Disclosed are nucleotide sequences encoding a novel polypeptide termed LSIRF. Also disclosed are methods of preparing the polypeptide and uses thereof.

BACKGROUND
 1. Field of the Invention
 This invention relates to novel polypeptides having DNA binding activity,
 and to nucleic acid molecules encoding the polypeptides. The polypeptides,
 previously referred to as "IRF-3" polypeptides, are now referred to as
 "LSIRF" polypeptides (lymphocyte specific interferon regulatory factor),
 and are new members of the class of polypeptides known as interferon
 regulatory factors.
 2. Description of Related Art
 Regulation of gene expression can occur at several different levels, but
 the activation of gene-specific transcription factors is considered the
 most fundamental to this process. One family of transcription factors, the
 interferon regulatory factors (IRFs), consists of four members: IRF-1,
 IRF-2, ISGF3.gamma., and ICSBP. All four IRFs are characterized by a
 strongly conserved, N-terminal DNA-binding domain containing a repeated
 tryptophan motif (Veals et al., (Mol. Cell. Biol., 12:3315-3324 [1992]).
 Interferon regulatory factors-1 (IRF-1) and -2 (IRF-2) were originally
 identified by studies of the transcriptional regulation of the human
 interferon-beta (IFN-.beta.) gene (Miyamoto et al., Cell, 54:903-913
 [1988]) and (Harada et al., Cell, 58:729-739 [1989]). cDNA expression
 studies have demonstrated that IRF-1 functions as a transcriptional
 activator of IFN and IFN-inducible genes, whereas IRF-2 represses the
 effect of IRF-1 (Fujita et al., Nature, 337:270-272 [1989]) and (Harada et
 al., Cell, 63:303-312 [1990]). Recent analyses have shown that IRF-1 can
 also act as a tumor suppressor gene and IRF-2 as a possible oncogene
 (Harada et al, Science, 259:971-974 [1993]). IRF-1 expression is induced
 by type-I (.alpha./.beta.) and type-II (.gamma.) IFNs (Miyamoto et al.,
 Cell, 54:903-913 [1988]; Kanno et al., Mol. Cell Biol., 13:3951-3963
 [1993]), whereas IRF-2 is both constitutively expressed and induced by
 type-I IFNs (Harada et al., Cell, 58:729-739 [1989]).
 Interferon-stimulated gene factor-3 gamma (ISGF3.gamma.) is an
 IFN-.gamma.-inducible protein which associates with ISGF3.alpha. subunits
 activated from a latent cytosolic form by type-I IFNs (Levy et al, EMBO
 J., 9:1105-1111 [1990]; Levy et al., New Biologist, 2:383-392 [1990]).
 Upon association, this complex has been shown to translocate to the
 nucleus and bind a specific DNA sequence found in the promoter region of
 IFN-inducible genes, known as the ISRE (IFN-stimulated response element;
 Veals et al., Mol. Cell. Biol., 12:3315-3324 [1992]). Recently,
 ISGF3.alpha. subunits of 91/84 kDa and 113 kDa have been cloned (Schindler
 et al, Proc. Natl. Acad. Sci. USA, 89:7836-7839 [1992]; Fu et al, Proc.
 Natl. Acad. Sci. USA, 89:7840-7843 [1992]) and designated as signal
 transducer and activator of transcription-1 (Stat-1) and -2 (Stat-2),
 respectively, which are targets of JAK kinase phosphorylation following
 type-I IFN/IFN-receptor engagement (Shuai et al, Science, 261:1744-1746
 [1993]; Darnell et al, Science, 261:1415-1421 [1994]).
 Interferon consensus sequence binding protein (ICSBP) is also an
 IFN-.gamma.-inducible protein, originally isolated as a protein that
 recognizes the ISRE motif (also called ICS) of the promoter of murine MHC
 class I, H-2L.sup.D gene (Driggers et al, Proc. Natl. Acad. Sci. USA,
 87:3743-3747 [1990]). However, unlike IRF-1, IRF-2, and ISGF3.gamma.,
 ICSBP exhibits a tissue-restricted pattern of expression, as it is induced
 exclusively in cells of macrophage and lymphoid lineages (Driggers et al,
 Proc. Natl. Acad. Sci. USA, 87:3743-3747 [1990]). Recent studies have
 suggested that ICSBP has a similar role to IRF-2 in antagonizing the
 effect of IRF-1 on the induction of IFN and IFN-inducible genes (Weisz et
 al., J. Biol. Chem., 267:25589-25596 [1992]; Nelson et al., Mol. Cell.
 Biol., 13:588-599 [1993]). The ISREs of interferon-inducible genes overlap
 IRF-E, the DNA sequences recognized by IRF-1 and -2 (Tanaka et al., Mol
 Cell. Biol. 13:4531-4538 [1993]). Very recently, ISGF3.gamma. was shown to
 bind the IRF-Es of the IFN-.beta. gene (Kawakami et al., FEBS Letters,
 358:225-229 [1995]).
 In view of the importance of IRFs in regulating the expression of the
 interferon genes and other genes, there is a need in the art to identify
 other IRFs, especially tissue specific IRFs.
 Accordingly, it is an object of this invention to identify novel members of
 the IRF gene family.
 Other objects will be readily apparent to one of ordinary skill in the art.
 SUMMARY OF THE INVENTION
 The present invention provides novel nucleic acid molecules encoding a
 lymphocyte specific interferon regulatory factor. The molecules, which
 were previously referred to as "IRF-3" molecules, are now referred to as
 "LSIRF" molecules, however this term may be used interchangeably with the
 term "LSIRF" molecules.
 In one aspect, the present invention provides an isolated nucleic acid
 molecule encoding a LSIRF polypeptide or fragment thereof, selected from
 the group consisting of:
 a) a nucleic acid molecule having a nucleotide sequence of SEQ. ID. NO: 1;
 b) a nucleic acid molecule having a nucleotide sequence of SEQ. ID. NO: 4;
 c) a nucleic acid molecule having a nucleotide sequence of SEQ. ID. NO: 24
 or the "Double Q" variant thereof;
 d) a nucleic acid molecule having a nucleotide sequence encoding the amino
 acid sequence of SEQ. ID. NO: 2;
 e) a nucleic acid molecule having a nucleotide sequence encoding the amino
 acid sequence of SEQ. ID. NO: 25 or the "Double Q" variant thereof; and
 f) a nucleic acid molecule having a nucleotide sequence which hybridizes
 with the nucleic acid molecule of (a), (b), (c), (d), (e), or with a
 fragment thereof.
 The invention further provides a polypeptide that is the product of the
 expression of these nucleic acid molecules in a host cell.
 Still further, the invention provides an antibody specifically binding the
 LSIRF polypeptide. Optionally, the antibody is a monoclonal antibody.
 In another aspect, the invention provides an isolated polypeptide or
 fragment thereof having the specific DNA binding activity of a LSIRF
 polypeptide.
 In another aspect, the present invention provides a vector comprising a DNA
 molecule encoding a LSIRF polypeptide.
 In still another aspect, the invention provides a host cell stably
 transformed or transfected with a vector comprising a DNA molecule
 encoding a LSIRF polypeptide.
 In yet another aspect, the invention provides an isolated LSIRF polypeptide
 or fragment thereof; the polypeptide may have the amino acid sequence of
 SEQ ID NO: 2.
 In a further aspect, the invention provides a LSIRF polypeptide that is the
 product of a prokaryotic or eukaryotic host cell expression of an
 exogenous LSIRF nucleic acid sequence.
 The invention further provides a method of producing a LSIRF polypeptide
 comprising culturing a prokaryotic or eukaryotic host cell under
 conditions that permit LSIRF expression.

DETAILED DESCRIPTION OF THE INVENTION
 The terms "IRF-3" and "LSIRF" are used interchangeably herein and refer to
 the same nucleic acid and amino acid sequences; both the "Single Q" and
 "Double Q" forms of LSIRF are included in this definition (see Example 5).
 As used herein, the term "biologically active" refers to a full length
 polypeptide or fragment thereof derived from any source, that binds ISRE
 (interferon stimulated response element) type DNA fragments such as murine
 MHCI ISRE, human ISG54, and/or ISRE mutants such as ISREm1 or ISREm4 (the
 sequences of which are set forth in Table 1). Biologically active
 polypeptides or fragments thereof also include those polypeptides or
 fragments that have immunological cross reactivity with an antibody
 (polyclonal or monoclonal) that is raised against, and reacts with, a full
 length LSIRF polypeptide such as the LSIRF polypeptides set forth in FIGS.
 2 and 25.
 As used herein, the term "stably transformed or transfected" refers to a
 nucleic acid molecule that has been inserted into a host cell and exists
 in the host cell, either as a part of the host cell genomic DNA or as an
 independent molecule (e.g., extra-chromosomally), and that is maintained
 and replicated in the parent host cell so that it is passed down through
 successive generations of the host cell.
 The term "synthetic DNA" refers to a nucleic acid molecule produced in
 whole or in part by chemical synthesis methods.
 The term "vector" refers to a nucleic acid molecule amplification,
 replication, and/or expression vehicle in the form of a plasmid or viral
 DNA system where the plasmid or viral DNA may be functional with
 bacterial, yeast, invertebrate, and/or mammalian host cells. The vector
 may remain independent of host cell genomic DNA or may integrate in whole
 or in part with the genomic DNA. The vector will contain all necessary
 elements so as to be functional in any host cell it is compatible with.
 Such elements are set forth below.
 One aspect of the present invention provides methods of preparing a LSIRF
 polypeptide. Typically, the polypeptide will be prepared by obtaining a
 nucleic acid molecule encoding the polypeptide, inserting this nucleic
 acid molecule into a suitable expression vector, inserting the vector into
 a compatible host cell, expressing the LSIRF polypeptide in the host cell,
 and purifying the LSIRF polypeptide.
 1. Preparation of DNA Encoding LSIRF Polypeptides
 A nucleic acid molecule encoding LSIRF can readily be obtained in a variety
 of ways, including, without limitation, chemical synthesis, cDNA or
 genomic library screening, expression library screening, and/or PCR
 amplification of cDNA. These methods and others useful for isolating such
 DNA are set forth, for example, by Sambrook et al. (Molecular Cloning: A
 Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring
 Harbor, N.Y. [1989]), by Ausubel et al., eds. (Current Protocols in
 Molecular Biology, Current Protocols Press [1994]), and by Berger and
 Kimmel (Methods in Enzymology: Guide to Molecular Cloning Techniques, vol.
 152, Academic Press, Inc., San Diego, Calif. [1987]). Preferred nucleic
 acid sequences encoding LSIRF are mammalian sequences. Most preferred
 nucleic acid sequences encoding LSIRF are human, rat, and mouse.
 Chemical synthesis of a LSIRF nucleic acid molecule can be accomplished
 using methods well known in the art, such as those set forth by Engels et
 al. (Angew. Chem. Intl. Ed., 28:716-734 [1989]). These methods include,
 inter alia, the phosphotriester, phosphoramidite and H-phosphonate methods
 of nucleic acid synthesis. Typically, the nucleic acid molecule encoding
 the full length LSIRF polypeptide will be several hundred base pairs (bp)
 or nucleotides in length. Nucleic acids larger than about 100 nucleotides
 in length can be synthesized as several fragments, each fragment being up
 to about 100 nucleotides in length. The fragments can then be ligated
 together, as described below, to form a full length nucleic acid encoding
 the LSIRF polypeptide. A preferred method is polymer-supported synthesis
 using standard phosphoramidite chemistry.
 Alternatively, the nucleic acid encoding a LSIRF polypeptide may be
 obtained by screening an appropriate cDNA library (i.e., a library
 prepared from one or more tissue source(s) believed to express the
 polypeptide) or a genomic library (a library prepared from total genomic
 DNA). The source of the cDNA library is typically a tissue from any
 species that is believed to express LSIRF in reasonable quantities (such
 as lymphoid tissue). The source of the genomic library may be any tissue
 or tissues from any mammalian or other species believed to harbor a gene
 encoding LSIRF or a LSIRF homologue. The library can be screened for the
 presence of the LSIRF cDNA/gene using one or more nucleic acid probes
 (oligonucleotides, cDNA or genomic DNA fragments that possess an
 acceptable level of homology to the LSIRF or LSIRF homologue cDNA or gene
 to be cloned) that will hybridize selectively with LSIRF or LSIRF
 homologue cDNA(s) or gene(s) that is(are) present in the library. The
 probes typically used for such library screening usually encode a small
 region of the LSIRF DNA sequence from the same or a similar species as the
 species from which the library was prepared. Alternatively, the probes may
 be degenerate, as discussed below.
 Library screening is typically accomplished by annealing the
 oligonucleotide probe or cDNA to the clones in the library under
 conditions of stringency that prevent non-specific binding but permit
 binding of those clones that have a significant level of homology with the
 probe or primer. Typical hybridization and washing stringency conditions
 depend in part on the size (i.e., number of nucleotides in length) of the
 cDNA or oligonucleotide probe, and whether the probe is degenerate. The
 probability of obtaining a clone(s) is also considered in designing the
 hybridization solution (i.e., whether a cDNA or genomic library is being
 screened; if it is a cDNA library, the probability that the cDNA of
 interest is present at a high level).
 Where DNA fragments (such as cDNAs) are used as probes, typical
 hybridization conditions are those for example as set forth in Ausubel et
 al., eds., supra. After hybridization, the blot containing the library is
 washed at a suitable stringency, depending on several factors such as
 probe size, expected homology of probe to clone, type of library being
 screened, number of clones being screened, and the like. Examples of
 stringent washing solutions (which are usually low in ionic strength and
 are used at relatively high temperatures) are as follows. One such
 stringent wash is 0.015 M NaCl, 0.005 M NaCitrate and 0.1 percent SDS at
 55-65.degree. C. Another such stringent buffer is 1 mM Na.sub.2 EDTA, 40
 mM NaHPO4, pH 7.2, and 1 percent SDS at about 40-50.degree. C. One other
 stringent wash is 0.2.times.SSC and 0.1 percent SDS at about 50-65.degree.
 C.
 Where oligonucleotide probes are used to screen cDNA or genomic libraries,
 two protocols for stringent washing conditions as follows may be used, for
 example. The first protocol uses 6.times.SSC with 0.05 percent sodium
 pyrophosphate at a temperature of between about 35 and 62.degree. C.,
 depending on the length of the probe. For example, 14 base probes are
 washed at 35-40.degree. C., 17 base probes at 45-50.degree. C., 20 base
 probes at 52-57.degree. C., and 23 base probes at 57-63.degree. C. The
 temperature can be increased 2-3.degree. C. where the background
 non-specific binding appears high. A second protocol uses
 tetramethylammonium chloride (TMAC) for washing. One such stringent
 washing solution is 3 M TMAC, 50 mM Tris-HCl, pH 8.0, and 0.2 percent SDS.
 The washing temperature using this solution is a function of the length of
 the probe. For example, a 17 base probe is washed at about 45-50.degree.
 C.
 Another suitable method for obtaining a nucleic acid encoding a LSIRF
 polypeptide is the polymerase chain reaction (PCR). In this method,
 poly(A)+RNA or total RNA is extracted from a tissue that expresses LSIRF
 (such as lymphoid tissue). cDNA is then prepared from the RNA using the
 enzyme reverse transcriptase. Two primers typically complementary to two
 separate regions of the LSIRF cDNA (oligonucleotides) are then added to
 the cDNA along with a polymerase such as Taq polymerase, and the
 polymerase amplifies the cDNA region between the two primers.
 Where the method of choice for preparing the nucleic acid encoding the
 LSIRF polypeptide requires the use of oligonucleotide primers or probes
 (e.g. PCR, cDNA or genomic library screening), the oligonucleotide
 sequences selected as probes or primers should be of adequate length and
 sufficiently unambiguous so as to minimize the amount of non-specific
 binding that will occur during library screening or PCR amplification. The
 actual sequence of the probes or primers is usually based on conserved or
 highly homologous sequences or regions from the same or a similar gene
 from another organism. Optionally, the probes or primers can be fully or
 partially degenerate, i.e., contain a mixture of probes/primers, all
 encoding the same amino acid sequence, but using different codons to do
 so. An alternative to preparing degenerate probes is to place an inosine
 in some or all of those codon positions that vary by species. The
 oligonucleotide probes or primers may be prepared by chemical synthesis
 methods for DNA as described above.
 LSIRF mutant or variant sequences are contemplated as within the scope of
 the present invention. A mutant or variant sequence as used herein is a
 sequence that contains one or more nucleotide substitutions, deletions,
 and/or insertions as compared to the wild type sequence that result in
 amino acid sequence variations as compared to the wild type amino acid
 sequence. In some cases, naturally occurring LSIRF amino acid mutants or
 variants may exist, due to the existence of natural allelic variation.
 Such naturally occurring variants are also within the scope of the present
 invention. Preparation of synthetic mutant sequences is well known in the
 art, and is described for example in Wells et al. (Gene, 34:315 [1985]),
 and in Sambrook et al, supra.
 2. Preparation of a LSIRF Polypeptide 5' Flanking Sequence
 Included within the scope of the present invention are LSIRF 5' flanking
 sequences (also referred to herein as "promoters") from any species. By
 promoter as used herein is meant the 5' flanking sequence of a LSIRF gene.
 The 5' flanking sequence may have various transcription factor binding
 sites, and also may possess a TATA box at about position -30, and a CCAAT
 box upstream from the TATA box. Such 5' flanking sequences are
 characterized as naturally regulating the transcription of a LSIRF gene in
 vivo, either alone or in combination with other factors such a enhancer
 elements, repressors, and the like (any or all of which may be very
 distally located). Preferred 5' flanking sequences are mammalian LSIRF 5'
 flanking sequences. Most preferred are human LSIRF 5' flanking sequences.
 The 5' flanking sequences of the present invention may be obtained from
 genomic libraries by screening the library with cDNAs or genomic LSIRF
 fragments that preferably hybridize to the 5' portion of the LSIRF gene.
 Such fragments may hybridize to a clone in the library that contains some
 or all of the LSIRF 5' flanking sequence, which is generally located just
 5' to the start of the coding sequence for LSIRF. Where the identified
 clone contains only a portion of the promoter, the clone itself, or a
 fragment of it, may be used for subsequent rounds of genomic library
 screening to obtain additional 5' flanking sequence. Screening with the
 fragments (including hybridization and washing) may be accomplished as
 described above for cloning a LSIRF gene and/or cDNA.
 3. Preparation of a Vector for LSIRF Expression
 After cloning, the cDNA or gene encoding a LSIRF polypeptide or fragment
 thereof has been isolated, it is typically inserted into an amplification
 and/or expression vector in order to increase the copy number of the gene
 and/or to express the polypeptide in a suitable host cell. The vector is
 often a commercially available vector, though "custom made" vectors may be
 used as well. The vector is selected to be functional in the particular
 host cell employed (i.e., the vector is compatible with the host cell
 machinery such that amplification of the LSIRF gene and/or expression of
 the gene can occur). The LSIRF polypeptide or fragment thereof may be
 amplified/expressed in prokaryotic, yeast, insect (baculovirus systems)
 and/or eukaryotic host cells. Selection of the host cell will depend at
 least in part on whether the LSIRF polypeptide or fragment thereof is to
 be glycosylated. If so, yeast, insect, or mammalian host cells are
 preferable; yeast cells will glycosylate the polypeptide, and insect and
 mammalian cells can glycosylate and/or phosphorylate the polypeptide as it
 naturally occurs on the LSIRF polypeptide (i.e., "native" glycosylation
 and/or phosphorylation).
 Typically, the vectors used in any of the host cells will contain 5'
 flanking sequence and other regulatory elements as well such as an
 enhancer(s), an origin of replication element, a transcriptional
 termination element, a complete intron sequence containing a donor and
 acceptor splice site, a signal peptide sequence, a ribosome binding site
 element, a polyadenylation sequence, a polylinker region for inserting the
 nucleic acid encoding the polypeptide to be expressed, and a selectable
 marker element. Optionally, the vector may contain a "tag" sequence, i.e.,
 an oligonucleotide sequence located at the 5' or 3' end of the LSIRF
 coding sequence that encodes polyHis (such as hexaHis) or another small
 immunogenic sequence. This tag will be expressed along with the protein,
 and can serve as an affinity tag for purification of the LSIRF polypeptide
 from the host cell. Optionally, the tag can subsequently be removed from
 the purified LSIRF polypeptide by various means such as using a selected
 peptidase for example.
 A. 5' Flanking Sequence Element
 The 5' flanking sequence may be homologous (i.e., from the same species
 and/or strain as the host cell), heterologous (i.e., from a species other
 than the host cell species or strain), hybrid (i.e., a combination of p5'
 flanking sequences from more than one source), synthetic, or it may be the
 native LSIRF 5' flanking sequence. As such, the source of the 5' flanking
 sequence may be any unicellular prokaryotic or eukaryotic organism, any
 vertebrate or invertebrate organism, or any plant, provided that the 5'
 flanking sequence is functional in, and can be activated by, the host cell
 machinery.
 The 5' flanking sequences useful in the vectors of this invention may be
 obtained by any of several methods well known in the art. Typically, 5'
 flanking sequences useful herein other than the LSIRF 5' flanking sequence
 will have been previously identified by mapping and/or by restriction
 endonuclease digestion and can thus be isolated from the proper tissue
 source using the appropriate restriction endonucleases. In some cases, the
 full nucleotide sequence of the 5' flanking sequence may be known. Here,
 the 5' flanking sequence may be synthesized using the methods described
 above for nucleic acid synthesis or cloning.
 Where all or only portions of the 5' flanking sequence are known, it may be
 obtained using PCR and/or by screening a genomic library with suitable
 oligonucleotide and/or 5' flanking sequence fragments from the same or
 another species.
 Where the 5' flanking sequence is not known, a fragment of DNA containing
 the some 5' flanking sequence may be isolated from a larger piece of DNA
 that may contain, for example, a coding sequence or even another gene or
 genes. Isolation may be accomplished by restriction endonuclease digestion
 using one or more carefully selected enzymes to isolate the proper DNA
 fragment. After digestion, the desired fragment may be isolated by agarose
 gel purification, Qiagen.RTM. column or other methods known to the skilled
 artisan. Selection of suitable enzymes to accomplish this purpose will be
 readily apparent to one of ordinary skill in the art.
 B. Origin of Replication Element
 This component is typically a part of prokaryotic expression vectors
 purchased commercially, and aids in the amplification of the vector in a
 host cell. Amplification of the vector to a certain copy number can, in
 some cases, be important for optimal expression of the LSIRF polypeptide.
 If the vector of choice does not contain an origin of replication site,
 one may be chemically synthesized based on a known sequence, and ligated
 into the vector.
 C. Transcription Termination Element
 This element is typically located 3' to the end of the LSIRF polypeptide
 coding sequence and serves to terminate transcription of the LSIRF
 polypeptide. Usually, the transcription termination element in prokaryotic
 cells is a G-C rich fragment followed by a poly T sequence. While the
 element is easily cloned from a library or even purchased commercially as
 part of a vector, it can also be readily synthesized using methods for
 nucleic acid synthesis such as those described above.
 D. Selectable Marker(s) Element
 Selectable marker genes encode proteins necessary for the survival and
 growth of a host cell grown in a selective culture medium. Typical
 selection marker genes encode proteins that (a) confer resistance to
 antibiotics or other toxins, e.g., ampicillin, tetracycline, or kanamycin
 for prokaryotic host cells, (b) complement auxotrophic deficiencies of the
 cell; or (c) supply critical nutrients not available from complex media.
 Preferred selectable markers are the kanamycin resistance gene, the
 ampicillin resistance gene, and the tetracycline resistance gene.
 E. Ribosome Binding Site Element
 This element, commonly called the Shine-Dalgarno sequence (prokaryotes) or
 the Kozak sequence (eukaryotes), is necessary for translation initiation
 of mRNA. The element is typically located 3' to the promoter and 5' to the
 coding sequence of the polypeptide to be synthesized. The Shine-Dalgarno
 sequence is varied but is typically a polypurine (i.e., having a high A-G
 content). Many Shine-Dalgarno sequences have been identified, each of
 which can be readily synthesized using methods set forth above.
 All of the elements set forth above, as well as others useful in this
 invention, are well known to the skilled artisan and are described, for
 example, in Sambrook et al. (Molecular Cloning:A Laboratory Manual, Cold
 Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. [1989]) and
 Berger et al., eds. (Guide to Molecular Cloning Techniques, Academic
 Press, Inc., San Diego, Calif. [1987]).
 F. Signal Sequence Element
 For those embodiments of the invention where the transgene is to be
 secreted, a signal sequence, is frequently present to direct the
 polypeptide encoded by the transgene out of the cell where it is
 synthesized. Typically, the signal sequence is positioned in the coding
 region of the transgene towards or at the 5' end of the coding region.
 Many signal sequences have been identified, and any of them that are
 functional in the transgenic tissue may be used in conjunction with the
 transgene. Therefore, the signal sequence may be homologous or
 heterologous to the transgene, and may be homologous or heterologous to
 the transgenic mammal. Additionally, the signal sequence may be chemically
 synthesized using methods set forth above. However, for purposes herein,
 preferred signal sequences are those that occur naturally with the
 transgene (i.e., are homologous to the transgene).
 G. Intron Element
 In many cases, transcription of the transgene is increased by the presence
 of one or more introns on the vector. The intron may be naturally
 occurring within the transgene sequence, especially where the transgene is
 a full length or a fragment of a genomic DNA sequence. Where the intron is
 not naturally occurring within the DNA sequence (as for most cDNAs), the
 intron(s) may be obtained from another source. The intron may be
 homologous or heterologous to the transgene and/or to the transgenic
 mammal. The position of the intron with respect to the promoter and the
 transgene is important, as the intron must be transcribed to be effective.
 As such, where the transgene is a cDNA sequence, the preferred position
 for the intron is 3' to the transcription start site, and 5' to the polyA
 transcription termination sequence. Preferably for cDNA transgenes, the
 intron will be located on one side or the other (i.e., 5' or 3') of the
 transgene sequence such that it does not interrupt the transgene sequence.
 Any intron from any source, including any viral, prokaryotic and
 eukaryotic (plant or animal) organisms, may be used to practice this
 invention, provided that it is compatible with the host cell(s) into which
 it is inserted. Also included herein are synthetic introns. Optionally,
 more than one intron may be used in the vector.
 H. Construction of Vectors
 Where one or more of the elements set forth above are not already present
 in the vector to be used, they may be individually obtained and ligated
 into the vector. Methods used for obtaining each of the elements are well
 known to the skilled artisan and are comparable to the methods set forth
 above (i.e., synthesis of the DNA, library screening, and the like).
 The final vectors used to practice this invention are typically constructed
 from a starting vectors such as a commercially available vector. This
 vector may or may not contain some of the elements to be included in the
 completed vector. If none of the desired elements are present in the
 starting vector, each element may be individually ligated into the vector
 by cutting the vector with the appropriate restriction endonuclease(s)
 such that the ends of the element to be ligated in and the ends of the
 vector are compatible for ligation. In some cases, it may be necessary to
 "blunt" the ends to be ligated together in order to obtain a satisfactory
 ligation. Blunting is accomplished by first filling in "sticky ends" using
 Klenow DNA polymerase or T4 DNA polymerase in the presence of all four
 nucleotides. This procedure is well known in the art and is described for
 example in Sambrook et al., supra.
 Alternatively, two or more of the elements to be inserted into the vector
 may first be ligated together (if they are to be positioned adjacent to
 each other) and then ligated into the vector.
 One other method for constructing the vector to conduct all ligations of
 the various elements simultaneously in one reaction mixture. Here, many
 nonsense or nonfunctional vectors will be generated due to improper
 ligation or insertion of the elements, however the functional vector may
 be identified and selected by restriction endonuclease digestion.
 Preferred vectors for practicing this invention are those which are
 compatible with bacterial, insect, and mammalian host cells. Such vectors
 include, inter alia, pCRII (Invitrogen Company, San Diego, Calif.), pBSII
 (Stratagene Company, LaJolla, Calif.), and pETL (BlueBacII; Invitrogen).
 After the vector has been constructed and a LSIRF nucleic acid has been
 inserted into the proper site of the vector, the completed vector may be
 inserted into a suitable host cell for amplification and/or LSIRF
 polypeptide expression. The host cells typically used include, without
 limitation: Prokaryotic cells such as gram negative or gram positive
 cells, i.e., any strain of E. coli, Bacillus, Streptomyces, Saccharomyces,
 Salmonella, and the like; eukaryotic cells such as CHO (Chinese hamster
 ovary) cells, human kidney 293 cells, COS-7 cells; insect cells such as
 Sf4, Sf5, Sf9, and Sf21 and High 5 (all from the Invitrogen Company, San
 Diego, Calif.); and various yeast cells such as Saccharomyces and Pichia.
 Insertion (also referred to as "transformation" or "transfection") of the
 vector into the selected host cell may be accomplished using such methods
 as calcium chloride, electroporation, microinjection, lipofection or the
 DEAE-dextran method. The method selected will in part be a function of the
 type of host cell to be used. These methods and other suitable methods are
 well known to the skilled artisan, and are set forth, for example, in
 Sambrook et al., supra.
 The host cells containing the vector (i.e., transformed or transfected) may
 be cultured using standard media well known to the skilled artisan. The
 media will usually contain all nutrients necessary for the growth and
 survival of the cells. Suitable media for culturing E. coli cells are for
 example, Luria Broth (LB) and/or Terrific Broth (TB). Suitable media for
 culturing eukaryotic cells are RPMI 1640, MEM, DMEM, all of which may be
 supplemented with serum and/or growth factors as required by the
 particular cell line being cultured. A suitable medium for insect cultures
 is Grace's medium supplemented with yeastolate, lactalbumin hydrolysate,
 and/or fetal calf serum as necessary.
 Typically, an antibiotic or other compound useful for selective growth of
 the transformed cells only is added as a supplement to the media. The
 compound to be used will be dictated by the selectable marker element
 present on the plasmid with which the host cell was transformed. For
 example, where the selectable marker element is kanamycin resistance, the
 compound added to the culture medium will be kanamycin.
 4. Evaluation of Expression
 The amount of LSIRF polypeptide produced in the host cell can be evaluated
 using standard methods known in the art. Such methods include, without
 limitation, Western blot analysis, SDS-polyacrylamide gel electrophoresis,
 non-denaturing gel electrophoresis, HPLC separation, immunoprecipitation,
 and/or activity assays such as DNA binding gel shift assays.
 5. Purification of the LSIRF polypeptide
 If the LSIRF polypeptide has been designed to be secreted from the host
 cells, the majority of polypeptide will likely be found in the cell
 culture medium. If however, the LSIRF polypeptide is not secreted from the
 host cells, it will be present in the cytoplasm (for eukaryotic, gram
 positive bacteria, and insect host cells) or in the periplasm (for gram
 negative bacteria host cells).
 For intracellular LSIRF, the host cells are first disrupted mechanically or
 osmotically to release the cytoplasmic contents into a buffered solution.
 LSIRF polypeptide is then isolated from this solution.
 Purification of LSIRF polypeptide from solution can be accomplished using a
 variety of techniques. If the polypeptide has been synthesized such that
 it contains a tag such as Hexahistidine (LSIRF/hexaHis) or other small
 peptide at either its carboxyl or amino terminus, it may essentially be
 purified in a one-step process by passing the solution through an affinity
 column where the column matrix has a high affinity for the tag or for the
 polypeptide directly (i.e., a monoclonal antibody specifically recognizing
 LSIRF). For example, polyhistidine binds with great affinity and
 specificty to nickel, thus an affinity column of nickel (such as the
 Qiagen nickel columns) can be used for purification of LSIRF/polyHis. (See
 for example, Ausubel et al., eds., Current Protocols in Molecular Biology,
 Section 10.11.8, John Wiley & Sons, New York [1993]).
 Where the LSIRF polypeptide has no tag and no antibodies are available,
 other well known procedures for purification can be used. Such procedures
 include, without limitation, ion exchange chromatography, molecular sieve
 chromatography, HPLC, native gel electrophoresis in combination with gel
 elution, and preparative isoelectric focusing ("Isoprime"
 machine/technique, Hoefer Scientific). In some cases, two or more of these
 techniques may be combined to achieve increased purity. Preferred methods
 for purification include polyHistidine tagging and ion exchange
 chromatography in combination with preparative isoelectric focusing.
 If it is anticipated that the LSIRF polypeptide will be found primarily in
 the periplasmic space of the bacteria or the cytoplasm of eukaryotic
 cells, the contents of the periplasm or cytoplasm, including inclusion
 bodies (bacteria) if the processed polypeptide has formed such complexes,
 can be extracted from the host cell using any standard technique known to
 the skilled artisan. For example, the host cells can be lysed to release
 the contents of the periplasm by French press, homogenization, and/or
 sonication. The homogenate can then be centrifuged.
 If the LSIRF polypeptide has formed inclusion bodies in the periplasm, the
 inclusion bodies can often bind to the inner and/or outer cellular
 membranes and thus will be found primarily in the pellet material after
 centrifugation. The pellet material can then be treated with a chaotropic
 agent such as guanidine or urea to release, break apart, and solubilize
 the inclusion bodies. The LSIRF polypeptide in its now soluble form can
 then be analyzed using gel electrophoresis, immunoprecipitation or the
 like. If it is desired to isolate the LSIRF polypeptide, isolation may be
 accomplished using standard methods such as those set forth below and in
 Marston et al. (Meth. Enz., 182:264-275 [1990]).
 If LSIRF polypeptide inclusion bodies are not formed to a significant
 degree in the periplasm of the host cell, the LSIRF polypeptide will be
 found primarily in the supernatant after centrifugation of the cell
 homogenate, and the LSIRF polypeptide can be isolated from the supernatant
 using methods such as those set forth below.
 In those situations where it is preferable to partially or completely
 isolate the LSIRF polypeptide, purification can be accomplished using
 standard methods well known to the skilled artisan. Such methods include,
 without limitation, separation by electrophoresis followed by
 electroelution, various types of chromatography (immunoaffinity, molecular
 sieve, and/or ion exchange), and/or high pressure liquid chromatography.
 In some cases, it may be preferable to use more than one of these methods
 for complete purification.
 The term "substance" as used herein refers to compounds useful in
 inhibiting either transcription of the LSIRF gene, translation of the
 LSIRF mRNA, or activity of the LSIRF polypeptide.
 The term "therapeutically effective" refers to the amount of the substance
 that is required in order to obtain the desired physiological response,
 i.e., to suppress the activation of lymphocytes in response to an antigen
 stimulus or autoimmune response, or increase lymphocyte number to
 stimulate the immune response to an antigen stimulus.
 The term "antigen stimulus" refers to a compound that is either found
 naturally in a mammal (endogenous) and elicits some aspect of the immune
 response, or is from an exogenous source and invades the mammal's system
 and elicits some aspect(s) of the immune response.
 The compositions useful for practicing the methods of the present invention
 may be prepared according to standard methods well known by those of
 ordinary skill in the art.
 Therapeutic Anti-LSIRF Antibodies
 Polyclonal or monoclonal therapeutic anti-LSIRF antibodies useful in
 practicing this invention may be prepared in laboratory animals or by
 recombinant DNA techniques using the following methods. Polyclonal
 antibodies to the LSIRF molecule or a fragment thereof containing the
 target amino acid sequence generally are raised in animals by multiple
 subcutaneous (sc) or intraperitoneal (ip) injections of the LSIRF molecule
 in combination with an adjuvant such as Freund's adjuvant (complete or
 incomplete). To enhance immunogenicity, it may be useful to first
 conjugate the LSIRF molecule or a fragment containing the target amino
 acid sequence of to a protein that is immunogenic in the species to be
 immunized, e.g., keyhole limpet hemocyanin, serum albumin, bovine
 thyroglobulin, or soybean trypsin inhibitor using a bifunctional or
 derivatizing agent, for example, maleimidobenzoyl sulfosuccinimide ester
 (conjugation through cysteine residues), N-hydroxysuccinimide (through
 lysine residues), glutaraldehyde, succinic anhydride, SOCl.sub.2, or
 R.sup.1 N=C=NR, where R and R.sup.1 are different alkyl groups.
 Alternatively, LSIRF-immunogenic conjugates can be produced recombinantly
 as fusion proteins.
 Animals are immunized against the immunogenic LSIRF conjugates or
 derivatives (such as a fragment containing the target amino acid sequence)
 by combining about 1 mg or about 1 .mu.g of conjugate (for rabbits or
 mice, respectively) with about 3 volumes of Freund's complete adjuvant and
 injecting the solution intradermally at multiple sites. Approximately 7 to
 14 days later, animals are bled and the serum is assayed for anti-LSIRF
 titer. Animals are boosted with antigen repeatedly until the titer
 plateaus. Preferably, the animal is boosted with the same LSIRF molecule
 or fragment thereof as was used for the initial immunization, but
 conjugated to a different protein and/or through a different cross-linking
 agent. In addition, aggregating agents such as alum are used in the
 injections to enhance the immune response.
 Monoclonal antibodies may be prepared by recovering spleen cells from
 immunized animals and immortalizing the cells in conventional fashion,
 e.g. by fusion with myeloma cells. The clones are then screened for those
 expressing the desired antibody. The monoclonal antibody preferably does
 not cross-react with other LSIRF polypeptides or LSIRF polypeptide
 isoforms.
 Preparation of antibodies using recombinant DNA methods such as the
 phagemid display method, may be accomplished using commercially available
 kits, as for example, the Recombinant Phagemid Antibody System available
 from Pharmacia (Uppsala, Sweden), or the SurfZAP.TM. phage display system
 (Stratagene Inc., La Jolla, Calif.).
 Preferably, antibodies for administration to humans, although prepared in a
 laboratory animal such as a mouse, will be "humanized", or chimeric, i.e.
 made to be compatible with the human immune system such that a human
 patient will not develop an immune response to the antibody. Even more
 preferably, human antibodies which can now be prepared using methods such
 as those described for example in Lonberg et al. (Nature Genetics, 7:
 13-21 [1994]) are preferred for therapeutic administration to patients.
 Antibodies produced using any of the above described methods can be
 conjugated to compounds that are able to penetrate the cell membrane and
 the nuclear membrane for import of the antibody into the nucleus using,
 for example, a nuclear targeting signal such as that found on the
 phosphorylated form of LSIRF.
 Therapeutic Compositions and Administration
 Therapeutic formulations of the compositions useful for practicing the
 present invention such as LSIRF antibodies may be prepared for storage by
 mixing the selected composition having the desired degree of purity with
 optional physiologically acceptable carriers, excipients, or stabilizers
 (Remington's Pharmaceutical Sciences, 18th edition, A. R. Gennaro, ed.,
 Mack Publishing Company [1990]) in the form of a lyophilized cake or an
 aqueous solution. Acceptable carriers, excipients or stabilizers are
 nontoxic to recipients and are preferably inert at the dosages and
 concentrations employed, and include buffers such as phosphate, citrate,
 or other organic acids; antioxidants such as ascorbic acid; low molecular
 weight polypeptides; proteins, such as serum albumin, gelatin, or
 immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino
 acids such as glycine, glutamine, asparagine, arginine or lysine;
 monosaccharides, disaccharides, and other carbohydrates including glucose,
 mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such
 as mannitol or sorbitol; salt-forming counterions such as sodium; and/or
 nonionic surfactants such as Tween, Pluronics or polyethylene glycol
 (PEG).
 The composition to be used for in vivo administration must be sterile. This
 is readily accomplished by filtration through sterile filtration
 membranes, prior to or following lyophilization and reconstitution. The
 composition for parenteral administration ordinarily will be stored in
 lyophilized form or in solution.
 Therapeutic compositions generally are placed into a container having a
 sterile access port, for example, an intravenous solution bag or vial
 having a stopper pierceable by a hypodermic injection needle.
 The route of administration of the composition is in accord with known
 methods, e.g. oral, injection or infusion by intravenous, intraperitoneal,
 intracerebral, intramuscular, intraocular, intraarterial, or intralesional
 routes, or by sustained release systems or implantation device. Where
 desired, the compositions may be administered continuously by infusion,
 bolus injection or by implantation device.
 Suitable examples of sustained-release preparations include semipermeable
 polymer matrices in the form of shaped articles, e.g. films, or
 microcapsules. Sustained release matrices include polyesters, hydrogels,
 polylactides (U.S. Pat. No. 3,773,919, EP 58,481), copolymers of
 L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al, Biopolymers,
 22: 547-556 [1983]), poly (2-hydroxyethyl-methacrylate) (Langer et al., J.
 Biomed. Mater. Res., 15: 167-277 [1981] and Langer, Chem. Tech., 12:
 98-105 [1982]), ethylene vinyl acetate (Langer et al., supra) or
 poly-D(-)-3-hydroxybutyric acid (EP 133,988). Sustained-release
 compositions also may include liposomes, which can be prepared by any of
 several methods known in the art (e.g., DE 3,218,121; Epstein et al.,
 Proc. Natl. Acad. Sci. USA, 82: 3688-3692 [1985]; Hwang et al., Proc.
 Natl. Acad. Sci. USA, 77: 4030-4034 [1980]; EP 52,322; EP 36,676; EP
 88,046; EP 143,949).
 An effective amount of the compositions to be employed therapeutically will
 depend, for example, upon the therapeutic objectives, the route of
 administration, and the condition of the patient. Accordingly, it will be
 necessary for the therapist to titer the dosage and modify the route of
 administration as required to obtain the optimal therapeutic effect. A
 typical daily dosage may range from about 1 |.mu.g/kg to up to 100 mg/kg
 or more, depending on the factors mentioned above. Typically, a clinician
 will administer the composition until a dosage is reached that achieves
 the desired effect. The progress of this therapy is easily monitored by
 conventional assays designed to evaluate.
 The LSIRF nucleic acid molecules, 5' flanking sequences, polypeptides, and
 antibodies of the present invention will have a variety of uses that are
 readily apparent to one of ordinary skill in the art.
 The LSIRF polypeptides will have utility as a target for therapeutic
 compounds used to regulate lymphocyte activation. By blocking either the
 expression of the LSIRF gene (via decreasing LSIRF transcription or
 translation) or the activity of the LSIRF polypeptide, it is possible to
 suppress lymphocyte activation in response to certain environmental
 stimuli. By increasing the level of expression of the LSIRF gene (via
 up-regulation of the LSIRF 5' flanking sequence), it is possible to
 stimulate lymphocyte activation and proliferation, thereby increasing the
 immune response to particular antigens.
 The antibodies of the present invention may be polyclonal or monoclonal,
 and may be raised against LSIRF from any mammal. These antibodies can be
 used to assess the presence and/or amount of LSIRF polypeptide in a given
 tissue or biological sample. In addition, they may be used to block the
 activity of LSIRF by binding to the active site of this polypeptide. Thus,
 the antibodies themselves may find use as therapeutic compounds to
 decrease the level of LSIRF polypeptide.
 The invention may be more readily understood by reference to the following
 Examples. These Examples should not be construed in any way as limiting
 the scope of the invention.
 EXAMPLES
 Example 1
 Cloning the Mouse LSIRF cDNA
 Two PCR (polymerase chain reaction) partially degenerate primers were used
 for PCR amplification of cDNA prepared from total RNA obtained from spleen
 tissue of a C57Bl/6 mouse. The primers were:
 ATCCTGGAACACGC (SEQ ID NO:5)
 GCACACGAACTGCCTTCCA (SEQ ID NO:6)
 Primer No. 5 contained three inosine bases which were located between
 nucleotides 2 and 3 (T and C), nucleotides 4 and 5 (C and T), and
 nucleotides 9 and 10 (A and C). Primer No. 6 contained four inosine bases
 in the sequence which were located between nucleotides 5 and 6 (A and C),
 nucleotides 7 and 8 (G and A), nucleotides 9 and 10 (A and C), and
 nucleotides 11 and 12 (T and G).
 PCR was carried out on a programmable thermal cycler (Perkin-Elmer Cetus,
 Norwalk, Conn.) in 50 .mu.l of PCR buffer (10 mM Tris-HCl pH 8.3, 1.5 mM
 MgCl.sub.2, and 50 mM KCl) containing 200 .mu.M dNTPs, 2 U Taq polymerase,
 and 100 pM of each primer. Thirty cycles of PCR were performed under the
 following temperature regime: 94.degree. C. for 60 seconds; 37.degree. C.
 for 60 seconds; and 72.degree. C. for 60 seconds. The PCR products were
 subsequently inserted directly into the pCRII plasmid using the TA-Cloning
 System (Invitrogen Corp., San Diego, Calif.). The plasmids containing the
 PCR product inserts were transformed into competent E. coli strain
 INV-alpha F' (Invitrogen Corp.) for amplification. Plasmid DNA from these
 host cells was prepared using the standard alkaline lysis method (Sambrook
 et al., Supra), and the plasmid DNA was then electrophoresed through an
 approximately 1.5 percent agarose gel. A portion of the DNA was blotted on
 to Hybond-N membrane paper (Amersham, Oakville, Ontario, Canada) and
 hybridized with random-primed, .sup.32 P labeled DNA fragments of murine
 IRF-1 and IRF-2 using the manufacturer's protocol (Amersham). Plasmid DNA
 from clones that did not hybridize with either IRF-1 or IRF-2 fragments
 was sequenced using the US Bioscience Sequenase kit (US Bioscience,
 Cleveland, Ohio). One clone, "Spl 5", contained a novel nucleotide
 sequence as determined from a search in Genbank. This clone was labeled
 with .sup.32 P by random priming (Amersham procedure) and was then used to
 screen a mouse IL-4 induced spleen cDNA library (Clonetech, Palo Alto,
 Calif.). After hybridization, the filters containing the cDNA library
 clones were washed first with 1.times.SSC and 0.1 percent SDS for about 30
 minutes at about 65.degree. C. and then with 0.2.times.SSC and 0.1 percent
 SDS for about 30 minutes at about 65 .degree. C. Two LSIRF cDNA clones
 lacking the ATG start codon were obtained. One of these clones, "C13", was
 used to rescreen the same library, yielding an approximately 5 kb clone,
 "C16", which also lacked the 5' sequence. Clone C16 was then used to
 screen a .lambda.ZAPII mouse spleen cDNA library (Stratagene, La Jolla,
 Calif.) and several partial clones having a putative ATG start codon were
 obtained. A complete cDNA sequence containing the entire coding LSIRF
 region was obtained by creating an artificial clone using PCR with a 5'
 extended primer. This clone was inserted into the vector pBSII to generate
 the plasmid PV-1, and the sequence of LSIRF was verified.
 The predicted amino acid sequence was obtained for each of the partial cDNA
 clones, and some of the clones had an extra glutamine at amino acid
 position 164. The full-length cDNA sequence of PV-1, which is about 1.4
 kb, is set forth in FIG. 1. The PV-1 cDNA contains the extra glutamine at
 amino acid position 164. A predicted full length amino acid sequence for
 LSIRF based on the LSIRF cDNA sequence is set forth in FIG. 2.
 Example 2
 Genomic Cloning of Mouse LSIRF
 An approximately 630 bp portion of the C16 clone of the LSIRF cDNA was PCR
 amplified using the following primers:
 CAGCCCGGGGTACTTGCCGCTGTC (SEQ ID NO:7)
 AGACCTTATGCTTGGCTCAATGGG (SEQ ID NO:8)
 PCR conditions were 94.degree. C. for 1 minute and 72.degree. C. for 30
 seconds.
 The PCR fragment obtained was purified by 1 percent agarose gel
 electrophoresis, followed by passage through a Spin-X column (CoStar
 Corp., Cambridge, Mass.). This fragment was then labeled with .sup.32 P
 using the random primer technique (Amersham), and subsequently used to
 screen a genomic library prepared from kidney tissue of a 129/J mouse.
 Several clones were obtained by washing at 65.degree. C. in 0.1.times.SSC
 and 0.1 percent SDS. Two of these clones (sizes 12 and 15 kb) were
 subcloned into the vector pBSII (Stratagene, La Jolla, Calif.) for
 sequencing. The clones contained overlapping sequence, permitting the
 identification of about 2 kb of 5' flanking sequence. The 5' flanking
 sequence is set forth in FIG. 3. A genomic sequence containing the exons
 and introns of a murine LSIRF gene is set forth in FIG. 4, and the
 inconsistencies in the sequence due to sequence uncertainty are indicated
 as "R" for A or G, "S" for G or C, "M" for A or C, and "K" for T or G. The
 ambiguities are:
 M at nucleotides 748, 4159, 7413, and 10357;
 R at nucleotides 5277, 5310, 10564, and 11713;
 K at nucleotides 4513, 5885, and 9812;
 S at nucleotide 6425.
 All ambiguities are in the introns, thus not affecting the actual
 nucleotide sequence of the exons that comprise the coding region of LSIRF.
 The nucleotide (cDNA and genomic) sequences and the deduced amino acid
 sequence of LSIRF were compared with all sequences in the GenBank and
 SwissProt databases, and no identical sequences were found. However, the
 amino terminus sequence of LSIRF had homology with other members of the
 IRF family. The highest homology was with the polypeptide ICSBP
 (interferon consensus sequence binding protein), which shares 83 percent
 homology (allowing for a one amino acid gap) with LSIRF at the amino
 terminus.
 Example 3
 Mouse LSIRF Expression
 The LSIRF full length cDNA sequence was excised from the plasmid PV-1 by
 EcoRI restriction digest. The LSIRF gene was isolated from a 0.7% agarose
 gel after electrophoresis, blunt ended using Klenow DNA polymerase, and
 ligated into the NheI site of the plasmid pETL (BlueBacII, Invitrogen
 Company) to generate the plasmid pETL-LSIRF. The plasmid was amplified in
 E. coli cells strain DH5-alpha (grown in the presence of ampicillin) using
 standard culturing methods and conditions. Purified plasmid containing the
 LSIRF gene in the proper orientation (as determined by restriction
 endonuclease mapping with EcoRI, HindIII, or PvuII digestion) was
 co-transfected into Sf9 insect cells (available from the American Type
 Culture Collection, 12301 Parklawn Drive, Rockville, Md USA) together with
 linearized baculovirus genomic DNA (Invitrogen Corp., San Diego, Calif.,
 USA), and the cells were incubated for about 48 hours at about 28.degree.
 C. in Grace's medium supplemented with yeastolate, lactalbumin
 hydrolysate, and 10 percent fetal calf serum.
 After incubation, the cells were harvested and plaque assays were performed
 (Richardson, ed., Meth. Mol. Biol., vol 39: Baculovirus Expression
 Protocols, Humana Press, Totowa, N.J. [1995]) in the presence of Bluo-gal
 (Gibco-BRL, Grand Island, N.Y., USA) in order to isolate recombinant
 virus. Blue recombinant plaques were selected after 5-7 days of culturing
 and the plaques were amplified in 24 well microtiter plates containing Sf9
 cells. Further amplification of recombinant virus was performed by
 large-scale cell culturing in tissue culture flasks until a titer of about
 10.sup.8 pfu/ml was obtained. Expression of LSIRF was verified by
 infecting Sf9 cells at a multiplicity of infection of about 1 pfu/cell and
 harvesting cells at 0, 24, 48, 72, and 96 hours post-infection. Cell
 lysates were then prepared by solubilization in SDS-PAGE sample buffer
 (100 mM DTT, 80 mM Tris-HCl, pH 6.8, 10 percent glycerol, 0.0012 percent
 bromophenol blue) and were analyzed by Western blot analysis.
 Protein extracts from both Sf9 cells and mouse peripheral lymphocytes were
 analyzed for the presence of LSIRF polypeptide. Lymphocytes were prepared
 from lymph nodes excised from mice by passing the lymph node tissue
 through a fine mesh screen. The lymphocytes were maintained in Iscove's
 medium supplemented with 10 percent fetal calf serum. Protein extracts
 from the Sf9 and lymphocyte cells were prepared using the manufacturer's
 protocol for Sf9 cells (Pharmingen, San Diego, Calif.) or methods set
 forth in Sambrook et al., (Molecular Cloning: A Laboratory Manual, Cold
 Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. [1989]; for
 lymphocyte cells). The proteins were resolved on an 8 percent
 polyacrylamide/0.1 percent SDS gel and the gel was transferred to
 Immobilon-P membrane (millipore Company) using standard procedures. The
 blot was first incubated with blocking buffer (4 percent skim milk and
 0.05 percent Tween-20 in 1.times.PBS) for 1 hour at room temperature.
 LSIRF rabbit polyclonal antisera raised against a LSIRF carboxy-terminus
 peptide was then added to the blot at dilution of about 1:2000 (in a
 solution of 1 part blocking buffer to 1 part PBS). The LSIRF peptide
 injected into the rabbit to generate antibody was:
 GYELPHEVTTPDYHR (SEQ ID NO.:9)
 After incubation with LSIRF antibody for about 1 hour, the blot was washed
 and the LSIRF antibody was detected with goat anti-rabbit horseradish
 peroxidase-conjugated antibody at a dilution of about 1:5000.
 The results indicate that an approximately 51 kD band (the predicted
 molecular weight of LSIRF) was recognized by anti LSIRF antibody for both
 peripheral T cells stimulated with anti-CD3 antibodies and recombinant Sf9
 cells.
 Example 4
 Mouse LSIRF Expression Analysis
 A. Tissue Blots
 To assess the tissue specificity of LSIRF transcripts, total RNA was
 prepared from mouse brain, lung, thymus, bone marrow, spleen, liver,
 intestine, pancreas, salivary gland, testis, heart and smooth muscle
 tissue using methods described by Wangm et al. (EMBO J., 10:2437-2450
 [1991]). The RNAs were electrophoresed through a 1 percent
 agarose/formaldehyde gel using standard procedures and then transferred to
 nitrocellulose paper as described in Sambrook et al., supra. The blots
 were then hybridized with a random-primed .sup.32 P labeled 1.4 kb cDNA
 containing the entire coding region of LSIRF (the insert from PV-1) and
 subsequently washed as described by Stewart et al. (Meth. Mol. Cell Biol.,
 1:73-76 [1989]) at about 50.degree. C. in 0.2.times.SSC and 0.1 percent
 SDS.
 The results as shown in FIG. 5 indicate that a LSIRF transcript of about
 5.5 kb is present largely in spleen and bone marrow tissue with weaker
 transcripts of the same size in thymus and lung tissues. Surprisingly, no
 additional bands were observed. In addition, FIG. 6 indicates that lymph
 node tissue also contains LSIRF transcripts.
 Various T cell lines including CTLL-2, D10.G4.1, HT-2, EL-4, and BW5147
 (all cells available from the American Type Culture Collection, 12301
 Parklawn Drive, Rockville, Md., USA) were evaluated for LSIRF expression
 using Northern blot analysis. RNA was extracted from these cell lines
 using the method of Chomczynski et al. (Anal. Biochem., 162:156-159
 [1987]). The cell lines were maintained at 37.degree. C. and 5 percent
 CO.sub.2 in Iscove's medium supplemented with 10 percent fetal calf serum
 and 2 mM L-glutamine. The first three cell lines are believed to be
 peripheral T cell lineages, while the last two are believed to be immature
 T cell lineages. Cultures of HT-2 and CTLL-2 cells were supplemented with
 50 U/ml of IL-2 (Genzyme Inc., Cambridge, Mass) and 50 .mu.M
 2-mercaptoethanol; cultures of D10.G4.1 were supplemented with 50 U/ml of
 IL-1 (Genzyme Inc., Cambridge, Mass.), 50 U/ml of IL-2, and 50 mM
 2-mercaptoethanol.
 Northern blots were prepared from total RNA, transferred to Hybond N paper,
 and probed with the 1.4 kb random primed cDNA as described above using the
 Stewart et al., supra methods.
 The results indicate that LSIRF transcripts are visible only in the
 peripheral T cell lines, suggesting that LSIRF is preferentially expressed
 in mature T cells. Similar analyses of mRNA transcripts in the pre-B cell
 line CB17.51, the B cell line WEHI231 (American Type Culture Collection),
 and plasmacytoma cell line J558 (American Type Culture Collection) show
 the presence of the transcript in all cell lines, with J558 having the
 strongest signal.
 The induction of LSIRF in primary lymphocytes obtained from spleen or lymph
 nodes was evaluated by adding various stimulators to the cultured cells
 and assessing the LSIRF mRNA levels. The stimulants used for lymph node
 cells were 1000 U/ml murine interferon-beta (IFN-beta; Lee Biomolecular
 Research, San Diego, Calif.), 100 U/ml murine interferon-gamma (IFN-gamma;
 Genzyme Inc., Cambridge, Mass.), or 10 ng/ml murine tumor necrosis factor
 (TNF; Genzyme Inc.). Splenocyte cells were treated with 20 .mu.g/ml
 anti-IgM antibodies, 10 .mu.g/ml lipopolysaccharide (LPS; a bacterial
 endotoxin), 10 ng/ml PMA (phorbol myristate acetate; Sigma Chemical Co.,
 St. Louis, Mo.), 1 mg/ml cyclosporin A (CsA; Sandoz Company, Basel,
 Switzerland), 10 .mu.g/ml of Concanavalin A (ConA; Sigma), or 1 or 10
 .mu.g/ml cycloheximide (CHX; Sigma). All cells were treated for 6 hours at
 37.degree. C.
 The results are shown in FIGS. 6, 7, and 8. In all Figures, beta actin is
 shown as an indicator of the quantity of total RNA analyzed.
 FIG. 6 shows that anti-CD3 antibodies did induce LSIRF transcription. Most
 surprisingly however, the interferons did not induce LSIRF transcripts.
 This is in stark contrast to other known IRFs, as transcripts of both of
 other known IRFs are induced by interferons.
 FIG. 7 shows that cycloheximide, a protein synthesis inhibitor, induces
 LSIRF transcription. This result was not expected, since cycloheximide
 does not induce transcription of the IRF-1 or IRF-2 genes.
 FIG. 8 shows that anti-IgM and PMA induce LSIRF transcripts. Such induction
 by anti-IgM was surprising, as it indicates that LSIRF is expressed in B
 cells as well as in T cells.
 B. Gel Shift Assay
 An electrophoretic mobility shift assay was conducted to assess whether the
 LSIRF polypeptide is a DNA binding protein. Nuclear extracts from control
 Sf9 cells (transfected with wild type baculovirus only) and LSIRF
 expressing Sf9 (transfected with baculovirus containing the LSIRF cDNA)
 cells were prepared as follows. The Sf9 cells were pelleted and were then
 washed twice in PBS. After the final wash, the cells were resuspended in
 0.5 ml of "H-buffer" (hypotonic buffer) per 107 cells (H-buffer consists
 of: 25 mM Hepes-NaOH, pH 8.0, 10 mM KCl, 5 mM M.sub.g Cl.sub.2, 0.5 mM
 EDTA, and 0.5 mM DTT) and were incubated on ice for about 30 min during
 which time the cells swelled due to the hypotonic buffer. The cells were
 then disrupted with 15 strokes of a type B pestle in a dounce homogenizer.
 The nuclei were isolated from the cell debris by pelleting at about
 4.degree. C. in a microfuge at 10 K rpm for about 10 min. The pellets,
 which contained the majority of nuclei, were then extracted by
 resuspending in 0.5 ml of N-buffer per 10.sup.7 cells (N-buffer consists
 of: 25 mM Hepes-NaOH pH 8.0, 400 mM KCl, 5 mM M.sub.g Cl.sub.2, 0.5 mM
 EDTA, 10 percent glycerol, and 0.5 mM DTT) and incubating on ice for about
 20 minutes. The suspension was then centrifuged at 4.degree. C. in a
 microfuge at 15K rpm for about 15 minutes. The supernatant, which
 contained the majority of LSIRF polypeptide, was buffer exchanged to
 remove excess salt using a Centricon 10 microconcentrator (Amicon
 Corporation). The diluting buffer for concentration was E-buffer (25 mM
 Hepes-NaOH, pH 8.0, 50 mM KCl, 5 mM M.sub.g Cl.sub.2, 0.5 mM EDTA, 15
 percent glycerol, and 0.5 mM DTT). H-buffer, N-buffer, and E-buffer all
 contained the following protease inhibitors: 0.5 mM PMSF, 0.5 .mu.g/ml
 leupeptin, and 0.5 .mu.g/ml aprotinin).
 To assess electrophoretic mobility of a particular DNA fragment due to
 LSIRF binding of the fragment,the extracts were incubated with a double
 stranded .sup.32 P-labeled DNA probe. The sequence of the sense strand of
 this probe, a wild-type murine MHC IRSE binding sequence, is set forth
 below:
 TGCAGAAGTGAAACTGAGG (SEQ ID NO: 10)
 For the binding reaction, about 25.times.10.sup.3 cpm (corresponding to
 about 1.times.10.sup.-11 moles of the probe) was prepared in binding
 reaction buffer (12 mM Hepes-KOH, pH 7.9, 30 mM KCl, 60 .mu.M EGTA, 0.3 mM
 DTT, 2.5 percent Ficoll, 0.6 .mu.g poly(dI-dC) [obtained from Pharmacia],
 and 0.05 percent NP-40). The nuclear extracts were prepared by diluting
 approximately 8-fold in E-buffer containing about 0.1 mg/ml of BSA (bovine
 serum albumin) to a final concentration of about 14 .mu.g total protein/ml
 for the LSIRF containing reactions, and about 22 .mu.g/ml for the control
 reactions. The binding reaction was started by adding about 1 .mu.l of the
 nuclear extract to about 6.24 .mu.l of probe solution, which, in some
 cases, also contained unlabeled "competitor" DNA fragments. The sequence
 of each of these fragments is set forth below in Table 1. The competitor
 fragments were added at an approximately 750 fold molar excess (as
 compared to the labeled fragment). The nuclear extract/probe solution was
 incubated at about 23.degree. C. for about 20 minutes and was then loaded
 on to a 9 percent polyacrylamide gel (prepared with 0.25.times.TBE) that
 had been pre-run at about 250 volts for about 2 hours before sample
 application. The gel was run for about two hours at about 300 volts to
 separate protein-DNA complexes from the unbound DNA probe. The gel was
 then dried and exposed to film to assess DNA probe migration shift due to
 protein binding.
 TABLE 1
 FRAGMENT SEQUENCE
 mMHC ISRE wt TGCAGAAGTGAAACTGAG (SEQ ID NO:11)
 mISRE mt1 TGCAGAAGTGAAACCTGG (SEQ ID NO:12)
 mISRE mt2 TGCAGAAGTGAACATGAG (SEQ ID NO:13)
 mISRE mt3 TGCAGAAGTGGTCCTGAG (SEQ ID NO:14)
 mISRE mt4 GCTAGAAGTGAAACTGAG (SEQ ID NO:15)
 mIg.lambda. B AAAGGAAGTGAAACCAAG (SEQ ID NO:16)
 mIgkappa E3' TGAGGAACTGAAAACAGA (SEQ ID NO:17)
 hISG54 ISRE GGGAAAGTGAAACTAG (SEQ ID NO:18)
 In Table 1, "m" indicates mouse sequence, and "h" indicates human sequence.
 The results are shown in FIG. 9. As can be seen, the wild type MHC ISRE
 sequence binds LSIRF protein. In addition, two ISRE DNA fragment mutants,
 m1 and m4, compete well for binding as do two other DNA fragments, Ig
 lambda B and ISG54.
 Example 5
 Human LSIRF Cloning
 To identify the human cDNA encoding LSIRF, a human lymphocyte cDNA library
 (Clontech, Palo Alto, Calif.; catalog number HL 1031a) was screened using
 the mouse PV-1 clone. Screening conditions were overnight at 65.degree. C.
 in Church buffer (Church and Gilbert, Proc. Natl. Acad. Sci. USA,
 81:1991-1995 [1984]). The filters were washed twice for about 30 minutes
 each in 2.times.SSC and 0.1 percent SDS. Of about one million plaques
 screened, two positive clones were identified, isolated, and the DNA was
 purified using standard techniques. The clones were subcloned into the
 EcoRI site of pBluescript (Stratagene, Lajolla, Calif.). The longest of
 these clones, termed H14, which was greater than about 2 kb, was
 sequenced. The seqeuence indicated that this clone was a hybrid of the TNF
 (tumor necrosis factor) receptor p55 (about 400 base pairs) and about 1 kb
 of sequence that was highly homologous to exons 3-9 of mouse LSIRF
 sequence. In addition, this clone had a conserved stop codon, a splice
 donor sequence, and about 600 base pairs of intron 9. It was thus
 concluded that this 1019 base pair seqeuence represented a portion of
 human LSIRF sequence. This 1019 base pair sequence was amplified by PCR
 using the following primers:
 CTGGACATCTCAGACCCGTACAAAGTG (SEQ ID NO: 19)
 CTTGACATTTTTCATTCTTGAATAGAG (SEQ ID NO: 20)
 Amplification conditions were 94.degree. C. for 30 seconds, 65.degree. C.
 for 30 seconds, and 72C. for about 90 seconds. About 500 ng of H14
 template was used in the presence of Taq polymerase, and about 15 cycles
 of PCR were conducted. The resulting PCR product was ligated directly into
 the TA cloning kit vector PCRII (Invitrogen, San Diego, Calif.) and
 sequenced to verify that the proper fragment had been amplified. This 1019
 base pair cDNA fragment, termed "FISH", was then used to screen a human
 leukocyte 5'-stretch cDNA library (Clontech; catalog number HL 1169x). The
 screening conditions were: about 65.degree. C. overnight in Church buffer,
 followed by rinsing twice for about 30 minutes in 2.times.SSC and 0.1
 percent SDS, and then twice in 0.2.times.SSC and 0.1 percent SDS for about
 30 minutes. One plaque of about 500,000 was identified, and the DNA
 purified and sequenced. This clone, termed HIRF4.lambda.DR2, contained
 intron 2 and full length exon 3 (only a portion of exon 3 was found in the
 H14 clone), as well as exons 5, 7, 8 and intron 8. Exons 4 and 6 were
 presumably spliced out or missing.
 To obtain the remainder of the LSIRF coding sequence, two approaches were
 employed. First, a human placental genomic library in the vector lambda
 fix 2 (Stratagene, LaJolla, Calif.) was screened using the FISH cDNA as a
 probe. Screening conditions were about 65.degree. C. overnight in Church
 buffer, followed by rinsing twice for about 30 minutes in 2.times.SSC and
 0.1 percent SDS, and then twice in 0.2.times.SSC and 0.1 percent SDS for
 about 30 minutes. Ten phage clones were isolated, and the DNA was purified
 from one clone, termed HG-1. This DNA was digested with restriction
 endonucleases Bam HI, Sac I, and xba I and the fragments were subcloned
 into the cloning vector pMOB (Strathmann et al., Proc. Natl. Acad. Sci.
 USA, 88:1247-1250 [1991]). The sequence of each fragment was obtained and
 compared with the mouse LSIRF sequence. The promoter, exon I, and exon II
 of human LSIRF were identified in this clone based on homology to the
 mouse sequence.
 The second approach used was a RACE reaction using the Clontech
 Marathon.RTM. kit and following the manufacturer's protocol. A B-cell
 lymphoma line called OCILY8 (see Blood, 69:1307-1314 [1987]) which had
 been shown by previous Northern blot analysis to have high LSIRF
 expression was used. The resulting RACE product was sequenced and was
 found to match the genomic sequence of exons one and two (obtained as
 described above).
 To produce an open reading frame the FISH cDNA was excised from the EcoRI
 site of the vector PCRII and ligated into the EcoRI site of PGEX4T3
 (Promega, Madison, Wis.) to form the vector pGEX4T3-FISH. To obtain the 5'
 end of the open reading frame in a form that would permit it to be fused
 to the FISH clone, human spleen Marathon.RTM. (Clontech, catalog no.
 7412-1) ready cDNA was used with the following two primers for
 amplification:
 TGCCCTCAGCTCCGAGTCCAG (SEQ. ID. NO.: 21)
 AACCATTTTCACAAGCTG (SEQ. ID. NO.: 22)
 Amplification was accomplished using PCR under the following conditions:
 94.degree. C. for 30 seconds, 64.degree. C. for 30 seconds, and 68.degree.
 C. for one minute. Thirty cycles were performed using Expand High Fidelity
 Polymerase (Boehringer Manheim). Using this procedure, the sequence of the
 N-terminus of the LSIRF was amplified giving an expected DNA fragment size
 of approximately 600 base pairs.
 The approximately 600 base pair fragment was re amplified by PCR using SEQ.
 ID. NO.: 22 (set forth above) and SEQ ID NO.: 23 as set forth below:
 GGATCCGGATCCATGAACTGGAGGGCGGCGGCCGAGGC (SEQ. ID. NO: 23)
 Fifteen cycles of PCR were conducted as follows: 94.degree. C. for 30
 seconds, 64.degree. C. for 30 seconds, and 72.degree. C. for 90 seconds
 using native PFU polymerase (Stratagene, LaJolla, Calif.).
 The PGEX4T3 vector containing the FISH insert (pGEX4T3-FISH) was digested
 with both BamHI and Sac II, thereby removing the 5' portion of the FISH
 insert. The approximately 600 base pair PCR product from above was
 digested with the same enzymes and ligated into the pGEX4T3-FISH vector to
 form the full length open reading frame construct pGEX4T3 LSIRF Bam
 HI/EcoRI, the coding region of which is set forth in FIG. 10. The
 predicted amino acid sequence is set forth in FIG. 11. This clone was
 evaluated by production of a GST fusion protein (Pharmacia) following the
 manufacturer's protocol. The predicted size of the fusion protein was
 about 79 kD, of which about 27 kD is GST protein, and about 52 kD is LSIRF
 protein. The fusion protein migrated on 8 percent SDS-PAGE to the expected
 size of about 79 kD as determined by Coomassie blue staining.
 Northern blot analysis of human LSIRF indicated that this gene is expressed
 primarily in spleen tissue and peripheral blood tissue, with a lower level
 seen in colon and intestinal tissue. In addition, using a multiple cancer
 cell line Northern blot obtained from Clontech (catalog no. 7757-1), weak
 expression of the gene was seen in the human B cell Burkitt's lymphoma
 line Raji, and strong expression was observed in the human melanoma line
 G361 cancer line.
 Based on DNA sequencing of several clones containing partial hLSIRF
 sequence, it is thought that two forms of the hLSIRF sequence exist. One
 form, the "Single Q" form, contains the "CAG" codon at bases 490-492,
 which codes for amino acid Q (Gln) at amino acid position 164. A second
 form of LSIRF DNA, the "Double Q" form, contains an additional "CAG" codon
 between bases 492 and 493 of the "Single Q" form, resulting in an
 additional amino acid Q (Gln) between amino acids 163 and 164 of the
 "Single Q" form. Aside from this one difference, the amino acid and
 nucleic acid sequences of the two forms are identical.
 The full length "Single Q" DNA sequence encoding human LSIRF (hLSIRF) in
 the vector pGEX4T3 was deposited with the ATCC as accession number 98016
 on Mar. 27, 1996. In addition, the full length human LSIRF sequence
 encoding the "Double Q" form of the hLSIRF protein was deposited with the
 ATCC on Mar. 27, 1996 as accession number 98017.
 SEQUENCE LISTING
 (1) GENERAL INFORMATION:
 (iii) NUMBER OF SEQUENCES: 25
 (2) INFORMATION FOR SEQ ID NO: 1:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 1353 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1
 ATGAACTTGG AGACGGGCAG CCGGGGCTCA GAGTTCGGCA TGAGCGCAGT GAGCTGCGGC 60
 AATGGGAAAC TCCGACAGTG GTTGATCGAC CAGATCGACA GCGGCAAGTA CCCCGGGCTG 120
 GTGTGGGAGA ACGAGGAGAA GAGCGTCTTC CGCATCCCGT GGAAACACGC GGGCAAGCAG 180
 GACTACAATC GTGAGGAGGA CGCTGCCCTC TTCAAGGCTT GGGCATTGTT TAAAGGCAAG 240
 TTCCGAGAAG GGATCGACAA GCCAGATCCT CCTACTTGGA AGACAAGATT ACGATGTGCT 300
 CTGAACAAGA GCAATGACTT TGAGGAATTG GTCGAGAGGA GCCAGCTGGA TATCTCTGAC 360
 CCATACAAGG TGTACAGGAT TGTTCCAGAG GGAGCCAAAA AAGGAGCAAA GCAGCTCACT 420
 TTGGATGACA CACAGATGGC CATGGGCCAC CCCTACCCCA TGACAGCACC TTATGGCTCT 480
 CTGCCAGCCC AGCAGGTTCA TAACTACATG ATGCCACCCC ATGACAGGAG CTGGAGGGAT 540
 TATGCCCCTG ACCAGTCACA CCCAGAAATC CCATATCAAT GTCCTGTGAC GTTTGGCCCA 600
 CGAGGCCACC ACTGGCAAGG CCCATCTTGT GAAAATGGTT GCCAGGTGAC AGGAACCTTT 660
 TATGCTTGTG CCCCACCTGA GTCCCAGGCT CCTGGAATCC CCATTGAGCC AAGCATAAGG 720
 TCTGCTGAAG CCTTGGCGCT CTCAGACTGC CGGCTGCATA TCTGCCTGTA TTACCGGGAC 780
 ATCCTCGTGA AAGAGCTGAC CACGACGAGC CCTGAAGGCT GCCGGATCTC CCACGGACAC 840
 ACCTATGATG TTAGCAACCT GGACCAGGTC CTGTTTCCCT ACCCGGACGA CAATGGACAG 900
 AGGAAGAACA TTGAGAAGTT GCTGAGCCAC CTGGAGAGGG GACTGGTCCT CTGGATGGCT 960
 CCAGATGGGC TTTATGCCAA AAGACTCTGC CAGAGTAGGA TCTACTGGGA TGGGCCCCTG 1020
 GCACTGTGCA GCGATCGGCC CAACAAGCTA GAAAGAGACC AGACTTGCAA GCTCTTTGAC 1080
 ACACAGCAGT TTCTATCAGA GCTGCAAGTG TTTGCTCACC ATGGCCGGCC AGCACCGAGA 1140
 TTCCAGGTGA CTCTGTGCTT TGGTGAGGAG TTTCCAGACC CTCAGAGACA GAGGAAGCTC 1200
 ATCACAGCTC ATGTGGAACC TCTGCTAGCC AGACAACTGT ATTACTTTGC TCAACAAAAC 1260
 ACTGGACATT TCCTGAGGGG CTACGAGTTA CCTGAACACG TTACCACTCC AGATTACCAC 1320
 CGCTCCCTCC GTCATTCTTC CATCCAAGAG TGA 1353
 (2) INFORMATION FOR SEQ ID NO: 2:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 450 amino acids
 (B) TYPE: amino acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: protein
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2
 Met Asn Leu Glu Thr Gly Ser Arg Gly Ser Glu Phe Gly Met Ser Ala
 1 5 10 15
 Val Ser Cys Gly Asn Gly Lys Leu Arg Gln Trp Leu Ile Asp Gln Ile
 20 25 30
 Asp Ser Gly Lys Tyr Pro Gly Leu Val Trp Glu Asn Glu Glu Lys Ser
 35 40 45
 Val Phe Arg Ile Pro Trp Lys His Ala Gly Lys Gln Asp Tyr Asn Arg
 50 55 60
 Glu Glu Asp Ala Ala Leu Phe Lys Ala Trp Ala Leu Phe Lys Gly Lys
 65 70 75 80
 Phe Arg Glu Gly Ile Asp Lys Pro Asp Pro Pro Thr Trp Lys Thr Arg
 85 90 95
 Leu Arg Cys Ala Leu Asn Lys Ser Asn Asp Phe Glu Glu Leu Val Glu
 100 105 110
 Arg Ser Gln Leu Asp Ile Ser Asp Pro Tyr Lys Val Tyr Arg Ile Val
 115 120 125
 Pro Glu Gly Ala Lys Lys Gly Ala Lys Gln Leu Thr Leu Asp Asp Thr
 130 135 140
 Gln Met Ala Met Gly His Pro Tyr Pro Met Thr Ala Pro Tyr Gly Ser
 145 150 155 160
 Leu Pro Ala Gln Gln Val His Asn Tyr Met Met Pro Pro His Asp Arg
 165 170 175
 Ser Trp Arg Asp Tyr Ala Pro Asp Gln Ser His Pro Glu Ile Pro Tyr
 180 185 190
 Gln Cys Pro Val Thr Phe Gly Pro Arg Gly His His Trp Gln Gly Pro
 195 200 205
 Ser Cys Glu Asn Gly Cys Gln Val Thr Gly Thr Phe Tyr Ala Cys Ala
 210 215 220
 Pro Pro Glu Ser Gln Ala Pro Gly Ile Pro Ile Glu Pro Ser Ile Arg
 225 230 235 240
 Ser Ala Glu Ala Leu Ala Leu Ser Asp Cys Arg Leu His Ile Cys Leu
 245 250 255
 Tyr Tyr Arg Asp Ile Leu Val Lys Glu Leu Thr Thr Thr Ser Pro Glu
 260 265 270
 Gly Cys Arg Ile Ser His Gly His Thr Tyr Asp Val Ser Asn Leu Asp
 275 280 285
 Gln Val Leu Phe Pro Tyr Pro Asp Asp Asn Gly Gln Arg Lys Asn Ile
 290 295 300
 Glu Lys Leu Leu Ser His Leu Glu Arg Gly Leu Val Leu Trp Met Ala
 305 310 315 320
 Pro Asp Gly Leu Tyr Ala Lys Arg Leu Cys Gln Ser Arg Ile Tyr Trp
 325 330 335
 Asp Gly Pro Leu Ala Leu Cys Ser Asp Arg Pro Asn Lys Leu Glu Arg
 340 345 350
 Asp Gln Thr Cys Lys Leu Phe Asp Thr Gln Gln Phe Leu Ser Glu Leu
 355 360 365
 Gln Val Phe Ala His His Gly Arg Pro Ala Pro Arg Phe Gln Val Thr
 370 375 380
 Leu Cys Phe Gly Glu Glu Phe Pro Asp Pro Gln Arg Gln Arg Lys Leu
 385 390 395 400
 Ile Thr Ala His Val Glu Pro Leu Leu Ala Arg Gln Leu Tyr Tyr Phe
 405 410 415
 Ala Gln Gln Asn Thr Gly His Phe Leu Arg Gly Tyr Glu Leu Pro Glu
 420 425 430
 His Val Thr Thr Pro Asp Tyr His Arg Ser Leu Arg His Ser Ser Ile
 435 440 445
 Gln Glu
 450
 (2) INFORMATION FOR SEQ ID NO: 3:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 2139 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3
 AAGGGGCCAC CTGGCCATTC CTTCCTCTCC ACCAGCAACA ATGGGAGCAT GTGATTCACA 60
 AGGGAATCAC ATTCAACTAA AAAGAGAAAC CGGGGTATGC TGTTTGCAAG GAACGGTTGA 120
 AACTGGAACT CAATATGTCG TGTGGTGTGA AATAAACGTG TGTCTCACAT GTTTTCCCAT 180
 GCTGGGGGCA GGGGTAAGAA AGTAAAAGGC AGACTGGTTA AAGACATGGG GTGGGGAGGG 240
 CTGGAGGGAC GAGTGGTAAG AAATGGCGAC AGAGGAGATG AAGGTAATGT CATAATGAAA 300
 CCCATCACTG CTGTGTGCAA CTAATAGATG CTAATAAAAT AGGAAGTTTT AATGATTTAG 360
 GTAGCTTATT GCTTGCATTC ACCTCACTGT TAAACTATCA CTTCTGGGGG ATCCACACAA 420
 CGAGCGAGCG AGTAAACCAG AAGATGGCGT TGGAAGATTA GTAATCATAT CTTTTAAACA 480
 AGATAACCAT GTGAAGTCTC AAAAGGTTTC TTGTAATGAC TGTTGTTTAA ACTTCTGAAA 540
 ACAGAGGATG TAGATTGGCT GAGGAAAATG TTGAAACCGC CTAAGTCAAG GTAGAAGACA 600
 CGTGTGTCTA AGTGAAAAAA AGAAAAAAGA AAAAAAAAAA AACCAAAAAC CTCGGGTTGG 660
 CTGCTTCTGT CCTTAGTCTG TGCACGCTTT GAAGAAATGT AATTCCTCAG CAGCAAGGCT 720
 GTGCTATCTG AAGCTACAAT CTCTGCTTTG CTCCGAGGTG TGTCTCTGGT GACCGGGATA 780
 GTTCCCGACA GACAGAAGGT GTTCAAAGAA TATTTTTGAA TGAATGAAAC CCCAAAGGAA 840
 GAAGAGGGGA AAATGGGTGT GACCAAAATT TTCTTTGAAC GAAACTCTGT TGTTTACTAC 900
 CAGGGCTCTG ACAATGGAAA ACTAATTGGG GTGAAAGAAC GACATGGCAT CCTGTTAATT 960
 TCTGAGAAAG CCTGTTGATG TTAGGAAAAA AAAACATGCC GGTGGGCATC TCTGCACCAG 1020
 TTTTCCTGTG GCCAAAATCA GATGTTTCTC CTAAAGTCCA GAACCCAGGA TGGAAGATTA 1080
 AAAGAAAAAC TGAGAAACAT GTGAAATGAA AAAGTTGTCA AAAGCTTTAC AAACGCTCCA 1140
 AGTTGACCTG TGGTGGTGGT AATCTAAAAT GATACAGAAA CTGGTAGTCT GCTTGCTTAC 1200
 CTGAAAACAC CAAGATAACA TATAAGCTCC AGGCATCCAA GCTGAGCTGG AGAAAGTCAG 1260
 CGGCAAAAGC TCATGGAGTT TACATATGAA GGTCAAAGAA AACACGAAAA TAAAGTAAAA 1320
 CCTTCAGTCA GCCTAGCTGT TCTATTTGGG GCATTGGTAC CTCACCGCCA ACTGCCTCCC 1380
 ACGAGGCTGA GGTTAAAATT ATCATTTTAA GGTGAATTGA CATCCGGAAG CGCGCTAACT 1440
 ACCTGAGTAC TCAGGGATCC CCCATCTCTT TTATGTTGCC ATGATTGAAA CTTTGGGGAC 1500
 TGTGCTTGTC TGAGTCATCT CAATTCGTCG GTTTCATTCA CCCAACATGT ATAAGCGTTT 1560
 CAAACACAGT ATTTGGGCCA CGGCTTATAA ACTTGCCTTT CTATTTTTCT TTTTAGTGAG 1620
 CGTGATATTC TCTAAACGCT CAGAGAGACA AGACTCCGCT TTGTTCAGGA TGCTCCCGAC 1680
 CTCTCTCAGT CTATCTCTTC TGTTACATCT GTGAGAACAA GTTCCCTGTG CTCCAGACTC 1740
 TCCATCACTT CCCACCTGTC GATGAGCAGT TAGTAGTTAT CAGCTATGCT CAGTGCAGAT 1800
 TCCAGTATCC CCTTTGTATG CCTCCACCTT CCACAGGAGG GGGGCCATAC CGACTTGTCC 1860
 CATCCGGTTG AGGATTTCTG AGTACATCAG AGTCCCCAGC CCCCTCCACA GGAGGAGCTG 1920
 AAGAAAGCCA GGGTTTGTCT GAAGTGGGAC AGCCCTTGAC CCGGTGGGCT CTAGTCCGAA 1980
 GCTCCTGTTC CTGCGGGACA CCCAGGCACA AGGCAGAGGT GGGGGGCGGT CCTGGGTATG 2040
 GCCAACCCAC GCCCTCTCAA GGCGGGGCCG AAGCGCCCGC CCTGCACTCC GCCTCCGGCT 2100
 CTATAAAGTT CCTCTTTCTC ACCTCACTTT CCTAGTTTC 2139
 (2) INFORMATION FOR SEQ ID NO: 4:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 12537 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4
 ACCACTTGAA CTTGGGACCC TTTGCTGCCC TCAGCTAAGA GTGCGGGTGA GGTAAGGCCT 60
 GTAGTCGGGC AGAAGGAGGA GTGTGAGGCT GGTGGCAGAG GAAGCCTGGC TTCCATCTCT 120
 GAGCCTGAGG GAGAATGCTG AGATAGCGGA CCCAGGCTCC GCTCATCTAC GCTGCCCTAG 180
 GACCTGTGCA CTTCGGGTTT TGTATGAAGC TGTTTGGGTG GGAGTTCCAG AACATCCCCC 240
 ACGGGCTGGG CGGGACGAGC TAATGGGACT GTGGTGTCAT CAAAGGATCG CACTGGCCAC 300
 AGCTTGTCCT CAGAGGGACA GCCTCTGACT CTCTCTGCTC CAGTGGAAAG CTCCTTTCCA 360
 GCCCTGGTTC CTAAAGGACC CAAACTCATC TAGGGCTCCA GAGCGTGATT CCTAGGCCGG 420
 GCAGCCAAGA AGAGCTGAGA GCTCCAAACT TAGGGTGCTC AGAGCCCCTT TCCCCGCATG 480
 CCCCTTCTTC ACTTCTCTGG CAAGAGTGCT AGTGTTGCTG TCCGCAGCAC CCCTTATTCC 540
 CAGCCTCGGC TTCATTCCTG CCAGGGTTCG CGCTGACATT CTGCAGGTTG GAATCTCCTG 600
 TTTCTTGGCT GCGCTGCTTG CCCCATAACC AGACTTCCAC TTGTTGCTTC CAGGACCCAC 660
 GTGATGGTCT CTGGTTGGGT AGGCCTGGGG TTATTCCGAG GACAAAGTAA GGGTGTCATA 720
 GAAGAAAGTC AAGAGAGTAA GCTAGGTMCC CCAAACCTGC ATGGCAGGGA CACAGGACCT 780
 GGACAAGGGC TAGTCCATGT GCCAGGTCCT TTTCGCCTGG GGCAGCCAGG GCAACCTAAA 840
 CCCAGGAAGG GGCAAGTGTA GAAACAGTGA GGGAAAAGTG GGATGAAAGC TACTTGGATC 900
 CAGCACAGAG GGACGAGTGA CCAAAGTGAG CGCCCCAGCG TGGCGCAAGA CTTGGGATCT 960
 GCAGAGAAGC TGTGTAGCTA GGAGCTTTCA ACGGAGCGTG TTAATGTAAA TGTAAATGAA 1020
 GAAATTACCT AATTTTTTTA ATAAAAGAAA GAACAGACAG GCAAAAAAAA AAAAAGGAGG 1080
 AGGAGGAGGA GGAGGATGGT GCGCGCCAAG GGATGCTCTC TATACCTTCG TCAAAGTACC 1140
 TTCTCTTGGG GGACTTCGGA GACTCTGTCA CTGCACCCGA GCACCTTGTC AGCCTCAGAG 1200
 ACTCGGGGCC TCGTGGGCAC TCCAAGAGTT TGGGACGGGG CTTCCTCCCG CCTCCAAAGT 1260
 GATACGAAGG TAGTTGCAGG GAATGTGTGT CTCTCCTCAG CGCACAAGCC CAGGAGGAGG 1320
 TCCCCACGCG TCATGAACTT GGAGACGGGC AGCCGGGGCT CAGAGTTCGG CATGAGCGCA 1380
 GTGAGCTGCG GCAATGGGAA ACTCCGACAG TGGTTGATCG ACCAGATCGA CAGCGGCAAG 1440
 TACCCCGGGC TGGTGTGGGA GAACGAGGAG AAGAGCGTCT TCCGCATCCC GTGGAAACAC 1500
 GCGGGCAAGC AGGACTACAA TCGTGAGGAG GACGCTGCCC TCTTCAAGGT TAGCAGCATT 1560
 CAGGGATCCC TGGGCAGGGG TGGGGGTGGG GATGGGGAAT CTGAAAGCTC TGAATGTCTG 1620
 TGGCTCCCGG GCAAGGGACT AAGAGGTGGG CTCCTGCAAG GAGGAGGCCA GAGCATCAAG 1680
 CATTGGACCC TGCTTAGGCA AAGTCCCCAG GAGAAGGGAA AGAGGTTGCA AACTCTCCGG 1740
 GGATTGCATA CACAAGAAAC CAGGTCCCAA TACTGTTTGT GTGGAGGAAA GAACTTCCAG 1800
 CTTCAGGGGC ATCTCTGGGG GACCGAGGTT CCGTTTGCAT AGCCCATTCG CTGTTTCCTG 1860
 CCACCACCAC CGACTGCTAG GGCCACTCTC TGCTTCCCTG TCTCTCTGTG TTTTGTTATT 1920
 TTTCTGAGTT TCTCTCTCTG GGTTTTGTTT CTTTGATTGG GCACCTCTAC TGTCTGGTTC 1980
 TAGTTCTAGA AGCTGCGATC TCTGATTTTC TTTCTTTGAG TAGCTTTGAC TATTCCGAGT 2040
 CTTTCTCTGG TATCCCCCTC CGACCCCGTG TGAGTCCCTT AGGACTGATG TCCCCAGAGA 2100
 ACTGGCTCAC TGAACTGTGA AGCCCCCAGC CTCCACCTGC CAGCAGGCCG AGGAAGGGGA 2160
 CTTCCTGCGG GAATTTGTTC AAAGTACCTC TGTGATTTTG TAGATGTCCT CTCTGGGGCC 2220
 TGCCCCCTCC ACAGCTCTGT CCCCAGTCTT GCCCACACTT GATTCAGGCG CTGGGCGTGT 2280
 ACAGCCCATA CTAGGGGTCT CAGGACCCCA CTAACATCAT GTTCCACATT TCAGGCAACA 2340
 GCAAATTTGA AACAGTAACC TTCCTTGCTG AAATGCAATC CATAGAATTC TTTTGACGCT 2400
 CTGGGCTTGA CTTTTCTTAT CATCGTTCTT AGGCTTGGGC ATTGTTTAAA GGCAAGTTCC 2460
 GAGAAGGGAT CGACAAGCCA GATCCTCCTA CTTGGAAGAC AAGATTACGA TGTGCTCTGA 2520
 ACAAGAGCAA TGACTTTGAG GAATTGGTCG AGAGGAGCCA GCTGGATATC TCTGACCCAT 2580
 ACAAGGTGTA CAGGATTGTT CCAGAGGGAG CCAAAAAAGG TAAGGGGTTT TCCCAGCCCA 2640
 GGTGGCAGGA TAAAGGCATT ATGGCACTCA GAGAGCCCTT CTTCCTAGAG ACAGTCACGT 2700
 CCTACCTCTG CTGTAGGTTA AGCCCAGATG TCCTTTTGCC CATGTCCTCT CTGTTATAAG 2760
 TGACAACCCT GTGGTGTTAG TATAGGATGA CCTGGCAGAC TTTAAGCCCC ATGGGTGTGT 2820
 GGGTTATGCA CTTGAAGGCA TTATTTTCAG TTACTCCATT CAGTTAGGAT CTGGATCAAA 2880
 TTTCCAAACA AAATCTGGAA AATCCATTAA ATGTTTACTT ACCTAATATC CTCTAGTAAG 2940
 CATTTTCAAG AGGAGAAAGC ACATCCCACA CCCCATACAT ATTCACACTT CTTGTAATAA 3000
 AACTGCTAGA GTTTCTGGTT TAACATGGCC TGCTAGGGTG GTTATGAATA TTCAGATCTT 3060
 GAGTTCCCTC TCTTCCAACT AGTCTACCTC AAGCAGTGCT CAGGAATCTG CATTTGGTTC 3120
 CAACCATACA GGATGCCTTA ACTAGGTACC ATCTCACAAC CAGAAACCAC TTGGTGGATC 3180
 ACAGGGATCC TGGGTGGTGT TTCCTTCCCT GGCTGTCACT CACAAGTCAG CAAATGTTTA 3240
 ATCAGTTTAA TGGCAAAGAC AAATATCTCT CTAAGAAATT GCTTGAAAAA CAAACAAACA 3300
 AACAAAACAA AACAAACCTA AAATACCCGA TTGGTTAATA GGGCTATGCA TTCTAAGAAT 3360
 TAAGTGCATA GGTACTTTTA TAAGATTTAA GTCAGTTCCT TGTCTTACTC TGTGTTCTCT 3420
 CTTCCTTTTC CCCAAACACA CAGGAGCAAA GCAGCTCACT TTGGATGACA CACAGATGGC 3480
 CATGGGCCAC CCCTACCCCA TGACAGCACC TTATGGCTCT CTGCCAGCCC AGGTATGTGG 3540
 TAGACTCTTG GTCTTGTGGA AGGCTGGCCC ATGCCCTTTT GACTGGCTCC ACACAGAGAG 3600
 GCAAACACAA ATGAAAAGTG TAGGGCTGAC TTCTTATTTG CTATGGCTAG TACACACGCT 3660
 GAACAAAAAC TTGGTCAGAG AAGGATGTTT CAGTTCCAGT GTGGTGTCAC TGTCCCTGAC 3720
 GCCACAGTTT TGTTGGGGAG TTTGATGTGT CCCACCTGTG GAGAGAGGCT TCCACTGATG 3780
 GTCAGATCTT CTGGGAATCA GACCTTTTGT GGAAGTCAAA GGTTTTGGAA GTAGTACTTT 3840
 ATCATGTGAA ACCGCAGAGC AGCTGACTTC TCTAGGCGTC CCTGATGTGA ATTACAGTAC 3900
 TGTTTTATTC ACTTTGGTGG CTTAAAAAGG GCAGATTTCA CTGCGGTATT CTTGGTGCCG 3960
 TGTTCAGCCA TATGATGAAG CCTTACAAAA ATCACAGCTT TATACAATGT CCTCATTGTG 4020
 CTTTCAGACC CTCTATGGCT GTTTTTTACC TAGTGTGATA GACAGTCCAT GTCACTTTTT 4080
 GGGCAAAATG ACTTGGCTGC TGGACAAAAA AAGGGGTTCC CTGAGGAGTT TGGGTGATAT 4140
 GAAAGGACTC CGACACCCMC TGATGTCTTC CTCTTAGCAA TCCCTGTTCT CTGTCAGCAG 4200
 GTTCATAACT ACATGATGCC ACCCCATGAC AGGAGCTGGA GGGATTATGC CCCTGACCAG 4260
 TCACACCCAG AAATCCCATA TCAATGTCCT GTGACGTTTG GCCCACGAGG CCACCACTGG 4320
 CAAGGCCCAT CTTGTGAAAA TGGTAAGGAT TGTGCCAGGG CAGCAGACAG AAGAACAACC 4380
 TGAGCTCGGG GTGTGGACAG CACCACAGGG CTTTTCCCTA CCATTGAGAT ACCAGAGACA 4440
 CATCATATGA AGCTGCTACT GTTGTTGTTG TTGTTGTTGC TGCTGCTGCT GCTGGGGTGG 4500
 TGGGGTGGTG GGKTGGTGGG GTGGTGGAGT GGTGGTGGTG GTGGTGGTTG TGGGGTGTTG 4560
 GGGTATGTTG CCTTGTCCTG TGAAATGTTG AAGTCCTTAG ATCCATGATA GGCCTCAGTC 4620
 TGTGTGGGGA CTTAACTAGA AGACCCCAGA GATCATTCCA AGTAGCTGAA AAGTGCCCCA 4680
 TTTTTAATAC ATAGAGAAAA ACATGGATGA CAACAAATTC TCAATGACAA GTAATGTCAA 4740
 TTATAAAACT CGTCTATATT TTGTTTTAAC TTGAGTTATC CCTTATTTCC GATGGTGATT 4800
 AAGTTGGGGG GTTTGTTGTA TCCCACCTAT CTCCCTAGTC TGTATCTTTC TACTCTCCTG 4860
 TAAAGTAGAG AGTTGTACCC AGTCCACCTC AGCAGGAAAT CATTGCTAGT TCATGTCTCT 4920
 TGAATAATAA TGAGTCATCT ATAGCTGTTC TTGGTACTAA GGAAGGAAGG ATCAGAGCGA 4980
 AAGTAATCCA CAAAGTGTCT CTACAAATGA GTGCCCTGCC CGAAAAGACC CACAGGGGTC 5040
 CCCCCATGCT AGCTGGGCTC TCACAGAAGA AACGCCCACT AACCAGACAC AAAAAAATTT 5100
 CACAAACTAT GTTCAGTGAG ACTTGGGTCC TTTAGTGTTT ATTTAGGTGA GTGCACCAAG 5160
 CTCCACCTCG GGTCCTTTTT TGGCTGTGTA TTTTAAGGTA GAGTCTTGCT AAATTACCAA 5220
 GGCTAGGATC TTCCTGCCTT CAACTCTTGA GTAGCTGGGA CTACAATCTT GTTCTARCGG 5280
 GCTGAACATA AAACAAGTTT TTAGGACTTR CAAGTTCACT GTTTAAATAT AAGTCTTGAC 5340
 ATGGGTCGCC GTGCGAGTAG TTCTTTTATA TTGTTCTGGC AATACTTTAC CTTGTGACAA 5400
 TTTCATCAAC ACCCTCACTC AGTCTGTGCA TGCTTACACT AATCTTGCTT TAGTGTGACA 5460
 TAACTTCTCT GCTGCCAGAG AACACGGTTC AGCCCCTCCC CCTAGCTAAC AAACAGTGAG 5520
 CAGAATAAAT GAGGGTTGAA TAATTAATTC ATCTTTGAAC TAGTCTTATA GAAGTTTGAA 5580
 CTCTGACCCT GCTGGTAACT TGCTATGTGG GCTGGTGCAA GTCCCTCTCC TTCTGGGCCT 5640
 CAGTTTCCCT ATAGATTTGG AGTGAGCCCC AGGTTTCCAT CCAGAGCTGT ACTGTGGCTC 5700
 CTTCCTTCAT CACCCTAATT TTTATCACTG GATGTGGACT TTGGACTTTG TCCCATAATC 5760
 ACACGTTATT CTGCTAGCAG GTGCTTAGAG GCTGTCAGGC TTGGGTTGGA GGCCATGGCC 5820
 TCTCCCAACT CAAGAGCCTC CCCGCACTCA GACTCGATAC TTAGACATCA TCTGATTTTT 5880
 ATTTKCAAAT GCAGGTTGCC AGGTGACAGG AACCTTTTAT GCTTGTGCCC CACCTGAGTC 5940
 CCAGGCTCCT GGAATCCCCA TTGAGCCAAG CATAAGGTCT GCTGAAGCCT TAGCGCTCTC 6000
 AGGTGAGTGT GGCGCTTCCT GTAAAGCTCC GAGGGAGGGG GCATCTCTCC TCTACTGAGG 6060
 TTGGGTGAGG ATTTAGACTC TCGCCTTGCA GGCCCCGGGG TCTGGAGTAG GCATGGTCCA 6120
 GGCTATGTGG ACATCACGCT GAGTCAAATA CACTATTAGA AATCTCCACA GCAGTACCAG 6180
 CTAGCCAAAT ACTATTTGGA CGATGTCTTT AACCTTCTAC ATCATTACCT GCCCAGTTTT 6240
 CCAGGAATGT GTAACCAGGC TCCTCCTCCA GCCGACATTC TCCATTCTCG CAGTGTGGAA 6300
 AGGCTTTATA GGCACAAAAG AATGCTGTTT GTCCTTTTAG GGTGTAGGGT TGGCCACAAA 6360
 CAGGTGGTCT GAGTTGCTTC CAAGGAACAC TGGTTCTGAA CCCTGGTCTC TGAGAAGTTC 6420
 TTATSCCCCC TAAAGGATCA TATAGGTCTG ACTCCCTCAC AACTTTGACA GAATTGCTGA 6480
 GCATGTGTGG ATGTGATCTG ATTTTAAAGT TCTGTTACTA AGGAAGCCTG CACTTGGAGA 6540
 TACTGACCAG CATTTTAAAA GCCCACACTC CGTGGAAGCA GACATCTTAT GTCCATTTAG 6600
 TCTTTAGATG ATTTTTTTGG ATGTTTTCAA ATGGAATTAT TAGAATTCTC ATCATGCCCT 6660
 CGGCTACCTT AAAAGCCTCT GACTGAAAAC ATCAACTGCA TTTTGACAAT TTTAGACACT 6720
 TCCCTTGTTC TCGAGGGAGG AAGAAGTTTT AAAATCTAGT TCCTTCCAGC TCTGATGCTC 6780
 AGGGAGACTT TGTGAGCCAC TCAAGAACAG CCGAGGAGCA CATCTGGGCA TCAGGGGTTG 6840
 TCACAGACAC TAGAATGCTC TAGATCCTCT TCTGGAGCGC CAAAGACTTG TGTGGGTGCC 6900
 CCAAGAGTAG GAAATAAACA GCTATTTATA TCTCTGCAAT CTTGTGATTT TGGTGACATT 6960
 AAATGAAATG AAACCTGCCC TACCACTCAC CTCAGATGGC CAACGCCCCC TCTCTTTGGG 7020
 TGCACCACTT GTGCTGTTCA TAGCTGCAGC TATCGAAGAC ACCATGATGT GGGCTGTCAG 7080
 AACTTGCCAT TGAAGAATAC GAGGCTTTTG TGGGTTTCTT CTTCTAGTTT GCATAATTAA 7140
 TTATCAACCC TGAGTGCACT TTTCAGAAAG CTATTCTTTC CAGGCATTGT TGGGGCTCCA 7200
 ACCACCAGCA CGGGTATCTA TCTCTGCCTG GGGAGCCCTT TGCACACCCA GCTTGCCCTT 7260
 TCGGCCCGTG GGTGGTATTT TAAAGTGGCT TCTGAAATCA ACAAAATCAT GTGTCAATAA 7320
 ATTCCTGTCT TAAAGCTGTA GAAAACCTAG TTGTTGGGTT CTTTTCAGAG TTGAACACGA 7380
 AGCTTAGAGG GATTTCAGGG GGTTTTACAT TAMCCACTGG CTTTTAGAGC AGCTCTCATC 7440
 AATTTCTTCC CCTACTCCAA GAGAGCTGAC TTAAAAATAA GAAAATAAAG GTATCATTTT 7500
 CCAGAGCCCA GAAATTGTTA TTTTAGTGCC TGTCTCTAAC ATATCTATGT GGGTTTTGTT 7560
 GTTGTGTGGT TTTACTTAAT GACATCATGG TAACACCTTA GGGAAGTTCC AGAGCTGAGG 7620
 ACACTATTTG CTTTTCTTCT AAGATGTTTC TGTATTTCTT TTACTAATAG AAATCTGTCC 7680
 CAGAGGTCAA CTCCAAAATC AAAATTGAGT TGCTGGAAAA CGAATTCCAA TTCGGTAGTA 7740
 TTATTTCATA TTGTAGACAA AATGCCACCA CTGTTAACAC CATCATCCGA AAAGCCCTCA 7800
 TAACAGGGGT GTGCTTTCTA ATAAAATTTG GCTGAAAATT CAAGAAATAT ATACCTCTCC 7860
 CCAAGAGAAG TAAATGGCCA CAACAACATT TGAAAATGAT CGTGTTAGAG AGATCAGTTT 7920
 CTTTCCACAA GCTTCTCTTA GTATTCTGTG CTTGAGGTCT AAGAATCTAC AGGGAATAAG 7980
 AGCAGCTAAC ATCTCCAAGA CTTCCTTGGT CCTAGGATCT TTCACTTGTT CGTGGAGCAT 8040
 CTTGACACTC AAGTGTTCCA CCTGCTGTCC TTCGTATCAG TCTAGTCACC GAGTTTTTGG 8100
 GGCTCTGAGC AAGGTGGCAC CTTTTTCAAA TCCATCAGCA CTGACTCCAG AGTTTTGTTC 8160
 ACAGACTGCC GGCTGCATAT CTGCCTGTAT TACCGGGACA TCCTCGTGAA AGAGCTGACC 8220
 ACGACGAGCC CTGAAGGCTG CCGGATCTCC CACGGACACA CCTATGATGT TAGCAACCTG 8280
 GACCAGGTCC TGTTTCCCTA CCCGGACGAC AATGGACAGA GGAAGAACAT TGAGAAGTTG 8340
 CTGAGCCACC TGGAGAGGGG ACTGGTCCTC TGGATGGCTC CAGATGGGCT TTATGCCAAA 8400
 AGACTCTGCC AGAGTAGGAT CTACTGGGAT GGGCCCCTGG CACTGTGCAG CGATCGGCCC 8460
 AACAAGCTAG AAAGAGACCA GACTTGCAAG CTCTTTGACA CACAGCAGTT TCTATCAGGT 8520
 AACACACCTC ACAGTCTGTT AGAATGGAGG TGGTGGTGGG TGCTGGCTAT AAAGGTCTCA 8580
 AATGGCAGTG TCTGCCTACC CCAGACAGAG GTCTTCCTCC TGAGATCTGT GAGCTCATGC 8640
 AGAAATAGAA TTCCTGCCTG ATTCATGCCT AGCCTTTGTC TGTTGTGTAC TCCCCTGATT 8700
 AGCAGAGGGC CAGAAAGAGG ATCCATATTT GCTGCCCAGG ATAGACACTG GTGTGGGTTG 8760
 ATCTCTTAAT TTATCATCAT TCTTTTCACT CTAGGCTTTT GTTTTGTTTG TTTTGTCAGA 8820
 ATATATGTAG CTCAGGCTGG CCTAGAACTC CTGCCTCGGG ATTTTATCTG TACACCAGCA 8880
 CATCTGGCCA ATGAATTAAA ATGTGGGCTT TCAGCGGCAT GTGCCCCACC CCCAGAGAGG 8940
 TTTCACTGTG TTGGCTCTCT GCTCTCAGCA AGTTTATCTG CTGACACCTC AGCTCTTTAG 9000
 GGGTTTCTAG AAGCAGTTCG GTTGCAGAGA GCAGTGGAAA TCTTTGATGT CTACCCATTC 9060
 TGGATTTGCA CCCCACTAGG GACAGTCCCC ATAGGCACAG TTGAGAATTC ATATCTGATC 9120
 AGGGCAGAGT CTTCATGCCT GCTCTGTGGA GGCAGCTTTT TAATGTCAGT TCTTTGATGC 9180
 AGACAAGACC TGGGAACCTA GCTCTGGGAG GAGGAATAAA GGTTAATGCC AGTGAGTGGA 9240
 TGTGGCTTTC TGCTTGTGCT GGGGGAGGAA GCCAAGGCCT TGCACATACA AGGCAAGTGC 9300
 TCTGCTCCAA GTGGCGATGC CCCCAGCCAT GGGCAGGTTT CTTTTCAGCA ATCTTGTCTG 9360
 TTTCATGTCT CTCAGGCAGG ACTAGCCTCA GCATGACATC CTTGTCAGAG GGGCTTCATT 9420
 GGTCCCCTTC TCCCTGTATC ATCCTGTCCC CAAAGTGAGA TTGAAGCCTA CTCTGGTTCT 9480
 CCAGTTATGG AGTTTTAGAC CTAGTGCCAA GTAGGACACA GCTGCCAACA GCTGGTGAGA 9540
 GAAACAGATG CTCTTGGTGC CCAGACACCA CGTGGCCTCC ATGGTTAGCT AGTGAGGTTA 9600
 AAAAAATAAC CCTGGGCCAT CAGAACATTG TGACTCTTTA CATTAAAATG TCTCCTTGGC 9660
 CTGTGCTGAT TGCTTGACTC AGCATGGCTA CTTTTCTTTT TCTTCTTTGT CTTCTTCTCT 9720
 TTGACCTTGT GCATTTCTGT GAGTGTAGTG CTGCAGACCC AAGTTCTTAA GGTTGGGTCA 9780
 TGTTCCTTAA GAGTAATGAA GTAAAACCAG TKCCAAGTCA GGAGATCATA TGTGAACTTG 9840
 ACCATGTGAT TTTGTGTCTA GGGTCTGCTC TAAGGGCTGG ACTTAGGGGA ACAGAGCCCG 9900
 GGCTCTCCCA AAGCAGACTT CCACGTGACT CTGGCTTTCC GTTCACCCGC TTTACCAGGT 9960
 GTCTGAACAG TTTGGTTTTT TTTTTTCTTT CTTTCTTGTG GGTTTTCAGA GCTGCAAGTG 10020
 TTTGCTCACC ATGGCCGGCC AGCACCGAGA TTCCAGGTGA CTCTGTGCTT TGGTGAGGAG 10080
 TTTCCAGACC CTCAGAGACA GAGGAAGCTC ATCACAGCTC ATGTGAGTAC CTGGTTACAT 10140
 CACCCGTAAA TCACACACTG TGGAGCTGTC CCTTTTAGAG AAGTGGCAAG TGACGAGTAA 10200
 ATGTCAGCTC ACCTGGGAAA ATAGATGTAG ACCTTAAAAT AGTGCAGGAG GAAGCAGGCT 10260
 CCAGTGAACA CCACAGCTCA GGGAGGCACC CGCAACCTAC TTCCAGACAA ATTCTGTCAC 10320
 CACCGAATCA GCAGGGCAGA TGACTTGGAC CCAAGGMTCT GTTTGTTCTG TATTCTTTAT 10380
 TGTTTCATAC AGACAGTTAC CTGCCCTTTT ATAGGAATTT TCAATAGTTG GGACCAAGTA 10440
 CTGCCCTTCG ACATCTCTGT TTCTTGTGTG GTTTTAAAGA TGCTGTCCTT TCGAGTAGAG 10500
 TAGCACTTTC TCCCTGGGAG GCTGCCTGTT ATGTATTATG CTTCATCGGG CCTCCTAACT 10560
 TCARATAGTT CCCAGACCCT CGCTTTGTTG CTGGACTTTA GGGAGTTATT TAACAGTTGG 10620
 ACAAGGGAGG TGGAGGAGGC TGAGTCTTCC CAGGAATCAG GTAGGTCGGT CTATCCTCAC 10680
 AGCTAGGGTT TATTCGGATA ATGTTCATCA CTCACTTAAT AATTAAAAGG TAATTCTGAA 10740
 TACATGATGT TTTTTAATTA GAAAATTTTA CTTAATTACA TATCTTGAAA AGTATGCAGT 10800
 GTGGAGTAAA GGTTGTGTCC CAGATAGCCA CAATATCTCA GTGCAAATGG GATATTAGCT 10860
 CTGATGATAT CTCTTAGTGG AGACTGAAGA CTAGGCATAC AGCGCAATGG AAGGCATTTG 10920
 CTAGGCAGTG GTAAAGCCCT GGGTTCTAAA CCCCGCCTAG GATGGGGGTT GGGCACTGAT 10980
 GTTGAACATC CAGCCTCCCT TCTCGGTTGG AAAAAGTAAA ATCTAAGAAG CAACAAACGG 11040
 GCTGGAGAGA TGGCTCAGTT GTTAAGAGCA CAGGCTGTTC TTCCAGAGGT CCTGAGTTTA 11100
 ATTCCTAGAA ACCACATGTG CCTTACAACC ATCTGCAGTG AGCTCTAATG CCATCTTCTG 11160
 GTGTGTTTGA AGACTGCTAC AGTGAACTCA CATACATATA AATCTTAAAA AAATAAAAGG 11220
 CAATGAAACT ATGATCCTGG CCTTGAGCCT TTTCTCAGTT CTAACTGGTG GTTGATATCA 11280
 AATGAGACTG CAGATGTGTG GATGAATCTA GCATAGATAA GCAGTATTTT TTTTTTAAGG 11340
 TAGTGAGTAA ATTCTAGCAT AGATCTCATT TTAAGGACTT TGGGTGCAGT GGGGCTCCGC 11400
 AAAAAGGGAG CAACAATAGT CATATAGGCA AAGGGCCTCA AAATGCTGCC CCGTGGTCCA 11460
 CAGATGGAAA ACATACATGG TCACCCATGA ACTCTGCTGG TCTCCTTATT ACAGACTTAA 11520
 TTCATATGGG TGCTTACAGA GGAATCCTAC CAGACATCAC ATATCAAATA ACAAAGAGGC 11580
 TTGATTTATT GATGATTGGT TGTTACAGAG CACACAGCCT GACTTGGTGA GGCTGGCTTT 11640
 GACTGGGGAT GCAATCGATG CTTATAAACA AACTAGGTCC ATCAGAGCCA GCGAGCTGCT 11700
 GTCTTGTGGC TGRCCAGCTC TGTCTTCTAC TTGTGGTTCA GAGTTCTGTC TATTTCACAG 11760
 TCATCTGGTT CTTCAGGATG AGCCCTTCTG TCAGACTCAT GAGCCTCACT TACCCAGCAT 11820
 GTTACTTAGC CTTTTAATTT GGTCATCTCA TTCAATAATG TCCAGTTAAC TCATTCGCTA 11880
 AATATCAAAT CCAAGAGGCG ATTGGTTTCA AAATGCCATA TTTATCTTCT ATTATAGAAT 11940
 CAAGAGTTCT TTTTCCAGGG TTTTTAATTC CAGGTATTGT AAGAGCAAAT GAAACTGGTT 12000
 TTTCAAATGG CTCTGAATGT GAACTGCTTC ACTGTGTTAT GTTATCCTGT GCAGCTTGTA 12060
 GGTTTTTACT TAGAGTCCTA GGGTCATTTC ATGATGTCCC AATTGTATGG TGTTGAGAAG 12120
 AATATTCTAG TGATGTCTTT TTTTCTTAAA TGTCTTATTA AAGGTGGAAC CTCTGCTAGC 12180
 CAGACAACTG TATTACTTTG CTCAACAAAA CACTGGACAT TTCCTGAGGG GCTACGAGTT 12240
 ACCTGAACAC GTTACCACTC CAGATTACCA CCGCTCCCTC CGTCATTCTT CCATCCAAGA 12300
 GTGAGAAGAA ATACTCTGAC AGGGCAGCCG GTTGCTGCCC TTTCTCTTTG GAAGAGCTAA 12360
 GAAGTGAGTG GGTTTCCACT TGAAGACAAC AACAGGGCTT TGTGAGGAAA ACAGCTGTAT 12420
 CTGCTCAACA GAGGAGCTTC CCCCAGAAGA GTGCCTGTCA GTCATCCAGG TCTTGACAAG 12480
 TGCCAGGACT TGGGTGACTG TGCCCTGGCT TATAACTGTG AAACTTGATC CGAATTC 12537
 (2) INFORMATION FOR SEQ ID NO: 5:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 14 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5
 ATCCTGGAAC ACGC 14
 (2) INFORMATION FOR SEQ ID NO: 6:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 19 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6
 GCACACGAAC TGCCTTCCA 19
 (2) INFORMATION FOR SEQ ID NO: 7:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 24 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7
 CAGCCCGGGG TACTTGCCGC TGTC 24
 (2) INFORMATION FOR SEQ ID NO: 8:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 24 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8
 AGACCTTATG CTTGGCTCAA TGGG 24
 (2) INFORMATION FOR SEQ ID NO: 9:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 15 amino acids
 (B) TYPE: amino acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: protein
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9
 Gly Tyr Glu Leu Pro His Glu Val Thr Thr Pro Asp Tyr His Arg
 1 5 10 15
 (2) INFORMATION FOR SEQ ID NO: 10:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 19 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10
 TGCAGAAGTG AAACTGAGG 19
 (2) INFORMATION FOR SEQ ID NO: 11:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11
 TGCAGAAGTG AAACTGAG 18
 (2) INFORMATION FOR SEQ ID NO: 12:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12
 TGCAGAAGTG AAACCTGG 18
 (2) INFORMATION FOR SEQ ID NO: 13:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13
 TGCAGAAGTG AACATGAG 18
 (2) INFORMATION FOR SEQ ID NO: 14:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14
 TGCAGAAGTG GTCCTGAG 18
 (2) INFORMATION FOR SEQ ID NO: 15:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15
 GCTAGAAGTG AAACTGAG 18
 (2) INFORMATION FOR SEQ ID NO: 16:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16
 AAAGGAAGTG AAACCAAG 18
 (2) INFORMATION FOR SEQ ID NO: 17:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17
 TGAGGAACTG AAAACAGA 18
 (2) INFORMATION FOR SEQ ID NO: 18:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 16 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18
 GGGAAAGTGA AACTAG 16
 (2) INFORMATION FOR SEQ ID NO: 19:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 27 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19
 CTGGACATCT CAGACCCGTA CAAAGTG 27
 (2) INFORMATION FOR SEQ ID NO: 20:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 27 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20
 CTTGACATTT TTCATTCTTG AATAGAG 27
 (2) INFORMATION FOR SEQ ID NO: 21:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 21 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21
 TGCCCTCAGC TCCGAGTCCA G 21
 (2) INFORMATION FOR SEQ ID NO: 22:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 18 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22
 AACCATTTTC ACAAGCTG 18
 (2) INFORMATION FOR SEQ ID NO: 23:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 38 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23
 GGATCCGGAT CCATGAACTG GAGGGCGGCG GCCGAGGC 38
 (2) INFORMATION FOR SEQ ID NO: 24:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 1353 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: cDNA
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24
 ATGAACCTGG AGGGCGGCGG CCGAGGCGGA GAGTTCGGCA TGAGCGCGGT GAGCTGCGGC 60
 AACGGGAAGC TCCGCCAGTG GCTGATCGAC CAGATCGACA GCGGCAAGTA CCCCGGGCTG 120
 GTGTGGGAGA ACGAGGAGAA GAGCATCTTC CGCATCCCCT GGAAGCACGC GGGCAAGCAG 180
 GACTACAACC GCGAGGAGGA CGCCGCGCTC TTCAAGGCTT GGGCACTGTT TAAAGGAAAG 240
 TTCCGAGAAG GCATCGACAA GCCGGACCCT CCCACCTGGA AGACGCGCCT GCGGTGCGCT 300
 TTGAACAAGA GCAATGACTT TGAGGAACTG GTTGAGCGGA GCCAGCTGGA CATCTCAGAC 360
 CCGTACAAAG TGTACAGGAT TGTTCCTGAG GGAGCCAAAA AAGGAGCCAA GCAGCTCACC 420
 CTGGAGGACC CGCAGATGTC CATGAGCCAC CCCTACACCA TGACAACGCC TTACCCTTCG 480
 CTCCCAGCCC AGGTTCACAA CTACATGATG CCACCCCTCG ACCGAAGCTG GAGGGACTAC 540
 GTCCCGGATC AGCCACACCC GGAAATCCCG TACCAATGTC CCATGACGTT TGGACCCCGC 600
 GGCCACCACT GGCAAGGCCC AGCTTGTGAA AATGGTTGCC AGGTGACAGG AACCTTTTAT 660
 GCTTGTGCCC CACCTGAGTC CCAGGCTCCC GGAGTCCCCA CAGAGCCAAG CATAAGGTCT 720
 GCCGAAGCCT TGGCGTTCTC AGACTGCCGG CTGCACATCT GCCTGTACTA CCGGGAAATC 780
 CTCGTGAAGG AGCTGACCAC GTCCAGCCCC GAGGGCTGCC GGATCTCCCA TGGACATACG 840
 TATGACGCCA GCAACCTGGA CCAGGTCCTG TTCCCCTACC CAGAGGACAA TGGCCAGAGG 900
 AAAAACATTG AGAAGCTGCT GAGCCACCTG GAGAGGGGCG TGGTCCTCTG GATGGCCCCC 960
 GACGGGCTCT ATGCGAAAAG ACTGTGCCAG AGCAGGATCT ACTGGGACGG GCCCCTGGCG 1020
 CTGTGCAACG ACCGGCCCAA CAAACTGGAG AGAGACCAGA CCTGCAAGCT CTTTGACACA 1080
 CAGCAGTTCT TGTCAGAGCT GCAAGCGTTT GCTCACCACG GCCGCTCCCT GCCAAGATTC 1140
 CAGGTGACTC TATGCTTTGG AGAGGAGTTT CCAGACCCTC AGAGGCAAAG AAAGCTCATC 1200
 ACAGCTCACG TAGAACCTCT GCTAGCCAGA CAACTATATT ATTTTGCTCA ACAAAACAGT 1260
 GGACATTTCC TGAGGGGCTA CGATTTACCA GAACACATCA GCAATCCAGA AGATTACCAC 1320
 AGATCTATCC GCCATTCCTC TATTCAAGAA TGA 1353
 (2) INFORMATION FOR SEQ ID NO: 25:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 450 amino acids
 (B) TYPE: amino acid
 (C) STRANDEDNESS: single
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: protein
 (vi) ORIGINAL SOURCE:
 (A) ORGANISM: not provided
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25
 Met Asn Leu Glu Gly Gly Gly Arg Gly Gly Glu Phe Gly Met Ser Ala
 1 5 10 15
 Val Ser Cys Gly Asn Gly Lys Leu Arg Gln Trp Leu Ile Asp Gln Ile
 20 25 30
 Asp Ser Gly Lys Tyr Pro Gly Leu Val Trp Glu Asn Glu Glu Lys Ser
 35 40 45
 Ile Phe Arg Ile Pro Trp Lys His Ala Gly Lys Gln Asp Tyr Asn Arg
 50 55 60
 Glu Glu Asp Ala Ala Leu Phe Lys Ala Trp Ala Leu Phe Lys Gly Lys
 65 70 75 80
 Phe Arg Glu Gly Ile Asp Lys Pro Asp Pro Pro Thr Trp Lys Thr Arg
 85 90 95
 Leu Arg Cys Ala Leu Asn Lys Ser Asn Asp Phe Glu Glu Leu Val Glu
 100 105 110
 Arg Ser Gln Leu Asp Ile Ser Asp Pro Tyr Lys Val Tyr Arg Ile Val
 115 120 125
 Pro Glu Gly Ala Lys Lys Gly Ala Lys Gln Leu Thr Leu Glu Asp Pro
 130 135 140
 Gln Met Ser Met Ser His Pro Tyr Thr Met Thr Thr Pro Tyr Pro Ser
 145 150 155 160
 Leu Pro Ala Gln Val His Asn Tyr Met Met Pro Pro Leu Asp Arg Ser
 165 170 175
 Trp Arg Asp Tyr Val Pro Asp Gln Pro His Pro Glu Ile Pro Tyr Gln
 180 185 190
 Cys Pro Met Thr Phe Gly Pro Arg Gly His His Trp Gln Gly Pro Ala
 195 200 205
 Cys Glu Asn Gly Cys Gln Val Thr Gly Thr Phe Tyr Ala Cys Ala Pro
 210 215 220
 Pro Glu Ser Gln Ala Pro Gly Val Pro Thr Glu Pro Ser Ile Arg Ser
 225 230 235 240
 Ala Glu Ala Leu Ala Phe Ser Asp Cys Arg Leu His Ile Cys Leu Tyr
 245 250 255
 Tyr Arg Glu Ile Leu Val Lys Glu Leu Thr Thr Ser Ser Pro Glu Gly
 260 265 270
 Cys Arg Ile Ser His Gly His Thr Tyr Asp Ala Ser Asn Leu Asp Gln
 275 280 285
 Val Leu Phe Pro Tyr Pro Glu Asp Asn Gly Gln Arg Lys Asn Ile Glu
 290 295 300
 Lys Leu Leu Ser His Leu Glu Arg Gly Val Val Leu Trp Met Ala Pro
 305 310 315 320
 Asp Gly Leu Tyr Ala Lys Arg Leu Cys Gln Ser Arg Ile Tyr Trp Asp
 325 330 335
 Gly Pro Leu Ala Leu Cys Asn Asp Arg Pro Asn Lys Leu Glu Arg Asp
 340 345 350
 Gln Thr Cys Lys Leu Phe Asp Thr Gln Gln Phe Leu Ser Glu Leu Gln
 355 360 365
 Ala Phe Ala His His Gly Arg Ser Leu Pro Arg Phe Gln Val Thr Leu
 370 375 380
 Cys Phe Gly Glu Glu Phe Pro Asp Pro Gln Arg Gln Arg Lys Leu Ile
 385 390 395 400
 Thr Ala His Val Glu Pro Leu Leu Ala Arg Gln Leu Tyr Tyr Phe Ala
 405 410 415
 Gln Gln Asn Ser Gly His Phe Leu Arg Gly Tyr Asp Leu Pro Glu His
 420 425 430
 Ile Ser Asn Pro Glu Asp Tyr His Arg Ser Ile Arg His Ser Ser Ile
 435 440 445
 Gln Glu
 450