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 13-FEB-2019, entry version 170. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Timmons C., Tram T., Coughlin S.R.; RT "Protease-activated receptor 3 is a second thrombin receptor in RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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. RT Identification within a PAR gene cluster and characterization in RT vascular endothelial 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., RA Coughlin S.R.; RT "Protease-activated receptors 1 and 4 mediate activation of human RT platelets 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 RT Pins homologues LGN and AGS3."; RL Biochem. Biophys. Res. Commun. 341:1001-1006(2006). CC -!- FUNCTION: Receptor for activated thrombin coupled to G proteins CC that stimulate phosphoinositide hydrolysis. CC {ECO:0000269|PubMed:10079109}. CC -!- SUBUNIT: Interacts with INSC/inscuteable and probably GPSM2. CC {ECO:0000269|PubMed:16458856}. CC -!- INTERACTION: CC 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 CC the bone marrow, lower in mature megakaryocytes, in platelets and CC in a 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 CC functions 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; Positions=374; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/f2rl2/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.42502; -. DR ProteinModelPortal; O00254; -. DR DIP; DIP-44337N; -. DR IntAct; O00254; 10. DR MINT; O00254; -. DR STRING; 9606.ENSP00000296641; -. DR ChEMBL; CHEMBL5477; -. DR iPTMnet; O00254; -. DR PhosphoSitePlus; O00254; -. DR BioMuta; F2RL2; -. DR PaxDb; O00254; -. DR PRIDE; O00254; -. DR ProteomicsDB; 47807; -. DR DNASU; 2151; -. DR Ensembl; ENST00000296641; ENSP00000296641; ENSG00000164220. [O00254-1] DR Ensembl; ENST00000504899; ENSP00000426703; ENSG00000164220. [O00254-2] DR GeneID; 2151; -. DR KEGG; hsa:2151; -. DR UCSC; uc003kem.4; human. [O00254-1] DR CTD; 2151; -. DR DisGeNET; 2151; -. DR EuPathDB; HostDB:ENSG00000164220.6; -. DR GeneCards; F2RL2; -. DR HGNC; HGNC:3539; F2RL2. DR MIM; 601919; gene. DR neXtProt; NX_O00254; -. DR OpenTargets; ENSG00000164220; -. DR PharmGKB; PA27948; -. DR eggNOG; ENOG410IJUX; Eukaryota. DR eggNOG; ENOG4111GWA; LUCA. DR GeneTree; ENSGT00940000159776; -. DR HOGENOM; HOG000116291; -. DR HOVERGEN; HBG105658; -. DR InParanoid; O00254; -. DR KO; K04235; -. DR OMA; SAIEGWT; -. DR OrthoDB; 892946at2759; -. DR PhylomeDB; O00254; -. DR TreeFam; TF330775; -. 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 SIGNOR; O00254; -. DR GeneWiki; F2RL2; -. DR GenomeRNAi; 2151; -. DR PMAP-CutDB; O00254; -. DR PRO; PR:O00254; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000164220; Expressed in 98 organ(s), highest expression level in pigmented layer of retina. 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:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. 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; KW Complete proteome; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Hemostasis; Membrane; Polymorphism; Receptor; KW Reference proteome; Signal; Transducer; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 21 {ECO:0000255}. FT PROPEP 22 38 Removed for receptor activation. FT {ECO:0000250}. FT /FTId=PRO_0000012756. FT CHAIN 39 374 Proteinase-activated receptor 3. FT /FTId=PRO_0000012757. FT TOPO_DOM 39 94 Extracellular. {ECO:0000255}. FT TRANSMEM 95 120 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 121 128 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 129 148 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 149 167 Extracellular. {ECO:0000255}. FT TRANSMEM 168 189 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 190 206 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 207 230 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 231 260 Extracellular. {ECO:0000255}. FT TRANSMEM 261 280 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 281 297 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 298 322 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 323 336 Extracellular. {ECO:0000255}. FT TRANSMEM 337 361 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 362 374 Cytoplasmic. {ECO:0000255}. FT SITE 38 39 Cleavage; by thrombin. {ECO:0000250}. FT CARBOHYD 25 25 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 82 82 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 331 331 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 166 245 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VAR_SEQ 1 22 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045116. FT VARIANT 15 15 L -> S (in dbSNP:rs2069649). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_012849. FT VARIANT 177 177 M -> V (in dbSNP:rs2069700). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_012850. FT VARIANT 250 250 N -> D (in dbSNP:rs2069683). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_012851. FT MUTAGEN 39 39 T->P: No proteolytic cleavage by FT thrombin. {ECO:0000269|PubMed:9087410}. FT MUTAGEN 40 40 F->A: Altered signal upon thrombin FT cleavage. {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 //