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31  structures 408  species 0  interactions 9909  sequences 471  architectures

Family: Zona_pellucida (PF00100)

Summary: Zona pellucida-like domain

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Zona pellucida-like domain Edit Wikipedia article

Zona pellucida-like domain

The Zona pellucida-like domain (ZP domain / ZP-like domain / ZP module)[1][2] is a large region, containing around 260 amino acids. It 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 395899. 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. PMC 3069177. 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. PMC 3695229. 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. PMC 4760807. 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. PMC 5464963. PMID 28564608. PDB: 5HZV
  11. ^ Callebaut I, Mornon JP, Monget P (2007). "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. PMC 5480393. 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

No Pfam abstract.

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

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan E-set (CL0159), which has the following description:

This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.

The clan contains the following 238 members:

A2M A2M_BRD A2M_recep AA9 Adeno_GP19K AlcCBM31 Alpha-amylase_N Alpha_adaptinC2 Alpha_E2_glycop Anth_Ig Arch_flagellin aRib Arylsulfotran_N ASF1_hist_chap ATG19 BACON BACON_2 BatD BIg21 Big_1 Big_10 Big_11 Big_12 Big_13 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_3_5 Big_4 Big_5 Big_6 Big_7 Big_8 Big_9 Bile_Hydr_Trans BiPBP_C bMG1 bMG10 bMG3 bMG5 bMG6 BslA BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_4 Cadherin_5 Cadherin_pro CagX Calx-beta Candida_ALS_N CARDB CBM39 CBM_X2 CD45 CelD_N Ceramidse_alk_C CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N ChiW_Ig_like Chlam_OMP6 CHU_C Coatamer_beta_C COP-gamma_platf CopC CshA_repeat Cyc-maltodext_N Cytomega_US3 DsbC DUF11 DUF1410 DUF1425 DUF1929 DUF2271 DUF3244 DUF3327 DUF3416 DUF3458 DUF3501 DUF3823_C DUF3859 DUF4165 DUF4179 DUF4426 DUF4469 DUF4625 DUF4879 DUF4959 DUF4981 DUF4982 DUF4998 DUF5001 DUF5008 DUF5011 DUF5065 DUF5115 DUF525 DUF5643 DUF6383 DUF916 EB_dh ECD EpoR_lig-bind ERAP1_C EstA_Ig_like Expansin_C Filamin FixG_C Flavi_glycop_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 fn3_6 FN3_7 Fn3_assoc fn3_PAP GBS_Bsp-like Glucodextran_B Glyco_hydro2_C5 Glyco_hydro_2 Gmad2 GMP_PDE_delta GPI-anchored Hanta_G1 He_PIG HECW_N HemeBinding_Shp Hemocyanin_C Herpes_BLLF1 HYR IFNGR1 Ig_GlcNase Ig_mannosidase IL12p40_C Il13Ra_Ig IL17R_fnIII_D1 IL17R_fnIII_D2 IL2RB_N1 IL3Ra_N IL4Ra_N IL6Ra-bind Inhibitor_I42 Inhibitor_I71 InlK_D3 Integrin_alpha2 Interfer-bind Invasin_D3 IRK_C IrmA Iron_transport LEA_2 Lep_receptor_Ig LIFR_N Lipase_bact_N LPMO_10 LRR_adjacent LTD Mannosidase_ig MetallophosC MG1 MG2 MG3 MG4 Mo-co_dimer N_BRCA1_IG Na_K-ATPase NEAT Neocarzinostat Neurexophilin NPCBM_assoc PapD_C PBP-Tp47_c Peptidase_C25_C Phlebo_G2_C PhoD_N PKD PKD_2 PKD_3 PKD_4 PKD_5 PKD_6 Por_Secre_tail Pox_vIL-18BP Psg1 PTP_tm Pur_ac_phosph_N Qn_am_d_aII Qn_am_d_aIII RabGGT_insert Reeler REJ RET_CLD1 RET_CLD3 RET_CLD4 RGI_lyase RHD_dimer Rho_GDI Rib RibLong SCAB-Ig SKICH SLAM SoxZ SprB SusE SVA SWM_repeat T2SS-T3SS_pil_N Tafi-CsgC TarS_C1 TcA_RBD TcfC TIG TIG_2 TIG_plexin TIG_SUH Tissue_fac Top6b_C Transglut_C Transglut_N TRAP_beta TraQ_transposon UL16 Velvet WIF Wzt_C Y_Y_Y YBD ZirS_C Zona_pellucida


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Curation and family details

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Curation View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: zona_pellucida;
Type: Family
Sequence Ontology: SO:0100021
Author: Sonnhammer ELL , Bateman A
Number in seed: 358
Number in full: 9909
Average length of the domain: 229.50 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 38.98 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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 20.8 20.9
Model length: 254
Family (HMM) version: 25
Download: download the raw HMM for this family

Species distribution

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Colour assignments

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 31 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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