GPR4_MOUSE
ID GPR4_MOUSE Reviewed; 365 AA.
AC Q8BUD0;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=G-protein coupled receptor 4;
GN Name=Gpr4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17145776; DOI=10.1128/mcb.01909-06;
RA Yang L.V., Radu C.G., Roy M., Lee S., McLaughlin J., Teitell M.A.,
RA Iruela-Arispe M.L., Witte O.N.;
RT "Vascular abnormalities in mice deficient for the G protein-coupled
RT receptor GPR4 that functions as a pH sensor.";
RL Mol. Cell. Biol. 27:1334-1347(2007).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=26068853; DOI=10.1126/science.aaa0922;
RA Kumar N.N., Velic A., Soliz J., Shi Y., Li K., Wang S., Weaver J.L.,
RA Sen J., Abbott S.B., Lazarenko R.M., Ludwig M.G., Perez-Reyes E.,
RA Mohebbi N., Bettoni C., Gassmann M., Suply T., Seuwen K., Guyenet P.G.,
RA Wagner C.A., Bayliss D.A.;
RT "PHYSIOLOGY. Regulation of breathing by CO(2) requires the proton-activated
RT receptor GPR4 in retrotrapezoid nucleus neurons.";
RL Science 348:1255-1260(2015).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32058960; DOI=10.1016/j.isci.2020.100848;
RA Krewson E.A., Sanderlin E.J., Marie M.A., Akhtar S.N., Velcicky J.,
RA Loetscher P., Yang L.V.;
RT "The Proton-Sensing GPR4 Receptor Regulates Paracellular Gap Formation and
RT Permeability of Vascular Endothelial Cells.";
RL IScience 23:100848-100848(2020).
CC -!- FUNCTION: Proton-sensing G-protein coupled receptor couples to multiple
CC intracellular signaling pathways, including GNAS/cAMP,
CC GNAQ/phospholipase C (PLC), and GNA12/GNA13/Rho pathways
CC (PubMed:17145776). Acidosis-induced GPR4 activation increases
CC paracellular gap formation and permeability of vascular endothelial
CC cells through the GNA12/GNA13/Rho GTPase signaling pathway
CC (PubMed:32058960). In the brain may mediate central respiratory
CC sensitivity to CO(2)/H(+) (PubMed:26068853).
CC {ECO:0000269|PubMed:17145776, ECO:0000269|PubMed:26068853,
CC ECO:0000269|PubMed:32058960}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P46093};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Detected in neurons of the brain-stem
CC retrotrapezoid nucleus (RTN). {ECO:0000269|PubMed:26068853}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice display partial neonatal and
CC postnatal lethality, hemorrhages, impaired association of vascular
CC smooth muscle cells with capillaries and small arteries and veins, and
CC impaired contact between mesangial cells and renal glomerular
CC capillaries (PubMed:17145776). The inflammatory response is reduced in
CC an inflammatory hindlimb ischemia-reperfusion model (PubMed:26068853).
CC Deficient mice display reduced central respiratory chemoreflex,
CC increased apnea frequency, and blunted ventilatory responses to CO2
CC (PubMed:32058960). {ECO:0000269|PubMed:17145776,
CC ECO:0000269|PubMed:26068853, ECO:0000269|PubMed:32058960}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AK085829; BAC39547.1; -; mRNA.
DR EMBL; CH466639; EDL23124.1; -; Genomic_DNA.
DR EMBL; BC099398; AAH99398.1; -; mRNA.
DR CCDS; CCDS20893.1; -.
DR RefSeq; NP_783599.1; NM_175668.4.
DR RefSeq; XP_006540111.1; XM_006540048.3.
DR AlphaFoldDB; Q8BUD0; -.
DR SMR; Q8BUD0; -.
DR STRING; 10090.ENSMUSP00000061243; -.
DR BindingDB; Q8BUD0; -.
DR ChEMBL; CHEMBL4105764; -.
DR GlyGen; Q8BUD0; 2 sites.
DR PhosphoSitePlus; Q8BUD0; -.
DR PaxDb; Q8BUD0; -.
DR PeptideAtlas; Q8BUD0; -.
DR PRIDE; Q8BUD0; -.
DR Antibodypedia; 2958; 211 antibodies from 30 providers.
DR DNASU; 319197; -.
DR Ensembl; ENSMUST00000060225; ENSMUSP00000061243; ENSMUSG00000044317.
DR GeneID; 319197; -.
DR KEGG; mmu:319197; -.
DR UCSC; uc009flb.2; mouse.
DR CTD; 2828; -.
DR MGI; MGI:2441992; Gpr4.
DR VEuPathDB; HostDB:ENSMUSG00000044317; -.
DR eggNOG; ENOG502QS9G; Eukaryota.
DR GeneTree; ENSGT01050000244810; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q8BUD0; -.
DR OMA; RTWEGCH; -.
DR OrthoDB; 716326at2759; -.
DR PhylomeDB; Q8BUD0; -.
DR TreeFam; TF331803; -.
DR Reactome; R-MMU-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 319197; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Gpr4; mouse.
DR PRO; PR:Q8BUD0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BUD0; protein.
DR Bgee; ENSMUSG00000044317; Expressed in molar tooth and 110 other tissues.
DR Genevisible; Q8BUD0; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:MGI.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IDA:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0072144; P:glomerular mesangial cell development; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IBA:GO_Central.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISO:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0043114; P:regulation of vascular permeability; IMP:UniProtKB.
DR GO; GO:0010447; P:response to acidic pH; IDA:MGI.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002276; GPR4_orph.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01147; GPR4RECEPTOR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
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 Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..365
FT /note="G-protein coupled receptor 4"
FT /id="PRO_0000379519"
FT TOPO_DOM 1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..94
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..179
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..291
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 92..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 365 AA; 41105 MW; 20D9F8128DE0EA37 CRC64;
MDNSTGTGEG CHVDSRVDHL FPPSLYIFVI GVGLPTNCLA LWAAYRQVRQ HNELGVYLMN
LSIADLLYIC TLPLWVDYFL HHDNWIHGPG SCKLFGFIFY SNIYISIAFL CCISVDRYLA
VAHPLRFARL RRVKTAVAVS SVVWATELGA NSAPLFHDEL FRDRYNHTFC FEKFPMERWV
AWMNLYRVFV GFLFPWALML LCYRGILRAV QSSVSTERQE KVKIKRLALS LIAIVLVCFA
PYHALLLSRS AVYLGRPWDC GFEERVFSAY HSSLAFTSLN CVADPILYCL VNEGARSDVA
KALHNLLRFL ASNKPQEMAN ASLTLETPLT SKRSTTGKSS GAVWAVPPTA QGDQVPLKVL
LPPAQ