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   24-JAN-2024, entry version 196.
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   GlyCosmos; O00254; 3 sites, No reported glycans.
DR   GlyGen; O00254; 3 sites.
DR   iPTMnet; O00254; -.
DR   PhosphoSitePlus; O00254; -.
DR   BioMuta; F2RL2; -.
DR   PaxDb; 9606-ENSP00000296641; -.
DR   PeptideAtlas; O00254; -.
DR   ProteomicsDB; 47807; -. [O00254-1]
DR   ProteomicsDB; 4833; -.
DR   Antibodypedia; 12465; 209 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   AGR; HGNC:3539; -.
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; DWAMYIK; -.
DR   OrthoDB; 4256130at2759; -.
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 1137 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 97 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0048018; F:receptor ligand activity; IEA:Ensembl.
DR   GO; GO:0015057; F:thrombin-activated receptor activity; TAS:ProtInc.
DR   GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR   GO; GO:1990806; P:ligand-gated ion channel signaling pathway; IEA:Ensembl.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
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   CDD; cd15371; 7tmA_PAR3; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
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   PANTHER; PTHR24232; G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR24232:SF0; PROTEINASE-ACTIVATED RECEPTOR 3; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01428; PROTEASEAR.
DR   PRINTS; PR01429; PROTEASEAR3.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; O00254; HS.
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
//