UniProt Accession

 PAR2_HUMAN; P55085; Q13317; Q13346; Q53XJ8 

Genbank Protein ID

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

Genbank Nucleotide ID

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

Protein Name

 Proteinase-activated receptor 2 

Protein Synonyms/Alias

 PAR-2; Coagulation factor II receptor-like 1; G-protein coupled receptor 11; Thrombin receptor-like 1; Proteinase-activated receptor 2, alternate cleaved 1; Proteinase-activated receptor 2, alternate cleaved 2 

Gene Name

 F2RL1 

Gene Synonyms/Alias

 GPR11; PAR2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
41	KGRSLIGKVDGTSHV	ubiquitination	[1, 2]
368	CRSVRTVKQMQVSLT	ubiquitination	[1, 2, 3, 4]
377	MQVSLTSKKHSRKSS	ubiquitination	[1, 2]
394	SSSSTTVKTSY****	ubiquitination	[1, 2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

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

 LIPID 361 361 S-palmitoyl cysteine.
 CARBOHYD 30 30 N-linked (GlcNAc...).
 CARBOHYD 222 222 N-linked (GlcNAc...).
 DISULFID 148 226 By similarity.  

Keyword

 Cell membrane; Complete proteome; Disulfide bond; G-protein coupled receptor; Glycoprotein; Immunity; Inflammatory response; Innate immunity; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 397 AA 

Protein Sequence

Gene Ontology

 GO:0005794; C:Golgi apparatus; TAS:ProtInc.
 GO:0005887; C:integral to plasma membrane; IDA:BHF-UCL.
 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: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:0051607; P:defense response to virus; IDA:UniProtKB.
 GO:0007204; P:elevation of cytosolic calcium ion concentration; IDA:UniProtKB.
 GO:0061028; P:establishment of endothelial barrier; IDA:UniProtKB.
 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:0002741; P:positive regulation of cytokine secretion involved in immune response; 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 cascade; 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 cascade; 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:0002286; P:T cell activation involved in immune response; ISS:UniProtKB. 

Interpro

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

Pfam

 PF00001; 7tm_1 

SMART

  

PROSITE

 PS00237; G_PROTEIN_RECEP_F1_1
 PS50262; G_PROTEIN_RECEP_F1_2 

PRINTS

 PR00237; GPCRRHODOPSN.
 PR01428; PROTEASEAR.
 PR01152; PROTEASEAR2.