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-MAY-2023, entry version 164.
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   GlyCosmos; Q12836; 7 sites, No reported glycans.
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   ProteomicsDB; 58977; -.
DR   Antibodypedia; 2377; 169 antibodies from 25 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   AGR; HGNC:15770; -.
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; LNCPDQT; -.
DR   OrthoDB; 5354962at2759; -.
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; 14 hits in 1138 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: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; 4.10.110.10; Spasmolytic Protein, domain 1; 1.
DR   Gene3D; 2.60.40.4100; Zona pellucida, ZP-C domain; 1.
DR   Gene3D; 2.60.40.3210; Zona pellucida, ZP-N domain; 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   PANTHER; PTHR23343; ZONA PELLUCIDA SPERM-BINDING PROTEIN; 1.
DR   PANTHER; PTHR23343:SF31; ZONA PELLUCIDA SPERM-BINDING PROTEIN 4; 1.
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; Trefoil; 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
//