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Gene Review

ZP3  -  zona pellucida glycoprotein 3 (sperm...

Homo sapiens

Synonyms: Sperm receptor, ZP3-372, ZP3-424, ZP3A, ZP3A/ZP3B, ...
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Disease relevance of ZP3


High impact information on ZP3

  • These receptors include the receptor tyrosine kinases that mediate the actions of growth factors such as epidermal growth factor, insulin, insulin-like growth factor as well as receptors for atrial natiuretic hormone or the zona pellucida protein (ZP3) and integrins [5].
  • A 95-kilodalton mouse sperm protein with characteristics of a protein tyrosine kinase has been identified as a receptor for ZP3, a glycoprotein in the egg's extracellular matrix [6].
  • Antibodies against a synthetic peptide from the intracellular domain recognized a 95-kilodalton human sperm protein that contains phosphotyrosine; human ZP3 stimulates the kinase activity of this sperm protein [6].
  • Our results demonstrate that the C-terminal transmembrane domain and short cytoplasmic tail of ZP2 and ZP3 are not required for secretion, but are essential for assembly [7].
  • The primacy of the T cell response in the pathogenesis of disease is further substantiated by defining oophoritogenic peptides as small as eight amino acids (Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln) that do not elicit an antibody response to the full-length ZP3 peptide [4].

Chemical compound and disease context of ZP3


Biological context of ZP3


Anatomical context of ZP3

  • In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3 [1].
  • Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells [13].
  • ZP3 is the ligand for primary sperm binding and important for the induction of the acrosome reaction [14].
  • Human ZP3 expressed in mouse oocytes had an apparent mass (64 kDa) indistinguishable from native human ZP3 and distinct from mouse ZP3 (83 kDa) [15].
  • Under reducing conditions, zonae from unfertilized eggs separated into three acidic proteins with molecular weight ranges of 90,000-110,000 (ZP1), 64,000-78,000 (ZP2) and 57,000-73,000 (ZP3) [16].

Associations of ZP3 with chemical compounds

  • Previous studies have suggested that the sperm receptor activity of the zona pellucida resides in specific oligosaccharide chains on the ZP3 glycoprotein [17].
  • These results support the model that initial interaction of the fertilizing spermatozoon with ZP3 involves the tyrosine phosphorylation of a 95 kDa tyrosine kinase protein and that this requires capacitation [18].
  • Multivalent oligosaccharides on ZP3, as well as synthetic polymers terminating in N-acetylglucosamine aggregate GalT, leading to activation of a heterotrimeric G protein cascade and culminating in the acrosome reaction [19].
  • Possum ZP3 has a 46% amino acid identity with eutherian ZP3 and shares similar structural characteristics including 12 conserved cysteine residues, N-linked glycosylation sites and hydrophobic regions [20].
  • Conserved ZPC domains and motifs present in the Xenopus sequence included a signal peptide sequence, an N-linked glycosylation site, and 12 aligned Cys residues [21].

Regulatory relationships of ZP3


Other interactions of ZP3

  • By using the polymerase chain reaction, a full-length cDNA of human ZP3 was isolated from human ovarian poly(A)+ RNA and used to deduce the structure of human ZP3 mRNA [24].
  • Taken together, these data suggest that partial duplications of human ZP3 and a POM121-like gene have resulted in a fusion transcript, POM-ZP3, that is expressed in multiple human tissues [11].
  • Recently, the hamster sperm receptor, a 56,000 Mr zona pellucida glycoprotein called hZP3, was identified and partially characterized (C. C. Moller et al., (1990). Dev. Biol. 137, 276-286) [25].
  • The ZP3 aa sequence similarities were examined using the GAP program (GCG) [26].
  • 11 (58%) of the embryos were judged to be "male" and 8 (42%) "female". The SRY and ZP3 gene primers selected are highly specific and give accurate results in sex determination and their use provides a new reliable method for routine preimplantation and general prenatal sex determination in man [22].

Analytical, diagnostic and therapeutic context of ZP3


  1. The zona pellucida: using molecular genetics to study the mammalian egg coat. Rankin, T., Dean, J. Rev. Reprod. (2000) [Pubmed]
  2. Baculovirus-expressed recombinant human zona pellucida glycoprotein-B induces acrosomal exocytosis in capacitated spermatozoa in addition to zona pellucida glycoprotein-C. Chakravarty, S., Suraj, K., Gupta, S.K. Mol. Hum. Reprod. (2005) [Pubmed]
  3. ZP2 and ZP3 Traffic Independently within Oocytes prior to Assembly into the Extracellular Zona Pellucida. Hoodbhoy, T., Avil??s, M., Baibakov, B., Epifano, O., Jim??nez-Movilla, M., Gauthier, L., Dean, J. Mol. Cell. Biol. (2006) [Pubmed]
  4. Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida. Rhim, S.H., Millar, S.E., Robey, F., Luo, A.M., Lou, Y.H., Yule, T., Allen, P., Dean, J., Tung, K.S. J. Clin. Invest. (1992) [Pubmed]
  5. Single transmembrane spanning heterotrimeric g protein-coupled receptors and their signaling cascades. Patel, T.B. Pharmacol. Rev. (2004) [Pubmed]
  6. Interaction of a tyrosine kinase from human sperm with the zona pellucida at fertilization. Burks, D.J., Carballada, R., Moore, H.D., Saling, P.M. Science (1995) [Pubmed]
  7. The ZP domain is a conserved module for polymerization of extracellular proteins. Jovine, L., Qi, H., Williams, Z., Litscher, E., Wassarman, P.M. Nat. Cell Biol. (2002) [Pubmed]
  8. Gene knockouts that cause female infertility: search for novel contraceptive targets. Naz, R.K., Rajesh, C. Front. Biosci. (2005) [Pubmed]
  9. Rat zona pellucida glycoproteins: molecular cloning and characterization of the three major components. Akatsuka, K., Yoshida-Komiya, H., Tulsiani, D.R., Orgebin-Crist, M.C., Hiroi, M., Araki, Y. Mol. Reprod. Dev. (1998) [Pubmed]
  10. Proteolytic processing of human zona pellucida proteins. Kiefer, S.M., Saling, P. Biol. Reprod. (2002) [Pubmed]
  11. POM-ZP3, a bipartite transcript derived from human ZP3 and a POM121 homologue. Kipersztok, S., Osawa, G.A., Liang, L.F., Modi, W.S., Dean, J. Genomics (1995) [Pubmed]
  12. Egg-sperm interactions at fertilization in mammals. Wassarman, P.M., Jovine, L., Litscher, E.S., Qi, H., Williams, Z. Eur. J. Obstet. Gynecol. Reprod. Biol. (2004) [Pubmed]
  13. Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells. Zhao, M., Boja, E.S., Hoodbhoy, T., Nawrocki, J., Kaufman, J.B., Kresge, N., Ghirlando, R., Shiloach, J., Pannell, L., Levine, R.L., Fales, H.M., Dean, J. Biochemistry (2004) [Pubmed]
  14. The zona pellucida "receptors". Hinsch, E., Hägele, W., Schill, W.B., Hinsch, K.D. Adv. Exp. Med. Biol. (1997) [Pubmed]
  15. Human ZP3 restores fertility in Zp3 null mice without affecting order-specific sperm binding. Rankin, T.L., Tong, Z.B., Castle, P.E., Lee, E., Gore-Langton, R., Nelson, L.M., Dean, J. Development (1998) [Pubmed]
  16. Characterization of the human zona pellucida from fertilized and unfertilized eggs. Shabanowitz, R.B., O'Rand, M.G. J. Reprod. Fertil. (1988) [Pubmed]
  17. Differential expression of glycoside residues in the mammalian zona pellucida. Avilés, M., Okinaga, T., Shur, B.D., Ballesta, J. Mol. Reprod. Dev. (2000) [Pubmed]
  18. Tyrosine phosphorylation of a 95 kDa protein and induction of the acrosome reaction in human spermatozoa by recombinant human zona pellucida glycoprotein 3. Brewis, I.A., Clayton, R., Browes, C.E., Martin, M., Barratt, C.L., Hornby, D.P., Moore, H.D. Mol. Hum. Reprod. (1998) [Pubmed]
  19. Galactosyltransferase function during mammalian fertilization. Nixon, B., Lu, Q., Wassler, M.J., Foote, C.I., Ensslin, M.A., Shur, B.D. Cells Tissues Organs (Print) (2001) [Pubmed]
  20. Cloning and characterisation of a zona pellucida 3 cDNA from a marsupial, the brushtail possum Trichosurus vulpecula. McCartney, C.A., Mate, K.E. Zygote (1999) [Pubmed]
  21. cDNA cloning and sequence analysis of the Xenopus laevis egg envelope glycoprotein gp43. Yang, J.C., Hedrick, J.L. Dev. Growth Differ. (1997) [Pubmed]
  22. Sex determination of preimplantation embryos by human testis-determining-gene amplification. Cui, K.H., Warnes, G.M., Jeffrey, R., Matthews, C.D. Lancet (1994) [Pubmed]
  23. Maternal autoantibody triggers de novo T cell-mediated neonatal autoimmune disease. Setiady, Y.Y., Samy, E.T., Tung, K.S. J. Immunol. (2003) [Pubmed]
  24. Human homolog of the mouse sperm receptor. Chamberlin, M.E., Dean, J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  25. Genomic organization and polypeptide primary structure of zona pellucida glycoprotein hZP3, the hamster sperm receptor. Kinloch, R.A., Ruiz-Seiler, B., Wassarman, P.M. Dev. Biol. (1990) [Pubmed]
  26. Comparison of ZP3 protein sequences among vertebrate species: to obtain a consensus sequence for immunocontraception. Zhu, X., Naz, R.K. Front. Biosci. (1999) [Pubmed]
  27. Cloning and characterization of the human sperm receptor ligand ZP3: evidence for a second polymorphic allele with a different frequency in the Caucasian and Japanese populations. van Duin, M., Polman, J.E., Verkoelen, C.C., Bunschoten, H., Meyerink, J.H., Olijve, W., Aitken, R.J. Genomics (1992) [Pubmed]
  28. Species specificity of human and murine anti-ZP3 synthetic peptide antisera and use of the antibodies for localization and identification of ZP3 or ZPC domains of functional significance. Hinsch, E., Oehninger, S., Schill, W.B., Hinsch, K.D. Hum. Reprod. (1999) [Pubmed]
  29. The human gene for the zona pellucida glycoprotein ZP3 and a second polymorphic locus are located on chromosome 7. van Duin, M., Polman, J.E., Suikerbuijk, R.F., Geurts-van Kessel, A.H., Olijve, W. Cytogenet. Cell Genet. (1993) [Pubmed]
  30. Immunocytochemical localization of ZP3 in primordial follicles of rabbit, marmoset, rhesus monkey and human ovaries using antibodies against human ZP3. Grootenhuis, A.J., Philipsen, H.L., de Breet-Grijsbach, J.T., van Duin, M. J. Reprod. Fertil. Suppl. (1996) [Pubmed]
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