PROSITE documentation PDOC00577
ZP domain signature and profile


The zona pellucida (ZP) domain is a protein polymerization module of ~260 amino acid module, which is found at the C-terminus of many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer [1,2,3,4]:

  • Sperm receptor proteins ZP2 and ZP3. Along with protein ZP1, proteins ZP2 and ZP3 are responsible for sperm-adhesion to the zona pellucida. ZP3 first binds to specific sperm proteins, thus mediating sperm contacts with the oocyte. ZP2 acts as a second sperm receptor reinforcing the interactions. ZP1 cross-links the polymers formed by ZP2 and ZP3.
  • Zona pellucida sperm-binding protein B (ZP-B) (also known as ZP-X in rabbit and ZP-3 α in pig).
  • Glycoprotein GP2, the major component of pancreatic secretory granule membranes.
  • TGF-β receptor type III (also known as βglycan). This protein is a proteoglycan that binds to TGF-β and could be involved in capturing and retaining TGF-β for presentation to the signalling receptors.
  • Uromodulin (also known as Tamm-Horsfall urinary glycoprotein). The function of this protein, which is the most abundant in human urine, is not yet clear.
  • Chicken β-tectorin, a major glycoprotein of avian tectorial membrane.

Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors [2].

The ZP domain contains eight strictly conserved cysteines, which form disulfide bridges. The disulfide bonds within the ZP domains are divided into two groups, suggesting that the ZP domain consists of two subdomains. In addition to the conserved cysteines, only a few aromatic or hydrophobic amino acids are absolutely invariant, probably as a result of structural rather than functional constraints [1,3,4].

The profile we developed covers the entire ZP domain.


Endoglins are reported to contain a region of homology with the N- terminal third of the ZP domain [5]. This truncated version of the ZP domain is not recognized by the profile.

Expert(s) to contact by email:

Bork P.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

ZP_2, PS51034; ZP domain profile  (MATRIX)

ZP_1, PS00682; ZP domain signature  (PATTERN)


1AuthorsBork P. Sander C.
TitleA large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor.
SourceFEBS Lett. 300:237-240(1992).
PubMed ID1313375

2AuthorsJovine L. Qi H. Williams Z. Litscher E. Wassarman P.M.
TitleThe ZP domain is a conserved module for polymerization of extracellular proteins.
SourceNat. Cell Biol. 4:457-461(2002).
PubMed ID12021773

3AuthorsYonezawa N. Nakano M.
TitleIdentification of the carboxyl termini of porcine zona pellucida glycoproteins ZPB and ZPC.
SourceBiochem. Biophys. Res. Commun. 307:877-882(2003).
PubMed ID12878193

4AuthorsJovine L. Qi H. Williams Z. Litscher E.S. Wassarman P.M.
TitleA duplicated motif controls assembly of zona pellucida domain proteins.
SourceProc. Natl. Acad. Sci. U.S.A. 101:5922-5927(2004).
PubMed ID15079052

5AuthorsGe A.Z. Butcher E.C.
TitleCloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand.
SourceGene 138:201-206(1994).
PubMed ID8125301

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