F2RL1
entrez
2150
canonical
uniprot
P55085
canonical
ensembl
ENSG00000164251
resolver
ensp
ENSP00000296677
resolver
enst
ENST00000296677
resolver
genesymbol
F2RL1
resolver
genesymbol_syn
GPR11
resolver
genesymbol_syn
PAR2
resolver
hgnc
HGNC:3538
resolver
uniprot
Q13317
resolver
uniprot
Q13346
resolver
uniprot
Q53XJ8
resolver
uniprot_entry
PAR2_HUMAN
resolver
uniprot_sec
Q13317
resolver
uniprot_sec
Q13346
resolver
uniprot_sec
Q53XJ8
resolver
activity_regulation
ACTIVITY REGULATION: Activated upon interaction by mucunain, a cowhage (Mucuna pruriens) plant cysteine proteinase. {ECO:0000269|PubMed:18434511}.
uniprot
proteins
amino_acid_sequence
MRSPSAAWLLGAAILLAASLSCSGTIQGTNRSSKGRSLIGKVDGTSHVTGKGVTVETVFSVDEFSASVLTGKLTTVFLPIVYTIVFVVGLPSNGMALWVFLFRTKKKHPAVIYMANLALADLLSVIWFPLKIAYHIHGNNWIYGEALCNVLIGFFYGNMYCSILFMTCLSVQRYWVIVNPMGHSRKKANIAIGISLAIWLLILLVTIPLYVVKQTIFIPALNITTCHDVLPEQLLVGDMFNYFLSLAIGVFLFPAFLTASAYVLMIRMLRSSAMDENSEKKRKRAIKLIVTVLAMYLICFTPSNLLLVVHYFLIKSQGQSHVYALYIVALCLSTLNSCIDPFVYYFVSHDFRDHAKNALLCRSVRTVKQMQVSLTSKKHSRKSSSYSSSSTTVKTSY
uniprot
proteins
function
FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G proteins (PubMed:28445455). 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 (PubMed:28445455). 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 (PubMed:23202369). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion (PubMed:10086357). 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. However, according to PubMed:21627585 can signal through G(i) subunit alpha. 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 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 pro-inflammatory 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. Probably mediates activation of pro-inflammatory and pro-fibrotic responses in fibroblasts, triggered by coagulation factor Xa (F10) (By similarity). Mediates activation of barrier protective signaling responses in endothelial cells, triggered by coagulation factor Xa (F10) (PubMed:22409427). {ECO:0000250|UniProtKB:P55086, ECO:0000269|PubMed:10086357, ECO:0000269|PubMed:10725339, ECO:0000269|PubMed:11413129, ECO:0000269|PubMed:11441110, ECO:0000269|PubMed:11447194, ECO:0000269|PubMed:11714832, ECO:0000269|PubMed:12832443, ECO:0000269|PubMed:15155775, ECO:0000269|PubMed:16359518, ECO:0000269|PubMed:16410250, ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:16714334, ECO:0000269|PubMed:17404307, ECO:0000269|PubMed:17500066, ECO:0000269|PubMed:18424071, ECO:0000269|PubMed:18453611, ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:18622013, ECO:0000269|PubMed:19494303, ECO:0000269|PubMed:19781631, ECO:0000269|PubMed:19864598, ECO:0000269|PubMed:19865078, ECO:0000269|PubMed:20826780, ECO:0000269|PubMed:21501162, ECO:0000269|PubMed:22409427, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28445455}.
uniprot
proteins
mass_dalton
44126
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="N->A: Increases sensitivity towards tryptase. Decreases cell surface expression; when associated with A-222."; /evidence="ECO:0000269|PubMed:12171601"; MUTAGEN 36; /note="R->A: Abolished and activation cleavage by GZMK."; /evidence="ECO:0000269|PubMed:35881628"; MUTAGEN 135; /note="H->Y: Slight reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 154; /note="F->A: Severe reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 157; /note="G->C,M: Severe reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 210; /note="Y->L: No defect in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 222; /note="N->A: Decreases cell surface expression; when associated with A-30. Loss of sensitivity towards all tested proteases."; /evidence="ECO:0000269|PubMed:12171601"; MUTAGEN 222; /note="N->Q: No defect in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 227; /note="H->A: No defect in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 227; /note="H->Q: Slight reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 228; /note="D->A,N: Severe reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 327; /note="I->L: Slight reduction in ligand-mediated receptor activation."; /evidence="ECO:0000269|PubMed:28445455"; MUTAGEN 355..363; /note="Missing: Abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through MAPK."; /evidence="ECO:0000269|PubMed:14607272"; MUTAGEN 361; /note="C->A: Loss of palmitoylation; increases surface expression and internalization following trypsin activation, decreases sensitivity and intracellular calcium signaling, increases ERK activation through G(i) subunit alpha."; MUTAGEN 363; /note="S->A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-366."; /evidence="ECO:0000269|PubMed:10725339"; MUTAGEN 366; /note="T->A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-363."; /evidence="ECO:0000269|PubMed:10725339
uniprot
proteins
post_translational_modification
PTM: A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand (PubMed:10805786, PubMed:10831593, PubMed:16478888, PubMed:19864598, PubMed:9020112). Activating serine proteases include trypsin, mast cell tryptase, GZMK, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14 (PubMed:10805786, PubMed:10831593, PubMed:16478888, PubMed:19864598, PubMed:23202369, PubMed:35881628, PubMed:9020112). Subsequent cleavage by serine proteases, including neutrophil elastase and cathepsin G, leads to receptor deactivation (PubMed:12594060). 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 (PubMed:12171601). In addition to conventional trypsin-like proteases activated by other proteases and glycosidases derived from bacteria, fungi and insects (PubMed:11441110, PubMed:11447194, PubMed:17404307, PubMed:18474671, PubMed:19864598). Activated by serine protease allergens such as dust mite Der p3 and Der p9 and mold Pen c13 (PubMed:11441110, PubMed:17404307). Activated by P.gingivalis arginine-specific (trypsin-like) cysteine proteinases called gingipains (PubMed:11447194). Activated by S.griseus exogenous chitinase (PubMed:18474671). Activated by A.alternata aspartate protease; the cleavage generates non-conventional processed forms (PubMed:19864598). Proteolytically cleaved by coagulation factor Xa (F10); cleavage results in activation of F2RL1-dependent signaling (PubMed:22409427). {ECO:0000269|PubMed:10805786, ECO:0000269|PubMed:10831593, ECO:0000269|PubMed:11441110, ECO:0000269|PubMed:11447194, ECO:0000269|PubMed:12171601, ECO:0000269|PubMed:12594060, ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:17404307, ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:19864598, ECO:0000269|PubMed:22409427, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:35881628, ECO:0000269|PubMed:9020112}.; PTM: N-glycosylated and sialylated. {ECO:0000269|PubMed:12171601}.; PTM: Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin. {ECO:0000269|PubMed:19815543}.; 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.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10086357
uniprot
proteins
pubmed
10725339
uniprot
proteins
pubmed
10788464
uniprot
proteins
pubmed
10805786
uniprot
proteins
pubmed
10831593
uniprot
proteins
pubmed
11413129
uniprot
proteins
pubmed
11441110
uniprot
proteins
pubmed
11447194
uniprot
proteins
pubmed
11714832
uniprot
proteins
pubmed
11859856
uniprot
proteins
pubmed
12171601
uniprot
proteins
pubmed
12594060
uniprot
proteins
pubmed
12832443
uniprot
proteins
pubmed
14519665
uniprot
proteins
pubmed
14607272
uniprot
proteins
pubmed
15155775
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15708858
uniprot
proteins
pubmed
15879675
uniprot
proteins
pubmed
15919826
uniprot
proteins
pubmed
16359518
uniprot
proteins
pubmed
16410250
uniprot
proteins
pubmed
16476770
uniprot
proteins
pubmed
16478888
uniprot
proteins
pubmed
16714334
uniprot
proteins
pubmed
17404307
uniprot
proteins
pubmed
17500066
uniprot
proteins
pubmed
17693410
uniprot
proteins
pubmed
18424071
uniprot
proteins
pubmed
18434511
uniprot
proteins
pubmed
18453611
uniprot
proteins
pubmed
18474671
uniprot
proteins
pubmed
18622013
uniprot
proteins
pubmed
19494303
uniprot
proteins
pubmed
19684015
uniprot
proteins
pubmed
19781631
uniprot
proteins
pubmed
19815543
uniprot
proteins
pubmed
19864598
uniprot
proteins
pubmed
19865078
uniprot
proteins
pubmed
20530726
uniprot
proteins
pubmed
20584806
uniprot
proteins
pubmed
20826780
uniprot
proteins
pubmed
21501162
uniprot
proteins
pubmed
21627585
uniprot
proteins
pubmed
22409427
uniprot
proteins
pubmed
23202369
uniprot
proteins
pubmed
28445455
uniprot
proteins
pubmed
35881628
uniprot
proteins
pubmed
7556175
uniprot
proteins
pubmed
8615752
uniprot
proteins
pubmed
8784787
uniprot
proteins
pubmed
9020112
uniprot
proteins
sequence_length
397
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
uniprot
proteins
transmembrane_region
TRANSMEM 72..101; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 109..137; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 150..177; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 184..211; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 236..269; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 278..317; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:28445455"; TRANSMEM 324..347; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:28445455
uniprot
proteins