ZP3

Zona pellucida sperm-binding protein 3, also known as zona pellucida glycoprotein 3 (Zp-3) or the sperm receptor, is a ZP module-containing protein that in humans is encoded by the ZP3 gene.[5] ZP3 is the glycoprotein in the zona pellucida most important for inducting the acrosome reaction of sperm cells at the beginning of fertilization.[6]

ZP3
Identifiers
AliasesZP3, ZP3A, ZP3B, ZPC, Zp-3, zona pellucida glycoprotein 3 (sperm receptor), zona pellucida glycoprotein 3, OOMD3
External IDsOMIM: 182889 MGI: 99215 HomoloGene: 5178 GeneCards: ZP3
Orthologs
SpeciesHumanMouse
Entrez

7784

22788

Ensembl

ENSG00000188372

ENSMUSG00000004948

UniProt

P21754

P10761

RefSeq (mRNA)

NM_007155
NM_001110354

NM_011776

RefSeq (protein)

NP_001103824
NP_009086

NP_035906

Location (UCSC)Chr 7: 76.4 – 76.44 MbChr 5: 136.01 – 136.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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" module, 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.[5]

Orthologs of these genes are found throughout Vertebrata. The western clawed frog appears to have two orthologs, and the sea lamprey has seven.[7]

3D Structure

X-ray crystallographic studies of the N-terminal half of mammalian ZP3 (PDB: 3D4C, 3D4G, 3EF7, 5OSQ)[8] as well as its full-length avian homolog (PDB: 3NK3, 3NK4)[9] revealed that the protein's ZP module consists of two immunoglobulin-like domains, ZP-N and ZP-C. The latter, which contains EHP as well as a ZP3-specific subdomain, interacts with the ZP-N domain of a second molecule to generate an antiparallel homodimeric arrangement required for protein secretion.[9]

References

  1. GRCh38: Ensembl release 89: ENSG00000188372 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000004948 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: zona pellucida glycoprotein 3 (sperm receptor)".
  6. Litscher, E. S.; Williams, Z.; Wassarman, P. M. (2009). "Zona pellucida glycoprotein ZP3 and fertilization in mammals". Molecular Reproduction and Development. 76 (10): 933–941. doi:10.1002/mrd.21046. PMID 19504560. S2CID 21186053.
  7. "EggNOG Database | Orthology predictions and functional annnotaion". eggnogdb.embl.de. Archived from the original on 4 March 2019. Retrieved 5 March 2019.
  8. 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. Bibcode:2008Natur.456..653M. doi:10.1038/nature07599. hdl:11563/8930. PMID 19052627. S2CID 4430083. PDB: 3D4C, 3D4G, 3EF7
  9. 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. S2CID 18583237. PDB: 3NK3, 3NK4

Further reading

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


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