{PDOC00577} {PS00682; ZP_1} {PS51034; ZP_2} {BEGIN} *********************************** * 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 alpha in pig). - Glycoprotein GP2, the major component of pancreatic secretory granule membranes. - TGF-beta receptor type III (also known as betaglycan). This protein is a proteoglycan that binds to TGF-beta and could be involved in capturing and retaining TGF-beta 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 beta-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. -Consensus pattern: [LIVMFYW]-x(7)-[STAPDNLR]-x(3)-[LIVMFYW]-x-[LIVMFYW]-x- [LIVMFYW]-x(2)-C-[LIVMFYW]-x-[STA]-[PSLT]-x(2,4)-[DENSG]- x-[STADNQLFM]-x(6)-[LIVM](2)-x(3,4)-C [The 2 C's may be involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: 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.; bork@embl-heidelberg.de -Last update: December 2004 / Pattern and text revised. [ 1] Bork P., Sander C. "A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor." FEBS Lett. 300:237-240(1992). PubMed=1313375 [ 2] Jovine L., Qi H., Williams Z., Litscher E., Wassarman P.M. "The ZP domain is a conserved module for polymerization of extracellular proteins." Nat. Cell Biol. 4:457-461(2002). PubMed=12021773; DOI=10.1038/ncb802 [ 3] Yonezawa N., Nakano M. "Identification of the carboxyl termini of porcine zona pellucida glycoproteins ZPB and ZPC." Biochem. Biophys. Res. Commun. 307:877-882(2003). PubMed=12878193 [ 4] Jovine L., Qi H., Williams Z., Litscher E.S., Wassarman P.M. "A duplicated motif controls assembly of zona pellucida domain proteins." Proc. Natl. Acad. Sci. U.S.A. 101:5922-5927(2004). PubMed=15079052; DOI=10.1073/pnas.0401600101 [ 5] Ge A.Z., Butcher E.C. "Cloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand." Gene 138:201-206(1994). PubMed=8125301 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}