BETA-DEFENSINS

Abstract: The present invention relates to polynucleotide and polypeptide molecules for zamp3 and zamp4, novel members of the beta -defensin family. The polypeptides, and polynucleotides encoding them, are useful in the study or treatment of microbial infections. The present invention also includes antibodies to the zamp3 or zamp4 polypeptides.

Description: Description BETA-DEFENSI S BACKGROUND OF THE INVENTION Biological defense strategies have evolved to protect organisms from invasion by other species. Microbial infection response systems include oxidative and non-oxidative mechanisms, utilizing compounds that are enzymatically synthesized in cells and peptides that are single gene products. Anti-microbial peptides constitute an oxygen-independent host defense system found in organisms encompassing many taxonomic families. One major class of anti-microbial peptides can be sequence-defined by conserved cysteine residue patterns and are termed defensins. Mammalian defensins, derived from skin, lung and intestine, exhibit antibiotic activity against a wide variety of pathogens, including gram- positive and gram-negative bacteria, fungi (e.g. Candida species) and viruses. See, for example, Porter et al., Infect. Irnmun. 6516): 2396-401, 1997. The amphipathic character of the defensin peptides appears to be the key to the general mechanism of microbial attack, Le , by creating pores, or "boring" through the cell wall. In addition, Daher et al., J. Virol. 60(3): 1068-74. 1986, reported that enveloped viruses, including herpes simplex types 1 and 2, cytomegalovirus and influenza virus (A/WSN), among others, were inactivated by incubation with human neutrophil peptide (HNP-1) and speculated that the binding of defensin molecules to viruses impairs the virus' ability to infect cells. The defensin family of anti-microbial peptides can be divided into two major subclasses based on two distinct consensus sequences. See, for example, Martin et al., J. Leuko. Bio. 58:128-36, 1995. The first defensin subclass, classic defensins, represented by HNPs are stored in the so-called large azurophil granules of neutrophils and macrophages and attack microorganisms that have been phagocytosed by these cells. The amino acid sequence of HNPs is consistent with a predicted disulfide bridging that is distinct from that of the β-defensin subclass. Epithelial cells can also be a source of defensins, and these cells appear to secrete these peptides into the external, extra-cellular environment. In the mouse, for example, Paneth cells of the small intestine and proximal colon, secrete defensin-like peptides, called cryptidins, into the lumen. See, for example, Ouellette and Selsted, The FASEB Journal 10:1280- 9, 1996. Support for the endogenous pathogen defense function of defensins was found using matrilysin homozygous knock-out mice. Mice deficient in matrilysin, a metalloproteinase necessary to regulate α-defensin activity, were found to have decreased anti-microbial activity and were more sensitive to pathogens (Wilson et al., Science 286:133-7, 1999). β-defensins, the second major defensin subclass, include peptides found in bovine lung (e.g., BNBD-bovine neutrophil β-defensins) as well as a secreted form (TAP - tracheal anti-microbial peptide). See, for example, Selsted et al., J. Biol. Chem. 268:6641-8, 1993. Two human β-defensins have been reported. SAP-1 (HBD1) was isolated from human psoriatic skin, and hBD-1 was found in low concentrations in human blood filtrate. See, for example, Bensch et al., FEBS Lett. 368:331-5, 1995). HBD2, Hardner et al., Nature 387:861, 1997. The amino acid sequence of these human β-defensins is most similar to the bovine BNDPs and TAP. See, for example, Harder et al., Nature 387:861, 1997, wherein SAP-1 is designated hBD-2. Murine β-defensins include MBD1, Huttner et al., FEBS Lett. 413:45-9, 1997, Bals et al., Infect. Immun. 67:42-7, 1997; MBD2, Morrison et al., FEBS Lett. 422:112-6,, 1999; MBD3, Bals et al., Infect. Immun. 67:3542-7, 1999; and MBD4, Jia et al., J. Biol. Chem. 1 [epub ahead of print], 2000. Other than the conserved cysteine residues the defensin family is quite sequence divergent. It is possible that the variant amino acid positions may be related to the site or conditions of activity or to the spectrum of pathogens attacked by a particular defensin. In addition to anti-microbial activities, particular defensins exhibit metabolically sensitive cytotoxic activity (Lichtenstein et al., Blood 68:1407-10, 1986 and Sheu et al., Antimicrob. Agents Chemother. 28:626-9, 1993), alter the response of adrenal cortical cells to ACTH (Zhu et al., Proc. Natl. Acad. Sci. (USA) 85:592-6, 1988) and have specific chemotactic activity for human monocytes (Territo et al., Clin. Invest. 84:2017-20, 1989). Recruitment of monocytes by neutrophils may, in part, be mediated by neutrophilic defensins and suggests a pro-inflammatory activity for these peptides in addition to their anti-microbial effects. Also, a decrease in defensin mRNA level has been demonstrated in SPG (specific granule disease). See, for example, Tamura et al., Japan. Int. J. Hematol. 59:137-42, 1994. Higazi et al., J. Biol. Chem. 271:17650-5, 1996, suggested that plasminogen bound to fibrin in the presence of defensin may be less susceptible to activation by tPA. Moieties having anti-microbial, immuno-stimulatory, pro-inflammatory and other properties of defensins are sought. The present invention provides such polypeptides for these and other uses that should be apparent to those skilled in the art from the teachings herein. BRIEF SUMMARY OF THE INVENTION The present invention provides a novel defensin proteins, designated "zamp2," "zamp3," and "zamp4." The present invention also provides zamp3 and zamp4 variant polypeptides and zamp3 and zamp4 fusion proteins, as well as nucleic acid molecules encoding such polypeptides and proteins, and methods for using these nucleic acid molecules and amino acid sequences. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the three disulfide bond structure of the conserved β- defensin motif. Figure 2 shows a alignment of the amino acid sequence of zamp3 with murine β defensin 3 (Mbdef3) (Bals et al., Infect. Immun. 67:3542-7, 1999) (SEQ ID NO: 11) and murine β defensin 4 (Mbdef4) Genbank Accession No. AAD38852 (SEQ ID NO: 12). The location of conserved cysteine residues within the cysteine domain are indicated by an asterisk "*". DETAILED DESCRIPTION OF THE INVENTION Prior to setting forth the invention in detail, it may be helpful to the understanding thereof to define the following terms. The term "affinity tag" is used herein to denote a peptide segment that can be attached to a polypeptide to provide for purification of the polypeptide or provide sites for attachment of the polypeptide to a substrate. In principal, any peptide or protein for which an antibody or other specific binding agent is available can be used as an affinity tag. Affinity tags include a poly-histidine tract, protein A (Nilsson et al., EMBO J. 4:1075, 1985; Nilsson et al., Meth. Enzvmol. 198:3. 1991), glutathione S transferase (Smith and Johnson, Gene 67:31, 1988), substance P, Flag™ peptide (Hopp et al., Biotechnology 6:1204-1210, 1988; available from Eastman Kodak Co., New Haven, CT), streptavidin binding peptide, or other antigenic epitope or binding domain. See, in general Ford et al., Protein Expression and Purification 2: 95-107, 1991. DNAs encoding affinity tags are available from commercial suppliers (e.g., Pharmacia Biotech, Piscataway, NJ). The term "allelic variant" denotes any of two or more alternative forms of a gene occupying the same chromosomal locus. Allelic variation arises naturally through mutation, and may result in phenotypic polymorphism within populations. Gene mutations can be silent (no change in the encoded polypeptide) or may encode polypeptides having altered amino acid sequence. The term allelic variant is also used herein to denote a protein encoded by an allelic variant of a gene. The terms "amino-terminal" and "carboxyl-terminal" are used herein to denote positions within polypeptides and proteins. Where the context allows, these terms are used with reference to a particular sequence or portion of a polypeptide or protein to denote proximity or relative position. For example, a certain sequence positioned carboxyl-terminal to a reference sequence within a protein is located proximal to the carboxyl terminus of the reference sequence, but is not necessarily at the carboxyl terminus of the complete protein. The term "complements of polynucleotide molecules" denotes polynucleotide molecules having a complementary base sequence and reverse orientation as compared to a reference sequence. For example, the sequence 5' ATGCACGGG 3' is complementary to 5' CCCGTGCAT 3'. The term "degenerate nucleotide sequence" denotes a sequence of nucleotides that includes one or more degenerate codons (as compared to a reference polynucleotide molecule that encodes a polypeptide). Degenerate codons contain different triplets of nucleotides, but encode the same amino acid residue (i.e., GAU and GAC triplets each encode Asp). The term "expression vector" denotes a DNA molecule, linear or circular, that comprises a segment encoding a polypeptide of interest operably linked to additional segments that provide for its transcription. Such additional segments may include promoter and terminator sequences, and may optionally include one or more origins of replication, one or more selectable markers, an enhancer, a polyadenylation signal, and the like. Expression vectors are generally derived from plasmid or viral DNA, or may contain elements of both. The term "isolated", when applied to a polynucleotide, denotes that the polynucleotide has been removed from its natural genetic milieu and is thus free of other extraneous or unwanted coding sequences, and is in a form suitable for use within genetically engineered protein production systems. Such isolated molecules are those that are separated from their natural environment and include cDNA and genomic clones. Isolated DNA molecules of the present invention are free of other genes with which they are ordinarily associated, but may include naturally occurring 5' and 3' untranslated regions such as promoters and terminators. The identification of associated regions will be evident to one of ordinary skill in the art (see for example, Dynan and Tijan, Nature 316:774-78, 1985). Another example of an isolated nucleic acid molecule is a chemically-synthesized nucleic acid molecule that is not integrated in the genome of an organism. An isolated nucleic acid molecule that has been isolated from a chromosome of a particular species is smaller than the complete DNA molecule of that chromosome. An "isolated" polypeptide or protein is a polypeptide or protein that is found in a condition other than its native environment, such as apart from blood and animal tissue. In a preferred form, the isolated polypeptide is substantially free of other polypeptides, particularly other polypeptides of animal origin. It is preferred to provide the polypeptides in a highly purified form, i.e. greater than 95% pure, more preferably greater than 99% pure. When used in this context, the term "isolated" does not exclude the presence of the same polypeptide in alternative physical forms, such as dimers or alternatively glycosylated or derivatized forms. The term "operably linked", when referring to DNA segments, denotes that the segments are arranged so that they function in concert for their intended purposes, e.g. transcription initiates in the promoter and proceeds through the coding segment to the terminator. The term "ortholog" denotes a polypeptide or protein obtained from one species that is the functional counterpart of a polypeptide or protein from a different species. Sequence differences among orthologs are the result of speciation. The term "paralogs" denotes distinct but structurally related proteins made by an organism. Paralogs are believed to arise through gene duplication. For example, α-globin, β-globin, and myoglobin are paralogs of each other. The term "polynucleotide" denotes a single- or double-stranded polymer of deoxyribonucleotide or ribonucleotide bases read from the 5' to the 3' end. Polynucleotides include RNA and DNA, and may be isolated from natural sources, synthesized in vitro, or prepared from a combination of natural and synthetic molecules. Sizes of polynucleotides are expressed as base pairs (abbreviated "bp"), nucleotides ("nt"), or kilobases ("kb"). Where the context allows, the latter two terms may describe polynucleotides that are single-stranded or double-stranded. When the term is applied to double-stranded molecules it is used to denote overall length and will be understood to be equivalent to the term "base pairs". It will be recognized by those skilled in the art that the two strands of a double-stranded polynucleotide may differ slightly in length and that the ends thereof may be staggered as a result of enzymatic cleavage; thus all nucleotides within a double-stranded polynucleotide molecule may not be paired. Such unpaired ends will in general not exceed 20 nt in length. A "polypeptide" is a polymer of amino acid residues joined by peptide bonds, whether produced naturally or synthetically. Polypeptides of less than about 10 amino acid residues are commonly referred to as "peptides". The term "promoter" denotes a portion of a gene containing DNA sequences that provide for the binding of RNA polymerase and initiation of transcription. Promoter sequences are commonly, but not always, found in the 5' non- coding regions of genes. The term "receptor" denotes a cell-associated protein that binds to a bioactive molecule (i.e., a ligand) and mediates the effect of the ligand on the cell. Membrane-bound receptors are characterized by a multi-domain structure comprising an extracellular ligand-binding domain and an intracellular effector domain that is typically involved in signal transduction. Binding of ligand to receptor results in a conformational change in the receptor that causes an interaction between the effector domain and other molecule(s) in the cell. This interaction in turn leads to an alteration in the metabolism of the cell. Metabolic events that are linked to receptor-ligand interactions include gene transcription, phosphorylation, dephosphorylation, increases in cyclic AMP production, mobilization of cellular calcium, mobilization of membrane lipids, cell adhesion, hydrolysis of inositol lipids and hydrolysis of phospholipids. Most nuclear receptors also exhibit a multi-domain structure, including an amino-terminal, transactivating domain, a DNA binding domain and a ligand binding domain. In general, receptors can be membrane bound, cytosolic or nuclear; monomeric (e.g., thyroid stimulating hormone receptor, beta-adrenergic receptor) or multimeric (e.g., PDGF receptor, growth hormone receptor, IL-3 receptor, GM-CSF receptor, G-CSF receptor, erythropoietin receptor and IL-6 receptor). The term "secretory signal sequence" denotes a DNA sequence that encodes a polypeptide (a "secretory peptide") that, as a component of a larger polypeptide, directs the larger polypeptide through a secretory pathway of a cell in which it is synthesized. The larger peptide is commonly cleaved to remove the secretory peptide during transit through the secretory pathway. A "soluble receptor" is a receptor polypeptide that is not bound to a cell membrane. Soluble receptors are most commonly ligand-binding receptor polypeptides that lack transmembrane and cytoplasmic domains. Soluble receptors can comprise additional amino acid residues, such as affinity tags that provide for purification of the polypeptide or provide sites for attachment of the polypeptide to a substrate, or immunoglobulin constant region sequences. Many cell-surface receptors have naturally occurring, soluble counterparts that are produced by proteolysis or translated from alternatively spliced mRNAs. Receptor polypeptides are the to be substantially free of transmembrane and intracellular polypeptide segments when they lack sufficient portions of these segments to provide membrane anchoring or signal transduction, respectively. Molecular weights and lengths of polymers determined by imprecise analytical methods (e.g., gel electrophoresis) will be understood to be approximate values. When such a value is expressed as "about" X or "approximately" X, the stated value of X will be understood to be accurate to ±10%. The present invention is based in part upon the discovery of novel DNA sequences that encode polypeptides having homology to proteins of the β-defensin family. That is, the zamp2, zamp3, and zamp4 polypeptides of the present invention exhibit a conserved motif shown in SEQ ID NO:4 and herein: C(X) 6 C(X) 3- 4 C(X) 7 GXC(X) CC wherein "(X)" is the number of preferably non-cysteine amino acid residues between specific amino acids. The cysteine position and spacing is characteristic of the β-defensin family. Figure 1 provides the three disulfide bond structure of the conserved β-defensin motif. The zamp3 polypeptide (Defb5) is a mouse homolog of bovine enteric β-defensin EPA (Gallager et al., Mamm. Genome 6:554-6, 1995 and Traver et al., Infect. Immun. 66:1045-56, 1998). The nucleotide sequence of the zamp3 polypeptide is described in SEQ ID NO:l, and its deduced amino acid sequence is described in SEQ ID NO: 2 were originally obtained by resolving a mutation found in the naturally occurring genomic sequence of a pseudogene encoding murine zamp3 (SEQ ID NO: 3). Further analysis of the genomic sequence (SEQ ID NO: 19) indicates that a second intron/exon splice site exists which does not result in a frameshift and translation of zamp3 could occur without the above mentioned repair. The zamp3 polypeptide includes a signal sequence, amino acid residues 1-22 of SEQ ID NO:2, nucleotides 10- 198 of SEQ ID NO:l. The mature polypeptide therefore ranges from amino acid residue 23 to amino acid residue 63 of SEQ ID NO:2, nucleotides 76-198 of SEQ ID NO:l. Within the mature polypeptide is a defensin cysteine motif C(X) 6 C(X) 3- 4 C(X) 7 GXC(X) 6 CC (amino acid residues 31-60, SEQ ID NO:2) wherein "(X)" is the number of preferably non-cysteine amino acid residues between specific amino acids. Figure 2 provides an alignment of zamp3 with murine β defensins 3 and 4 (SEQ ID Nos: 11 and 12). The invention provides isolated polypeptides and polynucleotides encoding polypeptides comprising amino acid residues 31-60 of SEQ ID NO:2, an polypeptide comprising the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ID NO:2, and polypeptides consisting of amino acid residues 31 to 60 of SEQ ID NO:2; amino acid residues 31 to 63 of SEQ ID NO:2, amino acid residues 23 to 60 of SEQ ID NO:2, amino acid residues 23 to 63 of SEQ ID NO:2, amino acid residues 1 to 60 of SEQ ID NO:2, and amino acid residues 1 to 63 of SEQ ID NO:2. The invention also provides isolated polynucleotides consisting of nucleotides 1 to 324 of SEQ ID NO:l, nucleotides 10 to 198 of SEQ ID NO:l, nucleotides 10 to 189 of SEQ ID NO:l, nucleotides 76 to 198 of SEQ ID NO:l, nucleotides 76 to 189 of SEQ ID NO: l, nucleotides 100 to 198 of SEQ ID NO:l, and nucleotides 100 to 189 of SEQ ID NO: l. The nucleotide sequence of the zamp4 polypeptide is described in SEQ JJD NO:5, and its deduced amino acid sequence is described in SEQ ID NO:6. The zamp4 polypeptide includes the amino acid residues 1-44 of SEQ ID NO:6, nucleotides 1-132 of SEQ ID NO:5. Additional 5' sequence, thought to be part of an additional exon can be found using methods known in the art. Within the zamp4 polypeptide is a defensin cysteine motif C(X) 6 C(X) 3-4 C(X) 7 GXC(X) 6 CC (amino acid residues 12-41, SEQ ID NO:6) wherein "(X)" is the number of preferably non-cysteine amino acid residues between specific amino acids. The invention provides isolated polypeptides and polynucleotides encoding polypeptides consisting of amino acid residues 12 to 41 of SEQ ID NO:6, amino acid residues 12 to 44 of SEQ ID NO:6, amino acid residues 1 to 41 of SEQ ID NO:6, and amino acid residues 1 to 44 of SEQ ID NO:6. The invention also provides polynucleotides consisting of nucleotides 1 to 296 of SEQ ID NO:5, nucleotides 1 to 132 of SEQ ID NO:5, nucleotides 1 to 123 of SEQ ID NO:5, nucleotides 34 to 123 of SEQ ID NO:5, and nucleotides 34 to 132 of SEQ ID NO:5. The zamp2 polypeptide is a human homolog of murine β-defensin 1 (Huttner et al., FEBS Lett. 413:45-9, 1997). There is 100% sequence identity between the mouse and human at the amino acid level and a 1 base pair difference at the nucleotide level. The nucleotide sequence of the zamp2 polypeptide is described in SEQ ID NO:7, and its deduced amino acid sequence is described in SEQ ID NO:8). Within the mature polypeptide is a defensin cysteine motif C(X) 6 C(X) 3- 4 C(X) 7 GXC(X) 6 CC (amino acid residues 37-67, SEQ ID NO:8) wherein "(X)" is the number of preferably non-cysteine amino acid residues between specific amino acids. Expression of zamp2 in bone marrow, placenta, skeletal muscle, small intestine and uterus was found using reverse transcript PCR (RT-PCR). A standard murine Northern blot tissue distribution of the mRNA corresponding to the zamp3 novel DNA revealed no expression. Neither did a murine embryo blot. A mouse RNA master blot revealed a faint positive signal corresponding to thyroid, ovary and epididymus. It appears that normal tissue levels of mRNA of zamp3 polypeptide are just at or below the detection sensitivity of the Northern blot. Such an observation is consistent with the knowledge in the art regarding defensins, i.e., that they are constitutively expressed at low levels but are highly inducible upon infection. Another aspect of the present invention includes zamp3 and zamp4 polypeptide fragments. Preferred fragments include the leader sequence, ranging from amino acid residues 1-22 of SEQ ID NO:2. Such leader sequences may be used to direct the secretion of other polypeptides. Such fragments of the present invention may be used as follows: the alternative secretion leader fragments are formed as fusion proteins with alternative proteins selected for secretion; plasmids bearing regulatory regions capable of directing the expression of the fusion protein are introduced into test cells; and secretion of the protein is monitored. Additional preferred fragments include the cysteine domain, amino acid residues 31-60 of SEQ ID NO:2 and zamp4, amino acid residues 12-41 of SEQ ID NO:4. The fragments provided by the invention would be useful in applications, described herein, where administration of zamp3 and zamp4 would be beneficial, such as anti-microbial agents (Thennarasu and Nagaraj, Biochem. Biophys. Res. Comm. 254:281-3, 1999). The present invention also provides fusion constructs incorporating the zamp3 or zamp4 polypeptide selected from the group consisting of: (a) amino acid residues 31-60 of SEQ ID NO:2; (b) amino acid residues 12-41 of SEQ ID NO:6; (c) SEQ ID NO:2, (d) SEQ ID NO:6, mammalian species homologs or human paralogs of (a) or (b); at least the mature polypeptide region of another defensin molecule; and, optionally, a polypeptide linker there between. When defensin molecules having disparate spectrum of pathogens, fusion constructs containing the same are expected to exhibit a broader range of anti-microbial effectiveness. Polypeptide linkers are preferably employed if necessary to provide separation of component polypeptides of the fusion or to allow for flexibility of the fusion protein, thereby preserving the anti-microbial activity of each defensin component of the fusion protein. Those of ordinary skill in the art are capable of designing such linkers. The highly conserved amino acids in the consensus domain of zamp3 and zamp4 polypeptide can be used as tools to identify new family members. For instance, reverse transcription-polymerase chain reaction (RT-PCR) can be used to amplify sequences encoding the conserved motif from RNA obtained from a variety of tissue sources. More specifically, the following probes can be employed to identify zamp3-like or zamp4-like β-defensins. A preferred embodiment of this aspect of the present invention the probes include (a) SEQ ID NO:2, (b) SEQ ID NO:6, (c) amino acid residues 23-63 of SEQ ID NO:2, (d) amino acid residues 31-60 of SEQ ID NO:2, and (e) amino acid residues 12-41 of SEQ ID NO:6. In particular, highly degenerate primers designed from the above sequences are useful for this purpose. The present invention also provides polynucleotide molecules, including DNA and RNA molecules, that encode the zamp3 and zamp4 polypeptides disclosed herein. Those skilled in the art will readily recognize that, in view of the degeneracy of the genetic code, considerable sequence variation is possible among these polynucleotide molecules. SEQ ID NO:9 is a degenerate polynucleotide sequence that encompasses all polynucleotides that encode the zamp3 polypeptide of SEQ ID NO: 2. SEQ ID NO: 10 is a degenerate polynucleotide sequence that encompasses all polynucleotides that encode the zamp4 polypeptide of SEQ ID NO:4. Thus, zamp3 polypeptide-encoding polynucleotides of SEQ ID NO:9 and SEQ ID NO: 10 are contemplated by the present invention. Those skilled in the art will recognize that the degenerate sequence of SEQ ID NO:9 and SEQ ID NO: 10 also provides all RNA sequences encoding SEQ ID NO:2 and SEQ ID NO:6 by substituting U for T. Table 2 sets forth the one-letter codes used within SEQ ED NOs:9 and 10 to denote degenerate nucleotide positions. "Resolutions" are the nucleotides denoted by a code letter. "Complement" indicates the code for the complementary nucleotide(s). For example, the code Y denotes either C or T, and its complement R denotes A or G, A being complementary to T, and G being complementary to C. TABLE 1 Nucleotide Resolutions Complement Resolutions A A T T C C G G G G C C T T A A R A|G Y C|T Y C|T R A|G M A|C K G|T G|T M A|C S C|G S A|T W A|T w C|G H A|C|T D A|G|T B C|G|T V A|C|G V A|C|G B C|G|T D A|G|T H A|C|T N A|C|G|T N A|C|G|T The degenerate codons used in SEQ ID No:9 and SEQ ID NO: 10, encompassing all possible codons for a given amino acid, are set forth in Table 2 below. TABLE 2 Amino Letter Codons Degenerate Acid Codon Cys C TGC TGT TGY Ser S AGC AGT TCA TCC TCG TCT WSN Thr T ACA ACC ACG ACT ACN Pro P CCA CCC CCG CCT CCN Ala A GCA GCC GCG GCT GCN Gly G GGA GGC GGG GGT GGN Asn N AAC AAT AAY Asp D GAC GAT GAY Glu E GAA GAG GAR Gin Q CAA CAG CAR His H CAC CAT CAY Arg R AGA AGG CGA CGC CGG CGT MGN Lys K AAA AAG AAR Met M ATG ATG He I ATA ATC ATT ATH Leu L CTA CTC CTG CTT TTA TTG YTN Val V GTA GTC GTG GTT GTN Phe F πc TTT TTY T r Y TAC TAT TAY Trp W TGG TGG Ter . TAA TAG TGA TRR Asn|Asp B RAY Glu|Gln Z SAR Any X NNN Gap - One of ordinary skill in the art will appreciate that some ambiguity is introduced in determining a degenerate codon, representative of all possible codons encoding each amino acid. For example, the degenerate codon for serine (WSN) can, in some circumstances, encode arginine (AGR), and the degenerate codon for arginine (MGN) can, in some circumstances, encode serine (AGY). A similar relationship exists between codons encoding phenylalanine and leucine. Thus, some polynucleotides encompassed by the degenerate sequence may encode variant amino acid sequences, but one of ordinary skill in the art can easily identify such variant sequences by reference to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:6. Variant sequences can be readily tested for functionality as described herein. One of ordinary skill in the art will also appreciate that different species can exhibit "preferential codon usage." In general, see, Grantham, et al., Nuc. Acids Res. 8:1893-912, 1980; Haas, et al. Curr. Biol. 6:315-24, 1996; Wain-Hobson, et al., Gene 13:355-64, 1981; Grosjean and Fiers, Gene 18:199-209, 1982; Holm, Nuc. Acids Res. 14:3075-87, 1986; JJcemura, J. Mol. Biol. 158:573-97, 1982. As used herein, the term "preferential codon usage" or "preferential codons" is a term of art referring to protein translation codons that are most frequently used in cells of a certain species, thus favoring one or a few representatives of the possible codons encoding each amino acid (See Table 3). For example, the amino acid threonine (Thr) may be encoded by ACA, ACC, ACG, or ACT, but in mammalian cells ACC is the most commonly used codon; in other species, for example, insect cells, yeast, viruses or bacteria, different Thr codons may be preferential. Preferential codons for a particular species can be introduced into the polynucleotides of the present invention by a variety of methods known in the art. Introduction of preferential codon sequences into recombinant DNA can, for example, enhance production of the protein by making protein translation more efficient within a particular cell type or species. Therefore, the degenerate codon sequence disclosed in SEQ ID NO:9 or SEQ ID NO: 10 serves as a template for optimizing expression of polynucleotides in various cell types and species commonly used in the art and disclosed herein. Sequences containing preferential codons can be tested and optimized for expression in various species, and tested for functionality as disclosed herein. As previously noted, the isolated polynucleotides of the present invention include DNA and RNA. Methods for preparing DNA and RNA are well known in the art. In general, RNA is isolated from a tissue or cell that produces large amounts of RNA. Such tissues and cells are identified by Northern blotting (Thomas, Proc. Natl. Acad. Sci. USA 77:5201, 1980). Total RNA can be prepared using guanidinium isothiocyanate extraction followed by isolation by centrifugation in a CsCl gradient (Chirgwin et al., Biochemistry 18:52-94, 1979). Poly (A) + RNA is prepared from total RNA using the method of Aviv and Leder (Proc. Natl. Acad. Sci. USA 69:1408-12, 1972). Complementary DNA (cDNA) is prepared from poly(A)+ RNA using known methods. In the alternative, genomic DNA can be isolated. Polynucleotides encoding zamp3 or zamp4 polypeptides are then identified and isolated by, for example, hybridization or PCR. Zamp3 or zamp4 polynucleotide sequences disclosed herein can also be used as probes or primers to clone 5' non-coding regions of a zamp3 or zamp4 gene. Promoter elements from a zamp3 or zamp4 gene could be used to direct the tissue-specific expression of heterologous genes in, for example, transgenic animals or patients treated with gene therapy. Cloning of 5' flanking sequences also facilitates production of zamp3 or zamp4 proteins by "gene activation" as disclosed in U.S. Patent No. 5,641,670. Briefly, expression of an endogenous zamp3 or zamp4 gene in a cell is altered by introducing into the zamp3 or zamp4 locus a DNA construct comprising at least a targeting sequence, a regulatory sequence, an exon, and an unpaired splice donor site. The targeting sequence is a zamp3 or zamp4 5' non-coding sequence that permits homologous recombination of the construct with the endogenous zamp3 or zamp4 locus, whereby the sequences within the construct become operably linked with the endogenous zamp3 or zamp4 coding sequence. In this way, an endogenous zamp3 or zamp4 promoter can be replaced or supplemented with other regulatory sequences to provide enhanced, tissue-specific, or otherwise regulated expression. Zamp3 and zamp4 polynucleotide probes can be RNA or DNA. DNA can be either cDNA or genomic DNA. Polynucleotide probes are single or double-stranded DNA or RNA, generally synthetic oligonucleotides, but may be generated from cloned cDNA or genomic sequences and will generally comprise at least 16 nucleotides, more often from 17 nucleotides to 25 or more nucleotides, sometimes 40 to 60 nucleotides, and in some instances a substantial portion, domain or even the entire zamp3 or zamp4 gene or cDNA. Exemplary probes and primers include a polynucleotide consisting of nucleotides 1 to 324, 10 to 198, 10 to 189, 76 to 198, 76 to 189, 100 to 198, 100 to 189, 1 to 296, 1 to 132, 1 to 123, 34 to 123 of SEQ ID NO:5, and 34 to 132 of SEQ ID NO:5. Probes and primers are generally synthetic oligonucleotides, but may be generated from cloned cDNA or genomic sequences or its complements. Analytical probes will generally be at least 20 nucleotides in length, although somewhat shorter probes (14-17 nucleotides) can be used. PCR primers are at least 5 nucleotides in length, preferably 15 or more nucleotides, more preferably 20-30 nucleotides. Short polynucleotides can be used when a small region of the gene is targeted for analysis. For gross analysis of genes, a polynucleotide probe may comprise an entire exon or more. Probes can be labeled to provide a detectable signal, such as with an enzyme, biotin, a radionuclide, fluorophore, chemiluminescer, paramagnetic particle and the like, which are commercially available from many sources, such as Molecular Probes, Inc., Eugene, OR, and Amersham Corp., Arlington Heights, IL, using techniques that are well known in the art. Preferred regions from which to construct probes include regions of homology with other thymopoietins and emerin as described herein, the ankyrin-like region, the calcium binding protein-like region, the signal sequence, and the like. Techniques for developing polynucleotide probes and hybridization techniques are known in the art, see for example, Ausubel et al., eds., Current Protocols in Molecular Biology, John Wiley and Sons, Inc., NY, 1991. Zamp3 and zamp4 polypeptides may be used within diagnostic systems to detect the presence of zamp 3 or zamp4 respectively. The information derived from such detection methods would provide insight into the significance of zamp3 and zamp4 polypeptides in various diseases, and as a would serve as diagnostic tools for diseases for which altered levels of zamp3 or zamp4 are significant. Altered levels of zamp3 or zamp4 polypeptides may be indicative of microbial infection and inflammation. In a basic assay, a single-stranded probe molecule is incubated with RNA, isolated from a biological sample, under conditions of temperature and ionic strength that promote base pairing between the probe and target zamp3 or zamp4 RNA species. After separating unbound probe from hybridized molecules, the amount of hybrids is detected. Well-established hybridization methods of RNA detection include northern analysis and dot/slot blot hybridization (see, for example, Ausubel ibid, and Wu et al. (eds.), "Analysis of Gene Expression at the RNA Level," in Methods in Gene Biotechnology, pages 225-239 (CRC Press, Inc. 1997)). Nucleic acid probes can be detectably labeled with radioisotopes such as 32 P or 35 S. Alternatively, zamp3 or zamp4 RNA can be detected with a nonradioactive hybridization method (see, for example, Isaac (ed.), Protocols for Nucleic Acid Analysis by Nonradioactive Probes, Humana Press, Inc., 1993). Typically, nonradioactive detection is achieved by enzymatic conversion of chromogenic or chemiluminescent substrates. Illustrative nonradioactive moieties include biotin, fluorescein, and digoxigenin. Zamp3 or zamp4 oligonucleotide probes are also useful for in vivo diagnosis. As an illustration, 18 F-labeled oligonucleotides can be administered to a subject and visualized by positron emission tomography (Tavitian et al, Nature Medicine 4:467, 1998). Numerous diagnostic procedures take advantage of the polymerase chain reaction (PCR) to increase sensitivity of detection methods. Standard techniques for performing PCR are well-known (see, generally, Mathew (ed.), Protocols in Human Molecular Genetics (Humana Press, Inc. 1991), White (ed.), PCR Protocols: Current Methods and Applications (Humana Press, Inc. 1993), Cotter (ed.), Molecular Diagnosis of Cancer (Humana Press, Inc. 1996), Hanausek and Walaszek (eds.), Tumor Marker Protocols (Humana Press, Inc. 1998), Lo (ed.), Clinical Applications of PCR (Humana Press, Inc. 1998), and Meltzer (ed.), PCR in Bioanalysis (Humana Press, Inc. 1998)). PCR primers can be designed to amplify a sequence encoding a particular zamp3 or zamp4 domain or region of homology, such as the cysteine motif, as described herein. One variation of PCR for diagnostic assays is reverse transcriptase-PCR (RT- PCR). In the RT-PCR technique, RNA is isolated from a biological sample, reverse transcribed to cDNA, and the cDNA is incubated with zamp3 or zamp4 primers (see, for example, Wu et al. (eds.), "Rapid Isolation of Specific cDNAs or Genes by PCR," in Methods in Gene Biotechnology, CRC Press, Inc., pages 15-28, 1997). PCR is then performed and the products are analyzed using standard techniques. As an illustration, RNA is isolated from biological sample using, for example, the guanidinium-thiocyanate cell lysis procedure described above. Alternatively, a solid-phase technique can be used to isolate mRNA from a cell lysate. A reverse transcription reaction can be primed with the isolated RNA using random oligonucleotides, short homopolymers of dT, or zamp3 or zamp4 anti-sense oligomers. Oligo-dT primers offer the advantage that various mRNA nucleotide sequences are amplified that can provide control target sequences. Zamp3 or zamp4 sequences are amplified by the polymerase chain reaction using two flanking oligonucleotide primers that are typically at least 5 bases in length. PCR amplification products can be detected using a variety of approaches. For example, PCR products can be fractionated by gel electrophoresis, and visualized by ethidium bromide staining. Alternatively, fractionated PCR products can be transferred to a membrane, hybridized with a detectably-labeled zamp3 or zamp4 probe, and examined by autoradiography. Additional alternative approaches include the use of digoxigenin-labeled deoxyribonucleic acid triphosphates to provide chemiluminescence detection, and the C-TRAK colorimetric assay. Another approach is real time quantitative PCR (Perkin-Elmer Cetus, Norwalk, Ct.). A fluorogenic probe, consisting of an oligonucleotide with both a reporter and a quencher dye attached, anneals specifically between the forward and reverse primers. Using the 5' endonuclease activity of Taq DNA polymerase, the reporter dye is separated from the quencher dye and a sequence-specific signal is generated and increases as amplification increases. The fluorescence intensity can be continuously monitored and quantified during the PCR reaction. Another approach for detection of zamp3 or zamp4 expression is cycling probe technology (CPT), in which a single-stranded DNA target binds with an excess of DNA-RNA-DNA chimeric probe to form a complex, the RNA portion is cleaved with RNase H, and the presence of cleaved chimeric probe is detected (see, for example, Beggs et al., J. Clin. Microbiol. 34:2985, 1996 and Bekkaoui et al., Biotechniques 20:240, 1996). Alternative methods for detection of zamp3 or zamp4 sequences can utilize approaches such as nucleic acid sequence-based amplification (NASBA), cooperative amplification of templates by cross-hybridization (CATCH), and the ligase chain reaction (LCR) (see, for example, Marshall et al., U.S. Patent No. 5,686,272 (1997), Dyer et al., J. Virol. Methods 60:161, 1996; Ehricht et al., Eur. J. Biochem. 243:358, 1997 and Chadwick et al., J. Virol. Methods 70:59, 1998). Other standard methods are known to those of skill in the art. Zamp3 or zamp4 probes and primers can also be used to detect and to localize zamp3 or zamp4 gene expression in tissue samples. Methods for such in situ hybridization are well-known to those of skill in the art (see, for example, Choo (ed.), In Situ Hybridization Protocols, Humana Press, Inc., 1994; Wu et al. (eds.), "Analysis of Cellular DNA or Abundance of mRNA by Radioactive In Situ Hybridization (RISH)," in Methods in Gene Biotechnology, CRC Press, Inc., pages 259-278, 1997 and Wu et al. (eds.), "Localization of DNA or Abundance of mRNA by Fluorescence In Situ Hybridization (RISH)," in Methods in Gene Biotechnology, CRC Press, Inc., pages 279- 289, 1997). Various additional diagnostic approaches are well-known to those of skill in the art (see, for example, Mathew (ed.), Protocols in Human Molecular Genetics Humana Press, Inc., 1991; Coleman and Tsongalis, Molecular Diagnostics. Humana Press, Inc., 1996 and Elles, Molecular Diagnosis of Genetic Diseases, Humana Press, Inc., 1996). The present invention further provides counterpart polypeptides and polynucleotides from other species (orthologs). These species include, but are not limited to mammalian, avian, amphibian, reptile, fish, insect and other vertebrate and invertebrate species. Of particular interest are zamp3 and zamp4 polypeptides from other mammalian species, including human, rat, porcine, ovine, bovine, canine, feline, equine and other primate proteins. Species homologs of the human proteins can be cloned using information and compositions provided by the present invention in combination with conventional cloning techniques. For example, a cDNA can be cloned using mRNA obtained from a tissue or cell type that expresses the protein. Suitable sources of mRNA can be identified by probing Northern blots with probes designed from the sequences disclosed herein. A library is then prepared from mRNA of a positive tissue of cell line. A zamp3 or zamp4 polypeptide-encoding cDNA can then be isolated by a variety of methods, such as by probing with a complete or partial human cDNA or with one or more sets of degenerate probes based on the disclosed sequences. A cDNA can also be cloned using the polymerase chain reaction, or PCR (Mullis, U.S. Patent 4,683,202), using primers designed from the sequences disclosed herein. Within an additional method, the cDNA library can be used to transform or transfect host cells, and expression of the cDNA of interest can be detected with an • antibody to zamp3 or zamp4 polypeptide. Similar techniques can also be applied to the isolation of genomic clones. Alternate species polypeptides of zamp 3 and zamp4 may have importance therapeutically. It has been demonstrated that in some cases use of a non- native protein, i.e., protein from a different species, can be more potent than the native protein. For example, salmon calcitonin has been shown to be considerably more effective in arresting bone resoφtion than human forms of calcitonin. There are several hypotheses as to why salmon calcitonin is more potent than human calcitonin in treatment of osteoporosis. These hypotheses include: 1) salmon calcitonin is more resistant to degradation; 2) salmon calcitonin has a lower metabolic clearance rate (MCR); and 3) salmon calcitonin may have a slightly different conformation, resulting in a higher affinity for bone receptor sites. Another example is found in the β- endoφhin family (Ho et al., Int. J. Peptide Protein Res. 29:521-24, 1987). Studies have demonstrated that the peripheral opioid activity of camel, horse, turkey and ostrich β- endoφhins is greater than that of human β-endoφhins when isolated guinea pig ileum was electrostimulated and contractions were measured. Vas deferens from rat, mouse and rabbit were assayed as well. In the rat vas deferens model, camel and horse β- endoφhins showed the highest relative potency. Synthesized rat relaxin was as active as human and porcine relaxin in the mouse symphysis pubis assay (Bullesbach and Schwabe, Eur. J. Biochem. 241:533-7, 1996). Thus, the murine zcys4 molecules of the present invention may have higher potency than the human endogenous molecule in human cells, tissues and recipients. Those skilled in the art will recognize that the sequences disclosed in SEQ ID NO:l, SEQ ID NO:2, and SEQ ID NO: 19 represent a single allele of the human zamp3 gene and polypeptide, and that the sequences in SEQ ID NO:5 and SEQ ID NO:6 represent a single allele of the human zamp4 gene and that allelic variation and alternative splicing are expected to occur. Allelic variants can be cloned by probing cDNA or genomic libraries from different individuals according to standard procedures. Allelic variants of the DNA sequence shown in SEQ ID NO:l, SEQ ID NO: 19, and SEQ ID NO:5, including those containing silent mutations and those in which mutations result in amino acid sequence changes, are within the scope of the present invention. Within preferred embodiments of the invention, the isolated nucleic acid molecules can hybridize under stringent conditions to nucleic acid molecules having at least a portion of the nucleotide sequence of SEQ ID NOs:l or 5 or to nucleic acid molecules having a nucleotide sequence complementary to those sequences. In general, stringent conditions are selected to be about 5°C lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. The T m is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. A pair of nucleic acid molecules, such as DNA-DNA, RNA-RNA and DNA-RNA, can hybridize if the nucleotide sequences have some degree of complementarity. Hybrids can tolerate mismatched base pairs in the double helix, but the stability of the hybrid is influenced by the degree of mismatch. The T m of the mismatched hybrid decreases by 1°C for every 1-1.5% base pair mismatch. Varying the stringency of the hybridization conditions allows control over the degree of mismatch that will be present in the hybrid. The degree of stringency increases as the hybridization temperature increases and the ionic strength of the hybridization buffer decreases. Stringent hybridization conditions encompass temperatures of about 5-25°C below the T m of the hybrid and a hybridization buffer having up to 1 M Na + . Higher degrees of stringency at lower temperatures can be achieved with the addition of formamide which reduces the T m of the hybrid about 1°C for each 1% formamide in the buffer solution. Generally, such stringent conditions include temperatures of 20-70°C and a hybridization buffer containing up to 6xSSC and 0-50% formamide. A higher degree of stringency can be achieved at temperatures of from 40-70°C with a hybridization buffer having up to 4xSSC and from 0-50% formamide. Highly stringent conditions typically encompass temperatures of 42-70°C with a hybridization buffer having up to lxSSC and 0-50% formamide. Different degrees of stringency can be used during hybridization and washing to achieve maximum specific binding to the target sequence. Typically, the washes following hybridization are performed at increasing degrees of stringency to remove non-hybridized polynucleotide probes from hybridized complexes. The above conditions are meant to serve as a guide and it is well within the abilities of one skilled in the art to adapt these conditions for use with a particular polypeptide hybrid. The T m for a specific target sequence is the temperature (under defined conditions) at which 50% of the target sequence will hybridize to a perfectly matched probe sequence. Those conditions which influence the T m include, the size and base pair content of the polynucleotide probe, the ionic strength of the hybridization solution, and the presence of destabilizing agents in the hybridization solution. Numerous equations for calculating T m are known in the art, and are specific for DNA, RNA and DNA-RNA hybrids and polynucleotide probe sequences of varying length (see, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual. Second Edition (Cold Spring Harbor Press 1989); Ausubel et al., (eds.), Current Protocols in Molecular Biology (John Wiley and Sons, Inc. 1987); Berger and Kimmel (eds.), Guide to Molecular Cloning Techniques, (Academic Press, Inc. 1987); and Wetmur, Crit. Rev. Biochem. Mol. Biol. 26:227 (1990)). Sequence analysis software, such as OLIGO 6.0 (LSR; Long Lake, MN) and Primer Premier 4.0 (Premier Biosoft International; Palo Alto, CA), as well as sites on the Internet, are available tools for analyzing a given sequence and calculating T m based on user defined criteria. Such programs can also analyze a given sequence under defined conditions and identify suitable probe sequences. Typically, hybridization of longer polynucleotide sequences, >50 base pairs, is performed at temperatures of about 20-25°C below the calculated T m . For smaller probes, <50 base pairs, hybridization is typically carried out at the T m or 5- 10°C below. This allows for the maximum rate of hybridization for DNA-DNA and DNA-RNA hybrids. The length of the polynucleotide sequence influences the rate and stability of hybrid formation. Smaller probe sequences, <50 base pairs, reach equilibrium with complementary sequences rapidly, but may form less stable hybrids. Incubation times of anywhere from minutes to hours can be used to achieve hybrid formation. Longer probe sequences come to equilibrium more slowly, but form more stable complexes even at lower temperatures. Incubations are allowed to proceed overnight or longer. Generally, incubations are carried out for a period equal to three times the calculated Cot time. Cot time, the time it takes for the polynucleotide sequences to reassociate, can be calculated for a particular sequence by methods known in the art. The base pair composition of polynucleotide sequence will effect the thermal stability of the hybrid complex, thereby influencing the choice of hybridization temperature and the ionic strength of the hybridization buffer. A-T pairs are less stable than G-C pairs in aqueous solutions containing sodium chloride. Therefore, the higher the G-C content, the more stable the hybrid. Even distribution of G and C residues within the sequence also contribute positively to hybrid stability. In addition, the base pair composition can be manipulated to alter the T m of a given sequence. For example, 5-methyldeoxycytidine can be substituted for deoxycytidine and 5-bromodeoxuridine can be substituted for thymidine to increase the T m> whereas 7-deazz-2'-deoxyguanosine can be substituted for guanosine to reduce dependence on T m . The ionic concentration of the hybridization buffer also affects the stability of the hybrid. Hybridization buffers generally contain blocking agents such as Denhardt's solution (Sigma Chemical Co., St. Louis, Mo.), denatured salmon sperm DNA, tRNA, milk powders (BLOTTO), heparin or SDS, and a Na + source, such as SSC (lx SSC: 0.15 M sodium chloride, 15 mM sodium citrate) or SSPE (lx SSPE: 1.8 M NaCl, 10 mM NaH PO 4 , 1 mM EDTA, pH 7.7). By decreasing the ionic concentration of the buffer, the stability of the hybrid is increased. Typically, hybridization buffers contain from between 10 mM - 1 M Na + . The addition of destabilizing or denaturing agents such as formamide, tetralkylammonium salts, guanidinium cations or thiocyanate cations to the hybridization solution will alter the T m of a hybrid. Typically, formamide is used at a concentration of up to 50% to allow incubations to be carried out at more convenient and lower temperatures. Formamide also acts to reduce non-specific background when using RNA probes. As an illustration, a nucleic acid molecule encoding a variant zamp3 or zamp4 polypeptide can be hybridized with a nucleic acid molecule having at least a portion of the nucleotide sequence of SEQ ID NOs: 1 or 5 (or their complements) at 42°C overnight in a solution comprising 50% formamide, 5x SSC (lx SSC: 0.15 M sodium chloride and 15 mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5x Denhardt's solution (lOOx Denhardt's solution: 2% (w/v) Ficoll 400, 2% (w/v) polyvinyl-pyrrolidone, and 2% (w/v) bovine serum albumin), 10% dextran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA. One of skill in the art can devise variations of these hybridization conditions. For example, the hybridization mixture can be incubated at a higher or lower temperature, such as about 65°C, in a solution that does not contain formamide. Moreover, premixed hybridization solutions are available (e.g., EXPRESSHYB Hybridization Solution from CLONTECH Laboratories, Inc.), and hybridization can be performed according to the manufacturer's instructions. Following hybridization, the nucleic acid molecules can be washed to remove non-hybridized nucleic acid molecules under stringent conditions, or under highly stringent conditions. Typical stringent washing conditions include washing in a solution of 0.5x-2x SSC with 0.1% sodium dodecyl sulfate (SDS) at 55-65°C. That is, nucleic acid molecules encoding a variant zamp3 or zamp4 polypeptide hybridize with a nucleic acid molecule having at least a portion of the nucleotide sequence of SEQ ID NOs:l or 5 (or their complements) under stringent washing conditions, in which the wash stringency is equivalent to 0.5x-2x SSC with 0.1% SDS at 50-65°C, including 0.5x SSC with 0.1% SDS at 55°C, or 2x SSC with 0.1% SDS at 65°C. One of skill in the art can readily devise equivalent conditions, for example, by substituting SSPE for SSC in the wash solution. Typical highly stringent washing conditions include washing in a solution of 0.1x-0.2x SSC with 0.1% sodium dodecyl sulfate (SDS) at 50-65°C. In other words, nucleic acid molecules encoding a variant zamp3 or zamp4 polypeptide hybridize with a nucleic acid molecule having at least a portion of the nucleotide sequence of SEQ ID NOs: 1 or 5 (or their complements) under highly stringent washing conditions, in which the wash stringency is equivalent to 0.1x-0.2x SSC with 0.1% SDS at 50-65°C, including O.lx SSC with 0.1% SDS at 50°C, or 0.2x SSC with 0.1% SDS at 65°C. The present invention also contemplates zamp3 or zamp4 variant nucleic acid molecules that can be identified using two criteria: a determination of the similarity between the encoded polypeptide with the amino acid sequence of SEQ ID NOs: 2 or 6, and a hybridization assay, as described above. Such zamp3 and zamp4 variants include nucleic acid molecules (1) that hybridize with at least a portion of a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 1 or 5 (or their complements) under stringent washing conditions, in which the wash stringency is equivalent to 0.5X- 2X SSC with 0.1% SDS at 50-65°C, and (2) that encode a polypeptide having at least 80%, at least 90%, at least 95% or greater than 95% sequence identity to the amino acid sequence of SEQ ID NOs: 2 or 6. Alternatively, zamp3 and zamp4 variants can be characterized as nucleic acid molecules (1) that hybridize with a nucleic acid molecule having at least a portion of the nucleotide sequence of SEQ ID NO: 1 or 5 (or their complements) under highly stringent washing conditions, in which the wash stringency is equivalent to 0.1X-0.2X SSC with 0.1% SDS at 50-65°C, and (2) that encode a polypeptide having at least 80%, at least 90%, at least 95% or greater than 95% sequence identity to the amino acid sequence of SEQ ID NOs:2 or 6. The present invention also provides isolated zamp3 and zamp4 polypeptides that are substantially homologous to the polypeptides of SEQ ID NO:2 or SEQ ID NO:6 and their species homologs/orthologs. The term "substantially homologous" is used herein to denote polypeptides having 50%, preferably 60%, more preferably at least 80%, sequence identity to the sequences shown in SEQ ID NO:2 or SEQ ID NO:6 or their orthologs or paralogs. Such polypeptides will more preferably be at least 90% identical, and most preferably 95% or more identical to SEQ ID NO:2 or SEQ ID NO:6 or its orthologs or paralogs. Percent sequence identity is determined by conventional methods. See, for example, Altschul et al., Bull. Math. Bio. 48: 603-616, 1986 and Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915-10919, 1992. Briefly, two amino acid sequences are aligned to optimize the alignment scores using a gap opening penalty of 10, a gap extension penalty of 1, and the "blosum 62" scoring matrix of Henikoff and Henikoff (ibid.) as shown in Table 3 (amino acids are indicated by the standard one-letter codes). The percent identity is then calculated as: Total number of identical matches x lOO [length of the longer sequence plus the number of gaps introduced into the longer sequence in order to align the two sequences] > -* CM ro CO rH ro CN CN 1 1 1 ft C- rH rH ro CN 1 1 1 1 1 En SΩ CN CN rH ro H 1 1 1 X, LO rH ro O CO CN CN 1 1 1 1 1 1 1 • * * CN CN o ro CN CN rH 1 1 1 1 1 ω • * CN ro H o ro CN H ro rH ro rH 1 1 1 1 1 Λ iτ co ro ro rH CN H CN rH CN CN CN ro H 1 1 1 1 1 1 1 1 1 O U> CN CN ro ro CN o CN CN ro ro 1 1 1 1 1 1 1 1 1 1 1 W in CN o ro ro H CN ro H o rH ro CN CN 1 1 1 1 1 1 1 1 1 σ in CN CN o ro CN rH o ro o rH CN H CN 1 1 1 1 1 1 1 1 u CΛ ro ro ro H H ro rH CN ro rH H CN CN rH 1 1 1 1 1 1 1 1 1 1 1 1 1 p >> ro o CN H rH ro H ro ro H o rH ro ro 1 1 1 1 1 1 1 1 1 1 a <£> H ro o O O H CO ro O CN ro CN H O CN ro 1 1 1 1 1 1 1 1 in O CN ro H O CN O ro CN CN H ro CN H H ro CN ro 1 1 1 1 1 1 1 1 1 1 1 1 <tf CN CN o H o CN H rH rH CN H rH o ro CN o 1 1 1 1 1 1 1 1 1 1 1 U P3 P U α W K H J « S in Λ CO EH ≥ > Sequence identity of polynucleotide molecules is determined by similar methods using a ratio as disclosed above. Those skilled in the art appreciate that there are many established algorithms available to align two amino acid sequences. The "FASTA" similarity search algorithm of Pearson and Lipman is a suitable protein alignment method for examining the level of identity shared by an amino acid sequence disclosed herein and the amino acid sequence of a putative variant zamp3 or zamp4. The FASTA algorithm is described by Pearson and Lipman, Proc. Nat. Acad. Sci. USA 85:2444, 1988, and by Pearson, Meth. Enzvmol. 183:63, 1990. Briefly, FASTA first characterizes sequence similarity by identifying regions shared by the query sequence (e.g., SEQ ID NOs:2 or 6) and a test sequence that have either the highest density of identities (if the ktup variable is 1) or pairs of identities (if ktup=2), without considering conservative amino acid substitutions, insertions, or deletions. The ten regions with the highest density of identities are then re-scored by comparing the similarity of all paired amino acids using an amino acid substitution matrix, and the ends of the regions are "trimmed" to include only those residues that contribute to the highest score. If there are several regions with scores greater than the "cutoff value (calculated by a predetermined formula based upon the length of the sequence and the ktup value), then the trimmed initial regions are examined to determine whether the regions can be joined to form an approximate alignment with gaps. Finally, the highest scoring regions of the two amino acid sequences are aligned using a modification of the Needleman-Wunsch-Sellers algorithm (Needleman and Wunsch, J. Mol. Biol. 48:444, 1970; Sellers, SIAM J. Appl. Math. 26:787, 1974), which allows for amino acid insertions and deletions. Preferred parameters for FASTA analysis are: ktup=l, gap opening penal ty= 10, gap extension penalty=l, and substitution matrix=BLOSUM62. These parameters can be introduced into a FASTA program by modifying the scoring matrix file ("SMATRIX"), as explained in Appendix 2 of Pearson, Meth. Enzvmol. 183:63, 1990. FASTA can also be used to determine the sequence identity of nucleic acid molecules using a ratio as disclosed above. For nucleotide sequence comparisons, the ktup value can range between one to six, preferably from three to six, most preferably three, with other parameters set as default. The present invention includes nucleic acid molecules that encode a polypeptide having one or more "conservative amino acid substitutions," compared with the amino acid sequence of SEQ ID NOs:2 or 6. Conservative amino acid substitutions can be based upon the chemical properties of the amino acids. That is, variants can be obtained that contain one or more amino acid substitutions of SEQ ID NOs:2 or 6, in which an alkyl amino acid is substituted for an alkyl amino acid in a zamp3 or zamp4 amino acid sequence, an aromatic amino acid is substituted for an aromatic amino acid in a zamp3 or zamp4 amino acid sequence, a sulfur-containing amino acid is substituted for a sulfur-containing amino acid in a zamp3 or zamp4 amino acid sequence, a hydroxy-containing amino acid is substituted for a hydroxy-containing amino acid in a zamp3 or zamp4 amino acid sequence, an acidic amino acid is substituted for an acidic amino acid in a zamp3 or zamp4 amino acid sequence, a basic amino acid is substituted for a basic amino acid in a zamp3 or zamp4 amino acid sequence, or a dibasic monocarboxylic amino acid is substituted for a dibasic monocarboxylic amino acid in a zamp3 or zamp4 amino acid sequence. Among the common amino acids, for example, a "conservative amino acid substitution" is illustrated by a substitution among amino acids within each of the following groups: (1) glycine, alanine, valine, leucine, and isoleucine, (2) phenylalanine, tyrosine, and tryptophan, (3) serine and threonine, (4) aspartate and glutamate, (5) glutamine and asparagine, and (6) lysine, arginine and histidine. The BLOSUM62 table is an amino acid substitution matrix derived from about 2,000 local multiple alignments of protein sequence segments, representing highly conserved regions of more than 500 groups of related proteins (Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915, 1992). Accordingly, the BLOSUM62 substitution frequencies can be used to define conservative amino acid substitutions that may be introduced into the amino acid sequences of the present invention. Although it is possible to design amino acid substitutions based solely upon chemical properties (as discussed above), the language "conservative amino acid substitution" preferably refers to a substitution represented by a BLOSUM62 value of greater than -1. For example, an amino acid substitution is conservative if the substitution is characterized by a BLOSUM62 value of 0, 1, 2, or 3. According to this system, preferred conservative amino acid substitutions are characterized by a BLOSUM62 value of at least 1 (e.g., 1, 2 or 3), while more preferred conservative amino acid substitutions are characterized by a BLOSUM62 value of at least 2 (e.g., 2 or 3). Conservative amino acid changes in a zamp3 or zamp4 gene can be introduced by substituting nucleotides for the nucleotides recited in SEQ ID NOs:l or 5. Such "conservative amino acid" variants can be obtained, for example, by oligonucleotide-directed mutagenesis, linker-scanning mutagenesis, mutagenesis using the polymerase chain reaction, and the like (see Ausubel (1995) at pages 8-10 to 8-22; and McPherson (ed.), Directed Mutagenesis: A Practical Approach (IRL Press 1991)). The ability of such variants to promote the anti-microbial or other properties of the wild-type protein can be determined using a standard methods, such as the assays described herein. Alternatively, a variant zamp3 or zamp4 polypeptide can be identified by the ability to specifically bind anti-zamp3 or zamp4 antibodies. Substantially homologous proteins and polypeptides are characterized as having one or more amino acid substitutions, deletions or additions. These changes are preferably of a minor nature, that is conservative amino acid substitutions and other substitutions that do not significantly affect the folding or activity of the protein or polypeptide; small deletions, typically of one to about 30 amino acids; and small amino- or carboxyl-terminal extensions, such as an amino-terminal methionine residue, a small linker peptide of up to about 20-25 residues, or a small extension that facilitates purification (an affinity tag), such as a poly-histidine tract, protein A (Nilsson et al., EMBO J. 4:1075, 1985; Nilsson et al., Methods Enzvmol. 198:3. 1991), glutathione S transferase (Smith and Johnson, Gene 67:31, 1988), maltose binding protein (Kellerman and Ferenci, Methods Enzvmol. 90:459-463, 1982; Guan et al., Gene 67:21-30, 1987), thioredoxin, ubiquitin, cellulose binding protein, T7 polymerase, or other antigenic epitope or binding domain. See, in general Ford et al., Protein Expression and Purification 2: 95-107, 1991. DNAs encoding affinity tags are available from commercial suppliers (e.g., Pharmacia Biotech, Piscataway, NJ; New England Biolabs, Beverly, MA). Polypeptides comprising affinity tags can further comprise a proteolytic cleavage site between the zamp3 or zamp4 polypeptide and the affinity tag. Preferred such sites include thrombin cleavage sites and factor Xa cleavage sites. The proteins of the present invention can also comprise, in addition to the 20 standard amino acids, non-naturally occurring amino acid residues. Non- naturally occurring amino acids include, without limitation, trans-3-methylproline, 2,4- methanoproline, cis-4-hydroxyproline, trans-4-hydroxyproline, N-methyl-glycine, allo- threonine, methylthreonine, hydroxyethyl-cysteine, hydroxyethylhomocysteine, nitroglutamine, homoglutamine, pipecolic acid, tert-leucine, norvaline, 2- azaphenylalanine, 3-azaphenylalanine, 4-azaphenyl-alanine, 4-fluorophenylalanine, 4- hydroxyproline, 6-N-methyl lysine, 2-aminoisobutyric acid, isovaline and α-methyl serine . Several methods are known in the art for incoφorating non-naturally occurring amino acid residues into proteins. For example, an in vitro system can be employed wherein nonsense mutations are suppressed using chemically aminoacylated suppressor tRΝAs. Methods for synthesizing amino acids and aminoacylating tRΝA are known in the art. Transcription and translation of plasmids containing nonsense mutations are carried out in a cell free system comprising an E. coli S30 extract and commercially available enzymes and other reagents. Proteins are purified by chromatography. See, for example, Robertson et al., J. Am. Chem. Soc. 113:2722, 1991; Ellman et al., Meth. Enzvmol. 202:301, 1991; Chung et al., Science 259:806-09, 1993; and Chung et al., Proc. Natl. Acad. Sci. USA 90:10145-49, 1993). In a second method, translation is carried out in Xenopus oocytes by microinjection of mutated mRNA and chemically aminoacylated suppressor tRNAs (Turcatti et al., J. Biol. Chem. 271: 19991-98, 1996). Within a third method, E. coli cells are cultured in the absence of a natural amino acid that is to be replaced (e.g., phenylalanine) and in the presence of the desired non-naturally occurring amino acid(s) (e.g., 2-azaphenylalanine, 3- azaphenylalanine, 4-azaphenylalanine, or 4-fluorophenylalanine). The non-naturally occurring amino acid is incoφorated into the protein in place of its natural counteφart. See, Koide et al., Biochem. 33:7470-76, 1994. Naturally occurring amino acid residues can be converted to non-naturally occurring species by in vitro chemical modification. Chemical modification can be combined with site-directed mutagenesis to further expand the range of substitutions (Wynn and Richards, Protein Sci. 2:395-403, 1993). A limited number of non-conservative amino acids, amino acids that are not encoded by the genetic code, non-naturally occurring amino acids, and unnatural amino acids may be substituted for zamp3 or zamp4 polypeptide amino acid residues. "Unnatural amino acids" have been modified after protein synthesis, and/or have a chemical structure in their side chain(s) different from that of the standard amino acids. Unnatural amino acids can be chemically synthesized, or preferably, are commercially available, and include pipecolic acid, thiazolidine carboxylic acid, dehydroproline, 3- and 4-methylproline, and 3,3-dimethylproline. Essential amino acids in the zamp3 or zamp4 polypeptides of the present invention can be identified according to procedures known in the art, such as site- directed mutagenesis or alanine-scanning mutagenesis (Cunningham and Wells, Science 244: 1081-5, 1989). In the latter technique, single alanine mutations are introduced at every residue in the molecule, and the resultant mutant molecules are tested for biological activity (e.g., anti-microbial activity) to identify amino acid residues that are critical to the activity of the molecule. See also, Hilton et al., J. Biol. Chem. 271:4699-708, 1996. Sites of ligand-receptor or other biological interaction can also be determined by physical analysis of structure, as determined by such techniques as nuclear magnetic resonance, crystallography, electron diffraction or photoaffinity labeling, in conjunction with mutation of putative contact site amino acids. See, for example, de Vos et al., Science 255:306-12, 1992; Smith et al., J. Mol. Biol. 224:899- 904, 1992; Wlodaver et al., FEBS Lett. 309:59-64, 1992. The identities of essential amino acids can also be inferred from analysis of homologies with related β-defensins. Multiple amino acid substitutions can be made and tested using known methods of mutagenesis and screening, such as those disclosed by Reidhaar-Olson and Sauer (Science 241:53-7, 1988) or Bowie and Sauer (Proc. Natl. Acad. Sci. USA 86:2152-6, 1989). Briefly, these authors disclose methods for simultaneously randomizing two or more positions in a polypeptide, selecting for functional polypeptide, and then sequencing the mutagenized polypeptides to determine the spectrum of allowable substitutions at each position. Other methods that can be used include phage display (e.g., Lowman et al., Biochem. 30: 10832-7, 1991; Ladner et al., U.S. Patent No. 5,223,409; Huse, WIPO Publication WO 92/06204) and region- directed mutagenesis (Derbyshire et al., Gene 46:145, 1986; Ner et al., DNA 7:127, 1988). Variants of the disclosed zamp3 or zamp4 DNA and polypeptide sequences can be generated through DNA shuffling as disclosed by Stemmer, Nature 370:389-91, 1994, Stemmer. Proc. Natl. Acad. Sci. USA 91:10747-51. 1994 and WIPO Publication WO 97/20078. Briefly, variant DNAs are generated by in vitro homologous recombination by random fragmentation of a parent DNA followed by reassembly using PCR, resulting in randomly introduced point mutations. This technique can be modified by using a family of parent DNAs, such as allelic variants or DNAs from different species, to introduce additional variability into the process. Selection or screening for the desired activity, followed by additional iterations of mutagenesis and assay provides for rapid "evolution" of sequences by selecting for desirable mutations while simultaneously selecting against detrimental changes. Mutagenesis methods as disclosed above can be combined with high- throughput, automated screening methods to detect activity of cloned, mutagenized polypeptides in host cells. Mutagenized DNA molecules that encode active polypeptides (e.g., anti-microbial activity) can be recovered from the host cells and rapidly sequenced using modern equipment. These methods allow the rapid determination of the importance of individual amino acid residues in a polypeptide of interest, and can be applied to polypeptides of unknown structure. Using the methods discussed above, one of ordinary skill in the art can identify and/or prepare a variety of polypeptides that are substantially homologous to residues 1-63 of SEQ ED NO:2 or to residues 1-43 of SEQ ID NO:6 or allelic variants thereof and retain the anti-microbial properties of the wild-type protein. Such polypeptides may include additional amino acids from affinity tags and the like. Such polypeptides may also include additional polypeptide segments as generally disclosed above. The polypeptides of the present invention, including full-length proteins, fragments thereof and fusion proteins, can be produced in genetically engineered host cells according to conventional techniques. However, host cells must be selected with some care as a result of the anti-microbial activity of the molecules of the present invention. For example, any cell culture-based system must be evaluated, because zamp3 or zamp4 polypeptides, fragments, fusion proteins, antibodies, agonists or antagonists may kill the host cell as a part of an anti-microbial function. Zamp3 or zamp4 polypeptides are of a small enough size to permit preparation by PCR or other protein chemistry techniques to avoid any potential host cell toxicity problems. Alternatively, native or engineered precursor proteins, prior to post-translational cleavage to yield the mature zamp3 or zamp4 polypeptide, are inactive, thereby limiting host cell cytotoxicity prior to lysosomal packaging. See, for example, Lehrer et al., Cell 64: 229-30, 1991. Thus, precursor proteins to zamp3 or zamp4 polypeptides may be produced in microbial cell culture. Suitable host cells are those cell types that can be transformed or transfected with exogenous DNA and grown in culture, and include bacteria, fungal cells, and cultured higher eukaryotic cells. Eukaryotic cells, particularly cultured cells of multicellular organisms, are preferred. Techniques for manipulating cloned DNA molecules and introducing exogenous DNA into a variety of host cells are disclosed by Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989, and Ausubel et al. (eds.), Current Protocols in Molecular Biology, John Wiley and Sons, Inc., NY, 1987. In general, a DNA sequence encoding a zamp3 or zamp4 polypeptide of the present invention is operably linked to other genetic elements required for its expression, generally including a transcription promoter and terminator within an expression vector. The vector will also commonly contain one or more selectable markers and one or more origins of replication, although those skilled in the art will recognize that within certain systems selectable markers may be provided on separate vectors, and replication of the exogenous DNA may be provided by integration into the host cell genome. Selection of promoters, terminators, selectable markers, vectors and other elements is a matter of routine design within the level of ordinary skill in the art. Many such elements are described in the literature and are available through commercial suppliers. To direct a zamp3 or zamp4 polypeptide into the secretory pathway of a host cell, a secretory signal sequence (also known as a leader sequence, prepro sequence or pre sequence) is provided in the expression vector. The secretory signal sequence may be that of the zamp3 or zamp4 polypeptide, or may be derived from another secreted protein (e.g., t-PA) or synthesized de novo. The secretory signal sequence is joined to the zamp3 or zamp4 polypeptide-encoding DNA sequence in the correct reading frame. Secretory signal sequences are commonly positioned 5' to the DNA sequence encoding the polypeptide of interest, although certain signal sequences may be positioned elsewhere in the DNA sequence of interest (see, e.g., Welch et al., U.S. Patent No. 5,037,743; Holland et al., U.S. Patent No. 5,143,830). The invention provides an expression vector comprising the following operably linked elements: a transcription promoter; a DNA segment encoding a zamp3 or zamp4 protein as described herein; and a transcription terminator. The invention also provides that the DNA segment further encodes a secretory signal sequence operably linked to said protein, such secretory signal sequence may be is a polypeptide having the sequence of amino acid residue 1 to amino acid residue 22 of SEQ ID NO:2. Alternatively, the secretory signal sequence contained in the polypeptides of the present invention is used to direct other polypeptides into the secretory pathway. The present invention provides for such fusion polypeptides. A signal fusion polypeptide can be made wherein a secretory signal sequence derived from amino acid residues 1-22 of SEQ ID NO:2, is operably linked to another polypeptide using methods known in the art and disclosed herein. The secretory signal sequence contained in the fusion polypeptides of the present invention is preferably fused amino-terminally to an additional peptide to direct the additional peptide into the secretory pathway. Such constructs have numerous applications known in the art. For example, these novel secretory signal sequence fusion constructs can direct the secretion of an active component of a normally non-secreted protein, such as a receptor. Such fusions may be used in vivo or in vitro to direct peptides through the secretory pathway. Cultured mammalian cells are also preferred hosts within the present invention. Methods for introducing exogenous DNA into mammalian host cells include calcium phosphate-mediated transfection (Wigler et al., Cell 14:725, 1978; Corsaro and Pearson, Somatic Cell Genetics 7:603, 1981: Graham and Van der Eb, Virology 52:456, 1973), electroporation (Neumann et al., EMBO J. 1:841-5, 1982), DEAE-dextran mediated transfection (Ausubel et al., eds., Current Protocols in Molecular Biology. John Wiley and Sons, Inc., NY, 1987), liposome-mediated transfection (Hawley-Nelson et al., Focus 15:73, 1993; Ciccarone et al., Focus 15:80, 1993), and viral vectors (Miller and Rosman, BioTechniques 7:980-90, 1989; Wang and Finer, Nature Med. 2:714-16, 1996). The production of recombinant polypeptides in cultured mammalian cells is disclosed, for example, by Levinson et al., U.S. Patent No. 4,713,339; Hagen et al., U.S. Patent No. 4,784,950; Palmiter et al., U.S. Patent No. 4,579,821; and Ringold, U.S. Patent No. 4,656,134. Preferred cultured mammalian cells include the COS-1 (ATCC No. CRL 1650), COS-7 (ATCC No. CRL 1651), BHK 570 (ATCC No. CRL 10314), 293 (ATCC No. CRL 1573; Graham et al., J. Gen. Virol. 36:59-72, 1977) and Chinese hamster ovary (e.g. CHO-K1; ATCC No. CCL 61) cell lines. Additional suitable cell lines are known in the art and available from public depositories such as the American Type Culture Collection, Rockville, Maryland. In general, strong transcription promoters are preferred, such as promoters from SV-40 or cytomegalovirus. See, e.g., U.S. Patent No. 4,956,288. Other suitable promoters include those from metallothionein genes (U.S. Patent Nos. 4,579,821 and 4,601,978) and the adenovirus major late promoter. Drug selection is generally used to select for cultured mammalian cells into which foreign DNA has been inserted. Such cells are commonly referred to as "transfectants". Cells that have been cultured in the presence of the selective agent and are able to pass the gene of interest to their progeny are referred to as "stable transfectants." A preferred selectable marker is a gene encoding resistance to the antibiotic neomycin. Selection is carried out in the presence of a neomycin-type drug, such as G-418 or the like. Selection systems may also be used to increase the expression level of the gene of interest, a process referred to as "amplification." Amplification is carried out by culturing transfectants in the presence of a low level of the selective agent and then increasing the amount of selective agent to select for cells that produce high levels of the products of the introduced genes. A preferred amplifiable selectable marker is dihydrofolate reductase, which confers resistance to methotrexate. Other drug resistance genes (e.g., hygromycin resistance, multi-drug resistance, puromycin acetyltransferase) can also be used. Alternative markers that introduce an altered phenotype, such as green fluorescent protein, or cell surface proteins such as CD4, CD8, Class I MHC, placental alkaline phosphatase may be used to sort transfected cells from untransfected cells by such means as FACS sorting or magnetic bead separation technology. Other higher eukaryotic cells can also be used as hosts, including plant cells, insect cells and avian cells. The use of Agrobacterium rhizogenes as a vector for expressing genes in plant cells has been reviewed by Sinkar et al., J. Biosci. (Bangalore) 11:47-58, 1987. Transformation of insect cells and production of foreign polypeptides therein is disclosed by Guarino et al., U.S. Patent No. 5,162,222 and WIPO publication WO 94/06463. Insect cells can be infected with recombinant baculovirus, commonly derived from Autographa californica nuclear polyhedrosis virus (AcNPV). DNA encoding the zamp3 or zamp4 polypeptide is inserted into the baculoviral genome in place of the AcNPV polyhedrin gene coding sequence by one of two methods. The first is the traditional method of homologous DNA recombination between wild-type AcNPV and a transfer vector containing the zamp3 or zamp4 flanked by AcNPV sequences. Suitable insect cells, e.g. SF9 cells, are infected with wild-type AcNPV and transfected with a transfer vector comprising a 3 or zamp4 polynucleotide operably linked to an AcNPV polyhedrin gene promoter, terminator, and flanking sequences. See, King and Possee, The Baculovirus Expression System: A Laboratory Guide, London, Chapman & Hall; O'Reilly et al., Baculovirus Expression Vectors: A Laboratory Manual, New York, Oxford University Press., 1994; and, Richardson, C. D., Ed., Baculovirus Expression Protocols. Methods in Molecular Biology, Totowa, NJ, Humana Press, 1995. Natural recombination within an insect cell will result in a recombinant baculovirus which contains zamp3 or zamp4 driven by the polyhedrin promoter. Recombinant viral stocks are made by methods commonly used in the art. The second method of making recombinant baculovirus utilizes a transposon-based system described by Luckow (Luckow et al., J Virol. 67:4566-79, 1993). This system is sold in the Bac-to-Bac kit (Life Technologies, Rockville, MD). This system utilizes a transfer vector, pFastBacl™ (Life Technologies) containing a Tn7 transposon to move the DNA encoding the zamp3 or zamp4 polypeptide into a baculovirus genome maintained in E. coli as a large plasmid called a "bacmid." The pFastBacl™ transfer vector utilizes the AcNPV polyhedrin promoter to drive the expression of the gene of interest, in this case zamp3 or zamp4. However, pFastBacl™ can be modified to a considerable degree. The polyhedrin promoter can be removed and substituted with the baculovirus basic protein promoter (also known as Vcor, p6.9 or MP promoter) which is expressed earlier in the baculovirus infection, and has been shown to be advantageous for expressing secreted proteins. See, Hill-Perkin and Possee, J. Gen. Virol. 71:971-6, 1990; Bonning. et al., J. Gen. Virol. 75:1551-6, 1994; and, Chazenbalk and Rapoport, J. Biol. Chem. 270:1543-9, 1995. In such transfer vector constructs, a short or long version of the basic protein promoter can be used. Moreover, transfer vectors can be constructed which replace the native zamp3 or zamp4 secretory signal sequences with secretory signal sequences derived from insect proteins. For example, a secretory signal sequence from Ecdysteroid Glucosyltransferase (EGT), honey bee Melittin (Invitrogen, Carlsbad, CA), or baculovirus gp67 (PharMingen, San Diego, CA) can be used in constructs to replace the native zamp3 or zamp4 secretory signal sequence. In addition, transfer vectors can include an in-frame fusion with DNA encoding an epitope tag at the C- or N-terminus of the expressed zamp3 or zamp4 polypeptide, for example, a Glu-Glu epitope tag (Grussenmeyer et al., Proc. Natl. Acad. Sci. 82:7952-4, 1985). Using a technique known in the art, a transfer vector containing zamp3 or zamp4 is transformed into E. coli, and screened for bacmids which contain an interrupted lacZ gene indicative of recombinant baculovirus. The bacmid DNA containing the recombinant baculovirus genome is isolated, using common techniques, and used to transfect Spodoptera frugiperda cells, e.g. Sf9 cells. Recombinant virus that expresses 3 or zamp4 is subsequently produced. Recombinant viral stocks are made by methods commonly used the art. The recombinant virus is used to infect host cells, typically a cell line derived from the fall armyworm, Spodoptera frugiperda. See, in general, Glick and Pasternak, Molecular Biotechnology: Principles and Applications of Recombinant DNA, ASM Press, Washington, D.C., 1994. Another suitable cell line is the High FiveO™ cell line (Invitrogen) derived from Trichoplusia ni (U.S. Patent #5,300,435). Commercially available serum-free media are used to grow and maintain the cells. Suitable media are Sf900 D™ (Life Technologies) or ESF 921™ (Expression Systems) for the Sf9 cells; and Ex-cellO405™ (JRH Biosciences, Lenexa, KS) or Express FiveO™ (Life Technologies) for the T. ni cells. The cells are grown up from an inoculation density of approximately 2-5 x 10 5 cells to a density of 1-2 x 10 6 cells at which time a recombinant viral stock is added at a multiplicity of infection (MOI) of 0.1 to 10, more typically near 3. The recombinant virus-infected cells typically produce the recombinant zamp3 or zamp4 polypeptide at 12-72 hours post-infection and secrete it with varying efficiency into the medium. The culture is usually harvested 48 hours post-infection. Centrifugation is used to separate the cells from the medium (supernatant). The supernatant containing the zamp3 or zamp4 polypeptide is filtered through micropore filters, usually 0.45 μm pore size. Procedures used are generally described in available laboratory manuals (King and Possee, ibid.; O'Reilly et al., ibid.; Richardson, ibid.). Subsequent purification of the zamp3 or zamp4 polypeptide from the supernatant can be achieved using methods described herein. Fungal cells, including yeast cells, can also be used within the present invention. Yeast species of particular interest in this regard include Saccharomyces cerevisiae, Pichia pastoris, and Pichia methanolica. Methods for transforming S. cerevisiae cells with exogenous DNA and producing recombinant polypeptides therefrom are disclosed by, for example, Kawasaki, U.S. Patent No. 4,599,311; Kawasaki et al., U.S. Patent No. 4,931,373; Brake, U.S. Patent No. 4,870,008; Welch et al., U.S. Patent No. 5,037,743; and Murray et al., U.S. Patent No. 4,845,075. Transformed cells are selected by phenotype determined by the selectable marker, commonly drug resistance or the ability to grow in the absence of a particular nutrient (e.g., leucine). A preferred vector system for use in Saccharomyces cerevisiae is the POT I vector system disclosed by Kawasaki et al. (U.S. Patent No. 4,931,373), which allows transformed cells to be selected by growth in glucose-containing media. Suitable promoters and terminators for use in yeast include those from glycolytic enzyme genes (see, e.g., Kawasaki, U.S. Patent No. 4,599,311; Kingsman et al., U.S. Patent No. 4,615,974; and Bitter, U.S. Patent No. 4,977,092) and alcohol dehydrogenase genes. See also U.S. Patents Nos. 4,990,446; 5,063,154; 5,139,936 and 4,661,454. Transformation systems for other yeasts, including Hansenula polymorpha, Schizosaccharomyces pombe, Kluyveromyces lactis, Kluyveromyces fragilis, Ustilago maydis, Pichia pastoris, Pichia methanolica, Pichia guillermondii and Candida maltosa are known in the art. See, for example, Gleeson et al., J. Gen. Microbiol. 132:3459-65, 1986 and Cregg, U.S. Patent No. 4,882,279. Aspergillus cells may be utilized according to the methods of McKnight et al., U.S. Patent No. 4,935,349. Methods for transforming Acremonium chrysogenum are disclosed by Sumino et al., U.S. Patent No. 5,162,228. Methods for transforming Neurospora are disclosed by Lambowitz, U.S. Patent No. 4,486,533. The use of Pichia methanolica as host for the production of recombinant proteins is disclosed in WIPO Publications WO 97/17450, WO 97/17451, WO 98/02536, and WO 98/02565. DNA molecules for use in transforming P. methanolica will commonly be prepared as double-stranded, circular plasmids, which are preferably linearized prior to transformation. For polypeptide production in P. methanolica, it is preferred that the promoter and terminator in the plasmid be that of a P. methanolica gene, such as a P. methanolica alcohol utilization gene (AUG1 or AUG2). Other useful promoters include those of the dihydroxyacetone synthase (DHAS), formate dehydrogenase (FMD), and catalase (CAT) genes. To facilitate integration of the DNA into the host chromosome, it is preferred to have the entire expression segment of the plasmid flanked at both ends by host DNA sequences. A preferred selectable marker for use in Pichia methanolica is a P. methanolica ADE2 gene, which encodes phosphoribosyl-5-aminoimidazole carboxylase (AIRC; EC 4.1.1.21), which allows ade2 host cells to grow in the absence of adenine. For large-scale, industrial processes where it is desirable to minimize the use of methanol, it is preferred to use host cells in which both methanol utilization genes (AUG1 and AUG2) are deleted. For production of secreted proteins, host cells deficient in vacuolar protease genes (PEP4 and PRB1) are preferred. Electroporation is used to facilitate the introduction of a plasmid containing DNA encoding a polypeptide of interest into P. methanolica cells. It is preferred to transform P. methanolica cells by electroporation using an exponentially decaying, pulsed electric field having a field strength of from 2.5 to 4.5 kV/cm, preferably about 3.75 kV/cm, and a time constant (τ) of from 1 to 40 milliseconds, most preferably about 20 milliseconds. Prokaryotic host cells, including strains of the bacteria Escherichia coli, Bacillus and other genera are also useful host cells within the present invention. Techniques for transforming these hosts and expressing foreign DNA sequences cloned therein are well known in the art (see, e.g., Sambrook et al., ibid.). When expressing a zamp3 or zamp4 polypeptide in bacteria such as E. coli, the polypeptide may be retained in the cytoplasm, typically as insoluble granules, or may be directed to the periplasmic space by a bacterial secretion sequence. In the former case, the cells are lysed, and the granules are recovered and denatured using, for example, guanidine isothiocyanate or urea. The denatured polypeptide can then be refolded and dimerized by diluting the denaturant, such as by dialysis against a solution of urea and a combination of reduced and oxidized glutathione, followed by dialysis against a buffered saline solution. In the latter case, the polypeptide can be recovered from the periplasmic space in a soluble and functional form by disrupting the cells (by, for example, sonication or osmotic shock) to release the contents of the periplasmic space and recovering the protein, thereby obviating the need for denaturation and refolding. Transformed or transfected host cells are cultured according to conventional procedures in a culture medium containing nutrients and other components required for the growth of the chosen host cells. A variety of suitable media, including defined media and complex media, are known in the art and generally include a carbon source, a nitrogen source, essential amino acids, vitamins and minerals. Media may also contain such components as growth factors or serum, as required. The growth medium will generally select for cells containing the exogenously added DNA by, for example, drug selection or deficiency in an essential nutrient which is complemented by the selectable marker carried on the expression vector or co- transfected into the host cell. P. methanolica cells are cultured in a medium comprising adequate sources of carbon, nitrogen and trace nutrients at a temperature of about 25 °C to 35°C. Liquid cultures are provided with sufficient aeration by conventional means, such as shaking of small flasks or sparging of fermentors. A preferred culture medium for P. methanolica is YEPD (2% D-glucose, 2% Bacto™ Peptone (Difco Laboratories, Detroit, MI), 1% Bacto™ yeast extract (Difco Laboratories), 0.004% adenine and 0.006% L-leucine). Expressed recombinant zamp3 or zamp4 polypeptides (or chimeric zamp3 or zamp4 polypeptides) can be purified using fractionation and/or conventional purification methods and media. Ammonium sulfate precipitation and acid or chaotrope extraction may be used for fractionation of samples. Exemplary purification steps may include hydroxyapatite, size exclusion, FPLC and reverse-phase high performance liquid chromatography. Suitable anion exchange media include derivatized dextrans, agarose, cellulose, polyacrylamide, specialty silicas, and the like. PEI, DEAE, QAE and Q derivatives are preferred, with DEAE Fast-Flow Sepharose (Pharmacia, Piscataway, NJ) being particularly preferred. Exemplary chromatographic media include those media derivatized with phenyl, butyl, or octyl groups, such as Phenyl-Sepharose FF (Pharmacia), Toyopearl butyl 650 (Toso Haas, Montgomeryville, PA), Octyl-Sepharose (Pharmacia) and the like; or polyacrylic resins, such as Amberchrom CG 71 (Toso Haas) and the like. Suitable solid supports include glass beads, silica-based resins, cellulosic resins, agarose beads, cross-linked agarose beads, polystyrene beads, cross-linked polyacrylamide resins and the like that are insoluble under the conditions in which they are to be used. These supports may be modified with reactive groups that allow attachment of proteins by amino groups, carboxyl groups, sulfhydryl groups, hydroxyl groups and/or carbohydrate moieties. Examples of coupling chemistries include cyanogen bromide activation, N-hydroxysuccinimide activation, epoxide activation, sulfhydryl activation, hydrazide activation, and carboxyl and amino derivatives for carbodumide coupling chemistries. These and other solid media are well known and widely used in the art, and are available from commercial suppliers. Methods for binding receptor polypeptides to support media are well known in the art. Selection of a particular method is a matter of routine design and is determined in part by the properties of the chosen support. See, for example, Affinity Chromatography: Principles & Methods, Pharmacia LKB Biotechnology, Uppsala, Sweden, 1988. The invention provides a cultured cell into which has been introduced an expression vector as described herein; wherein the cultured cell expresses a zamp3 or zamp 4 polypeptide encoded by the DNA segment. The invention also provides a method of producing a protein comprising culturing a cell into which has been introduced an expression vector described herein; whereby the cultured cell expresses a zamp3 or zamp4 polypeptide encoded by the DNA segment; and recovering the expressed polypeptide. The polypeptides of the present invention can be isolated by exploitation of their structural properties. For example, immobilized metal ion adsoφtion (IMAC) chromatography can be used to purify histidine-rich proteins or proteins having a His- affinity tag. Briefly, a gel is first charged with divalent metal ions to form a chelate (Sulkowski, Trends in Biochem. 3:1-7, 1985). Histidine-rich proteins will be adsorbed to this matrix with differing affinities, depending upon the metal ion used, and will be eluted by competitive elution, lowering the pH, or use of strong chelating agents. Other methods of purification include purification of glycosylated proteins by lectin affinity chromatography and ion exchange chromatography (Methods in Enzvmol.. Vol. 182, "Guide to Protein Purification", M. Deutscher, (ed.), Acad. Press, San Diego, 1990, pp.529-39). Within additional embodiments of the invention, a fusion of the polypeptide of interest and an affinity tag (e.g., maltose-binding protein, an immunoglobulin domain) may be constructed to facilitate purification. Protein refolding (and optionally reoxidation) procedures may be advantageously used. It is preferred to purify the protein to >80% purity, more preferably to >90% purity, even more preferably >95%, and particularly preferred is a pharmaceutically pure state, that is greater than 99.9% pure with respect to contaminating macromolecules, particularly other proteins and nucleic acids, and free of infectious and pyrogenic agents. Preferably, a purified protein is substantially free of other proteins, particularly other proteins of animal origin. Zamp3 or zamp4 polypeptides or fragments thereof may also be prepared through chemical synthesis. Zamp3 or zamp4 polypeptides may be monomers or multimers; glycosylated or non-glycosylated; pegylated or non-pegylated; amidated or non-amidated; sulfated or non-sulfated; and may or may not include an initial methionine amino acid residue. For example, zamp3 or zamp4 polypeptides can be synthesized by exclusive solid phase synthesis, partial solid phase methods, fragment condensation or classical solution synthesis. The polypeptides are preferably prepared by solid phase peptide synthesis, for example as described by Merrifield, J. Am. Chem. Soc. 85:2149, 1963. The synthesis is carried out with amino acids that are protected at the alpha-amino terminus. Trifunctional amino acids with labile side-chains are also protected with suitable groups to prevent undesired chemical reactions from occurring during the assembly of the polypeptides. The alpha-amino protecting group is selectively removed to allow subsequent reaction to take place at the amino-terminus. The conditions for the removal of the alpha-amino protecting group do not remove the side-chain protecting groups. The alpha-amino protecting groups are those known to be useful in the art of stepwise polypeptide synthesis. Included are acyl type protecting groups (e.g., formyl, trifluoroacetyl, acetyl), aryl type protecting groups (e.g., biotinyl), aromatic urethane type protecting groups [e.g., benzyloxycarbonyl (Cbz), substituted benzyloxycarbonyl and 9-fluorenylmethyloxy-carbonyl (Fmoc)], aliphatic urethane protecting groups [e.g., t-butyloxycarbonyl (tBoc), isopropyloxycarbonyl, cyclohexloxycarbonyl] and alkyl type protecting groups (e.g., benzyl, triphenylmethyl). The preferred protecting groups are tBoc and Fmoc. The side-chain protecting groups selected must remain intact during coupling and not be removed during the deprotection of the amino-terminus protecting group or during coupling conditions. The side-chain protecting groups must also be removable upon the completion of synthesis using reaction conditions that will not alter the finished polypeptide. In tBoc chemistry, the side-chain protecting groups for trifunctional amino acids are mostly benzyl based. In Fmoc chemistry, they are mostly tert-butyl or trityl based. In tBoc chemistry, the preferred side-chain protecting groups are tosyl for arginine, cyclohexyl for aspartic acid, 4-methylbenzyl (and acetamidomethyl) for cysteine, benzyl for glutamic acid, serine and threonine, benzyloxymethyl (and dinitrophenyl) for histidine, 2-Cl-benzyloxycarbonyl for lysine, formyl for tryptophan and 2-bromobenzyl for tyrosine. In Fmoc chemistry, the preferred side-chain protecting groups are 2,2,5,7,8- pentamethylchroman-6-sulfonyl (Pmc) or 2,2,4,6,7-penta- methyldihydrobenzofuran-5-sulfonyl (Pbf) for arginine, trityl for asparagine, cysteine, glutamine and histidine, tert-butyl for aspartic acid, glutamic acid, serine, threonine and tyrosine, tBoc for lysine and tryptophan. For the synthesis of phosphopeptides, either direct or post-assembly incoφoration of the phosphate group is used. In the direct incoφoration strategy, the phosphate group on serine, threonine or tyrosine may be protected by methyl, benzyl, or tert-butyl in Fmoc chemistry or by methyl, benzyl or phenyl in tBoc chemistry. Direct incoφoration of phosphotyrosine without phosphate protection can also be used in Fmoc chemistry. In the post-assembly incoφoration strategy, the unprotected hydroxyl groups of serine, threonine or tyrosine are derivatized on solid phase with di-tert-butyl-, dibenzyl- or dimethyl-N,N'-diisopropyl-phosphoramidite and then oxidized by tert- butylhydro-peroxide. Solid phase synthesis is usually carried out from the carboxyl-terminus by coupling the alpha-amino protected (side-chain protected) amino acid to a suitable solid support. An ester linkage is formed when the attachment is made to a chloromethyl, chlorotrityl or hydroxymethyl resin, and the resulting polypeptide will have a free carboxyl group at the C-terminus. Alternatively, when an amide resin such as benzhydrylamine or p-methylbenzhydrylamine resin (for tBoc chemistry) and Rink amide or PAL resin (for Fmoc chemistry) are used, an amide bond is formed and the resulting polypeptide will have a carboxamide group at the C-terminus. These resins, whether polystyrene- or polyamide-based or polyethyleneglycol-grafted, with or without a handle or linker, with or without the first amino acid attached, are commercially available, and their preparations have been described by Stewart et al., "Solid Phase Peptide Synthesis" (2nd Edition), (Pierce Chemical Co., Rockford, IL, 1984) and Bayer and Rapp, Chem. Pept. Prot. 3:3, 1986; and Atherton et al., Solid Phase Peptide Synthesis: A Practical Approach, IRL Press, Oxford, 1989. The C-terminal amino acid, protected at the side chain if necessary, and at the alpha-amino group, is attached to a hydroxylmethyl resin using various activating agents including dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIPCDI) and carbonyldiimidazole (CDI). It can be attached to chloromethyl or chlorotrityl resin directly in its cesium tetramethylammonium salt form or in the presence of triethylamine (TEA) or diisopropylethylamine (DIEA). First amino acid attachment to an amide resin is the same as amide bond formation during coupling reactions. Following the attachment to the resin support, the alpha-amino protecting group is removed using various reagents depending on the protecting chemistry (e.g., tBoc, Fmoc). The extent of Fmoc removal can be monitored at 300- 320 nm or by a conductivity cell. After removal of the alpha-amino protecting group, the remaining protected amino acids are coupled stepwise in the required order to obtain the desired sequence. Various activating agents can be used for the coupling reactions including DCC, DIPCDI, 2-chloro-l,3-dimethylimidium hexafluorophosphate (CIP), benzotriazol- 1 -yl-oxy-tris-(dimethylamino)-phosphonium hexafluoro-phosphate (BOP) and its pyrrolidine analog (PyBOP), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP), O-(benzotriazol-l-yl)-l,l,3,3-tetramethyl-uronium hexafluorophosphate (HBTU) and its tetrafluoroborate analog (TBTU) or its pyrrolidine analog (HBPyU), O-(7-azabenzotriazol-l-yl)-l,l,3,3-tetramethyl-uronium hexafluorophosphate (HATU) and its tetrafluoroborate analog (TATU) or its pyrrolidine analog (HAPyU). The most common catalytic additives used in coupling reactions include 4- dimethylaminopyridine (DMAP), 3-hydroxy-3,4-dihydro-4-oxo- 1 ,2,3-benzotriazine (HODhbt), N-hydroxybenzotriazole (HOBt) and l-hydroxy-7-azabenzotriazole (HO At). Each protected amino acid is used in excess (>2.0 equivalents), and the couplings are usually carried out in N-methylpyrrolidone (NMP) or in DMF, CH2C12 or mixtures thereof. The extent of completion of the coupling reaction can be monitored at each stage, e.g., by the ninhydrin reaction as described by Kaiser et al., Anal. Biochem. 34:595, 1970. After the entire assembly of the desired peptide, the peptide-resin is cleaved with a reagent with proper scavengers. The Fmoc peptides are usually cleaved and deprotected by TFA with scavengers (e.g., H 2 O, ethanedithiol, phenol and thioanisole). The tBoc peptides are usually cleaved and deprotected with liquid HF for 1-2 hours at -5 to 0° C, which cleaves the polypeptide from the resin and removes most of the side-chain protecting groups. Scavengers such as anisole, dimethylsulfide and p- thiocresol are usually used with the liquid HF to prevent cations formed during the cleavage from alkylating and acylating the amino acid residues present in the polypeptide. The formyl group of tryptophan and the dinitrophenyl group of histidine need to be removed, respectively by piperidine and thiophenyl in DMF prior to the HF cleavage. The acetamidomethyl group of cysteine can be removed by mercury(H)acetate and alternatively by iodine, thallium(IH) trifluoroacetate or silver tetrafluoroborate which simultaneously oxidize cysteine to cystine. Other strong acids used for tBoc peptide cleavage and deprotection include trifluoromethanesulfonic acid (TFMSA) and trimethylsilyltrifluoroacetate (TMSOTf). A zamp3 or zamp4 polypeptide ligand-binding polypeptide can also be used for purification of ligand. The polypeptide is immobilized on a solid support, such as beads of agarose, cross-linked agarose, glass, cellulosic resins, silica-based resins, polystyrene, cross-linked polyacrylamide, or like materials that are stable under the conditions of use. Methods for linking polypeptides to solid supports are known in the art, and include amine chemistry, cyanogen bromide activation, N-hydroxysuccinimide activation, epoxide activation, sulfhydryl activation, and hydrazide activation. The resulting medium will generally be configured in the form of a column, and fluids containing ligand are passed through the column one or more times to allow ligand to bind to the receptor polypeptide. The ligand is then eluted using changes in salt concentration, chaotropic agents (guanidine HCl), or pH to disrupt ligand-receptor binding. An assay system that uses a ligand-binding receptor (or an antibody, one member of a complement/ anti-complement pair) or a binding fragment thereof, and a commercially available biosensor instrument (BIAcore™, Pharmacia Biosensor, Piscataway, NJ) may be advantageously employed. Such receptor, antibody, member of a complement/anti-complement pair or fragment is immobilized onto the surface of a receptor chip. Use of this instrument is disclosed by Karlsson, J. Immunol. Methods 145:229-40, 1991 and Cunningham and Wells, J. Mol. Biol. 234:554-63, 1993. A receptor, antibody, member or fragment is covalently attached, using amine or sulfhydryl chemistry, to dextran fibers that are attached to gold film within the flow cell. A test sample is passed through the cell. If a ligand, epitope, or opposite member of the complement/anti-complement pair is present in the sample, it will bind to the immobilized receptor, antibody or member, respectively, causing a change in the refractive index of the medium, which is detected as a change in surface plasmon resonance of the gold film. This system allows the determination of on- and off-rates, from which binding affinity can be calculated, and assessment of stoichiometry of binding. As used herein the term "complement/anti-complement pair" denotes non-identical moieties that form a non-covalently associated, stable pair under appropriate conditions. For instance, biotin and avidin (or streptavidin) are prototypical members of a complement/anti-complement pair. Other exemplary complement/anti- complement pairs include receptor/ligand pairs, antibody/antigen (or hapten or epitope) pairs, sense/antisense polynucleotide pairs, and the like. Where subsequent dissociation of the complement/anti-complement pair is desirable, the complement/anti-complement pair preferably has a binding affinity of <10^ M "1 . Ligand-binding receptor polypeptides can also be used within other assay systems known in the art. Such systems include Scatchard analysis for determination of binding affinity (see Scatchard, Ann. NY Acad. Sci. 5V. 660-72, 1949) and calorimetric assays (Cunningham et al., Science 253:545-48, 1991; Cunningham et al., Science 245:821-25, 1991). The invention also provides anti-zamp3 or anti-zamp4 antibodies. Antibodies to zamp3 or zamp4 can be obtained, for example, using as an antigen the product of a zamp3 or zamp4 expression vector, or zamp3 or zamp4 isolated from a natural source. Particularly useful are anti-zamp3 antibodies that "bind specifically" with zamp3 and anti-zamp4 antibodies that "bind specifically" with zamp4. Antibodies are considered to be specifically binding if the antibodies bind to a zamp3 or zamp4 polypeptide, peptide or epitope with a binding affinity (K a ) of 10 M " or greater, 7 -1 8 -1 preferably 10 M or greater, more preferably 10 M " or greater, and most preferably 10 9 M -1 or greater. The binding affinity of an antibody can be readily determined by one of ordinary skill in the art, for example, by Scatchard analysis (Scatchard, Ann. NY Acad. Sci. 5 660, 1949). Suitable antibodies include antibodies that bind with zamp3 in particular domains or bind with zamp4 in particular domains. Anti-zamp3 or anti-zamp4 antibodies can be produced using antigenic zamp3 epitope-bearing peptides and polypeptides or zamp4 epitope-bearing peptides and polypeptides respectfully. Antigenic epitope-bearing peptides and polypeptides of the present invention contain a sequence of at least nine, preferably between 15 to about 30 amino acids contained within SEQ ID NOs: 2 or 4. However, peptides or polypeptides comprising a larger portion of an amino acid sequence of the invention, containing from 30 to 50 amino acids, or any length up to and including the entire amino acid sequence of a polypeptide of the invention, also are useful for inducing antibodies that bind with zamp3 or zamp4. It is desirable that the amino acid sequence of the epitope-bearing peptide is selected to provide substantial solubility in aqueous solvents (i.e., the sequence includes relatively hydrophilic residues, while hydrophobic residues are preferably avoided). Hydrophilic peptides can be predicted by one of skill in the art from a hydrophobicity plot, see for example, Hopp and Woods (Proc. Nat. Acad. Sci. USA 78:3824-8, 1981) and Kyte and Doolittle (J. Mol. Biol. 157: 105-142, 1982). Moreover, amino acid sequences containing proline residues may be also be desirable for antibody production. Polyclonal antibodies to recombinant zamp3 or zamp4 proteins or to zamp3 or zamp4 isolated from natural sources can be prepared using methods well- known to those of skill in the art. See, for example, Green et al., "Production of Polyclonal Antisera," in Immunochemical Protocols (Manson, ed.), pages 1-5 (Humana Press 1992), and Williams et al., "Expression of foreign proteins in E. coli using plasmid vectors and purification of specific polyclonal antibodies," in DNA Cloning 2: Expression Systems, 2nd Edition, Glover et al. (eds.), page 15 (Oxford University Press 1995). The i munogenicity of a zamp3 or zamp4 polypeptide can be increased through the use of an adjuvant, such as alum (aluminum hydroxide) or Freund's complete or incomplete adjuvant. Polypeptides useful for immunization also include fusion polypeptides, such as fusions of zamp3 or zamp4 or a portion thereof with an immunoglobulin polypeptide or with maltose binding protein. The polypeptide immunogen may be a full-length molecule or a portion thereof. If the polypeptide portion is "hapten-like," such portion may be advantageously joined or linked to a macromolecular carrier (such as keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA) or tetanus toxoid) for immunization. Although polyclonal antibodies are typically raised in animals such as horses, cows, dogs, chicken, rats, mice, rabbits, hamsters, guinea pigs, goats, or sheep, an anti-zamp3 or anti-zamp4 antibody of the present invention may also be derived from a subhuman primate antibody. General techniques for raising diagnostically and therapeutically useful antibodies in baboons may be found, for example, in Goldenberg et al., international patent publication No. WO 91/11465, and in Losman et al., Int. J. Cancer 46:310, 1990. Antibodies can also be raised in transgenic animals such as transgenic sheep, cows, goats or pigs, and can also be expressed in yeast and fungi in modified forms as will as in mammalian and insect cells. Alternatively, monoclonal anti-zamp3 or anti-zamp4 antibodies can be generated. Rodent monoclonal antibodies to specific antigens may be obtained by methods known to those skilled in the art (see, for example, Kohler et al., Nature 256:495 (1975), Coligan et al. (eds.), Current Protocols in Immunology. Vol. 1, pages 2.5.1-2.6.7 (John Wiley & Sons 1991), Picksley et al., "Production of monoclonal antibodies against proteins expressed in E. coli," in DNA Cloning 2: Expression Systems, 2nd Edition, Glover et al. (eds.), page 93 (Oxford University Press 1995)). Briefly, monoclonal antibodies can be obtained by injecting mice with a composition comprising a zamp3 or zamp4 gene product, verifying the presence of antibody production by removing a serum sample, removing the spleen to obtain B- lymphocytes, fusing the B-lymphocytes with myeloma cells to produce hybridomas, cloning the hybridomas, selecting positive clones which produce antibodies to the antigen, culturing the clones that produce antibodies to the antigen, and isolating the antibodies from the hybridoma cultures. In addition, an anti-zamp3 or zamp4 antibody of the present invention may be derived from a human monoclonal antibody. Human monoclonal antibodies are obtained from transgenic mice that have been engineered to produce specific human antibodies in response to antigenic challenge. In this technique, elements of the human heavy and light chain locus are introduced into strains of mice derived from embryonic stem cell lines that contain targeted disruptions of the endogenous heavy chain and light chain loci. The transgenic mice can synthesize human antibodies specific for human antigens, and the mice can be used to produce human antibody-secreting hybridomas. Methods for obtaining human antibodies from transgenic mice are described, for example, by Green et al., Nature Genet. 7:13, 1994, Lonberg et al., Nature 368:856, 1994, and Taylor et al., Int. Immun. 6:579, 1994. Monoclonal antibodies can be isolated and purified from hybridoma cultures by a variety of well-established techniques. Such isolation techniques include affinity chromatography with Protein-A Sepharose, size-exclusion chromatography, and ion-exchange chromatography (see, for example, Coligan at pages 2.7.1-2.7.12 and pages 2.9.1-2.9.3; Baines et al., "Purification of Immunoglobulin G (IgG)," in Methods in Molecular Biology. Vol. 10, pages 79-104 (The Humana Press, Inc. 1992)). For particular uses, it may be desirable to prepare fragments of anti- zamp3 or anti-zamp4 antibodies. Such antibody fragments can be obtained, for example, by proteolytic hydrolysis of the antibody. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. As an illustration, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab') 2 . This fragment can be further cleaved using a thiol reducing agent to produce 3.5S Fab' monovalent fragments. Optionally, the cleavage reaction can be performed using a blocking group for the sulfhydryl groups that result from cleavage of disulfide linkages. As an alternative, an enzymatic cleavage using pepsin produces two monovalent Fab fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. patent No. 4,331,647, Nisonoff et al., Arch Biochem. Biophys. 89:230, 1960, Porter, Biochem. J. 73:119, 1959, Edelman et al., in Methods in Enzymology Vol. 1, page 422 (Academic Press 1967), and by Coligan, ibid. Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody. For example, Fv fragments comprise an association of V H and V L chains. This association can be noncovalent, as described by Inbar et al., Proc. Natl. Acad. Sci. USA 69:2659, 1972. Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross-linked by chemicals such as gluteraldehyde (see, for example, Sandhu, Crit. Rev. Biotech. 12:437, 1992). The Fv fragments may comprise V H and V L chains which are connected by a peptide linker. These single-chain antigen binding proteins (scFv) are prepared by constructing a structural gene comprising DNA sequences encoding the V H and V L domains which are connected by an oligonucleotide. The structural gene is inserted into an expression vector which is subsequently introduced into a host cell, such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing scFvs are described, for example, by Whitlow et al., Methods: A Companion to Methods in Εnzymology 2:97, 1991, also see, Bird et al., Science 242:423, 1988, Ladner et al., U.S. Patent No. 4,946,778, Pack et al.. Bio/Technology 11:1271, 1993, and Sandhu, ibid. As an illustration, a scFV can be obtained by exposing lymphocytes to zamp3 or zamp4 polypeptide in vitro, and selecting antibody display libraries in phage or similar vectors (for instance, through use of immobilized or labeled zamp3 or zamp4 protein or peptide). Genes encoding polypeptides having potential zamp3 or zamp4 polypeptide binding domains can be obtained by screening random peptide libraries displayed on phage (phage display) or on bacteria, such as E. coli. Nucleotide sequences encoding the polypeptides can be obtained in a number of ways, such as through random mutagenesis and random polynucleotide synthesis. These random peptide display libraries can be used to screen for peptides which interact with a known target which can be a protein or polypeptide, such as a ligand or receptor, a biological or synthetic macromolecule, or organic or inorganic substances. Techniques for creating and screening such random peptide display libraries are known in the art (Ladner et al., U.S. Patent No. 5,223,409, Ladner et al., U.S. Patent No. 4,946,778, Ladner et al., U.S. Patent No. 5,403,484, Ladner et al., U.S. Patent No. 5,571,698, and Kay et al., Phage Display of Peptides and Proteins (Academic Press, Inc. 1996)) and random peptide display libraries and kits for screening such libraries are available commercially, for instance from Clontech (Palo Alto, CA), Invitrogen Inc. (San Diego, CA), New England Biolabs, Inc. (Beverly, MA), and Pharmacia LKB Biotechnology Inc. (Piscataway, NJ). Random peptide display libraries can be screened using the zamp3 or zamp4 sequences disclosed herein to identify proteins which bind to zamp3 or zamp4 respectfully. Another form of an antibody fragment is a peptide coding for a single complementarity-determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells (see, for example, Larrick et al., Methods: A Companion to Methods in Enzymology 2:106, 1991), Courtenay-Luck, "Genetic Manipulation of Monoclonal Antibodies," in Monoclonal Antibodies: Production, Engineering and Clinical Application. Ritter et al. (eds.), page 166 (Cambridge University Press, 1995), and Ward et al., "Genetic Manipulation and Expression of Antibodies," in Monoclonal Antibodies: Principles and Applications, Birch et al., (eds.), page 137 (Wiley-Liss, Inc. 1995)). Alternatively, an anti-zamp3 or anti-zamp4 antibody may be derived from a "humanized" monoclonal antibody. Humanized monoclonal antibodies are produced by transferring mouse complementary determining regions from heavy and light variable chains of the mouse immunoglobulin into a human variable domain. Typical residues of human antibodies are then substituted in the framework regions of the murine counteφarts. The use of antibody components derived from humanized monoclonal antibodies obviates potential problems associated with the immunogenicity of murine constant regions. General techniques for cloning murine immunoglobulin variable domains are described, for example, by Orlandi et al., Proc. Nat. Acad. Sci. USA 86:3833, 1989. Techniques for producing humanized monoclonal antibodies are described, for example, by Jones et al., Nature 321:522, 1986, Carter et al., Proc. Nat. Acad. Sci. USA 89:4285, 1992, Sandhu, Crit. Rev. Biotech. 12:437, 1992, Singer et al., J. Immun. 150:2844, 1993, Sudhir (ed.), Antibody Engineering Protocols (Humana Press, Inc. 1995), Kelley, "Engineering Therapeutic Antibodies," in Protein Engineering: Principles and Practice, Cleland et al. (eds.), pages 399-434 (John Wiley & Sons, Inc. 1996), and by Queen et al., U.S. Patent No. 5,693,762 (1997). Polyclonal anti-idiotype antibodies can be prepared by immunizing animals with anti-zamp3 or anti-zamp4 antibodies or antibody fragments, using standard techniques. See, for example, Green et al., "Production of Polyclonal Antisera," in Methods In Molecular Biology: Immunochemical Protocols, Manson (ed.), pages 1-12 (Humana Press 1992). Also, see Coligan, ibid, at pages 2.4.1-2.4.7. Alternatively, monoclonal anti-idiotype antibodies can be prepared using anti-zamp3 or anti-zamp4 antibodies or antibody fragments as immunogens with the techniques, described above. As another alternative, humanized anti-idiotype antibodies or subhuman primate anti-idiotype antibodies can be prepared using the above-described techniques. Methods for producing anti-idiotype antibodies are described, for example, by Irie, U.S. Patent No. 5,208,146, Greene, et. al., U.S. Patent No. 5,637,677, and Varthakavi and Minocha, J. Gen. Virol. 77:1875, 1996. Genes encoding polypeptides having potential zamp3 or zamp4 polypeptide binding domains, "binding proteins", can be obtained by screening random or directed peptide libraries displayed on phage (phage display) or on bacteria, such as E. coli. Nucleotide sequences encoding the polypeptides can be obtained in a number of ways, such as through random mutagenesis and random polynucleotide synthesis. Alternatively, constrained phage display libraries can also be produced. These peptide display libraries can be used to screen for peptides which interact with a known target which can be a protein or polypeptide, such as a ligand or receptor, a biological or synthetic macromolecule, or organic or inorganic substances. Techniques for creating and screening such peptide display libraries are known in the art (Ladner et al., US Patent NO. 5,223,409; Ladner et al., US Patent NO. 4,946,778; Ladner et al., US Patent NO. 5,403,484 and Ladner et al., US Patent NO. 5,571,698) and peptide display libraries and kits for screening such libraries are available commercially, for instance from Clontech (Palo Alto, CA), Invitrogen Inc. (San Diego, CA), New England Biolabs, Inc. (Beverly, MA) and Pharmacia LKB Biotechnology Inc. (Piscataway, NJ). Peptide display libraries can be screened using the zamp3 or zamp4 sequences disclosed herein to identify proteins which bind to zamp3 or zamp4. These "binding proteins" which interact with zamp3 or zamp4 polypeptides can be used essentially like an antibody. Within another aspect of the present invention there is provided a pharmaceutical composition comprising purified zamp3 or zamp4 polypeptide in combination with a pharmaceutically acceptable vehicle. Such pharmaceutical compositions are used in the treatment of conditions associated with pathological microbes, including bacterial, fungal and viral infections. Antibacterial applications of zamp3 or zamp4 polypeptide include situations where the pathogen has become resistant to standard treatments. For example, hospital sepsis is an increasing problem, since Staphylococcus strains have become resistant to commonly used antibiotics. In general, anti-microbial activity of zamp3 or zamp4 polypeptides, fragments, fusions, antibodies, agonists and antagonists can be evaluated by techniques that are known in the art. More specifically, anti-microbial activity can be assayed by evaluating the sensitivity of microbial cell cultures to test agents and by evaluating the protective effect of test agents on infected mice. See, for example, Musiek et al., Antimicrob. Agents Chemothr. 3: 40, 1973. Antiviral activity can also be assessed by protection of mammalian cell cultures. Known techniques for evaluating anti-microbial activity include, for example, Barsum et al., Eur. Respir. J. 8(5): 709-14, 1995; Sandovsky-Losica et al., J. Med. Vet. Mvcol (England) 28(4): 279-87, 1990; Mehentee et al.. J. Gen. Microbiol (England) 135 (Pt. 8): 2181-8, 1989; Segal and Savage, Journal of Medical and Veterinary Mycology 24: 477-479, 1986 and the like. Known assays specific for anti-viral activity include, for example, those described by Daher et al., Virol. 60(3): 1068-74, 1986. In addition, contract laboratories offer services in evaluating anti- microbial properties. For example, Panlabs, Inc. of Bothell, Washington offers in vitro or in vivo testing for bacteria, gram negative (Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhimurium and Serratia marcescens), gram positive (Bacillus subtilis, Brevebacterium ammoniagenes, Corynebacterium minutissimum, Micrococcus luteus, Mycobacterium ranae, Staphylococcus strains and Streptococcus strains) and anaerobic organisms (Actinomyces viscosus, Bacteroides fragilis, Clostridium sporogenes, Corynebacterium acnes, Helicobacter pylori and Porphyromonas gingivalis), as well as for protozoa (Trichomonas foetus) and fungi (e.g., Candida albicans, Epidermophyton floccosum, Exophiala jeanselmei, Microsporum strains, Trichophyton strains and the like). Also, Molecular Probes of Oregon has commercially available fluorescence technology for use in bacteriology. If desired, zamp3 or zamp4 polypeptide, fragment, fusion protein, agonist, antagonist or antibody performance in this regard can be compared to proteins known to be functional in this regard, such as proline-rich proteins, lysozyme, histatins, lactoperoxidase or the like. In addition, zamp3 or zamp4 polypep tides, fragments, fusion proteins, antibodies, agonists or antagonists may be evaluated in combination with one or more anti-microbial agents to identify synergistic effects. Defensin polypeptides comprising the cysteine motif are commercially available as antibiotic peptides, monocyte and dendritic chemotactic peptides. Commercial suppliers include Research Diagnostics, Inc, Flanders, NJ, Peninsula Laboratories, Inc., Belmont, CA, America Peptide, Co., Sunnyvale, CA. Zamp3 polypeptides comprising amino acid residues 31-60 of SEQ ID NO:2, and zamp4 polypeptides comprising amino acid residues 12-41 of SEQ ID NO:6, would be useful for this puφose. Defensins have been found associated with the tissues and secretions of the human eye and are useful in treating microbial-related diseases of the eye (Cullor et al., Arch. Ophthalmol. 108:861-4, 1990; Muφhy et al., US Patent No. 5,242,902; Hattenbach et al., Antimicrob. Agent. Chemother. 42:332, 1998; Haynes et al., Lancet 354:451-2, 1998 and Haynes et al., Br. J. Ophthalmol. 83:737-41, 1999). Addition of defensin polypeptides reduced microbial contamination of corneal preservation medium. Such agents are useful for reducing infectious postoperative complications associated with such transplantations (Schwab et al., Cornea ϋ:370-5, 1992). Thus, zamp3 or zamp4 polypeptides, agonists or antagonists thereof may be therapeutically useful for treatment of infection and inflammation associated with the eye. To verify the presence of this capability in zamp3 or zamp4 polypeptides, agonists or antagonists of the present invention, such zamp3 or zamp4 polypeptides, agonists or antagonists are evaluated with respect to their anti-microbial and chemotactic activities according to procedures known in the art. If desired, zamp3 or zamp4 polypeptide performance in this regard can be compared to other oc and β defensins, rabbit neutrophil defensins and the like. In addition, zamp3 or zamp4 polypeptides or agonists or antagonists thereof may be evaluated in combination with one or more anti-microbial molecules to identify synergistic effects. Similarly, zamp3 or zamp4 polypeptides of the present invention would also be therapeutically useful for treatment of infection and inflammation associated with the ear. The invention provides a method of treating a microbial-related disease comprising administering to a mammal a therapeutically effective amount of a zamp3 or zamp4 polypeptide whereby the polypeptide ameliorates the disease. Preferably such polypeptides include amino acid residues 31-60 of SEQ ID NO:2, amino acid residues 23-63, or amino acid residues 12-41 of SEQ ID NO:6. One such application would be for microbial-related disease is associated with the eye, such as conjunctivitis. Application could also be made for diseases associated with the ear. The invention also provides a method of contraception wherein a therapeutically effective amount of the polypeptides of the present invention is administered to a mammal. Such administration would be useful in preventing implantation and/or development of the embryo. Defensins have also been found to activate the complement cascade (Prohaszka et al., Mol Immunol. 34:809-16, 1997 and Prohaszka and Fust, Lancet 352:1152, 1998) The complement component Clq plays a role in host defense against infectious agents, such as bacteria and viruses. Clq is known to exhibit several specialized functions. For example, Clq triggers the complement cascade via interaction with bound antibody or C-reactive protein (CRP). Also, Clq interacts directly with certain bacteria, RNA viruses, mycoplasma, uric acid crystals, the lipid A component of bacterial endotoxin and membranes of certain intracellular organelles. Clq binding to the Clq receptor is believed to promote phagocytosis. Clq also appears to enhance the antibody formation aspect of the host defense system. See, for example, Johnston, Pediatr. Infect. Dis. J. 12: 933-41, 1993. Thus, complement-activating defensins would act as enhanced anti-microbial agents, promoting lysis or phagocytosis of infectious agents. The anti-microbial activity of defensins is also useful for contraceptive applications (Sawicki and Mystkovska, Lancet 353:464-5, 1999). The pharmaceutical compositions of the present invention may also be used when pro-inflammatory activity is desired. Applications for such pro- inflammatory activity include the treatment of chronic tissue damage, particularly in areas having a limited or damaged vascular system, e.g., damage in extremities associated with diabetes. In contrast, antagonists to zamp3 or zamp4 polypeptides may be useful as anti-inflammatory agents. Zamp3 or zamp4 polypeptide pharmaceutical compositions of the present invention may also be used in the treatment of conditions where stimulation of immune responsiveness is desired. Such conditions include the treatment of patients having incompetent immune systems, such as AIDs patients or individuals that have undergone chemotherapy, radiation treatment or the like. Human B-defensins (HBD1 and HBD2) exhibit chemotactic activity for immature dendritic cells (Yang et al., Science 286:525-8, 1999). This chemotactic activity suggests that defensins are immuno-stimulatory in addition to their anti-microbial activity. The chemotaxis is mediated through the CCR6 receptor which is found on the surface of immature dendritic cells as well as memory T cells. Zamp3 and zamp4 would be useful in modulating the adaptive immune response. Specifically, such β-defensin peptides may be used to promote immune responses in immunocompromised individuals. Conversely modified peptides derived from beta-defensins could be used to block the interaction of endogenous immunostimulatory molecules with their receptors and thereby achieve immuno- suppressive and anti-inflammatory effects. Other members of the β defensin family have been found in bronchial epithelia tissue and cystic fibrosis is characterized by frequent microbial infection, pharmaceutical compositions containing zamp3 or zamp4 polypeptides are also contemplated for use in the treatment of lung infections associated with cystic fibrosis. Also contemplated by the present invention are engineered zamp3 or zamp4 polypeptides that are characterized by decreased sensitivity to salt concentration. Decreased sensitivity to high salt concentration will preserve anti-microbial activity of engineered zamp3 or zamp4 polypeptides in high salt environments, such as in the lung airways of patients suffering from cystic fibrosis. In this manner, pharmaceutical compositions containing engineered zamp3 or zamp4 polypeptides that are formulated for delivery to the lungs can be used to treat lung infections associated with cystic fibrosis. Radiation hybrid mapping is a somatic cell genetic technique developed for constructing high-resolution, contiguous maps of mammalian chromosomes (Cox et al., Science 250:245-50, 1990). Partial or full knowledge of a gene's sequence allows one to design PCR primers suitable for use with chromosomal radiation hybrid mapping panels. Commercially available radiation hybrid mapping panels which cover the entire human genome, such as the Stanford G3 RH Panel and the GeneBridge 4 RH Panel (Research Genetics, Inc., Huntsville, AL), are available. These panels enable rapid, PCR-based chromosomal localizations and ordering of genes, sequence-tagged sites (STSs), and other nonpolymoφhic and polymoφhic markers within a region of interest. This includes establishing directly proportional physical distances between newly discovered genes of interest and previously mapped markers. The precise knowledge of a gene's position can be useful for a number of puφoses, including: 1) determining if a sequence is part of an existing contig and obtaining additional surrounding genetic sequences in various forms, such as YACs, BACs or cDNA clones; 2) providing a possible candidate gene for an inheritable disease which shows linkage to the same chromosomal region; and 3) cross-referencing model organisms, such as mouse, which may aid in determining what function a particular gene might have. The murine zamp3 gene was mapped in mouse to chromosome 8 using a T31 whole genome radiation hybrid (WGRH) panel (Research Genetics, Inc., Huntsville, AL) and Map Manager QT linkage analysis program. At P= 0.0001, murine zamp3 linked to the marker D8Mitl41 with a LOD score of 5.6. D8Mitl41 has been mapped at 6.0 cM on mouse chromosome 8. The murine zamp4 was mapped in mouse to chromosome using the commercially available mouse T31 whole genome radiation hybrid (WGRH). The results showed that murine zamp4 maps 25.88 cR_3000 distal of the framework marker D14Mitl56 on the mouse chromosome 14 WICGR radiation hybrid map. Proximal and distal framework markers were D14Mitl56 and D14Mit31, respectively. No other defensins have been mapped to a location other than mouse chromosome 8. This region is a known conserved syntenic region to human chromosome 8p21-p23 which overlaps the location of the human defensin cluster. The present invention also provides reagents which will find use in diagnostic applications. For example, the zamp3 gene, a probe comprising zamp3 DNA or RNA or a subsequence thereof can be used to determine if the zamp3 gene is present on mouse chromosome 8 or if a mutation has occurred. Detectable chromosomal aberrations at the zamp3 gene locus include but are not limited to aneuploidy, gene copy number changes, insertions, deletions, restriction site changes and rearrangements. Such aberrations can be detected using polynucleotides of the present invention by employing molecular genetic techniques, such as restriction fragment length polymoφhism (RFLP) analysis, short tandem repeat (STR) analysis employing PCR techniques, and other genetic linkage analysis techniques known in the art (Sambrook et al., ibid.; Ausubel, et. al., ibid.; Marian, Chest. 108: 255-265, 1995). Another aspect of the present invention involves the detection of zamp3 or zamp4 polypeptides in cell culture or in a serum sample or tissue biopsy of a patient undergoing evaluation for SPG, Chediak-Higashi syndrome or other conditions characterized by an alteration in defensin concentration. Zamp3 or zamp4 polypeptides can be detected using immunoassay techniques and antibodies capable of recognizing a zamp3 or zamp4 polypeptide epitope. More specifically, the present invention contemplates methods for detecting zamp3 or zamp4 polypeptide comprising: exposing a solution or sample or cell culture lysate or supernatant, possibly containing zamp3 or zamp4 polypeptide, to an antibody attached to a solid support, wherein the antibody binds to a first epitope of a zamp3 or zamp4 polypeptide; washing the immobilized antibody-polypeptide to remove unbound contaminants; exposing the immobilized antibody-polypeptide to a second antibody directed to a second epitope of a zamp3 or zamp4 polypeptide, wherein the second antibody is associated with a detectable label; and detecting the detectable label. Zamp3 or zamp4 polypeptide concentration differing from that of controls may be indicative of SPG, Chediak- Higashi syndrome or other conditions characterized by an alteration in defensin concentration. In addition, expression of zamp3 or zamp4 may be monitored in cystic fibrosis patients as a predictor of the onset of infectious crises. Also, high defensin, such as zamp3 or zamp4 polypeptide, levels have been associated with cytotoxic effects in lung, indicating that zamp3 or zamp4 polypeptide levels can be used to direct treatment for averting or addressing such cytotoxicity. For example, antibodies directed to zamp3 or zamp4 polypeptide can be administered to inactivate the same in a treatment modality. Within additional aspects of the invention there are provided antibodies or synthesized binding proteins(e.g., those generated by phage display, E. coli Fab, and the like) that specifically bind to the zamp3 or zamp4 polypeptides described above. Such antibodies are useful for, among other uses as described herein, preparation of anti-idiotypic antibodies. Synthesized binding proteins may be produced by phage display using commercially available kits, such as the Ph.D.™ Phage Display Peptide Library Kits available from New England Biolabs, Inc. (Beverly, Massachusetts). Phage display techniques are described, for example, in US Patent Nos. 5,223,409, 5,403,484 and 5,571,698. An additional aspect of the present invention provides methods for identifying agonists or antagonists of the zamp3 or zamp4 polypeptides disclosed above, which agonists or antagonists may have valuable properties as discussed further herein. Within one embodiment, there is provided a method of identifying zamp3 or zamp4 polypeptide agonists, comprising providing cells responsive thereto, culturing the cells in the presence of a test compound and comparing the cellular response with the cell cultured in the presence of the zamp3 or zamp4 polypeptide, and selecting the test compounds for which the cellular response is of the same type. Within another embodiment, there is provided a method of identifying antagonists of a zamp3 or zamp4 polypeptide, comprising providing cells responsive to a zamp3 or zamp4 polypeptide, culturing a first portion of the cells in the presence of a zamp3 or zamp4 polypeptide, culturing a second portion of the cells in the presence of the a zamp3 or zamp4 polypeptide and a test compound, and detecting a decrease in a cellular response of the second portion of the cells as compared to the first portion of the cells. A further aspect of the invention provides a method of studying chemoattraction of monocytes in cell culture, comprising incubating monocytes in a culture medium comprising a zamp3 or zamp4 polypeptide, fragment, fusion protein, antibody, agonist or antagonist to study or evaluate monocyte chemoattraction. Such evaluation may be conducted using methods known in the art, such as those described by Territo et al. ibid. Melanocortin receptors are G-coupled protein receptors which activate adenylate cyclase and cause calcium flux. The agouti protein (which contains a 36 amino acid domain that is toxin-like) is thought to inhibit the binding of MSH-alpha to MCI and MC4. In addition, the agouti protein is thought to be an antagonist of calcium channels, and certain toxins are believed to modulate ion flux. Experimental evidence has been generated, suggesting that defensins are capable of blocking calcium channels. A further aspect of the invention provides a method of studying activity of the melanocortin family of receptors in cell culture, comprising incubating cells that endogenously bear such receptors (e.g., ACTH receptors or the like) or cells that have been engineered to bear such receptors in a culture medium comprising a ligand or putative ligand and zamp3 or zamp4 polypeptide, fragment, fusion protein, antibody, agonist or antagonist to study or evaluate ligand or putative ligand binding and/or ion flux regulation or modulation. Such evaluation may be conducted using methods known in the art, such as those described by Zhu et al. ibid . A further aspect of the invention provides a method of studying ion flux in cell culture, comprising incubating cells that are capable of ion flux, such as calcium flux, sodium flux, potassium flux or the like, in a culture medium comprising a zamp3 or zamp4 polypeptide, fragment, fusion protein, antibody, agonist or antagonist to study or evaluate ion flux regulation or modulation. A further aspect of the invention provides a method of studying cytocidal activity against mammalian cells, such as tumor cells, in cell culture, comprising incubating such cells in a culture medium comprising a zamp3 or zamp4 polypeptide, fragment, fusion protein, antibody, agonist or antagonist at high test agent and low cell concentration to study or evaluate cytocidal activity. Such evaluation may be conducted using methods known in the art, such as those described by Lichtenstein et al., Blood 68: 1407-10, 1986 and Sheu et al., Antimicrob. Agents Chemother. 28: 626-9, 1993. Another aspect of the present invention involves the use of zamp3 or zamp4 polypeptides, fragments, fusion proteins or agonists as cell culture reagents in in vitro studies of exogenous microorganism infection, such as bacterial, viral or fungal infection. Such moieties may also be used in in vivo animal models of infection. An additional aspect of the present invention is to study epithelial cell defensin induction in cell culture. In this aspect of the present invention, epithelial cells are cultured and exposed to pathogenic stimuli. Induction of zamp3 or zamp4 polypeptide production by the epithelial cells is then measured. Polynucleotides and polypeptides of the present invention will find use as educational tools in laboratory practicum kits for courses related to genetics and molecular biology, protein chemistry, and antibody production and analysis. Due to its unique polynucleotide and polypeptide sequences, molecules of zamp3 or zamp4 can be used as standards or as "unknowns" for testing puφoses. For example, zamp3 or zamp4 polynucleotides can be used as an aid, such as, for example, to teach a student how to prepare expression constructs for bacterial, viral, or mammalian expression, including fusion constructs, wherein zamp3 or zamp4 is the gene to be expressed; for determining the restriction endonuclease cleavage sites of the polynucleotides; determining mRNA and DNA localization of zamp3 or zamp4 polynucleotides in tissues (i.e., by northern and Southern blotting as well as polymerase chain reaction); and for identifying related polynucleotides and polypeptides by nucleic acid hybridization. As an illustration, students will find that Alw I digestion of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO: 1 provides two fragments of about 13 base pairs, and 187 base pairs, and that CviR I digestion yields fragments of about 58 base pairs, a doublet at 54 base pairs, 30 base pairs, and 12 base pairs. Zamp3 or zamp4 polypeptides can be used as an aid to teach preparation of antibodies; identifying proteins by western blotting; protein purification; determining the weight of expressed zamp3 or zamp4 polypeptides as a ratio to total protein expressed; identifying peptide cleavage sites; coupling amino and carboxyl terminal tags; amino acid sequence analysis, as well as, but not limited to monitoring biological activities of both the native and tagged protein (i.e., protease inhibition) in vitro and in vivo. Zamp3 or zamp4 polypeptides can be used as an aid to teach preparation of antibodies; identifying proteins by western blotting; protein purification; determining the weight of produced zamp3 or zamp4 polypeptides as a ratio to total protein produced; identifying peptide cleavage sites; coupling amino and carboxyl terminal tags; amino acid sequence analysis, as well as, but not limited to monitoring biological activities of both the native and tagged protein in vitro and in vivo. Zamp3 or zamp4 polypeptides can also be used to teach analytical skills such as mass spectrometry, circular dichroism to determine conformation, especially of the four alpha helices, x-ray crystallography to determine the three-dimensional structure in atomic detail, nuclear magnetic resonance spectroscopy to reveal the structure of proteins in solution. For example, a kit containing the zamp3 or zamp4 can be given to the student to analyze. Since the amino acid sequence would be known by the instructor, the protein can be given to the student as a test to determine the skills or develop the skills of the student, the instructor would then know whether or not the student has correctly analyzed the polypeptide. Since every polypeptide is unique, the educational utility of zamp3 or zamp4 would be unique unto themselves. The antibodies which bind specifically to zamp3 or zamp4 can be used as a teaching aid to instruct students how to prepare affinity chromatography columns to purify zamp3 or zamp4, cloning and sequencing the polynucleotide that encodes an antibody and thus as a practicum for teaching a student how to design humanized antibodies. The zamp3 or zamp4 gene, polypeptide, or antibody would then be packaged by reagent companies and sold to educational institutions so that the students gain skill in art of molecular biology. Because each gene and protein is unique, each gene and protein creates unique challenges and learning experiences for students in a lab practicum. Such educational kits containing the zamp3 or zamp4 gene, polypeptide, or antibody are considered within the scope of the present invention. The present invention provides within one aspect an isolated protein comprising a polypeptide selected from the group consisting of: a) amino acid residues 31-60 of SEQ H NO:2; and b) amino acid residues 12-41 of SEQ ID NO:6. Within one embodiment the protein comprises a polypeptide having the sequence selected from the group consisting of: a) a polypeptide consisting of the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ID NO:2; and b) a polypeptide consisting of the sequence of amino acid residue 23 to amino acid residue 63 of SEQ ID NO:2. Within another embodiment the protein comprises a polypeptide consisting of the sequence of amino acid residue 1 to amino acid residue 43 of SEQ ID NO:4. The invention also provides an isolated protein comprising a polypeptide that is at least 80% identical to a polypeptide selected from the group consisting of: a) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ID NO:2, wherein the polypeptide has cysteine residues corresponding to amino acid residues 31, 32, 38, 42, 52, 59 and 60 of SEQ ID NO:2; b) a polypeptide having the sequence of amino acid residue 23 to amino acid residue 60 of SEQ ID NO:2, wherein the polypeptide has cysteine residues corresponding to amino acid residues 31, 32, 38, 42, 52, 59 and 60 of SEQ ED NO:2; and c) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 43 of SEQ ID NO:6, wherein the polypeptide has cysteine residues corresponding to amino acid residues 12, 19, 24, 34, 40 and 41 of SEQ ED NO:6. Within one embodiment the amino acid percent identity is determined using a FASTA program with ktup=l, gap opening penalty=10, gap extension penalty=l, and substitution matrix=BLOSUM62, with other parameters set as default. Within another embodiment any differences between the polypeptide and SEQ ID NOs:2 or 6 are due to conservative amino acid substitutions. Also provided is a polypeptide selected from the group consisting of: a) amino acid residue 31 to amino acid residue 60 of SEQ ID NO:2; and b) amino acid residue 12 to amino acid residue 41 of SEQ ED NO:6. The invention also provides a polypeptide as described above, in combination with a pharmaceutically acceptable vehicle. Within another aspect the invention provides a method of producing an antibody to a polypeptide comprising: inoculating an animal with a polypeptide as described above, wherein the polypeptide elicits an immune response in the animal to produce the antibody; and isolating the antibody from the animal. The invention also provides an antibody that specifically binds to a protein as described above. Also provided is an anti-idiotypic antibody of an antibody which specifically binds to a protein as described above. Within another aspect the invention provides an isolated polynucleotide encoding a protein comprising a polypeptide selected from the group consisting of: a) amino acid residues 31-60 of SEQ ID NO:2; and b) amino acid residues 12-41 of SEQ ED NO:6. Within one embodiment the protein comprises a polypeptide having the sequence selected from the group consisting of: a) a polypeptide consisting of the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ID NO:2; and b) a polypeptide consisting of the sequence of amino acid residue 23 to amino acid residue 63 of SEQ ED NO: 2. Within another embodiment the protein comprises a polypeptide consisting of the sequence of amino acid residue 1 to amino acid residue 43 of SEQ ID NO:4. Within another embodiment the polynucleotide remains hybridized following stringent wash conditions to a polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO:5 or their complements. The invention also provides an isolated polynucleotide encoding a protein comprising a polypeptide that is at least 80% identical to a polypeptide selected from the group consisting of: a) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ID NO: 2, wherein the polypeptide has cysteine residues corresponding to amino acid residues 31, 32, 38, 42, 52, 59 and 60 of SEQ ID NO: 2; b) a polypeptide having the sequence of amino acid residue 23 to amino acid residue 63 of SEQ ED NO:2, wherein the polypeptide has cysteine residues corresponding to amino acid residues 31, 32, 38, 42, 52, 59 and 60 of SEQ ID NO:2; and c) a polypeptide having the sequence of amino acid residue 1 to amino acid residue 43 of SEQ ID NO:6, wherein the polypeptide has cysteine residues corresponding to amino acid residues 12, 19, 24, 34, 40 and 41 of SEQ ID NO:6. Within one embodiment the amino acid percent identity is determined using a FASTA program with ktup=l, gap opening penalty=10, gap extension penalty=l, and substitution matrix=BLOSUM62, with other parameters set as default. Within another embodiment any differences between the polypeptide and SEQ ID NOs:2 or 6 are due to conservative amino acid substitutions. Within another embodiment the polynucleotide remains hybridized following stringent wash conditions to a polynucleotide consisting of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO:5 or their complements. The invention also provides a polynucleotide encoding a polypeptide selected from the group consisting of: a) amino acid residue 31 to amino acid residue 60 of SEQ ID NO:2; and b) amino acid residue 12 to amino acid residue 41 of SEQ ED NO:6. Also provided is an isolated polynucleotide selected from the group consisting of: a) nucleotide 1 to nucleotide 324 of SEQ ED NO:l, b) nucleotide 10 to nucleotide 198 of SEQ ID NO:l, c) nucleotide 76 to nucleotide 198 of SEQ ID NO:l, d) nucleotide 100 to nucleotide 189 of SEQ ID NO: l, e) nucleotide 1 to nucleotide 296 of SEQ ID NO:5, f) nucleotide 1 to nucleotide 132 of SEQ ID NO:5, and g) nucleotide 34 to nucleotide 123 of SEQ ID NO:5. Within another aspect the invention also provides an expression vector comprising the following operably linked elements: a transcription promoter; a DNA segment encoding a protein as described above; and a transcription terminator. Within one embodiment the DNA segment further encodes a secretory signal sequence operably linked to the protein. Within another embodiment the secretory signal sequence is a polypeptide having the sequence of amino acid residue 1 to amino acid residue 22 of SEQ ID NO:2. The invention also provides a cultured cell into which has been introduced an expression vector as described above; wherein the cell expresses the polypeptide encoded by the DNA segment. The invention further provides a method of producing a protein comprising: culturing a cell into which has been introduced an expression vector as described above; whereby the cell expresses the polypeptide encoded by the DNA segment; and recovering the expressed polypeptide. Within another aspect the invention provides a method of treating a microbial-related disease comprising administering to a mammal a therapeutically effective amount of a polypeptide selected from the group consisting of: a) a polypeptide of SEQ ID NO:2; b) a polypeptide of SEQ ID NO:6; c) a polypeptide consisting of amino acid residues 23-63 of SEQ ID NO:2; d) a polypeptide consisting of amino acid residues 31-60 of SEQ ID NO:2; and e) a polypeptide consisting of amino acid residues 12-40 of SEQ ED NO:6; whereby the polypeptide ameliorates the disease. Within one embodiment the microbial-related disease is associated with the eye. Within another embodiment the microbial-related disease is conjunctivitis. Within another embodiment the microbial-related disease is associated with the ear. Also provided by the invention is a method of contraception comprising administering to a mammal a therapeutically effective amount of a polypeptide selected from the group consisting of: a) a polypeptide of SEQ ID NO:2; b) a polypeptide of SEQ ED NO:6; c) a polypeptide consisting of amino acid residues 23-63 of SEQ ED NO:2; d) a polypeptide consisting of amino acid residues 31-60 of SEQ ID NO:2; and e) a polypeptide consisting of amino acid residues 12-40 of SEQ ID NO:6. The invention is further illustrated by the following non-limiting examples. Example 1 Tissue Distribution A mouse Multiple Tissue Northern Blot (MTN™; Clontech, Palo Alto, CA) was probed to determine the tissue distribution of murine zamp3 expression. An approximately 214 bp PCR derived probe (SEQ ID NO:8) was amplified from a mouse genomic DNA. Oligonucleotide primers ZC22848 (SEQ ID NO: 13) and ZC22847 (SEQ ID NO: 14) were used as primers. The probe was amplified in a polymerase chain reaction as follows: 1 cycle at 94°C for 30 seconds; 30 cycles of 94°C for 15 seconds and 68°C for 1 minute, followed by 1 cycle at 68°C for 3 minutes. The resulting DNA fragment was electrophoresed on a 1.5% agarose gel (OmniPure Agarose,EM Science, Gibbstown, NJ), the fragment was purified using the QIAquickTM me thod (Qiagen, Chatsworth, CA), and the sequence was confirmed by sequence analysis. The probe was radioactively labeled using the RediPrime EL Random Prime Labeling System (Amersham, Arlington Heights, EL), according to the manufacturer's specifications. The probe was purified using a NUCTRAP push column (Stratagene, La Jolla, CA). ExpressHybTM (Clontech) solution was used for prehybridization and as a hybridizing solution for the Northern blots. Hybridization took place overnight at 65°C using 1 x lθ6 cpm/ml of labeled probe. The blots were then washed at room temperature in 2X SSC, 0.1% SDS for 1 hour, followed by 50°C in 0.1X SSC, 0.1% SDS for 1 hour. No expression was observed. It thus appears that normal tissue levels of mRNA of zamp3 polypeptide are below the detection sensitivity of the Northern blot. Such an observation is consistent with the knowledge in the art regarding some defensins, Le , that they are constitutively expressed at low levels but are highly inducible upon infection. A mouse embryo multiple tissue Northern blot (MTN™, Clontech) was probed and hybridized as described above. No expression was observed. A mouse RNA Master Blot^M (Clontech) was probed as described above. Expression was detected as a faint signal in thyroid, ovary and epididymus. Example 2 Chromosomal Assignment and Placement of Murine Zamp3 Murine zamp3 was mapped in mouse to chromosome 8 using the commercially available mouse T31 whole genome radiation hybrid (WGRH) panel (Research Genetics, Inc., Huntsville, AL) and Map Manager QT linkage analysis program. At P=0.0001, murine zamp3 linked to the marker D8Mitl41 with a LOD score of 5.6. D8MU141 has been mapped at 6.0 cM on mouse chromosome 8. The T31 WGRH panel contains PCRable DNAs from each of 100 radiation hybrid clones, plus two control DNAs (the 129aa donor and the A23 recipient). For the mapping of murine zamp3 with the T31 WGRH panel, 20 μl reactions were set up in 96-well microtiter plates (Stratagene, La Jolla, CA) and used in a RoboCycler Gradient 96 thermal cycler (Stratagene). Each of the 102 PCR reactions consisted of 2 μl 10X KlenTaq PCR reaction buffer (Clontech Laboratories, Inc., Palo Alto, CA), 1.6 μl dNTPs mix (2.5 mM each, Perkin-Elmer, Foster City, CA), 1 μl sense primer, ZC 19960, (SEQ ID NO: 15), 1 μl antisense primer, ZC 19961, (SEQ ID NO: 16), 2 μl RediLoad (Research Genetics, Inc.), 0.4 μl 50X Advantage KlenTaq Polymerase Mix (Clontech), 25 ng of DNA from an individual hybrid clone or control and ddH 2 O for a total volume of 20 μl. The reactions were overlaid with an equal amount of mineral oil and sealed. The PCR cycler conditions were as follows: an initial 1 cycle 5 minute denaturation at 94°C, 35 cycles of a 45 seconds denaturation at 94°C, 45 seconds annealing at 60°C and 1 minute extension at 72°C, followed by a final 1 cycle extension of 7 minutes at 72°C. The reactions were separated by electrophoresis on a 2% agarose gel (Life Technologies, Gaithersburg, MD). Murine zamp4 was mapped in mouse to chromosome 14 using the commercially available mouse T31 whole genome radiation hybrid (WGRH) as described above. Sense primer ZC 25,260 (SEQ ID NO: 17), and antisense primer ZC 25,261(SEQ ID NO: 18), were used in the reaction. The results showed that murine zamp4 maps 25.88 cR_3000 distal of the framework marker D14Mitl56 on the mouse chromosome 14 WICGR radiation hybrid map. Proximal and distal framework markers were D14Mitl56 and D14Mit31, respectively. From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for puφoses of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.

Claims: CLA S WHAT IS CLAIMED IS: 1. An isolated polypeptide comprising amino acid residues 31-60 of SEQ ID NO:2. 2. An isolated polypeptide comprising the sequence of amino acid residue 1 to amino acid residue 63 of SEQ ED NO:2. 3. A polypeptide selected from the group consisting of: a) a polypeptide consisting of amino acid residues 31 to 60 of SEQ ED NO:2; b) a polypeptide consisting of amino acid residues 31 to 63 of SEQ ED NO:2, c) a polypeptide consisting of amino acid residues 23 to 60 of SEQ ED NO:2, d) a polypeptide consisting of amino acid residues 23 to 63 of SEQ ID NO:2, e) a polypeptide consisting of amino acid residues 1 to 60 of SEQ ED NO:2, f) a polypeptide consisting of amino acid residues 1 to 63 of SEQ ID NO:2, g) a polypeptide consisting of amino acid residues 12 to 41 of SEQ ID NO:6, h) a polypeptide consisting of amino acid residues 12 to 44 of SEQ ID NO:6, i) a polypeptide consisting of amino acid residues 1 to 41 of SEQ ID NO:6, and j) a polypeptide consisting of amino acid residues 1 to 44 of SEQ ID NO:6. 4. A polypeptide according to claim 1, in combination with a pharmaceutically acceptable vehicle. 5 . A method of producing an antibody to a polypeptide comprising: inoculating an animal with a polypeptide according to claim 1, wherein said polypeptide elicits an immune response in the animal to produce the antibody; and isolating the antibody from the animal. 6. An antibody that specifically binds to a protein of claim 1. 7. An anti-idiotypic antibody of an antibody which specifically binds to a protein of claim 1. 8. An isolated polynucleotide encoding a polypeptide comprising amino acid residues 31-60 of SEQ ID NO:2. 9. An isolated polynucleotide encoding a polypeptide comprising amino acid residue 1 to amino acid residue 63 of SEQ ID NO:2. 10. An isolated polynucleotide encoding a polypeptide selected from the group consisting of: a) a polypeptide consisting of amino acid residues 31 to 60 of SEQ ID NO:2; b) a polypeptide consisting of amino acid residues 31 to 63 of SEQ ID NO: 2, c) a polypeptide consisting of amino acid residues 23 to 60 of SEQ ID NO:2, d) a polypeptide consisting of amino acid residues 23 to 63 of SEQ ID NO: 2, e) a polypeptide consisting of amino acid residues 1 to 60 of SEQ ID NO:2, f) a polypeptide consisting of amino acid residues 1 to 63 of SEQ ID NO:2, g) a polypeptide consisting of amino acid residues 12 to 41 of SEQ ID NO:6, h) a polypeptide consisting of amino acid residues 12 to 44 of SEQ ID NO:6, i) a polypeptide consisting of amino acid residues 1 to 41 of SEQ ID NO: 6, and j) a polypeptide consisting of amino acid residues 1 to 44 of SEQ ED NO:6. 11. An isolated polynucleotide selected from the group consisting of: a) a polynucleotide consisting of nucleotides 1 to 324 of SEQ ID NO: 1, b) a polynucleotide consisting of nucleotides 10 to 198 of SEQ ID NO: 1, c) a polynucleotide consisting of nucleotides 10 to 189 of SEQ ID NO: 1, d) a polynucleotide consisting of nucleotides 76 to 198 of SEQ ID NO: 1 , e) a polynucleotide consisting of nucleotides 76 to 189 of SEQ ID NO: 1 , f) a polynucleotide consisting of nucleotides 100 to 198 of SEQ ID NO: 1 , g) a polynucleotide consisting of nucleotides 100 to 189 of SEQ ID NO:l, h) a polynucleotide consisting of nucleotides 1 to 296 of SEQ ID NO:5, i) a polynucleotide consisting of nucleotides 1 to 132 of SEQ ED NO:5, j) a polynucleotide consisting of nucleotides 1 to 123 of SEQ ED NO:5 k) a polynucleotide consisting of nucleotides 34 to 123 of SEQ ID NO: 5, and 1) a polynucleotide consisting of nucleotides 34 to 132 of SEQ ED NO:5. 12. An expression vector comprising the following operably linked elements: a transcription promoter; a DNA segment encoding a protein of claim 1 ; and a transcription terminator. 13. An expression vector according to claim 12, wherein said DNA segment further encodes a secretory signal sequence operably linked to said protein. 14. An expression vector according the claim 13, wherein said secretory signal sequence is a polypeptide having the sequence of amino acid residue 1 to amino acid residue 22 of SEQ ID NO:2. 15. A cultured cell into which has been introduced an expression vector according to claim 12; wherein said cell expresses said polypeptide encoded by said DNA segment. 16. A method of producing a protein comprising: culturing a cell into which has been introduced an expression vector according to claim 12; whereby said cell expresses said polypeptide encoded by said DNA segment; and recovering said expressed polypeptide. 17. A method of treating a microbial-related disease comprising administering to a mammal a therapeutically effective amount of a polypeptide selected from the group consisting of: a) a polypeptide of SEQ ID NO:2; b) a polypeptide of SEQ ID NO:6; c) a polypeptide consisting of amino acid residues 23-63 of SEQ ID NO:2; d) a polypeptide consisting of amino acid residues 31-60 of SEQ ED NO:2; and e) a polypeptide consisting of amino acid residues 12-40 of SEQ DD NO:6; whereby said polypeptide ameliorates said disease.

Inventors: ADLER DAVID A, GAO ZEREN, HOLLOWAY JAMES L, PRESNELL SCOTT R, ADLER, DAVID, A., GAO, ZEREN, HOLLOWAY, JAMES, L., PRESNELL, SCOTT, R.
Applicants: ZYMOGENETICS INC, ZYMOGENETICS, INC.
Application year: 2000
Main classification: C07K14
IPC codes: A61K38, A61P31, C07K14, C07K16, C12N1, C12N5, C12N15, C12P21