GPR18_MOUSE
ID GPR18_MOUSE Reviewed; 331 AA.
AC Q8K1Z6; Q3T9N3;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=N-arachidonyl glycine receptor;
DE Short=NAGly receptor;
DE AltName: Full=G-protein coupled receptor 18;
GN Name=Gpr18 {ECO:0000312|EMBL:AAH34872.1, ECO:0000312|MGI:MGI:107859};
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] {ECO:0000312|EMBL:BAE42987.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD {ECO:0000312|EMBL:BAE42987.1};
RC TISSUE=Spleen {ECO:0000312|EMBL:BAE42987.1};
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] {ECO:0000312|EMBL:AAH34872.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH34872.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH34872.1};
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23461720; DOI=10.1111/bph.12136;
RA Caldwell M.D., Hu S.S., Viswanathan S., Bradshaw H., Kelly M.E.,
RA Straiker A.;
RT "A GPR18-based signalling system regulates IOP in murine eye.";
RL Br. J. Pharmacol. 169:834-843(2013).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23104136; DOI=10.1124/mol.112.081182;
RA Lu V.B., Puhl H.L. III, Ikeda S.R.;
RT "N-Arachidonyl glycine does not activate G protein-coupled receptor 18
RT signaling via canonical pathways.";
RL Mol. Pharmacol. 83:267-282(2013).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25348153; DOI=10.1084/jem.20140646;
RA Wang X., Sumida H., Cyster J.G.;
RT "GPR18 is required for a normal CD8alphaalpha intestinal intraepithelial
RT lymphocyte compartment.";
RL J. Exp. Med. 211:2351-2359(2014).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26197390; DOI=10.1371/journal.pone.0133854;
RA Becker A.M., Callahan D.J., Richner J.M., Choi J., DiPersio J.F.,
RA Diamond M.S., Bhattacharya D.;
RT "GPR18 controls reconstitution of mouse small intestine intraepithelial
RT lymphocytes following bone marrow transplantation.";
RL PLoS ONE 10:E0133854-E0133854(2015).
RN [8]
RP FUNCTION.
RX PubMed=27893106; DOI=10.1167/iovs.16-19437;
RA Miller S., Leishman E., Oehler O., Daily L., Murataeva N., Wager-Miller J.,
RA Bradshaw H., Straiker A.;
RT "Evidence for a GPR18 role in diurnal regulation of intraocular pressure.";
RL Invest. Ophthalmol. Vis. Sci. 57:6419-6426(2016).
CC -!- FUNCTION: Receptor for endocannabinoid N-arachidonyl glycine (NAGly)
CC (By similarity). However, conflicting results about the role of NAGly
CC as an agonist are reported (PubMed:23104136). Can also be activated by
CC plant-derived and synthetic cannabinoid agonists (By similarity). The
CC activity of this receptor is mediated by G proteins which inhibit
CC adenylyl cyclase (By similarity). May contribute to regulation of the
CC immune system (By similarity). Is required for normal homeostasis of
CC CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and
CC CD8alphabeta IELs) in small intstine by supporting preferential
CC migration of CD8alphaalpha T-cells to intraepithelial compartment over
CC lamina propria compartment, and by mediating their reconstitution into
CC small intestine after bone marrow transplant (PubMed:25348153,
CC PubMed:26197390). Plays a role in hypotensive responses, mediating
CC reduction in intraocular and blood pressure (PubMed:23461720,
CC PubMed:27893106). Mediates NAGly-induced process of reorganization of
CC actin filaments and induction of acrosomal exocytosis (By similarity).
CC {ECO:0000250|UniProtKB:Q14330, ECO:0000269|PubMed:23104136,
CC ECO:0000269|PubMed:23461720, ECO:0000269|PubMed:25348153,
CC ECO:0000269|PubMed:26197390, ECO:0000269|PubMed:27893106}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23104136};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q14330}.
CC -!- TISSUE SPECIFICITY: Expressed in the eye including cornea, retina, iris
CC and ciliary epithelium (at protein level) (PubMed:23461720). Expressed
CC in spleen, liver and lymphocytes with highest expression levels in
CC intestinal intraepithelial lymphocytes (PubMed:25348153,
CC PubMed:26197390). {ECO:0000269|PubMed:23461720,
CC ECO:0000269|PubMed:25348153, ECO:0000269|PubMed:26197390}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:26197390). However,
CC reduced number of CD8alphaalpha gammadeltaT IELs has been reported
CC (PubMed:25348153). {ECO:0000269|PubMed:25348153,
CC ECO:0000269|PubMed:26197390}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AK156039; BAE33557.1; -; mRNA.
DR EMBL; AK156868; BAE33880.1; -; mRNA.
DR EMBL; AK157029; BAE33938.1; -; mRNA.
DR EMBL; AK172401; BAE42987.1; -; mRNA.
DR EMBL; BC034872; AAH34872.1; -; mRNA.
DR CCDS; CCDS27342.1; -.
DR RefSeq; NP_877958.1; NM_182806.1.
DR AlphaFoldDB; Q8K1Z6; -.
DR SMR; Q8K1Z6; -.
DR IntAct; Q8K1Z6; 1.
DR STRING; 10090.ENSMUSP00000061410; -.
DR GlyGen; Q8K1Z6; 2 sites.
DR iPTMnet; Q8K1Z6; -.
DR PhosphoSitePlus; Q8K1Z6; -.
DR PaxDb; Q8K1Z6; -.
DR PRIDE; Q8K1Z6; -.
DR ProteomicsDB; 271448; -.
DR Antibodypedia; 2954; 373 antibodies from 30 providers.
DR DNASU; 110168; -.
DR Ensembl; ENSMUST00000055475; ENSMUSP00000061410; ENSMUSG00000050350.
DR GeneID; 110168; -.
DR KEGG; mmu:110168; -.
DR UCSC; uc007vap.1; mouse.
DR CTD; 2841; -.
DR MGI; MGI:107859; Gpr18.
DR VEuPathDB; HostDB:ENSMUSG00000050350; -.
DR eggNOG; ENOG502QT1V; Eukaryota.
DR GeneTree; ENSGT01050000244980; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q8K1Z6; -.
DR OMA; CYLVIIY; -.
DR OrthoDB; 1122184at2759; -.
DR PhylomeDB; Q8K1Z6; -.
DR TreeFam; TF330775; -.
DR Reactome; R-MMU-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 110168; 0 hits in 76 CRISPR screens.
DR PRO; PR:Q8K1Z6; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8K1Z6; protein.
DR Bgee; ENSMUSG00000050350; Expressed in peripheral lymph node and 54 other tissues.
DR Genevisible; Q8K1Z6; MM.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0002300; P:CD8-positive, alpha-beta intraepithelial T cell differentiation; IDA:MGI.
DR GO; GO:0002305; P:CD8-positive, gamma-delta intraepithelial T cell differentiation; IDA:MGI.
DR GO; GO:0002689; P:negative regulation of leukocyte chemotaxis; IMP:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP: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:0035025; P:positive regulation of Rho protein signal transduction; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR028335; GPR18.
DR PANTHER; PTHR24232:SF1; PTHR24232:SF1; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..331
FT /note="N-arachidonyl glycine receptor"
FT /id="PRO_0000278174"
FT TOPO_DOM 1..26
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..138
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..191
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..268
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 23
FT /note="I -> V (in Ref. 1; BAE42987)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 37691 MW; 702FD55C911B4787 CRC64;
MATLSNHNQL DLSNGSHPEE YKIAALVFYS CIFLIGLFVN VTALWVFSCT TKKRTTVTIY
MMNVALLDLV FILSLPFRMF YYAKGEWPFG EYFCHILGAL VVFYPSLALW LLAFISADRY
MAIVQPKYAK ELKNTGKAVL ACGGVWVMTL TTTVPLLLLY EDPDKASSPA TCLKISDITH
LKAVNVLNFT RLIFFFLIPL FIMIGCYVVI IHSLLRGQTS KLKPKVKEKS IRIIMTLLLQ
VLVCFVPFHI CFAVLMLQGQ ENSYSPWGAF TTFLMNLSTC LDVVLYYIVS KQFQARVISV
MLYRNYLRSV RRKSVRSGSL RSLSNMNSEM L
