ID   ZP1_HUMAN               Reviewed;         638 AA.
AC   P60852;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2004, sequence version 1.
DT   24-JAN-2024, entry version 146.
DE   RecName: Full=Zona pellucida sperm-binding protein 1;
DE   AltName: Full=Zona pellucida glycoprotein 1;
DE            Short=Zp-1;
DE   Contains:
DE     RecName: Full=Processed zona pellucida sperm-binding protein 1;
DE   Flags: Precursor;
GN   Name=ZP1;
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].
RX   PubMed=10542331; DOI=10.1016/s0167-4781(99)00181-5;
RA   Hughes D.C., Barratt C.L.;
RT   "Identification of the true human orthologue of the mouse Zp1 gene:
RT   evidence for greater complexity in the mammalian zona pellucida?";
RL   Biochim. Biophys. Acta 1447:303-306(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3]
RP   INVOLVEMENT IN OZEMA1.
RX   PubMed=24670168; DOI=10.1056/nejmoa1308851;
RA   Huang H.L., Lv C., Zhao Y.C., Li W., He X.M., Li P., Sha A.G., Tian X.,
RA   Papasian C.J., Deng H.W., Lu G.X., Xiao H.M.;
RT   "Mutant ZP1 in familial infertility.";
RL   N. Engl. J. Med. 370:1220-1226(2014).
RN   [4]
RP   INTERACTION WITH ZP3.
RX   PubMed=28886344; DOI=10.1016/j.ajhg.2017.08.001;
RA   Chen T., Bian Y., Liu X., Zhao S., Wu K., Yan L., Li M., Yang Z., Liu H.,
RA   Zhao H., Chen Z.J.;
RT   "A recurrent missense mutation in ZP3 causes empty follicle syndrome and
RT   female infertility.";
RL   Am. J. Hum. Genet. 101:459-465(2017).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=29895852; DOI=10.1038/s41436-018-0064-y;
RA   Dai C., Hu L., Gong F., Tan Y., Cai S., Zhang S., Dai J., Lu C., Chen J.,
RA   Chen Y., Lu G., Du J., Lin G.;
RT   "ZP2 pathogenic variants cause in vitro fertilization failure and female
RT   infertility.";
RL   Genet. Med. 21:431-440(2019).
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       ZP1 ensures the structural integrity of the zona pellucida.
CC   -!- SUBUNIT: Polymers of ZP2 and ZP3 organized into long filaments cross-
CC       linked by ZP1 homodimers (By similarity). Interacts with ZP3
CC       (PubMed:28886344). {ECO:0000250|UniProtKB:P20239,
CC       ECO:0000269|PubMed:28886344}.
CC   -!- SUBCELLULAR LOCATION: [Processed zona pellucida sperm-binding protein
CC       1]: Zona pellucida {ECO:0000269|PubMed:29895852}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P48829};
CC       Single-pass type I membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in oocytes (at protein level).
CC       {ECO:0000269|PubMed:29895852}.
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   -!- PTM: O-glycosylated. {ECO:0000250}.
CC   -!- DISEASE: Oocyte/zygote/embryo maturation arrest 1 (OZEMA1)
CC       [MIM:615774]: An autosomal recessive infertility disorder caused by
CC       defective oocyte maturation that results in abnormal eggs lacking a
CC       zona pellucida. Affected females have normal menstrual cycles and sex
CC       hormone levels, no obstruction in the fallopian tubes or abnormalities
CC       of the uterus or adnexa. {ECO:0000269|PubMed:24670168}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the ZP domain family. ZPB subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AC004126; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS31572.1; -.
DR   RefSeq; NP_997224.2; NM_207341.3.
DR   AlphaFoldDB; P60852; -.
DR   SMR; P60852; -.
DR   BioGRID; 116579; 3.
DR   IntAct; P60852; 3.
DR   STRING; 9606.ENSP00000278853; -.
DR   MEROPS; S01.969; -.
DR   GlyCosmos; P60852; 4 sites, No reported glycans.
DR   GlyGen; P60852; 4 sites.
DR   iPTMnet; P60852; -.
DR   PhosphoSitePlus; P60852; -.
DR   BioMuta; ZP1; -.
DR   DMDM; 46397079; -.
DR   MassIVE; P60852; -.
DR   PaxDb; 9606-ENSP00000278853; -.
DR   PeptideAtlas; P60852; -.
DR   Antibodypedia; 43518; 199 antibodies from 23 providers.
DR   DNASU; 22917; -.
DR   Ensembl; ENST00000278853.10; ENSP00000278853.5; ENSG00000149506.12.
DR   GeneID; 22917; -.
DR   KEGG; hsa:22917; -.
DR   MANE-Select; ENST00000278853.10; ENSP00000278853.5; NM_207341.4; NP_997224.2.
DR   AGR; HGNC:13187; -.
DR   CTD; 22917; -.
DR   DisGeNET; 22917; -.
DR   GeneCards; ZP1; -.
DR   HGNC; HGNC:13187; ZP1.
DR   HPA; ENSG00000149506; Not detected.
DR   MalaCards; ZP1; -.
DR   MIM; 195000; gene.
DR   MIM; 615774; phenotype.
DR   neXtProt; NX_P60852; -.
DR   OpenTargets; ENSG00000149506; -.
DR   Orphanet; 404466; Female infertility due to zona pellucida defect.
DR   PharmGKB; PA37755; -.
DR   VEuPathDB; HostDB:ENSG00000149506; -.
DR   eggNOG; ENOG502RYNN; Eukaryota.
DR   GeneTree; ENSGT00940000161188; -.
DR   HOGENOM; CLU_034433_0_0_1; -.
DR   InParanoid; P60852; -.
DR   OMA; RFEVNNC; -.
DR   OrthoDB; 5354962at2759; -.
DR   PhylomeDB; P60852; -.
DR   TreeFam; TF332794; -.
DR   PathwayCommons; P60852; -.
DR   Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR   SignaLink; P60852; -.
DR   SIGNOR; P60852; -.
DR   BioGRID-ORCS; 22917; 16 hits in 1143 CRISPR screens.
DR   ChiTaRS; ZP1; human.
DR   GenomeRNAi; 22917; -.
DR   Pharos; P60852; Tbio.
DR   PRO; PR:P60852; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P60852; Protein.
DR   Bgee; ENSG00000149506; Expressed in oocyte and 110 other cell types or tissues.
DR   ExpressionAtlas; P60852; baseline and differential.
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; IBA:GO_Central.
DR   GO; GO:0035804; F:structural constituent of egg coat; ISS:UniProtKB.
DR   GO; GO:0007339; P:binding of sperm to zona pellucida; IBA:GO_Central.
DR   GO; GO:0060468; P:prevention of polyspermy; IBA:GO_Central.
DR   CDD; cd00111; Trefoil; 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; IPR048290; ZP_chr.
DR   InterPro; IPR001507; ZP_dom.
DR   InterPro; IPR017977; ZP_dom_CS.
DR   PANTHER; PTHR23343; ZONA PELLUCIDA SPERM-BINDING PROTEIN; 1.
DR   PANTHER; PTHR23343:SF41; ZONA PELLUCIDA SPERM-BINDING PROTEIN 1; 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.
DR   Genevisible; P60852; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW   Extracellular matrix; Fertilization; Glycoprotein; Membrane;
KW   Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..553
FT                   /note="Zona pellucida sperm-binding protein 1"
FT                   /id="PRO_0000041677"
FT   CHAIN           26..?
FT                   /note="Processed zona pellucida sperm-binding protein 1"
FT                   /id="PRO_0000304553"
FT   PROPEP          554..638
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000041678"
FT   TOPO_DOM        26..601
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        602..622
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        623..638
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          234..274
FT                   /note="P-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DOMAIN          279..553
FT                   /note="ZP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT   REGION          165..208
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          549..594
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        76
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        561
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        596
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        236..261
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        245..260
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        255..270
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   DISULFID        457..478
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00779"
FT   VARIANT         158
FT                   /note="T -> I (in dbSNP:rs489172)"
FT                   /id="VAR_052996"
SQ   SEQUENCE   638 AA;  70049 MW;  052107CCFFEDFF21 CRC64;
     MAGGSATTWG YPVALLLLVA TLGLGRWLQP DPGLPGLRHS YDCGIKGMQL LVFPRPGQTL
     RFKVVDEFGN RFDVNNCSIC YHWVTSRPQE PAVFSADYRG CHVLEKDGRF HLRVFMEAVL
     PNGRVDVAQD ATLICPKPDP SRTLDSQLAP PAMFSVSTPQ TLSFLPTSGH TSQGSGHAFP
     SPLDPGHSSV HPTPALPSPG PGPTLATLAQ PHWGTLEHWD VNKRDYIGTH LSQEQCQVAS
     GHLPCIVRRT SKEACQQAGC CYDNTREVPC YYGNTATVQC FRDGYFVLVV SQEMALTHRI
     TLANIHLAYA PTSCSPTQHT EAFVVFYFPL THCGTTMQVA GDQLIYENWL VSGIHIQKGP
     QGSITRDSTF QLHVRCVFNA SDFLPIQASI FPPPSPAPMT QPGPLRLELR IAKDETFSSY
     YGEDDYPIVR LLREPVHVEV RLLQRTDPNL VLLLHQCWGA PSANPFQQPQ WPILSDGCPF
     KGDSYRTQMV ALDGATPFQS HYQRFTVATF ALLDSGSQRA LRGLVYLFCS TSACHTSGLE
     TCSTACSTGT TRQRRSSGHR NDTARPQDIV SSPGPVGFED SYGQEPTLGP TDSNGNSSLR
     PLLWAVLLLP AVALVLGFGV FVGLSQTWAQ KLWESNRQ
//