ZP3

Zona pellucida glycoprotein 3 (sperm receptor)
Crystal structure of full-length ZP3[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3D4C​, 3D4G​, 3EF7​, 3NK3​, 3NK4​
Identifiers
Symbols	ZP3 ; ZP3A; ZP3B; ZPC; Zp-3
External IDs	OMIM: 182889 MGI: 99215 HomoloGene: 5178 GeneCards: ZP3 Gene
Gene ontology Molecular function • signal transducer activity • manganese ion transmembrane transporter activity • protein binding • store-operated calcium channel activity • carbohydrate binding • acrosin binding Cellular component • acrosomal vesicle • outer acrosomal membrane • extracellular region • proteinaceous extracellular matrix • extracellular space • cytoplasm • multivesicular body • endoplasmic reticulum • Golgi apparatus • plasma membrane • integral component of membrane • secretory granule • extracellular matrix • perinuclear region of cytoplasm Biological process • positive regulation of type IV hypersensitivity • blastocyst formation • humoral immune response mediated by circulating immunoglobulin • positive regulation of leukocyte migration • positive regulation of humoral immune response • manganese ion transport • intracellular protein transport • single fertilization • binding of sperm to zona pellucida • positive regulation of phosphatidylinositol biosynthetic process • multicellular organism reproduction • positive regulation of interferon-gamma production • positive regulation of interleukin-4 production • intracellular signal transduction • egg coat formation • positive regulation of T cell proliferation • positive regulation of protein kinase activity • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • phosphatidylinositol-mediated signaling • oocyte development • positive regulation of inflammatory response • positive regulation of protein kinase B signaling • protein kinase C signaling • calcium ion transmembrane transport • manganese ion transmembrane transport • positive regulation of calcium ion import • positive regulation of acrosome reaction • negative regulation of binding of sperm to zona pellucida • positive regulation of acrosomal vesicle exocytosis • positive regulation of ovarian follicle development • positive regulation of antral ovarian follicle growth Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7784	22788
Ensembl	ENSG00000188372	ENSMUSG00000004948
UniProt	P21754	P10761
RefSeq (mRNA)	NM_001110354	NM_011776
RefSeq (protein)	NP_001103824	NP_035906
Location (UCSC)	Chr 7: 76.4 – 76.44 Mb	Chr 5: 135.98 – 135.99 Mb
PubMed search

Zona pellucida sperm-binding protein 3, also known as zona pellucida glycoprotein 3 (Zp-3) or the sperm receptor, is a protein that in humans is encoded by the ZP3 gene.^[2][3] ZP3 is the receptor in the zona pellucida which binds sperm at the beginning of fertilization.

Function

The zona pellucida (ZP) is a specialized extracellular matrix that surrounds the oocyte and early embryo. It is composed of three or four glycoproteins (ZP1-4) with various functions during oogenesis, fertilization and preimplantation development. The protein encoded by this gene is a major structural component of the ZP and functions in primary binding and stimulation of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a consensus furin cleavage site (CFCS), a polymerization-blocking external hydrophobic patch (EHP), and a C-terminal transmembrane domain. Cleavage at the CFCS separates the mature protein from the EHP, allowing it to incorporate into nascent ZP filaments. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene.^[2]

References

1. PDB: 3NK3​ PDB: 3NK4​; Han L, Monné M, Okumura, H, Schwend, T, Cherry, AL, Flot, D, Matsuda, T, Jovine, L (2010). "Insights into egg coat assembly and egg-sperm interaction from the X-ray structure of full-length ZP3". Cell 143 (3): 404–15. doi:10.1016/j.cell.2010.09.041. PMID 20970175.
2. "Entrez Gene: zona pellucida glycoprotein 3 (sperm receptor)".
3. van Duin M, Polman JE, Verkoelen CC, Bunschoten H, Meyerink JH, Olijve W, Aitken RJ (December 1992). "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". Genomics 14 (4): 1064–70. doi:10.1016/S0888-7543(05)80130-2. PMID 1478648.

Further reading

• Bansal P, Chakrabarti K, Gupta SK (2009). "Functional activity of human ZP3 primary sperm receptor resides toward its C-terminus". Biol. Reprod. 81 (1): 7–15. doi:10.1095/biolreprod.108.074716. PMID 19246320.
• Choudhury S, Ganguly A, Chakrabarti K, et al. (2009). "DNA vaccine encoding chimeric protein encompassing epitopes of human ZP3 and ZP4: immunogenicity and characterization of antibodies". J. Reprod. Immunol. 79 (2): 137–47. doi:10.1016/j.jri.2008.09.002. PMID 19004505.
• Chiu PC, Wong BS, Chung MK, et al. (2008). "Effects of native human zona pellucida glycoproteins 3 and 4 on acrosome reaction and zona pellucida binding of human spermatozoa". Biol. Reprod. 79 (5): 869–77. doi:10.1095/biolreprod.108.069344. PMID 18667750.
• Gook DA, Edgar DH, Borg J, Martic M (2008). "Detection of zona pellucida proteins during human folliculogenesis". Hum. Reprod. 23 (2): 394–402. doi:10.1093/humrep/dem373. PMID 18033806.
• Monné M, Han L, Schwend T, Burendahl S, Jovine L (2008). "Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats". Nature 456 (7222): 653–7. doi:10.1038/nature07599. PMID 19052627. PDB: 3D4C​ PDB: 3D4G​ PDB: 3EF7​
• Törmälä RM, Jääskeläinen M, Lakkakorpi J, et al. (2008). "Zona pellucida components are present in human fetal ovary before follicle formation". Mol. Cell. Endocrinol. 289 (1-2): 10–5. doi:10.1016/j.mce.2008.01.029. PMID 18502569.
• Ni Y, Li K, Xu W, et al. (2007). "Acrosome reaction induced by recombinant human zona pellucida 3 peptides rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 and their mechanism". J. Androl. 28 (3): 381–8. doi:10.2164/jandrol.106.001289. PMID 17192598.
• Caballero-Campo P, Chirinos M, Fan XJ, et al. (2006). "Biological effects of recombinant human zona pellucida proteins on sperm function". Biol. Reprod. 74 (4): 760–8. doi:10.1095/biolreprod.105.047522. PMID 16407501.
• Furlong LI, Harris JD, Vazquez-Levin MH (2005). "Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP) glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC". Fertil. Steril. 83 (6): 1780–90. doi:10.1016/j.fertnstert.2004.12.042. PMID 15950651.
• Jovine L, Qi H, Williams Z, Litscher ES, Wassarman PM (2004). "A duplicated motif controls assembly of zona pellucida domain proteins". Proc. Natl. Acad. Sci. U.S.A. 101 (16): 5922–7. doi:10.1073/pnas.0401600101. PMC 395899. PMID 15079052.
• Zhao M, Boja ES, Hoodbhoy T, et al. (2004). "Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells". Biochemistry 43 (38): 12090–104. doi:10.1021/bi048958k. PMID 15379548.
• Dell A, Chalabi S, Easton RL, et al. (2003). "Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15631–6. doi:10.1073/pnas.2635507100. PMC 307619. PMID 14673092.
• Jovine L, Qi H, Williams Z, Litscher E, Wassarman PM (2002). "The ZP domain is a conserved module for polymerization of extracellular proteins". Nat Cell Biol. 4 (6): 457–61. doi:10.1038/ncb802. PMID 12021773.
• Kiefer SM, Saling P (2002). "Proteolytic processing of human zona pellucida proteins". Biol. Reprod. 66 (2): 407–14. doi:10.1095/biolreprod66.2.407. PMID 11804956.
• Qi H, Williams Z, Wassarman PM (2002). "Secretion and assembly of zona pellucida glycoproteins by growing mouse oocytes microinjected with epitope-tagged cDNAs for mZP2 and mZP3". Mol. Biol. Cell 13 (2): 530–41. doi:10.1091/mbc.01-09-0440. PMC 65647. PMID 11854410.
• Zhao M, Gold L, Ginsberg AM, et al. (2002). "Conserved furin cleavage site not essential for secretion and integration of ZP3 into the extracellular egg coat of transgenic mice". Mol. Cell. Biol. 22 (9): 3111–20. doi:10.1128/MCB.22.9.3111-3120.2002. PMC 133755. PMID 11940668.
• Wassarman PM, Jovine L, Litscher ES (2001). "A profile of fertilization in mammals". Nat Cell Biol. 3 (2): E59–64. doi:10.1038/35055178. PMID 11175768.
• Rankin T, Dean J (2000). "The zona pellucida: using molecular genetics to study the mammalian egg coat". Rev. Reprod. 5 (2): 114–21. doi:10.1530/ror.0.0050114. PMID 10864856.
• Chamberlin ME, Dean J (1990). "Human homolog of the mouse sperm receptor". Proc. Natl. Acad. Sci. U.S.A. 87 (16): 6014–8. doi:10.1073/pnas.87.16.6014. PMC 54462. PMID 2385582.
• Florman HM, Wassarman PM (1985). "O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity". Cell 41 (1): 313–24. doi:10.1016/0092-8674(85)90084-4. PMID 2986849.
• Bleil JD, Wassarman PM (1980). "Mammalian sperm-egg interaction: identification of a glycoprotein in mouse egg zonae pellucidae possessing receptor activity for sperm". Cell 20 (3): 873–82. doi:10.1016/0092-8674(80)90334-7. PMID 7418009.

External links

• ZP3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.