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 receptor in the zona pellucida which binds sperm at the beginning of fertilization.

Zp3 structure pdb 3nk3.png
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
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 7: 76.4 – 76.44 MbChr 5: 135.98 – 135.99 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse


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.[6]

3D StructureEdit

X-ray crystallographic studies of the N-terminal half of mammalian ZP3 (PDB: 3D4C, 3D4G, 3EF7​)[7] as well as its full-length avian homolog (PDB: 3NK3, 3NK4​)[8] 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.[8]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000188372 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Entrez Gene: zona pellucida glycoprotein 3 (sperm receptor)".
  6. ^ "EggNOG Database | Orthology predictions and functional annnotaion". eggnogdb.embl.de. Retrieved 5 March 2019.
  7. ^ 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. PMID 19052627. S2CID 4430083. PDB: 3D4C, 3D4G, 3EF7
  8. ^ a b 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 readingEdit

External linksEdit

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