ZP1_HUMAN
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 03-AUG-2022, entry version 138.
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 OOMD1.
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 maturation defect 1 (OOMD1) [MIM:615774]: An
CC infertility disorder caused by defective oocyte maturation that results
CC in abnormal eggs lacking a zona pellucida. Affected females have normal
CC menstrual cycles and sex hormone levels, no obstruction in the
CC fallopian tubes or abnormalities of the uterus or adnexa.
CC {ECO:0000269|PubMed:24670168}. Note=The disease is caused by variants
CC affecting the gene represented in this 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; 2.
DR IntAct; P60852; 3.
DR STRING; 9606.ENSP00000278853; -.
DR MEROPS; S01.969; -.
DR GlyGen; P60852; 4 sites.
DR iPTMnet; P60852; -.
DR PhosphoSitePlus; P60852; -.
DR BioMuta; ZP1; -.
DR DMDM; 46397079; -.
DR MassIVE; P60852; -.
DR PaxDb; P60852; -.
DR PeptideAtlas; P60852; -.
DR PRIDE; P60852; -.
DR Antibodypedia; 43518; 171 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 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; RHSYDCG; -.
DR OrthoDB; 586615at2759; -.
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; 15 hits in 1065 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 108 other tissues.
DR ExpressionAtlas; P60852; baseline and differential.
DR Genevisible; P60852; 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; 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; -; 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; 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;
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
