GPR18_HUMAN
ID GPR18_HUMAN Reviewed; 331 AA.
AC Q14330; Q6GTM3; Q96HI6; Q9H2L2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=N-arachidonyl glycine receptor;
DE Short=NAGly receptor;
DE AltName: Full=G-protein coupled receptor 18;
GN Name=GPR18; Synonyms=GPCRW;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9205118; DOI=10.1006/geno.1997.4752;
RA Gantz I., Muraoka A., Yang Y.-K., Samuelson L.C., Zimmerman E.M., Cook H.,
RA Yamada T.;
RT "Cloning and chromosomal localization of a gene (GPR18) encoding a novel
RT seven transmembrane receptor highly expressed in spleen and testis.";
RL Genomics 42:462-466(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16844083; DOI=10.1016/j.bbrc.2006.06.175;
RA Kohno M., Hasegawa H., Inoue A., Muraoka M., Miyazaki T., Oka K.,
RA Yasukawa M.;
RT "Identification of N-arachidonylglycine as the endogenous ligand for orphan
RT G-protein-coupled receptor GPR18.";
RL Biochem. Biophys. Res. Commun. 347:827-832(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dendritic cell;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RT "Novel genes expressed in human dendritic cell.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Testis;
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 [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24762058; DOI=10.1111/bph.12746;
RA Console-Bram L., Brailoiu E., Brailoiu G.C., Sharir H., Abood M.E.;
RT "Activation of GPR18 by cannabinoid compounds: a tale of biased agonism.";
RL Br. J. Pharmacol. 171:3908-3917(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ALA-108.
RX PubMed=27018161; DOI=10.7717/peerj.1835;
RA Finlay D.B., Joseph W.R., Grimsey N.L., Glass M.;
RT "GPR18 undergoes a high degree of constitutive trafficking but is
RT unresponsive to N-Arachidonoyl Glycine.";
RL PeerJ 4:E1835-E1835(2016).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27572937; DOI=10.1038/srep32255;
RA Flegel C., Vogel F., Hofreuter A., Wojcik S., Schoeder C.,
RA Kiec-Kononowicz K., Brockmeyer N.H., Mueller C.E., Becker C.,
RA Altmueller J., Hatt H., Gisselmann G.;
RT "Characterization of non-olfactory GPCRs in human sperm with a focus on
RT GPR18.";
RL Sci. Rep. 6:32255-32255(2016).
CC -!- FUNCTION: Receptor for endocannabinoid N-arachidonyl glycine (NAGly)
CC (PubMed:16844083, PubMed:24762058, PubMed:27572937). However,
CC conflicting results about the role of NAGly as an agonist are reported
CC (PubMed:27018161). Can also be activated by plant-derived and synthetic
CC cannabinoid agonists (PubMed:24762058). The activity of this receptor
CC is mediated by G proteins which inhibit adenylyl cyclase
CC (PubMed:16844083). May contribute to regulation of the immune system.
CC Is required for normal homeostasis of CD8+ subsets of intraepithelial
CC lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small
CC intstine by supporting preferential migration of CD8alphaalpha T-cells
CC to intraepithelial compartment over lamina propria compartment, and by
CC mediating their reconstitution into small intestine after bone marrow
CC transplant (By similarity). Plays a role in hypotensive responses,
CC mediating reduction in intraocular and blood pressure (By similarity).
CC Mediates NAGly-induced process of reorganization of actin filaments and
CC induction of acrosomal exocytosis (PubMed:27572937).
CC {ECO:0000250|UniProtKB:Q8K1Z6, ECO:0000269|PubMed:16844083,
CC ECO:0000269|PubMed:24762058, ECO:0000269|PubMed:27572937}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24762058,
CC ECO:0000269|PubMed:27018161}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:24762058}.
CC -!- TISSUE SPECIFICITY: Expressed in midpiece of spermatozoon (at protein
CC level) (PubMed:27572937). Most abundant in testis and spleen
CC (PubMed:16844083). Highly expressed in CD4 and CD8-positive T-cells as
CC well as CD19-positive B-cells (PubMed:16844083).
CC {ECO:0000269|PubMed:16844083, ECO:0000269|PubMed:27572937}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44671.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L42324; AAB65819.1; -; Genomic_DNA.
DR EMBL; AF261135; AAG44671.1; ALT_FRAME; mRNA.
DR EMBL; BT009907; AAP88909.1; -; mRNA.
DR EMBL; AL160155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008569; AAH08569.1; -; mRNA.
DR EMBL; BC050646; AAH50646.1; -; mRNA.
DR EMBL; BC066927; AAH66927.1; -; mRNA.
DR CCDS; CCDS9491.1; -.
DR RefSeq; NP_001091670.1; NM_001098200.1.
DR RefSeq; NP_005283.1; NM_005292.3.
DR RefSeq; XP_006720009.1; XM_006719946.3.
DR AlphaFoldDB; Q14330; -.
DR SMR; Q14330; -.
DR BioGRID; 109100; 106.
DR IntAct; Q14330; 11.
DR STRING; 9606.ENSP00000343428; -.
DR BindingDB; Q14330; -.
DR ChEMBL; CHEMBL2384898; -.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR DrugCentral; Q14330; -.
DR GuidetoPHARMACOLOGY; 89; -.
DR GlyGen; Q14330; 1 site.
DR iPTMnet; Q14330; -.
DR PhosphoSitePlus; Q14330; -.
DR BioMuta; GPR18; -.
DR DMDM; 92087006; -.
DR MassIVE; Q14330; -.
DR PaxDb; Q14330; -.
DR PeptideAtlas; Q14330; -.
DR PRIDE; Q14330; -.
DR ProteomicsDB; 59966; -.
DR Antibodypedia; 2954; 373 antibodies from 30 providers.
DR DNASU; 2841; -.
DR Ensembl; ENST00000340807.3; ENSP00000343428.3; ENSG00000125245.14.
DR Ensembl; ENST00000397470.5; ENSP00000380610.2; ENSG00000125245.14.
DR Ensembl; ENST00000397473.7; ENSP00000380613.2; ENSG00000125245.14.
DR Ensembl; ENST00000416594.2; ENSP00000401611.2; ENSG00000125245.14.
DR GeneID; 2841; -.
DR KEGG; hsa:2841; -.
DR MANE-Select; ENST00000397470.5; ENSP00000380610.2; NM_001098200.2; NP_001091670.1.
DR UCSC; uc001voe.5; human.
DR CTD; 2841; -.
DR DisGeNET; 2841; -.
DR GeneCards; GPR18; -.
DR HGNC; HGNC:4472; GPR18.
DR HPA; ENSG00000125245; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MIM; 602042; gene.
DR neXtProt; NX_Q14330; -.
DR OpenTargets; ENSG00000125245; -.
DR PharmGKB; PA28860; -.
DR VEuPathDB; HostDB:ENSG00000125245; -.
DR eggNOG; ENOG502QT1V; Eukaryota.
DR GeneTree; ENSGT01050000244980; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q14330; -.
DR OMA; CYLVIIY; -.
DR OrthoDB; 1122184at2759; -.
DR PhylomeDB; Q14330; -.
DR TreeFam; TF330775; -.
DR PathwayCommons; Q14330; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q14330; -.
DR BioGRID-ORCS; 2841; 2 hits in 1066 CRISPR screens.
DR ChiTaRS; GPR18; human.
DR GeneWiki; GPR18; -.
DR GenomeRNAi; 2841; -.
DR Pharos; Q14330; Tchem.
DR PRO; PR:Q14330; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q14330; protein.
DR Bgee; ENSG00000125245; Expressed in sperm and 116 other tissues.
DR ExpressionAtlas; Q14330; baseline and differential.
DR Genevisible; Q14330; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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; IEA:Ensembl.
DR GO; GO:0002305; P:CD8-positive, gamma-delta intraepithelial T cell differentiation; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0002689; P:negative regulation of leukocyte chemotaxis; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
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_0000069537"
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..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..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:0000250|UniProtKB:Q8K1Z6"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 108
FT /note="A->N: Increased cell surface expression."
FT /evidence="ECO:0000269|PubMed:27018161"
FT CONFLICT 12
FT /note="P -> T (in Ref. 1; AAB65819)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="E -> A (in Ref. 1; AAB65819)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="L -> I (in Ref. 1; AAB65819)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="V -> G (in Ref. 3; AAG44671)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="L -> F (in Ref. 3; AAG44671)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="V -> SS (in Ref. 3; AAG44671)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="M -> L (in Ref. 1; AAB65819)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 38134 MW; 5B0B755A74FBBB36 CRC64;
MITLNNQDQP VPFNSSHPDE YKIAALVFYS CIFIIGLFVN ITALWVFSCT TKKRTTVTIY
MMNVALVDLI FIMTLPFRMF YYAKDEWPFG EYFCQILGAL TVFYPSIALW LLAFISADRY
MAIVQPKYAK ELKNTCKAVL ACVGVWIMTL TTTTPLLLLY KDPDKDSTPA TCLKISDIIY
LKAVNVLNLT RLTFFFLIPL FIMIGCYLVI IHNLLHGRTS KLKPKVKEKS IRIIITLLVQ
VLVCFMPFHI CFAFLMLGTG ENSYNPWGAF TTFLMNLSTC LDVILYYIVS KQFQARVISV
MLYRNYLRSM RRKSFRSGSL RSLSNINSEM L
