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Proteinase-activated receptor 1 (PAR-1) (Thrombin receptor)

 PAR1_CRILO              Reviewed;         428 AA.
Q00991; Q60461;
01-APR-1993, integrated into UniProtKB/Swiss-Prot.
01-NOV-1997, sequence version 2.
29-SEP-2021, entry version 120.
RecName: Full=Proteinase-activated receptor 1;
Short=PAR-1;
AltName: Full=Thrombin receptor;
Flags: Precursor;
Name=F2R; Synonyms=PAR1;
Cricetulus longicaudatus (Long-tailed dwarf hamster) (Chinese hamster).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
Cricetidae; Cricetinae; Cricetulus.
NCBI_TaxID=10030;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Lung;
PubMed=1652467; DOI=10.1016/0014-5793(91)81017-3;
Rasmussen U.B., Vouret-Craviari V., Jallat S., Schlesinger Y., Pages G.,
Pavirani A., Lecocq J.-P., Pouyssegur J., Obberghen-Schilling E.;
"cDNA cloning and expression of a hamster alpha-thrombin receptor coupled
to Ca2+ mobilization.";
FEBS Lett. 288:123-128(1991).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 42-428.
PubMed=7488069; DOI=10.1006/bbrc.1995.2559;
Hartmann T., Grace M.B., Buzard G.S., Ruoss S.J.;
"Thrombin receptor polymorphism in Chinese hamster.";
Biochem. Biophys. Res. Commun. 215:974-980(1995).
-!- FUNCTION: High affinity receptor for activated thrombin coupled to G
proteins that stimulate phosphoinositide hydrolysis.
-!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
-!- DOMAIN: The cleaved signal peptide may not be degraded and may function
as an intracellular angiogenesis inhibitor peptide known as parstatin.
{ECO:0000250}.
-!- PTM: A proteolytic cleavage generates a new N-terminus that functions
as a tethered ligand.
-!- PTM: Phosphorylated in the C-terminal tail; probably mediating
desensitization prior to the uncoupling and internalization of the
receptor. {ECO:0000250}.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
{ECO:0000255|PROSITE-ProRule:PRU00521}.
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EMBL; X61958; CAA43957.1; -; mRNA.
EMBL; U34047; AAA86747.1; -; mRNA.
PIR; S17148; S17148.
SMR; Q00991; -.
GO; GO:0005901; C:caveola; ISS:UniProtKB.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0031094; C:platelet dense tubular network; ISS:UniProtKB.
GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
GO; GO:0031681; F:G-protein beta-subunit binding; ISS:UniProtKB.
GO; GO:0015057; F:thrombin-activated receptor activity; ISS:UniProtKB.
GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
GO; GO:0000186; P:activation of MAPKK activity; ISS:UniProtKB.
GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; ISS:UniProtKB.
GO; GO:0007529; P:establishment of synaptic specificity at neuromuscular junction; ISS:UniProtKB.
GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISS:UniProtKB.
GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
GO; GO:0003105; P:negative regulation of glomerular filtration; ISS:UniProtKB.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
GO; GO:1900134; P:negative regulation of renin secretion into blood stream; ISS:UniProtKB.
GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
GO; GO:0030194; P:positive regulation of blood coagulation; ISS:UniProtKB.
GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:UniProtKB.
GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISS:UniProtKB.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB.
GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0045907; P:positive regulation of vasoconstriction; ISS:UniProtKB.
GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
GO; GO:0032651; P:regulation of interleukin-1 beta production; ISS:UniProtKB.
GO; GO:0051930; P:regulation of sensory perception of pain; ISS:UniProtKB.
GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
GO; GO:0009611; P:response to wounding; ISS:UniProtKB.
GO; GO:0070493; P:thrombin-activated receptor signaling pathway; ISS:UniProtKB.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
InterPro; IPR003912; Protea_act_rcpt.
InterPro; IPR000935; Thrmbn_rcpt.
Pfam; PF00001; 7tm_1; 1.
PRINTS; PR00237; GPCRRHODOPSN.
PRINTS; PR01428; PROTEASEAR.
PRINTS; PR00908; THROMBINR.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
2: Evidence at transcript level;
Blood coagulation; Cell membrane; Disulfide bond;
G-protein coupled receptor; Glycoprotein; Hemostasis; Membrane;
Phosphoprotein; Receptor; Signal; Transducer; Transmembrane;
Transmembrane helix.
SIGNAL 1..21
/evidence="ECO:0000250"
PROPEP 22..41
/note="Removed for receptor activation"
/evidence="ECO:0000250"
/id="PRO_0000012738"
CHAIN 42..428
/note="Proteinase-activated receptor 1"
/id="PRO_0000012739"
TOPO_DOM 42..105
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 106..131
/note="Helical; Name=1"
/evidence="ECO:0000255"
TOPO_DOM 132..140
/note="Cytoplasmic"
/evidence="ECO:0000255"
TRANSMEM 141..160
/note="Helical; Name=2"
/evidence="ECO:0000255"
TOPO_DOM 161..179
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 180..201
/note="Helical; Name=3"
/evidence="ECO:0000255"
TOPO_DOM 202..221
/note="Cytoplasmic"
/evidence="ECO:0000255"
TRANSMEM 222..242
/note="Helical; Name=4"
/evidence="ECO:0000255"
TOPO_DOM 243..271
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 272..291
/note="Helical; Name=5"
/evidence="ECO:0000255"
TOPO_DOM 292..314
/note="Cytoplasmic"
/evidence="ECO:0000255"
TRANSMEM 315..337
/note="Helical; Name=6"
/evidence="ECO:0000255"
TOPO_DOM 338..352
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 353..377
/note="Helical; Name=7"
/evidence="ECO:0000255"
TOPO_DOM 378..428
/note="Cytoplasmic"
/evidence="ECO:0000255"
SITE 41..42
/note="Cleavage; by thrombin"
/evidence="ECO:0000250"
MOD_RES 421
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P25116"
CARBOHYD 65
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 78
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 253
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 262
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 178..257
/evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
VARIANT 84
/note="Missing (in an allele)"
CONFLICT 384
/note="H -> T (in Ref. 1; CAA43957)"
/evidence="ECO:0000305"
SEQUENCE 428 AA; 47603 MW; E5492AB2CD877E2F CRC64;
MGPQRLLLVA AGLSLCGPLL SSRVPVRQPE SEMTDATVNP RSFFLRNPGE NTFELIPLGD
EEEKNESTLP EGRAIYLNKS HSPPAPLAPF ISEDASGYLT SPWLRLFIPS VYTFVFVVSL
PLNILAIAVF VLKMKVKKPA VVYMLHLAMA DVLFVSVLPL KISYYFSGSD WQFGSGMCRF
ATAAFYCNMY ASIMLMTVIS IDRFLAVVYP IQSLSWRTLG RANFTCLVIW VMAIMGVVPL
LLKEQTTRVP GLNITTCHDV LNETLLQGFY SYYFSAFSAV FFLVPLIIST ICYMSIIRCL
SSSSVANRSK KSRALFLSAA VFCVFIVCFG PTNVLLIMHY LLLSDSPATE KAYFAYLLCV
CVSSVSCCID PLIYYYASSE CQRHLYGILC CKESSDPNSY NSTGQLMPSK MDTCSSHLNN
SIYKKLLA


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WP2355: Corticotropin-releasing hormone
WP878: EPO Receptor Signaling
WP1004: Kit Receptor Signaling Pathway
WP1869: Neuroransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
WP57: Signal Transduction of S1P Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP68: Androgen Receptor Signaling Pathway
WP1284: EPO Receptor Signaling
WP26: Signal Transduction of S1P Receptor
WP894: T Cell Receptor Signaling Pathway
WP1025: B Cell Receptor Signaling Pathway
WP926: TGF-beta Receptor Signaling Pathway
WP1067: Toll-like receptor signaling pathway
WP1965: VEGF-receptor Signal Transduction
WP734: Serotonin Receptor 4/6/7 and NR3C Signaling
WP1341: Kit Receptor Signaling Pathway
WP285: B Cell Receptor Signaling Pathway
WP1354: B Cell Receptor Signaling Pathway
WP352: T Cell Receptor Signaling Pathway
WP949: Toll-like receptor signaling pathway
WP1130: T Cell Receptor Signaling Pathway
WP2140: MaxYvesSuperCombo
WP774: Kit Receptor Signaling Pathway
WP1161: TGF-beta Receptor Signaling Pathway

Related Genes :
[F2RL1 GPR11 PAR2] Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (G-protein coupled receptor 11) (Thrombin receptor-like 1) [Cleaved into: Proteinase-activated receptor 2, alternate cleaved 1; Proteinase-activated receptor 2, alternate cleaved 2]
[F2rl1 Gpcr11 Gpr11 Par2] Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (G-protein coupled receptor 11) (Thrombin receptor-like 1)
[F2rl1 Par2] Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (Thrombin receptor-like 1)
[F2RL1 PAR2] Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (Thrombin receptor-like 1)
[F2RL3 PAR4] Proteinase-activated receptor 4 (PAR-4) (Coagulation factor II receptor-like 3) (Thrombin receptor-like 3)
[F2rl3 Par4] Proteinase-activated receptor 4 (PAR-4) (Coagulation factor II receptor-like 3) (Thrombin receptor-like 3)
[F2rl3 Par4] Proteinase-activated receptor 4 (PAR-4) (Coagulation factor II receptor-like 3) (Thrombin receptor-like 3)
[F2] Prothrombin (EC 3.4.21.5) (Coagulation factor II) [Cleaved into: Activation peptide fragment 1; Activation peptide fragment 2; Thrombin light chain; Thrombin heavy chain]
[Or22a AN11 DOR22A.1 dor53 Or22A.1 CG12193] Odorant receptor 22a
[Rack1 Gnb2-rs1 Gnb2l1] Receptor of activated protein C kinase 1 (12-3) (Guanine nucleotide-binding protein subunit beta-2-like 1) (Receptor for activated C kinase) (Receptor of activated protein kinase C 1) (p205) [Cleaved into: Receptor of activated protein C kinase 1, N-terminally processed (Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed)]
[Rack1 Gnb2l1] Receptor of activated protein C kinase 1 (Guanine nucleotide-binding protein subunit beta-2-like 1) (Receptor for activated C kinase) (Receptor of activated protein kinase C 1) [Cleaved into: Receptor of activated protein C kinase 1, N-terminally processed]
[Met] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[Oprm1 Mor Oprm] Mu-type opioid receptor (M-OR-1) (MOR-1)
[RACK1 GNB2L1] Receptor of activated protein C kinase 1 (Guanine nucleotide-binding protein subunit beta-2-like 1) (Receptor for activated C kinase) (Receptor of activated protein kinase C 1) [Cleaved into: Receptor of activated protein C kinase 1, N-terminally processed]
[RACK1 GNB2L1] Receptor of activated protein C kinase 1 (Guanine nucleotide-binding protein subunit beta-2-like 1) (Receptor for activated C kinase) (Receptor of activated protein kinase C 1) [Cleaved into: Receptor of activated protein C kinase 1, N-terminally processed]
[RACK1 GNB2L1 HLC7 PIG21] Receptor of activated protein C kinase 1 (Cell proliferation-inducing gene 21 protein) (Guanine nucleotide-binding protein subunit beta-2-like 1) (Guanine nucleotide-binding protein subunit beta-like protein 12.3) (Human lung cancer oncogene 7 protein) (HLC-7) (Receptor for activated C kinase) (Small ribosomal subunit protein RACK1) [Cleaved into: Receptor of activated protein C kinase 1, N-terminally processed (Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed)]
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[NR1H4 BAR FXR HRR1 RIP14] Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14)
[MED1 ARC205 CRSP1 CRSP200 DRIP205 DRIP230 PBP PPARBP PPARGBP RB18A TRAP220 TRIP2] Mediator of RNA polymerase II transcription subunit 1 (Activator-recruited cofactor 205 kDa component) (ARC205) (Mediator complex subunit 1) (Peroxisome proliferator-activated receptor-binding protein) (PBP) (PPAR-binding protein) (Thyroid hormone receptor-associated protein complex 220 kDa component) (Trap220) (Thyroid receptor-interacting protein 2) (TR-interacting protein 2) (TRIP-2) (Vitamin D receptor-interacting protein complex component DRIP205) (p53 regulatory protein RB18A)
[RACK1 GNB2L1] Receptor of activated protein C kinase 1 (Guanine nucleotide-binding protein subunit beta-like protein 12.3) (Receptor for activated C kinase) (Receptor of activated protein kinase C 1) (RACK1)
[Capn1 Canp1 Capa1] Calpain-1 catalytic subunit (EC 3.4.22.52) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (Calpain-1 large subunit) (Micromolar-calpain) (muCANP)
[Nr1h4 Bar Fxr Rip14] Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14)
[Nr1h4 Bar Fxr Rip14] Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14)
[Med1 Crsp210 Drip205 Pbp Pparbp Trap220 Trip2] Mediator of RNA polymerase II transcription subunit 1 (Mediator complex subunit 1) (Peroxisome proliferator-activated receptor-binding protein) (PBP) (PPAR-binding protein) (Thyroid hormone receptor-associated protein complex 220 kDa component) (Trap220) (Thyroid receptor-interacting protein 2) (TR-interacting protein 2) (TRIP-2)
[PPARG NR1C3] Peroxisome proliferator-activated receptor gamma (PPAR-gamma) (Nuclear receptor subfamily 1 group C member 3)
[OPRM1 MOR1] Mu-type opioid receptor (M-OR-1) (MOR-1) (Mu opiate receptor) (Mu opioid receptor) (MOP) (hMOP)
[Tnk2 Ack1] Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Non-receptor protein tyrosine kinase Ack) (Tyrosine kinase non-receptor protein 2)
[Oprm1 Ror-b] Mu-type opioid receptor (M-OR-1) (MOR-1) (Opioid receptor B)
[SLC52A1 GPR172B PAR2 RFT1] Solute carrier family 52, riboflavin transporter, member 1 (Porcine endogenous retrovirus A receptor 2) (PERV-A receptor 2) (huPAR-2) (Protein GPR172B) (Riboflavin transporter 1) (hRFT1)
[TRPM4 LTRPC4] Transient receptor potential cation channel subfamily M member 4 (hTRPM4) (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (Melastatin-4)

Bibliography :
[34944024] Pleiotropic Effects of the Protease-Activated Receptor 1 (PAR1) Inhibitor, Vorapaxar, on Atherosclerosis and Vascular Inflammation.
[34904279] High glucose upregulates PAR-1 in SH-SY5Y cells via deficiency of miR-20a and miR-190a.
[34873055] aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis.
[34846535] Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.
[34831181] Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1.
[34827666] Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves.
[34827556] The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies.
[34808540] Sex-specific platelet activation through protease-activated receptor-1 in patients undergoing cardiac catheterization.
[34794000] Direct evidence of edge-to-face CH/π interaction for PAR-1 thrombin receptor activation.
[34792626] Lack of miRNA-17 family mediates high glucose-induced PAR-1 upregulation in glomerular mesangial cells.