F2R Gene - Coagulation Factor II Thrombin Receptor | Function, Mutations & Diseases

F2R encodes protease-activated receptor 1 (PAR1), a G protein-coupled receptor that is the prototypical member of the protease-activated receptor family. PAR1 is activated by thrombin-mediated cleavage of its N-terminal extracellular domain, exposing a tethered ligand that binds intramolecularly to initiate intracellular signaling. This receptor plays a central role in platelet activation, vascular endothelial function, and inflammatory responses. It is expressed in platelets, endothelial cells, smooth muscle cells, fibroblasts, and various cancer cells.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Thrombin signaling through PAR1 (Reactome: R-HSA-456926)

• GPCR downstream signaling (Reactome: R-HSA-388396)

• Platelet activation

• signaling and aggregation (Reactome: R-HSA-76002)

• Protease-activated receptor signaling (KEGG: hsa04611)

The F2R protein (PAR1) is a 425-amino acid seven-transmembrane G protein-coupled receptor. It is synthesized as a precursor and cleaved intracellularly; the mature receptor is activated by thrombin which cleaves the N-terminal exodomain between Arg41 and Ser42, exposing a tethered ligand (SFLLRN). This ligand binds to the receptor's extracellular loops, triggering conformational changes that activate Gq, Gi, and G12/13 pathways. PAR1 is critical for hemostasis and thrombosis, and its dysregulation contributes to cancer progression and inflammatory diseases.