ID   GPR55_HUMAN             Reviewed;         319 AA.
AC   Q9Y2T6; Q8N580;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 2.
DT   24-JAN-2024, entry version 164.
DE   RecName: Full=G-protein coupled receptor 55;
GN   Name=GPR55;
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 [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=9931487; DOI=10.1016/s0169-328x(98)00277-0;
RA   Sawzdargo M., Nguyen T., Lee D.K., Lynch K.R., Cheng R., Heng H.H.Q.,
RA   George S.R., O'Dowd B.F.;
RT   "Identification and cloning of three novel human G protein-coupled receptor
RT   genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human
RT   brain.";
RL   Brain Res. Mol. Brain Res. 64:193-198(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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   LIGAND-BINDING.
RX   PubMed=17765871; DOI=10.1016/j.bbrc.2007.08.078;
RA   Oka S., Nakajima K., Yamashita A., Kishimoto S., Sugiura T.;
RT   "Identification of GPR55 as a lysophosphatidylinositol receptor.";
RL   Biochem. Biophys. Res. Commun. 362:928-934(2007).
RN   [5]
RP   SUBCELLULAR LOCATION, CHARACTERIZATION, AND LIGAND-BINDING.
RX   PubMed=18757503; DOI=10.1096/fj.08-108670;
RA   Henstridge C.M., Balenga N.A., Ford L.A., Ross R.A., Waldhoer M.,
RA   Irving A.J.;
RT   "The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent
RT   Ca2+ signaling and NFAT activation.";
RL   FASEB J. 23:183-193(2009).
RN   [6]
RP   LIGAND-BINDING.
RX   PubMed=19723626; DOI=10.1074/jbc.m109.050187;
RA   Kapur A., Zhao P., Sharir H., Bai Y., Caron M.G., Barak L.S., Abood M.E.;
RT   "Atypical responsiveness of the orphan receptor GPR55 to cannabinoid
RT   ligands.";
RL   J. Biol. Chem. 284:29817-29827(2009).
RN   [7]
RP   TISSUE SPECIFICITY, AND FUNCTION.
RX   PubMed=19805329; DOI=10.1073/pnas.0902743106;
RA   Whyte L.S., Ryberg E., Sims N.A., Ridge S.A., Mackie K., Greasley P.J.,
RA   Ross R.A., Rogers M.J.;
RT   "The putative cannabinoid receptor GPR55 affects osteoclast function in
RT   vitro and bone mass in vivo.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:16511-16516(2009).
RN   [8]
RP   FUNCTION.
RX   PubMed=36142844; DOI=10.3390/ijms231810932;
RA   Nakajima K., Oka S., Tanikawa T., Nemoto-Sasaki Y., Matsumoto N.,
RA   Ishiguro H., Arata Y., Sugiura T., Yamashita A.;
RT   "Lysophosphatidylinositol Induced Morphological Changes and Stress Fiber
RT   Formation through the GPR55-RhoA-ROCK Pathway.";
RL   Int. J. Mol. Sci. 23:0-0(2022).
RN   [9]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=36523570; DOI=10.1038/s44161-022-00155-0;
RA   Guillamat-Prats R., Hering D., Derle A., Rami M., Haerdtner C.,
RA   Santovito D., Rinne P., Bindila L., Hristov M., Pagano S., Vuilleumier N.,
RA   Schmid S., Janjic A., Enard W., Weber C., Maegdefessel L., Faussner A.,
RA   Hilgendorf I., Steffens S.;
RT   "GPR55 in B cells limits atherosclerosis development and regulates plasma
RT   cell maturation.";
RL   Nat. Cardiovasc. Res. 1:1056-1071(2022).
RN   [10]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=37544935; DOI=10.1038/s41598-023-39904-x;
RA   Shimai R., Hanafusa K., Nakayama H., Oshima E., Kato M., Kano K.,
RA   Matsuo I., Miyazaki T., Tokano T., Hirabayashi Y., Iwabuchi K.,
RA   Minamino T.;
RT   "Lysophosphatidylglucoside/GPR55 signaling promotes foam cell formation in
RT   human M2c macrophages.";
RL   Sci. Rep. 13:12740-12740(2023).
CC   -!- FUNCTION: G-protein coupled receptor that binds to several ligands
CC       including 2-arachidonoyl lysophosphatidylinositol or
CC       lysophosphatidylglucoside with high affinity, leading to rapid and
CC       transient activation of numerous intracellular signaling pathways
CC       (PubMed:36142844, PubMed:36523570, PubMed:37544935). Induces the Ca(2+)
CC       release from intracellular stores via ERK, the heterotrimeric G protein
CC       GNA13 and RHOA leading to morphological changes including cell rounding
CC       and stress fiber formation (PubMed:36142844). In macrophages, acts
CC       downstream of lysophosphatidylglucoside to inhibit the translocation of
CC       the phospholipid-transporting ABCA1 to plasma membrane and subsequent
CC       cholesterol efflux leading to lipid accumulation and foam cell
CC       formation (PubMed:37544935). {ECO:0000269|PubMed:19805329,
CC       ECO:0000269|PubMed:36142844, ECO:0000269|PubMed:36523570,
CC       ECO:0000269|PubMed:37544935}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18757503};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:18757503}.
CC   -!- TISSUE SPECIFICITY: Expressed in the caudate nucleus and putamen, but
CC       not detected in the hippocampus, thalamus, pons cerebellum, frontal
CC       cortex of the brain or in the liver. Expressed in osteoclasts and
CC       osteoblasts. Higly expressed in macrophages and B-cells
CC       (PubMed:36523570, PubMed:37544935). {ECO:0000269|PubMed:19805329,
CC       ECO:0000269|PubMed:36523570, ECO:0000269|PubMed:37544935,
CC       ECO:0000269|PubMed:9931487}.
CC   -!- MISCELLANEOUS: The classification of this protein as a cannabinoid
CC       receptor remains a contentious issue due to conflicting pharmacological
CC       results.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD22410.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF096786; AAD22410.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; CR541776; CAG46575.1; -; mRNA.
DR   EMBL; BC032694; AAH32694.1; -; mRNA.
DR   CCDS; CCDS2480.1; -.
DR   RefSeq; NP_005674.2; NM_005683.3.
DR   RefSeq; XP_005247009.1; XM_005246952.3.
DR   RefSeq; XP_011510477.1; XM_011512175.2.
DR   RefSeq; XP_011510478.1; XM_011512176.2.
DR   AlphaFoldDB; Q9Y2T6; -.
DR   SMR; Q9Y2T6; -.
DR   BioGRID; 114705; 88.
DR   IntAct; Q9Y2T6; 2.
DR   STRING; 9606.ENSP00000498258; -.
DR   BindingDB; Q9Y2T6; -.
DR   ChEMBL; CHEMBL1075322; -.
DR   DrugBank; DB09061; Cannabidiol.
DR   DrugBank; DB14009; Medical Cannabis.
DR   DrugBank; DB14011; Nabiximols.
DR   DrugBank; DB06155; Rimonabant.
DR   DrugBank; DB11755; Tetrahydrocannabivarin.
DR   DrugCentral; Q9Y2T6; -.
DR   GuidetoPHARMACOLOGY; 109; -.
DR   GlyCosmos; Q9Y2T6; 2 sites, No reported glycans.
DR   GlyGen; Q9Y2T6; 2 sites.
DR   PhosphoSitePlus; Q9Y2T6; -.
DR   BioMuta; GPR55; -.
DR   DMDM; 71159390; -.
DR   MassIVE; Q9Y2T6; -.
DR   PaxDb; 9606-ENSP00000375894; -.
DR   PeptideAtlas; Q9Y2T6; -.
DR   ProteomicsDB; 85898; -.
DR   Antibodypedia; 20197; 236 antibodies from 26 providers.
DR   DNASU; 9290; -.
DR   Ensembl; ENST00000392039.2; ENSP00000375893.2; ENSG00000135898.10.
DR   Ensembl; ENST00000392040.5; ENSP00000375894.1; ENSG00000135898.10.
DR   Ensembl; ENST00000444078.5; ENSP00000410267.1; ENSG00000135898.10.
DR   Ensembl; ENST00000622008.4; ENSP00000482381.1; ENSG00000135898.10.
DR   Ensembl; ENST00000650999.1; ENSP00000498258.1; ENSG00000135898.10.
DR   GeneID; 9290; -.
DR   KEGG; hsa:9290; -.
DR   MANE-Select; ENST00000650999.1; ENSP00000498258.1; NM_005683.4; NP_005674.2.
DR   UCSC; uc002vrf.4; human.
DR   AGR; HGNC:4511; -.
DR   CTD; 9290; -.
DR   DisGeNET; 9290; -.
DR   GeneCards; GPR55; -.
DR   HGNC; HGNC:4511; GPR55.
DR   HPA; ENSG00000135898; Tissue enhanced (brain, lymphoid tissue, testis).
DR   MIM; 604107; gene.
DR   neXtProt; NX_Q9Y2T6; -.
DR   OpenTargets; ENSG00000135898; -.
DR   PharmGKB; PA28900; -.
DR   VEuPathDB; HostDB:ENSG00000135898; -.
DR   eggNOG; ENOG502QWNM; Eukaryota.
DR   GeneTree; ENSGT01040000240444; -.
DR   InParanoid; Q9Y2T6; -.
DR   OMA; TCFHNMS; -.
DR   OrthoDB; 5133474at2759; -.
DR   PhylomeDB; Q9Y2T6; -.
DR   TreeFam; TF335700; -.
DR   PathwayCommons; Q9Y2T6; -.
DR   Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; Q9Y2T6; -.
DR   SIGNOR; Q9Y2T6; -.
DR   BioGRID-ORCS; 9290; 9 hits in 1139 CRISPR screens.
DR   ChiTaRS; GPR55; human.
DR   GeneWiki; GPR55; -.
DR   GenomeRNAi; 9290; -.
DR   Pharos; Q9Y2T6; Tclin.
DR   PRO; PR:Q9Y2T6; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q9Y2T6; Protein.
DR   Bgee; ENSG00000135898; Expressed in monocyte and 86 other cell types or tissues.
DR   ExpressionAtlas; Q9Y2T6; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0004949; F:cannabinoid receptor activity; IDA:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR   GO; GO:0007202; P:activation of phospholipase C activity; IDA:UniProtKB.
DR   GO; GO:0045453; P:bone resorption; IDA:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IDA:UniProtKB.
DR   CDD; cd15165; 7tmA_GPR55-like; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24232; G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR24232:SF56; G-PROTEIN COUPLED RECEPTOR 55; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; Q9Y2T6; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; G-protein coupled receptor; Glycoprotein; Membrane;
KW   Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..319
FT                   /note="G-protein coupled receptor 55"
FT                   /id="PRO_0000069577"
FT   TOPO_DOM        1..21
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        22..42
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        43..58
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        59..79
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        80..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..137
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        138..158
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        159..180
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        181..201
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        202..231
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        232..252
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        253..271
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        272..292
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        293..319
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        5
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        171
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         195
FT                   /note="G -> V (in dbSNP:rs3749073)"
FT                   /id="VAR_024257"
FT   VARIANT         215
FT                   /note="T -> N (in dbSNP:rs34229723)"
FT                   /id="VAR_049395"
SQ   SEQUENCE   319 AA;  36637 MW;  D6E5C6CA8426E7D5 CRC64;
     MSQQNTSGDC LFDGVNELMK TLQFAVHIPT FVLGLLLNLL AIHGFSTFLK NRWPDYAATS
     IYMINLAVFD LLLVLSLPFK MVLSQVQSPF PSLCTLVECL YFVSMYGSVF TICFISMDRF
     LAIRYPLLVS HLRSPRKIFG ICCTIWVLVW TGSIPIYSFH GKVEKYMCFH NMSDDTWSAK
     VFFPLEVFGF LLPMGIMGFC CSRSIHILLG RRDHTQDWVQ QKACIYSIAA SLAVFVVSFL
     PVHLGFFLQF LVRNSFIVEC RAKQSISFFL QLSMCFSNVN CCLDVFCYYF VIKEFRMNIR
     AHRPSRVQLV LQDTTISRG
//