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21  structures 235  species 1  interaction 4052  sequences 219  architectures

Family: Zona_pellucida (PF00100)

Summary: Zona pellucida-like domain

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This is the Wikipedia entry entitled "Zona pellucida-like domain". More...

Zona pellucida-like domain Edit Wikipedia article

Zona pellucida-like domain
Symbol Zona_pellucida
Pfam PF00100
InterPro IPR001507

The Zona pellucida-like domain (ZP domain / ZP-like domain / ZP module) defines a family of evolutionarily related proteins.[1][2]

A large "ZP domain" region, containing around 260 amino acids, has been recognised in a variety of receptor-like eukaryotic glycoproteins.[1] All of these proteins are mosaic proteins composed of various domains and that all have a large extracellular region, often followed by either a transmembrane region and a very short cytoplasmic region or by a GPI-anchor.[2] Functional and crystallographic studies revealed that the "ZP domain" region common to all these proteins is a protein polymerization module that consists of two distinct but structurally related immunoglobulin-like domains, ZP-N and ZP-C.[3][4][5][6][7][8][9] The ZP module is located in the C-terminal portion of the extracellular region and - with the exception of non-polymeric family member ENG[10] - contains 8 or 10 conserved Cys residues involved in disulfide bonds.[5][6][9]

Additional copies of isolated ZP-N domains are found in the N-terminal region of egg coat protein subunits involved in fertilization in both vertebrates and invertebrates, such as human zona pellucida components ZP1, ZP2 and ZP4 and mollusk vitelline envelope receptor for egg lysin (VERL).[5][11][12]


Humans genes encoding proteins containing this domain include:


  1. ^ a b Bork P, Sander C (1992). "A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor". FEBS Lett. 300 (3): 237–40. doi:10.1016/0014-5793(92)80853-9. PMID 1313375. 
  2. ^ a b Jovine L, Darie CC, Litscher ES, Wassarman PM (2005). "Zona pellucida domain proteins". Annu. Rev. Biochem. 74: 83–114. doi:10.1146/annurev.biochem.74.082803.133039. PMID 15952882. 
  3. ^ 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. 
  4. ^ 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 395899Freely accessible. PMID 15079052. 
  5. ^ a b c 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, 3D4G, 3EF7
  6. ^ 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.  PDB: 3NK3, 3NK4
  7. ^ Lin SJ, Hu Y, Zhu J, Woodruff TK, Jardetzky TS (2011). "Structure of betaglycan zona pellucida (ZP)-C domain provides insights into ZP-mediated protein polymerization and TGF-beta binding". Proc Natl Acad Sci U S A. 108 (13): 5232–6. doi:10.1073/pnas.1010689108. PMID 21402931.  PDB: 3QW9
  8. ^ Diestel U, Resch M, Meinhardt K, Weiler S, Hellmann TV, Mueller TD, Nickel J, Eichler J, Muller YA (2013). "Identification of a Novel TGF-β-Binding Site in the Zona Pellucida C-terminal (ZP-C) Domain of TGF-β-Receptor-3 (TGFR-3)". PLoS One. 8 (6): e67214. doi:10.1371/journal.pone.0067214. PMID 23826237.  PDB: 4AJV
  9. ^ a b Bokhove M, Nishimura K, Brunati M, Han L, de Sanctis D, Rampoldi L, Jovine L (2016). "A structured interdomain linker directs self-polymerization of human uromodulin". Proc. Natl. Acad. Sci. U.S.A. 113 (6): 1552–1557. doi:10.1073/pnas.1519803113. PMID 26811476.  PDB: 4WRN, 5BUP
  10. ^ Saito T, Bokhove M, Croci R, Zamora-Caballero S, Han L, Letarte M, de Sanctis D, Jovine L (2017). "Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1". Cell Reports. 19 (9): 1917–1928. doi:10.1016/j.celrep.2017.05.011. PMID 28564608.  PDB: 5HZV
  11. ^ Callebaut I, Mornon JP, Monget P. "Isolated ZP-N domains constitute the N-terminal extensions of Zona Pellucida proteins". Bioinformatics. 23: 1871–1874. doi:10.1093/bioinformatics/btm265. PMID 17510169. 
  12. ^ Raj I, Sadat Al Hosseini H, Dioguardi E, Nishimura K, Han L, Villa A, de Sanctis D, Jovine L (2017). "Structural Basis of Egg Coat-Sperm Recognition at Fertilization". Cell. 169 (7): 1315–1326. doi:10.1016/j.cell.2017.05.033. PMID 28622512.  PDB: 5II4, 5II5, 5II6, 5MR2, 5IIC, 5IIA, 5IIB, 5MR3

This article incorporates text from the public domain Pfam and InterPro IPR001507

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Zona pellucida-like domain Provide feedback

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Literature references

  1. Bork P, Sander C; , FEBS Lett 1992;300:237-240.: A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor. PUBMED:1313375 EPMC:1313375

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001507

The zona pellucida (ZP) domain is a protein polymerisation 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 [PUBMED:1313375, PUBMED:12021773, PUBMED:12878193, PUBMED:15079052]. Proteins containing a ZP domain include:

  • 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 [PUBMED:12021773].

The ZP domain contains eight strictly conserved cysteines, which form disulphide bridges. The disulphide 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 [PUBMED:1313375, PUBMED:12878193, PUBMED:15079052].

Domain organisation

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Curation and family details

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Seed source: Swissprot_feature_table
Previous IDs: zona_pellucida;
Type: Family
Author: Sonnhammer ELL, Bateman A
Number in seed: 432
Number in full: 4052
Average length of the domain: 225.40 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 41.80 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 250
Family (HMM) version: 22
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Zona_pellucida domain has been found. There are 21 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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