F2RL1 Human Recombinant Protein

Coagulation factor II (thrombin) receptor-like 1 (F2RL1) is a member of the large family of 7-transmembrane-region receptors that couple to guanosine-nucleotide-binding proteins. F2RL1 is also a member of the protease-activated receptor family. It is activated by trypsin, but not by thrombin. It is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. The F2RL1 gene contains two exons and is widely expressed in human tissues. The predicted protein sequence is 83% identical to the mouse receptor sequence. [provided by RefSeq, Jul 2008]

F2RL1: a G-protein coupled receptor for trypsin and trypsin-like enzymes. Acts as a sensor for proteolytic enzymes generated during infection. Modulates pro-inflammatory responses, and innate and adaptive immunity. It is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. Activates several signaling molecules including phospholipase C (PLC), mitogen-activated protein kinase (MAPK), IKK/NFkB and Rho. Elevates intracellular calcium. Can also be transactivated by cleaved PAR1. 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. 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 G alpha-q, G alpha-11, G alpha-14, G alpha- 12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, may signal through G(i) subunit alpha. Believed to be a class B receptor that 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 G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G alpha-q/11 and involves promotion of cofilin dephosphoryltaion 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. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders. Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small intestine, and colon. Moderate expression is detected in many organs, but none in brain or skeletal muscle. Belongs to the G-protein coupled receptor 1 family.

Protein type: GPCR, family 1; Membrane protein, multi-pass; Membrane protein, integral; Receptor, GPCR

Chromosomal Location of Human Ortholog: 5q13

Cellular Component: Golgi apparatus; integral to plasma membrane; early endosome; plasma membrane; pseudopodium

Molecular Function: G-protein coupled receptor activity; protein binding; G-protein alpha-subunit binding; G-protein beta-subunit binding; receptor activity; thrombin receptor activity; receptor binding

Biological Process: negative regulation of JNK cascade; positive regulation of positive chemotaxis; positive regulation of cytokine secretion during immune response; positive regulation of JNK cascade; positive regulation of leukocyte chemotaxis; positive regulation of vasodilation; regulation of JNK cascade; negative regulation of toll-like receptor 3 signaling pathway; T cell activation during immune response; elevation of cytosolic calcium ion concentration; positive regulation of glomerular filtration; positive regulation of superoxide release; interleukin-1 beta secretion; inflammatory response; regulation of I-kappaB kinase/NF-kappaB cascade; defense response to virus; positive regulation of toll-like receptor 3 signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB cascade; neutrophil activation; positive regulation of actin filament depolymerization; positive regulation of eosinophil degranulation; positive regulation of chemotaxis; positive regulation of toll-like receptor 4 signaling pathway; positive regulation of Rho protein signal transduction; positive regulation of toll-like receptor 2 signaling pathway; positive regulation of phosphoinositide 3-kinase cascade; G-protein coupled receptor protein signaling pathway; positive regulation of pseudopodium formation; regulation of blood coagulation; innate immune response; positive regulation of transcription from RNA polymerase II promoter; blood coagulation; positive regulation of phagocytosis, engulfment; leukocyte migration; positive regulation of cell migration