PAR3_HUMAN
ID PAR3_HUMAN Reviewed; 374 AA.
AC O00254; B2R754; B4DQ13; Q52M68; Q7Z3W3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Proteinase-activated receptor 3;
DE Short=PAR-3;
DE AltName: Full=Coagulation factor II receptor-like 2;
DE AltName: Full=Thrombin receptor-like 2;
DE Flags: Precursor;
GN Name=F2RL2; Synonyms=PAR3;
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), AND MUTAGENESIS OF THR-39 AND
RP PHE-40.
RX PubMed=9087410; DOI=10.1038/386502a0;
RA Ishihara H., Connolly A.J., Zeng D., Kahn M.L., Zheng Y.-W., Timmons C.,
RA Tram T., Coughlin S.R.;
RT "Protease-activated receptor 3 is a second thrombin receptor in humans.";
RL Nature 386:502-506(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thymus;
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 MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-15; VAL-177 AND
RP ASP-250.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=9614115; DOI=10.1074/jbc.273.24.15061;
RA Schmidt V.A., Nierman W.C., Maglott D.R., Cupit L.D., Moskowitz K.A.,
RA Wainer J.A., Bahou W.F.;
RT "The human proteinase-activated receptor-3 (PAR-3) gene. Identification
RT within a PAR gene cluster and characterization in vascular endothelial
RT cells and platelets.";
RL J. Biol. Chem. 273:15061-15068(1998).
RN [9]
RP FUNCTION.
RX PubMed=10079109; DOI=10.1172/jci6042;
RA Kahn M.L., Nakanishi-Matsui M., Shapiro M.J., Ishihara H., Coughlin S.R.;
RT "Protease-activated receptors 1 and 4 mediate activation of human platelets
RT by thrombin.";
RL J. Clin. Invest. 103:879-887(1999).
RN [10]
RP INTERACTION WITH INSC.
RX PubMed=16458856; DOI=10.1016/j.bbrc.2006.01.050;
RA Izaki T., Kamakura S., Kohjima M., Sumimoto H.;
RT "Two forms of human Inscuteable-related protein that links Par3 to the Pins
RT homologues LGN and AGS3.";
RL Biochem. Biophys. Res. Commun. 341:1001-1006(2006).
CC -!- FUNCTION: Receptor for activated thrombin coupled to G proteins that
CC stimulate phosphoinositide hydrolysis. {ECO:0000269|PubMed:10079109}.
CC -!- SUBUNIT: Interacts with INSC/inscuteable and probably GPSM2.
CC {ECO:0000269|PubMed:16458856}.
CC -!- INTERACTION:
CC O00254; P16333: NCK1; NbExp=2; IntAct=EBI-1751853, EBI-389883;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00254-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00254-2; Sequence=VSP_045116;
CC -!- TISSUE SPECIFICITY: Highest expression in the megakaryocytes of the
CC bone marrow, lower in mature megakaryocytes, in platelets and in a
CC variety of other tissues such as heart and gut.
CC {ECO:0000269|PubMed:9614115}.
CC -!- PTM: A proteolytic cleavage generates a new N-terminus that functions
CC as a tethered ligand.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97628.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/f2rl2/";
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DR EMBL; U92971; AAC51218.1; -; mRNA.
DR EMBL; AK312848; BAG35701.1; -; mRNA.
DR EMBL; AK298585; BAG60775.1; -; mRNA.
DR EMBL; BX537386; CAD97628.1; ALT_FRAME; mRNA.
DR EMBL; AF374726; AAK51564.1; -; Genomic_DNA.
DR EMBL; AC026725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471084; EAW95778.1; -; Genomic_DNA.
DR EMBL; BC093648; AAH93648.1; -; mRNA.
DR EMBL; BC093650; AAH93650.1; -; mRNA.
DR CCDS; CCDS4031.1; -. [O00254-1]
DR CCDS; CCDS58959.1; -. [O00254-2]
DR RefSeq; NP_001243495.1; NM_001256566.1. [O00254-2]
DR RefSeq; NP_004092.1; NM_004101.3. [O00254-1]
DR AlphaFoldDB; O00254; -.
DR SMR; O00254; -.
DR BioGRID; 108450; 6.
DR DIP; DIP-44337N; -.
DR IntAct; O00254; 10.
DR MINT; O00254; -.
DR STRING; 9606.ENSP00000296641; -.
DR ChEMBL; CHEMBL5477; -.
DR GlyGen; O00254; 3 sites.
DR iPTMnet; O00254; -.
DR PhosphoSitePlus; O00254; -.
DR BioMuta; F2RL2; -.
DR PaxDb; O00254; -.
DR PeptideAtlas; O00254; -.
DR PRIDE; O00254; -.
DR ProteomicsDB; 47807; -. [O00254-1]
DR ProteomicsDB; 4833; -.
DR Antibodypedia; 12465; 185 antibodies from 28 providers.
DR DNASU; 2151; -.
DR Ensembl; ENST00000296641.5; ENSP00000296641.3; ENSG00000164220.7. [O00254-1]
DR Ensembl; ENST00000504899.1; ENSP00000426703.1; ENSG00000164220.7. [O00254-2]
DR GeneID; 2151; -.
DR KEGG; hsa:2151; -.
DR MANE-Select; ENST00000296641.5; ENSP00000296641.3; NM_004101.4; NP_004092.1.
DR UCSC; uc003kem.4; human. [O00254-1]
DR CTD; 2151; -.
DR DisGeNET; 2151; -.
DR GeneCards; F2RL2; -.
DR HGNC; HGNC:3539; F2RL2.
DR HPA; ENSG00000164220; Tissue enhanced (gallbladder).
DR MIM; 601919; gene.
DR neXtProt; NX_O00254; -.
DR OpenTargets; ENSG00000164220; -.
DR PharmGKB; PA27948; -.
DR VEuPathDB; HostDB:ENSG00000164220; -.
DR eggNOG; ENOG502QWI1; Eukaryota.
DR GeneTree; ENSGT01050000244840; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; O00254; -.
DR OMA; HHINYYY; -.
DR OrthoDB; 892946at2759; -.
DR PhylomeDB; O00254; -.
DR TreeFam; TF330775; -.
DR PathwayCommons; O00254; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR SignaLink; O00254; -.
DR SIGNOR; O00254; -.
DR BioGRID-ORCS; 2151; 9 hits in 1061 CRISPR screens.
DR GeneWiki; F2RL2; -.
DR GenomeRNAi; 2151; -.
DR Pharos; O00254; Tbio.
DR PRO; PR:O00254; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O00254; protein.
DR Bgee; ENSG00000164220; Expressed in stromal cell of endometrium and 96 other tissues.
DR Genevisible; O00254; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc.
DR GO; GO:0015057; F:thrombin-activated receptor activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IBA:GO_Central.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0009611; P:response to wounding; TAS:ProtInc.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003943; Prot_act_rcpt_3.
DR InterPro; IPR003912; Protea_act_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01428; PROTEASEAR.
DR PRINTS; PR01429; PROTEASEAR3.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood coagulation; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Hemostasis; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..38
FT /note="Removed for receptor activation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000012756"
FT CHAIN 39..374
FT /note="Proteinase-activated receptor 3"
FT /id="PRO_0000012757"
FT TOPO_DOM 39..94
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..120
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..148
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..189
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..230
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..280
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..322
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..361
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 38..39
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 166..245
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1..22
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045116"
FT VARIANT 15
FT /note="L -> S (in dbSNP:rs2069649)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_012849"
FT VARIANT 177
FT /note="M -> V (in dbSNP:rs2069700)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_012850"
FT VARIANT 250
FT /note="N -> D (in dbSNP:rs2069683)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_012851"
FT MUTAGEN 39
FT /note="T->P: No proteolytic cleavage by thrombin."
FT /evidence="ECO:0000269|PubMed:9087410"
FT MUTAGEN 40
FT /note="F->A: Altered signal upon thrombin cleavage."
FT /evidence="ECO:0000269|PubMed:9087410"
SQ SEQUENCE 374 AA; 42508 MW; C45C15A695DD1ABB CRC64;
MKALIFAAAG LLLLLPTFCQ SGMENDTNNL AKPTLPIKTF RGAPPNSFEE FPFSALEGWT
GATITVKIKC PEESASHLHV KNATMGYLTS SLSTKLIPAI YLLVFVVGVP ANAVTLWMLF
FRTRSICTTV FYTNLAIADF LFCVTLPFKI AYHLNGNNWV FGEVLCRATT VIFYGNMYCS
ILLLACISIN RYLAIVHPFT YRGLPKHTYA LVTCGLVWAT VFLYMLPFFI LKQEYYLVQP
DITTCHDVHN TCESSSPFQL YYFISLAFFG FLIPFVLIIY CYAAIIRTLN AYDHRWLWYV
KASLLILVIF TICFAPSNII LIIHHANYYY NNTDGLYFIY LIALCLGSLN SCLDPFLYFL
MSKTRNHSTA YLTK
