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Protein

N-arachidonyl glycine receptor

Gene

GPR18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for endocannabinoid N-arachidonyl glycine (NAGly) (PubMed:16844083, PubMed:24762058, PubMed:27572937). However, conflicting results about the role of NAGly as an agonist are reported (PubMed:27018161). Can also be activated by plant-derived and synthetic cannabinoid agonists (PubMed:24762058). The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase (PubMed:16844083). May contribute to regulation of the immune system. Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small intstine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (By similarity). Plays a role in hypotensive responses, mediating reduction in intraocular and blood pressure (By similarity). Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis (PubMed:27572937).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-373076. Class A/1 (Rhodopsin-like receptors).
R-HSA-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
N-arachidonyl glycine receptor
Short name:
NAGly receptor
Alternative name(s):
G-protein coupled receptor 18
Gene namesi
Name:GPR18
Synonyms:GPCRW
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:4472. GPR18.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 26ExtracellularSequence analysisAdd BLAST26
Transmembranei27 – 47Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini48 – 56CytoplasmicSequence analysis9
Transmembranei57 – 77Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini78 – 95ExtracellularSequence analysisAdd BLAST18
Transmembranei96 – 116Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini117 – 138CytoplasmicSequence analysisAdd BLAST22
Transmembranei139 – 159Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini160 – 191ExtracellularSequence analysisAdd BLAST32
Transmembranei192 – 212Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini213 – 232CytoplasmicSequence analysisAdd BLAST20
Transmembranei233 – 253Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini254 – 268ExtracellularSequence analysisAdd BLAST15
Transmembranei269 – 289Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini290 – 331CytoplasmicSequence analysisAdd BLAST42

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi108A → N: Increased cell surface expression. 1 Publication1

Organism-specific databases

DisGeNETi2841.
OpenTargetsiENSG00000125245.
PharmGKBiPA28860.

Chemistry databases

ChEMBLiCHEMBL2384898.
DrugBankiDB00145. Glycine.
GuidetoPHARMACOLOGYi89.

Polymorphism and mutation databases

BioMutaiGPR18.
DMDMi92087006.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000695371 – 331N-arachidonyl glycine receptorAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi14N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi94 ↔ 172PROSITE-ProRule annotation
Modified residuei322PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ14330.
PaxDbiQ14330.
PeptideAtlasiQ14330.
PRIDEiQ14330.

PTM databases

iPTMnetiQ14330.
PhosphoSitePlusiQ14330.

Expressioni

Tissue specificityi

Expressed in midpiece of spermatozoon (at protein level) (PubMed:27572937). Most abundant in testis and spleen (PubMed:16844083). Highly expressed in CD4 and CD8-positive T-cells as well as CD19-positive B-cells (PubMed:16844083).2 Publications

Gene expression databases

BgeeiENSG00000125245.
CleanExiHS_GPR18.
ExpressionAtlasiQ14330. baseline and differential.
GenevisibleiQ14330. HS.

Organism-specific databases

HPAiHPA013873.

Interactioni

Protein-protein interaction databases

BioGridi109100. 13 interactors.
STRINGi9606.ENSP00000343428.

Chemistry databases

BindingDBiQ14330.

Structurei

3D structure databases

ProteinModelPortaliQ14330.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFPC. Eukaryota.
ENOG410YP7X. LUCA.
GeneTreeiENSGT00730000110768.
HOGENOMiHOG000112785.
HOVERGENiHBG105013.
InParanoidiQ14330.
KOiK08410.
OMAiSLPFRMF.
OrthoDBiEOG091G0BF1.
PhylomeDBiQ14330.
TreeFamiTF330775.

Family and domain databases

InterProiView protein in InterPro
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028335. GPR18.
PANTHERiPTHR24232:SF70. PTHR24232:SF70. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q14330-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MITLNNQDQP VPFNSSHPDE YKIAALVFYS CIFIIGLFVN ITALWVFSCT
60 70 80 90 100
TKKRTTVTIY MMNVALVDLI FIMTLPFRMF YYAKDEWPFG EYFCQILGAL
110 120 130 140 150
TVFYPSIALW LLAFISADRY MAIVQPKYAK ELKNTCKAVL ACVGVWIMTL
160 170 180 190 200
TTTTPLLLLY KDPDKDSTPA TCLKISDIIY LKAVNVLNLT RLTFFFLIPL
210 220 230 240 250
FIMIGCYLVI IHNLLHGRTS KLKPKVKEKS IRIIITLLVQ VLVCFMPFHI
260 270 280 290 300
CFAFLMLGTG ENSYNPWGAF TTFLMNLSTC LDVILYYIVS KQFQARVISV
310 320 330
MLYRNYLRSM RRKSFRSGSL RSLSNINSEM L
Length:331
Mass (Da):38,134
Last modified:March 7, 2006 - v2
Checksum:i5B0B755A74FBBB36
GO

Sequence cautioni

The sequence AAG44671 differs from that shown. Reason: Frameshift at positions 78, 81 and 129.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12P → T in AAB65819 (PubMed:9205118).Curated1
Sequence conflicti86E → A in AAB65819 (PubMed:9205118).Curated1
Sequence conflicti97L → I in AAB65819 (PubMed:9205118).Curated1
Sequence conflicti102V → G in AAG44671 (Ref. 3) Curated1
Sequence conflicti112L → F in AAG44671 (Ref. 3) Curated1
Sequence conflicti145V → SS in AAG44671 (Ref. 3) Curated1
Sequence conflicti310M → L in AAB65819 (PubMed:9205118).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L42324 Genomic DNA. Translation: AAB65819.1.
AF261135 mRNA. Translation: AAG44671.1. Frameshift.
BT009907 mRNA. Translation: AAP88909.1.
AL160155 Genomic DNA. No translation available.
BC008569 mRNA. Translation: AAH08569.1.
BC050646 mRNA. Translation: AAH50646.1.
BC066927 mRNA. Translation: AAH66927.1.
CCDSiCCDS9491.1.
RefSeqiNP_001091670.1. NM_001098200.1.
NP_005283.1. NM_005292.3.
XP_006720009.1. XM_006719946.3.
UniGeneiHs.741589.

Genome annotation databases

EnsembliENST00000340807; ENSP00000343428; ENSG00000125245.
ENST00000397470; ENSP00000380610; ENSG00000125245.
ENST00000397473; ENSP00000380613; ENSG00000125245.
GeneIDi2841.
KEGGihsa:2841.
UCSCiuc001voe.5. human.

Similar proteinsi

Entry informationi

Entry nameiGPR18_HUMAN
AccessioniPrimary (citable) accession number: Q14330
Secondary accession number(s): Q6GTM3, Q96HI6, Q9H2L2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 7, 2006
Last modified: August 30, 2017
This is version 154 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families