ID PAR4_HUMAN Reviewed; 385 AA.
AC Q96RI0; O76067; Q6DK42;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 01-MAY-2013, entry version 115.
DE RecName: Full=Proteinase-activated receptor 4;
DE Short=PAR-4;
DE AltName: Full=Coagulation factor II receptor-like 3;
DE AltName: Full=Thrombin receptor-like 3;
DE Flags: Precursor;
GN Name=F2RL3; Synonyms=PAR4;
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], AND VARIANT THR-120.
RX PubMed=9722561; DOI=10.1074/jbc.273.36.23290;
RA Kahn M.L., Hammes S.R., Botka C., Coughlin S.R.;
RT "Gene and locus structure and chromosomal localization of the
RT protease-activated receptor gene family.";
RL J. Biol. Chem. 273:23290-23296(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-120.
RX PubMed=9716134; DOI=10.1038/29325;
RA Kahn M.L., Zheng Y.-W., Huang W., Bigornia V., Zeng D., Moff S.,
RA Farese R.V. Jr., Tam C., Coughlin S.R.;
RT "A dual thrombin receptor system for platelet activation.";
RL Nature 394:690-694(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ARG-47 AND ARG-68, AND
RP VARIANT THR-120.
RC TISSUE=Lymphoma;
RX PubMed=9618465; DOI=10.1073/pnas.95.12.6642;
RA Xu W.-F., Andersen H., Whitmore T.E., Presnell S.R., Yee D.P.,
RA Ching A., Gilbert T., Davie E.W., Foster D.C.;
RT "Cloning and characterization of human protease-activated receptor
RT 4.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6642-6646(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-296 AND LEU-310.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
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).
CC -!- FUNCTION: Receptor for activated thrombin or trypsin coupled to G
CC proteins that stimulate phosphoinositide hydrolysis. May play a
CC role in platelets activation.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in lung,
CC pancreas, thyroid, testis and small intestine. Not expressed in
CC brain, kidney, spinal cord and peripheral blood leukocytes. Also
CC detected in platelets.
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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/f2rl3/";
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DR EMBL; AF080214; AAC28860.1; -; mRNA.
DR EMBL; AF055917; AAC25699.1; -; mRNA.
DR EMBL; AY431102; AAR08487.1; -; mRNA.
DR EMBL; AF384819; AAK61908.1; -; Genomic_DNA.
DR EMBL; BC074782; AAH74782.2; -; mRNA.
DR IPI; IPI00022557; -.
DR RefSeq; NP_003941.2; NM_003950.2.
DR UniGene; Hs.137574; -.
DR PDB; 2ZPK; X-ray; 1.80 A; P/Q=46-53.
DR PDB; 3QDZ; X-ray; 2.80 A; E/F=39-47.
DR PDBsum; 2ZPK; -.
DR PDBsum; 3QDZ; -.
DR ProteinModelPortal; Q96RI0; -.
DR SMR; Q96RI0; 51-357.
DR STRING; 9606.ENSP00000248076; -.
DR PhosphoSite; Q96RI0; -.
DR DMDM; 116242700; -.
DR PaxDb; Q96RI0; -.
DR PRIDE; Q96RI0; -.
DR Ensembl; ENST00000248076; ENSP00000248076; ENSG00000127533.
DR GeneID; 9002; -.
DR KEGG; hsa:9002; -.
DR UCSC; uc002nfa.3; human.
DR CTD; 9002; -.
DR GeneCards; GC19P017001; -.
DR HGNC; HGNC:3540; F2RL3.
DR MIM; 602779; gene.
DR neXtProt; NX_Q96RI0; -.
DR PharmGKB; PA27949; -.
DR eggNOG; NOG148814; -.
DR HOGENOM; HOG000116291; -.
DR HOVERGEN; HBG096365; -.
DR InParanoid; Q96RI0; -.
DR KO; K04236; -.
DR OMA; YYVSAEF; -.
DR OrthoDB; EOG4KD6MW; -.
DR PhylomeDB; Q96RI0; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR BindingDB; Q96RI0; -.
DR ChEMBL; CHEMBL4691; -.
DR EvolutionaryTrace; Q96RI0; -.
DR GenomeRNAi; 9002; -.
DR NextBio; 33761; -.
DR PMAP-CutDB; Q96RI0; -.
DR Bgee; Q96RI0; -.
DR CleanEx; HS_F2RL3; -.
DR Genevestigator; Q96RI0; -.
DR GermOnline; ENSG00000127533; Homo sapiens.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0015057; F:thrombin receptor activity; TAS:ProtInc.
DR GO; GO:0007200; P:phospholipase C-activating G-protein coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0060155; P:platelet dense granule organization; IC:BHF-UCL.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IDA:BHF-UCL.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003944; Prot_act_rcpt_4.
DR InterPro; IPR003912; Protea_act_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01428; PROTEASEAR.
DR PRINTS; PR01430; PROTEASEAR4.
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 3D-structure; Blood coagulation; Cell membrane; Complete proteome;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Hemostasis;
KW Membrane; Polymorphism; Receptor; Reference proteome; Signal;
KW Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1 17 Potential.
FT PROPEP 18 47 Removed for receptor activation (By
FT similarity).
FT /FTId=PRO_0000012762.
FT CHAIN 48 385 Proteinase-activated receptor 4.
FT /FTId=PRO_0000012763.
FT TOPO_DOM 48 82 Extracellular (Potential).
FT TRANSMEM 83 103 Helical; Name=1; (Potential).
FT TOPO_DOM 104 108 Cytoplasmic (Potential).
FT TRANSMEM 109 129 Helical; Name=2; (Potential).
FT TOPO_DOM 130 151 Extracellular (Potential).
FT TRANSMEM 152 172 Helical; Name=3; (Potential).
FT TOPO_DOM 173 192 Cytoplasmic (Potential).
FT TRANSMEM 193 213 Helical; Name=4; (Potential).
FT TOPO_DOM 214 247 Extracellular (Potential).
FT TRANSMEM 248 268 Helical; Name=5; (Potential).
FT TOPO_DOM 269 283 Cytoplasmic (Potential).
FT TRANSMEM 284 304 Helical; Name=6; (Potential).
FT TOPO_DOM 305 319 Extracellular (Potential).
FT TRANSMEM 320 343 Helical; Name=7; (Potential).
FT TOPO_DOM 344 385 Cytoplasmic (Potential).
FT COMPBIAS 301 305 Poly-Leu.
FT SITE 47 48 Cleavage; by thrombin or trypsin (By
FT similarity).
FT CARBOHYD 56 56 N-linked (GlcNAc...) (Potential).
FT DISULFID 149 228 By similarity.
FT VARIANT 120 120 A -> T (in dbSNP:rs773902).
FT /FTId=VAR_028300.
FT VARIANT 215 215 R -> Q (in dbSNP:rs2230799).
FT /FTId=VAR_028301.
FT VARIANT 296 296 F -> V (in dbSNP:rs2227346).
FT /FTId=VAR_012852.
FT VARIANT 310 310 P -> L (in dbSNP:rs2227376).
FT /FTId=VAR_012853.
FT MUTAGEN 47 47 R->A: No proteolytic cleavage (by
FT thrombin or trypsin).
FT MUTAGEN 68 68 R->A: No effect on receptor activation.
FT STRAND 44 46
SQ SEQUENCE 385 AA; 41133 MW; FACE32F10D5C561E CRC64;
MWGRLLLWPL VLGFSLSGGT QTPSVYDESG STGGGDDSTP SILPAPRGYP GQVCANDSDT
LELPDSSRAL LLGWVPTRLV PALYGLVLVV GLPANGLALW VLATQAPRLP STMLLMNLAA
ADLLLALALP PRIAYHLRGQ RWPFGEAACR LATAALYGHM YGSVLLLAAV SLDRYLALVH
PLRARALRGR RLALGLCMAA WLMAAALALP LTLQRQTFRL ARSDRVLCHD ALPLDAQASH
WQPAFTCLAL LGCFLPLLAM LLCYGATLHT LAASGRRYGH ALRLTAVVLA SAVAFFVPSN
LLLLLHYSDP SPSAWGNLYG AYVPSLALST LNSCVDPFIY YYVSAEFRDK VRAGLFQRSP
GDTVASKASA EGGSRGMGTH SSLLQ
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