Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At fertilization, mammalian sperm bind is a species-specific manner to the extracellular zona pellucida that surrounds ovulated eggs. ZP3, an 83,000-85,000 Da glycoprotein of the murine zona pellucida, has been shown to inhibit sperm binding via its O-linked oligosaccharide side chains. We have recently isolated cDNA clones coding for ZP3 and have demonstrated that ZP3 transcripts are accumulated in oocytes where their expression is developmentally regulated during oogenesis. We now report that ZP3 mRNA is 1317 nt long with an estimated poly(A) tail of 200-300 nt. The short 29-nt 5' untranslated region is followed by a single open reading frame coding for a polypeptide chain of 46,307 Da which includes six possible sites for N-linked oligosaccharides. The N-terminus of ZP3 contains a potential 22-amino acid signal peptide which upon cleavage would result in a secreted core protein of 43,943 Da. The termination codon is a part of the AATAAA polyadenylation signal and is contained in an unusually short 16-nt 3' untranslated region. Sequences homologous to ZP3 are conserved among mammals and are expressed in ovarian tissue as mature transcripts with indistinguishable molecular weights.
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PMID:Molecular analysis of cDNA coding for ZP3, a sperm binding protein of the mouse zona pellucida. 337 65

The zona pellucida is an extracellular coat that surrounds all mammalian eggs. Sperm must penetrate the zona pellucida in order to reach and fuse with the plasma membrane of unfertilized eggs. Penetration is accomplished by a sequence of events involving both egg and sperm. First, sperm must bind to the outer margin of the zona pellucida. Such binding is mediated in a relatively species-specific manner by "sperm receptors" in the zona pellucida. Second, sperm must undergo the "acrosome reaction", a membrane fusion event, in order to traverse the zona pellucida. Here we review results from our own laboratory which demonstrate that, during the course of sperm-egg interaction in mice, zona pellucida glycoprotein ZP3 serves as both receptor for sperm and inducer of the acrosome reaction. Furthermore, we review evidence from our laboratory indicating that the sperm receptor activity of ZP3 is dependent only on its 0-linked carbohydrate components, whereas acrosome reaction-inducing activity is dependent on the polypeptide portion of ZP3 as well.
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PMID:Nature of the mouse egg's receptor for sperm. 354 45

During the course of sperm-egg interaction in mice, zona pellucida glycoprotein ZP3 (approximately equal to 80 kDa) serves as both receptor for sperm (J. D. Bleil and P. M. Wassarman, 1980c, Cell 20, 873-882) and inducer of the acrosome reaction (J. D. Bleil and P. M. Wassarman, 1983, Dev. Biol. 95, 317-324). In this investigation, small ZP3 glycopeptides (approximately equal to 1.5-6 kDa), obtained by extensive digestion of the purified glycoprotein with insoluble Pronase, were assayed for both sperm receptor and acrosome reaction-inducing activities. While ZP3 glycopeptides were virtually as effective as intact ZP3 in inhibiting binding of sperm to eggs in vitro ("receptor activity"), unlike intact ZP3, they failed to induce sperm to undergo the acrosome reaction. The latter was determined by indirect immunofluorescence using a monoclonal antibody directed against the acrosomal cap region of sperm. These results suggest that the sperm receptor activity of ZP3 is dependent only on its carbohydrate components, whereas acrosome reaction-inducing activity is dependent on the polypeptide chain of ZP3 as well.
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PMID:Enzymatic dissection of the functions of the mouse egg's receptor for sperm. 638 71

Tunicamycin, an inhibitor of asparagine-linked glycosylation of glycoprotein, has been used here to examine the role of N-linked oligosaccharides in secretion of ZP2 and ZP3, two of the three glycoproteins that constitute the mouse egg's extracellular coat (zona pellucida). In the absence of tunicamycin, growing mouse oocytes cultured in vitro synthesize a 91,000-Mr ZP2 precursor and 53,000 and 56,000 Mr ZP3 precursors. All of these precursors contain high mannose-type oligosaccharides that are processed to complex-type prior to secretion of mature ZP2 (120,000 Mr) and ZP3 (80,000 Mr) (Greve, J. M., Salzmann, G. S., Roller, R. J., and Wassarman, P. M. (1982) Cell 31, 749-759; Salzmann, G. S., Greve, J. M., Roller, R. J., and Wassarman, P. M. (1983) Eur. Mol. Biol. Org. J. 2, 1451-1456). In the presence of 5 micrograms/ml of tunicamycin, growing oocytes cultured in vitro are unable to carry out "core" glycosylation of nascent ZP2 and ZP3. Consequently, under these conditions, ZP2 and ZP3 appear as 81,000 and 44,000 Mr polypeptide chains, respectively. The apparent rates of synthesis of core-glycosylated ZP2 and ZP3 precursors synthesized in the absence of tunicamycin and of precursors synthesized in the presence of the drug are virtually identical. On the other hand, in the presence of tunicamycin, nascent ZP3 is incorporated into the zona pellucida as an extremely heterogeneous species (approximately equal to 51,000 Mr) at about three times the rate observed for mature ZP3 in the absence of tunicamycin. In the presence of tunicamycin, ZP2 is incorporated into the zona pellucida as 81,000 and 76,000 Mr species at about one-sixth the rate observed for mature ZP2 in the absence of the drug. Results of pulse-chase experiments indicate that the low degree of incorporation of ZP2 lacking N-linked oligosaccharides into the zona pellucida is due to a greatly decreased rate of secretion as compared to the core-glycosylated precursor. ZP2 synthesized in the presence of tunicamycin is relatively stable and accumulates intracellularly. These results suggest that N-linked oligosaccharides are necessary for normal secretion of ZP2, but are probably not necessary for ZP3 secretion.
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PMID:Role of asparagine-linked oligosaccharides in secretion of glycoproteins of the mouse egg's extracellular coat. 663 Feb 29

A summary is presented of published and some unpublished observations from studies on the immunological response of mice to a 13-mer peptide of the murine ovarian zona pellucida glycoprotein ZP3. The findings have the following implications for the design of immunocontraceptive vaccines. To be reversible, a ZP3 vaccine must not contain pathogenic T cell epitopes of ZP3, but contraception without autoimmune oophoritis may be feasible. The immune response to the ZP3 mini-autoantigen is highly variable among inbred mouse strains, suggesting that a single oophoritogenic peptide would not achieve irreversible contraception in an outbred population. The discovery of antigen mimicry at the level of T cell peptide has thrown doubt on the validity of current strategy in detecting relevant self-antigens that might cross react with vaccine immunogens and on the feasibility of fully predicting the cross-reactive autoimmunogenic potential of a peptide or polypeptide vaccine antigen. Autoantibodies directed against epitopes outside the ZP3 mini-autoantigen, produced by immunization with the pure T cell epitope, react with high affinity, with native zona pellucida, and may be useful in identifying B cell epitopes in ZP3.
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PMID:Contraceptive vaccine assessment based on a murine ZP3 mini-autoantigen. 753 Mar 82

The mammalian zona pellucida is an extracellular matrix that surrounds growing oocytes, ovulated eggs and early embryos. The mouse zona is composed of three sulfated glycoproteins: ZP1, ZP2 and ZP3. Each is critically involved in fertilization, the postfertilization block to polyspermy and protection of the preimplantation embryo. We have previously isolated cDNAs encoding mouse ZP2 and ZP3 and now report the isolation of a full-length cDNA encoding ZP1. Mouse ZP1 is composed of a 623 amino acid polypeptide chain with a signal peptide and a carboxyl terminal transmembrane domain, typical of all zona proteins. Sequence comparison demonstrate that mouse ZP1 is an orthologue of a rabbit zona protein, R55. The expression of R55 has been reported previously in both oocytes and granulosa cells. However, by northern analysis and in situ hybridization with 33P-labelled antisense probes to each of the three mouse zona mRNAs, we have determined that the expression of each mouse zona gene is restricted to the oocyte. ZP2 transcripts, but not ZP1 or ZP3, are detected in resting (15 microns diameter) oocytes, and all three zona transcripts coordinately accumulate as oocytes begin to grow. Together they represent approximately 1.5% of the total poly(A)+ RNA in 50-60 microns oocytes. In the latter stages of oogenesis, their abundance declines and each zona transcript is present in ovulated eggs at less than 5% of its maximal level. No zona transcripts were detected above background signal in granulosa cells. We conclude that, in mice, the three zona pellucida genes are expressed in a coordinate, oocyte-specific manner during the growth phase of oogenesis. Our data support the hypothesis that the transcription of the zona genes is controlled, in part, by shared regulatory element(s).
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PMID:Coordinate expression of the three zona pellucida genes during mouse oogenesis. 763 43

During fertilization in mice, sperm bind to mouse ZP3 (mZP3), a M(r) approximately 83,000 glycoprotein present in the ovulated egg extracellular coat, or zona pellucida. Sperm recognize and bind to specific serine/threonine-linked (O-linked) oligosaccharides present at the mZP3 combining site for sperm. Binding to mZP3 induces sperm to undergo a form of exocytosis, the acrosome reaction. To map the mZP3 combining site for sperm, we examined the effect of exon swapping and site-directed mutagenesis on the glycoprotein's two activities, sperm binding and induction of the acrosome reaction. Stably transfected embryonal carcinoma cell lines were established that synthesized recombinant glycoproteins and secreted them into the culture medium. The glycoproteins were partially purified from culture medium and assayed for sperm-binding and acrosome reaction-inducing activities. Results of these assays suggest that glycosylation of one or more of five serine residues, clustered together in a polypeptide region encoded by mZP3 gene exon 7, is required for activity. Interestingly, this polypeptide region exhibits considerable sequence divergence during evolution and may be related to the proposed role for oligosaccharides in species-specific gamete adhesion during mammalian fertilization.
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PMID:Mapping the mouse ZP3 combining site for sperm by exon swapping and site-directed mutagenesis. 781 29

The zona pellucida surrounding the mammalian oocyte contains a major glycoprotein species, ZP3, that serves as a cell- and species-specific receptor for spermatozoa. In this study we have determined the primary amino acid structure of marmoset ZP3 (marZP3) and examined the expression of marZP3 mRNA within the ovary. The marZP3 gene possesses an open reading frame of 1272 nucleotides which is expressed specifically by the oocyte and encodes a polypeptide chain of 424 amino acids that exhibits 91% homology with the human ZP3 sequence. The disparity between these molecules was confined to a short domain spanning residues 322-352; otherwise the molecules were very similar, showing conservation of many structural features including the N-linked glycosylation sites, location and number of cysteine and proline residues and hydrophobicity profile. The results of this study have important implications for the use of the marmoset monkey as an animal model for the development of contraceptive vaccines targeting ZP3.
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PMID:Cloning, sequencing and oocyte-specific expression of the marmoset sperm receptor protein, ZP3. 808 14

Southern blot analysis of genomic DNA and gene-cloning experiments have recently shown that the human ZP3 gene is not a single-copy gene. The human genome harbors sequences encoding a protein of 424 amino acids and, in addition, a polymorphic locus with the potential to give rise to a probably nonfunctional polypeptide of 372 residues. In this report it is shown, by screening of a panel of human x hamster hybrid cell lines, that both the ZP3 and ZP3P loci are located on human chromosome 7.
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PMID:The human gene for the zona pellucida glycoprotein ZP3 and a second polymorphic locus are located on chromosome 7. 846 8

The cDNA encoding bonnet monkey zona pellucida ZP3 from bonnet ovary has been amplified by polymerase chain reaction. The ZP3 gene has an open reading frame of 1272 nucleotides encoding a polypeptide of 424 amino acid residues which shares 93.9% overall identity with human ZP3. Bonnet ZP3 has four potential attachment sites for N-linked sugar chains which are also conserved in human ZP3. Bonnet ZP3 has 14 cysteine residues compared with 15 in human ZP3. The highest disparity between these molecules was restricted to a domain represented by amino acid residues 370-398. These results have important implications for the use of bonnet monkey as an animal model for evaluation and development of contraceptive vaccine based on ZP3 for human use.
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PMID:Nucleotide sequence of cDNA encoding bonnet monkey (Macaca radiata) zona pellucida glycoprotein-ZP3. 884 88


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