InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: F2RL1

Summary

InnateDB Protein

IDBP-29715.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

F2RL1

Protein Name

coagulation factor II (thrombin) receptor-like 1

Synonyms

GPR11; PAR2;

Species

Homo sapiens

Ensembl Protein

ENSP00000296677

InnateDB Gene

IDBG-29713 (F2RL1)

Protein Structure

UniProt Annotation

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. 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, 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-alpha stimulated JNK phosphorylation via coupling to G alpha-q/11; 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 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 immnune 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. {ECO:0000269PubMed:10086357, ECO:0000269PubMed:10725339, ECO:0000269PubMed:11413129, ECO:0000269PubMed:11441110, ECO:0000269PubMed:11447194, ECO:0000269PubMed:11714832, ECO:0000269PubMed:12832443, ECO:0000269PubMed:15155775, ECO:0000269PubMed:16359518, ECO:0000269PubMed:16410250, ECO:0000269PubMed:16478888, ECO:0000269PubMed:16714334, ECO:0000269PubMed:17404307, ECO:0000269PubMed:17500066, ECO:0000269PubMed:18424071, ECO:0000269PubMed:18453611, ECO:0000269PubMed:18474671, ECO:0000269PubMed:18622013, ECO:0000269PubMed:19494303, ECO:0000269PubMed:19781631, ECO:0000269PubMed:19864598, ECO:0000269PubMed:19865078, ECO:0000269PubMed:20826780, ECO:0000269PubMed:21501162}.

Subcellular Localization

Cell membrane; Multi-pass membrane protein.

Disease Associations

Tissue Specificity

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.

Experimentally validated
Total	6 [view]
Protein-Protein	6 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001965	G-protein alpha-subunit binding
GO:0004872	receptor activity
GO:0004930	G-protein coupled receptor activity
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0015057	thrombin receptor activity
GO:0031681	G-protein beta-subunit binding

Biological Process

GO:0002286	T cell activation involved in immune response
GO:0002690	positive regulation of leukocyte chemotaxis
GO:0002741	positive regulation of cytokine secretion involved in immune response
GO:0003104	positive regulation of glomerular filtration
GO:0006954	inflammatory response
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007596	blood coagulation
GO:0010804	negative regulation of tumor necrosis factor-mediated signaling pathway
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0030193	regulation of blood coagulation
GO:0030335	positive regulation of cell migration
GO:0030836	positive regulation of actin filament depolymerization
GO:0031274	positive regulation of pseudopodium assembly
GO:0032930	positive regulation of superoxide anion generation
GO:0034137	positive regulation of toll-like receptor 2 signaling pathway
GO:0034140	negative regulation of toll-like receptor 3 signaling pathway
GO:0034141	positive regulation of toll-like receptor 3 signaling pathway
GO:0034145	positive regulation of toll-like receptor 4 signaling pathway
GO:0035025	positive regulation of Rho protein signal transduction
GO:0035926	chemokine (C-C motif) ligand 2 secretion
GO:0042119	neutrophil activation
GO:0043122	regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043311	positive regulation of eosinophil degranulation
GO:0045087	innate immune response (InnateDB)
GO:0045909	positive regulation of vasodilation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046328	regulation of JNK cascade
GO:0046329	negative regulation of JNK cascade
GO:0046330	positive regulation of JNK cascade
GO:0050702	interleukin-1 beta secretion
GO:0050900	leukocyte migration
GO:0050921	positive regulation of chemotaxis
GO:0050927	positive regulation of positive chemotaxis
GO:0051607	defense response to virus
GO:0060100	positive regulation of phagocytosis, engulfment
GO:0061028	establishment of endothelial barrier
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070493	thrombin receptor signaling pathway
GO:0070661	leukocyte proliferation
GO:0070963	positive regulation of neutrophil mediated killing of gram-negative bacterium
GO:0072608	interleukin-10 secretion
GO:0072643	interferon-gamma secretion
GO:0090195	chemokine secretion
GO:0090198	negative regulation of chemokine secretion
GO:0097029	mature dendritic cell differentiation
GO:1900135	positive regulation of renin secretion into blood stream
GO:2000484	positive regulation of interleukin-8 secretion
GO:2000778	positive regulation of interleukin-6 secretion

Cellular Component

GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane
GO:0031143	pseudopodium

Protein Structure and Domains

PDB ID

InterPro

IPR000276 G protein-coupled receptor, rhodopsin-like
IPR002281 Protease-activated receptor 2
IPR003912 Protease-activated receptor
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019427 7TM GPCR, serpentine receptor class w (Srw)

PFAM

PF00001
PF10324

PRINTS

PR00237
PR01152
PR01428

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P55085