PAR2_BOVIN
ID PAR2_BOVIN Reviewed; 395 AA.
AC Q2HJA4;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 25-MAY-2022, entry version 92.
DE RecName: Full=Proteinase-activated receptor 2;
DE Short=PAR-2;
DE AltName: Full=Coagulation factor II receptor-like 1;
DE AltName: Full=Thrombin receptor-like 1;
DE Flags: Precursor;
GN Name=F2RL1; Synonyms=PAR2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G
CC proteins. Its function is mediated through the activation of several
CC signaling pathways including phospholipase C (PLC), intracellular
CC calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-
CC kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1.
CC Involved in modulation of inflammatory responses and regulation of
CC innate and adaptive immunity, and acts as a sensor for proteolytic
CC enzymes generated during infection. Generally is promoting
CC inflammation. Can signal synergistically with TLR4 and probably TLR2 in
CC inflammatory responses and modulates TLR3 signaling. Has a protective
CC role in establishing the endothelial barrier; the activity involves
CC coagulation factor X. Regulates endothelial cell barrier integrity
CC during neutrophil extravasation, probably following proteolytic
CC cleavage by PRTN3. Proposed to have a bronchoprotective role in airway
CC epithelium, but also shown to compromise the airway epithelial barrier
CC by interrupting E-cadherin adhesion. Involved in the regulation of
CC vascular tone; activation results in hypotension presumably mediated by
CC vasodilation. Associates with a subset of G proteins alpha subunits
CC such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o)
CC alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. Believed to be a
CC class B receptor which internalizes as a complex with arrestin and
CC traffic with it to endosomal vesicles, presumably as desensitized
CC receptor, for extended periods of time. Mediates inhibition of TNF-
CC alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11;
CC the function involves dissociation of RIPK1 and TRADD from TNFR1.
CC Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at
CC 'Ser-536'; the function involves IKBKB and is predominantly independent
CC of G proteins. Involved in cellular migration. Involved in cytoskeletal
CC rearrangement and chemotaxis through beta-arrestin-promoted scaffolds;
CC the function is independent of GNAQ and GNA11 and involves promotion of
CC cofilin dephosphorylation and actin filament severing. Induces
CC redistribution of COPS5 from the plasma membrane to the cytosol and
CC activation of the JNK cascade is mediated by COPS5. Involved in the
CC recruitment of leukocytes to the sites of inflammation and is the major
CC PAR receptor capable of modulating eosinophil function such as pro-
CC inflammatory cytokine secretion, superoxide production and
CC degranulation. During inflammation promotes dendritic cell maturation,
CC trafficking to the lymph nodes and subsequent T-cell activation.
CC Involved in antimicrobial response of innate immune cells; activation
CC enhances phagocytosis of Gram-positive and killing of Gram-negative
CC bacteria. Acts synergistically with interferon-gamma in enhancing
CC antiviral responses. {ECO:0000250|UniProtKB:P55085}.
CC -!- SUBUNIT: Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ,
CC GNA11, GNA12, GNA13 and GNA14 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein.
CC -!- PTM: A proteolytic cleavage generates a new N-terminus that functions
CC as a tethered ligand. Activating serine proteases include trypsin, mast
CC cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and
CC membrane-type serine protease 1/ST14. Proposed subsequent cleavage by
CC serine proteases is leading to receptor deactivation and include
CC neutrophil elastase and cathepsin G. At least in part, implicated
CC proteases are also shown to activate the receptor; the glycosylation
CC status of the receptor is thought to contribute to the difference.
CC {ECO:0000250|UniProtKB:P55085}.
CC -!- PTM: N-glycosylated and sialylated. {ECO:0000250|UniProtKB:P55085}.
CC -!- PTM: Multiple phosphorylated on serine and threonine residues in the
CC cytoplasmic region upon receptor activation; required for receptor
CC desensitization and recruitment of beta-arrestin.
CC -!- PTM: Monoubiquitinated by CBL at the plasma membrane and in early
CC endosomes; not required for receptor endocytosis but for translocation
CC to late endosomes or lysosomes. Deubiquitination involves STAMBP and
CC USP8; required for lysosomal trafficking and receptor degradation (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Synthetic PAR agonist peptides (APs) that mimic the
CC first six amino acids of the newly formed N-terminus activate the
CC native, uncleaved receptor nonenzymatically by binding directly to the
CC corresponding second extracellular loop to mediate signaling.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; BC113233; AAI13234.1; -; mRNA.
DR RefSeq; NP_001039748.1; NM_001046283.1.
DR AlphaFoldDB; Q2HJA4; -.
DR SMR; Q2HJA4; -.
DR STRING; 9913.ENSBTAP00000046225; -.
DR PaxDb; Q2HJA4; -.
DR GeneID; 526525; -.
DR KEGG; bta:526525; -.
DR CTD; 2150; -.
DR eggNOG; ENOG502QR8S; Eukaryota.
DR InParanoid; Q2HJA4; -.
DR OrthoDB; 892946at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031143; C:pseudopodium; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR GO; GO:0031681; F:G-protein beta-subunit binding; ISS:UniProtKB.
DR GO; GO:0015057; F:thrombin-activated receptor activity; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050900; P:leukocyte migration; ISS:UniProtKB.
DR GO; GO:0070661; P:leukocyte proliferation; ISS:UniProtKB.
DR GO; GO:0097029; P:mature conventional dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0042119; P:neutrophil activation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISS:UniProtKB.
DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; ISS:UniProtKB.
DR GO; GO:1900135; P:positive regulation of renin secretion into blood stream; ISS:UniProtKB.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0002286; P:T cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0042311; P:vasodilation; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002281; Pro_rcpt_2.
DR InterPro; IPR003912; Protea_act_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01428; PROTEASEAR.
DR PRINTS; PR01152; PROTEASEAR2.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Immunity; Inflammatory response; Innate immunity; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Signal;
KW Transducer; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..34
FT /note="Removed for receptor activation"
FT /evidence="ECO:0000250"
FT /id="PRO_0000239869"
FT CHAIN 35..395
FT /note="Proteinase-activated receptor 2"
FT /id="PRO_0000239870"
FT TOPO_DOM 35..69
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 70..99
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 100..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 107..135
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 136..147
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 148..175
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 176..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 182..209
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 210..233
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 234..267
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 268..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 276..315
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 316..321
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TRANSMEM 322..345
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT TOPO_DOM 346..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55085"
FT SITE 34..35
FT /note="Cleavage; by trypsin"
FT /evidence="ECO:0000250"
FT LIPID 359
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 146..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 395 AA; 43766 MW; 8203BFCC68718139 CRC64;
MRSPSAAWLL GGVLLLAASG SCNRTVPGNK SKGRSLIGNV DNSPVVAGRG VTVKPGFSVD
EFSTSVLTGK LTTVFLPVVY TIVFVVGLPS NGMALWVFLF RTKKKHPAVI YMANLALADL
LSVTWFPLKI AYHIHGNNWI YGESLCKVLI GFFYGNMYCS ILFMTCLSVQ RYWVIVNPMV
HPKKQANIAI GVSLGIWLLI LLLTIPLYVV KQTSYIRALN ITTCHDVLPE EVLVGDMFNY
FLSLAIGVFL FPAFLTASAY VLMIRTLQSS AMDESSGKKR RRAIKLIVTV LAMYLICFTP
SNLLLVVHYF LIKTRGQSHV YALYIVALCL STLNSCIDPF VYYFISQDFR DHAKNALLCR
SVRTVKRMQV SLSSKKFSGK SSSYSSSSTS VKGSY
