Proteinase-activated receptor 1
Also known as: CF2R, F2R, PAR1, TR
Function
High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores. The thrombin-activated receptor signaling pathway is mediated through PTX-insensitive G proteins, activation of phospholipase C resulting in the production of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) which binds to InsP3 receptors causing calcium release from the stores (By similarity). In astrocytes, the calcium released into the cytosol allows the Ca(2+)-dependent release of L-glutamate into the synaptic cleft through BEST1, that targets the neuronal postsynaptic GRIN2A/NMDAR receptor resulting in the synaptic plasticity regulation (By similarity). May play a role in platelets activation and in vascular development. Mediates up-regulation of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, triggered by coagulation factor Xa (F10) in cardiac fibroblasts and umbilical vein endothelial cells.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Protea_act_rcpt, Thrmbn_rcpt
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 13
- 1NRN X-ray 3.10A
- 1NRO X-ray 3.10A
- 1NRP X-ray 3.00A
- 1NRQ X-ray 3.50A
- 1NRR X-ray 2.40A
- 3BEF X-ray 2.20A
- 3HKI X-ray 2.20A
- 3HKJ X-ray 2.60A
- 3LU9 X-ray 1.80A
- 3VW7 X-ray 2.20A
- 8XOR EM 3.00A
- 8XOS EM 3.20A
- … and 1 more
A predicted model is available from AlphaFold.
Gene Ontology · 56
- GO:0005901 caveola
- GO:0009986 cell surface
- GO:0005769 early endosome
- GO:0005576 extracellular region
- GO:0005794 Golgi apparatus
- GO:0005770 late endosome
- GO:0031594 neuromuscular junction
- GO:0005886 plasma membrane
- GO:0031094 platelet dense tubular network
- GO:0045211 postsynaptic membrane
- GO:0004930 G protein-coupled receptor activity
- GO:0001965 G-protein alpha-subunit binding
- GO:0031681 G-protein beta-subunit binding
- GO:0005102 signaling receptor binding
- GO:0015057 thrombin-activated receptor activity
- GO:0009653 anatomical structure morphogenesis
- GO:0045217 cell-cell junction maintenance
- GO:0002248 connective tissue replacement involved in inflammatory response wound healing
- GO:0007529 establishment of synaptic specificity at neuromuscular junction
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0048873 homeostasis of number of cells within a tissue
- GO:0006954 inflammatory response
- GO:0008285 negative regulation of cell population proliferation
- GO:0003105 negative regulation of glomerular filtration
- GO:0043524 negative regulation of neuron apoptotic process
- GO:1900134 negative regulation of renin secretion into blood stream
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0030168 platelet activation
- GO:0060155 platelet dense granule organization
- GO:0043065 positive regulation of apoptotic process
- GO:0030194 positive regulation of blood coagulation
- GO:0051928 positive regulation of calcium ion transport
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0032967 positive regulation of collagen biosynthetic process
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0032755 positive regulation of interleukin-6 production
- GO:0032757 positive regulation of interleukin-8 production
- GO:0043410 positive regulation of MAPK cascade
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
- GO:0051281 positive regulation of release of sequestered calcium ion into cytosol
- GO:0035025 positive regulation of Rho protein signal transduction
- GO:0045987 positive regulation of smooth muscle contraction
- GO:0045907 positive regulation of vasoconstriction
- GO:0030193 regulation of blood coagulation
- GO:0032651 regulation of interleukin-1 beta production
- GO:0048167 regulation of synaptic plasticity
- GO:0051209 release of sequestered calcium ion into cytosol
- GO:0032496 response to lipopolysaccharide
- GO:0009611 response to wounding
- GO:0070493 thrombin-activated receptor signaling pathway
- GO:0099553 trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
Drugs targeting this protein · 3
- ATOPAXAR antagonist
- VORAPAXAR SULFATE antagonist
- PZ-128 inhibitor
Related proteins · sequence + function similarity
- Proteinase-activated receptor 1 1.00
- Proteinase-activated receptor 1 0.99
- Proteinase-activated receptor 1 0.98
- Proteinase-activated receptor 1 0.98
- Proteinase-activated receptor 1 0.97
- Proteinase-activated receptor 1 0.94
- Proteinase-activated receptor 2 0.94
- Proteinase-activated receptor 2 0.93
- Proteinase-activated receptor 2 0.93
- Proteinase-activated receptor 2 0.92
- Proteinase-activated receptor 3 0.92
- P2Y purinoceptor 8 0.91
Co-cited proteins · studied together in the literature
- FXa-directed anticoagulant 1 shared papers
- Proteinase-activated receptor 3 1 shared papers
- Coagulation factor X 3 shared papers
- Proteinase-activated receptor 4 1 shared papers
- C-C motif chemokine 2 2 shared papers
- Granzyme K 1 shared papers
- Cathepsin G 1 shared papers
- Proteinase-activated receptor 2 1 shared papers
- Interleukin-6 1 shared papers
- Prothrombin 1 shared papers
Literature · 14 cited papers
- Granzyme K initiates IL-6 and IL-8 release from epithelial cells by activating protease-activated receptor 2. PLoS ONE · 2022
- Alboserpin, the Main Salivary Anticoagulant from the Disease Vector Aedes albopictus, Displays Anti-FXa-PAR Signaling In Vitro and In Vivo. Immunohorizons · 2022
- Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1. Cells · 2021
- TAK-442, a Direct Factor Xa Inhibitor, Inhibits Monocyte Chemoattractant Protein 1 Production in Endothelial Cells via Involvement of Protease-Activated Receptor 1. Front. Pharmacol. · 2018
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- The protease-activated receptor 1 possesses a functional and cleavable signal peptide which is necessary for receptor expression. FEBS Lett. · 2012
- Parstatin, the cleaved peptide on proteinase-activated receptor 1 activation, is a potent inhibitor of angiogenesis. J. Pharmacol. Exp. Ther. · 2009
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. · 1999
- Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J. Clin. Invest. · 1999
- Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization. J. Biol. Chem. · 1996
- Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes. Biochemistry · 1994
- … and 2 more in the literature graph