LipidDB ID

LipidDB-9606-00307

Entry Name

UniProt Accession

P55085; Q13317; Q13346; Q53XJ8;

Theoretical PI

9.66

Molecular Weight

44126.34

Genbank Protein ID

CAA90290.1; CAA90290.1; AAB47871.1; AAP97012.1; AAK77914.1; AAP88858.1; EAW95782.1; AAH12453.1; AAH18130.1; AAA90957.1;

Genbank Nucleotide ID

Z49993; Z49994; U34038; AY336105; AF400075; BT009856; CH471084; BC012453; BC018130; U36753;

Protein Name

Proteinase-activated receptor 2, alternate cleaved 2

Protein Synonyms/Alias

PAR-2; Coagulation factor II receptor-like 1; G-protein coupled receptor 11; Thrombin receptor-like 1;

Gene Name

F2RL1

Gene Synonyms/Alias

GPR11; PAR2;

Created Date

01-OCT-1996

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Botham A, Guo X, Xiao YP, Morice AH, Compton SJ, Sadofsky LR. Palmitoylationof human proteinase-activated receptor-2 differentially regulatesreceptor-triggered ERK1/2 activation, calcium signalling and endocytosis. BiochemJ. 2011 Sep 1;438(2):359-67. doi: 10.1042/BJ20101958.[PMID:21627585]

Functional Description

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.

Sequence Annotation

Topological domain: 37 75 Extracellular.
Transmembrane: 76 101 Helical; Name=1.
Topological domain: 102 110 Cytoplasmic.
Transmembrane: 111 130 Helical; Name=2.
Topological domain: 131 149 Extracellular.
Transmembrane: 150 171 Helical; Name=3.
Topological domain: 172 190 Cytoplasmic.
Transmembrane: 191 211 Helical; Name=4.
Topological domain: 212 241 Extracellular.
Transmembrane: 242 260 Helical; Name=5.
Topological domain: 261 285 Cytoplasmic.
Transmembrane: 286 308 Helical; Name=6.
Topological domain: 309 323 Extracellular.
Transmembrane: 324 347 Helical; Name=7.
Topological domain: 348 397 Cytoplasmic.
Functional site: 36 37 Cleavage; by trypsin.

Protein Length

397 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005794; C:Golgi apparatus; TAS:ProtInc
GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL
GO:0005886; C:plasma membrane; TAS:Reactome
GO:0031143; C:pseudopodium; ISS:UniProtKB
GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB
GO:0031681; F:G-protein beta-subunit binding; ISS:UniProtKB
GO:0004930; F:G-protein coupled receptor activity; IMP:UniProtKB
GO:0004872; F:receptor activity; TAS:ProtInc
GO:0005102; F:receptor binding; TAS:ProtInc
GO:0015057; F:thrombin receptor activity; IEA:InterPro
GO:0007596; P:blood coagulation; IEA:InterPro
GO:0035926; P:chemokine (C-C motif) ligand 2 secretion; IDA:UniProtKB
GO:0090195; P:chemokine secretion; IDA:UniProtKB
GO:0051607; P:defense response to virus; IDA:UniProtKB
GO:0061028; P:establishment of endothelial barrier; IDA:UniProtKB
GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc
GO:0006954; P:inflammatory response; IEA:UniProtKB-KW
GO:0045087; P:innate immune response; IEA:UniProtKB-KW
GO:0072643; P:interferon-gamma secretion; ISS:UniProtKB
GO:0050702; P:interleukin-1 beta secretion; IDA:UniProtKB
GO:0072608; P:interleukin-10 secretion; IDA:UniProtKB
GO:0050900; P:leukocyte migration; IDA:UniProtKB
GO:0070661; P:leukocyte proliferation; ISS:UniProtKB
GO:0097029; P:mature dendritic cell differentiation; IDA:UniProtKB
GO:0090198; P:negative regulation of chemokine secretion; IDA:UniProtKB
GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB
GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB
GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB
GO:0042119; P:neutrophil activation; IDA:UniProtKB
GO:0030836; P:positive regulation of actin filament depolymerization; IDA:UniProtKB
GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB
GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB
GO:0002741; P:positive regulation of cytokine secretion involved in immune response; IDA:UniProtKB
GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB
GO:0043311; P:positive regulation of eosinophil degranulation; IDA:UniProtKB
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB
GO:0003104; P:positive regulation of glomerular filtration; ISS:UniProtKB
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB
GO:2000778; P:positive regulation of interleukin-6 secretion; IDA:UniProtKB
GO:2000484; P:positive regulation of interleukin-8 secretion; IDA:UniProtKB
GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB
GO:0002690; P:positive regulation of leukocyte chemotaxis; IDA:BHF-UCL
GO:0070963; P:positive regulation of neutrophil mediated killing of gram-negative bacterium; IDA:UniProtKB
GO:0060100; P:positive regulation of phagocytosis, engulfment; IDA:UniProtKB
GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB
GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL
GO:0031274; P:positive regulation of pseudopodium assembly; ISS:UniProtKB
GO:1900135; P:positive regulation of renin secretion into blood stream; ISS:UniProtKB
GO:0035025; P:positive regulation of Rho protein signal transduction; IMP:UniProtKB
GO:0032930; P:positive regulation of superoxide anion generation; IDA:UniProtKB
GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB
GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB
GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB
GO:0045909; P:positive regulation of vasodilation; ISS:UniProtKB
GO:0030193; P:regulation of blood coagulation; IDA:BHF-UCL
GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB
GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB
GO:0002286; P:T cell activation involved in immune response; ISS:UniProtKB

Interpro

InterPro; IPR000276; GPCR_Rhodpsn
InterPro; IPR017452; GPCR_Rhodpsn_7TM
InterPro; IPR002281; Pro_rcpt_2
InterPro; IPR003912; Protea_act_rcpt

Pfam

Pfam; PF00001; 7tm_1;

SMART

PROSITE

PROSITE; PS50262; G_PROTEIN_RECEP_F1_2;

PRINTS

PRINTS; PR00237; GPCRRHODOPSN;
PRINTS; PR01428; PROTEASEAR;
PRINTS; PR01152; PROTEASEAR2;