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. Note: This description may include information from UniProtKB.
Protein type: GPCR, family 1; Membrane protein, integral; Membrane protein, multi-pass; Receptor, GPCR
Biological Process: defense response to virus; elevation of cytosolic calcium ion concentration; elevation of cytosolic calcium ion concentration during G-protein signaling, coupled to IP3 second messenger (phospholipase C activating); G-protein coupled receptor protein signaling pathway; interleukin-1 beta secretion; leukocyte migration; negative regulation of JNK cascade; negative regulation of toll-like receptor 3 signaling pathway; neutrophil activation; positive regulation of actin filament depolymerization; positive regulation of cell migration; positive regulation of chemotaxis; positive regulation of cytokine secretion during immune response; positive regulation of eosinophil degranulation; positive regulation of glomerular filtration; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of JNK cascade; positive regulation of leukocyte chemotaxis; positive regulation of phagocytosis, engulfment; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of positive chemotaxis; positive regulation of pseudopodium formation; positive regulation of Rho protein signal transduction; positive regulation of superoxide release; positive regulation of toll-like receptor 2 signaling pathway; positive regulation of toll-like receptor 3 signaling pathway; positive regulation of toll-like receptor 4 signaling pathway; positive regulation of transcription from RNA polymerase II promoter; regulation of blood coagulation; regulation of I-kappaB kinase/NF-kappaB cascade; regulation of JNK cascade; T cell activation during immune response