a homolog of the protein which is the target of the pharmaceutical agent or the protein used as a vaccine. As such, related organisms do not need to be bacterial but may be fungal or viral pathogens.


[0164] The pharmaceutical agents and compositions of the present invention may be administered in a convenient manner, such as by the oral, topical, intravenous, intraperitoneal, intramuscular, subcutaneous, intranasal or intradermal routes. The pharmaceutical compositions are administered in an amount which is effective for treating and/or prophylaxis of the specific indication. In general, they are administered in an amount of at least about 1 mg/kg body weight and in most cases they will be administered in an amount not in excess of about 1 g/kg body weight per day. In most cases, the dosage is from about 0.1 mg/kg to about 10 g/kg body weight daily, taking into account the routes of administration, symptoms, etc.


[0165] The agents of the present invention can be used in native form or can be modified to form a chemical derivative. As used herein, a molecule is said to be a “chemical derivative” of another molecule when it contains additional chemical moieties not normally a part of the molecule. Such moieties may improve the molecule's solubility, absorption, biological half life, etc. The moieties may alternatively decrease the toxicity of the molecule, eliminate or attenuate any undesirable side effect of the molecule, etc. Moieties capable of mediating such effects are disclosed in, among other sources, REMINGTON'S PHARMACEUTICAL SCIENCES (1980) cited elsewhere herein.


[0166] For example, such moieties may change an immunological character of the functional derivative, such as affinity for a given antibody. Such changes in immunomodulation activity are measured by the appropriate assay, such as a competitive type immunoassay. Modifications of such protein properties as redox or thermal stability, biological half-life, hydrophobicity, susceptibility to proteolytic degradation or the tendency to aggregate with carriers or into multimers also may be effected in this way and can be assayed by methods well known to the skilled artisan.


[0167] The therapeutic effects of the agents of the present invention may be obtained by providing the agent to a patient by any suitable means (e.g., inhalation, intravenously, intramuscularly, subcutaneously, enterally, or parenterally). It is preferred to administer the agent of the present invention so as to achieve an effective concentration within the blood or tissue in which the growth of the organism is to be controlled. To achieve an effective blood concentration, the preferred method is to administer the agent by injection. The administration may be by continuous infusion, or by single or multiple injections.


[0168] In providing a patient with one of the agents of the present invention, the dosage of the administered agent will vary depending upon such factors as the patient's age, weight, height, sex, general medical condition, previous medical history, etc. In general, it is desirable to provide the recipient with a dosage of agent which is in the range of from about 1 pg/kg to 10 mg/kg (body weight of patient), although a lower or higher dosage may be administered. The therapeutically effective dose can be lowered by using combinations of the agents of the present invention or another agent.


[0169] As used herein, two or more compounds or agents are said to be administered “in combination” with each other when either (1) the physiological effects of each compound, or (2) the serum concentrations of each compound can be measured at the same time. The composition of the present invention can be administered concurrently with, prior to, or following the administration of the other agent.


[0170] The agents of the present invention are intended to be provided to recipient subjects in an amount sufficient to decrease the rate of growth (as defined above) of the target organism.


[0171] The administration of the agent(s) of the invention may be for either a “prophylactic” or “therapeutic” purpose. When provided prophylactically, the agent(s) are provided in advance of any symptoms indicative of the organisms growth. The prophylactic administration of the agent(s) serves to prevent, attenuate, or decrease the rate of onset of any subsequent infection. When provided therapeutically, the agent(s) are provided at (or shortly after) the onset of an indication of infection. The therapeutic administration of the compound(s) serves to attenuate the pathological symptoms of the infection and to increase the rate of recovery.


[0172] The agents of the present invention are administered to a subject, such as a mammal, or a patient, in a pharmaceutically acceptable form and in a therapeutically effective concentration. A composition is said to be “pharmacologically acceptable” if its administration can be tolerated by a recipient patient. Such an agent is said to be administered in a “therapeutically effective amount” if the amount administered is physiologically significant. An agent is physiologically significant if its presence results in a detectable change in the physiology of a recipient patient.


[0173] The agents of the present invention can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby these materials, or their functional derivatives, are combined in a mixture with a pharmaceutically acceptable carrier vehicle. Suitable vehicles and their formulation, inclusive of other human proteins, e.g., human serum albumin, are described, for example, in REMINGTON'S PHARMACEUTICAL SCIENCES, 16th Ed., Osol, A., Ed., Mack Publishing, Easton, Pa. (1980). In order to form a pharmaceutically acceptable composition suitable for effective administration, such compositions will contain an effective amount of one or more of the agents of the present invention, together with a suitable amount of carrier vehicle.


[0174] Additional pharmaceutical methods may be employed to control the duration of action. Control release preparations may be achieved through the use of polymers to complex or absorb one or more of the agents of the present invention. The controlled delivery may be effectuated by a variety of well known techniques, including formulation with macromolecules such as, for example, polyesters, polyamino acids, polyvinyl, pyrrolidone, ethylenevinylacetate, methylcellulose, carboxymethylcellulose, or protamine, sulfate, adjusting the concentration of the macromolecules and the agent in the formulation, and by appropriate use of methods of incorporation, which can be manipulated to effectuate a desired time course of release. Another possible method to control the duration of action by controlled release preparations is to incorporate agents of the present invention into particles of a polymeric material such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylene vinylacetate copolymers. Alternatively, instead of incorporating these agents into polymeric particles, it is possible to entrap these materials in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization with, for example, hydroxymethylcellulose or gelatine-microcapsules and poly(methylmethacylate) microcapsules, respectively, or in colloidal drug delivery systems, for example, liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules or in macroemulsions. Such techniques are disclosed in REMINGTON'S PHARMACEUTICAL SCIENCES (1980).


[0175] The invention further provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.


[0176] In addition, the agents of the present invention may be employed in conjunction with other therapeutic compounds.


[0177] 6. Shot-Gun Approach to Megabase DNA Sequencing


[0178] The present invention further demonstrates that a large sequence can be sequenced using a random shotgun approach. This procedure, described in detail in the examples that follow, has eliminated the up front cost of isolating and ordering overlapping or contiguous subclones prior to the start of the sequencing protocols.


[0179] Certain aspects of the present invention are described in greater detail in the examples that follow. The examples are provided by way of illustration. Other aspects and embodiments of the present invention are contemplated by the inventors, as will be clear to those of skill in the art from reading the present disclosure.



Illustrative Examples

[0180] Libraries and Sequencing


[0181] 1. Shotgun Sequencing Probability Analysis


[0182] The overall strategy for a shotgun approach to whole genome sequencing follows from the Lander and Waterman (Landerman and Waterman, Genomics 2:231(1988)) application of the equation for the Poisson distribution. According to this treatment, the probability, P , that any given base in a sequence of size L, in nucleotides, is not sequenced after a certain amount, n, in nucleotides, of random sequence has been determined can be calculated by the equation P=e−m, where m is L/n, the fold coverage. For instance, for a genome of 2.8 Mb, m=1 when 2.8 Mb of sequence has been randomly generated (1× coverage). At that point, P=e−1=0.37. The probability that any given base has not been sequenced is the same as the probability that any region of the whole sequence L has not been determined and, therefore, is equivalent to the fraction of the whole sequence that has yet to be determined. Thus, at one-fold coverage, approximately 37% of a polynucleotide of size L, in nucleotides has not been sequenced. When 14 Mb of sequence has been generated, coverage is 5× for a 2.8 Mb and the unsequenced fraction drops to 0.0067 or 0.67%. 5× coverage of a 2.8 Mb sequence can be attained by sequencing approximately 17,000 random clones from both insert ends with an average sequence read length of 410 bp.


[0183] Similarly, the total gap length, G, is determined by the equation G=Le−m, and the average gap size, g, follows the equation, g=L/n. Thus, 5× coverage leaves about 240 gaps averaging about 82 bp in size in a sequence of a polynucleotide 2.8 Mb long.


[0184] The treatment above is essentially that of Lander and Waterman, Genomics 2: 231 (1988).


[0185] 2. Random Library Construction


[0186] In order to approximate the random model described above during actual sequencing, a nearly ideal library of cloned genomic fragments is required. The following library construction procedure was developed to achieve this end.


[0187]

Streptococcus pneumoniae
DNA is prepared by phenol extraction. A mixture containing 200 μg DNA in 1.0 ml of 300 mM sodium acetate, 10 mM Tris-HCl, 1 mM Na-EDTA, 50% glycerol is processed through a nebulizer (IPI Medical Products) with a stream of nitrogen adjusted to 35 Kpa for 2 minutes. The sonicated DNA is ethanol precipitated and redissolved in 500 μl TE buffer.


[0188] To create blunt-ends, a 100 μl aliquot of the resuspended DNA is digested with 5 units of BAL31 nuclease (New England BioLabs) for 10 min at 30° C. in 200 μl BAL31 buffer. The digested DNA is phenol-extracted, ethanol-precipitated, redissolved in 100 μl TE buffer, and then size-fractionated by electrophoresis through a 1.0% low melting temperature agarose gel. The section containing DNA fragments 1.6-2.0 kb in size is excised from the gel, and the LGT agarose is melted and the resulting solution is extracted with phenol to separate the agarose from the DNA. DNA is ethanol precipitated and redissolved in 20 μl of TE buffer for ligation to vector.


[0189] A two-step ligation procedure is used to produce a plasmid library with 97% inserts, of which >99% were single inserts. The first ligation mixture (50 ul) contains 2 μg of DNA fragments, 2 μg pUC18 DNA (Pharmacia) cut with SmaI and dephosphorylated with bacterial alkaline phosphatase, and 10 units of T4 ligase (GIBCO/BRL) and is incubated at 14° C. for 4 hr. The ligation mixture then is phenol extracted and ethanol precipitated, and the precipitated DNA is dissolved in 20 μl TE buffer and electrophoresed on a 1.0% low melting agarose gel. Discrete bands in a ladder are visualized by ethidium bromide-staining and UV illumination and identified by size as insert (I), vector (v), v+I, v+2i, v+3i, etc. The portion of the gel containing v+I DNA is excised and the v+I DNA is recovered and resuspended into 20 μl TE. The v+I DNA then is blunt-ended by T4 polymerase treatment for 5 min. at 37° C. in a reaction mixture (50 ul) containing the v+I linears, 500 μM each of the 4 dNTPs, and 9 units of T4 polymerase (New England BioLabs), under recommended buffer conditions. After phenol extraction and ethanol precipitation the repaired v+I linears are dissolved in 20 μl TE. The final ligation to produce circles is carried out in a 50 μl reaction containing 5 μl of v+I linears and 5 units of T4 ligase at 14° C. overnight. After 10 min. at 70° C. the following day, the reaction mixture is stored at −20° C.


[0190] This two-stage procedure results in a molecularly random collection of single-insert plasmid recombinants with minimal contamination from double-insert chimeras (<1%) or free vector (<3%).


[0191] Since deviation from randomness can arise from propagation the DNA in the host, E. coli host cells deficient in all recombination and restriction functions (A. Greener, Strategies 3 (1):5 (1990)) are used to prevent rearrangements, deletions, and loss of clones by restriction. Furthermore, transformed cells are plated directly on antibiotic diffusion plates to avoid the usual broth recovery phase which allows multiplication and selection of the most rapidly growing cells.


[0192] Plating is carried out as follows. A 100 μl aliquot of Epicurian Coli SURE II Supercompetent Cells (Stratagene 200152) is thawed on ice and transferred to a chilled Falcon 2059 tube on ice. A 1.7 μl aliquot of 1.42 M beta-mercaptoethanol is added to the aliquot of cells to a final concentration of 25 mM. Cells are incubated on ice for 10 min. A 1 μl aliquot of the final ligation is added to the cells and incubated on ice for 30 min. The cells are heat pulsed for 30 sec. at 42° C. and placed back on ice for 2 min. The outgrowth period in liquid culture is eliminated from this protocol in order to minimize the preferential growth of any given transformed cell. Instead the transformation mixture is plated directly on a nutrient rich SOB plate containing a 5 ml bottom layer of SOB agar (5% SOB agar: 20 g tryptone, 5 g yeast extract, 0.5 g NaCl, 1.5% Difco Agar per liter of media). The 5 ml bottom layer is supplemented with 0.4 ml of 50 mg/ml ampicillin per 100 ml SOB agar. The 15 ml top layer of SOB agar is supplemented with 1 ml X-Gal (2%), 1 ml MgCl (1 M), and 1 ml MgSO /100 ml SOB agar. The 15 ml top layer is poured just prior to plating. Our titer is approximately 100 colonies/10 μl aliquot of transformation.


[0193] All colonies are picked for template preparation regardless of size. Thus, only clones lost due to “poison” DNA or deleterious gene products are deleted from the library, resulting in a slight increase in gap number over that expected.


[0194] 3. Random DNA Sequencing


[0195] High quality double stranded DNA plasmid templates are prepared using a “boiling bead” method developed in collaboration with Advanced Genetic Technology Corp. (Gaithersburg, Md.) (Adams et al., Science 252:1651 (1991); Adams et al., Nature 355:632 (1992)). Plasmid preparation is performed in a 96-well format for all stages of DNA preparation from bacterial growth through final DNA purification. Template concentration is determined using Hoechst Dye and a Millipore Cytofluor. DNA concentrations are not adjusted, but low-yielding templates are identified where possible and not sequenced.


[0196] Templates are also prepared from two Streptococcus pneumoniae lambda genomic libraries. An amplified library is constructed in the vector Lambda GEM-12 (Promega) and an unamplified library is constructed in Lambda DASH II (Stratagene). In particular, for the unamplified lambda library, Streptococcus pneumoniae DNA (>100 kb) is partially digested in a reaction mixture (200 ul) containing 50 μg DNA, 1× Sau3AI buffer, 20 units Sau3AI for 6 min. at 23° C. The digested DNA was phenol-extracted and electrophoresed on a 0.5% low melting agarose gel at 2 V/cm for 7 hours. Fragments from 15 to 25 kb are excised and recovered in a final volume of 6 ul. One ul of fragments is used with 1 μl of DASHII vector (Stratagene) in the recommended ligation reaction. One μl of the ligation mixture is used per packaging reaction following the recommended protocol with the Gigapack II XL Packaging Extract (Stratagene, #227711). Phage are plated directly without amplification from the packaging mixture (after dilution with 500 μl of recommended SM buffer and chloroform treatment). Yield is about 2.5×103 pfu/ul. The amplified library is prepared essentially as above except the lambda GEM-12 vector is used. After packaging, about 3.5×104 pfu are plated on the restrictive NM539 host. The lysate is harvested in 2 ml of SM buffer and stored frozen in 7% dimethylsulfoxide. The phage titer is approximately 1×109 pfu/ml.


[0197] Liquid lysates (100 μl) are prepared from randomly selected plaques (from the unamplified library) and template is prepared by long-range PCR using T7 and T3 vector-specific primers.


[0198] Sequencing reactions are carried out on plasmid and/or PCR templates using the AB Catalyst LabStation with Applied Biosystems PRISM Ready Reaction Dye Primer Cycle Sequencing Kits for the M13 forward (M13-21) and the M13 reverse (M13RP1) primers (Adams et al., Nature 368:474 (1994)). Dye terminator sequencing reactions are carried out on the lambda templates on a Perkin-Elmer 9600 Thermocycler using the Applied Biosystems Ready Reaction Dye Terminator Cycle Sequencing kits. T7 and SP6 primers are used to sequence the ends of the inserts from the Lambda GEM-12 library and T7 and T3 primers are used to sequence the ends of the inserts from the Lambda DASH II library. Sequencing reactions are performed by eight individuals using an average of fourteen AB 373 DNA Sequencers per day. All sequencing reactions are analyzed using the Stretch modification of the AB 373, primarily using a 34 cm well-to-read distance. The overall sequencing success rate very approximately is about 85% for M13-21 and M13RP1 sequences and 65% for dye-terminator reactions. The average usable read length is 485 bp for M13-21 sequences, 445 bp for M13RP1 sequences, and 375 bp for dye-terminator reactions.


[0199] Richards et al., Chapter 28 in AUTOMATED DNA SEQUENCING AND ANALYSIS, M. D. Adams, C. Fields, J. C. Venter, Eds., Academic Press, London, (1994) described the value of using sequence from both ends of sequencing templates to facilitate ordering of contigs in shotgun assembly projects of lambda and cosmid clones. We balance the desirability of both-end sequencing (including the reduced cost of lower total number of templates) against shorter read-lengths for sequencing reactions performed with the M13RP1 (reverse) primer compared to the M13-21 (forward) primer. Approximately one-half of the templates are sequenced from both ends. Random reverse sequencing reactions are done based on successful forward sequencing reactions. Some M13RP1 sequences are obtained in a semi-directed fashion: M13-21: sequences pointing outward at the ends of contigs are chosen for M13RP1 sequencing in an effort to specifically order contigs.


[0200] 4. Protocol for Automated Cycle Sequencing


[0201] The sequencing is carried out using ABI Catalyst robots and AB 373 Automated DNA Sequencers. The Catalyst robot is a publicly available sophisticated pipetting and temperature control robot which has been developed specifically for DNA sequencing reactions. The Catalyst combines pre-aliquoted templates and reaction mixes consisting of deoxy- and dideoxynucleotides, the thermostable Taq DNA polymerase, fluorescently-labelled sequencing primers, and reaction buffer. Reaction mixes and templates are combined in the wells of an aluminum 96-well thermocycling plate. Thirty consecutive cycles of linear amplification (i.e., one primer synthesis) steps are performed including denaturation, annealing of primer and template, and extension; i.e., DNA synthesis. A heated lid with rubber gaskets on the thermocycling plate prevents evaporation without the need for an oil overlay.


[0202] Two sequencing protocols are used: one for dye-labelled primers and a second for dye-labelled dideoxy chain terminators. The shotgun sequencing involves use of four dye-labelled sequencing primers, one for each of the four terminator nucleotide. Each dye-primer is labelled with a different fluorescent dye, permitting the four individual reactions to be combined into one lane of the 373 DNA Sequencer for electrophoresis, detection, and base-calling. ABI currently supplies pre-mixed reaction mixes in bulk packages containing all the necessary non-template reagents for sequencing. Sequencing can be done with both plasmid and PCR-generated templates with both dye-primers and dye-terminators with approximately equal fidelity, although plasmid templates generally give longer usable sequences.


[0203] Thirty-two reactions are loaded per AB373 Sequencer each day, for a total of 960 samples. Electrophoresis is run overnight following the manufacturer's protocols, and the data is collected for twelve hours. Following electrophoresis and fluorescence detection, the ABI 373 performs automatic lane tracking and base-calling. The lane-tracking is confirmed visually. Each sequence electropherogram (or fluorescence lane trace) is inspected visually and assessed for quality. Trailing sequences of low quality are removed and the sequence itself is loaded via software to a Sybase database (archived daily to 8 mm tape). Leading vector polylinker sequence is removed automatically by a software program. Average edited lengths of sequences from the standard ABI 373 are around 400 bp and depend mostly on the quality of the template used for the sequencing reaction. ABI 373 Sequencers converted to Stretch Liners provide a longer electrophoresis path prior to fluorescence detection and increase the average number of usable bases to 500-600 bp.



Informatics

[0204] 1. Data Management


[0205] A number of information management systems for a large-scale sequencing lab have been developed. (For review see, for instance, Kerlavage et al., Proceedings of the Twenty-Sixth Annual Hawaii International Conference on System Sciences, IEEE Computer Society Press, Washington, D.C., 585 (1993)) The system used to collect and assemble the sequence data was developed using the Sybase relational database management system and was designed to automate data flow wherever possible and to reduce user error. The database stores and correlates all information collected during the entire operation from template preparation to final analysis of the genome. Because the raw output of the ABI 373 Sequencers was based on a Macintosh platform and the data management system chosen was based on a Unix platform, it was necessary to design and implement a variety of multi-user, client-server applications which allow the raw data as well as analysis results to flow seamlessly into the database with a minimum of user effort.


[0206] 2. Assembly


[0207] An assembly engine (TIGR Assembler) developed for the rapid and accurate assembly of thousands of sequence fragments was employed to generate contigs. The TIGR assembler simultaneously clusters and assembles fragments of the genome. In order to obtain the speed necessary to assemble more than 104 fragments, the algorithm builds a hash table of 12 bp oligonucleotide subsequences to generate a list of potential sequence fragment overlaps. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Beginning with a single seed sequence fragment, TIGR Assembler extends the current contig by attempting to add the best matching fragment based on oligonucleotide content. The contig and candidate fragment are aligned using a modified version of the Smith-Waterman algorithm which provides for optimal gapped alignments (Waterman, M. S., Methods in Enzymology 164:765 (1988)). The contig is extended by the fragment only if strict criteria for the quality of the match are met. The match criteria include the minimum length of overlap, the maximum length of an unmatched end, and the minimum percentage match. These criteria are automatically lowered by the algorithm in regions of minimal coverage and raised in regions with a possible repetitive element. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Fragments representing the boundaries of repetitive elements and potentially chimeric fragments are often rejected based on partial mismatches at the ends of alignments and excluded from the current contig. TIGR Assembler is designed to take advantage of clone size information coupled with sequencing from both ends of each template. It enforces the constraint that sequence fragments from two ends of the same template point toward one another in the contig and are located within a certain range of base pairs (definable for each clone based on the known clone size range for a given library).


[0208] The process resulted in 391 contigs as represented by SEQ ID NOs:1-391.


[0209] 3. Identifying Genes


[0210] The predicted coding regions of the Streptococcus pneumoniae genome were initially defined with the program GeneMark, which finds ORFs using a probabilistic classification technique. The predicted coding region sequences were used in searches against a database of all nucleotide sequences from GenBank (October, 1997), using the BLASTN search method to identify overlaps of 50 or more nucleotides with at least a 95% identity. Those ORFs with nucleotide sequence matches are shown in Table 1. The ORFs without such matches were translated to protein sequences and compared to a non-redundant database of known proteins generated by combining the Swiss-prot, PIR and GenPept databases. ORFs that matched a database protein with BLASTP probability less than or equal to 0.01 are shown in Table 2. The table also lists assigned functions based on the closest match in the databases. ORFs that did not match protein or nucleotide sequences in the databases at these levels are shown in Table 3.



Illustrative Applications

[0211] 1. Production of an Antibody to a Streptococcus pneumoniae Protein


[0212] Substantially pure protein or polypeptide is isolated from the transfected or transformed cells using any one of the methods known in the art. The protein can also be produced in a recombinant prokaryotic expression system, such as E. coli, or can be chemically synthesized. Concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/mil. Monoclonal or polyclonal antibody to the protein can then be prepared as follows.


[0213] 2. Monoclonal Antibody Production by Hybridoma Fusion


[0214] Monoclonal antibody to epitopes of any of the peptides identified and isolated as described can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C., Nature 256:495 (1975) or modifications of the methods thereof. Briefly, a mouse is repetitively inoculated with a few micrograms of the selected protein over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media). The successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued. Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by immunoassay procedures, such as ELISA, as originally described by Engvall, E., Meth. Enzymol. 70:419 (1980), and modified methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al., Basic Methods in Molecular Biology, Elsevier, New York. Section 21-2 (1989).


[0215] 3. Polyclonal Antibody Production by Immunization


[0216] Polyclonal antiserum containing antibodies to heterogenous epitopes of a single protein can be prepared by immunizing suitable animals with the expressed protein described above, which can be unmodified or modified to enhance immunogenicity. Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. For example, small molecules tend to be less immunogenic than others and may require the use of carriers and adjuvant. Also, host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable. An effective immunization protocol for rabbits can be found in Vaitukaitis, J. et al., J. Clin. Endocrinol. Metab. 33:988-991 (1971).


[0217] Booster injections can be given at regular intervals, and antiserum harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, O. et al., Chap. 19 in: Handbook of Experimental Immunology, Wier, D., ed, Blackwell (1973). Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12M). Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D., Chap. 42 in: Manual of Clinical Immunology, second edition, Rose and Friedman, eds., Amer. Soc. For Microbiology, Washington, D.C. (1980)


[0218] Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample. In addition, antibodies are useful in various animal models of pneumococcal disease as a means of evaluating the protein used to make the antibody as a potential vaccine target or as a means of evaluating the antibody as a potential immunotherapeutic or immunoprophylactic reagent.


[0219] 4. Preparation of PCR Primers and Amplification of DNA


[0220] Various fragments of the Streptococcus pneumoniae genome, such as those of Tables 1-3 and SEQ ID NOS:1-391 can be used, in accordance with the present


[0221] 4. Preparation of PCR Primers and Amplification of DNA


[0222] Various fragments of the Streptococcus pneumoniae genome, such as those of Tables 1-3 and SEQ ID NOS: 1-391 can be used, in accordance with the present invention, to prepare PCR primers for a variety of uses. The PCR primers are preferably at least 15 bases, and more preferably at least 18 bases in length. When selecting a primer sequence, it is preferred that the primer pairs have approximately the same G/C ratio, so that melting temperatures are approximately the same. The PCR primers and amplified DNA of this Example find use in the Examples that follow.


[0223] 5. Gene expression from DNA Sequences Corresponding to ORFs


[0224] A fragment of the Streptococcus pneumoniae genome provided in Tables 1-3 is introduced into an expression vector using conventional technology. Techniques to transfer cloned sequences into expression vectors that direct protein translation in mammalian, yeast, insect or bacterial expression systems are well known in the art. Commercially available vectors and expression systems are available from a variety of suppliers including Stratagene (La Jolla, Calif.), Promega (Madison, Wis.), and Invitrogen (San Diego, Calif.). If desired, to enhance expression and facilitate proper protein folding, the codon context and codon pairing of the sequence may be optimized for the particular expression organism, as explained by Hatfield et al., U.S. Pat. No. 5,082,767, incorporated herein by this reference.


[0225] The following is provided as one exemplary method to generate polypeptide(s) from cloned ORFs of the Streptococcus pneumoniae genome fragment. Bacterial ORFs generally lack a poly A addition signal. The addition signal sequence can be added to the construct by, for example, splicing out the poly A addition sequence from pSG5 (Stratagene) using BglI and SalI restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXT1 (Stratagene) for use in eukaryotic expression systems. pXT1 contains the LTRs and a portion of the gag gene of Moloney Murine Leukemia Virus. The positions of the LTRs in the construct allow efficient stable transfection. The vector includes the Herpes Simplex thymidine kinase promoter and the selectable neomycin gene. The Streptococcus pneumoniae DNA is obtained by PCR from the bacterial vector using oligonucleotide primers complementary to the Streptococcus pneumoniae DNA and containing restriction endonuclease sequences for PstI incorporated into the 5′ primer and BglII at the 5′ end of the corresponding Streptococcus pneumoniae DNA 3′ primer, taking care to ensure that the Streptococcus pneumoniae DNA is positioned such that its followed with the poly A addition sequence. The purified fragment obtained from the resulting PCR reaction is digested with PstI, blunt ended with an exonuclease, digested with BglII, purified and ligated to pXT1, now containing a poly A addition sequence and digested BglII.


[0226] The ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc., Grand Island, N.Y.) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600 ug/ml G418 (Sigma, St. Louis, Mo.). The protein is preferably released into the supernatant. However if the protein has membrane binding domains, the protein may additionally be retained within the cell or expression may be restricted to the cell surface. Since it may be necessary to purify and locate the transfected product, synthetic 15-mer peptides synthesized from the predicted Streptococcus pneumoniae DNA sequence are injected into mice to generate antibody to the polypeptide encoded by the Streptococcus pneumoniae DNA.


[0227] Alternatively and if antibody production is not possible, the Streptococcus pneumoniae DNA sequence is additionally incorporated into eukaryotic expression vectors and expressed as, for example, a globin fusion. Antibody to the globin moiety then is used to purify the chimeric protein. Corresponding protease cleavage sites are engineered between the globin moiety and the polypeptide encoded by the Streptococcus pneumoniae DNA so that the latter may be freed from the formed by simple protease digestion. One useful expression vector for generating globin chimerics is pSG5 (Stratagene). This vector encodes a rabbit globin. Intron II of the rabbit globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression. These techniques are well known to those skilled in the art of molecular biology. Standard methods are published in methods texts such as Davis et al., cited elsewhere herein, and many of the methods are available from the technical assistance representatives from Stratagene, Life Technologies, Inc., or Promega. Polypeptides of the invention also may be produced using in vitro translation systems such as in vitro Express™ Translation Kit (Stratagene).


[0228] While the present invention has been described in some detail for purposes of clarity and understanding, one skilled in the art will appreciate that various changes in form and detail can be made without departing from the true scope of the invention.


[0229] All patents, patent applications and publications referred to above are hereby incorporated by reference.
1TABLE 1S. pneumoniae - Coding regions containing known sequencesContigORFStartStopmatchpercentHSP ntORF ntIDID(nt)(nt)acessionmatch gene nameidentlengthlength1114371003gb|U41735|Streptococcus pneumoniae peptide methionine sulfoxide92200567reductase (msrA) and homoserine kinase homolog (thrB) genes,complete cds2561695720gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and96450450insertion sequence IS1202 transposase gene, complete cds2665926167emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]98426426genes, dTDP-rhamnose biosynthesis genes and aliA gene31197709147emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]94624624genes, dTDP-rhamnose biosynthesis genes and eliA gene3121104899671emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]91819819genes, dTDP-rhamnose biosynthesis genes and aliA gene3131154612019gb|U43526|Streptococcus pneumoniae neuraminidese B (nanB) gene,99474474complete cds, and neuraminidase (nanA) gene, partial cds314112017113375gb|U43526|Streptococcus pneumoniae neuraminidase B (nanB) gene,9913591359complete cds, and neuraminidase (nanA) gene, partial cds315113421114338gb|U43526|Streptococcus pneumoniae neuraminidase B (nanB) gene,99918918complete cds, and neuraminidase (nanA) gene, partial cds316114329115171gb|U43526|Streptococcus pneumoniae neuraminidase B (nanB) gene,99843843complete cds, and neuraminidase (nanA) gene, partial cds317115132117282gb|U43526|Streptococcus pneumoniae neuraminidase B (nanB) gene,9921512151complete cds, and neuraminidase (nanA) gene, partial cds318117267118397gb|U43S26|Streptococcus pneumoniae neuraminidase B (nanB) gene,9910691131complete cds, and neuraminidase (nanA) gene, partial cds41461188emb|Y11463|SPDNStreptococcus pneumoniae dnaG, rpoD, cpoA genes and9911431143ORF3 and ORF54211982529emb|Y11463|SPDNStreptococtus pneumoniae dnaG, rpoD, cpoA genes and998761332ORF3 and ORF55711297111473gb|U41735|Streptococcus pneumoniae peptide methionine82175177sulfoxide reductase (msrA) and homoserine kinase homolog(thrB) genes, complete cds6771257364emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)932382406873227570emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1381 (966 bp)951602496975337985emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1381 (966 bp)99453453623120197119733emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]96465465genes, dTDP-rhamnose biosynthesis genes and aliA gene71083057682emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]95624624genes, dTDP-rhamnose biosynthesis genes and aliA gene71190248206emb|Z83335|SPZ8S.pneumoniae dexs, cap1[A, B, C, D, E, F, G, H, I, J, K]95819819genes, dTDP-rhamnose biosynthesis genes and aliA gene101393048078gb|L29323|Streptococcus pneumoniae methyl transferase (mtr) gene cluster,935131227complete cds112548919emb|Z7969|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes993163721138921980emb|Z7969|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes991089 108911530403477emb|Z7969|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpx and regR genes9925943811634803247emb|Z7969|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes9923423411736014557emb|57969↑SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes9895795711845084886emb|Z7969|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes9938138111948847142emb|X16387|SPPBStreptococcus pneumoniae pbpX gene for penicillin9922592259binding protein 2X111071328124emb|X16367|SPPBStreptococcus pneumoniae pbpX gene for penicillin9870993binding protein 2X131531126gb|M31296|S.pneumoniae recP gene, complete cds99437107414318372148emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]8796312genes, dTDP-rhamnose biosynthesis genes and aliA gene14425182108gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and98411411SAICAR synthetase (purC) genes, complete cds15989428511gb|U09239|Streptococcus pneumoniae type 19F capsular polysaccharide89340432biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes,complete cds, and aliA gene, partial cds17739103458emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)9845345317843043873emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)9638243219141529emb|X94909|SPIGS.pneumoniae iga gene75368489192554757gb|L07752|Streptococcus pnenmoniae attachment site (attB), DNA sequence991672041939461827gb|L07752|Streptococcus pneumoniae attachment site (attB), DNA sequence94100882201937182gb|U33315|Streptococcus pneumoniae orfL gene, partial cds, competence99756756stimulating peptide precursor (comC), histidine protein kinase(comD) and response regulator (comE) genes, complete cds,tRNA-Arg and tRNA-Gln genes2022271931gb|U33315|Streptococcus pneumoniae orfL gene, partial cds, competences981341 1341timulating peptide precursor (comC), histidine protein kinase(comD) and response regulator (comE) genes, complete cds,tRNA-Arg and tRNA-Gln genes20331752684gb|U76218|Streptococcus pneumoniae competence stimulating peptide99492492precursor ComC (comC), histidine kinase homolog ComD(comD), and response regulator homolog ComE (comE) genes,complete cds20433224527gb|AF000658|Streptococcus pneumoniae R801 tRRNA-Arg gene,9912061206partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ), initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds20545735343gb|AF000658|Streptococcus pneumoniae R801 tRNA-Arg gene,99771771partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ), initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds20655326917gb|AF000658|Streptococcus pneumoniae R801 tRNA-Arg gene,9913861386 partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ), initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds20769958212gb|AF000658|Streptococcus pneumoniae R801 tRNA-Arg gene,9912181218partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ), initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds20882148471gb|AF000658|Streptococcus pneumoniae R801 tRNA-Arg gene,98258258partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ) , initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds20985349670gb|AF000658|Streptococcus pneumoniae R801 tRNA-Arg gene,991341137partial sequence, and putative serine protease (sphtra),SPSpoJ (spspoJ), initiator protein (spdnaa) and betasubunit of DNA polymerase III (spdnan) genes, complete cds22141188712267emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)9922638122151270812256emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)9735345322161316512662emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)98504504 22231839818910emb|Z86112|SPZ8S.pneumoniae genes encoding galacturonosyl transferase and95463513transposase and insertion sequence IS151522241882919299emb|Z86112|SPZ8S.pneumoniae genes encoding galacturonosyl transferase and99443471transposase and insertion sequence IS151523556244203emb|X52474|SPPLS.pneumoniae ply gene for pneumolysin991422142223660635629gb|M17717|S.pneumoniae pneumolysin gene, complete cds9819743526155002emb|X94909|SPIGS.pneumoniae iga gene873487549926258235584gb|U47687|Streptococcus pneumoniae immunoglobulin A1 protease99151240(iga) gene, complete cds26368785685gb|U47687|Streptococcus pneumoniae immunoglobulin A1 protease100501194(iga) gene, complete cds2681449814854emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]99338357genes, dTDP-rhamnose biosynthesis genes and aliA gene2691476314924emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]10094162genes, dTDP-rhamnose biosynthesis genes and aliA gene26101492215173gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidese gene and97242252insertion sequence IS1202 transposase gene, complete cds28180505emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]99426426genes, dTDP-rhamnose biosynthesis genes and aliA gene282503952gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and97450450insertion sequence IS1202 transposase gene, complete cds2837801298gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and96181519insertion sequence IS1202 transposase gene, complete cds3412071523gb|L08611|Streptococcus pneumoniae maltose/maltodextrin uptake (malX)9913171317and two meltodextrin permease (malC and malD) genes,complete cds34214772367gb|L08611|Streptococcus pneumoniae maltose/maltodextrin uptake (malX)96795891and two maltodextrin permease (malC and malD) genes,complete cds34325933420gb|L21856|Streptococcus pneumoniae malA gene, complete cds;96446828malR gene, complete cds34427902647gb|L21856|Streptococcus pneumoniae malA gene, complete cds;98137144malR gene, complete cds34534184416gb|L21856|Streptococcus pneumoniae malA gene, complete cds;96999999malR gene, complete cds34977647507gb|U41735|Streptococcus pneumoniae peptide methionine sulfoxide93201258reductase (msrA) and homoserine kinase homolog (thrB) genes,complete cds34161056210257emb|X63602|SPBOS.pneumoniae mmsA-Box9223830635411761439emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]87248264genes, dTDP-rhamnose biosynthesis genes and aliA gene35514561961gb|U09239|Streptpcoccus pneumoniae type 19F capsular polysaccharide98264504biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes,complete cds, and aliA gene, partial cds351711617215477emb|X65767|SPCPS.pneumoniae dexB, cps14A, cps14B, cps14C, cps14D, cps14E,97696696cps14E, cps14G, cps14H, cps14I, cps14J, cps14K, cps14L,tasA genes35181696116170emb|Z83335|SPZ8S.pneumoniae dexB, cap1(A, B, C, D, E, F, G, H, I, J, K]86792792genes, dTDP-rhamnose biosynthesis genes and aliA gene35191762016871gb|U09239|Streptococcus pneumoniae type 19F capsular polysaccharide83750750biosynthesis operon, (cps19fASCDEFGHIJKLMNO) genes,complete cds, and aliA gene, partial cds35201906117604emb|X95787|SPCPS.pneumoniae dexB, cps14A, cps14B, cps14C, cps14D, cps14E,9414581458cps14F, cps14G, cps14H, cps14I, cps14J, cps14K, cps14L,tasA genes36191896018352gb|U40786|Streptococcus pneumoniae surface antigen A variant precursor99609609(psaA) and 18 kDa protein genes, complete cds, and ORF1 gene,partial cds36201993418966gb|U53509|Streptococcus pneumoniae surface adhesin A precursor (psaA)99969969gene, complete cds3712743179emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and9925652565unknown orf37229852824emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and100162162unknown orf37350343070emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and9919651965unknown orf37451345790emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and99657657unknown orf37561715833emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and96339339unknown orf38191296913268gb|N28679|S.pneumoniae promoter region DNA1006430039212562137gb|U41735|Streptococcus pneumoniae peptide methionine99882882sulfoxide reductase (msrA) and homoserine kinase homolog(thrB) genes, complete cds39324053370gb|U41735|Streptococcus pneumoniae peptide methionine99966966sulfoxide reductase (msrA) and homoserine kinase homolog(thrB) genes, complete cds40952537208gb|M29686|S.pneumoniae mismatch repair (hexB) gene, complete cds99195619564131037emb|Z17307|SPRES.pneumoniae recA gene encoding RecA991027103541213282713emb|Z34303|SPCIStreptococcus pneumoniae cin operon encoding the9913861386cinA, recA, dinF, lytA genes, and downstream sequences41330834045gb|M13812|S.pneumoniae autolysin (lytA) gene, complete cds9996396341432723096gb|N13812|S.pneumoniae autolysin (lytA) gene, complete cds10017717741536033860gb|M13812|S.pneumoniae autolysin (lytA) gene, complete cds10025825841647555162gb|L36660|Streptococcus pneumoniae ORF, complete cds9840840841752705716gb|L36660|Streptococcus pneumoniae ORF, complete cds9844744741861126918gb|L36660|Streptococcus pneumoniae ORF, complete cds9843180741969167119gb|L36660|Streptococcus pneumoniae ORF, complete cds100204204411070827660gb|L36660|Streptococcus pneumoniae ORF, complete cds97552579411176807979gb|L36660|Streptococcus pneumoniae ORF, complete cds9881300411291698717emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)97353453411395339132emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1381 (966 bp)95160402411496699475emb|Z82001|SPZ8S.pneumoniae pcpA gene and open reading frames10016919544571907555emb|Z82001|SPZ8S.pneumoniae pcpA gene and open reading frames9936636644680597607emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)9745345344784238022emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1381 (966 bp)9516040244885598365emb|Z82001|SPZ8S.pneumoniae pcpA gene and open reading frames10018919548964804687gb|L39074|Streptococcus pneumoniae pyruvate oxidase (spxB) gene,9917941794complete cds4922312603gb|L20561|Streptococcus pneumoniae Exp7 gene, partial cds100216237353624072156gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and97242252insertion sequence IS1202 transposase gene, complete cds53725662405emb|583335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]10094162genes, dTDP-rhamnose biosynthesis genes end aliA gene53828312475emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]99338357genes, dTDP-rhamnose biosynthesis genes and aliA gene54131240911105emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]675911305genes, dTDP-rhamnose biosynthesis genes and aliA gene55222048819949emb|Z84379|HSZ8S.pneumoniae dfr gene (isolate 92)995405406111118649900emb|Z16082|PNALStreptococcus pneumoniae alis gene98196519656313239gb|M18729|S.pneumoniae mismatch repair protein (hexA) gene,100237237complete cds6322332611gb|M18729|S.pneumoniae mismatch repair protein (hexA) gene,9923302379complete cds63325572823gb|M18729|S.pneumoniae mismatch repair protein (hexA) gene,99266267complete cds63429584664gb|M18729|S.pneumoniae mismatch repair protein (hexA) gene,95691707complete cds67637703399gb|L20670|Streptococcus pneumoniae hyaluronidase gene, complete cds9637237267771614171gb|L20670|Streptococcus pneumoniae hyaluronidase gene, complete cds99293829917011702gb|M14340|S.pneumoniae DpnI gene region encoding dpnC and dpnD,100693702complete cds7026781160gb|M14340|S.pneumoniae DpnI gene region encoding dpnC and dpnD,100483483complete cds70324901210gb|M14339|S.pneumoniae DpnII gene region encoding dpnM, dpnA, dpnB,984621281complete cds70742304424gb|J04234|S.pneumoniae exodeoxyribonuclease (exoA) gene, complete cds9914719570851974316gb|J04234|S.pneumoniae exodeoxyribonuclease (exoA) gene, complete cds99881882701381089874gb|L20562|Streptococcus pneumoniae Exp8 gene, partial cds93234176771222796428341emb|X63602|SPBOS.pneumoniae mmsA-Box9323337872546073552emb|Z26850|SPATS.pneumoniae (M222) genes for ATPase a subunit,971021056ATPase b subunit and ATPase c subunit731471133emb|X63602|SPBOS.pneumoniae mmsA-Box911933397333658977gb|J04479|S.pneumoniae DNA polymerase I (polA) gene, complete cds992682268273848645379gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and98318516SAICAR synthetase (purC) genes, complete cds77326221999emb|Z83335|SPZ8S.pneumoniae dexH, cap1[A, B, C, D, E, F, G, H, I, J, K]95624624genes, dTDP-rhamnose biosynthesis genes and aliA gene77433412523emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]91819819genes, dTDP-rhamnose biosynthesis genes and aliA gene7813413emb|X77249|SPR6S.pneumoniae (R6) ciaR/ciaH genes993393397821095325emb|X77249|SPR6S.pneumoniae (R6) ciaR/ciaH genes9977177182101143610816gb|U90721|Streptococcus pneumoniae signal peptidase I (spi) gene,97621621complete cds82111240211434gb|U93576|Streptococcus pneumoniae ribonuclease HII (rnhB) gene,98953969complete cds82121238112704gb|U93576|Streptococcus pneumoniae ribonuclease HII (rnhB) gene,10051324complete cds83832123550emb|Z77727|SPIAS.pneumoniae DNA for insertion sequence IS1318 (823 bp)97290339831046626851gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and9921902190SAICAR synthetase (purC) genes, complete cds831168498213gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and9913651365SAICAR synthetase (purC) genes, complete cds831282369090gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and99855855SAICAR synthetase (purC) genes, complete cds8313928313017gb|L15190|Streptococcus pneumoniae SAICAR synthetase (purC) gene,1001073735complete cds83232214723313gb|L36923|Streptococcus pneumoniae beta-N-acetylhexosaminidase (strH)982181167gene, complete cds83242326823450gb|L36923|Streptococcus pneumoniae beta-N-acetylhexosaminidase (strH)98172183gene, complete cds83252752723505gb|L36923|Streptococcus pneumoniae beta-N-acetylhexosaminidase (strH)9938264023gene, complete cds83262847227771gb|L36923|Streptococcus pneumoniae beta-N-acetylhexosaminidase (strH)99416702gene, complete cds84445546173emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]986971620genes, dTDP-rhasmose biosynthesis genes and aliA gene87659515318emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1318 (966 bp)9643963688529573511gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and94555555SAICAR synthetase (purC) genes, complete cds88634664269gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and94804804SAICAR synthetase (purC) genes, complete cds8913987810093gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and97211216SAICAR synthetase (purC) genes, complete cds89141006210412emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]97335351genes, dTDP-rhamnose bidsynthesis genes and aliA gene931053034941emb|X63602|SPBOS.pneumoniae mmsA-Box8923736397417081520gb|U41735|Streptococcus pneumoniae peptide methionine sulfoxide91140189reductase (msrA) and homoserine kinase homolog (thrB) genes,complete cds99189700emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]93592612genes, dTDP-rhamnose biosynthesis genes and aliA gene9921773775emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring99998999aminopterin resistance99327941712emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring991083 1083aminopterin resistance99437322788emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring100945945aminopterin resistance99552493714emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring10015361536aminopterin resistance99672625277emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring9919861986aminopterin resistance10112161538emb|X54225|SPENS.pneumoniae epuA and endA genes for 7 kDa991461323protein and membrane endonuclease101214921719emb|X54225|SPENS.pneumoniae epuA and endA genes for 7 kDa99228228protein and membrane endonuclease101316941855emb|X54225|SPENS.pneumoniae epuA and endA genes for 7 kDa100162162protein and membrane endonuclease101417012582emb|X54225|SPENS.pneumoniae epuA and endA genes for 7 kDa100882882protein and membrane endonuclease103755565041emb|Z95914|SPZ9Streptococcus pneumoniae sodA gene100396516104213471556emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)83206210105553815028emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and98353354unknown orf105660895379emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and9884711unknown orf1074278511880emb|X18022|SPPES.pneumoniae penA gene9872906107529134988emb|X16022|SPPES.pneumoniae penA gene9916922076107649815595emb|X13136|SPPEStreptococcus pneumoniae penA gene for penicillin91107615binding protein 28 lacking N-term. (penicillin resistant strain)108990688718emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and95342351unknown orf108121130810922emb|Z87739|SPPAS.pneumoniae parC, parE and transposase genes and99199387unknown orf109327682241emb|Z77725|SPISS.pneumoniae DNA for insertion sequence IS1318 (966 bp)9661528109428882855emb|Z77726|SPIAS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)96148168109528623269emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)97353408109653203584gb|M18729|S.pneumoniae mismatch repair protein (hexA) gene,1003711737complete cds11314313gb|N36180|Streptococcus pneumoniae transposase, (comA and comB) and95429429SAICAR synthetase (purC) genes, complete cds1131097888532emb|X99400|SPDAS.pneumoniae dacA gene and ORF991257125711311987010985emb|X99400|SPDAS.pneumoniae dacA gene and ORF9911161116114325302030gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and95481501SAICAR synthetase (purC) genes, complete cds115111130310932gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and97372372insertion sequence IS1202 transposase gene, complete cds11718973302emb|X72967|SPNAS.pneumoniae nanA gene9924022406117232773831emb|X72967|SPNAS.pneumoniae nanA gene98237555117343273899gb|M36180|Streptococcus pneumoniae transposase, (comA and comB) and98429429SAICAR synthetase (purC) genes, complete cds121213691941gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK) gene,99202573complete cds and DnaJ (dnaJ) gene, partial cds121324124253gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK) gene,9918421842complete cds and Dna3 (dnaJ) gene, partial cds122850665587gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and64451522insertion sequence IS1202 transposase gene, complete cds12511811189gh|M36180|Streptococcus pneumoniae transposase, (comA and comB) and92991623SAICAR synthetase (purC) genes, complete cds128151249611204emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J K]917051293genes, dTDP-rhamnose biosynthesis genes and aliA gene13411492emb|Y10818|SPY1S.pneumoniae spsA gene9920349213425562652gb|AP019904|Streptococcus pneumoniae choline binding protein A (cbpA)866852097gene, partial cds13431160837emb|Y10818|SPY1S.pneumoniae spsA gene86324324134439522882gb|AF019904|Streptococcus pneumoniae choline binding protein A (cbpA)982151071gene, partial cds134879929848gb|U12567|Streptococcus pneumoniae P13 glycerol-3-phosphate992851857dehydrogenase (glpD) gene, partial cds, and glycerol uptakefacilitator (glpF) and ORF3 genes, complete cds1349984610622gb|U12567|Streptococcus pneumoniae P13 glycerol-3-phosphate99570777dehydrogenase (glpD) gene, partial cds, and glycerol uptakefacilitator (glpF) and ORF3 genes, complete cds134101080511122gb|U12567|Streptococcus pneumoniae P13 glycerol-3-phosphate100318318dehydrogenase (glpD) gene, partial cds, and glycerol uptakefacilitator (glpF) and ORF3 genes, complete cds1371379708443gb|U09239|Streptococcus pneumoniae type 19F capsular90420474polysaccharide biosynthesis operon,(cps19fABCDEFGHIJKLMNO) genes, complete cds,and aliA gene, partial cds1371485908775emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]94174186genes, dTDP-rhamnose biosynthesis genes and aliA gene1371587738967emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, j, K]98195195genes, dTDP-rhamnose biosynthesis genes and aliA gene1371692239687emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)9644646513717964110051emb|Z77727|SPISS.pneumoniae DNA for insertion sequence IS1318 (823 bp)96293411139101299812702emb|X63602|SPBOS.pneumoniae masA-Box90234297141878058938emb|Z49988|SPMMStreptococcus pneumoniae mmsA gene9933811341419893610972emb|Z49988|SPMMStreptococcus pneumoniae mmsA gene9920372037141101147212467emb|Z49988|SPMMStreptococcus pneumoniae mmsA gene100769961422257814gb|M80215|Streptococcus pneumoniae uvs402 protein gene, complete cds981745581423787957gb|M80215|Streptococcus pneumoniae uvs402 protein gene, complete cds10014217114249803022gb|M80215|Streptococcus pneumoniae uvs402 protein gene, complete cds9519972043142530203595gb|M80215|Streptococcus pneumoniae uvs402 protein gene, complete cds10015357814511219emb|Z35135|SPALS.pneumoniae aliA gene for amiA-like gene A9718521914521711994gb|L20556|Streptococcus pneumoniae plpA gene, partial cds9918111824145322877599emb|Z47210|SPDES.pneumoniae dexB, cap3A, cap3B and cap3C genes and orfs9910525313145499347766gh|M90527|Streptococcus pneumoniae penicillin-binding protein (ponA)9921692169gene, complete cds1455104889922gb|M90527|Streptococcus pneumoniae penicillin-binding protein (ponA)99512567gene, complete cds14611594emb|Z82002|SPZ8S.pneuaoniae pcpB and pcpC genes98156156146234490emb|Z82002|SPZ8S.pneumoniae pcpB and pcpC genes98255255146161179510794emb|Z82002|SPZ8S.pneumoniae pcpB and pcpC genes85276100214711067810202emb|Z21702|SPUNS.pneumoniae ung gene and mutX genes encoding uracil-DNA98477477glycosylase and 8-oxodGTP nucleoside triphosphatase14721133810676emb|Z21702|SPUNS.pneumoniae ung gene and mutX genes encoding uracil-DNA99663663glycosylase and 8-oxodGTP nucleoside triphosphatase1481290098815gb|U41735|Streptococcus pneumoniae peptide methionine sulfoxide90180195reductase (merA) and homoserine kinase homolog (thrB)genes, complete cds156411541402emb|X63602|SPBOS.pneumoniae mmsA-Box941852491591390488521gb|M36180|Streptococcus pneumoniae transposase, (comA and comB)98526528and SAICAR synthetase (purC) genes, complete cds16011147emb|Z26851|SPATS.pneumoniae (R6) genes for ATPase a subunit,100142147ATPase b subunit and ATPase c subunit1602179898emb|Z26851|SPATS.pneumoniae (R6) genes for ATPase a subunit,99720720ATPase b subunit and ATPase c subunit16039061406emb|Z26850|SPATS.pneumoniae (M222) genes for ATPase a subunit,95501501ATPase b subunit and ATPase c subunit 160413731942emb|Z26850|SPATS.pneumoniae (M222) genes for ATPase a subunit,87306570ATPase b subunit and ATPase c subunit16111984emb|X77249|SPR6S.pneumoniae (R6) ciaR/cieH genes99984984161769107497emb|X83917|SPGYS.pneumoniae orflgyrB and gyrB gene encoding DNA99437588gyrase B subunit161874439386emb|X83917|SPGYS.pneumoniae orflgyrB and gyrB gene encoding DNA9819121944gyrase B subunit163122155gb|L20559|Streptococcus pneumoniae Exp5 gene, partial cds9832721541651321618gb|J01796|S.pneumoniae malX and malM genes encoding membrane9915871587protein and amylomaltase, complete cds, and malP geneencoding phosphorylase165216083902gb|J01796|S.pneumoniae malX and malM genes encoding membrane1002802295protein and amylomaltase, complete cds, and malP geneencoding phosphorylase16613784emb|Y11463|SPDNStreptococcus pneumoniae dnaG, rpoD, cpoA genes and100375375ORF3 and ORF516621507320emb|Y11463|SPDNStreptococcus pneumoniae dnaG, rpoD, cpoA genes and9911881188ORF3 and ORF5166332401432emb|Y11463|SPDNStreptococcus pneumoniae dnaG, rpoD, cpoA genes and995631809ORF3 and ORF516711077328emb|Z71552|SPADStreptococcus pneumoniae adcCBA operon9415575016721844999emb|Z71552|SPADStreptococcus pneumoniae adcCBA operon98405846167327141842emb|Z71552|SPADStreptococcus pneumoniae adcCBA operon97604873167433992641emb|Z71552|SPADStreptococcus pneumoniae adcCBA operon99703759168112259gb|L20558|Streptococcus pneumoniae Exp4 gene, partial cds9928222591701073387685emb|Z77726|SPISS.pneumoniae DNA for insertion sequence IS1318 (1372 bp)95315348172624624981gb|U47625|Streptococcus pneumoniae formate acetyltransferase (exp72)973652520gene, partial cds175137320gb|M36180|Streptococcus pneumoniae transposese, (comA and comB) and89353354SAICAR synthetase (purC) genes, complete cds175418433621emb|Z47210|SPDES.pneumoniae dexB, cap3A, cap3B and cap3C genes and orfs95891779176539842980emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and1005731005unknown orf17813425emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and95423423unknown orf179142670emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]99338357genes, dTDP-rhamnose biosynthesis genes and aliA gene180330841855emb|X95718|SPGYS.pnaumoniae gyrA gene99381123018617144emb|Z79691|SOORS.pneumoniae yorf[A, B, C, D, E], pbpX and regR genes985971118622254608emb|Z79691|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes9831516471863707880emb|Z79691|SOORS.pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes9817417418912259gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK)99258258gene, complete cds and DnaJ (dnaJ) gene, partial cds1892600385gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK)98204216gene, complete cds and DnaJ (dnaJ) gene, partial cds18931018851gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK)99168168gene, complete cds and DnaJ (dnaJ) gene, partial cds189410122154gb|U72720|Streptococcus pneumoniae heat shock protein 70 (dnaK)9910621143gene, complete cds and DnaJ (dnaJ) gene, partial cds191978297524emb|X63802|SPBOS.pneumoniae mmsA-Box952343061194117291gb|M36180|Streptococcus pneumoniae transposase, (comA and comB)91728729and SAICAR synthetase (purC) genes, complete cds19921117881emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]96211237genes, dTDP-rhamnose biosynthesis genes and aliA gene199414991762emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]89248264genes, dTDP-rhamnose biosynthesis genes and aliA gene199517812284emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]98504504 genes, dTDP-rhamnose biosynthesis genes and aliA gene20311977337gb|L20563|Streptococcus pneumoniae Exp9 gene, partial cds993421641204111453gb|L36131|Streptococcus pneumoniae Exp10 gene, complete cds, recA gene,99114311435′ end2081592296gb|U89711|Streptococcus pneumoniae pneumococcal surface protein A904712238PspA (pspA) gene, complete cds213324552123emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]96332333genes, dTDP-rhamnose biosynthesis genes and aliA gene216136812emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]99338357genes, dTDP-rhamnose biosynthesis genes and aliA gene216326502327gb|M28678|S.pneumoniae promoter sequence DNA988632422214174emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]94414414genes, dTDP-rhamnose biosynthesis genes and aliA gene227352664238emb|AJ000336|SPStreptococcus pneumoniae 1dh gene991029102923911804gb|M31296|S.pneumoniae recP gene, complete cds95484804247316251807gb|M36180|Streptococcus pneumoniae transposase, (comA and comB)94178183and SAICAR synthetase (purC) genes, complete cds24939211364emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]94443444genes, dTDP-rhamnose biosynthesis genes and aliA gene25313623gb|M36180|Streptococcus pneumoniae transposase, (comA and comB)99360360and SAICAR synthetase (purC) genes, complete cds253512382050emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]95420813genes, dTDP-rhamnose biosynthesis genes and aliA gene253620692572emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]97504504genes, dTDP-rhamnose biosynthesis genes and aliA gene25513800emb|Z82002|SPZ8S.pneumoniae pcpB and pcpC genes9753179825527981841emb|Z82002|SPZ8S.pneumoniae pcpB end pcpC genes976721044255324931969emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and92435525unknown orf2572985770emb|X17337|SPAMStreptococcus pneumoniae ami locus conferring96117216aminopterin resistance25731245907gb|N36180|Streptococcus pneumoniae transposase, (comA and comB)97339339and SAICAR synthetase (purC) genes, complete cds26724951208gb|U1656|Streptococcus pneumoniae dihydropteroate synthase (sulA),9584714dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolasepyrophosphokinase (sub) genes, complete cds267312912277gb|U16156|Streptococcus pneumoniae dihydropteroate synthase (sulA),97755987dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolasepyrophosphokinase (sulD) genes, complete cds267422613601gb|U16156|Streptococcus pneumoniae dihydropteroate synthase (sulA),9813411341dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolasepyrophosphokinase (sulD) genes, complete cds267535614136gb|U16156|Streptococcus pneumoniae dihydropteroate synthase (sulA),99576576dihydrofolate synthetase (sulB), guanosine triphoephate cyclohydrolase (sulC), aldolasepyrophosphokinase (sulD) genes, complete cds267641644949gb|U16156|Streptococcus pneumoniae dihydropteroate synthase (sulA),99748786dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolasepyrophosphokinase (sulD) genes, complete cds267755445140gb|U16156|Streptococcus pneumoniae dihydropteroate synthase (sulA),100186405dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolesepyrophosphokinase (sub) genes, complete cds268417931990emb|X63602|SPBOS.pneumoniae mmsA-Box891941982711562104gb|M29686|S.pneumoniae mismatch repair (hexB) gene, complete cds93160459291175524gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and96450450insertion sequence IS1202 transposase gene, complete cds29121001525emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]87205477genes, dTDP-rhamnose biosynthesis genes and aliA gene2913807559emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]90170249genes, dTDP-rhamnose biosynthesis genes and aliA gene291413741099gb|M36180|Streptococcus pneumoniae transposase,(comA and comB)85264276and SAICAR synthetase (purC) genes, complete cds293131673emb|Z67740|SPGYS.pneumoniae gyrB gene and unknown orf98553167129611434151emb|Z47210|SPDES.pneumoniae dexB, cap3A, cap3B and cap3C genes and orfs9943012843171157510emb|Z67739|SPPAS.pneumoniae parC, parE and transposase genes and89353354unknown orf32521237485emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]91299753genes, dTDP-rhamnose biosynthesis genes and aliA gene32611462emb|Z82001|SPZ8S.pneumoniae pcpA gene and open reading frames100233462327160364emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]9489540genes, dTDP-rhamnose biosynthesis genes and aliA gene3341153545gb|U41735|Streptococcus pneumoniae peptide methionine sulfoxide8791393reductase (msrA) and homoserine kinase homolog (thrE)genes, complete cds336130893emb|Z26850|SPATS.pneumoniae (M222) genes for ATPase a subunit,97102216ATPase b subunit and ATPase c subunit36011519emb|Z67739|SPPAS.pneuaoniae parC, parE and transposase genes95435519and unknown orf360415981960emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]94353363genes, dTDP-rhamnose biosynthesis genes and aliA gene36216732emb|Z83335|SPZ8S.pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, K]9563672genes, dTDP-rhamnose biosynthesis genes and aliA gene362211687281gb|U04047|Streptococcus pneumoniae SSZ dextran glucosidase gene and96441441insertion sequence IS1202 transposase gene, complete cds3841347111emb|X85787|SPCPS.pneumoniae dexE, cps14A, cpa14B, cps14C, cps14D,9454237cps14E, cps14F, cps14G, cps14H, cps14I, cps14J, cps14K,cps14L, tasA genes


[0230]

2





TABLE 2












S. pneumoniae
- Putative coding regions of novel proteins similar to known proteins
















Contig
ORF
Start
Stop
match

percent
HSP nt
ORF nt


ID
ID
(nt)
(nt)
acession
match gene name
ident
length
length


















228
2
1760
1942
pir|P60663|F806
translation elongation factor Tu - Streptococcus oralis
100
100
183


319
1
2
2051
gi|984927
neomycin phosphotransferase (Cloning vector pBSL99)
100
100
204


260
1
2
1138
pi|F60663|F606
translation elongation factor Tu - Streptococcus oralis
99
98
1137


25
2
486
1394
gi|1574495
hypothetical [Haemophilus influenzae]
98
96
909


94
2
685
1002
gi|310627
phosphoenolpyruvate: sugar phosphotransferase system HPr
98
93
318







[Streptococcus mutans]


312
1
190
2
gi|347999
ATP-dependent protease proteolytic suhunit
98
95
189







[Streptococcus salivarius]


329
1
1
807
gi|924848
inosine monophosphate dehydrogenase [Streptococcus pyogenes]
98
94
807


336
2
290
589
gi|987050
lacZ gene product [unidentified cloning vector]
98
98
300


181
9
5948
7366
gi|153755
phospho-beta-D-galactosidase (EC 3.2.1.85)
97
94
1419







[Lactococcus lactis cremoris]


312
2
1044
361
gi|347998
uracil phosphoribosyltransferase [Streptococcus salivarius]
97
88
684


32
8
6575
7486
sp|P37214|ERA_S
GTP-BINDING PROTEIN ERA HOMOLOG.
96
91
912


94
3
951
2741
gi|153615
phosphoenolpyruvato: sugar phosphotransferase system
96
92
1791







enzyme I [Streptococcus


127
1
1
168
gi|581299
initiation factor IF-1 [Lactococcus lactis]
96
89
168


128
14
10438
11154
gi|1276873
DeoD [Streptococcus thermophilus]
96
93
717


181
4
1362
1598
gi|46606
lacD polypeptide (AA 1-326) [Staphylococcus aureus]
96
80
237


218
1
1
8341
gi|1743856
intragenaric coaggregation-relevant adhesin
96
93
834







[Streptococcus gordonii]


319
2
115
441
gi|208225
heat-shock protein 82/neomcyn phosphotransferase fusion
96
96
327







protein (hsp82-neo) (unidentified cloning vector)


54
12
8622
10967
gnl|PID|d100972
Pyruvate formate-lyase [Streptococcus mutans]
95
89
2346


181
2
606
1289
gi|149396
lacD [Lactococcus lactis]
95
89
684


46
3
3410
3045
gi|1850606
YlxM [Streptococcus mutans]
94
86
366


89
10
7972
7337
gi|703442
thymidine kinase [Streptococcus gordonii]
94
86
636


148
9
6431
7354
gi|995767
UDP-glucose pyrophosphorylase [Streptococcus pyogenas]
94
85
924


160
7
4430
5848
gi|153573
H+ ATPase [Enterococcus fascalis]
94
87
1419


2
3
4598
3513
gi|153763
plasmin receptor [Streptococcus pyoganes]
93
86
1086


12
8
7877
6204
gi|1103865
formyl-tetrahydrofolate synthetasa [Streptococcus mutans]
93
84
1674


65
11
4734
5120
gi|40150
L14 protein (AA 1-122) [Bacillus subtilis]
93
87
3871


68
1
53
1297
gi|47341
antitumor protein [Streptococcus pyogenes]
93
87
1245


80
1
3
299
gnl|PID|d101166
ribosomal protein S7 [Bacillus subtilis]
93
84
297


127
3
695
1093
gi|142462
ribosomal protein 511 [Bacillus subtilis]
93
86
399


160
5
1924
3462
gi|773264
ATPase, alpha subunit [Streptococcus mutens]
93
85
1539


211
5
3757
3047
gi|535273
aminopeptidase C [Streptococcus thermophilus]
93
82
711


262
1
16
564
gi|149394
lacB [Lactococcus lactis]
93
90
549


366
1
197
3
gi|295259
tryptophan synthase beta subunit [Synechocystis sp.]
93
91
195


25
3
1392
1976
gi|574496
hypothetical [Haemophilus influenzae]
92
80
585


36
21
120781
119927
gi|310632
hydrophobic membrane protein [Streptococcus gordonli]
92
86
855


181
3
1265
1534
gi|149396
lacD [Lactococcus lactis]
92
83
2701


181
7
3682
4060
gi|149410
enzyme III [Lactococcus lactic]
92
83
3991


32
4
5631
3937
gnl|PID|e294090
fibronectin-hinding protein-like protein A
91
85
1695







[Streptococcus gordonli]


46
2
3054
1462
gi|1850607
signal recognition particle Ffh [Streptococcus mutans]
91
84
1593


65
10
4442
4726
pir|S17865|S178
ribosomal protein S17 - Bacillus stearothermophilus
91
80
285


77
2
260
1900
gi|287871
groEL gene product [Lactococcus lactis]
91
82
1641


84
1
2
2056
gi|871784
Clp-like ATP-dependent protease binding subunit [Boa taurus]
91
79
2055


99
8
110750
9272
gi|153740
sucrose phosphorylase [Streptococcus mutans]
91
84
1479


99
9
111947
11072
gi|153739
membrane protein [Streptococcus mutans]
91
78
876


127
5
2065
2469
pir|S07223|R5BS
ribosomal protein L17 - Bacillus stearothermophilus
91
78
405


132
6
9539
9390
gi|143065
hubst [Bacillus stearothermophilus]
91
89
150


137
8
4765
6153
gnl|PID|d100347
Na+ -ATPase beta subunit [Enterococcus hirea]
91
79
1389


151
7
111119
9734
gi|1815634
glutamine synthetase type 1 [Streptococcus agalactiae]
91
82
1386


201
2
1798
278
gi|2208998
dextran glucosidase DexS [Streptococcus suis]
91
79
1521


222
2
673
1839
gi|153741
ATP-binding protein [Streptococcus mutans]
91
85
1167


293
5
4113
4400
gi|1196921
unknown protein [Insertion sequence IS861]
91
71
288


32
7
6166
8570
pir|A36933|A369
diacylglycerol kinase homolog - Streptococcus mutans
90
77
405


33
2
841
527
gi|1196921
unknown protein [Insertion sequence IS861]
90
70
315


48
27
20908
19757
gnl|PID|e274705
lactate oxidase [Streptococcus iniae]
90
80
1152


55
21
119777
118515
gnl|PID|e221213
ClpX protein [Bacillus subtilis]
90
75
1263


56
2
717
977
gi|1710133
flagellar filament cap [Borrelia burgdorferi]
90
50
261


65
1
1
606
gi|1165303
L3 [Bacillus subtilis]
90
75
606


114
1
2
988
gi|153562
aspartate beta-semialdehyde dehydrogenase (EC 1.2.1.11)
90
80
987







[Streptococcus mutans]


120
1
1345
827
gi|407880
ORF1 [Streptococcus equisimilis]
90
75
519


159
12
7690
8298
gi|143012
GMP synthetase [Bacillus subtilis]
90
84
609


166
4
4076
3282
gi|1661179
high affinity branched chain amino acid transport protein
90
78
795







[Streptococcus mutans]


183
1
28
1395
gi|308858
ATP: Pyruvate 2-O-phosphotransferase [Lactococcus lactis]
90
76
1368


191
3
2891
1662
gi|149521
tryptophan synthase beta subunit [Lactococcus lactis]
90
78
1230


198
2
1551
436
gi|2323342
(AF014460) CcpA [Streptococcus mutans]
90
76
1116


305
1
37
783
gi|1573551
asparagins synthetase A (asnA) [Haemophilus influenzae]
90
80
747


8
3
2285
3343
gi|149434
putative [Lactococcus lactis]
89
78
1059


46
8
7577
7362
pir|A45434|A454
ribosomel protein L19 - Bacillus stearothermophilus
89
76
216


49
9
8363
10342
gi|153792
recP peptide [Streptococcus pneumoniae]
89
83
1980


51
14
18410
19447
gi|308857
ATP: D-fructose 6-phosphate 1-phosphotransferase
89
81
1038







[Lactococcus lactis]


57
11
9686
110669
gnl|PID|d100932
H2O-forming NADH Oxidese [Streptococcus mutans]
89
77
984


65
5
2418
2786
gi|1165307
S19 [Bacillus subtilis]
89
81
369


65
8
3806
4225
sp|P14577|RL16
50S RIBOSOMAL PROTEIN L16.
89
82
420


65
18
8219
8719
gi|143417
ribosomal protein S5 [Bacillus stearothermophilus]
89
76
501


73
9
6337
5315
gi|532204
prs [Listens monocytogenes]
89
70
1023


76
3
3360
1465
gnl|PID|e200671
lepA gene product [Bacillus subtilis]
89
76
1896


99
10
12818
11919
gi|153738
membrane protein [Streptococcus mutans]
89
73
900


120
2
3552
1300
gi|407881
stringent response-like protein [Streptococcus equisimilis]
89
79
2253


122
5
4512
2791
gnl|PID|e280490
unknown [Streptococcus pneumoniae]
89
81
1722


176
1
669
4
gi|47394
5-oxoprolyl-peptidase [Streptococcus pyogenes]
89
78
666


177
6
3050
3934
gi|912423
putative [Lactococcus lactis]
89
71
885


181
8
4033
5751
gi|149411
enzyme III [Lactococcus lactis]
89
80
1719


211
4
3149
2793
gi|535273
aminopeptidase C [Streptococcus thermophilus]
89
83
357


361
1
431
838
gi|1196922
unknown protein (Insertion sequence IS861)
89
70
408


34
17
11839
10535
sp|P30053|SYH_S
HISTIDYL-TRNA SYNTHETASE (EC 6.1.1.21)
88
78
1305







(HISTIDINE--TRNA LIGASE) (HISRS).


38
3
1646
2623
gi|2058544
putative ABC transporter subunit ComYA
88
78
978







[Streptococcus gordonii]


54
1
3
227
gnl|PID|d101320
YqgU [Bacillus subtilis]
88
66
225


57
2
611
1468
gnl|PID|e134943
putative reductase 2 [Saccharomyces cerevisias]
88
75
858


65
3
5497
6069
pir|A29102|R5BS
ribosomal protein 1.5 - Bacillus stearothermophilus
88
75
573


65
20
9030
9500
gi|2078381
ribosomal protein L15 [Staphylococcus aureus]
88
83
471


78
3
3636
1108
gnl|PID|d100781
lysyl-aminopeptidase [Lactococcus lactis]
88
80
2529


106
12
12965
12054
gi|2407215
(AF017421) putative heat shock protein HtpX
88
72
912







[Streptococcus gordonii]


107
2
219
962
gnl|PID|e339862
putative acylneuraminate lyase [Clostridium tertium]
88
75
744


111
8
14073
10420
gi|402363
RNA polymerase beta-subunit [Bacillus subtilis]
88
74
3654


126
9
13096
12062
gnl|PID|e311468
unknown [Bacillus subtilis]
88
74
1035


140
17
19143
18874
gi|1573659


H. influenzae
predicted coding region H10659

88
61
270







[Haemophilus influenzae]


144
1
394
555
gnl|PID|e274705
lactate oxidase [Streptococcus iniae]
88
75
162


148
4
2723
3493
gi|1591672
phosphate transport system ATP-binding protein
88
68
771







[Methanococcus jannaschii]


160
8
5853
6278
gi|1773267
ATPase, epsilon subunit [Streptococcus mutans]
88
65
426


177
4
1770
2885
gi|149426
putative [Lactococcus lactis]
88
72
1116


211
6
4140
3613
gi|535273
aminopeptidase C [Streptococcus thermophilus]
88
74
528


231
4
580
957
gi|40186
homologous to E.coli ribosomal protein L27 [Bacillus subtilis]
88
78
378


260
5
2387
2998
gi|1196922
unknown protein [Insertion sequence IS861]
88
69
612


291
6
2017
3375
gnl|PID|d100571
adenylosuccinate synthetase [Bacillus subtilis]
88
75
1359


319
4
658
317
gi|603578
serine/threonine kinase [Phytophthora capsici]
88
88
342


40
5
4353
4514
gi|153672
lactose repressor [Streptococcus mutans]
87
56
162


49
10
10660
10929
gi|1196921
unknown protein [Insertion sequence IS861]
87
72
270


65
7
3140
3808
gi|1165309
S3 [Bacillus subtilis]
87
73
669


65
15
6623
7039
gi|1044978
ribosomal protein S8 [Bacillus subtilis]
87
73
417


75
8
5411
6625
gi|1877422
galactokinase [Streptococcus mutans]
87
78
1215


80
2
703
2805
gnl|PID|d101166
elongation factor G [Bacillus subtilis]
87
76
2103


82
1
541
248
gi|1196921
unknown protein [Insertion sequence IS861]
87
69
294


140
23
25033
23897
gnl|PID|e254999
phenylalany-tRNA synthetase beta subunit [Bacillus subtilis]
87
74
1137


214
14
10441
8516
gi|2281305
glucose inhibited division protein homolog GidA
87
75
1926







[Lactococcus lactis cremoris]


220
2
2742
874
gnl|PID|e324358
product highly similar to elongation factor EF-G
87
73
1869







[Bacillus subtilis]


260
4
2096
2389
gi|1196921
unknown protein [Insertion sequence IS861]
87
72
294


323
1
27
650
gi|897795
30S ribosomal protein [Pediococcus acidilactici]
87
73
624


357
1
154
570
gi|1044978
ribosomal protein S8 [Bacillus subtilis]
87
73
417


49
11
10927
11445
gi|1196922
unknown protein [Insertion sequence IS861]
86
63
519


59
12
7461
9224
gi|951051
relaxase [Streptococcus pneumoniae]
86
68
1764


65
4
1553
2401
pir|A02759|R5BS
ribosomal protein L2 - Bacillus stearothermophilus
86
77
849


65
23
10957
11610
gi|44074
adenylate kinase [Lactococcus lactis]
86
76
6541


82
4
4374
4856
gi|153745
mannitol-specific enzyme III [Streptococcus mutans]
86
72
483


102
4
270
4986
gnl|PID|e264705
CMP decarboxylase [Lactococcus lactis]
86
76
717


106
6
7824
6880
gnl|PID|e137598
aspartate transcarbamylasa [Lactobacillus leichmannii]
86
68
945


107
1
1
273
gnl|PID|e339862
putative acylneuraminate lyase [Clostridium tertiula]
86
71
273


111
7
10432
6710
gnl|PID|e228283
DNA-dependent RNA polymerase [Streptococcus pyogenes]
86
80
3723


131
9
5704
4892
gi|1661193
polipoprotein diacyiglycerol transferasa [Streptococcus mutans]
86
71
813


134
7
6430
7980
gi|2388637
glycerol kinase [Enterococcus feacalis]
86
73
1551


146
11
7473
6583
gi|1591731
melvalonate kinasa [Methanococcus jannaschii]
86
72
891


153
2
595
2010
gi|2160707
dipeptidase [Lactococcus lactis]
86
78
1416


154
1
2
1435
gi|1857246
6-phosphogluconate dehydrogenase [Lactococcus lactis]
86
74
1434


161
5
5025
6284
gi|47529
Unknown [Streptococcus selivarius]
86
66
1260


184
1
2
1483
gi|642667
NADP-dependent glyceraldehyde-3-phosphate dehydrogenase
86
73
1482







[Streptococcus mutans]


210
8
3659
6571
gi|153661
translational initiation factor IF2 [Enterococcus faecium]
86
76
2913


250
1
2
187
gi|1573551
asparagine synthetase A (asnA) [Haemophilus influenzae]
86
68
186


36
4
2644
3909
gi|2149909
cell division protein [Enterococcus feecalis]
85
73
1266


38
4
2475
3587
gi|2058545
putative ABC transporter subunit ComYB
85
72
1113







[Streptococcus gordonii]


38
5
3577
3915
gi|2058546
ComYC [Streptococcus gordonii]
85
80
339


57
5
2797
3789
gnl|PID|d101316
YgfJ [Bacillus subtilis]
85
72
993


82
5
4915
6054
gi|153746
mannitol-phosphate dehydrogenase [Streptococcus isutens]
85
68
1140


83
15
14690
15793
gi|143371
phosphoribosyl aminoimidezole synthetase (PUR-M)
85
69
1104







[Bacillus subtilis]


87
2
1417
2388
gi|184967
ScrR [Streptococcus mutans]
85
69
972


108
3
2666
3154
gi|153566
ORF (19K protein) [Enterococcus fascalis]
85
67
489


127
2
312
692
gi|1044989
ribosomal protein S13 [Bacillus subtilis]
85
72
381


128
3
1534
2409
gi|1685110
tetrahydrofolate dehydrogenase/cyclohydrolase
85
71
876







[Streptococcus thermophilus]


137
7
2962
4767
gnl|PID|d100347
Na+ -ATPase alpha subunit [Enterococcus hirae]
85
74
1806


170
2
2622
709
gnl|PID|d102006
(AF001488) FUNCTION UNKNOWN,
85
70
1914







SIMILAR PRODUCT IN E.COLI, N. INFLUENZAE AND









NEISSERIA MENINGITIDIS.
[Bacillus subtilis]



187
5
3760
4386
gi|727436
putative 20-kDa protein [Lactococcus lactis]
85
65
627


233
2
728
1873
gi|1163116
ORF-5 [Streptococcus pneumoniae]
85
67
1146


234
3
962
1255
gi|2293155
(AF008220) YtiA [Bacillus subtilis]
85
61
294


240
1
309
1931
gi|143597
CTP synthetase [Bacillus subtilis]
85
70
1623


6
1
199
1521
gi|508979
GTP-binding protein [Bacillus subtilis]
84
72
1323


10
4
4375
3443
gnl|PID|e339862
putative ecylneureminate lyase [Clostridium tertium]
84
70
933


14
1
63
2093
gi|520753
DNA topoisomerase I [Bacillus subtilis]
84
69
2031


19
4
1793
2593
gi|2352484
(AF005098) RNAseH II [Lectococcus lactis]
84
68
801


20
17
17720
19687
gnl|PID|d100584
cell division protein [Bacillus subtilis]
84
71
1968


22
28
21723
20884
gi|299163
alanine dehydrogenase [Bacillus subtilis]
84
68
840


30
10
7730
6792
gnl|PID|d100296
fructokinase [Streptococcus mutans]
84
75
939


33
9
5650
5300
gi|147194
phnA protein [Escherichia coli]
84
71
351


36
22
21551
20772
gi|310631l
ATP binding protein [Streptococcus gordonii]
84
72
780


48
4
2837
2505
gi|8826D9
6-phospho-beta-glucosidase [Eacherichia coli]
84
69
333


58
1
41
1518
gi|450849
emylese [Streptococcus bovis]
84
73
1478


59
10
6715
7116
gi|951053
ORF10, putative (Streptococcus pneumoniae]
84
74
402


62
1
21
644
gi|806487
ORF211; putative [Lactococcus lactis]
84
66
624


65
17
7779
8207
gi|1044980
ribosomal protein LiS [Bacillus subtilis]
84
73
429


65
21
9507
10397
gi|44073
SecY protein [Lactococcus lactis]
84
68
891


108
4
5474
2262
gnl|PID|e199387
carbamoyl-phosphate synthase [Lactobacillus plantarum]
84
73
3213


159
1
147
4
gi|806487
ORF211; putative [Lactococcus lactis]
84
63
144


163
4
4690
5910
gi|2293l64
(AP008220) SAN synthase [Bacillus subtilis]
84
69
1221


192
1
46
1308
gi|495046
tripeptidase [Lactococcus lactis]
84
73
1263


348
1
671
61
gi|1787753
(AE000245) f346; 79 pct identical to 336 amino acids of
84
71
666







ADH1_ZYMMO SW: P20368 but has 10 additional N-ter







residues [Eacherichia coli]


3
4
1572
3575
gi|143766
(thrSv) (EC 6.1.1.3) [Bacillus subtilis]
83
65
2004


9
6
3893
3417
gnl|PID|d100576
single strand DNA binding protein [Bacillus subtilis]
83
68
477


17
15
7426
8457
gi|520738
comA protein [Streptococcus pneumoniae]
83
66
1032


20
12
13860
14144
gnl|PID|d100583
unknown [Bacillus subtilis]
83
61
285


23
4
3358
2606
gi|1788294
(AE000290) o238; This 238 aa orf is 40 pct identical (5 gaps)
83
74
753







to 231 residues of an approx. 248 aa protein







YEBC_ECOLI SW: P24237 [Escherichia coli]


28
6
3304
3005
gi|1573659


H. influenzae
predicted coding region H10659

83
57
300







[Haemophilus influenzae]


35
7
5108
3867
gi|311707
hypothetical nucleotide binding protein [Acholeplasma laidlawii]
83
63
1242


55
19
17932
17528
gi|537085
ORF_f141 [Escherichia coli]
83
59
405


55
20
18539
17919
gi|496558
orfX [Bacillus subtilis]
83
69
621


65
6
2795
3142
gi|1165308
L22 [Bacillus subtilis]
83
64
348


68
6
6877
6683
gi|1213494
immunoglobulin A1 protease [Streptococcus pneumoniae]
83
54
195


87
15
15112
14771
gnl|PID|e323522
putative rpoZ protein [Bacillus subtilis]
83
54
342


96
12
8963
9631
gi|47394
5-oxoprolyl-peptidase [Streptococcus pyogenes]
83
73
669


98
1
3
263
gi|1183885
glutamine-binding subunit (Bacillus subtilis]
83
55
261


120
4
7170
5233
gi|310630
zinc metalloprotease [Streptococcus gordonii]
83
72
1938


127
7
2998
4347
gi|1500567


M. jannaschii
predicted coding region MJ1665

83
72
1350







[Methanococcus jannaschii]


137
1
3
440
gi|472918
v-type Na-ATPase [Enterococcus hirae]
83
60
438


160
6
3466
4356
gi|1773265
ATPase, gamma subunit [Streptococcus mutens]
83
67
891


214
4
2278
2964
gi|663279
transposase [Streptococcus pneumoniae]
83
72
687


226
3
2367
2020
gi|142154
thioredoxin [Synechococcus PCC6301]
83
58
348


303
1
3
1049
gi|40046
phosphoglucose isomerase A (AA 1-449)
83
67
1047







[Bacillus stearothermophilus]


303
2
1155
1931
gi|289282
glutamyl-tRNA synthetase [Bacillus subtilis]
83
67
777


6
17
15370
14318
gi|633147
ribose-phosphate pyrophosphokinase [Bacillus caldolyticus]
82
64
1053


7
1
299
961
gi|143648
ribosomal protein L28 [Bacillus subtilis]
82
69
204


9
3
1479
1090
gi|385178
unknown [Bacillus subtilis]
82
46
390


9
7
4213
3899
gnl|PID|d100576
ribosomal protein S6 [Bacillus subtilis]
82
60
315


12
6
4688
3942
gnl|PID|d100571
unknown [Bacillus subtilis]
82
68
747


22
17
13422
14837
gi|520754
putative [Bacillus subtilis]
82
69
1416


22
18
14897
15658
gnl|PID|d101929
uridine monophosphate kinase [Synechocystis sp.]
82
62
762


33
16
11471
10641
gnl|PID|d101190
ORF4 [Streptococcus mutans]
82
68
831


35
9
7400
6255
gi|1881543
UDP-N-acetylglucosamine-2-epimerase [Streptococcus
82
68
1146







pneumoniae]


40
10
8003
7533
gi|1173519
riboflavin synthase beta subunit [Actinobacillus
82
68
471







pleuropneumoniae]


48
32
23159
23437
gi|1930092
outer membrane protein [Campylobacter jejuni]
82
61
279


52
14
13833
14765
gi|142521
deoxyribodipyrimidine photolyase [Bacillus subtilis]
82
61
933


60
4
4737
1849
gnl|PID|d102221
(AB001610) uvrA [Deinococcus radiodurans]
82
66
2889


62
4
2131
1457
gi|2246749
(AF009622) thioredoxin reductase [Listeria monocytogenes]
82
63
675


71
11
16586
17518
gnl|PID|e322063
ss-1,4-galactosyltransferase [Streptococcus pneumoniae]
82
60
933


73
13
9222
7837
gnl|PID|d100586
unknown [Bacillus subtilis]
82
65
1386


74
1
1
3771
gnl|PID|d101199
alkaline amylopullulanese [Bacillus sp.]
82
68
3771


83
9
3696
3983
gnl|PID|e305362
unnamed protein product [Streptococcus thermophilus]
82
52
288


186
11
10776
9394
gi|6835831
5-enolpyruvylshikimate-3-phosphate synthase
82
67
1383







[Lactococcus lactia]


189
12
8295
9752
gi|40025
homologous to E.coli 50K [Bacillus subtilis]
82
66
1458


115
9
10347
8912
gnl|PID|d102090
(AB003927) phospho-beta-galactosidase 1 [Lactobacillus
82
74
1536







gasseri]


118
1
1
1332
gnl|PID|d100579
seryl-tRNA synthetase [Bacillus subtilis]
82
71
1332


151
3
4657
6246
pir|S06097|S060
type I site-specific deoxyribonuclease (EC 3.1.21.3)
82
66
1590







CfrA chain S - Citrobacter freundli


173
6
4183
3503
gi|2313836
(AE000584) conserved hypothetical protein [Helicobacter pylon]
82
68
681


177
12
5491
7442
gnl|PID|101999
(AB001343) NcrB [Escherichia coli]
82
58
1962


193
2
178
576
pir|S08564|R3BS
ribosomal protein S9 - Bacillus stearothermophilus
82
70
399


245
2
258
845
gi|146402
EcoA type I restriction-modification enzyme S subunit
82
68
588







[Escherichia coli]


9
5
3400
3146
gnl|PID|d100576
ribosomel protein S18 [Bacillus subtilis]
81
66
255


16
7
7484
8413
gi|110074
tryptophanyl-tRNA synthetase [Clostridium longisporum]
81
70
930


20
11
10308
13820
gnl|PID|d100583
transcription-repair coupling factor [Bacillus subtilis]
81
63
3513


38
2
1232
1606
gi|2058543
putative DNA binding protein [Streptococcus gordonii]
81
63
375


45
2
3061
1751
gi|460259
enolase [Bacillus subtilis]
81
67
1311


46
1
2
1267
gi|431231
uracil permease [Bacillus caldolyticus]
81
61
1266


148
3
2453
1440
gnl|PID|d100453
Mannosephosphate Isomarase [Streptococcus mutans]
81
70
1014


54
2
1106
336
gi|154752
transport protein [Agrohactanium tumefaciens]
81
64
771


65
22
10306
10821
gi|44073
SecY protein [Lactococcus lactis]
81
66
516


89
4
3874
2603
gi|556886
serine hydroxymethyltransferase [Bacillus subtilis]
81
69
1272


99
16
19126
18929
gi|2313526
(AE000557) H. pylon predicted coding region HP0411
81
75
198







[Helicohacter pylon]


106
7
8373
7822
gnl|PID|e199384
pyrR [Lactobacillus plantarum]
81
61
552


108
6
5054
6877
gi|1469939
group B oligopeptidase PepB [Streptococcus agalactiae]
81
66
1824


113
15
15899
18283
pir|S09411|S094
spoIIIE protein - Bacillus subtilis]
81
65
2385


128
5
3359
3634
gi|1685111
orf1091 [Streptococcus thermophilus]
81
69
276


151
1
830
3211
gi|304896
EcoK type I restriction-modification enzyme R subunit
81
59
2382







[Escherichia coli]


159
11
6722
7837
gi|2239288
GMP synthetase [Bacillus subtilis]
81
69
1116


170
1
739
458
gnl|PID|d102008
(AB001488) FUNCTION UNKNOWN. [Bacillus subtilis]
81
55
282


191
2
1759
893
gi|149522
tryptophan synthase alpha subunit [Lactococcus lactis]
81
65
867


214
3
2290
1994
gi|157587
reverse transcriptese endonuclease [Drosophila virilis]
81
43
297


217
4
4415
4008
gi|466473
cellobiose phosphotransferase enzyme II′
81
59
408







[Bacillus stearothermophilus]


262
2
569
868
gi|153675
tagatose 6-P kinase [Streptococcus mutans]
81
68
300


299
1
863
4
gnl|PID|e301154
StySKI methylase [Salmonella enterica]
81
60
660


366
2
376
83
gi|149521
tryptophan synthase beta subunit [Lectococcus lactis]
81
65
294


12
10
8768
9242
gi|1218490
DNA/pantothenate metabolism flavoprotein
80
64
477







[Streptococcus mutans]


17
11
6050
5748
gn|PID|e305362
unnamed protein product [Streptococcus thermophilus]
80
67
303


17
16
8455
9066
gi|703126
leucocin A translocator [Leuconostoc gelidum]
80
59
612


18
3
2440
1613
gi|1591672
phosphate transport system ATP-binding protein
80
58
828







[Methanococcus jannaschii]


27
3
4248
1579
gi|452309
valyl-tRNA synthetase [Bacillus subtilis]
80
69
2670


28
7
3671
3288
gi|1573660


H. influenzae
predicted coding region H10680

80
63
384







[Haemophilus influenzae]


32
2
902
1933
gnl|PID|e264499
dihydroorotate dehydrogenase B [Lactococcus lactic]
80
66
1032


39
1
1
1266
gnl|PID|e234078
hom [Lactococcus lactis]
80
63
1266


52
5
4363
3593
gi|1183884
ATP-binding subunit [Bacillus subtilis]
80
57
771


54
5
4550
4744
gi|2198820
(AF004225) Cux/CDP(1B1); CuX/CDP homeoprotein
80
60
195







[Mus musculus]


59
11
7109
7486
gi|951052
ORF9, putative [Streptococcus pneursoniae]
80
68
378


65
3
1230
1550
pir|A02815|R5BS
ribosomal protein L23 - Bacillus stearothermophilus
80
69
321


65
12
5174
5503
pir|A02819|R5BS
ribosomal protein L24 - Bacillus stearothermophilus
80
70
330


66
9
9884
10687
gi|2313836
(AE000584) conserved hypothetical protein [Helicobacter pylon]
80
68
804


82
2
648
2438
gi|622991
mannitol transport protein [Bacillus stearothermophilus]
80
65
1791


85
1
950
630
gi|528995
polyketide synthase [Bacillus subtilis]
80
46
321


89
8
6870
5779
gi|853776
peptide chain release factor 1 [Bacillus subtilis]
80
63
1092


93
12
8718
7438
gnl|PID|d101959
hypothetical protein [Synechocystis sp.]
80
60
1281


106
5
6854
5751
gnl|PID|e199386
glutaminase of carbamoyl-phosphate synthase
80
65
1104







[Lactohacillus plantarum]


109
2
2160
1450
gi|40056
phoP gene product [Bacillus suhtilis]
80
59
711


124
9
4246
3953
gnl|PID|d102254
30S ribosomal protein S16 [Bacillus suhtilis]
80
65
294


128
8
5148
6428
gi|2281308
phosphopentomutase [Lectococcus lactis cremoris]
80
66
1281


137
19
12665
11376
gi|159109
NADP-dependent glutamate dehydrogenase [Giardia
80
68
1290







intestinalis]


140
19
19699
19457
gi|517210
putative transposase [Streptococcus pyogenes]
80
70
243


158
2
2474
984
gi|1877423
galactose-1-P-uridyl transferasa [Streptococcus mutans]
80
65
1491


171
10
7474
7728
gi|397800
cyclophilin C-associated protein [Mus musculus]
80
60
255


181
1
2
6191
gi|149395
lacC [Lactococcus lactic]
80
66
618


313
1
27
539
gi|143467
ribosomal protein S4 [Bacillus subtilis]
80
70
513


329
2
1652
858
gi|533080
RecF protein [Streptococcus pyogenes]
80
63
795


371
1
2
958
gi|442360
ClpC adenosine triphosphatase [Bacillus subtilis]
80
58
957


8
7
4312
5580
gi|149435
putative [Lactococcus lactic]
79
64
1269


23
1
1175
135
gi|1542975
AbcB [Thermoanaerobacterium thermosulfurigenes]
79
61
1041


33
14
9244
8201
gnl|PID|5253891
UDP-glucose 4-epimerase [Bacillus subtilis]
79
62
1044


36
3
1242
2633
gnl|PID|e324218
ftsA [Enterococcus hirae]
79
58
1392


38
13
7155
8378
gi|405134
acetate kinase [Bacillus subtilis]
79
58
1224


55
7
9011
8229
gi|1146234
dihydrodipicolinate reductase [Bacillus subtilis]
79
56
783


65
19
8661
8915
gi|2078380
ribosomal protein L30 [Staphylococcus aureus]
79
68
255


69
4
3678
2128
gnl|PID|e311452
unknown [Bacillus subtilis]
79
64
1551


69
9
7881
7279
gi|677850
hypothetical protein [Staphylococcus aureus]
79
59
603


72
10
8491
9783
gnl|PID|d101091
hypothetical protein [Synechocystis sp.]
79
62
1293


80
3
2906
7300
gi|143342
polymerase III [Bacillus subtilis]
79
65
4395


82
14
13326
15689
gnl|PID|e255093
hypothetical protein [Bacillus subtilis]
79
65
2364


86
13
12233
11118
gi|683582
prephenate dehydrogenase [Lactococcus lactic]
79
58
1116


92
3
940
1734
gi|537286
triosephosphate isomerase [Lactococcus lactis]
79
65
795


98
6
4023
4742
gnl|PID|d100262
LivG protein [Salmonella typhimurium]
79
63
720


99
12
16315
14150
gi|153736
a-galactosidase [Streptococcus mutans]
79
64
2166


107
7
5684
6406
gi|460080
D-alanine: D-alanine ligase-related protein [Enterococcus
79
58
723







faecalis]


113
9
6858
8303
gi|466982
pps1; B1496_C2_189 [Mycobacterium leprae]
79
64
1446


151
10
13424
12213
gi|450686
3-phosphoglycerate kinase [Thermotoga maritima]
79
60
1212


162
2
1158
3017
gi|506700
CapD [Staphylococcus aureus]
79
67
1860


177
5
2876
3052
gi|912423
putative [Lactococcus lactis]
79
61
177


177
8
4198
4563
gi|149429
putative [Lactococcus lactic]
79
61
3681


187
3
2728
2907
gnl|PID|d102002
(AB001488) FUNCTION UNKNOWN. [Bacillus subtilis]
79
53
180


189
7
3589
4350
gnl|PID|e183449
putative ATP-binding protein of ABC-type [Bacillus subtilis]
79
61
762


191
5
4249
3449
gi|149519
indoleglycerol phosphate synthase [Lactococcus lactis]
79
66
801


211
3
1805
2737
gi|147404
mannose permease suhunit II-M-Man [Escherichia coli]
79
57
933


212
3
3863
3621
gnl|PID|e209004
glutaredoxin-like protein [Lactococcus lactis]
79
58
243


215
1
987
715
gi|2293242
(AF008220) arginine succinate synthase [Bacillus subtilis]
79
64
273


323
2
530
781
gi|897795
30S ribosomal protein [Pediococcus acidilactici]
79
67
252


380
1
694
2
gi|1184680
polynucleotide phosphorylase [Bacillus subtilis]
79
64
693


384
2
655
239
gi|143328
phoP protein (put.); putative [Bacillus subtilis]
79
59
417


6
3
2820
4091
gi|853767
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
78
62
1272







[Bacillus subtilis]


8
1
50
1786
gi|149432
putative [Lactococcus lactic]
78
63
1737


9
1
351
124
gi|897793
y98 gene product [Pediococcus acidilactici]
78
59
228


15
8
7364
8314
gnl|PID|d100585
cysteine synthetase A [Bacillus subtilis]
78
63
951


20
10
9738
10310
gnl|PID|d100583
stage V sporulation [Bacillus subtilis]
78
58
573


20
16
17165
17713
gi|49105
hypoxanthine phosphoribosyltransferase [Lactococcus lactis]
78
59
549


22
22
17388
18416
gnl|PID|d101315
YqfE [Bacillus subtilis]
78
60
1029


22
27
20971
20612
gi|299163
alanine dehydrogenase [Bacillus subtilis]
78
59
360


34
8
7407
7105
gi|41015
aspartate-tRNA ligase [Escherichia coli]
78
55
303


35
8
6257
5196
gi|657644
Cap8E [Staphylococcus aureus]
78
60
1062


40
11
9287
8001
gi|1173518
GTP cyclohydrase II/ 3,4-dihydroxy-2-butanone-4-phosphate
78
58
1287







synthase [Actinobacillus pleuropneumoniae]


48
131
22422
23183
gi|2314330
(AE000623) glutamine ABC transporter, ATE-binding protein
78
58
762







(glnQ) [Helicobacter pylon]


52
2
2101
1430
gi|1183887
integral membrane protein [Bacillus subtilis]
78
57
672


55
14
13605
12712
gnl|PID|d102026
(AB002150) YbbP [Bacillus subtilis]
78
58
894


55
17
16637
15612
gnl|PID|e313027
hypothetical protein [Bacillus subtilis]
78
51
1026


71
14
19756
19598
gi|179764
calcium channel alpha-1D subunit [Homo sapiens]
78
57
159


74
11
1503
14018
gi|1573279
Holliday junction DNA helicase (ruvB) [Haemophilus
78
57
1014









influenase
]



75
9
6623
7972
gi|1877423
galactose-1-P-uridyl transferase [Streptococcus mutans]
78
62
1350


81
12
12125
13906
gi|1573607
L-fucose isomerase (fucI) [Haemophilus influenzae]
78
66
1782


82
3
2423
4417
gi|1537440
ORF X; putative [Streptococcus mutans]
78
64
1995


83
18
16926
18500
gi|143373
phosphoribosyl aminoimidazole carboxy formyl
78
63
1575







formyltransferase/inosine monophosphate cyclohydrolase







(PUR-H(J)) [Bacillus subtilis]


83
20
20212
20775
gi|143364
phosphoribosyl aminoimidazole carboxylase I (PUR-E)
78
64
564







[Bacillus subtilis]


92
2
165
878
gnl|PID|d101190
PRF2 [Streptococcus mutans]
78
62
714


98
8
5863
6909
gi|2331287
(AE013188) release factor 2 [Bacillus subtilis]
78
63
1047


113
3
1071
2741
gi|580914
dnaZX [Bacillus subtilis]
78
64
1671


127
4
1133
2071
gi|142463
RNA polymerase alpha-core-subunit [Bacillus subtilis]
78
59
939


132
1
2782
497
gi|1561763
pullulanase [Bactaroides thetaiotaomicron]
78
58
2286


135
4
2698
3537
gi|1788036
(AE000269) NH3-dependent NAD synthetase [Escherichia coli]
78
66
840


140
24
26853
25423
gi|1100077
phospho-beta-glucosidase [Clostridium longisporum]
78
64
1431


150
5
4690
4514
gi|149464
amino peptidase [Lactococcus lactis]
78
42
177


152
1
1
795
gi|639915
NADH dehydrogenase subunit [Thunbergia alata]
78
43
795


162
4
4997
4110
gnl|PID|e323528
putative YhaP protein [Bacillus subtilis]
78
64
888


181
10
8651
7947
gi|149402
lactose repressor (lacR; alt.) [Lactococcus lactis]
78
48
705


200
4
3627
4958
gnl|PID|d100172
invertase [Zymomonas mobilis]
78
61
1332


203
3
3230
3015
gi|1174237
CycK [Pseudomonas fluorescens]
78
57
216


210
9
6789
7172
gi|580902
ORF6 gene product [Bacillus subtilis]
78
42
384


214
6
3810
2797
gnl|PID|d102049


P. haemolytica
o-sialoglycoprotein endopeptidese; P36175 (660)

78
60
1014







transmembrane [Bacillus subtilis]


214
13
6322
8163
gi|1377831
unknown [Bacillus subtilis]
78
62
1842


217
1
9
2717
gi|1488430
alcohol dehydrogenase 2 [Entamoeba histolytica]
78
64
2709


222
3
2316
3098
gi|1573047
spore germination and vegetative growth protein (gerC2)
78
65
783







[Haemophilus influenzae]


268
1
742
8
gi|517210
putative transposase [Streptococcus pyogenes]
78
65
735


276
1
223
753
gnl|PID|d100306
ribosomal protein L1 [Bacillus subtilis]
78
65
531


312
3
1567
1079
gi|289261
comE ORF2 [Bacillus subtilis]
78
54
489


339
1
117
794
gi|1916729
CadD [Staphylococcus aureus]
78
53
678


342
2
762
265
gi|1842439
phosphatidylglycerophosphate synthase [Bacillus subtilis]
78
59
498


383
1
737
3
gi|1184680
polynucleotide phosphorylase [Bacillus subtilis]
78
64
735


7
15
11923
11018
gi|1399855
carboxyltransferase beta subunit [Synechococcus P007942]
77
63
906


8
2
1698
2255
gi|149433
putative [Lactococcus lactic]
77
59
558


17
14
6948
7550
gi|520738
comA protein [Streptococcus pneumoniae]
77
60
603


30
12
9761
8967
gi|100451
TraP [Bacillus subtilis]
77
43
795


36
14
11421
12131
gi|1573766
phosphoglyceromutase (gpmA) [Haemophilus influenzae]
77
64
711


55
3
3836
4098
gi|1708840
YeaB [Bacillus subtilis]
77
55
261


61
8
8377
8054
gi|1890649
multidrug resistance protein LisrA [Lactococcus lactic]
77
51
324


65
2
607
1254
gi|40103
ribosomal protein L4 [Bacillus stearothermophilus]
77
63
648


68
8
7509
7240
gi|47551
MRP [Streptococcus suis]
77
68
270


69
1
1083
118
gnl|PID|e311493
unknown [Bacillus subtilis]
77
57
966


77
5
4583
4026
gnl|PID|e281578
hypothetical 12.2 kd protein [Bacillus subtilis]
77
60
558


83
14
13104
14552
gi|1590947
amidophosphoribosyltransferase [Methanococcus jannaschii]
77
56
1449


94
4
3006
5444
gnl|PID|e329895
(AJ000496) cyclic nucleotide-gated channel beta subunit
77
66
2439







[Rattus norvegicus]


96
11
8518
8880
gi|5518791
ORF 1 [Lactococcus lactis]
77
62
363


99
11
14082
12799
gi|153737
sugar-binding protein [Streptococcus mutans]
77
61
1284


106
2
361
1176
gi|148921
LicD protein [Haemophilus influenzae]
77
51
816


108
4
3152
4030
gi|1574730
tellurite resistance protein (tehB) [Haemophilus influenzae]
77
58
879


118
4
3520
3131
gi|1573900
D-alanine permease (dagA) [Haemophilus influenzae]
77
57
390


124
4
1798
1071
gi|1573162
tRNA (guanine-N1)-methyltransferese (trmD)
77
58
728







[Haemophilus influenzae]


126
4
5909
4614
gnl|PID|d101163
Srb [Bacillus subtilis]
77
62
1298


128
2
630
1373
gnl|PID|d101328
YqiZ [Bacillus subtilis]
77
58
744


130
1
1
1287
gnl|PID|e325013
hypothetical protein [Bacillus subtilis]
77
61
1287


139
5
4388
3639
gi|2293302
(AF008220) YtqA [Bacillus subtilis]
77
59
750


140
11
10931
9582
gi|289284
cysteinyl-tRNA synthetase [Bacillus subtilis]
77
64
1350


140
18
19451
19283
gi|517210
putative transposase [Streptococcus pyogenes]
77
66
189


141
2
976
1683
gnl|PID|e157887
URF5 (aa 1-573) [Drosophila yakuba]
77
50
708


141
4
2735
5293
gi|556258
secA [Listeria monocytogenes]
77
59
2559


144
2
671
2173
gnl|PID|d100585
lysyl-tRNA thynthetase [Bacillus subtilis]
77
61
1503


163
5
6412
7398
gi|511015
dihydroorotate dehydrogenese A [Lactococcus lactis]
77
62
987


164
10
7841
7074
gnl|PID|d100964
homologue of iron dicitrate transport ATP-binding protein FacE
77
52
768







of E. coli [Bacillus subtilis]


191
8
7257
5791
gi|149516
anthranilate synthase alpha subunit [Lactococcus lactis]
77
57
1467


198
8
5377
5177
gi|1573856
hypothetical [Haemophilus influenzae]
77
66
201


213
1
202
462
gi|743860
Brca2 [Mus musculus]
77
50
261


250
2
231
509
gnl|PID|e334776
YlbH protein [Bacillus subtilis]
77
60
279


289
3
1737
1276
gnl|PID|d100947
Ribosomal Protein L10 [Bacillus subtilis]
77
62
462


292
2
1399
668
gi|143004
transfer RNA-Gln synthetase [Bacillus stearothermophilus]
77
58
732


7
3
2734
1166
gnl|PID|d101824
peptide-chain-release factor 3 [Synechocystis sp.]
76
53
1569


7
23
18474
18235
gi|455157
acyl carrier protein [Cryptomonas phi]
76
57
240


9
8
5706
4342
gi|1146247
asparaginyl-tRNA synthetase [Bacillus subtilis]
76
61
1365


10
5
4531
4385
gnl|PID|e314495
hypothetical protein [Clostridium perfringens]
76
53
147


18
2
1615
842
gi|1591672
phosphate transport system ATP-binding protein
76
56
774







[Methanococcus jannsschii]


22
37
27796
28173
gnl|PID|e13389
translation initiation factor 1F3 (AA 1-172) [Bacillus
76
64
378









stearothermophilus
]



35
6
3869
2662
gi|1773346
Cap5G [Staphylococcus aureus]
76
61
1188


48
28
21113
21787
gi|2314328
(AE000623) glutamins ABC transporter, permease protein (glnP)
76
52
675







[Helicobacter pylon]


52
12
12881
13786
gi|142521
deoxyribodipyrimidine photolyase [Bacillus subtilis]
76
58
906


55
10
11521
10571
gnl|PID|e283110
femD [Staphylococcus aureus]
76
61
951


57
8
7824
6559
gi|290561
o188 [Escherichia coli]
76
47
1266


62
5
2406
2095
gnl|PID|e313024
hypothetical protein [Bacillus subtilis]
76
79
312


65
9
4223
4441
gi|40148
L29 protein (AA 1-66) [Bacillus subtilis]
76
58
219


68
2
1328
2371
gnl|PID|e284233
anabolic ornithine carbamoyltransferase [Lactobacillus
76
61
1044









plantarum
]



69
8
7297
6005
gnl|PID|d101420
pyrimidine nucleoside phosphorylase [Bacillus
76
61
1293









stearothermophilus
]



73
12
7839
7267
gnl|PID|e243629
unknown [Mycobacterium tuberculosis]
76
53
573


74
5
8433
7039
gnl|PID|d102048
C. thermocellum beta-glucosidase; P26208 (985)
76
60
1395







[Bacillus subtilis]


80
5
7643
7936
gi|2314030
(AE000599) conserved hypothetical protein [Helicobacter pylon]
76
61
294


82
15
16019
16996
gi|1573900
D-alanine permease (dagA) [Hasmophilus influenzae]
76
56
978


83
19
18616
19884
gi|143374
phosphoribosyl glycinamide synthetase (PUR-D; gtg start codon)
76
60
1269







[Bacillus subtilis]


86
14
13409
12231
gi|143806
AroF [Bacillus subtilis]
76
58
1179


87
1
3
1442
gi|153804
sucrose-6-phosphate hydrolase [Streptococcus mutans]
76
59
1440


87
16
15754
15110
gnl|PID|e323500
putative Gmk protein [Bacillus subtilis]
76
56
645


93
4
1769
1539
gi|1574820
1,4-alpha-glucan branching enzyme (plgB) [Haemophilus
76
46
231









influenzae
]



94
1
51
365
gi|144313
6.0 kd ORF [Plasmid ColE1]
76
73
315


116
2
2151
1678
gi|153841
pneumococcei surface protein A [Streptococcus pneumoniae]
76
59
474


123
6
3442
5895
gi|1314297
ClpC ATPase [Listeria monocytogenes]
76
59
2454


126
12
2156
2932
gnl|PID|d101328
YqiZ [Bacillus subtilis]
76
61
777


128
10
6973
7797
gi|944944
Purina nucleoside phosphorylase [Bacillus subtilis]
76
60
825


131
11
6186
5812
gi|1674310
(A5000058) Mycoplasma pneumoniae, MG085 homolog, from
76
47
375









M. genitalium
[Mycoplasma pneumoniae]



139
4
3641
3192
gi|2293302
(AF008220) YtqA [Bacillus subtilis]
76
53
450


140
14
14872
12536
gi|1184680
polynucleotide phosphorylase [Bacillus subtilis]
76
62
2337


143
2
2583
3905
gi|143795
transfer RNA-Tyr synthetase [Bacillus subtilis]
76
61
1323


170
6
5095
6114
gnl|PID|d100959
ycgQ [Bacillus subtilis]
76
44
1020


180
2
1927
557
gi|400191
ORF 821 (as 1-821) [Bacillus subtilis]
76
53
1371


191
7
5815
5228
gi|551880
anthranilate synthase bets subunit [Lactococcus lactis]
76
61
588


195
3
3829
2444
gi|2149905
D-glutamic acid adding enzyme [Enterococcus faecalis]
76
60
1386


200
3
1914
3629
gi|4312721
lysis protein [Bacillus subtilis]
76
58
1716


201
1
431
207
gi|2208998
dextran glucosidase DexS [Streptococcus suis]
76
57
225


214
2
1283
2380
gi|663278
transposase [Streptococcus pneumoniael
76
55
1098


225
3
2338
3411
gi|1552775
ATP-binding protein [Escherichia coli]
76
56
1074


233
1
2
724
gi|1163115
neuraminidase B [Streptococcus pneumoniae]
76
60
723


347
1
523
38
gi|5370331
ORF_f356 [Escherichia coli]
76
60
486


356
2
842
165
gi|2149905
D-glutamic acid adding enzyme [Enterococcus faecalis]
76
61
678


366
3
734
348
gi|149520
phosphoribosyl anthranilate isomerasa [Lactococcus lactic]
76
69
387


5
8
12599
11484
gi|1574293
fimbrial transcription regulation repressor (pilB)
75
61
1116







[Haemophilus influenzae]


6
13
12553
11894
gnl|PID|d102050
ydiH [Bacillus subtilis]
75
51
660


9
10
7282
6062
gi|142538
aspartate aminotransferase [Bacillus sp.]
75
55
1221


10
12
8080
7940
gi|149493
SCRFI methylase [Lactococcus lactic]
75
56
141


18
5
4266
3301
gnl|PID|d101319
YqgH [Bacillus subtilis]
75
52
966


22
4
1838
2728
gi|1373157
orf-X; hypothetical protein; Method: conceptual translation
75
62
891







supplied by author [Bacillus subtilis]


30
11
9015
7828
gi|153801
enzyme scr-II [Streptococcus mutans]
75
64
1188


31
5
2362
2030
gi|229321
(AF008220) putative thioredoxin [Bacillus subtilis]
75
53
333


32
9
7484
8359
gnl|PID|d100560
formamidopyrimidine-DNA glycosylasa [Streptococcus mutans]
75
61
876


33
4
1735
1448
gi|413976
ipa-52r gene product [Bacillus subtilis]
75
53
288


33
10
6470
5769
gi|533105
unknown [Bacillus subtilis]
75
56 702


33
12
6878
7183
pir|A00205|FECL
ferredoxin [4Fe-4S] - Clostridium thermaceticum
75
56
306


36
1
181
2
gi|2088739
(AF003141) strong similarity to the FABP/P2/CRBP/CRABP
75
43
180







family of transporters [Caenorhabditis elegans]


38
22
14510
15379
gi|1574056
hypothetical [Haemophilus influenzae]
75
56
870


48
33
23398
24066
gi|1930092
outer membrane protein [Campylobacter jejuni]
75
56
669


51
1
2
319
gi|43985
nifS-like gene [Lactobacillus delbrueckii]
75
55
318


51
10
8318
1683
gi|5371921
CG Site No. 620; alternate gene names hs, hsp, hsr, rm; apparent
75
50
3366







frameshift in GenBank Accession Muster X06545







[Escherichia coli]


54
18
19566
20759
gi|666069
orf2 gene product [Lactobacillus leichmannii]
75
58
1194


57
9
8448
7822
gi|290561
o188 [Escherichia coli]
75
50
627


65
14
6072
6356
gi|606241
30S ribosomal subunit protein S14 [Escherichia coli]
75
64
285


70
4
3071
2472
gi|1256617
adenine phosphoribosyltranaferase [Bacillus subtilis]
75
57
600


71
24
30399
29404
gi|1574390
C4-dicarboxylate transport protein [Haemophilus influenzae]
75
57
996


73
2
910
455
gnl|PID|e249656
YneT [Bacillus subtilis]
75
57
456


79
1
1810
491
gi|1146219
28.2% of identity to the Escherichia coli DTP-binding protein
75
59
1320







Era; putative [Bacillus subtilis]


82
6
6360
6536
gi|1655715
BztD [Rhodobacter capsulatus]
75
55
177


83
6
1938
2975
gnl|PID|e323529
putative PlaX protein [Bacillus subtilis]
75
56
1038


93
11
7368
5317
gi|39989
methionyl-tRNA synthetase [Bacillus stearothermophilus]
75
58
2052


93
13
9409
6699
gi|1591493
glutamine transport ATP-binding protein Q [Methanococcus
75
54
711







jannaschii]


95
1
17951
47
gnl|PID|e323510
YloV protein [Bacillus subtilis]
75
57
1749


103
2
362
1186
gnl|PID|e266928
unknown [Mycobacterium tuberculosis]
75
64
825


104
1
691
915
gi|460026
repressor protein [Streptococcus pneumoniae]
75
54
225


113
5
2951
3883
gnl|PID|d101119
ABC transporter subunit [Synechocystis sr.]
75
55
933


121
1
320
1390
gi|2145131
repressor of class I heat shock gene expression HrcA
75
58
1071







[Streptococcus mutans]


127
6
2614
3000
gi|1500451


M. jennaschii
predicted coding region MJ1558

75
44
367







[Methanococcus jannaschii]


137
18
10082
10687
gi|393116
P-glycoprotein 5 [Entamoeba hiatolytica]
75
52
606


149
11
8499
9338
gnl|PID|d100582
unknown [Bacillus subtilis]
75
55
840


151
6
9100
7673
gi|40467
HsdS polypeptide, part of CfrA family [Citrobacter freundil]
75
57
1428


158
1
986
3
gnl|PID|e253891
UDP-glucose 4-epimerase [Bacillus subtilis]
75
63
984


172
8
5653
6774
gi|142978
glycerol dehydrogenase [Bacillus stearothermophilus]
75
56
1122


172
9
7139
9730
gnl|PID|e26B4S6
unknown [Mycobactarium tuberculosis]
75
58
2592


173
1
261
79
gnl|PID|e236469
C10C5.6 [Caenorhabditis alegans]
75
50
183


185
3
3066
2014
gi|1574906
spermidine/putrescine transport ATP-binding protein (potA)
75
56
1053







[Haemophilus influenzae]


191
6
5235
4213
gi|149518
phosphoribosyl anthranilate transferase [Lactococcus lactis]
75
61
1023


226
2
1774
1181
gi|2314588
(AE000642) conserved hypothetical protein [Helicobacter pylon]
75
65
594


231
1
1
153
gi|40173
homolog of E.coli ribosomal protein L21 [Bacillus subtilis]
75
57
153


234
1
2
418
gi|2293259
(AF008220) YtqI [Bacillus subtilis]
75
59
417


279
1
552
151
gi|1119198
unknown protein [Bacillus subtilis]
75
50
402


291
7
3558
3827
gi|40011
ORF17 (AA 1-161) [Bacillus subtilis]
75
48
270


375
2
137
628
gi|410137
ORFX13 [Bacillus subtilis]
75
58
492


6
20
16721
17560
gi|2293323
(AF008220) YtdI [Bacillus subtilis]
74
53
840


7
6
4682
6052
gi|1354211
PET112-like protein [Bacillus subtilis]
74
60
1371


18
4
3341
2427
gnl|PID|d101319
YggI [Bacillus subtilis]
74
54
915


21
6
5885
4800
gi|107238
glutamyl-aminopeptidase [Lactococcus lactis]
74
59
1086


24
2
739
548
gi|2314762
(AE000655) ABC transporter, permease protein (yaeE)
74
46
192







[Helicobacter pylon]


25
1
2
367
gnl|PID|d100932
H2O-forming NADH Oxidase [Streptococcus mutans]
74
63
366


38
18
11432
12964
gi|537034
ORF_o488 [Eschenichia coli]
74
57
1533


48
10
8924
6669
gi|1513069
P-type adenosine triphosphatase [Listeria monocytogenes]
74
53
2256


55
11
11964
11401
gnl|PID|e283110
femD [Staphylococcus aureus]
74
64
564


61
2
1782
427
gi|2293216
(AF008220) putative UDP-N-acetylmuramate-alanine ligase
74
55
1356







[Bacillus subtilis]


76
10
9414
8065
gnl|PID|d101325
YqiB [Bacillus subtilis]
74
54
1350


83
2
666
9261
pir|C33496|C334
hisC homolog - Bacillus subtilis
74
55
261


86
9
8985
8080
gi|683585
prephenate dehydratase [Lactococcus lactis]
74
55
906


102
5
5005
5652
gi|143394
OMP-PRPP transferase [Bacillus subtilis]
74
57
648


103
5
4364
3267
gnl|PID|e323524
YloN protein [Bacillus subtilis]
74
62
1098


108
7
6864
7592
gnl|PID|e257631
methyltransferase [Lactococcus lactis]
74
56
729


131
2
478
146
gnl|PID|d101320
YqgZ [Bacillus subtilis]
74
45
333


133
2
1380
919
gnl|PID|e313025
hypothetical protein [Bacillus subtilis]
74
60
462


137
9
6167
6787
gnl|PID|d100479
Na+ -ATPase subunit D [Enterococcus hirae]
74
53
621


149
4
3008
3883
gnl|PID|d100581
high level kasgamycin resistance [Bacillus subtilis]
74
55
876


157
2
243
824
gi|1573373
methylated-DNA-protein-cysteine methyltransferasa (dat1)
74
48
582







[Haemophilus influenzae]


164
6
3515
4249
gi|410131
ORFX7 [Bacillus subtilis]
74
48
735


167
7
5446
5201
gi|413927
ipa-3r gene product [Bacillus subtilis]
74
55
246


171
1
1
1818
gnl|PID|d102251
beta-galactosidase [Bacillus circulans]
74
62
1818


172
4
1064
2392
gi|466474
cellobiose phosphotransferase enzyme II′′ [Bacillus
74
50
1329







stearothermophilus]


185
1
326
3
gi|1573646
Mg(2+) transport ATPase protein C (mgtC) (SP:P22037)
74
68
324







[Haemophilus influenzae]


188
2
1089
2018
gi|1573008
ATP dependent translocator homolog (ashA)
74
44
930







[Haemophilus influenzae]


189
11
6491
7174
gi|1661199
sakacin A production response regulator [Streptococcus mutans]
74
60
684


210
2
520
1287
gi|2293207
(AE008220) YtmQ [Bacillus subtilis]
74
60
768


261
1
836
192
gi|666983
putative ATP binding subunit [Bacillus subtilis]
74
55
645


263
3
1619
3655
gi|663232
Similarity with S. cerevisise hypothetical 137.7 kD protein in
74
42
2037







subtelomeric Y′ repeat region [Saccharomyces cerevisise]


265
2
644
1227
gi|49272
Asparaginase [Bacillus licheniformis]
74
64
384


368
1
1
942
gi|603998
unknown [Saccharomyces cerevisiae]
74 39
942


7
16
13357
11921
gnl|PID|d101324
YqhX [Bacillus subtilis]
73
57
1437


17
10
5706
5449
gnl|PID|e305362
unnamed protein product [Streptococcus thermophilus]
73
47
258


31
2
522
244
gnl|PID|d100576
single strand DNA binding protein [Bacillus subtilis]
73
55
279


32
6
5667
6194
gnl|PID|d101315
YqfG [Bacillus subtilis]
73
58
528


34
15
10281
9790
gnl|PID|d102151
(A8001684) ORF42c [Chlorella vulgaris]
73
46
492


40
12
9876
9226
gi|1173517
riboflavin synthase alpha subunit [Actinobacillus
73
55
651







pleuropneumoniae]


55
2
3592
839
gnl|PID|d101887
cation-transporting ATPase PacL [Synechocystis sp.]
73
60
2754


55
18
17494
16586
gnl|PID|e265580
unknown [Mycobacterium tuberculosis]
73
52
909


65
16
7213
7767
gi|143419
ribosomal protein L6 [Bacillus stearothermophilus]
73
60
555


66
3
3300
3659
gnl|PID|e269883
LacF [Bactobacillus casei]
73
52
360


70
10
5557
5733
gi|857631
envelope protein [Human immunodeficiency virus type 1]
73
60
177


71
4
6133
8262
gnl|PID|e322063
ss-1,4-galactosyltransferase [Streptococcus pneumoniae]
73
45
2130


72
1
3
851
gi|2293177
(AF008220) transporter [Bacillus subtilis]
73
50
849


76
7
7019
6195
gnl|PID|d101325
YqiF [Bacillus subtilis]
73
66
825


76
12
10009
9533
gi|1573086
uridine kinase (uridine monophosphokinase) (udk)
73
54
477







[Haemophilus influenzae]


80
7
8113
9372
gi|1377823
aminopeptidase [Bacillus subtilis]
73
60
1260


97
5
3389
1668
gnl|PID|d101954
dihydroxyacid dehydratase [Synechocystis sp.]
73
54
1722


98
9
6912
7619
gnl|PID|e314991
FtsE [Mycobacterium tuberculosis]
73
54
708


108
11
10928
10440
gi|388109
regulatory protein [Enterococcus faecalis]
73
54
489


128
6
3632
4222
gi|1685111
orf1091 [Streptococcus thermophilus]
73
63
591


138
2
1575
394
gi|147326
transport protein [Escherichia coli]
73
60
1182


140
13
12538
11903
pir|E53402|E534
serine O-acetyltransferase (EC 2.3.1.30) - Bacillus
73
55
636









stearothermophilus




162
5
5701
4991
gnl|PID|e32351
putative YhaQ protein [Bacillus subtilis]
73
50
711


164
4
2323
2790
gi|1592076
hypothetical protein (SP:P25768) [Methanococcus jannaschii]
73
52
468


164
8
4815
5546
gi|410137
ORFX13 [Bacillus subtilis]
73
56
732


170
5
4394
5302
gnl|PID|d100959
homologue of unidentified protein of E. coli [Bacillus subtilis]
73
46
909


178
7
3893
4855
gi|46242
modulation protein B, 5′end [Rhizobium loti]
73
56
963


204
6
5096
4278
gnl|PID|e214719
PlcR protein [Bacillus thuringiensis]
73
41
819


213
2
832
2037
gi|1565296
ribosomal protein S1 homolog; sequence specific DNA-binding
73
55
1206







protein [Leuconostoc lactis]


231
2
84
287
gi|40173
homolog of E.coli ribosomal protein L21 [Bacillus subtilis]
73
61
204


237
1
2
505
gi|1773151
adenine phosphoribosyltransferase [Escherichia coli]
73
51
504


269
1
2
691
gnl|PID|d101328
YqiX [Bacillus subtilis]
73
36
690


289
2
1272
832
pir|A0277|R7MC
ribosomal protein L7/L12 - Micrococcus luteus
73
66
441


343
1
14
484
gi|1788125
(AE000276) hypothetical 30.4 kD protein in manZ-cspC
73
47
471







intergenic region [Escherichia coli]


356
1
222
4
gi|2149905
D-glutamic acid adding enzyme [Enterococcus faecalis]
73
50
219


7
5
3165
4691
gnl|PID|d101833
lamidase [Synechocystis sp.]
72
52
1527


7
5
7195
7647
gi|146976
nusB [Escherichia coli]
72
54
453


7
17
13743
13300
gnl|PID|e289141
similar to hydroxymyristoyl-(acyl carrier protein) dehydratase
72
59
444







[Bacillus subtilis]


22
19
15637
16224
gnl|PID|d101929
ribosome releasing factor [Synechocystis sp.]
72
51
588


33
17
12111
11425
gnl|PID|d101190
ORF3 [Streptococcus mutans]
72
55
6871


34
7
7147
5627
gi|396501
aspartyl-tRNA synthatase [Theraus thermophilus]
72
52
1521


38
23
15372
16085
pir|H64108[H641
L-ribulose-phosphate 4-epimerase (araD) homolog -
72
54
714









Haemophilus influenase
(strain Rd RW20)



39
5
5094
6905
gnl|PID|a254877
unknown [Mycobacterium tuberculosis]
72
56
1812


40
6
4469
4636
gi|153672
lactose repressor [Streptococcus mutans]
72
58
168


48
2
1459
1253
gi|310380
inhibin beta-A-subunit [Ovis arias]
72
33
207


48
29
21729
22424
gi|2314329
(AE000623) glutamine ABC transporter, permease protein (glnP)
72
49
696







[Helicobactar pylon]


50
5
4529
3288
gi|1750108
YnbA [Bacillus subtilis]
72
54
1242


51
3
1044
2282
gi|2293230
(AF008220) YtbJ [Bacillus subtilis]
72
54
1239


52
3
13681
13938
gi|142521
deoxyribodipyrimidine photolyase [Bacillus subtilis]
72
45
258


55
1
841
35
gi|882518
ORF_o304; GTG start [Escherichia coli]
72
59
807


75
5
2832
3191
gnl|PID|e209886
mercuric resistance operon regulatory protein [Bacillus subtilis]
72
44
360


76
6
6229
5771
gi|142450
ahrC protein [Bacillus subtilis]
72
53
459


79
5
5065
4592
gi|2293279
(AP008220) YtcG [Bacillus subtilis]
72
46
474


87
14
14726
12309
gnl|PID|e323502
putative PriA protein [Bacillus subtilis]
72
52
2418


91
1
444
662
gi|500691
MYO1 gene product [Saccharomyces ceravisiae]
72
50
219


91
7
4516
4764
gi|829615
skeletal muscle sodium channel alpha-subunit [Equus caballus]
72
38
249


95
2
2004
1717
gnl|PID|e323527
putative Asp23 protein [Bacillus subtilis]
72
40
288


109
1
1452
118
gi|143331
alkaline phosphatase regulatory protein [Bacillus subtilis]
72
52
1335


126
1
3
2192
gnl|PID|d101831
glutemine-binding periplasmic protein [Synechocystis sp.]
72
46
2190


130
3
1735
2478
gi|2415396
(AP015775) carboxypeptidase [Bacillus subtilis]
72
53
744


137
6
2585
2929
gi|472922
v-tpe Na-ATPase [Enterococcus hirae]
72
46
345


140
10
9601
9203
gi|49224
URF 4 [Synechococcus sp.]
72
48
399


146
15
1906
1247
gnl|PID|e324945
hypothetical protein [Bacillus subtilis]
72
45
660


147
2
2084
1083
gnl|PID|e325016
hypothetical protein [Bacillus subtilis]
72
56
1002


147
5
6156
5146
gi|472327
TPP-dependent acetoin dehydrogenase beta-subunit
72
56
1011







[Clostridium magnum]


148
8
5381
6433
gi|974332
NAD(P)H-dependent dihydroxyacetone-phosphate reductase
72
54
1053







[Bacillus subtilis]


148
14
10256
9675
gnl|PID|d101319
YqgN [Bacillus subtilis]
72
50
582


159
8
4005
4949
gi|1788770
(AE000330) o463; 24 pct identical (44 gaps) to 338 residues
72
43
945







from penicillin-binding protein 4*, PBPE_BACSU SW:







P32959 (451 aa) [Escherichia coli]


172
10
9907
10620
gi|763387
unknown [Saccharomyces cerevisise]
72
55
714


220
3
2862
3602
gi|1574175
hypothetical [Haemophilus influenzae]
72
50
741


267
1
3
449
gi|290513
f470 [Escherichia coli]
72
48
447


281
2
899
540
gnl|PID|d100964
homologue of aspartokinase 2 alpha and beta subunits LysC of
72
45
360









B. subtilis
[Bacillus subtilis]



290
1
1018
14
gi|474195
This ORF is homologous to a 40.0 kd hypothetical protein in the
72
54
1005







htrB 3′region from E. coli, Accession Number X61000







[Mycoplasma-like organism]


300
1
63
587
gi|746399
transcription elongation factor [Escherichia coli]
72
50
525


316
1
1326
4
gi|158127
protein kinase C [Drosophila melanogaster]
72
40
1323


342
1
227
13
gnl|PID|d101164
unknown [Bacillus subtilis]
72
54
225


354
1
1
1005
gnl|PID|d102048


C. thermocellum
beta-glucosidase: P26208 (985)

72
52
1005







[Bacillus subtilis]


6
10
8134
10467
gnl|PID|e264229
unknown [Nycohacterium tuberculosis]
71
57
2334


7
12
16231
15464
gi|18046
3-oxoacyl-[acyl-carrier protein] reductese [Cuphea lanceolata]
71
52
768


15
1
1297
2
gnl|PID|d100571
replicative DNA helicase [Bacillus subtilis]
71
51
1296


15
4
4435
3869
gi|499384
orfl89 [Bacillus subtilis]
71
47
567


18
6
5120
4218
gnl|PID|d101318
YqgG [Bacillus subtilis]
71
51
903


29
1
1
540
gi|1773142
similar to the 20.2 kd protein in TETE-EXOA region of
71
56
540









B. subtilis
[Escherichia coli]



38
20
13327
13830
gi|537036
ORF_o158 [Escherichia coli]
71
48
504


51
12
15015
12676
gi|149528
dipeptidyl peptidase IV [Lactococcus lactis]
71
55
2340


55
23
21040
20585
gi|2343285
(AF015453) surface located protein [Lactobacillus rhamnosus]
71
58
456


60
2
705
265
gnl|PID|d101320
YqgZ [Bacillus subtilis]
71
44
441


71
18
24679
26226
gi|580920
rodD (gtaA) polypeptide (AA 1-673) [Bacillus subtilis]
71
44
1548


71
25
30587
30360
gi|606028
ORF_o414; Geneplot suggests frameshift near start but none
71
50
228







found [Escherichia coli]


72
6
5239
6729
gi|580835
lysine decarboxylase [Bacillus subtilis]
71
48
1491


72
14
11991
12878
gi|624085
similar to rat beta-alanine synthetase encoded by GenBank
71
54
888







Accession Number S27881; contains ATP/GTP binding motif







[Paramecium bursaria Chlorella virus 1]


73
11
7269
7033
gi|106594
PN1 [Rattus norvegicus]
71
42
237


74
6
10385
8517
gi|1573733
prolyl-tRNA synthetase (pros) [Haemophilus influenzae]
71
52
1869


81
9
5772
6578
gi|147404
mammose permease subunit II-M-Man [Escherichia coli]
71
45
807


86
5
4602
3604
gnl|PID|e322063
ss-1,4-galactosyltransferase [Streptococcus pneumoniae]
71
53
999


105
4
3619
4707
gi|2323341
(AF014460) PepQ [Streptococcus mutans]
71
58
1089


106
13
13557
12955
gi|1519287
LemA [Listens monocytogenes]
71
48
603


114
2
1029
1979
gi|310303
mosA [Rhizobium meliloti]
71
55
951


122
2
564
1205
gi|1649037
glutamine transport ATP-binding protein GLNQ
71
50
642







[Salmonella typhimunium]


132
5
9018
7063
gnl|PID|d102049


H. influensas
hypothetical ABC transporter; P44808 (974)

71
51
1956







[Bacillus subtilis]


140
1
1141
227
gi|1673788
(AE000015) Mycoplasma pneumoniae, fructose-bisphosphate
71
49
915







aldolase; similar to Swiss-Prot Accession Number P13243,







from B. subtilis [Mycoplasma pneumoniae]


140
5
5635
4973
gnl|PID|d100964
homologue of hypothetical protein in a rapamycin synthesis gene
71
48
663







cluster of Streptomyces hygroscopicus [Bacillus subtilis]


141
7
7369
7845
gnl|PID|d102005
(AB001488) FUNCTION UNKNOWN,
71
51
477







SIMILAR PRODUCT IN E. COLI AND MYCOPLASMA









PNEUMONIAE
.[Bacillus subtilis]



193
1
1
165
gi|46912
ribosomal protein L13 [Staphylococcus carnosus]
71
59
165


194
3
2205
1594
gi|535351
CodY [Bacillus subtilis]
71
52
612


199
3
1510
1319
gi|2182574
(AE000090) Y4pE [Rhizobium sp. NGR234]
71
45
192


208
2
2616
3752
gi|1787378
(A5000213) hypothetical protein in purB 5′ region
71
57
1137







[Escherichia coli]


209
2
2022
1141
gi|41432
fepC gene product [Escherichia coli]
71
46
882


210
5
1911
3071
gi|49316
ORF2 gene product [Bacillus subtilis]
71
45
1161


210
6
3069
3386
gi|580900
ORF3 gene product [Bacillus subtilis]
71
48
318


212
2
3561
1381
gi|557567
ribonucleotide reductase R1 subunit [Mycobacterium
71
53
2181









tuberculosis
]



233
3
2003
2920
gnl|PID|d101320
YqgR [Bacillus subtilis]
71
50 918


244
1
13
1053
gnl|PID|d100964
homologue of aspartokinase 2 alpha end beta subunits LysC
71
55
1041







of B. subtilis [Bacillus subtilis]


251
2
1008
1874
gi|755601
unknown [Bacillus subtilis]
71
46
867


282
2
906
712
gi|1353874
unknown [Rhodobacter capsulatus]
71
46
195


312
4
2137
1565
gnl|PID|d102245
(AB005554) yxbF [Bacillus subtilis]
71
34
573


338
1
3
683
gi|1591045
hypothetical protein (SP:P31466) [Methanococcus jannaschii]
71
48
681


346
1
3
164
gi|1591234
hypothetical protein (SP:P42297) [Methanococcus jannaschii]
71
36
162


374
1
619
2
gi|397526
clumping factor [Staphylococcus aureus]
71
23
618


377
1
688
2
gi|397526
clumping factor [Staphylococcus aureus]
71
23
687


3
8
7419
6958
gnl|PID|e269486
Unknown [Bacillus subtilis]
70
42
462


3
10
8395
9075
gnl|PID|e255543
putative iron dependent repressor [Staphylococcus epidermidis]
70
46
681


7
14
11024
10254
gnl|PID|d100290
undefined open reading frame [Bacillus stearothermophilus]
70
55
771


7
18
14213
13719
gnl|PID|d101090
biotin carboxyl carrier protein of acetyl-CoA carboxylase
70
56
495







[Synechocystis sp.]


9
2
1057
287
gnl|PID|d100581
unknown [Bacillus subtilis]
70
52
771


12
4
2610
1789
gnl|PID|d101195
yycJ [Bacillus subtilis]
70
52
822


21
2
2586
1846
gi|2293447
(AF008930) ATPase [Bacillus subtilis]
70
54
741


22
13
10955
11512
gi|1165295
Ydr540cp [Saccharomyces cerevisiae]
70
50
558











30
6
4315
3980
gi|39478
ATP binding protein of transport ATPases [Bacillus firmus]
70
51
336


31
1
370
113
gi|662792
single-stranded DNA binding protein [unidentified eubacterium]
70
36
258


33
15
10639
9521
gi|1161219
homolgous to D-amino acid dehydrogenese enzyme
70
50
1119







[Pseudomonas aeruginosa]


38
6
3812
4312
gi|2058547
ComYD [Streptococcus gordonii]
70
48
501


38
25
17986
18477
gi|537033
ORF_f356 [Escherichia coli]
70
58
492


40
13
11054
9846
gi|1173516
riboflavin-specific deaminase [Actinobecillus pleuropneumoniee]
70
52
1209


42
2
722
1954
gi|1146183
putative [Bacillus subtilis]
70
51
1233


43
3
2373
1612
gi|1591493
glutamine transport ATP-binding protein Q
70
48
762







[Methanococcus jannaschii]


45
8
9197
8049
gnl|PID|d102036
subunit of ADP-glucose pyrophosphorylase
70
54
1149







[Bacillus stearothermophilus]


59
2
567
956
gnl|PID|d100302
neopullulanase [Bacillus sp.]
70
42
390


60
3
1874
795
gnl|PID|e276466
aminopeptidase P [Lactococcus lactis]
70
48
1080


61
4
5553
2437
gnl|PID|e275074
SNF [Bacillus cereus]
70
51
3117


61
7
7914
6802
gi|1573037
cystathionine gamma-synthase (metB) [Haemophilus influenzae]
70
52
1113


63
7
5372
7222
gnl|PID|d100974
unknown [Bacillus subtilis]
70
54
1851


68
7
7126
6962
gi|1263014
emm18.1 gene product [Streptococcus pyogenes]
70
37
165


72
12
10081
10911
gi|23130931
(AE000524) carboxynorspermidine decarboxylase (nspc)
70
56
831







[Helicobacter pylori]


75
10
7888
8124
gi|1877423
galactose-1-P-uridyl transferase [Streptococcus mutans]
70
59
237


79
3
3424
2525
gi|39881
ORF 311 (AA 1-311) [Bacillus subtilis]
70
47 900


87
10
9369
7324
gnl|PID|e323506
putative Pkn2 protein [Bacillus subtilis]
70
52
2046


96
14
10640
11788
gi|1573209
tRNA-guanine tranaglycosylase (tgt) [Haemophilus influenzae]
70
52
1149


113
2
574
1086
gi|433630
Al80 [Saccharomyces cerevisiae]
70
59
513


123
5
2901
3461
gnl|PID|d100585
unknown [Bacillus subtilis]
70
45
561


125
5
4593
4282
gnl|PID|e276474
capacitative calcium entry channel 1 [Bos taurus]
70
35
312


129
5
4500
3454
gnl|PID|d101314
YqeT [Bacillus subtilis]
70
47
1047


133
3
2608
1394
gi|2293312
(AF008220) YtfP [Bacillus subtilis]
70
50
1215


135
1
420
662
gnl|PID|e265530
yorfE [Streptococcus pneumoniae]
70
47
243


137
3
438
932
gi|472919
v-type Na-ATPase [Enterococcus hirae]
70
57
495


138
1
440
3
gi|147336
transmembrane protein [Escherichia coli]
70
42
438


140
16
18796
16364
gi|976441
N5-methyltetrahydrofolate homocysteine methyltransferase
70
53
2433







[Saccharomyces cerevisiae]


167
10
8263
6695
gi|149535
D-alanine activating enzyme [Lactobacillus casei]
70
52
1569


204
4
3226
2747
gnl|PID|d102049


E. coli
hypothetical protein; P31805 (267) [Bacillus subtilis]

70
51
480


207
3
2627
2869
gnl|PID|e309213
racGAP [Dictyostelium discoideum]
70
45
243


282
3
1136
882
gi|1353874
unknown [Rhodobacter capsulatus]
70
50
255


6
21
17554
18453
gnl|PID|e233879
hypothetical protein [Bacillus subtilis]
69
44
900


6
22
18482
19471
gi|580883
ipa-88d gene product [Bacillus subtilis]
69
53
990


22
8
46825
824
gi|2209379
(AF006720) ProJ [Bacillus subtilis]
69
48
1143


22
9
7992
8651
gnl|PID|d100580
unknown [Bacillus subtilis]
69
51
660


22
12
9871
10767
gnl|PID|d100581
unknown [Bacillus subtilis]
69
51
897


27
7
5857
5348
gnl|PID|d102012
(AB001488) FUNCTION UNKNOWN. [Bacillus subtilis]
69
28
510


36
10
7294
10116
gi|437916
isoleucyl-tRNA synthetase [Staphylococcus aureus]
69
53
2823


38
1
2
1090
gi|141900
alcohol dehydrogenase (EC 1.1.1.1) [Alcaligenes eutrophus]
69
48
1089


40
14
11333
11944
gi|1573280
Holliday junction DNA helicase (ruvA) [Haemophilus influenzae]
69
44
612


40
15
11942
12517
gi|1573653
DNA-3-methyladenine glycosidase I (tagI) [Haemophilus influenzae]
69
50
576


45
8
6947
5490
gi|580887
starch (bacterial glycogen) synthase [Bacillus subtilis]
69
47
1458


48
34
24932
24153
gnl|PID|e233870
hypothetical protein [Bacillus subtilis]
69
36
780


49
6
6183
6521
gi|398297
similar tophosphotransferase system enzyme II [Escherichia coli]
69
50
339


49
8
7586
8338
gi|396420
similar to Alcaligenes eutrophus pHG1 D-ribulose-5-phosphate
69
49
753







3 epimerase [Escherichia coli]


55
6
8262
7033
gi|1146238
poly(A) polymerase [Bacillus subtilis]
69
50
1230


59
3
954
2333
gnl|PID-e313038
hypothetical protein [Bacillus subtilis]
69
54
1380


62
3
1170
1418
gnl|PID|d101915
hypothetical protein [Synechocystis sp.]
69
49
249


63
8
7298
7762
gi|293017
ORF3 (put.); putative [Lactococcus lactis]
69
42
465


66
4
3657
5081
gi|153755
phospho-beta-D-galactosidase (EC 3.2.1.85)
69
49
1425







[Lactococcus lactis cremoris]


66
5
5126
6829
gi|433809
enzyme II [Streptococcus mutans]
69
46
1704


71
6
10017
10664
gnl|PID|e322083
ss-1,4-galactosyltransferase [Streptococcus pneumoniae]
69
39
648


71
21
27730
27966
gnl|PID|d100649
DE-cadherin [Drosophila melanogaster]
69
30
237


77
1
1
237
gi|287870
groES gene product [Lactococcus lactis]
69
44
237


81
5
3622
4101
gi|1573605
fucose operon protein (fucU) [Haemophilus influenzae]
69
52
480


83
1
40
7141
pir|C33496|C334
hisC homolog - Bacillus subtilis
69
46
675


83
16
15742
16335
gi|143372
phosphoribosyl glycinamide formyltransferase (PUR-N)
69
46
594







[Bacillus subtilis]


85
2
1212
916
gi|194097
IFN-response element binding factor 1 [Mus musculus]
69
48
297


91
5
3678
4274
gi|1574712
anaerobic ribonuleoside-triphosphate reductase activating
69
44
597







protein (nrdG)


98
5
3247
4032
gnl|PID|d100262
LivF protein [Salmonella typhimurium]
69
51
786


108
5
4085
5056
gnl|PID|e257629
transcription factor [Lactococcus lactis]
69
49
972


126
3
3078
4568
gnl|PID|d101329
YqjJ [Bacillus subtilis]
69
49
1491


131
6
4121
2889
gnl|PID|d101314
YqeR [Bacillus subtilis]
69
47
1233


136
2
1505
2299
gnl|PID|d100581
unknown [Bacillus subtilis]
69
47
795


149
5
3852
4763
gnl|PID|e323525
YloQ protein [Bacillus subtilis]
69
50
912


149
12
9336
10655
gi|151571
Homology with E.coli and P.aeruginosa lysA gene;
69
52
1320







product of unknown function; putative [Pseudomonas syringae]


153
4
3191
3829
gi|1710373
BrnQ [Bacillus subtilis]
69
44
639


169
3
849
2324
gnl|PID|d100582
temperature sensitive cell division [Bacillus subtilis]
69
49
1476


180
1
566
3
gi|488339
alpha-amylase (unidentified cloning vector]
69
50
564


212
1
1196
231
gi|1395209
ribonucleotide reductase R2-2 small aubunit
69
53
966







[Mycobacterium tuberculosis]


226
1
2
661
pir|JQ2285|JQ22
nodulin-26 - soybean
69
41
660


233
5
3249
4766
gi|472918
v-type Na-ATPase [Enterococcus hirae]
69
56
1518


235
3
660
1766
gi|148945
methylasa [Haemophilus influenzae]
69
43
1107


243
2
865
2361
gnl|PID|d100225
ORF5 (Barley yellow dwarf virus]
69
69
1497


251
3
2899
1967
gi|228923
macrolide-efflux protein [Streptococcus agalactiae]
69
51
933


310
1
1
282
gnl|PID|e322442
peptide deformylase [Clostridium beijerinckii]
69
55
282


369
1
868
2
gi|397526
clumping factor [Staphylococcus aureus]
69
22
867


370
1
749
3
gi|397526
clumping factor [Staphylococcus aureus]
69
21
747


379
1
44
290
gnl|PID|d100649
DE-cadherin [Drosophila melanogaster]
69
30
237


388
1
260
72
gi|1787524
(AE000225) hypothetical 32.7 kD protein in trpL-btuR
69
44
189







intergenic region [Escherichia coli]


1
2
2006
3040
gnl|PID|d101809
ABC transporter [Synechocystis sp.]
68
43
1035


12
5
3958
2600
gi|2182992
histidine kinase [Lactococcus lactis crersoris]
68
45
1359


15
2
1790
1311
pir|S16974|R5BS
ribosomal protein L9 - Bacillus stearothermophilus
68
56
480


16
6
7353
5701
gi|1787041
(AE000184) o530; This 530 aa orf is 33 pct identical (14 gaps)
525
68
45
1653







to residues of an approx. 640 aa protein YHES_HAEIN SW:







P44808 [Escherichia coli]


17
12
6479
6805
gi|553165
acetylcholinesterase [Homo sapiens]
68
68
327


20
13
14128
14505
gi|142700
competence protein (ttg start codon) (put.); putative
68
40
378







[Bacillus subtilis]


22
32
24612
25397
gi|289262
comE ORF3 [Bacillus subtilis]
68
36
786


30
7
4548
4288
gi|311388
ORF1 [Azorhizobium caulinodans]
68
46
261


36
5
3911
4585
gi|1573041
hypothetical [Haemophilus influensae]
68
54
675


46
6
5219
6040
gi|1790131
(AE000446) hypothetical 29.7 kD protein in ibpA-gyrB
68
47
822







intergenic region [Escherichia coli]


54
10
6235
7086
gi|882579
CG Site No. 29739 [Escherichia coli]
68
55
852


55
5
7069
5165
gnl|PID|d101914
ABC transporter [Synechocystis sp.]
68
45
1905


71
3
6134
5613
gi|1573353
outer membrane integrity protein (tolA) [Haemophilus influenzae]
68
50
522


71
10
15342
16613
gi|580866
ipa-12d gene product [Bacillus subtilis]
68
31
1272


71
12
17560
18792
gi|44073
SecY protein [Lactococcus lactis]
68
35
1233


71
17
22295
24703
gi|1762349
involved in protein export [Bacillus subtilis]
68
50
2409


73
16
10208
9729
gi|1353537
dUTPase [Bacteriophage rlt]
68
51
480


86
18
17198
16011
gi|413943
ipa-19d gene product [Bacillus subtilis]
68
53
1188


87
17
17491
15866
gi|150209
ORF 1 [Mycoplasma mycoides]
68
43
1626


89
6
5139
4354
gi|1498824


M. jannaschii
predicted coding region MJ0062

68
40
786







[Methanococcus jannaschii]


89
11
8021
8242
gi|1509741
4-oxalocrotonate tautomerase [Pseudomonas putida]
68
43
222


97
8
6755
5394
gi|2367358
(AE000491) hypothetical 52.9 kD protein in aidB-rpsF
68
41
1362







intergenic region [Escherichia coli]


98
3
1418
2308
gnl|PID|d100261
LivA protein [Salmonella typhimurium]
68
40
891


99
13
16414
17280
gi|455363
regulatory protein [Streptococcus mutans]
88
50
867


115
3
5054
3693
gi|466474
cellobiose phosphotrensferase enzyme II′′
68
44
1362







[Bacillus stearothermophilus]


124
7
3394
3221
gnl|PID|d100702
cut14 protein [Schizosaccheromyces pombe]
68
56
174


125
2
2923
1922
gi|450566
transmembrane protein [Bacillus subtilis]
68
50
1002


132
2
4658
2888
gnl|PID|d101732
DNA ligase [Synechocystis sp.]
68
52
1971


140
7
7765
7580
gi|120971
unknown [Saccharomyces cerevisiae]
68
47
186


150
1
539
3
gi|402490
ADP-ribosylarginine hydrolase [Mus musculus]
68
59
537


164
1
58
867
gnl|PID|e255114
glutamate racemase [Bacillus subtilis]
68
49
810


164
2
819
1835
gnl|PID|e255117
hypothetical protein [Bacillus subtilis]
68
50
1017


169
7
3946
4104
pir|B54545|B545
hypothetical protein - Lactococcus lactis subap.
68
40
159







lactis plasmid pSL2


170
4
4247
4396
gi|304146
spore coat protein [Bacillus subtilis9
68
52
150


171
8
6002
7054
gi|38722
precursor (aa −20 to 381) [Acinetobacter calcoacericus)
68
54
1053


199
3
2473
1871
gnl|PID|e313075
hypothetical protein [Bacillus subtilis]
68
46
603


211
2
969
1802
gi|1439528
EIIC-man [Lactobacillus curvatus]
68
45
834


214
8
4926
4231
gnl|PID|d102049


H. influenzae
hypothetical protein; P43990 (182) [Bacillus subtilis]

68
50
696


217
6
4955
5170
gnl|PID|e326966
similar to B.vulgaris CMS-associated mitochondrial . . . (reverse
68
36
216







transcriptase) [Arabidopsis thaliana]


218
7
3930
4745
gi|2293198
(AF008220) YtgP [Bacillus subtills]
68
38
816


220
6
4628
4336
gnl|PID|e325791
(AJ000005) orf1 [Bacillus megeterium]
66
51
291


236
1
746
108
gi|410137
ORFX13 [Bacillus subtilis]
68
46
639


237
2
675
1451
gi|396348
homoserine transauccinylase [Escherichia coli]
68
49
777


250
4
771
1229
gi|310859
ORF2 [Synechococcus sp.]
68
50
459


254
1
517
155
gi|1787105
(AE000189) o648 was o669; This 669 as orf is 40 pct identical
68
44
363







(1 gaps) to







217 residues of an approx. 232 aa protein YBBA_HAEIN SW; P45247







[Escherichia coli]


337
1
1
774
gnl|PID|e261990
putative orf [Bacillus subtilis]
68
47
774


345
1
3
653
gi|149513
thymidylate synthase (EC 2.1.1.45) [Lactococcus lactis]
68
61
651


386
2
417
4
gi|1573353
outer membrane integrity protein (tolA) [Haemophilus influenzae]
68
51
414


2
4
5722
4697
gi|1592141


M. jannaschii
predicted coding region MJ1507

67
26
1026







[Methanococcus jannaschii]


3
6
5397
4591
gi|2293175
(AF008220) signal transduction regulator [Bacillus subtilis]
67
44
807


5
2
2301
574
gi|2313385
(AE000547) pare-aminobensoate synthetase (pabB)
67
48
1728







[Helicobacter pylon]


6
19
16063
16758
gi|413931
ipa-7d gene product [Bacillus subtilis]
67
41
696


22
8
7094
7897
gi|1928982
pyrroline-5-carboxylate reductase [Actinidia deliciosa]
67
51
804


29
10
8335
9072
gi|468745
gtcR gene product [Bacillus brevis]
67
41
738


31
3
1379
585
gi|2425123
(AF019986) PksB [Dictyostelium discoideum]
67
49
795


32
11
8849
10150
gi|420291
ORF1 gene product [Escherichia coli]
67
47
1302


36
16
14830
15546
gi|1592142
ABC transporter, probable ATP-binding subunit
87
43
717







[Methanococcus jannaschii]


38
9
4958
5392
gnl|PID|e214803
T22B3.3 [Caenorhabditis elegans]
67
47
435


38
21
13775
14512
gi|537037
ORF_o216 [Escherichia coli]
67
52
738


45
9
10428
9181
gi|551710
branching enzyme (glgB) (EC 2.4.1.18)
67
51
1248







[Bacillus stearothermophilus]


48
23
18344
17514
gi|413949
ipa-25d gene product [Bacillus subtilis]
67
50
831


50
2
1773
952
gnl|PID|d101330
YqjQ [Bacillus subtilis]
67
55
822


53
1
431
3
gi|1574291
fimbrial transcription regulation repressor (pilB)
67
40
429







[Haemophilus influenzae]


55
13
12740
11946
gnl|PID|e252990
ORF YDL037c [Saccharomyces cerevisiae]
67
51
7951


61
9
9210
8329
gnl|PID|e264711
ATP-binding cassette transporter A [Staphylococcus aureus]
67
50
882


71
2
5614
6117
gi|1197667
vitellogenin [Anolis pulchellus]
67
36
504


81
7
4489
4983
gi|1142714
phosphoenolpyruvate:mannose phosphotransferase element IIB
67
42
495







[Lactobacillus curvatus]


83
7
2957
3214
gi|1276746
Acyl carrier protein [Porphyra purpurea]
67
37
258


86
8
8140
6809
gi|1147744
PSR [Enterococcus hirae]
67
45
1332


97
3
986
1366
gnl|PID|d102235
(AB000631) unnamed protein product [Streptococcus mutans]
67
43
381


102
1
601
1413
gi|682765
mccB gene product [Escherichia coli]
67
36
813


106
3
1109
1987
gi|148921
LicD protein [Haemophilus influenzae]
67
43
879


115
4
5982
5656
gi|895750
putative cellobiose phosphotransferase enzyme III
67
44
327







[Bacillus subtilis]


115
7
8421
8077
gi|466473
cellobiosa phosphotransferase enzyme II′
67
51
345







[Bacillus stearothensophilus]


127
13
8127
7021
gi|147326
transport protein [Escherichia coli]
67
45
1107


136
3
2215
2659
gnl|PID|d100581
unknown [Bacillus subtilis]
67
49
645


140
21
23317
20906
gnl|PID|d101912
phenylalanyl-tRNA synthatase [Synechocystis sp.]
67
43
2412


146
6
2894
1893
gi|2182994
histidine kinase [Lactococcus lactic cremoris]
67
44
1002


151
8
11476
11117
gnl|PID|d100085
ORF129 [Bacillus cereus]
67
48
360


160
10
7453
8646
gi|2281317
OrfB; similar to a Streptococcus pneumoniae putative
67
46
1194







membrane protein encoded by GenBank Accession







Number X99400; inactivation of the OrfB gene leads to







UV-sensitivity and to decrease of homologous recombination







(plasmidic test) (Lactococcus 1


163
3
3099
4505
gnl|PID|d101317
YqfR [Bacillus subtilis]
67
47
1407


167
8
6704
5454
gi|1161933
DltB [Lectobacillus casei]
67
45
1251


169
4
2322
2879
gnl|PID|d101331
YqkG [Bacillus subtilis]
67
41
558


171
11
7656
8384
gi|153841
pneumococcal surface protein A [Streptococcus pneumoniae]
67
50
729


188
3
1930
3723
gi|1542975
AbcB [Thermoanaerobacterium thermosulfurigenes]
67
46
1794


189
6
3599
3141
gnl|PID|e325178
Hypothetical protein [Bacillus subtilis]
67
52
459


205
3
1663
2211
gi|606073
ORF_o169 [Escherichia coli]
67
47
549


207
4
2896
3456
gi|2276374
DtxR/iron regulated lipoprotein precursor
67
49
561







[Corynabacteriuls diphtheriae]


217
3
4086
3703
gi|895750
putative cellobiose phosphotransferase enzyme III
67
42
384







[Bacillus subtilis]


246
2
291
662
gi|1842438
unknown [Bacillus subtilis]
67
43
372


252
1
2
1745
gi|2351768
PspA [Streptococcus pneumoniae]
67
41
744


265
3
1134
1811
gi|2313847
(AE000585) L-asparaginase II (anaB) [Helicobacter pylon]
67
42
678


295
1
1
375
gi|2276374
DtxR/iron regulated lipoprotain precursor [Corynebacterium diphtheriae]
67
43
375


1
7
4898
5146
gnl|PID|e255179
unknown [Mycobacterium tuberculosis]
66
56
249


3
1
389
3
gnl|PID|e269548
Unknown [Bacillus subtilis]
66
48
387


3
20
19267
20805
gi|39956
IIGlc [Bacillus subtilis]
66
50
1539


4
3
2545
2718
gi|1787564
(AE000228) phage shock protein C [Escherichia coli]
66
36
174


5
9
13197
12592
gi|1574291
fimbrial transcription regulation repressor (pilB)
66
46
606







[Haemophilus influenzae]





9
4
2872
1451
gnl|PID|e266928
unknown [Mycobacterium tuberculosis]
66
43
1422


12
2
1469
1200
gi|520407
orf2; GTG start codon [Bacillus thuringiensis]
66
42
270


15
12
10979
9897
gi|2314738
(AE000653) translation elongation factor EF-Ts (tsf)
66
49
1083







[Helicobacter pylon]


16
2
1312
734
gnl|PID|d102245
(AB005554) yxbF [Bacillus subtilis]
66
35
579


22
3
1372
1851
gi|1480916
signal peptidase type II [Lactococcus lactic]
66
38
480


22
7
5828
7096
gnl|PID|e20626
gamma-glutamyl phosphate reductase [Streptococcus
66
51
1289









thermophilus
]



22
20
16194
17138
gnl|PID|e281914
YitL [Bacillus subtilis]
66
50
945


30
2
530
976
gi|2314379
(AE000627) ABC transporter, ATP-binding protein (yhcG)
66
40
447







[Helicobacter pylon]


32
1
199
984
gi|312444
ORF2 [Bacillus caldolyticus]
66
49
786


33
13
8352
7234
gi|1387979
44% identity over 302 residues with hypothetical protein from
66
44
1119







Synechocystis sp, accession D64006_CD; expression induced







by environmental stress; some similarity to glycosyl transferases;







two potential membrane-spanning helices [Bacillus subtil


34
6
5658
4708
gnl|PID|e250724
orf2 [Lactobacillus sake]
66
39
951


34
14
9792
9574
gi|1590997


H. jannaschii
predicted coding region MJ0272

66
48
219







[Methanococcus jannaschii]


35
16
15163
14501
gi|1773352
Cap5M [Staphylococcus aureus]
66
46
663


36
9
6173
6976
gi|1518680
minicell-associated protein DivIVA [Bacillus subtilis]
68
35
804


36
11
10396
10824
bbs|155344
insulin activator factor, INSAF [human, Pancreatic
66
43
429







insulinoma, Peptide Partial, 744 as] [Homo sapiens]


48
1
28
1419
gnl|PID|e325204
hypothetical protein [Bacillus subtilis]
66
50
1392


48
7
3810
4112
gi|2182574
(AE000090) Y4pE [Rhizobium sp. NGR234]
66
40
303


52
4
3595
2789
gi|388565
major cell-binding factor [Campylobacter jejuni]
66
52
807


54
3
2662
1076
gnl|PID|d101831
glutamine-binding periplasmic protein [Synechocystis sp.]
66
43
1587


61
10
9740
9183
gnl|PID|e154144
mdr gene product [Staphylococcus aureus]
66
44
558


72
13
10893
11993
gi|2313129
(AE000526) H. pylon predicted coding region HP0049
66
44
1101







[Helicobacter pylon]


74
9
13267
12476
gi|1573941
hypothetical [Haemophilus influenzae]
66
43
792


75
1
2
868
gi|1574631
nicotinamide mononucleotide transporter (pnuC)
66
48
867







[Haemophilus influenzae]


75
7
5303
4275
gi|41312
put. EBG repressor protein [Escherichia coli]
66
40
1029


82
7
6813
8123
gnl|PID|e255128
trigger factor [Bacillus subtilis]
66
53
1311


83
3
905
1219
pir|C33496|C334
hisC homolog - Bacillus subtilis
66
44
315


86
10
9407
8925
gi|683584
shikimate kinese [Lactococcus lactis]
66
41
483


88
10
7001
6060
gi|2098719
putative fimbrial-associated protein [Actinomyces naeslundii]
66
52
942


89
1
951
4
gi|410118
ORFX19 [Bacillus subtilis]
66
41
948


93
7
3661
2711
gi|1787936
(AE000260) f298; This 298 as orf is 51 pct identical (5 gaps) to 297
66
49
951







residues of an approx. 304 as protein YCSN_BACSU SW: 242972







[Escherichia coli]


104
3
1805
3049
gi|1469784
putative cell division protein ftsW [Enterococcus hirae]
66
48
1245


106
14
13576
14253
gi|40027
homologous to E.coli gidB [Bacillus subtilis]
66
52
676


107
3
965
1864
gi|144858
ORF A [Clostridium perfringens]
66
49
900


112
7
5718
6593
gi|609332
DprA [Haemophilus influensae]
66
43
876


115
1
3
302
gi|727367
Hyrlp [Saccharomyces cerevisise]
66
56
300


122
1
3
566
gnl|PID|d101328
YqiY [Bacillus subtilis]
66
36
564


126
8
11759
11046
gnl|PID|d101163
ORF3 [Bacillus subtilis]
66
48
714


128
11
8201
8431
gi|726288
growth associated protein GAP-43 [Xenopus laevis]
66
41
231


131
8
4894
4508
gi|486661
TMnm related protein [Sacoharomyces cerevisiae]
66
39
387


140
3
3236
2574
gi|40056
phoP gene product [Bacillus subtilis]
66
36
663


140
15
16318
15434
gi|16581891
5,10-methylenetetrahydrofolate reductase [Erwinia carotovora]
66
48
885


146
12
7926
7636
gnl|PID|d101140
transposase [Synechocystis sp.]
66
42
291


147
6
7137
6154
gi|472326
TPP-dependent acetoin dehydroganase alpha-subunit
66
48
984







[Clostridium magnum]


149
6
4435
5430
gnl|PID|d101887
pentose-5-phosphate-3-epimerase [Synechocystis sp.]
66
46
996


149
13
10754
11575
gi|42371
pyruvate formate-lyase activating enzyme (AA 1-246)
66
42
822







[Escherichia coli]


186
4
2578
2270
gnl|PID|d101199
ORF11 [Enterococcus faecalis]
66
41
309


207
2
2340
2597
gnl|PID|e321893
envelope glycoprotein gp160 [Human immunodeficiency
66
46
258







virus type 1]


210
7
3358
3678
gi|49318
ORF4 gene product [Bacillus subtilis]
66
46
321


217
8
5143
5355
gi|49538
thrombin receptor [Cricetulus longicaudatus]
66
38
213


220
4
3875
3642
gi|466648
alternate name ORFD of L23635 [Escherichia coli]
66
33
234


223
1
1070
138
gnl|PID|e247187
zinc finger protein [Bacteriophage phigle]
66
45
933


224
2
1864
2640
gi|1176399
putative ABC transporter subunit [Staphylococcus epidermidis]
66
41
777


243
1
3
672
dbj||AB000617_2
(AB000617) YcdH [Bacillus subtilis]
66
45 870


268
2
891
568
gi|517210
putative transposase [Streptococcus pyogenes]
66
60
324


322
1
2
643
gi|1499836
Zn protease [Methanococcus jannaschii]
66
40
642


5
10
13909
13178
gi|1574292
hypothetical [Haemophilus influenzae]
65
34
732


6
11
10465
11190
gi|142854
homologous to E. coli radC gene product and to unidentified
65
46
726







protein from Staphylococcus aureus [Bacillus subtilis]


7
2
647
405
pir|C64146|C641
hypothetical protein 1410259 - Haemophilus influenzae
65
42
243







(strain Rd KW20)


7
7
6246
6621
gnl|PID|d101323
YqhU [Bacillus subtilis]
65
50
576


10
2
1873
1397
gi|1163111
ORF-1 [Streptococcus pneumoniae]
65
54
477


16
3
1426
2222
gnl|PID|e325010
hypothetical protein [Bacillus subtilis]
65
45
795


21
4
3815
3357
gnl|PID|e314910
hypothetical protein [Staphylococcus sciuri]
65
40
459


22
34
25776
26384
gi|1123030
CpXA [Actinobacillus pleuropneumoniae]
65
42
609


43
2
16481
290
gi|1044826
F14E5.1 [Caenorhabditis elegans]
65
38
1359


48
13
10062
10856
gi|1573390
hypothetical [Haemophilus influenzae]
65
45
795


48
22
17521
16883
gi|1573391
hypothetical [Haemophilus influenzae]
65
37
639


48
25
19027
18533
gnl|PID|e264484
YCR020c, len:215 [Saccharomyces cerevisise]
65
38
495


49
3
3856
5334
gi|1480429
putative transcriptional regulator [Bacillus stearothermophilus]
65
32
1479


50
6
5337
4519
gi|171963
tRNA isopentenyl transferase [Saccharomyces cerevisiae]
65
42
819


52
15
14728
15588
gi|1499745


M. jannaschii
predicted coding region MJ0912

65
46
861







[Methanococcus jannaschii]


59
7
3963
4745
gi|496514
orf zeta [Streptococcus pyogenes]
65
42
783


68
3
2500
3483
gi|887824
ORF_o310 [Escherichia coli]
65
46
984


69
3
2171
1077
gnl|PID|e311453
unknown [Bacillus subtilis]
65
42
1095


69
7
6029
5325
gi|809660
deoxyribose-phosphate aldolase [Bacillus subtilis]
65
55
705


71
5
8536
9783
gi|1573224
glycosyl transferase lgtC (GP:U14554_4)
65
42
1248







[Haemophilus influenzae]


72
8
7664
8527
gnl|PID|e267589
Unknown, highly similar to several spermidine synthases
65
39
864







[Bacillus subtilis]


76
5
5773
4097
gnl|PID|d101723
DNA REPAIR PROTEIN RECN (RECOMBINATION PROTEIN N).
65
44
1677







[Escherichia coli]


76
9
8099
7875
gi|1574276
exodeoxyribonuclease, small subunit (xseB)
65
38
225







[Haemophilus influenzae]


84
2
2870
2352
gi|2313188
(AE000532) conserved hypothetical protein [Helicobacter pylon]
65
41
519


86
15
14495
13407
gnl|PID|d101880
3-dehydroquinate synthase [Synechocystis sp.]
65
44
1089


87
3
3706
2423
gi|151259
HMG-CoA reductase (BC 1.1.1.88) [Pseudomonas mevalonii]
65
51
1284


88
3
2425
2736
gi|1098510
unknown [Lactococcus lactis]
65
30
312


89
2
1627
1007
gnl|PID|d102008
(AB001488) SIMILAR TO ORF14 OF ENTEROCOCCUS
65
41
621









FAECALIS
TRANSPOSON TN916. [Bacillus subtilis]



111
6
6635
6186
gnl|PID|e246063
NM23/nucleoside diphosphate kinase [Xenopus laevis]
65
50
450


116
1
3
1016
gnl|PID|d101125
queuosine biosynthesis protein QueA [Synechocystis sp.]
65
44
1014


123
1
69
389
gi|498839
ORF2 [Clostridium perfringens]
65
36
321


123
7
6522
7190
gi|1575577
DNA-binding response regulator [Thermotoga maritima]
65
39
669


125
3
3821
2859
gnl|PID|e257609
sugar-binding transport protein [Anaerocellum thermophilum]
65
47
963


137
12
8015
7818
gi|2182574
(AE000090) Y4pE [Rhizobium sp. NGR234]
65
41
198


147
4
5021
3885
gi|472329
dihydrolipoamide acetyltransferase [Clostridium magnum]
65
47
1137


148
2
1053
1931
gnl|PID|d101319
YqgN [Bacillus subtilis]
65
42
879


151
2
3212
4687
gi|304897
Ecos type I restriction modification enzyme M subunit [Escherichia coli]
65
50
1476


156
2
730
437
gi|310893
membrane protein [Theileria parva]
65
47
294


164
7
4256
4637
gi|410132
ORFX8 [Bacillus subtilis]
65
48
582


169
6
3192
3914
gi|1552737
similar to purina nucleoside phosphorylase (deoD)
65
41
723







[Escherichia coli]


176
4
2951
2220
gnl|PID|e339500
oligopeptide binding lipoprotein [Streptococcus pneumoniae]
65
43
732


195
4
4556
3900
gi|1592142
ABC transporter, probable ATP-binding subunit
65
40
657







[Methanococcus jannaschii]


196
1
1601
572
gnl|PID|d102004
(AB001488) PROBABLE UDP-N-
65
51
1413







ACETYLMURAMOYLALANYL-D-GLUTAMYL-







2,6-DIAMINOLIGASE (SC 6.3.2.15). [Bacillus subtilis]


204
2
2246
1215
gi|143156
membrane bound protein [Bacillus subtilis]
65
37
1032


210
4
1544
1891
gi|49315
ORF1 gene product [Bacillus subtilis]
65
48
348


242
2
1625
723
gi|1787540
(AE000226) f249; This 249 aa orf is 32 pct identical (8 gaps) to 244
65
42
903







residues of an approx. 272 aa protein AGAR_COLI SW: P42902 [Escherichia







coli]


284
1
1
900
gi|559861
clyM [Plasmid pAD1]
65
36
900


304
1
2
574
gnl|PID|e290934
unknown [Mycobacterium tuberculosis]
65
52
573


315
1
2
1483
gi|790694
mannuronan C-5-epimerase [Azotobacter vinelandii]
65
57
1482


320
1
3
569
gnl|PID|d102048


K. serogenes
, histidine utilization repressor;

65
46
567







P12380 (199) DNA binding







[Bacillus subtilis]


356
1
1
309
gnl|PID|e323508
YloS protein [Bacillus subtilis]
65
55
309


2
7
7571
6696
gi|1498753
nicotinate-nucleotide pyrophosphorylase [Rhodospirillum
64
47
876









rubrum
]



6
6
5924
6802
gnl|PID|d101111
methionine aminopeptidase [Synechocystis sp.]
64
52
879


8
4
3417
3686
gi|1045935
DNA helicase II [Mycoplasma genitalium]
64
58
270


11
4
3249
2689
gnl|PID|e265529
OrfB [Streptococcus pneumoniae]
64
46
561


15
7
6504
7145
gi|1762328
Ycr59c/YigZ homolog [Bacillus subtilis]
64
45
642


22
11
9548
9895
gnl|PID|d100581
unknown [Bacillus subtilis]
64
38
348


22
30
22503
23174
gi|289260
comE ORF1 [Bacillus subtilis]
64
44
672


26
7
14375
14199
gi|409286
bmrU [Bacillus subtilis]
64
30
177


27
2
1510
1334
gi|40795
DdeI methylase [Desulfovibrio vulgaris]
64
51
177


29
2
614
297
gi|2326168
type VII collagen [Mus musculus]
64
50
318


35
2
368
721
pir|JC1151|JC11
hypothetical 20.3K protein (insertion sequence IS1131) -
64
50
354









Agrobacterium tumefaciens
(strain P022) plasmid Ti



40
1
3
449
gi|46970
epiD gene product [Staphylococcus epidermidis]
64
41
447


40
7
4683
4976
gnl|PID|e325792
(AJ000005) glucose kinase [Bacillus megaterium]
64
45
294


45
7
8068
6920
gnl|PID|d102036
subunit of ADP-glucose pyrophosphorylase
64
40
1149







[Bacillus stearothermophilus]


51
2
301
1059
gi|43985
nifS-like gene [Lactobacillus delbrueckii]
64
54
759


51
13
15251
18397
gi|2293260
(AE008220) DNA-polymerese III alpha-chain [Bacillus subtilis]
64
46
3147


53
3
1157
555
gi|1574292
hypothetical [Haemophilus influenzae]
64
47
603


58
2
4236
1606
gi|1573826
alany-t-RRNA synthetase (alaS) [Haemophilus influenzae]
64
51
2631


66
1
3
1259
gi|895749
putative cellobinse phosphotransferase enzyme II′′
64
42
1257







[Bacillus subtilis]


68
5
5213
6556
gi|436965
(malA) gene products [Bacillus stearothermophilus]
64
47
1344


69
6
5356
4949
gnl|PID|d101316
Cdd [Bacillus subtilis]
64
52
408


74
4
6948
5038
gi|726480
L-glutamine-D-fructose-6-phosphate amidotransferase
64
50
1911







[Bacillus subtilis]


75
3
1283
1465
bbs|133379
TLS-CHOP = fusion protein (CHOP = C/EBP transcription
64
57
183







factor, TLS = nuclear RNA binding protein) [human,







myxoid liposarcomas cells, Peptide Mutant, 462 aa]







[Homo sapiens]


81
13
14016
14231
gi|143175
methanol dehydrogenase alpha-10 subunit [Bacillus sp.]
64
35
216


83
22
21851
22090
gnl|PID|d101315
YqfA [Bacillus subtilis]
64
44
240


87
11
10046
9300
gnl|PID|e323505
putative Ptc1 protein [Bacillus subtilis]
64
43
747


98
17
5032
5706
gnl|PID|e233880
hypothetical protein [Bacillus subtilis]
64
38
675


105
1
2
1276
gi|1657503
similar to S. aureus mercury (II) reductase [Escherichia coli]
64
45
1275


113
7
5136
6410
gnl|PID|d101119
NifS [Synechocystis sp.]
64
50
1275


119
1
2
1297
gnl|PID|e320520
hypothetical protein
64
37
1296







[Natronobacterium pharaonis]


123
3
1125
2156
gnl|PID|e253284
ORF YDL244w [Saccharomyces cerevisise]
64
40
1032


124
5
2331
1780
gnl|PID|d101884
hypothetical protein [Synechocystis sp.]
64
50
552


129
4
3467
2709
gnl|PID|d101314
Yqeu [Bacillus subtilis]
64
52
759


131
1
152
3
gi|1377841
unknown [Bacillus subtilis]
64
42
150


137
11
7196
7549
pir|JC1151|JC11
hypothetical 20.3K protein (insertion sequence IS1131) - Agrobacterium
64
50
354









tumefaciens
(strain 2022) plasmid Ti



139
3
3226
2651
gi|2293301
(AF008220) YtqB [Bacillus subtilis]
64
44
576


146
10
6730
5648
gi|1322245
mevalonate pyrophosphate decarboxylase [Rattus norvegicus]
64
45
1083


147
1
2
1018
gnl|PID|e137033
unknown gene product [Lactobacillus leichmannii]
64
46
1017


148
11
8430
8783
gi|2130630
(AF000430) dynamin-like protein [Homo sapiens]
64
28
354


156
7
4313
3612
gnl|PID|d102050
transmembrane [Bacillus subtilis]
64
31
702


157
4
1299
2114
gnl|PID|d100892
homologous to Gln transport system permease proteins [Bacillus subtilis]
64
43
816


162
6
5880
6362
gi|517204
ORF1, putative 42 kDa protein [Streptococcus pyogenes]
64
58
483


164
13
9707
8769
gnl|PID|d100964
homologue of ferric anguibactin transport system permerase protein FatD of
64
40
939









V. anguillarum
[Bacillus subtilis]



175
5
3906
14598
gi|534045
antiterminator [Bacillus subtilis]
64
39
693


189
10
6154
6507
gi|581307
response regulator [Lactobacillus plantarum]
64
33
354


191
4
3519
2863
gi|149520
phosphoribosyl anthranilate isomerase [Lactococcus lactis]
64
46
657


202
1
76
1140
gnl|PID|e293806
O-acetylhomoserine sulfhydrylase [Leptospira meyeri]
64
47
1065


224
1
234
1571
gi|1573393
collagenase (prtC) [Haemophilus influenzae]
64
42
1338


231
3
291
647
gi|40174
ORF X [Bacillus subtilis]
64
43
35


253
3
709
1089
pir|JC115|JC11
hypothetical 20.3K protein (insertion sequence IS1131) - Agrobacterium
64
50
381







tumefaciens (strain P022) plasmid Ti


265
1
820
2
gi|1377832
unknown [Bacillus subtilis]
64
31
819


297
1
1
660
gi|190871
collagenase [Nethanococcus jannaschii]
64
48
660


328
1
263
21
gi|992651
Gln4p [Saccharomyces cerevisiae]
64
41
243


5
14
8730
8098
gi|556885
Unknown [Bacillus subtilis]
63
48
633


10
6
5178
4483
gi|1573101
hypothetical [Haemophilus influenzae]
63
40
696


12
11
9324
9902
gi|806536
membrane protein [Bacillus acidopullulyticus]
63
42
579


15
10
8897
9187
gi|722339
unknown [Acetobecter xylinum]
63
40
291


17
2
1031
309
gnl|PID|e217602
PlnU [Lactobacillus planterum]
63
32
723


18
8
7778
6975
gi|1377843
unknown [Bacillus subtilis]
63
45
804


26
4
9780
7078
gi|142440
ATP-dependent nuclease [Bacillus subtilis]
63
46
2703


29
5
3488
14192
gi|1377829
unknown [Bacillus subtilis]
63
35
705


34
11
8830
7988
gnl|PID|d101198
ORF8 [Enterococcus faecalis]
63
45
843


35
3
1187
876
gi|722339
unknown [Acetobacter xylinum]
63
39
312


48
15
12509
11691
gi|1573389
hypothetical [Haemophilus influenzae]
83
41
819


51
11
12719
12189
gi|142450
ahrC protein [Bacillus subtilis]
63
35
531


55
4
3979
5022
gi|1708640
YeaB [Bacillus subtilis]
63
41
1044


55
15
13669
14670
gnl|PID|e311502
thioredoxine reductase [Bacillus subtilis]
63
44
1002


68
10
9242
8919
sp|P37686|YIAY
HYPOTHETICAL 40.2 KD PROTEIN IN AVTA-SELB INTERGENIC REGION (F382).
63
40
324


86
7
6554
5685
gi|1574382
lic-1 operon protein (licD) [[Haemophilus influenzae]
63
41
870


88
8
6085
5180
gi|2098719
putative fimbrial-associated protein [Actinomyces naeslundii]
63
43
906


96
8
5858
6484
gi|1052803
orflgyrb gene product [Streptococcus pneumoniae]
63
38
627


100
1
240
1940
gi|7171
fucosidase [Dictyostelium discoideum]
63
36
1701


104
4
3063
5765
gi|144985
phosphoenolpyruvate carboxylase [Corynebacterium glutamicum]
63
46
2703


106
8
9189
8554
gi|533099
endonuclease III [Bacillus subtilis]
63
45
636


122
6
4704
4886
gnl|PID|d101139
transposase [Synechocystis sp.]
63
39
183


128
7
4517
5203
gnl|PID|d101434
orf2 [Methanobacterium thermoautotrophicum]
63
50
687


137
4
963
1547
gi|472920
v-type Na-ATPase [Enterococcus hirae]
63
27
585


142
7
4100
4585
gnl|PID|e313025
hypothetical protein [Bacillus subtilis]
63
44
486


159
5
1741
2571
gi|1787043
(AE000184) f271; This 271 aa orf is 24 pct identical (16 gaps) to 285
63
39
831







residues of an approx. 272 aa protein YIDA_ECOLI SW: P09997 [Escherichia







coli]


171
12
8803
14406
gnl|PID|e324918
IgA1 protease [Streptococcus sanguis]
63
48
5604


177
1
3
347
gi|1773150
hypothetical 14.8 kd protein [Escherichia coli]
63
34
345


178
2
423
917
gi|722339
unknown [Acetobacter xylinum]
63
41
495


178
3
794
1012
gi|1591582
cobalamin biosynthesis protein N [Methanococcus jannaschii]
63
36
219


195
1
1377
175
gnl|PID|e324217
ftsQ [Enterococcus hirae]
63
33
1203


234
5
1739
1527
gi|1591582
cobalamin biosynthesis protein N [Methanococcus jannaschii]
63
36
213


249
1
81
257
gi|1000453
TreR [Bacillus subtilis]
63
41
177


283
1
127
1347
gi|396486
ORF8 [Bacillus subtilis]
63
44 1221


293
3
2804
3466
gi|722339
unknown [Acetobacter xylinum]
63
37
663


311
1
905
486
gi|1877424
UDP-galactoae 4-epimerase [Streptococcus mutana]
63
46
420


324
1
2
556
gi|477741
histidine periplasmic binding protein P29 [Campylobacter jejuni]
63
36
555


365
1
219
13
gi|2252843
(AF013293) No definition line found [Arabidopsis thaliana]
63
33
207


382
1
88
378
gi|722339
unknown [Acetobactar xylinum]
63
40
291


385
3
364
158
gi|2252843
(AF013293) No definition line found [Arabidopsis thaliana]
63
33
207


2
1
2495
288
gnl|PID|e325007
penicillin-binding protein [Bacillus saubtilis]
62
42
2208


3
23
23374
24231
gnl|PID|e254993
hypothetical protein [Bacillus subtilis]
62
35
858


6
16
14320
13193
gnl|PID|e349614
nifS-like protein [Mycobacterium lepras]
62
37
1128


7
8
6819
7232
gnl|PID|d101324
YghY [Bacillus subtilis]
62 32
414


7
19
15466
14207
gnl|PID|d101804
beta ketoacyl-acyl carrier protein synthase [Synechocystis sp.]
62
43
1260


7
21
17155
16229
gnl|PID|e323514
putative FabD protein [Bacillus subtilis]
62
46
927


7
24
19526
18519
gi|1276434
beta-ketoacyl-ACP synthase III [Cuphea wrightii]
62
37
1008


12
7
5904
4702
gi|1573768
A/G-specific adenine glycosylase (mutY) [Haemophilus influenzae]
62
43
1203


12
9
8032
8793
gi|1591567
pentothenate metabolism flavoprotein [Methanococcus jannaschii]
62
33
762


15
11
9678
9328
pir|JC1151|JC11
hypothetical 20.3K protein (insertion sequence IS1131) - Agrobacterium
62
43
351









tumefeciens
(strain P022) plasmid Ti



17
4
2609
2442
gi|1591081


M. janneschii
predicted coding region MJ0374 [Methanococcus jannaechii]

62
43
168


17
5
3053
2835
gi|149570
role in the expression of lactacin F, part of the laf operon [Lactobacillus sp.]
62
44
219


22
10
8627
9538
gnl|PID|d100580
similar to B. subtilis DnaH [Bacillus subtilis]
62
43
912


30
3
865
2043
gi|2314379
(AE000627) ABC transporter. ATP-binding protein (yhcG) [Helicobacter
62
43
1179









pylon
]



33
5
2235
1636
gi♂413976
ipa-52r gene product [Bacillus subtilis]
62
44
600


38
11
5689
6123
gi|148231
o251 [Escherichia coli]
62
34
435


40
17
14272
13328
gnl|PID|d101904
hypothetical protein [Synechocystis sp.]
62
43
945


42
1
3
3111
gi|1146182
putative [Bacillus subtilis]
62
41
309


44
2
1267
4005
gi|1786952
(AE000176) o877; 100 pct identical to the first 66 residues of the 100 aa
62
43
2739







hypothetical protein fragment YBGB_ECOLI SW: P54746 [Escherichie coli]


48
12
9732
9304
gi|662920
repressor protein [Enterococcus hirae]
62
32
429


51
8
5664
7181
gnl|PID|e301153
StySKI methylase [Salmonella enterica]
62
44
1518


52
3
2791
2099
gi|1183886
integral membrane protein [Bacillus subtilis]
62
41
693


55
16
15702
14704
gnl|PID|e313028
hypothetical protein [Bacillus subtilis]
62
40
999


59
6
3416
3984
gi|2065483
unknown [Lactococcus lactic lactic]
62
32
567


63
5
4997
4809
gi|149771
pilin gene inverting protein (PivML) [Moraxella lacunata]
62
28
189


70
14
10002
10739
gi|992977
bp1G gene product [Bordetella pertussis]
62
45
738


71
13
18790
20382
gi|1280135
coded for by C. elegens cDMA cm21e6; coded for by C. elegans cDNA cm01e2;
62
62
1593







similar to melibiose carrier protein (thiomethylgalactoside permease II)







[Caenorhabditis elegans]


71
28
32217
32768
gnl|PID|d101312
YqeG [Bacillus subtilis]
62
35
552


74
7
11666
10383
gi|1552753
hypothetical [Escherichia coli]
62
38
1264


80
8
9370
9609
gnl|PID|d102002
(AB001488) FUNCTION UNKNOWN. [Bacillus subtilis]
62
46
240


97
10
9068
7041
gi|882463
protein-N(pi)-phosphohistidine-sugar phosphotransferase [Escherichia coli]
62
42
2026


98
4
2306
3268
gnl|PID|d101498
BraE (integral membrane protein) [Pseudomonas aeruginosa]
62
42
963


102
3
2823
3539
gnl|PID|e313010
hypothetical protein [Bacillus subtilis]
62
24
717


103
3
2795
1242
gnl|PID|d102049


H. influenzae
hypothetical ABC transporter; p44806 (974) [Bacillus

62
41
1554







subtilis]


111
2
2035
3462
gi|581297
NisP [Lactococcus lactis]
62
44
1428


112
4
3154
4080
gi|1574379
lic-1 operon protein (licA) [Haemophilus influenzae]
62
39
927


112
6
4939
5649
gi|1574381
lic-l operon protein (licC) [Haemophilus influenzae]
62
39
711


124
3
1137
721
gi|1573024
anaerobic ribonucleoside-triphosphate reductase (nrdD) [Haemophilus
62
45
417







influenzae]


124
6
3162
2329
gi|609076
leucyl aminopeptidase [Lactobacillus delbrueckii]
62
40
834


126
7
11073
7516
gnl|PID|d101163
ORF4 [Bacillus subtilis]
62
38
3558


129
6
4983
4540
pir|S41509|S415
zinc finger protein EF6 - Chilo iridescent virus
62
48
444


131
7
4510
4103
gi|1857245
unknown [Lactococcus lactis]
62
42
406


149
2
1923
2579
gi|1592142
ABC transporter, probable ATP-binding subunit [Methanococcus jannaschii]
62
41
657


149
7
5360
6055
gnl|PID|e323508
YloS protein [Bacillus subtilis]
62
40
696


156
1
450
238
gnl|PID|e254644
membrane protein [Streptococcus pneumoniae]
62
40
213


156
6
3606 2935
gnl|PID|d102050
transmembrane [Bacillus subtilis]
62
37
672


171
2
1779 2291
gi|43941
EIII-B Sor PTS [Kiebsiella pneumoniae]
62
35
513


172
2
385
723
gi|895750
putative cellobiosa phosphotransferase enzyme III [Bacillus subtilis]
62
39
339


173
3
2599
893
gi|1591732
cobalt transport ATP-binding protein O [Methanococcus jannaschii]
62
42
1707


179
2
492
1754
gi|1574071


H. influenzae
predicted coding region HI1038 [Haemophilus influenzae]

62
38
1263


181
6
2856
3707
gi|1777435
LacT [Lactobacillus casei]
62
42
852


185
2
2074
311
gi|2182397
(AE000073) Y4fN [Rhizobium sp. NGR234]
62
41
1764


200
2
1061
1984
gi|450566
transmembrane protein [Bacillus subtilis]
62
37
924


202
3
2583
3473
gi|42219
P35 gene product (AA 1 - 314) [Escherichia coli]
62
41
891


210
3
1374
1565
gi|49315
ORF1 gene product [Bacillus subtilis]
62
45
192


211
1
3
971
gi|147402
mannose permease subunit III-Man [Escherichia coli]
62
43
969


223
2
1495
1034
gnl|PID|d101190
ORF2 [Streptococcus mutans]
62
41
462


228
1
34
9091
gi|530063
glycerol uptake facilitator [Streptococcus pneumoniae]
62
44
876


234
2
90
917
gi|2293259
(AF008220) YtqI [Bacillus subtilis]
62
38
828


282
5
1765
1487
gnl|PID|e276475
galactokinase [Arabidopsis thaliana]
62
33
279


375
1
1
159
gi|1674231
(AE00052) Mycoplasma pneumoniae, hypothetical protein homolog; similar to
62
40
159







Swiss-Prot Accession Number P35155, from B. subtilis [Mycoplasma







pneumoniae]


385
5
584
357
gi|1573353
outer membrane integrity protein (tolA) [Haemophilus influenzae]
82
47
228


3
19
18550
19269
gi|606162
ORF_f229 [Escherichia coli]
61
41
720


7
4
2725
3225
gi|2114425
similar to Synechocystis sp. hypothetical protein, encoded by GenBank
61
42
501







Accession Number D64006 [Bacillus subtilis]


17
6
3326
3054
gi|149569
lactacin F [Lactobacillus sp.]
61
43
273


44
3
4061
4957
gnl|PID|d101068
xylose repressor [Synechocystis sp.]
61
38
897


54
11
8388
7234
gnl|PID|d101329
YqjH [Bacillus subtilis]
61
42
1155


57
6
3974
6037
gnl|PID|d101316
YqfK [Bacillus subtilis]
61
42
2064


58
5
7356
6565
sp|P45169|POTC
SPERMIDINE/PUTRESCINE TRANSPORT SYSTEM PERMEASE PROTEIN POTC.
61
34
792


67
1
3
692
gi|537108
ORF_f254 [Escherichia coli]
61
46
690


68
9
8816
7890
gi|19501
pPLZ12 gene product (AA 1-184) [Lupinus polyphyllus]
61
41
927


70
15
10737
12008
gi|992976
bplF gene product [Bordetella pertussis]
61
44
1272


72
11
9759
10202
gnl|PID|d101833
carboxynorspermidine decarboxylase [Synechocystis sp.]
61
36
444


76
8
7881
7003
gnl|PID|d100305
farnesyl diphosphate synthase [Bacillus stearothermophilus]
61
45
879


87
4
4914
3697
gi|528991
unknown [Bacillus subtilis]
61
42
1218


87
13
12311
11361
gi|1789683
(AE000407) methionyl-tRNA formyltransferase [Escherichia coli]
61
44
951


91
2
731
2989
gi|537080
ribonucleoside triphosphate reductase [Escherichia coli]
61
45
2259


105
3
2711
3499
gnl|PID|d10185
hypothetical protein [Synechocystis sp.]
61
44
789


115
6
7968
6478
gi|895747
putative cel operon regulator [Bacillus subtilis]
61
36
1491


123
8
7181
8518
gi|1209527
protein histidine kinese [Enterococcus faecalis]
61
40
1338


126
6
7525
6725
gi|1787043
(AE000184) f271; This 271 aa orf is 24 pct identical (16 gaps) to 265
61
38
801







residues of an approx. 272 as protein YIDA_ECOLI SW: P09997 [Escherichia







coli]


128
1
1
639
gnl|PID|d101328
YgiY [Bacillus subtilis]
61
41
639


139
7
4794
5054
gi|1022726
unknown [Staphylococcus haemolyticus]
61
41
261


139
9
12632
5913
gnl|PID|e270014
beta-galactosidase [Thermoanaerobacter ethanolicus]
61
41
6720


143
1
2552
42
gi|520541
penicillin-binding proteins 1A and 1B [Bacillus subtilis]
61
42
2511


148
16
12125
11424
gi|1552743
tetrahydrodipicolinete N-succinyltransferase [Escherichia coli]
61
42
702


162
3
4112
3456
gnl|PID|d101829
phosphoglycolate phosphatase [Synechocystis sp.]
61
30
657


172
3
727
1077
gnl|PID|d102048


B. subtilis
, cellobiose phosphotransferase system, celA; P46318 (220)

61
44
351







[Bacillus subtilis]


177
3
1101
1772
gnl|PID|d100574
unknown [Bacillus subtilis]
61
43
672


202
2
1278
2585
gi|1045831
hypothetical protein (GB:L189656) [Mycoplasma genitalium]
61
36
1308


224
3
2782
3144
gi|1591144


M. jannaschii
predicted coding region MJ0440 [Methanococcus janneachil]

61
30
363


225
4
3395
3766
gi|1552774
hypothetical [Escherichia coli]
61
40
372


249
2
212
802
gi|1000453
TreR [Bacillus subtilis]
61
42
591


254
2
843
484
gnl|PID|d100417
ORF120 [Escherichia coli]
61
36
360


257
1
3
350
gnl|PID|e255315
unknown [iMycobacterium tuberculosis]
61
42
348


293
4
3971
3657
pir|JC1151|JC11
hypothetical 20.3K protein (insertion sequence IS1131) - Agrobacterium
61
45
315







tumefaciens (strain P022) plasmid Ti


301
1
949
17
gi|2291209
(AF016424) contains similarity to acyltransferases [Caenorhabditis elegans]
61
33
933


373
1
1066
287
gi|393396
Tb-292 membrane associated protein [Trypanosoma brucei subgroup]
61
38
780


3
24
24473
24955
gi|537093
ORF_o153b [Escherichia coli]
60
27
483


6
5
4616
5739
gi|2293258
(AF008220) YtoI [Bacillus subtilis]
60
35
1104


6
12
11936
11187
gi|293017
ORF3 (put.); putative [Lactococcus lactis]
60
44
750


17
13
6708
6484
gi|149569
lactacin F [Lactobacillus sp.]
60
32
225


18
7
6977
5670
gi|1788140
(AE000278) o481; This 481 aa orf is 35 pct identical (19 gaps) to 309
60
43
1308







residues of an approx. 856 aa protein NOL1_HUMAN SW: P46087 [Escherichia









coli
]



20
15
15878
17167
gnl|PID|d100584
unknown [Bacillus subtilis]
60
44
1290


22
1
1
243
gnl|PID|d102050
transmembrane [Bacillus subtilis]
60
36
243


32
10
8296
8964
gi|2293275
(AF008220) YtaG [Bacillus subtilis]
60
37
669


38
15
8837
9697
gi|40023


B.subtilis
genes rpmH, rnpA, 50kd, gidA and gidB [Bacillus

60
35
861







subtilis]


43

6
8610
5944
gi|171787
protein kinase 1 [Saccharomyces cerevisime]
60
36
2667


44
1
1
1269
gnl|PID|e235823
unknown [Schizosaccharomyces pombe]
60
44
1269


45
10
11138
10368
gi|397488
1,4-alpha-glucan branching enzyme [Bacillus subtilis]
60
43
771


48
19
15766
14378
gnl|PID|e205173
orf1 [Lactobacillus belveticus]
80
39
1389


48
21
16727
16951
gnl|PID|d102041
(AB002688) unnamed protein product [Haemophilus
60
32
225









actinomycetemcomitans
]



50
1
2
898
gnl|PID|e246537
ORF286 protein [Pseudomonas stutzeri]
60
31
897


62
2
638
1177
gnl|PID|d100587
unknown [Bacillus subtilis]
60
42
540


68
4
3590
5203
gi|1573583


H. influenzae
predicted coding region HI0594

60
36
1614







[Haemophilus influenzae]


70
11
5781
6182
gnl|PID|d102014
(AB001488) SIMILAR TO YDFR GENE PRODUCT OF THIS
60
33
402







ENTRY (YDFR_BACSU).







[Bacillus subtilis]


70
12
8343
8133
gnl|PID|e324970
hypothetical protein [Bacillus subtilis]
60
38
1791


71
8
11701
14157
gi|580866
ipa-12d gene product [Bacillus subtilis]
60
33
2457


74
8
12509
11664
gnl|PID|d101832
phosphatidate cytidylyltransferase [Synechocystis sp.]
60
45
846


76
4
4116
3367
gi|2352096
orf; similar to serine/threonine protein phosphatase
60
39
750







[Fervidobacterium islandicum]


80
4
7372
7665
gi|1786420
(AE000131) f86; 100 pct identical to GB: ECODINJ_6
60
30
294







ACCESSION: D38582 [Escherichia coli]


81
6
4073
4522
gi|147402
mannose permease subunit III-Man [Escherichia coli]
60
35
450


86
1
940
155
gi|143177
putative [Bacillus subtilis]
60
26
786


92
1
1
192
gi|396348
homoserine transsuccinylase [Escherichia coli]
60
45
192


93
14
10619
9384
gi|1788389
(AE000297) o464; This 464 aa orf is 33 pct identical
60
27
1236







(9 gaps) to 331 residues of an approx. 416 aa protein







MTRC_NEIGO SW: P43505 [Escherichia coli]


94
5
5548
8121
gnl|PID|e329895
(AJ000496) cyclic nucleotide-gated channel beta subunit
60
50
2574







[Rattus norvegicus]


97
7
5396
4533
gi|1591396
transketolase [Methanococcus jannaschii]
60
43
864


102
2
2081
2833
gnl|PID|e320929
hypothetical protein [Mycobacterium tuberculosis]
60
43
753


106
9
9773
9183
gnl|PID|e334782
YlbN protein [Bacillus subtilis]
60
31
591


113
8
6361
6837
gi|466875
nifU; B1496_C1_157 [Mycobacterium leprae]
60
43
477


115
2
2755
524
gnl|PID|e328143
(AJ000332) Clucosidase II [Homo sapiens]
60
32
2232


122
7
4763
5068
gnl|PID|d101876
transposase [Synechocystis sp.]
60
39
306


127
8
4510
5283
gi|1777938
Pgm [Treponema pallidum]
60
38
774


138
4
3082
2672
gnl|PID|e325196
hypothetical protein [Bacillus subtilis]
60
36
411


139
1
77
4
gnl|PID|d100680
ORF [Thermos thermophilus]
60
39
174


139
11
14520
13009
gi|537145
ORF_f437 [Escherichia coli]
60
30
1512


140
2
2592
1249
gi|1209527
protein histidine kinase [Enterococcus faecalis]
60
37
1344


141
1
210
1049
gi|463181
E5 ORF from bp 3842 to 4081; putative [Human
60
34
840







papillomavirus type 33]


141
5
5368
6405
gi|145362
tyrosine-sensitive DAHP synthase (aroF) [Escherichia coli]
60
41
1038


142
6
3558
4049
gi|600711
putative [Bacillus subtilis]
60
37
492


148
10
7742
8713
gnl|PID|e313022
hypothetical protein [Bacillus subtilis]
60
27
972


153
5
3667
4278
gi|2293322
(AF008220) branch-chain amino acid transporter
60
42
612







[Bacillus subtilis]


155
1
1413
748
gi|2104504
putative UDP-glucose dehydrogenase [Escherichia coli]
60
40
666


158
3
3116
2472
gnl|PID|d100872
a negative regulator of pho regulon [Pseudomonas aeruginosa]
60
37
645


159
3
778
1386
gnl|PID|e308090
product highly similar to [Bacillus anthracis CapA protein
60
48
609







[Bacillus subtilis]


163
7
8049
8468
gnl|PID|d101313
YqeN [Bacillus subtilis]
60
38
420


170
3
4130
2688
gi|1574179


H. influenzae
predicted coding region HI1244

60
39
1443







[Haemophilus influenzae]


171
7
4717
5901
gi|606076
ORF_o384 [Escherichia coli]
60
44
1185


183
3
2440
2135
gi|1877427
repressor [Streptococcus pyogenes phage T12]
60
38
306


191
10
9444
8428
gi|415664
catabolite control protein [Bacillus megaterium]
60
42
1017


200
1
139
1083
gi|438462
transmembrane protein [Bacillus subtilis]
60
37
945


201
3
3895
1928
gi|475112
enzyme IIabc [Pediococcus pentosaceus]
80
39
1968


214
15
10930
10439
gi|1573407
hypothetical [Haemophilus influenzae]
60
39
492


218
4
2145
2363
gi|608520
myosin heavy chain kinase A [Dictyostelium discoideum]
60
31
219


226
4
2518
2351
gi|437705
hydaluronidase [Streptococcus pneumoniae]
60
53
168


242
1
725
3
gi|43938
Sor regulator [Klebsiella pneumoniae]
60
41
723


245
1
1
288
gi|304897
EcoE type I restriction modification enzyme 14 subunit
60
56
286







[Escherichia coli]


251
1
905
45
gi|671632
unknown [Staphylococcus aureus]
60
36
861


259
1
969
82
gi|153794
rgg [Streptococcus gordonli]
60
32
888


260
2
1492
1662
pir|S31840|S318
probable transposase - Bacillus stearothermophilus
60
26
171


274
1
836
96
gi|1592173
N-ethylammeline chlorohydrolase [Methanococcus jannaschii]
60
40
741


308
1
463
2
gi|1787397
(AE000214) o157 [Escherichia coli]
60
43
462


318
1
3
308
gnl|PID|e137594
xerC recombinase [Lactobecillus leichmannii]
60
42
306


344
1
73
522
gi|509872
repressor protein [Bacteriophage Tuc2009]
60
32
450


5
1
576
4
gi|2293147
(AF008220) YtxM [Bacillus subtilis]
59
31
573


7
22
18140
17142
gnl|PID|e280724
unknown [Mycobacterium tuberculosis]
59
39
999


10
1
1413
4
gi|1353880
sialidase L [Macrobdella decora]
59
41
1410


15
6
6463
5156
gi|580841
F1 [Bacillus subtilis]
59
35
1308


22
2
479
1393
gi|142469
als operom regulatory protein [Bacillus subtilis]
59
34
915


22
5
2698
4614
gnl|PID|e280623
PCPA [Streptococcus pneumoniae]
59
44
1917


30
1
208
558
gnl|PID|e233868
hypothetical protein [Bacillus subtilis]
59 37
351


30
4
3678
2455
gnl|PID|e202290
unknown [Lactobacillus sake]
59
33
1224


35
13
12201
11071
gnl|PID|e238664
hypothetical protein [Bacillus subtilis]
59
35
1131


35
14
13288
12182
gi|1657647
Cap8H [Staphylococcus aureus]
59
39
1107


36
18
18076
17897
gi|1500535


M. jannaschii
predicted coding region MJ1635

59
33
180







[Methanococcus jannaschii]


38
12
6172
7137
gi|2293239
(AF008220) YtxK [Bacillus subtilis]
59
34
966


42
3
1952
3361
gi|1684845
pinin [Canis familiaris]
59
40
1410


50
3
2678
1728
gnl|PID|d101329
YqjK [Bacillus subtilis]
59
41
951


56
5
1870
2388
gnl|PID|e137594
xerC recombinase [Lactobacillus leichmannii]
59
41
519


61
6
6812
5628
gnl|PID|e311516
aminotransferase [Bacillus subtilis]
59
40
1185


67
5
2382
3023
gi|1146190
2-keto-3-deoxy-6-phosphogluconate aldolase [Bacillus subtilis]
59
36
642


69
10
8567
8899
gi|1573628
antothenate kinase (coaA) [Haemophilus influenzae]
59
38
333


87
12
1383
10055
gnl|PID|e323504
putative Fmu protein [Bacillus subtilis]
59
44
1329


113
14
13927
15894
gi|1673731
(AE000010) Mycoplasma pneumoniae, fructose-permease IIBC
59
43
1968







component; similar to Swiss-Prot Accession Number P20966, from E. coli







[Mycoplasma pneumoniae]


115
8
8786
8521
gi|1590886


M. jennaschii
predicted coding region MJ0110

59
38
246







[Methanococcus jannaschii]


119
2
1966
1526
gnl|PID|e209005
homologous to ORF2 in nrdEF operons of E.coli and
59
43
441









Styphimurium
[Lactococcus lactis]



128
17
13438
13178
gnl|PID|e279632
unknown [Mycobacterium tuberculosis]
59
38
261


140
22
23903
23388
gi|482922
protein with homology to pail repressor of B.subtilis
59
40
516







[Lactobacillus delbrueckii]


148
13
9697
9014
gnl|PID|d102005
(AB001488) FUNCTION UNKNONN, SIMILAR PRODUCT
59
32
684







IN H. INFLUENZAE AND SYNECHOCYSTIS.







[Bacillus subtilis]


149
10
7213
8244
gi|710422
cmp-binding-factor 1 [Staphylococcus aureus]
59
40
1032


164
9
6993
6013
gnl|PID|d100965
ferric anguibactin-binding protein precusor FatB of
59
41
981









V. anguillarum
[Bacillus subtilis]



164
12
8836
7823
gnl|PID|d100964
homologue of ferric anguibactin transport system permerase
59
35
1014







protein FatC of V. anguillarum [Bacillus subtilis]


177
2
401
1072
gi|289759
coded for by C. elegans cDNA CE2G3 (GenBank:Z14728);
59
40
672







putative [Caenorhabditis elegans]


177
7
3841
4200
gi|2313445
(AE000551) H. pylon predicted coding region HP0342
59
38
360







[Helicobacter pylon]


183
4
2768
2508
gi|509672
repressor protein [Bacteriophage Tuc2009]
59
50
261


186
6
3398
2820
gi|606080
ORF_o290; Geneplot suggests frameshift linking to o267,
59
38
579







not found [Escherichia coli]


190
3
3120
1711
gi|1613768
histidine protein kinase [Streptococcus pneumoniae]
59
32
1410


194
2
1621
1019
gnl|PID|d100579
unknown [Bacillus subtilis]
59
40
603


198
7
5205
4306
gnl|PID|e313073
hypothetical protein [Bacillus subtilis]
59
38
900


220
5
4362
3958
gnl|PID|d101322
YqhL [Bacillus subtilis]
59
46
405


242
3
1573
2367
gi|1787045
(AE000184) f308; This 308 aa orf is 35 pct identical (35 gaps)
59
42
795







to 305 residues of an approx. 296 aa protein PFLC_ECOLI SN: P32675







[Escherichia coli]


247
2
1154
1480
gi|40073
ORF107 [Bacillus subtilis]
59
39
327


256
1
868
2
gnl|PID|d101924
hemolysin [Synechocystis sp.]
59
39
867


258
1
65
820
gi|2246532
ORF 73, contains large complex repeat CR 73
59
20
756







[Kaposi's sarcoma-associated herpesvirus]


270
1
386
1126
gnl|PID|d102092
YfnB [Bacillus subtilis]
59
40
741


281
1
552
166
gi|666062
putative [Lactococcus lactis]
59
31
387


309
1
3
479
gi|405879
yeiH [Escherichia coli]
59
36
477


363
1
2
1994
gi|915208
gastric mucin [Sus scrofa]
59
31
1893


387
2
425
84
gi|160671
antigen precursor [Plasmodium falciparum]
59
44
342


5
6
11223
10465
gnl|PID|d101812
LumQ [Synechocystis sp.]
58
29
759


29
4
2098
3513
gnl|PID|d100479
Na+ -ATPase subunit J [Enterococcus hirae]
58
39
1416


30
5
4058
3651
gi|39478
ATP binding protein of transport ATPases [Bacillus firmus]
58
34
408


33
6
2983
2210
gnl|PID|d101164
unknown [Bacillus subtilis]
58
45
774


36
8
5316
6179
gi|1518679
orf [Bacillus subtilis]
58
32
864


43
5
5926
3971
gi|1788150
(AE000278) protease II [Escherichia coli]
58
37
1956


46
5
3704
5221
gnl|PID|e267329
Unknown [Bacillus subtilis]
58 42
1518


48
14
11722
11066
gnl|PID|d101771
thiamin biosynthetic bifunctional enzyme [Synechocystis sp.]
58
34
657


52
1
1229
3
gnl|PID|d101291
reductase [Pseudomonas aeruginosa]
58
35
1227


53
2
702
412
gi|2313357
(AE000545) cytochrome c biogenesis protein (ccdA)
58
25
291







[Helicobacter pylon]


58
4
6586
5498
gi|147329
transport protein [Escherichia coli]
58
41
1089


69
5
4934
3807
gnl|PID|e311492
unknown [Bacillus subtilis]
58
41
1128


71
27
31357
32277
gi|2408014
hypothetical protein [Schizosaccharomyces pombe]
58
33
921


72
4
35861
2882
gi|18694
nodulin-21 (AA 1-201) [Glycine max]
58
34
705


74
3
4937
4230
gi|2293252
(AE008220) YtmO [Bacillus subtilis]
58
33
708


79
4
4594
3422
gi|1217989
ORF3 [Streptococcus pneumoniae]
58
44
1173


82
8
10585
8171
gi|882711
exonuclease V alpha-subunit [Escherichia coli]
58
38
2415


86
17
16017
15337
gi|47642
5-dehydroquinate hydrolyase (3-dehydroguinase)
58
32
681







[Salmonella typhi]


97
2
931
560
gi|153794
rgg [Streptococcus gordonii]
58
32
372


108
2
358
2724
gi|537020
vacB gene product [Escherichia coli]
58
37
2367


111
5
4593
5240
gi|1592142
ABC transporter, probable ATP-binding subunit
58
36
648







[Methanococcus jannaschii]


120
3
4421
5110
gnl|PID|d101320
YqgX [Bacillus subtilis]
58
47
690


126
16
13131
12673
gi|662919
ORF U [Enterococcus hirae]
58
42
459


132
3
6174
4939
gi|1800301
macrolide-efflux determinant [Streptococcus pneumoniae]
58
35
1236


133
1
111
890
gnl|PID|e269488
Unknown [Bacillus subtilis]
58
36
760


160
11
8615
9865
gi|473901
ORF1 [Lactococcus lactis]
58
39
1251


161
6
6268
6849
gnl|PID|d101024
DJ-1 protein [Homo sapiens]
58
32
582


169
1
214
2
gnl|PID|d100447
translation elongation factor-3 [Chlorella virus]
58
31
213


187
1
487
2
gi|475114
regulatory protein [Pediococcus pentosaceus]
58
38
486


187
6
4384
4620
gi|167475
dessication-related protein [Craterostigma plantagineum]
58
55
237


190
2
1464
1640
gnl|PID|e246727
competence pheromone [Streptococcus gordonii]
58
38
177


192
2
2012
1344
gnl|PID|d100556
rat GCP360 [Rattus rattus]
58
44
669


206
1
1292
696
gnl|PID|e202579
product similar to WrbA [Lactobacillus sake]
58
35
597


216
2
2333
555
gnl|PID|e325036
hypothetical protein [Bacillus subtilis]
58
33
1779


217
5
5250
4321
gi|466474
cellobiose phosphotransferase enzyme II′′
58
38
930







[Bacillus stearothermophilus]


217
7
5636
5106
gnl|PID|d102048


B. subtilis
cellobiose phosphotransferase system celB;

58
44
531







P46317 (998) transmembrane [Bacillus subtilis]


232
1
2
811
gi|1573777
cell division ATP-binding protein (ftsE)
58
39
810







[Haemophilus influenzae]


264
1
2
7151
gi|973330
NatA [Bacillus subtilis]
58
32
714


280
1
33
767
gi|1786187
(AE000111) hypothetical 29.6 kD protein in thrC-talB
58
31
735







intergenic region [Escherichia coli]


306
1
845
3
gnl|PID|e334780
YlbL protein [Bacillus subtilis]
58
47
843


360
3
1556
1092
sp|P46351|YZGD
HYPOTHETICAL 45.4 KD PROTEIN IN THIAMINASE I
58
32
465







5′REGION.


363
5
2160
1867
gi|160671
S antigen precursor [Plasmodium falciparum]
58
51
294


372
1
806
3
gi|393394
Tb-291 membrane associated protein [Trypanosoma brucei
58
37
804







subgroup]


382
2
749
519
pir|JC1151|JC11
hypothetical 20.3K protein (insertion sequence IS1131) -
58
41
231









Agrobacterium tumefaciens
(strain P022) plasmid Ti



3
9
8409
7471
gi|1499745


M. jannaschii
predicted coding region MJ0912

57
38
939







[Methanococcus jannaschii]


10
10
7674
7507
gi|1737169
homologue to SKP1 [Arabidopsis thaliena]
57
30
168


11
1
2
412
gnl|PID|d100139
ORF [Acetobacter pasteurienus]
57
42
411


31
4
2032
1388
gi|2293213
(AF008220) YtpR [Bacillus subtilis]
57
37
645


33
11
6931
6449
gnl|PID|e324949
hypothetical protein [Bacillus subtilis]
57
36
483


45
5
5446
5060
gi|1592204
phosphoserine phosphatase [Methanococcus jannaschii]
57
44
387


49
7
6523
7632
gi|155369
PTS enzyme-II fructose [Xanthomonas campestris]
57
35
1110


52
6
4520
6850
gi|1574144
single-stranded-DNA-specific exonuclease (recJ)
57
35
2331







[Haemophilus influenzae]


53
5
2079
1795
gi|1843580
replicase-associated polyprotein [oat blue dwarf virus]
57
46
285


63
6
5312
4995
gi|2182608
(AE000094) Y4rJ [Rhizobium sp. NGR234]
57
39
318


72
15
13883
13059
gnl|PID|d100892
homologous to SwissProt:YIDA_ECOLI hypothetical protein
57
40
825







[Bacillus subtilis]


79
2
2561
1815
gnl|PID|d100965
homologue of NADPH-flavin oxidoreductese Frp of V. harveyi
57
44
747







[Bacillus subtilis]


82
9
9596
9763
gi|1206045
short region of similarity to glycerophosphoryl diester
57
35
168







phosphodiesterases [Caenorhabditis elegans]


88
16
15371
14493
gi|1787983
(AE000264) o288; 92 pct identical (1 gaps) to 222 residues
57
34
879







of fragment YDIB_ECOLI SW: P28244 (223 aa)







[Escherichia coli]


93
3
1695
1177
gi|1500003
mutator mutT protein [Methanococcus jenneschii]
57
33
519


96
6
3026
4519
gi|559882
threonine synthase [Arabidopsis thaliana]
57
43
1494


99
14
17211
18212
gi|773349
BirA protein [Bacillus subtilis]
57
44
1002


112
8
7448
7903
gi|1591393


M. jannaschii
predicted coding region MJ0678

57
30
456







[Methanococcus janneschii]


113
16
18627
18328
pir|A45605|A456
mature-parasite-infected erythrocyte surface antigen MESA -
57
22
300









Plasmodium falciparum




123
2
343
1110
pir|F64149|F641
hypothetical protein HI0355 - Haemophilus influenzae
57
38
768







(strain Rd KW20)


123
4
2108
2884
gnl|PID|d102148
(AB001684) sulfate transport system permease protein
57
39
777







[Chlorella vulgaris]


127
10
6477
5587
gi|1573082
nitrogenase C (nifC) [Haemophilus influenzae]
57
35
891


128
13
9251
9790
gi|153692
pneumolysin [Streptococcus pneumoniae]
57
38
540


131
4
2139
1363
gi|42081
nagD gene product (AA 1-250) [Escherichia coli]
57
36
777


136
1
214
1221
bbs|148453
SpaA = endocarditis immunodominant antigen [Streptococcus
57
44
1008









sobrinus
, MUCOB 263, Peptide, 1566 aa]








[Streptococcus sobrinus]


140
25
28701
26851
gi|505576
beta-glucoside permease [Bacillus subtilis]
57
38
1851


141
6
6395
7438
gi|995580
unknown [Schizosaccharomyces pombe]
57
41
1044


144
3
3231
2785
gnl|PID|d100139
ORF [Acetobacter pasteurianus]
57
42
447


155
4
5454
4564
gi|600431
glycosyl transerase [Erwinia amylovora]
57
34
891


159
9
4877
5854
gi|290509
o307 [Escherichia coli]
57
35
978


167
11
9710
9249
gnl|PID|d100139
ORF [Acetobacter pasteurianus]
57
42
462


171
6
4023
4438
gi|147402
mannose permease subunit III-Man [Escherichia coli]
57
29
414


178
4
2170
1076
gnl|PID|d102004
(AB001488) ATP-DEPENDENT RNA HELICASE DEAD
57
39
1095







HOMOLOG. [Bacillus subtilis]


190
1
145
1455
gi|149420
export/processing protein [Lactococcus lactis]
57
30
1311


198
1
298
951
gi|522268
unidentified ORF22 [Bacteriophage bIL67]
57
36
204


203
2
3195
2110
gnl|PID|e283915
orf c01003 [Sulfolobus solfataricus]
57
41
1086


205
1
40
507
gi|1439527
EII-man [Lactobacillus curvatus]
57
28
468


214
7
4243
3797
gnl|PID|d102049


H. influenzae
, rihosomal protein alanine acetyltransferase;

57
48
447







P44305 (189) [Bacillus subtilis]


268
3
1767
1278
gi|43979


L.curvatus
small cryptic plasmid gene for rep protein

57
36
492







[Lactohacillus curvatus]


351
1
324
34
gnl|PID|e275871
T03F6.b ]Caenorhabditis elegans]
57
31
291


386
1
226
2
gi|16067
S antigen precursor [Plasmodium falciparum]
57
45
225


5
5
10486
8777
gi|405857
yehU [Escherichia coli]
56
33
1710


8
5
36743
9101
gi|467199
pksC; L518_F1_2 [Mycobacterium leprae]
58
39
237


10
3
3442
1874
gnl|PID|d101907
sodium-coupled permease [Synechocystis sp.]
56
36
1569


21
1
1880
333
gi|2313949
(AE000593) osmoprotection protein (proWX)
56
33
1548







[Helicobacter pylon]


22
29
21968
22456
gnl|PID|d102001
(AB001488) PROBABLE ACETYLTRANSFERASE.
56
37
489







[Bacillus subtilis]


27
1
1361
3
gi|215132
ea59 (525) [Bacteriophage lambda]
56
30
1359


28
9
4667
4278
gi|1592090
DNA repair protein RAD2 [Methanococcus jannaschii]
56
29
390


33
1
3
386
gnl|PID|d100139
ORF [Acetobacter pasteurianus]
56
41
384


36
7
5122
5397
pir|PQ0053|PQ00
hypothetical protein (proC 3′ region) -
56
28
276









Pseudomonas aeruginosa
(strain PAO)



40
4
3137
4318
gi|1800301
macrolide-efflux determinant [Streptococcus pneumoniae]
56
27
1182


40
16
12511
13191
gnl|PID|e217602
PlnU [Lactobacillus plantarum]
56
38
681


48
17
13775
13023
gi|143729
transcription activator [Bacillus subtilis]
56
35
753


75
4
1674
2594
gn|PID|d102036
membrane protein [Bacillus stearothermophilus]
56
25
921


85
3
1842
1459
gnl|PID|d100139
ORF [Acetobacter pasteurienus]
56
41
384


89
7
5815
4940
gi|853777
product similar to E.coli PRFA2 protein [Bacillus subtilis]
56
42
876


105
2
1360
2718
gnl|PID|d101913
hypothetical protein [Synechocystis sp.]
56
37
1359


112
3
2151
3194
gi|537201
ORF_o345 [Escherichia coli]
56
31
1044


113
4
2754
2963
gn|PID|d100340
ORF [Plum pox virus]
56
28
210


122
3
1203
2054
gi|1649035
high-affinity periplasmic glutemine binding protein
56
30
852







[Salmonella typhimurium]


124
8
3939
3694
gn|PID|e248893
unknown [Mycobacterium tuberculosis]
56
27
246


125
4
4403
4107
gnl|PID|d100247
human non-muscle myosin heavy chain [Homo sapiens]
56
32
297


127
11
6608
6405
gi|2182397
(AE000073) Y4fN [Rhizobium sp. NGR234]
56
35
204


134
5
4769
3849
gn|PID|d101870
hypothetical protein [Synechocystis sp.]
56
39
921


137
10
6814
7245
gi|1592011
sulfate permease (cysA) [Methanococcus jannaschii]
56
34
432


142
8
5019
4582
pir|A47071|A470
orf1 immediately 5′ of nifS - Bacillus subtilis
56
29
438


146
8
4676
3660
gnl|PID|d101911
hypothetical protein [Synechocystis sp.]
56
32
1017


148
3
1906
2739
gnl|PID|d101099
phosphate transport system permeasa protein PstA
56
36
834







[Synechocystis sp.]


150
4
4449
2743
gnl|PID|e304628
probably site-specific recombinase of the resolvase
56
27
1707







family of enzymes [Bacteriophage TP21]


172
1
2
208
gi|1787791
(AE000249) f317; This 317 aa orf is 27 pct identical (16 gaps)
56
34
207







to 301 residues of an approx. 320 as protein







YXXC_BACSU SW: P39140 [Escherichia coli]


172
7
4979
5668
gi|396293
similar to Bacillus subtilis hypoth. 20 kDa protein, in tsr 3′
56
40
690







region [Escherichia coli]


186
7
3732
3367
gi|1732200
PTS permease for mannose subunit IIPMan [Vibrio furnissii]
56
36
366


187
2
2402
819
pir|557904|S579
virR49 protein - Streptococcus pyogenes
56
35
1584







(strain CS101, serotype M49)


204
3
2772
2239
gi|606376
ORF_o162 [Escherichia coli]
56
35
534


206
2
3342
1633
gi|559861
clyM [Plasmid pAD1]
56
38
1710


219
3
1689
1096
gi|1146197
putative [Bacillus subtilis]
56
27
594


230
2
409
1485
pir|C60328|C603
hypothetical protein 2 (sr 5′ region) -
56
40
1077









Streptococcus mutans
(strain OMZ175, serotype f)



233
4
2930
3268
gi|1041785
rhoptry protein [Plasmodium yoelii]
56
24
339


273
2
1543
2724
gi|143089
iep protein [Bacillus subtilis]
56
32
1182


353
1
1
516
gnl|PID|e325000
hypothetical protein [Bacillus subtilis]
56
41
516


359
1
87
641
gif|1786952
(AE000176) o877; 100 pct identical to the first 86 residues of
56
46
555







the 100 aa hypothetical protein fragment







YBGB_ECOLI SW: P54746 [Escherichia coli]


363
7
4482
4198
gi|1573353
outer membrane integrity protein (tolA)
56
38
285







[Haemophilus influenzae]


376
1
2
508
gnl|PID|e325031
hypothetical protein [Bacillus subtilis]
56
33
507


18
1
836
177
gnl|PID|d100872
a negative regulator of pho regulon
55
31
660







[Pseudomonas aeruginosa]


28
4
1824
1618
gnl|PID|e316518
STAT protein [Dictyostelium discoideum]
55
40
207


29
6
4486
5041
gi|1088261
unknown protein [Anabaena sp.]
55
31
546


38
16
9695
10702
gi|580905


B.subtilis
genes rpmH, rnpA, 50kd, gidA and gidB

55
31
1008







[Bacillus subtilis]


49
5
5727
6182
gi|1786951
(AE000176) heat-responsive regulatory protein
55
29
456







[Escherichia coli]


51
4
2381
3241
gnl|PID|d101293
YbbA [Bacillus subtilis]
55
42
861


52
9
9640
10866
gi|1530161
ORF 419 protein [Staphylococcus aureus]
55
23
1227


53
4
1813
1349
gi|896042
OspE [Borrelia burgdorferi]
55
30
465


60
5
4794
5756
gi|1499876
magnesium and cobalt transport protein
55
38
963







[Methanococcus jannaschii]


71
9
14176
15408
gi|1857120
glycosyl transferase [Neisseria meningitidis]
55
41
1233


75
6
3189
4229
gnl|PID|e209890
NAD alcohol dehydrogenase [Bacillus subtilis]
55
44
1041


108
10
10488
9820
gnl|PID|e324997
hypothetical protein [Bacillus subtilis]
55
36
669


113
12
12273
13037
gnl|PID|e311496
unknown [Bacillus subtilis]
55
34
765


113
13
13007
13945
gi|1573423
1-phosphofructokinase (fruK) [Haemophilus influenzae]
55
39
939


126
5
6764
5907
gi|1790131
(AE000446) hypothetical 29.7 kD protein in ibpA-gyrB
55
37
858







intergenic region [Escherichia coli]


129
3
2719
902
gnl|PID|d101425
Pz-peptidese [Bacillus licheniformis]
55
35
1818


138
3
2593
1610
gi|142833
ORF2 [Bacillus subtilis]
55
37
984


140
6
6916
5633
gnl|PID|d100964
homologue of hypothetical protein in a rapemycin synthesis
55
26
1284







gene cluster of [Streptomyces hygroscopicus [Bacillus subtilis]


147
3
3854
2136
gi|472330
dihydrolipoamide dehydrogenese [Clostridium magnum]
55
39
1719


147
10
10204
8921
gnl|PID|e73078
dihydroorotase [Lactobacillus leichnannii]
55
38
1284


148
5
3430
4119
gi|290572
peripheral membrane protein U [Escherichia coli]
55
29
690


149
6
4171
4650
gi|895769
trensposase [Xanthobacter autotrophicus]
55
37
480


149
14
12564
11650
gnl|PID|d101329
YqjG [Bacillus subtilis]
55
32
915


156
3
1113
5501
gi|2314496
(AE000634) conserved hypothetical integral membrane protein
55
34
564







[Helicobacter pylon]


159
10
6625
5897
gi|290533
similar to E. coli ORF adjacent to suc operon;
55
29
729







similar to gntR class of regulatory proteins [Escherichia coli]


164
3
1784
2332
gnl|PID|e255118
hypothetical protein [Bacillus subtilis]
55
37
549


164
5
2772
3521
gi|40348
put. resolvase Tnp I (AA 1 - 284) [Bacillus thuringiensis]
55
35
750


164
11
7428
7216
gnl|PID|e248407
unknown [Mycobacterium tuberculosis]
55
38
213


167
5
3860
3345
gi|535052
involved in protein secretion [Bacillus subtilis]
55
28
516


186
5
2880
2563
gi|606080
ORF_o290; Geneplot suggests frameshift linking to o267,
55
35
318







not found [Escherichia coli]


189
8
4311
5396
gnl|PID|e183450
hypothetical EcsB protein [Bacillus subtilis]
55
32
1086


192
5
3270
3079
gi|1196504
vitellogenin convertase [Aedes aegypt1]
55
38
192


195
2
2454
1384
gi|1574693
transferase, peptidoglycan synthesis (murG)
55
33
1071







[Haemophilus influenzae]


198
4
3013
2471
gnl|PID|e313074
hypothetical protein [Bacillus subtilis]
55
29
543


214
1
373
744
gnl|PID|d101741
transposase [Synechocystis sp.]
55
33
372


219
2
1115
456
gi|288301
ORF2 gene product [Bacillus megaterium]
55
30
660


263
7
3742
3443
gi|18137
cgcr-4 product [Chlamydomones reinhardtii]
55
48
300


265
1
2
829
gnl|PID|d100974
unknown [Bacillus subtilis]
55
40
828


286
1
650
249
gi|396844
ORF (18 kDa) [Vibrin cholerae]
55
31
402


297
2
1229
1696
gi|150848
prtC [Porphyromonas gingivalis]
55
39
468


309
2
218
982
gi|1574491
hypothetical [Haemophilus influenzae]
55
35
765


328
2
646
224
gi|571500
prohibitin [Saccharomyces cerevisiae]
55
27
423


330
1
1340
474
gi|396397
soxS [Escherichia coli]
55
29
867


364
3
2538
1546
gi|393394
Tb-291 membrane associated protein [Trypanosoma
55
36
993









brucei
subgroup]



368
3
941
105
gi|1606715
antigen precursor [Plasmodium falciparum]
55
40
837


3
5
4604
3624
gi|2293176
(AF008220) signal transduction protein kinase
54
26
961







[Bacillus subtilis]


9
11
7746
7246
gi|1146245
putative [Bacillus subtilis]
54
38
501


38
24
16213
17937
gi|1480429
putative transcriptional regulator [Bacillus
54
27
1725







stearothermophilus]


40
8
5076
4862
gi|39989
methionyl-tRNA synthetase [Bacillus stearothermophilus]
54
35
195


43
4
3980
2367 gnl|PID|e148611
ABC transporter [Lactobacillus helveticus]
54
25
1614


52
10
10844
12103
gi|1762962
EmmA [Staphylococcus simulans]
54
29
1260


57
1
3
512
gi|558177
endo-1,4-beta-xylanase [Cellulomones fimi]
54
36
510


58
3
4749
4246
gnl|PID|d101237
hypothetical [Bacillus subtilis]
54
29
504


71
7
10664
1703
gi|510255
orf3 [Escherichia coli]
54
31
1020


71
20
27546
27737
gi|202543
serotonin receptor [Rattus norvegicus]
54
31
192


72
2
844
1096
gi|148613
srnB gene product [Plasmid F]
54
37
2551


72
10
7438
6695
gi|1196496
recombinase [Morexella bovis]
54
38
744


74
10
14043
13465
gi|1200342
ORF 3 gene product [Bradyrhizobium japonicum]
54
32
579


74
12
16483
15995
gi|2317798
maturase-related protein [Pseudomonas alcaligenes]
54
30
489


86
3
2877
2155
gi|46988
orf9.6 possibly encodes the O unit polymerase
54
34
723







[Salmonella enterica]


89
5
4433
3921
gi|147211
phnO protein [Escherichia coli]
54
41
513


90
1
3
464
gi|2317798
maturase-releted protein [Pseudomonas alcaligenes]
54
30
462


96
10
8058
8510
gnl|PID|d102015
(AB001488) SIMILAR TO SALMONELLA TYPHIMURIUM
54
32
453







SLYY GENE REQUIRED FOR SURVIVAL IN







MACROPHAGE. [Bacillus subtilia]


97
6
4662
3604
gi|1591394
transketolase′′ [Methanococcus jannaschii]
54
30
1059


106
11
10406
12010
gi|606286
ORF_o637 [Escherichia coli]
54
32
1605


147
8
8663
7404
gnl|PID|d101615
ORF_ID:o319#7; similar to [SwissProt Accession
54
35
1260







Number P37340][Escherichia coli]


171
4
2477
3223
gi|1439528
EIIC-man [Lactobacillus curvetus]
54
36
747


174
2
2068
1787
gnl|PID|d100518
motor protein [Homo sapiens]
54
35
282


188
1
526
1188
gnl|PID|e250352
unknown [Mycobacterium tuberculosis]
54
31
663


198
5
3582
2884
gnl|PID|e313074
hypothetical protein [Bacillus subtilis]
54
33
699


207
1
1
1641
gnl|PID|d101813
hypothetical protein [Synechocystis sp.]
54
24
1641


210
1
2
6551
gi|2293206
(AF008220) YtmP [Bacillus subtilis]
54
29
654


225
2
986
2357
gnl|PID|e330194
R11H6.1 [Caenorhabditis elegans]
54
39
1392


241
1
1681
347
gnl|PID|d101813
hypothetical protein [Synechocystis sp.]
54
26
1335


263
2
907
1395
gnl|PID|d101886
transposase [Synechocystis sp.]
54
30
489


263
6
3450
2977
gi|160671
antigen precursor [Plasmodium falciparum]
54
47
474


277
3
2517
1363
gi|1196926
unknown protein [Streptococcus mutans]
54
30
1155


307
1
828
4
gi|2293198
(AF008220) YtgP [Bacillus subtilis]
54
28
825


325
1
19
7681
gi|2182507
(AE000083) Y41H [Rhizobium sp. NGR234]
54
37
750


332
2
898
5901
gi|1591815
ADP-ribosylglycohydrolase (draG) [Methanococcus jannaschii]
54
32
309


385
4
240
479
gi|530878
amino acid feature: N-glycosylation sites, aa 41 . . . 43, 46 . . .
54
49
240







48, 51 . . . 53, 72 . . . 74, 107 . . . 109, 128 . . . 130, 132 . . .







134, 158 . . . 160, 163 . . . 165; amino acid feature:







Rod protein domain, aa 169 . . . 340; amino acid feature:







globular protein domain


7
25
19702
19493
gnl|PID|e255111
hypothetical protein [Bacillus subtilis]
53
32
210


23
3
2497
2033
gnl|PID|d102015
(AB001488) SIMILAR TO SALMONELLA TYPHIMURIUM
53
25
465







SLYY GENE REQUIRED FOR SURVIVAL IN







MACROPHAGE. [Bacillus subtilis]


29
11
9042
10121
gi|143331
alkaline phosphatase regulatory protein
53
31
1080







[Bacillus subtilis]


33
3
1479
1009
pir|S10655|S106
hypothetical protein X -
53
33
471









Pyrococcus woesei
(fragment)



36
6
4583
5134
gnl|PID|e316029
unknown [Mycobacterium tuberculosis]
53
30
552


38
14
8521
8898
gi|580904
homologous to E.coli rnpA [Bacillus subtilis]
53
30
378


52
7
7007
8686
gi|1377831
unknown [Bacillus subtilis]
53
29
1680


54
17
17555
19564
gi|666069
orf2 gene product [Lactobacillus leichmannii]
53
36
2010


56
1
1
681
gi|1592266
restriction modification system S subunit
53
32
681







[Methanococcus jannaschii]


57
10
9431
8487
gi|1788543
(AE000310) f351; Residues 1-121 are 100 pct identical to
53
31
945







YOJL_ECOLI SW: P33944 (122 aa) and aa 152-351 are







100 pct identical to YOJK_ECOLI SW: P33943







[Escherichia coli]


61
1
429
4
gnl|PID|e236467
B0024.12 [Caenorhabditis elegans]
53
33
426


71
1
5772
4
gi|393394
Tb-291 membrane associated protein [Trypanosoma
53
33
5769









brucei
subgroup]



72
3
894
2840
gi|2293178
(AF008220) YtsD [Bacillus subtilis]
53
27
1947


73
14
9793
9212
gi|1778556
putative cobalamin synthesis protein [Escherichia coli]
53
32
582


88
7
5217
4342
gi|2098719
putative fimbrial-associated protein [Actinomyces naeslundii]
53
38
876


93
5
2395
1688
gi|563366
gluconate oxidoreductase [Gluconobacter oxydans]
53
33
708


96
9
6632
7762
gi|517204
ORF1, putative 42 kDa protein [Streptococcus pyogenes]
53
42
1131


108
8
7629
8600
gi|149581
maturation protein [Lactobacillus paracesmi]
53
32
972


128
9
6412
6972
gnl|PID|e317237
unknown [Mycobacterium tuberculosis]
53
36
561


128
12
8429
9253
gi|311070
pentraxin fusion protein [Xenopus laevis]
53
31
825


148
1
3
850
pir|A61607|A616
probable hemolysin precursor - Streptococcus agalactiae
53
36
948







(strain 74-360)


163
2
2162
3022
gi|1755150
nocturnin [Xenopus laevis]
53
30
861


171
3
2304
2624
gi|1732200
PTS permease for mannose subunit IIPMan [Vibrio furnissii]
53
32
321


182
5
3785
3051
gnl|PID|d100572
unknown [Bacillus subtilis]
53
35
735


209
3
2948
1935
gi|1778505
ferric enterobactin transport protein [Escherichia coli]
53
28
1014


218
5
3884
2406
gi|40162
murE gene product [Bacillus subtilis]
53
34
1479


250
3
473
790
gnl|PID|e334776
YlbH protein [Bacillus subtilis]
53
30
318


275
1
1
1611
gnl|PID|d101314
YqeW [Bacillus subtilis]
53
35
1611


332
1
544
2
gi|409286
bmrU [Bacillus subtilis]
53
31
543


2
2
2543
3445
gnl|PID|e233879
hypothetical protein [Bacillus subtilis]
52
39
903


3
22
22402
23376
gi|389691
lacF gene product [Agrobacterium radiobacter]
52
36
975


5
3
8094
2356
gnl|PID|e324915
IgA1 protease [Streptococcus sanguis]
52
32
5739


22
26
19961
20212
gi|152901
ORF 3 [Spirochaeta aurantia]
52
35
252


22
31
23140
24666
gi|289262
comE ORF3 [Bacillus subtilis]
52
32
1527


27
6
5397
4801
gi|39573
P20 (AA 1-178) [Bacillus licheniformis]
52
35
597


35
10
8604
7357
gi|508241
putative O-antigen transporter [Escherichia coli]
52
27
1248


45
4
4801
3662
gnl|PID|d102243
(AB005554) homologs are found in E. coli and H. influenzae;
52
36
1140







see SWISSS_PROT ACC#: P42100 [Bacillus subtilis]


48
18
14385
13726
gnl|PID|e205174
orf2 [Lactobacillus helveticus]
52
25
660


49
4
5321
5755
gi|2317740
(AF013987) nitrogen regulatory IIA protein [Vibrio cholerae]
52
19
435


54
4
2773
4668
gi|1500472


M. jannaschii
predicted coding region MJ1577

52
36
1896







[Methanococcus janneachii]


54
6
5250
4969
gi|2182453
(AE000079) Y4iO [Rhizobium sp. NGR234]
52
40
282


66
6
8400
6955
gi|43140
TrkG protein [Escherichia coli]
52
30
1446


71
26
30659
31312
gnl|PID|e314893
unknown [Mycobacterium tuberculosis]
52
23
654


75
2
1673
1035
gnl|PID|d102271
(A8001683) FarA [Streptomyces sp.]
52
27
639


81
8
1439
2893
gnl|PID|e311458
rhamnulose kinase [Bacillus subtilis]
52
32
1455


81
8
4987
5781
gi|147403
mannose permease subunit II-P-Man [Escherichia coli]
52
37
795


83
21
20687
21853
gi|143365
phosphoribosyl aminoimidazole carboxylase II
52
37
1167







(PUR-K; ttg start codon) [Bacillus subtilis]


86
6
5785
4592
gi|1276879
EpsF [Streptococcus thermophilus]
52
26
1194


86
20
19390
17861
gi|454844
ORF 3 [Schistosoma mansoni]
52
26
1530


96
13
10540
9659
gi|288299
ORF1 gene product [Bacillus megeterium]
52
33
882


111
1
2
2026
gi|148309
cytolysin B transport protein [Enterococcus faecalis]
52
27
2025


112
2
1457
2167
gi|471234
orf1 [Haemophilus influenzae]
52
33
711


118
3
2931
2365
bbs|151233
Mip = 24 kda macrophage infectivity potentiator protein
52
33
567







[Legionella pneumophila, Philadelphia-1, Peptide, 184 aa]







[Legionella pneumophila]


122
9
5646
5951
gi|8214
myosin heavy chain [Drosophila melanogaster]
52
36
306


122
11
8159
6374
gi|434025
dihydrolipoamide acetyltransferase [Pelobacter carbinolicus]
52
52
216


134
6
4880
6313
gi|153733
protein trans-acting positive regulator [Streptococcus pyogenes]
52
43
1434


135
3
1238
2716
gnl|PID|e245024
unknown [Mycobacterium tuberculosis]
52
35
1479


141
3
1681
2319
gnl|PID|d100573
unknown [Bacillus subtilis]
52
32
639


161
4
2562
5024
gi|1146243
22.4% identity with Escherichia coli DNA-damage inducible
52
36
2463







protein . . . ; putative [Bacillus subtilis]


173
2
968
183
gi|1215693
putative orf; GT9_orf434 [Mycoplasma pneumoniae]
52
30
786


198
6
4400
3567
gnl|PID|e313010
hypothetical protein [Bacillus subtilis]
52
26
834


210
12
8844
9107
gi|497647
DNA gyrase subunit B [Mycoplasma genitalium]
52
38
264


214
10
5264
5431
gi|550697
envelope protein [Human immunodeficiency virus type 1]
52
36
168


225
1
15
884
gi|1552773
hypothetical [Escherichia coli]
52
34
870


230
1
38
362
gnl|PID|d100582
unknown [Bacillus subtilis]
52
28
324


287
1
871
2
gnl|PID|e335028
protease/peptidase [Mycobacterium leprae]
52
29
870


363
2
1305
4
gi|393394
Tb-291 membrane associated protein [Trypanosoma brucei
52
32
1302







subgroup]


23
2
2048
1173
gnl|PID|e254943
unknown [Mycobacterium tuberculosis]
51
30
876


29
3
742
1521
gi|929900
5′-methylthioadenosine phosphorylase [Sulfolobus solfataricus]
51
31
780


45
1
410
1597
gi|1877429
integrase [Streptococcus pyogenes phage T12]
51
32
1188


48
26
19227
18946
gi|2314455
(AE000633) transcriptional regulator (tenA)
51
33
282







[Helicobacter pylori]


73
5
4276
4016
gi|474177
alpha-D-1,4-glucosidase [Staphylococcus xylosus]
51
31
261


81
11
8935
12057
gi|311070
pentraxin fusion protein [Xenopus laevis]
51
31
3123


83
5
1195
1986
gnl|PID|d101316
YqfI [Bacillus subtilis]
51
33
792


98
10
7531
8538
gi|41500
ORF 3 (AA 1-352); 38 kD (put. ftsX) [Escherichia coli]
51
28
1008


113
6
3908
5173
gi|466882
pps1; B1496_C2_189 [Mycobacterium leprae]
51
27
1266


124
1
326
57
gi|2191168
(AF007270) contains similarity to myosin heavy chain
51
32
270







[Arabidopsis thaliana]


129
10
7286
6816
gi|1046241
orf14 [Bacteriophage HP1]
51
30
471


143
3
4963
3983
gi|1354935
probable copper-transporting atpase [Escherichia coli]
51
26
981


148
15
1359
10226
gi|2293256
(AF008220) putative hippurate hydrolase [Bacillus subtilis]
51
38
1134


149
8
8003
7313
gi|1633572


Herpesvirus saimiri
ORF73 homolog [Kaposi's sarcoma-

51
21
1311







associated herpes-like virus]


151
9
12092
11550
gnl|PID|e281580
hypothetical 40.7 kd protein [Bacillus subtilis]
51
34
543


159
6
2555
3208
gi|146944
CMP-N-acetylneuraminic acid synthetase [Escherichia coli]
F
51
36
654


174
1
1797
4
gi|1773166
probable copper-transporting atpase [Eschenichia coli]
51
28
1794


265
4
2231
1773
gnl|PID|e256400
anti-P.falciparum antigenic polypeptide [Saimiri sciureus]
51
18
459


277
2
643
1311
pir|532915|S329
pilD protein - Neisseria gonorrhoeae
51
33
669


350
1
890
3
gi290509
o307 [Escherichia coli]
51
30
888


363
4
1228
4485
gi|1707247
partial CDS [Caenorhabditis elegans]
51
23
3258


367
1
1701
4
gi|393394
Tb-291 membrane associated protein [Trypanosoma brucei
51
32
1698







subgroup]


15
5
5174
4497
gnl|PID|e58151
F3 [Bacillus subtilis]
50
38
678


16
4
2220
2582
gnl|PID|e325010
hypothetical protein [Bacillus subtilis]
50
29
363


19
5
2591
4159
gi|1552733
similar to voltage-gated chloride channel protein
50
30
1569







[Escherichia coli]


25
4
2701
1997
gi|887849
ORF_f219 [Escherichia coli]
50
27
705


35
1
211
417
gnl|PID|e236697
unknown [Saccharomyces cerevisiae]
50
33
207


39
4
3416
5152
gnl|PID|d100974
unknown [Bacillus subtilis]
50
27
1737


51
7
4000
5181
gi|1592027
carbamoyl-phosphate synthase, pyrimidine-specific,
50
27
1182







large subunit [Methanococcus jannaschii]


51
9
7179
8303
gi|1591847
type I restriction-modification enzyme, S subunit
50
28
1125







[Methanococcus jannaschii]


52
8
8740
9534
gi|144297
acetyl esterase (XynC) [Caldocellum saccharolyticum]
50
34
795


52
16
18591
15770
gi|2108229
basic surface protein [Lactobacillus fermentum]
50
34
822


57
7
6031
8336
gi|2275264
60S ribosomal protein L7B [Schizosaccharomyces pombe]
50
40
306


71
23
29348
28383
gnl|PID|d101328
YqjA [Bacillus subtilis]
50
30
986


86
12
11155
10769
gnl|PID|e324964
hypothetical protein [Bacillus subtilis]
50
24
387


93
2
1205
330
gi|1066016
similar to Escherichia coli pyruvate, water dikinase, Swiss-Prot
50
24
876







Accession Number P23538 [Pyrococcus furiosus]


96
5
1673
2959
gnl|PID|e322433
gamma-glutamylcysteine synthetase [Brassica juncea]
50
29
1287


98
2
218
1171
gi|151110
leucine-, isoleucine-, and valine-binding protein
50
30
954







[Pseudomonas aeruginosa]


103
4
3303
2785
gi|154330
O-antigen ligase [Salmonella typhimurium]
50
31
519


115
5
6480
5980
gi|895747
putative cel operon regulator [Bacillus subtilis]
50
26
501


129
11
7559
7305
gi|121647
skeletal muscle ryanodine receptor [Homo sapiens]
50
32
255


129
13
8192
7965
gi|152271
319-kDA protein [Rhizobium meliloti]
50
30
228


151
5
7634
8819
gi|40348
put. resolvase Tnp I (AA 1 - 284) [Bacillus thuringiensis]
50
35
816


153
1
1
597
gnl|PID|d102015
(AB001488) SIMILAR TO NITROREDUCTASE.
50
29
597







[Bacillus subtilis]


155
5
5986
5432
gi|1276880
EpsG [Streptococcus thermophilus]
50
28
555


160
9
7390
6323
gi|1786983
(AE000179) o331; 92 pct identical to the 333 aa hypotheticel
50
30
1068







protein YBHE_ECOLI SW: P52697; 26 pct identical (7 gaps) to







167 residues of the 373 aa protein MLE_TRICU SW: P46057;







SW: P52697 [Escherichia coli]


163
6
7396
8091
gnl|PID|d101313
YqeN [Bacillus subtilis]
50
22
696


167
6
5232
3940
gi|413926
ipa-2r gene product [Bacillus subtilis]
50
27
1293


169
2
607
130
gnl|PID|e304540
endolysin [Bacteriophage Bastille]
50
35
678


171
5
3168
4025
gi|606080
ORF_o290; Geneplot suggests frameshift linking to o267,
50
27
858







not found [Escherichia coli]


210
11
8151
8414
gi|330038
HRV 2 polyprotein [Human rhinovirus]
50
25
264


364
1
1538
135
gi|393396
Tb-292 membrane associated protein [Trypenosoma brucei
50 31
1404







subgroup]


10
7
5911
5090
gi|144859
ORF B [Clostridium perfringens]
49
24
8221


26
5
10754
9768
gi|142440
ATP-dependent nuclease [Bacillus subtilis]
49
31
987


66
7
9777
8398
gi|414170
trkA gene product [Methanosarcina mazeii]
49
26
1380


77
6
5364
4648
gnl|PID|e285322
RecX protein [Mycobacterium smegmatis]
49
28
717


82
13
12689
13249
gnl|PID|e255091
hypothetical protein [Bacillus subtilis]
49
20
561


93
9
4866
4531
gi|40067
X gene product [Bacillus sphaericus]
49
26
336


112
5
4019
4948
gi|1574380
lic-1 operon protein (licB) [Haemophilus influenzae]
49
27
930


129
7
6058
4949
gnl|PID|e267587
Unknown [Bacillus subtilis]
49
35
1110


135
5
3875
4436
gi|39573
P20 (AA 1-178) [Bacillus licheniformis]
49
25
564


154
2
1423
1953
gnl|PID|d101102
regulatory components of sensory transduction system
49
29
531







[Synechocystis sp.]


156
5
2878
1637
gnl|PID|d101732
hypothetical protein [Synechocystis sp.]
49
25
1242


173
5
3500
2940
gi|490324
ORF X gene product (unidentified)
49
30 5611


182
1
1057
2
gi|331002
first methionine codon in the ECLF1 ORF
49
25
1056







[Saimirline herpesvirus 2]


192
6
5352
3667
gi|2394472
(AE024499) contains similarity to homeobox domains
49
23
1686







[Caenorhabditis elegans]


253
4
1129
1350
gi|531116
SIR4 protein [Saccharomyces cerevisise]
49
23
222


277
1
600
136
gi|396844
ORF (18 kDa) [Vibrio cholerae]
49
32
465


327
3
1435
887
gi|733524
Phosphatidylinositol-4,5-diphosphate 3-kinase
49
24
549







[Dictyostelium discoideum]


365
3
1436
132
gi|393394
Tb-291 membrane associated protein [Trypanosoma brucei
49
31
1305







subgroup]


33
7
4461
3277
gi|145644
codes for a protein of unknown function [Escherichia coli]
48
26
1185


40
2
652
1776
gnl|PID|e290649
ornithine decarboxylase [Nicotiana tabacum]
48
29
1125


67
4
1377
2384
gi|1772652
2-keto-3-deoxygluconate kinase [Haloferax alicantei]
48
30
1008


74
2
4269
3871
gi|2182678
(AEC00101) Y4vJ [Rhizobium sp. NOR234]
48
27
399


81
2
1326
541
gi|153672
lactose repressor [Streptococcus mutans]
48
33
786


81
4
2981
3646
gi|146042
fuculose-1-phosphate aldolase (fucA) [Escherichia coli]
48
30
666


97
1
602
51
gi|153794
rgg [Streptococcus gordonii]
48
29
552


110
1
1
3132
gi|1381114
prtB gene product [Lactobacillus delbrueckli]
48
23
3132


131
5
2914
2147
gnl|PID|e183811
Acyl-ACP thioesterase [Brassica napus]
48
27
768


133
4
3494
2628
gnl|PID|e261988
putative ORF [Bacillus subtilis]
48
27
867


139
6
4231
4599
gi|1049388
ZK470.1 gene product [Caenorhabditis elegans]
48
23
369


139
8
5036
5665
gi|1022725
unknown [Staphylococcus haemolyticus]
48
29
6301


140
12
11936
11007
gnl|PID|d102049


H. influenzae
, ribosomal protein alanine acetyltransferase;

48
27
930







P44305 (189) [Bacillus subtilis]


146
9
5670
4654
gi|1591731
melvalonate kinese [Methanococcus jannaschii]
48
24
1017


161
3
1280
2374
gnl|PID|d101578
Collagenase precursor (ED 3.4.-.-). [Escherichia coli]
48
24
1095


172
11
10581
11048
gn|PID|d101132
hypothetical protein [Synechocystis sp.]
48
27
468


182
4
2930
2586
gi|40067
X gene product [Bacillus sphaericus]
48
37
345


210
15
10786
11196
sp|P13940|LE29
LATE EMBRYOGENESIS ABUNDANT PROTEIN D-29
48
30
411







(LEA D-29).


214
12
6231
6482
gi|40389
non-toxic components [Clostridium botulinum]
48
26
252


221
1
704
3
gi|1573364


H. influenzae
predicted coding region HI0392

48
27
702







[Haemophilus influenzae]


227
2
647
3928
gi|1673693
(AE000005) Mycoplasma pneumoniae, C09_orf718 Protein
48
30
3282







[Mycoplasma pneumoniae]


253
2
480
758
gnl|PID|e236697
unknown [Saccharomyces cerevisiae]
48
31
279


363
3
1874
1122
gi|18137
cgcr-4 product [Chlamydomonas reinhardtii]
48
40
753


389
1
505
2
gi|18137
cgcr-4 product [Chlamydomonas reinhardtii]
48
38
504


3
21
20879
22258
gnl|PID|e264778
putative maltose-binding pootein [Streptomyces coelicolor]
47
33
1380


6
4
4089
4658
gi|39573
P20 (AA 1-178) [Bacillus licheniformis]
47
23
570


15
3
3736
1760
gnl|PID|d100572
unknown [Bacillus subtilis]
47
25
1977


35
15
4516
13263
gi|1773351
Cap5L [Staphylococcus aureus]
47
20
1254


51
6
3547
4002
pir|A37024|A370
32K antigen precursor - Mycohacterium tuberculosis]
47
38
456


55
8
10154
92731
gi|39848
U3 [Bacillus subtilis]
47
26
882


92
4
1753
3276
gnl|PID|e280611
PCPC [Streptococcus pneumoniae]
47
35
1524


127
9
5589
5388
gi|1786458
(A2000134) f120; This 120 aa orf is 76 pct identical (0 gaps)
47
32
204







to 42 residues of an approx. 48 aa protein Y127_HAEIN SW:







P43949 [Escherichia coli]


130
2
1232
1759
gnl|PID|e266555
unknown [Mycobacterium tuberculosis]
47
23
528


140
4
4951
3542
gnl|PID|d100964
homologue of hypothetical protein in a rapamycin synthesis
47
24
1410







gene cluster of Streptomyces hygroscopicus [Bacillus subtilis]


151
4
6814
6200
gi|1522674


H. jannaschii
predicted coding region MJECL41

47
27
615







[Methanococcus jannaschii]


157
3
803
1174
gnl|PID|d101320
YqgZ [Bacillus subtilis]
47
25
372


178
5
3267
2155
gi|2367190
(AE000390) o334; sequence change joins ORFs ygjR & ygjS
47
30
1113







from earlier version (YGJR_ECOLI SW: P42599 and







YGJS_ECOLI SW: P42600) [Escherichia coli]


273
1
2
1549
gnl|PID|e254973
autolysin sensor kinase [Bacillus subtilis]
47
32
1548


300
2
880
644
gi|1835755
zinc finger protein Png-1 [Mus musculus]
47
22
237


54
14
14182
12638
pir|S43609|S436
rofA protein - Streptococcus pyogenes
46
24
1545


88
1
2
1018
gnl|PID|e22389
xylose repressor [Anaerocellum thermophilum]
46
27
1017


96
7
4553
5860
gnl|PID|d101652
ORF_ID:o347#5; similar to [SwissProt Accession Number P45272]
46
23
1308







[Escherichia coli]


112
1
1127
3
gi|2209215
(AP004325) putative oligosaccharide repeat unit transporter
46
24
1125







[Streptococcus pneumoniae]


122
13
7308
7982
gi|1054776
hr44 gene product [Homo sapiens]
46
34
675


127
14
9198
8125
gi|1469286
afuA gene product [Actinobacillus pleuropneumoniae]
46
28
1074


132
4
7093
6197
gi|153794
rgg [Streptococcus gordonii]
46
26
897


140
8
8220
7723
gi|1235795
pullulanase [Thermoanaerobacterium thermosulfurigenes]
46
21
498


140
9
9205
8315
gi|407878
leucine rich protein [Streptococcus equisimilis]
46
27
891


162
1
1
1251
gi|1143209
ORF7; Method: conceptual translation supplied by author
46
25
1125







[Shigella sonnei]


199
1
1
5851
gi|1947171
(AP000299) No definition line found [Caenorhabditis elegans]
46
28
585


223
3
1971
1477
sp|P02562|MYSS
MYOSIN HEAVY CHAIN, SKELETAL MUSCLE
46
27
495







(FRAGMENTS).


232
2
760
1608
gi|1016112
ycf38 gene product [Cyanophora paradoxa]
46
28
849


292
1
687
220
gi|1673744
(AE000011) Mycoplasma pneumoniae, cytidine deaminase;
46
29
468







similar to GenBank Accession Number C53312,







from M. pirum [Mycoplasms pneumoniae]


30
8
5843
6472
gi|1788049
(AE000270) o235; This 235 aa orf is 29 pct identical (10 gaps)
45
24
630







to 198 residues of an approx. 216 as protein YTXB_BACSU







SW: P06568 [Escherichia coli]


48
6
3461
3868
gi|722339
unknown [Acetobacter xylinum]
45
29
408


60
1
307
2
gi|1699079
coded for by C. elegans cDNA yk41h4.3; coded for by
45
36
306









C. elegans cDNA yk148g10.5; coded for by


C. elegans









cDNA yk152g5.5; coded for by C. elegans cDNA yk59a10.5;







coded for by C. elegans cDNA yk41h4.5; coded for







by C. elegans cDNA cm20g10; coded


72
16
14371
14874
gi|1321900
NADH dehydrogenase (ubiguinone) [Artemis franciscans]
45
25
504


99
7
9158
7941
gi|152192
mutation causes a succinoglucan-minus phenotype; ExoQ is
45
28
1218







atransmembrane protein; third gene of the exoYFQ operon;;







putative [Rhizobium meliloti]


127
12
7046
6606
bbs|153689
HitB = iron utilization protein [Haemophilus influenzae,
45
24
441







type b, DL42, NTHI TN106, Peptide, 506 aa]







[Haemophilus influenzae]


137
5
1561
2619
gi|472921
v-type Na-ATPase [Enterococcus hirae]
45
33
1059


209
1
774
364
gi|304141
restriction endonuclease beta subunit [Bacillus coagulans]
45
28
411


314
1
604
2
gi|1480457
latex allergen [Havea brasiliensis]
45
31
603


20
18
19782
20288
gi|433942
ORF [Lactococcus lactis]
44
26
507


87
8
7030
6452
gi|537207
ORF_f277 [Escherichia coli]
44
26
579


166
5
4909
4037
gnl|PID|e308082
membrane transport protein [Bacillus subtilis]
44
25
873


247
1
818
75
gnl|PID|d100718
ORF1 [Bacillus sp.]
44
20
744


32
3
1885
3876
gi|2351768
PspA [Streptococcus pneumoniae]
43
24
1992


36
17
15467
18256
gi|1045739


M. genitalium
predicted coding region MG064

43
26
2790







[Mycoplasma genitalium]


54
15
14656
17343
gi|520541
penicillin-binding proteins 1A end 1B [Bacillus subtilis]
43
27
2688


67
2
696
1352
gi|536934
yjcA gene product [Escherichia coli]
43
29
657


139
2
2416
338
gi|396400
similar to eukaryotic Na+/H+exchangers [Escherichia coli]
43
24
2079


298
1
3
8091
gi|413972
ipa-48r gene product [Bacillus subtilis]
43
24
807


387
1
47
427
gi|2315652
(AF016669) No definition line found [Caenorhabditis elegans]
43
30
381


185
4
4221
3127
gi|2182399
(AE000073) Y4fP [Rhizobium sp. NGR234]
41
25
1095


340
1
582
70
gnl|PID|e218681
CDP-diacylglycerol synthetase [Arabidopsis thaliana]
41
20
513


363
6
4205
1914
gi|1256742
R27-2 protein [Trypanosoma cruzi]
41
27
2292


368
2
2
9431
gi|21783
LMW glutenin (AA 1-356) (8 Triticum aestivum]
41
34
942


155
3
4489
2861
gi|42023
member of ATP-dependent transport family, very similar to
40
18
1629







mdr proteins and hemolysin B, export protein [Escherichia coli]


365
2
95
1438
gi|1633572
Herpesvirus saimiri ORF73 homolog [Kaposi's sarcoma-
40
21
1344







associated herpes-like virus)


1
3
2979
3860
gnl|PID|d101908
hypothetical protein [Synechocystis sp.]
39
26
882


1
5
3814
4647
gn|PID|d10196
hypothetical protein [Synechocystis sp.]
39
19
834


26
6
14035
10724
gi|142439
ATP-dependent nuclease [Bacillus subtilis]
38
20
3312


47
1
3
4916
gi|632549
NF-180 [Petromyzon marinus]
36
23
4914










[0231]

3





TABLE 3












S. pneumoniae
-



Putative coding regions of novel proteins not similar to known proteins












Contig
ORF
Start
Stop



ID
ID
(nt)
(nt)
















1
4
3428
3009



1
6
4611
4964



3
2
818
994



3
3
1182
1574



3
7
5382
6497



3
25
25046
25396



3
26
25625
26317



6
2
1519
1689



6
14
12875
12618



6
15
13215
12841



6
18
15977
15390



7
12
9955
9419



7
13
10161
9910



8
6
3915
4280



9
9
6024
5704



10
8
6909
6298



10
9
7136
6888



10
11
7968
7672



12
1
1140
4



12
3
1779
1456



14
2
1913
1434



16
1
1
243



16
5
5675
3087



17
1
324
34



17
3
1451
1050



17
9
4890
4465



20
14
14544
15893



21
3
3359
2589



21
5
4802
4482



22
21
17099
17362



22
25
19467
19982



22
33
25540
25764



22
35
26388
26218



22
36
26382
27572



23
7
6655
6032



23
8
7132
6653



24
1
36
518



25
5
3009
2641



27
4
4819
4223



27
5
4789
4956



28
5
3017
1797



28
8
4272
3850



28
10
5028
4597



28
11
5746
5072



29
7
5596
4919



29
8
5039
5518



29
9
5595
8207



30
9
6511
6263



31
6
2664
2344



32
5
5203
5538



33
8
5327
4668



34
10
8024
7740



34
12
9360
8641



34
13
9667
9377



34
18
13104
11902



35
11
9688
8588



35
12
11073
9670



36
2
334
1041



36
12
11120
10893



36
13
10993
11388



36
15
12172
14595



38
7
4269
4577



38
8
4480
5001



38
10
5517
5711



38
17
10732
11376



40
3
1728
3143



43
1
172
5



43
7
8884
8732



43
8
9568
9071



44
4
4831
6831



45
3
3204
3665



46
4
3875
3468



46
7
6074
7081



48
5
3196
3582



48
8
4579
4229



48
11
9323
8922



48
16
13042
12494



48
20
16342
15764



48
24
17971
18351



48
30
21979
21776



49
1
209
3



50
4
3307
2672



51
5
3239
3598



52
11
12146
12883



54
7
5588
5187



54
8
6013
5459



54
9
6004
6210



54
16
17685
17506



55
9
10515
10123



55
12
11947
12141



56
3
935
1387



56
4
1496
1939



57
3
1624
2130



57
4
2100
2501



58
6
7541
7335



59
1
2
430



59
4
2436
2736



59
5
2734
3063



59
8
4743
5549



59
9
5459
5929



60
6
5741
6451



61
3
2395
1772



61
5
3316
3176



64
1
2722
2



66
2
1180
3147



66
8
9082
9495



67
3
1343
1182



69
2
1165
980



70
5
4059
3922



70
6
4215
4057



70
9
5268
5504



71
15
20351
21901



71
16
21859
22338



71
19
26204
27556



72
9
8458
8081



73
4
3815
4216



73
6
4214
4582



73
7
4369
4773



73
10
7183
6428



73
15
9462
9668



76
1
524
195



76
2
867
535



76
11
8602
9210



80
6
7924
8109



81
1
244
2



81
10
6631
8931



83
4
1872
1150



83
17
16810
16460



84
3
4464
2929



86
2
2147
1092



86
4
3606
2875



86
19
16767
17114



87
5
5326
5000



87
7
6459
6001



87
9
7224
7006



87
18
17930
17670



87
19
18275
17928



88
2
1619
1840



88
4
2711
2878



88
9
6252
6016



89
3
2634
1621



89
9
7371
6868



90
2
899
2395



90
3
1143
952



91
3
2959
3141



91
4
3170
3691



91
6
4253
4573



93
1
391
2



93
6
2648
2379



93
8
4533
3712



96
1
3
182



96
2
904
632



96
3
1407
1147



96
4
1250
1420



97
9
7043
6753



99
15
18522
18692



99
17
19717
19541



100
2
4094
1980



103
1
48
299



103
6
4924
4373



104
5
6142
6735



105
7
6098
6517



106
1
1
363



106
10
9832
10212



108
1
2
268



111
3
3417
3788



111
4
3809
4606



115
10
10854
10438



116
3
2873
2121



118
2
2274
1357



122
4
2698
2333



122
10
5858
6199



122
12
6301
7416



124
2
346
690



128
4
2544
3368



129
1
689
102



129
2
1011
724



129
8
6454
6056



129
9
6540
6277



129
12
7809
7621



131
3
1433
756



131
10
5972
5673



134
11
11838
11209



135
2
625
1140



136
4
2913
3830



137
2
325
134



139
12
14027
14521



139
13
14840
14532



139
14
15363
14875



140
20
19822
20838



142
1
1
285



146
3
760
479



146
4
1149
778



146
7
3604
2885



146
13
8223
9401



146
14
9399
10676



146
15
10052
9750



147
7
7488
7276



147
9
8913
8647



148
7
5298
4765



149
1
2
1936



149
3
2557
2880



149
9
6258
6070



150
2
1355
579



150
3
2556
1909



153
3
2061
2642



154
3
1953
1741



155
2
2181
1411



156
8
4550
4311



157
1
37
294



159
2
631
780



159
4
1384
1722



159
7
3271
4017



161
2
1332
1018



165
3
5535
4945



166
6
5406
4972



167
9
6075
6395



169
5
2828
3205



170
7
6485
6243



170
8
6964
6362



170
9
7303
6362



170
11
8790
7906



171
9
7150
7476



172
5
2298
1948



173
4
2913
2677



175
2
659
835



175
3
893
1789



176
2
1487
546



176
3
2200
1466



177
9
4686
4925



177
10
4923
5177



177
11
5111
5347



177
13
7396
8703



178
6
3452
3724



181
5
1853
2473



182
2
2112
1102



182
3
2617
2006



183
2
2126
2320



185
5
4683
4219



185
6
4846
4634



187
4
2940
3557



188
4
3686
4363



188
5
4183
4821



188
6
5882
6493



189
5
3143
2844



189
9
5956
5564



191
1
618
4



191
11
10357
10001



192
3
2861
2268



192
4
3081
2878



192
7
6800
5331



193
3
997
839



194
4
2315
2127



195
5
6249
4543



195
6
6620
6231



196
2
1553
1849



197
1
1
861



198
9
6844
6644



200
5
5329
5769



200
6
5993
6595



204
5
3914
3276



205
2
447
1709



209
4
2038
2460



209
5
2458
2682



210
10
7370
8230



210
13
9029
10441



210
14
10439
10705



214
5
2581
2330



214
9
5065
5277



214
11
5996
5754



217
2
541
194



218
2
914
1432



218
3
1430
1972



218
6
3639
3821



219
1
458
39



220
1
869
600



223
4
2617
1964



227
1
1
510



234
4
1539
1312



234
6
2116
1838



235
1
52
312



235
2
310
687



238
1
660
64



246
1
1
270



248
1
3
362



248
2
443
1222



254
3
2789
792



258
2
1179
1616



260
3
1770
2123



263
1
653
177



263
4
2244
1900



263
5
3569
2973



266
1
1
342



266
2
177
1022



270
2
1124
1681



272
1
857
186



275
2
1684
2295



278
1
2
406



282
1
714
391



282
4
1463
1134



287
2
1119
826



288
1
540
4



289
1
684
4



291
5
1589
1858



293
2
2539
2925



294
1
21
608



296
2
494
700



296
3
670
843



302
1
261
530



309
3
559
350



310
2
249
1889



316
2
2087
1818



317
2
1048
584



318
2
313
777



319
3
477
133



327
2
912
607



331
1
1
549



333
1
2
535



333
2
465
82



333
3
127
342



341
1
1
705



345
2
895
701



346
2
750
199



349
1
1
198



350
2
81
413



355
1
44
973



358
2
636
448



360
2
948
628



364
2
1639
1265



378
1
345
1004



379
2
683
510



381
1
109
693



385
1
150
4



385
2
269
30











Claims
  • 1. Computer readable medium having recorded thereon the nucleotide sequence depicted in SEQ ID NOS:1-391, a representative fragment thereof or a nucleotide sequence at least 95% identical to a nucleotide sequence depicted in SEQ ID NOS:1-391.
  • 2. Computer readable medium having recorded thereon any one of the fragments of SEQ ID NOS:1-391 depicted in Tables 2 and 3 or a degenerate variant thereof.
  • 3. The computer readable medium of claim 1, wherein said medium is selected from the group consisting of a floppy disc, a hard disc, random access memory (RAM), read only memory (ROM), and CD-ROM.
  • 4. The computer readable medium of claim 3, wherein said medium is selected from the group consisting of a floppy disc, a hard disc, random access memory (RAM), read only memory (ROM), and CD-ROM.
  • 5. A computer-based system for identifying fragments of the Streptococcus pneumoniae genome of commercial importance comprising the following elements: a) a data storage means comprising the nucleotide sequence of SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95% identical to a nucleotide sequence of SEQ ID NOS:1-391; b) search means for comparing a target sequence to the nucleotide sequence of the data storage means of step (a) to identify homologous sequence(s), and c) retrieval means for obtaining said homologous sequence(s) of step (b).
  • 6. A method for identifying commercially important nucleic acid fragments of the Streptococcus pneumoniae genome comprising the step of comparing a database comprising the nucleotide sequences depicted in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95% identical to a nucleotide sequence of SEQ ID NOS:1-391 with a target sequence to obtain a nucleic acid molecule comprised of a complementary nucleotide sequence to said target sequence, wherein said target sequence is not randomly selected.
  • 7. A method for identifying an expression modulating fragment of Streptococcus pneumoniae genome comprising the step of comparing a database comprising the nucleotide sequences depicted in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95% identical to the nucleotide sequence of SEQ ID NOS:1-391 with a target sequence to obtain a nucleic acid molecule comprised of a complementary nucleotide sequence to said target sequence, wherein said target sequence comprises sequences known to regulate gene expression.
  • 8. An isolated protein-encoding nucleic acid fragment of the Streptococcus pneumoniae genome, wherein said fragment consists of the nucleotide sequence of any one of the fragments of SEQ ID NOS:1-391 depicted in Tables 2 and 3, or a, degenerate variant thereof.
  • 9. A vector comprising any one of the fragments of the Streptococcus pneumoniae genome SEQ ID NOS:1-391 depicted in Tables 2 and 3 or a degenerate variant thereof.
  • 10. An isolated fragment of the Streptococcus pneumoniae genome, wherein said fragment modulates the expression of an operably linked open reading frame, wherein said fragment consists of the nucleotide sequence from about 10 to 200 bases in length which is 5′ to any one of the open reading frames depicted in Tables 2 and 3 or a degenerate variant thereof.
  • 11. A vector comprising any one of the fragments of the Streptococcus pneumoniae genome of claim 8.
  • 12. An organism which has been altered to contain any one of the fragments of the Streptococcus pneumoniae genome of claim 8.
  • 13. An organism which has been altered to contain any one of the fragments of the Streptococcus pneumoniae genome of claim 10.
  • 14. A method for regulating the expression of a nucleic acid molecule comprising the step of covalently attaching to said nucleic acid molecule a nucleic acid molecule consisting of the nucleotide sequence from about 10 to 100 bases 5′ to any one of the fragments of the Streptococcus pneumoniae genome depicted in SEQ ID NOS:1-391 and Tables 2 and 3 or a degenerate variant thereof.
  • 15. An isolated nucleic acid molecule encoding a homolog of any of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and Tables 2 and 3, wherein said nucleic acid molecule is produced by a process comprising steps of: a) screening a genomic DNA library using as a probe a target sequence defined by any of SEQ ID NOS:1-391 and Tables 2 and 3, including fragments thereof; b) identifying members of said library which contain sequences that hybridize to said target sequence; and c) isolating the nucleic acid molecules from said members identified in step (b).
  • 16. An isolated DNA molecule encoding a homolog of any one of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and Tables 2 and 3, wherein said nucleic acid molecule is produced a process comprising steps of: a) isolating mRNA, DNA, or cDNA produced from an organism; b) amplifying nucleic acid molecules whose nucleotide sequence is homologous to amplification primers derived from said fragment of said Streptococcus pneumoniae genome to prime said amplification; c) isolating said amplified sequences produced in step (b).
  • 17. An isolated polypeptide encoded by any of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and depicted in Table 2 and 3 or by a degenerate variant of said fragments.
  • 18. An isolated polynucleotide molecule encoding any one of the polypeptides of claim 17.
  • 19. An antibody which selectively binds to any one of the polypeptides of claim 17.
  • 20. A method for producing a polypeptide in a host cell comprising the steps of: a) incubating a host containing a heterologous nucleic acid molecule whose nucleotide sequence consists of any one of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and depicted in Tables 2 and 3, under conditions where said heterologous nucleic acid molecule is expressed to produce said protein, and b) isolating said protein.
Provisional Applications (1)
Number Date Country
60029960 Oct 1996 US