F2R
Domain
The cleaved signal peptide may not be degraded and may function as an intracellular angiogenesis inhibitor peptide known as parstatin.
Function
High affinity receptor that binds the activated thrombin, leading to calcium release from intracellular stores (PubMed:1672265, PubMed:8136362). 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 (PubMed:10079109). 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 (PubMed:30568593, PubMed:34831181).
Post-translational modifications
Proteolytic cleavage by thrombin generates a new N-terminus that functions as a tethered ligand (PubMed:1672265, PubMed:7744748). Also proteolytically cleaved by cathepsin CTSG (PubMed:7744748). Cleavage at 41-Arg-|-Ser-42 by CTSG results in receptor activation while cleavage at 55-Phe-|-Trp-56 results in inhibition of receptor activation (PubMed:7744748).
Phosphorylated in the C-terminal tail; probably mediating desensitization prior to the uncoupling and internalization of the receptor.
Sequence Similarities
Belongs to the G-protein coupled receptor 1 family.
Tissue Specificity
Platelets and vascular endothelial cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
CF2R, PAR1, TR, F2R, Proteinase-activated receptor 1, PAR-1, Coagulation factor II receptor, Thrombin receptor