ZP4_HUMAN
ID ZP4_HUMAN Reviewed; 540 AA.
AC Q12836; B2RAE1;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Zona pellucida sperm-binding protein 4;
DE AltName: Full=Zona pellucida glycoprotein 4;
DE Short=Zp-4;
DE AltName: Full=Zona pellucida protein B;
DE Contains:
DE RecName: Full=Processed zona pellucida sperm-binding protein 4;
DE Flags: Precursor;
GN Name=ZP4; Synonyms=ZPB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Ovary;
RX PubMed=7841460; DOI=10.3109/10425179409010186;
RA Harris J.D., Hibler D.W., Fontenot G.K., Hsu K.T., Yurewicz E.C.,
RA Sacco A.G.;
RT "Cloning and characterization of zona pellucida genes and cDNAs from a
RT variety of mammalian species: the ZPA, ZPB and ZPC gene families.";
RL DNA Seq. 4:361-393(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Component of the zona pellucida, an extracellular matrix
CC surrounding oocytes which mediates sperm binding, induction of the
CC acrosome reaction and prevents post-fertilization polyspermy. The zona
CC pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4.
CC ZP4 may act as a sperm receptor.
CC -!- INTERACTION:
CC Q12836; P10323: ACR; NbExp=2; IntAct=EBI-11783805, EBI-21280149;
CC Q12836; P21266: GSTM3; NbExp=2; IntAct=EBI-11783805, EBI-350350;
CC Q12836; Q12836: ZP4; NbExp=6; IntAct=EBI-11783805, EBI-11783805;
CC -!- SUBCELLULAR LOCATION: [Processed zona pellucida sperm-binding protein
CC 4]: Zona pellucida {ECO:0000250|UniProtKB:Q00193}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q00193};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in oocytes.
CC -!- DOMAIN: The ZP domain is involved in the polymerization of the ZP
CC proteins to form the zona pellucida.
CC -!- PTM: Proteolytically cleaved before the transmembrane segment to yield
CC the secreted ectodomain incorporated in the zona pellucida.
CC -!- SIMILARITY: Belongs to the ZP domain family. ZPB subfamily.
CC {ECO:0000305}.
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DR EMBL; U05781; AAA74391.1; -; Genomic_DNA.
DR EMBL; AK314151; BAG36838.1; -; mRNA.
DR EMBL; AL359924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW70072.1; -; Genomic_DNA.
DR EMBL; BC069521; AAH69521.1; -; mRNA.
DR CCDS; CCDS1615.1; -.
DR PIR; S70403; S70403.
DR RefSeq; NP_067009.1; NM_021186.4.
DR AlphaFoldDB; Q12836; -.
DR SMR; Q12836; -.
DR IntAct; Q12836; 12.
DR MINT; Q12836; -.
DR STRING; 9606.ENSP00000482304; -.
DR GlyGen; Q12836; 7 sites.
DR iPTMnet; Q12836; -.
DR PhosphoSitePlus; Q12836; -.
DR BioMuta; ZP4; -.
DR DMDM; 46397080; -.
DR MassIVE; Q12836; -.
DR PaxDb; Q12836; -.
DR PeptideAtlas; Q12836; -.
DR PRIDE; Q12836; -.
DR Antibodypedia; 2377; 166 antibodies from 24 providers.
DR DNASU; 57829; -.
DR Ensembl; ENST00000366570.5; ENSP00000355529.4; ENSG00000116996.10.
DR Ensembl; ENST00000611898.4; ENSP00000482304.1; ENSG00000116996.10.
DR GeneID; 57829; -.
DR KEGG; hsa:57829; -.
DR MANE-Select; ENST00000366570.5; ENSP00000355529.4; NM_021186.5; NP_067009.1.
DR UCSC; uc001hym.3; human.
DR CTD; 57829; -.
DR DisGeNET; 57829; -.
DR GeneCards; ZP4; -.
DR HGNC; HGNC:15770; ZP4.
DR HPA; ENSG00000116996; Not detected.
DR MIM; 613514; gene.
DR neXtProt; NX_Q12836; -.
DR OpenTargets; ENSG00000116996; -.
DR PharmGKB; PA38036; -.
DR VEuPathDB; HostDB:ENSG00000116996; -.
DR eggNOG; ENOG502QU54; Eukaryota.
DR GeneTree; ENSGT00940000161324; -.
DR HOGENOM; CLU_034433_0_0_1; -.
DR InParanoid; Q12836; -.
DR OMA; RTWSHGS; -.
DR OrthoDB; 586615at2759; -.
DR PhylomeDB; Q12836; -.
DR TreeFam; TF332794; -.
DR PathwayCommons; Q12836; -.
DR Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR SignaLink; Q12836; -.
DR BioGRID-ORCS; 57829; 12 hits in 1060 CRISPR screens.
DR GeneWiki; ZP4; -.
DR GenomeRNAi; 57829; -.
DR Pharos; Q12836; Tbio.
DR PRO; PR:Q12836; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q12836; protein.
DR Bgee; ENSG00000116996; Expressed in oocyte and 13 other tissues.
DR Genevisible; Q12836; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0035805; C:egg coat; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032190; F:acrosin binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035804; F:structural constituent of egg coat; ISS:UniProtKB.
DR GO; GO:0060478; P:acrosomal vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IBA:GO_Central.
DR GO; GO:2000360; P:negative regulation of binding of sperm to zona pellucida; IDA:UniProtKB.
DR GO; GO:2000344; P:positive regulation of acrosome reaction; IDA:UniProtKB.
DR GO; GO:0002922; P:positive regulation of humoral immune response; IDA:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB.
DR GO; GO:0060468; P:prevention of polyspermy; IBA:GO_Central.
DR CDD; cd00111; Trefoil; 1.
DR Gene3D; 2.60.40.4100; -; 1.
DR Gene3D; 4.10.110.10; -; 1.
DR InterPro; IPR017957; P_trefoil_CS.
DR InterPro; IPR000519; P_trefoil_dom.
DR InterPro; IPR044913; P_trefoil_dom_sf.
DR InterPro; IPR042235; ZP-C.
DR InterPro; IPR001507; ZP_dom.
DR InterPro; IPR017977; ZP_dom_CS.
DR Pfam; PF00088; Trefoil; 1.
DR Pfam; PF00100; Zona_pellucida; 1.
DR PRINTS; PR00023; ZPELLUCIDA.
DR SMART; SM00018; PD; 1.
DR SMART; SM00241; ZP; 1.
DR SUPFAM; SSF57492; SSF57492; 1.
DR PROSITE; PS00025; P_TREFOIL_1; 1.
DR PROSITE; PS51448; P_TREFOIL_2; 1.
DR PROSITE; PS00682; ZP_1; 1.
DR PROSITE; PS51034; ZP_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW Extracellular matrix; Fertilization; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..462
FT /note="Zona pellucida sperm-binding protein 4"
FT /id="PRO_0000041727"
FT CHAIN 19..?
FT /note="Processed zona pellucida sperm-binding protein 4"
FT /id="PRO_0000304578"
FT PROPEP 463..540
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000041728"
FT TOPO_DOM 19..505
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..540
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 141..183
FT /note="P-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT DOMAIN 188..466
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 474
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 367..442
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT VARIANT 114
FT /note="A -> V (in dbSNP:rs34370253)"
FT /id="VAR_052997"
FT VARIANT 295
FT /note="P -> S (in dbSNP:rs34811980)"
FT /id="VAR_052998"
SQ SEQUENCE 540 AA; 59400 MW; 9DAC310D808E1AC3 CRC64;
MWLLRCVLLC VSLSLAVSGQ HKPEAPDYSS VLHCGPWSFQ FAVNLNQEAT SPPVLIAWDN
QGLLHELQND SDCGTWIRKG PGSSVVLEAT YSSCYVTEWD SHYIMPVGVE GAGAAEHKVV
TERKLLKCPM DLLARDAPDT DWCDSIPARD RLPCAPSPIS RGDCEGLGCC YSSEEVNSCY
YGNTVTLHCT REGHFSIAVS RNVTSPPLLL DSVRLALRND SACNPVMATQ AFVLFQFPFT
SCGTTRQITG DRAVYENELV ATRDVKNGSR GSVTRDSIFR LHVSCSYSVS SNSLPINVQV
FTLPPPFPET QPGPLTLELQ IAKDKNYGSY YGVGDYPVVK LLRDPIYVEV SILHRTDPYL
GLLLQQCWAT PSTDPLSQPQ WPILVKGCPY IGDNYQTQLI PVQKALDLPF PSHHQRFSIF
TFSFVNPTVE KQALRGPVHL HCSVSVCQPA ETPSCVVTCP DLSRRRNFDN SSQNTTASVS
SKGPMILLQA TKDPPEKLRV PVDSKVLWVA GLSGTLILGA LLVSYLAVKK QKSCPDQMCQ
