Showing Protein Proteinase-activated receptor 2 (CDBP05659)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 compounds
Identification
HMDB Protein ID CDBP05659
Secondary Accession Numbers Not Available
Name Proteinase-activated receptor 2
Description Not Available
Synonyms Not Available
Gene Name F2RL1
Protein Type Receptor
Biological Properties
General Function thrombin-activated receptor activity
Specific 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-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. 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.
GO Classification
Biological Process
positive regulation of phagocytosis, engulfment
G-protein coupled receptor signaling pathway
positive regulation of chemotaxis
positive regulation of positive chemotaxis
inflammatory response
cell-cell junction maintenance
neutrophil activation
negative regulation of tumor necrosis factor-mediated signaling pathway
chemokine (C-C motif) ligand 2 secretion
positive regulation of superoxide anion generation
chemokine secretion
positive regulation of ERK1 and ERK2 cascade
interferon-gamma secretion
blood coagulation
interleukin-1 beta secretion
defense response to virus
interleukin-10 secretion
positive regulation of pseudopodium assembly
innate immune response
leukocyte proliferation
positive regulation of renin secretion into blood stream
positive regulation of actin filament depolymerization
mature conventional dendritic cell differentiation
positive regulation of Rho protein signal transduction
positive regulation of transcription from RNA polymerase II promoter
negative regulation of chemokine secretion
positive regulation of toll-like receptor 2 signaling pathway
positive regulation of GTPase activity
positive regulation of I-kappaB kinase/NF-kappaB cascade
negative regulation of toll-like receptor 3 signaling pathway
positive regulation of toll-like receptor 3 signaling pathway
elevation of cytosolic calcium ion concentration
positive regulation of toll-like receptor 4 signaling pathway
negative regulation of JNK cascade
positive regulation of cytokine secretion involved in immune response
regulation of blood coagulation
regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of cell migration
positive regulation of blood vessel diameter
positive regulation of JNK cascade
positive regulation of eosinophil degranulation
regulation of JNK cascade
leukocyte migration
establishment of endothelial barrier
positive regulation of glomerular filtration
T cell activation involved in immune response
positive regulation of interleukin-6 secretion
positive regulation of phosphatidylinositol 3-kinase cascade
positive regulation of leukocyte chemotaxis
positive regulation of interleukin-8 secretion
elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway
positive regulation of neutrophil mediated killing of gram-negative bacterium
Cellular Component
plasma membrane
Golgi apparatus
early endosome
integral to plasma membrane
cell
pseudopodium
Molecular Function
thrombin-activated receptor activity
receptor binding
signaling receptor activity
G protein-coupled receptor activity
G-protein alpha-subunit binding
G-protein beta-subunit binding
Cellular Location
  1. Cell membrane
Pathways
Gene Properties
Chromosome Location 5
Locus 5q13.3
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 397
Molecular Weight 44125.87
Theoretical pI Not Available
Pfam Domain Function
Signals
  • ["1-25"]
Transmembrane Regions
  • ["72-101", "109-137", "150-177", "184-211", "236-269", "278-317", "324-347"]
Protein Sequence 
>Proteinase-activated receptor 2
MRSPSAAWLLGAAILLAASLSCSGTIQGTNRSSKGRSLIGKVDGTSHVTGKGVTVETVFS
VDEFSASVLTGKLTTVFLPIVYTIVFVVGLPSNGMALWVFLFRTKKKHPAVIYMANLALA
DLLSVIWFPLKIAYHIHGNNWIYGEALCNVLIGFFYGNMYCSILFMTCLSVQRYWVIVNP
MGHSRKKANIAIGISLAIWLLILLVTIPLYVVKQTIFIPALNITTCHDVLPEQLLVGDMF
NYFLSLAIGVFLFPAFLTASAYVLMIRMLRSSAMDENSEKKRKRAIKLIVTVLAMYLICF
TPSNLLLVVHYFLIKSQGQSHVYALYIVALCLSTLNSCIDPFVYYFVSHDFRDHAKNALL
CRSVRTVKQMQVSLTSKKHSRKSSSYSSSSTTVKTSY
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P55085
UniProtKB/Swiss-Prot Entry Name PAR2_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID HGNC:3538
References
General References Not Available