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Protein

Proteinase-activated receptor 2

Gene

F2rl1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-RNO-375276. Peptide ligand-binding receptors.
R-RNO-416476. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Proteinase-activated receptor 2
Short name:
PAR-2
Alternative name(s):
Coagulation factor II receptor-like 1
Thrombin receptor-like 1
Gene namesi
Name:F2rl1
Synonyms:Par2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi620866. F2rl1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini37 – 7539ExtracellularSequence analysisAdd
BLAST
Transmembranei76 – 10126Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini102 – 1109CytoplasmicSequence analysis
Transmembranei111 – 13020Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini131 – 14919ExtracellularSequence analysisAdd
BLAST
Transmembranei150 – 17122Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini172 – 19019CytoplasmicSequence analysisAdd
BLAST
Transmembranei191 – 21121Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini212 – 24130ExtracellularSequence analysisAdd
BLAST
Transmembranei242 – 26019Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini261 – 28525CytoplasmicSequence analysisAdd
BLAST
Transmembranei286 – 30823Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini309 – 32315ExtracellularSequence analysisAdd
BLAST
Transmembranei324 – 34724Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini348 – 39750CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2429706.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Propeptidei26 – 3611Removed for receptor activationBy similarityPRO_0000012754Add
BLAST
Chaini37 – 397361Proteinase-activated receptor 2PRO_0000012755Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence analysis
Disulfide bondi148 ↔ 226PROSITE-ProRule annotation
Glycosylationi222 – 2221N-linked (GlcNAc...)Sequence analysis
Lipidationi361 – 3611S-palmitoyl cysteineBy similarity

Post-translational modificationi

A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/Prtn3 and membrane-type serine protease 1/St14. Proposed subsequent cleaveage by serine proteases is leading to receptor deactivation and include neutrophil elastase and cathepsin G. 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 (By similarity).By similarity
N-glycosylated and sialylated.By similarity
Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin.
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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei36 – 372Cleavage; by trypsinBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63645.
PRIDEiQ63645.

PTM databases

PhosphoSiteiQ63645.

Miscellaneous databases

PMAP-CutDBQ63645.

Expressioni

Gene expression databases

GenevisibleiQ63645. RN.

Interactioni

Subunit structurei

Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tmed2Q635242EBI-4303358,EBI-918600

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250560. 2 interactions.
IntActiQ63645. 1 interaction.
STRINGi10116.ENSRNOP00000058298.

Chemistry

BindingDBiQ63645.

Structurei

3D structure databases

ProteinModelPortaliQ63645.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi383 – 39210Poly-Ser

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGEM. Eukaryota.
ENOG4111CWR. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG105658.
InParanoidiQ63645.
KOiK04234.
OMAiLAMYLIC.
OrthoDBiEOG7DNNVR.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002281. Pro_rcpt_2.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01152. PROTEASEAR2.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63645-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRSLSLAWLL GGITLLAASA SCNRTVNAPG PNSKGRSLIG RLDTPPPITG
60 70 80 90 100
KGAPVEPGFS VDEFSASVLT GKLTTVFLPV IYIIVFVIGL PSNGMALWVF
110 120 130 140 150
FFRTKKKHPA VIYMANLALA DLLSVIWFPL KISYHLHGND WTYGDALCKV
160 170 180 190 200
LIGFFYGNMY CSILFMTCLS VQRYWVIVNP MGHSRKRANI AVGVSLAIWL
210 220 230 240 250
LIFLVTIPLY VMRQTIYIPA LNITTCHDVL PEEVLVGDMF SYFLSLAIGV
260 270 280 290 300
FLFPALLTAS AYVLMIKTLR SSAMDEHSEK KRRRAIRLII TVLSMYFICF
310 320 330 340 350
APSNVLLVVH YFLIKSQRQS HVYALYLVAL CLSTLNSCID PFVYYFVSKD
360 370 380 390
FRDQARNALL CRSVRTVKRM QISLTSNKFS RKSSSYSSSS TSVKTSY
Length:397
Mass (Da):44,441
Last modified:November 1, 1996 - v1
Checksum:i27DE0C3ACABC798D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61373 mRNA. Translation: AAC52703.1.
BC099765 mRNA. Translation: AAH99765.1.
RefSeqiNP_446349.1. NM_053897.2.
UniGeneiRn.10543.

Genome annotation databases

EnsembliENSRNOT00000061580; ENSRNOP00000058298; ENSRNOG00000018003.
GeneIDi116677.
KEGGirno:116677.
UCSCiRGD:620866. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61373 mRNA. Translation: AAC52703.1.
BC099765 mRNA. Translation: AAH99765.1.
RefSeqiNP_446349.1. NM_053897.2.
UniGeneiRn.10543.

3D structure databases

ProteinModelPortaliQ63645.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250560. 2 interactions.
IntActiQ63645. 1 interaction.
STRINGi10116.ENSRNOP00000058298.

Chemistry

BindingDBiQ63645.
ChEMBLiCHEMBL2429706.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ63645.

Proteomic databases

PaxDbiQ63645.
PRIDEiQ63645.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000061580; ENSRNOP00000058298; ENSRNOG00000018003.
GeneIDi116677.
KEGGirno:116677.
UCSCiRGD:620866. rat.

Organism-specific databases

CTDi2150.
RGDi620866. F2rl1.

Phylogenomic databases

eggNOGiENOG410IGEM. Eukaryota.
ENOG4111CWR. LUCA.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG105658.
InParanoidiQ63645.
KOiK04234.
OMAiLAMYLIC.
OrthoDBiEOG7DNNVR.

Enzyme and pathway databases

ReactomeiR-RNO-375276. Peptide ligand-binding receptors.
R-RNO-416476. G alpha (q) signalling events.

Miscellaneous databases

PMAP-CutDBQ63645.
PROiQ63645.

Gene expression databases

GenevisibleiQ63645. RN.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002281. Pro_rcpt_2.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01152. PROTEASEAR2.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue."
    Saifeddine M., Al-Ani B., Cheng C.H., Wang L., Hollenberg M.D.
    Br. J. Pharmacol. 118:521-530(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Intestine and Kidney.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  3. "Protease-activated receptor-2 activation causes EDHF-like coronary vasodilation: selective preservation in ischemia/reperfusion injury: involvement of lipoxygenase products, VR1 receptors, and C-fibers."
    McLean P.G., Aston D., Sarkar D., Ahluwalia A.
    Circ. Res. 90:465-472(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "p24A, a type I transmembrane protein, controls ARF1-dependent resensitization of protease-activated receptor-2 by influence on receptor trafficking."
    Luo W., Wang Y., Reiser G.
    J. Biol. Chem. 282:30246-30255(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TMED2.

Entry informationi

Entry nameiPAR2_RAT
AccessioniPrimary (citable) accession number: Q63645
Secondary accession number(s): Q499T9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding second extracellular loop to mediate signaling.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.