ZP2_HUMAN
ID ZP2_HUMAN Reviewed; 745 AA.
AC Q05996; B2R7J2; Q4VAN9; Q4VAP0; Q4VAP1;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Zona pellucida sperm-binding protein 2;
DE AltName: Full=Zona pellucida glycoprotein 2;
DE Short=Zp-2;
DE AltName: Full=Zona pellucida protein A;
DE Contains:
DE RecName: Full=Processed zona pellucida sperm-binding protein 2;
DE Flags: Precursor;
GN Name=ZP2; Synonyms=ZPA;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=8385033; DOI=10.1006/dbio.1993.1087;
RA Liang L.-F., Dean J.;
RT "Conservation of mammalian secondary sperm receptor genes enables the
RT promoter of the human gene to function in mouse oocytes.";
RL Dev. Biol. 156:399-408(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
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] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-36.
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).
RN [6]
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 [7]
RP INVOLVEMENT IN OOMD6, SUBCELLULAR LOCATION, FUNCTION, AND TISSUE
RP 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
CC (PubMed:29895852). The zona pellucida is composed of 3 to 4
CC glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP2 may act as a secondary sperm
CC receptor (PubMed:29895852). {ECO:0000269|PubMed:29895852}.
CC -!- SUBUNIT: Can form homopolymers that assemble into long fibers (in
CC vitro). 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 -!- INTERACTION:
CC Q05996; P10323: ACR; NbExp=4; IntAct=EBI-1755919, EBI-21280149;
CC Q05996; P45880-3: VDAC2; NbExp=2; IntAct=EBI-1755919, EBI-11614013;
CC Q05996; Q05996: ZP2; NbExp=6; IntAct=EBI-1755919, EBI-1755919;
CC -!- SUBCELLULAR LOCATION: [Processed zona pellucida sperm-binding protein
CC 2]: Zona pellucida {ECO:0000269|PubMed:29895852}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P20239};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P20239}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q05996-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q05996-2; Sequence=VSP_054508;
CC -!- TISSUE SPECIFICITY: Expressed in occytes(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. {ECO:0000250|UniProtKB:P20239}.
CC -!- PTM: Proteolytically cleaved before the transmembrane segment to yield
CC the secreted ectodomain incorporated in the zona pellucida.
CC {ECO:0000250|UniProtKB:P20239}.
CC -!- PTM: Proteolytically cleaved in the N-terminal part by the
CC metalloendopeptidase ASTL exocytosed from cortical granules after
CC fertilization, yielding a N-terminal peptide of about 30 kDa which
CC remains covalently attached to the C-terminal peptide via disulfide
CC bond(s). This cleavage may play an important role in the post-
CC fertilization block to polyspermy. Additional proteolytically cleavage
CC of the N-terminal peptide of 30 kDa occurs in one-cell and two-cell
CC embryos. {ECO:0000250|UniProtKB:P20239}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P20239}.
CC -!- PTM: O-glycosylated; contains sulfate-substituted glycans.
CC {ECO:0000250|UniProtKB:P20239}.
CC -!- DISEASE: Oocyte maturation defect 6 (OOMD6) [MIM:618353]: An autosomal
CC recessive infertility disorder characterized by oocyte fertilization
CC failure, due to defective sperm-binding to an abnormally thin zona
CC pellucida in patient oocytes. {ECO:0000269|PubMed:29895852}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ZP domain family. ZPA subfamily.
CC {ECO:0000305}.
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DR EMBL; M90366; AAA61335.1; -; mRNA.
DR EMBL; AK313003; BAG35839.1; -; mRNA.
DR EMBL; AF001550; AAB67599.1; -; Genomic_DNA.
DR EMBL; CH471228; EAW66859.1; -; Genomic_DNA.
DR EMBL; BC096304; AAH96304.1; -; mRNA.
DR EMBL; BC096305; AAH96305.1; -; mRNA.
DR EMBL; BC096306; AAH96306.1; -; mRNA.
DR EMBL; BC096307; AAH96307.1; -; mRNA.
DR CCDS; CCDS10596.1; -. [Q05996-1]
DR CCDS; CCDS73843.1; -. [Q05996-2]
DR PIR; A48833; A48833.
DR RefSeq; NP_001277033.1; NM_001290104.1.
DR RefSeq; NP_003451.1; NM_003460.2. [Q05996-1]
DR AlphaFoldDB; Q05996; -.
DR SMR; Q05996; -.
DR BioGRID; 113564; 18.
DR IntAct; Q05996; 11.
DR MINT; Q05996; -.
DR STRING; 9606.ENSP00000460971; -.
DR GlyGen; Q05996; 3 sites.
DR iPTMnet; Q05996; -.
DR PhosphoSitePlus; Q05996; -.
DR BioMuta; ZP2; -.
DR DMDM; 466206; -.
DR MassIVE; Q05996; -.
DR MaxQB; Q05996; -.
DR PaxDb; Q05996; -.
DR PeptideAtlas; Q05996; -.
DR PRIDE; Q05996; -.
DR ProteomicsDB; 58364; -. [Q05996-1]
DR ProteomicsDB; 62288; -.
DR Antibodypedia; 2312; 131 antibodies from 24 providers.
DR DNASU; 7783; -.
DR Ensembl; ENST00000574002.1; ENSP00000460971.1; ENSG00000103310.11. [Q05996-1]
DR Ensembl; ENST00000574091.6; ENSP00000458991.2; ENSG00000103310.11. [Q05996-1]
DR Ensembl; ENST00000638300.1; ENSP00000492703.1; ENSG00000284588.3. [Q05996-1]
DR Ensembl; ENST00000640487.3; ENSP00000491583.3; ENSG00000284588.3. [Q05996-2]
DR GeneID; 7783; -.
DR KEGG; hsa:7783; -.
DR MANE-Select; ENST00000574091.6; ENSP00000458991.2; NM_001376232.1; NP_001363161.1.
DR UCSC; uc002dii.3; human. [Q05996-1]
DR CTD; 7783; -.
DR DisGeNET; 7783; -.
DR GeneCards; ZP2; -.
DR HGNC; HGNC:13188; ZP2.
DR HPA; ENSG00000103310; Tissue enriched (brain).
DR MalaCards; ZP2; -.
DR MIM; 182888; gene.
DR MIM; 618353; phenotype.
DR neXtProt; NX_Q05996; -.
DR OpenTargets; ENSG00000103310; -.
DR Orphanet; 404466; Female infertility due to zona pellucida defect.
DR PharmGKB; PA37756; -.
DR VEuPathDB; HostDB:ENSG00000103310; -.
DR eggNOG; ENOG502QPI2; Eukaryota.
DR GeneTree; ENSGT00940000160133; -.
DR HOGENOM; CLU_024386_0_0_1; -.
DR InParanoid; Q05996; -.
DR OMA; CHYSRDD; -.
DR OrthoDB; 586615at2759; -.
DR PhylomeDB; Q05996; -.
DR TreeFam; TF332794; -.
DR PathwayCommons; Q05996; -.
DR Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR SignaLink; Q05996; -.
DR BioGRID-ORCS; 7783; 14 hits in 1063 CRISPR screens.
DR GeneWiki; ZP2; -.
DR GenomeRNAi; 7783; -.
DR Pharos; Q05996; Tbio.
DR PRO; PR:Q05996; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q05996; protein.
DR Bgee; ENSG00000103310; Expressed in cerebellar cortex and 48 other tissues.
DR Genevisible; Q05996; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:UniProtKB.
DR GO; GO:0035805; C:egg coat; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS: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:0005771; C:multivesicular body; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032190; F:acrosin binding; IPI:UniProtKB.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035804; F:structural constituent of egg coat; IMP:UniProtKB.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; ISS:UniProtKB.
DR GO; GO:0060468; P:prevention of polyspermy; ISS:UniProtKB.
DR Gene3D; 2.60.40.4100; -; 1.
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; SM00241; ZP; 1.
DR PROSITE; PS00682; ZP_1; 1.
DR PROSITE; PS51034; ZP_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues;
KW Disulfide bond; Extracellular matrix; Fertilization; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..38
FT CHAIN 39..640
FT /note="Zona pellucida sperm-binding protein 2"
FT /id="PRO_0000041689"
FT CHAIN 39..?
FT /note="Processed zona pellucida sperm-binding protein 2"
FT /id="PRO_0000304559"
FT PROPEP 641..745
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT /id="PRO_0000041690"
FT TOPO_DOM 39..716
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 717..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 737..745
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 371..637
FT /note="ZP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00375"
FT REGION 469..491
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT REGION 673..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..708
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 172..173
FT /note="Cleavage; by ASTL"
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT SITE 640..641
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 462
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT DISULFID 55..138
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 88..106
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 372..465
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 403..424
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 545..615
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 566..634
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT DISULFID 620..630
FT /evidence="ECO:0000250|UniProtKB:P20239"
FT VAR_SEQ 460..468
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054508"
FT VARIANT 36
FT /note="G -> V (in dbSNP:rs2075520)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_024705"
SQ SEQUENCE 745 AA; 82357 MW; 2614DA79738F2CDD CRC64;
MACRQRGGSW SPSGWFNAGW STYRSISLFF ALVTSGNSID VSQLVNPAFP GTVTCDEREI
TVEFPSSPGT KKWHASVVDP LGLDMPNCTY ILDPEKLTLR ATYDNCTRRV HGGHQMTIRV
MNNSAALRHG AVMYQFFCPA MQVEETQGLS ASTICQKDFM SFSLPRVFSG LADDSKGTKV
QMGWSIEVGD GARAKTLTLP EAMKEGFSLL IDNHRMTFHV PFNATGVTHY VQGNSHLYMV
SLKLTFISPG QKVIFSSQAI CAPDPVTCNA THMTLTIPEF PGKLKSVSFE NQNIDVSQLH
DNGIDLEATN GMKLHFSKTL LKTKLSEKCL LHQFYLASLK LTFLLRPETV SMVIYPECLC
ESPVSIVTGE LCTQDGFMDV EVYSYQTQPA LDLGTLRVGN SSCQPVFEAQ SQGLVRFHIP
LNGCGTRYKF EDDKVVYENE IHALWTDFPP SKISRDSEFR MTVKCSYSRN DMLLNINVES
LTPPVASVKL GPFTLILQSY PDNSYQQPYG ENEYPLVRFL RQPIYMEVRV LNRDDPNIKL
VLDDCWATST MDPDSFPQWN VVVDGCAYDL DNYQTTFHPV GSSVTHPDHY QRFDMKAFAF
VSEAHVLSSL VYFHCSALIC NRLSPDSPLC SVTCPVSSRH RRATGATEAE KMTVSLPGPI
LLLSDDSSFR GVGSSDLKAS GSSGEKSRSE TGEEVGSRGA MDTKGHKTAG DVGSKAVAAV
AAFAGVVATL GFIYYLYEKR TVSNH
