| IED ID | IndEnz0002006220 |
| Enzyme Type ID | protease006220 |
| Protein Name |
Proteinase-activated receptor 2 PAR-2 Coagulation factor II receptor-like 1 Thrombin receptor-like 1 |
| Gene Name | F2RL1 PAR2 |
| Organism | Bos taurus (Bovine) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Artiodactyla Ruminantia Pecora Bovidae Bovinae Bos (oxen cattle) Bos taurus (Bovine) |
| Enzyme Sequence | MRSPSAAWLLGGVLLLAASGSCNRTVPGNKSKGRSLIGNVDNSPVVAGRGVTVKPGFSVDEFSTSVLTGKLTTVFLPVVYTIVFVVGLPSNGMALWVFLFRTKKKHPAVIYMANLALADLLSVTWFPLKIAYHIHGNNWIYGESLCKVLIGFFYGNMYCSILFMTCLSVQRYWVIVNPMVHPKKQANIAIGVSLGIWLLILLLTIPLYVVKQTSYIRALNITTCHDVLPEEVLVGDMFNYFLSLAIGVFLFPAFLTASAYVLMIRTLQSSAMDESSGKKRRRAIKLIVTVLAMYLICFTPSNLLLVVHYFLIKTRGQSHVYALYIVALCLSTLNSCIDPFVYYFISQDFRDHAKNALLCRSVRTVKRMQVSLSSKKFSGKSSSYSSSSTSVKGSY |
| Enzyme Length | 395 |
| Uniprot Accession Number | Q2HJA4 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. {ECO:0000250|UniProtKB:P55085}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Disulfide bond (1); Glycosylation (3); Lipidation (1); Propeptide (1); Signal peptide (1); Site (1); Topological domain (8); Transmembrane (7) |
| Keywords | Cell membrane;Disulfide bond;G-protein coupled receptor;Glycoprotein;Immunity;Inflammatory response;Innate immunity;Lipoprotein;Membrane;Palmitate;Phosphoprotein;Receptor;Reference proteome;Signal;Transducer;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane protein. |
| Modified Residue | |
| Post Translational Modification | PTM: A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14. Proposed subsequent cleavage by serine proteases is leading to receptor deactivation and include neutrophil elastase and cathepsin G. At least in part, implicated proteases are also shown to activate the receptor; the glycosylation status of the receptor is thought to contribute to the difference. {ECO:0000250|UniProtKB:P55085}.; PTM: N-glycosylated and sialylated. {ECO:0000250|UniProtKB:P55085}.; PTM: Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin.; PTM: Monoubiquitinated by CBL at the plasma membrane and in early endosomes; not required for receptor endocytosis but for translocation to late endosomes or lysosomes. Deubiquitination involves STAMBP and USP8; required for lysosomal trafficking and receptor degradation (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 43,766 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |