GPR39_HUMAN
ID GPR39_HUMAN Reviewed; 453 AA.
AC O43194; B2RC12; B6V9G4; Q08AS2; Q53R01;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=G-protein coupled receptor 39;
GN Name=GPR39;
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.
RC TISSUE=Brain;
RX PubMed=9441746; DOI=10.1006/geno.1997.5069;
RA McKee K.K., Tan C.P., Palyha O.C., Liu J., Feighner S.D., Hreniuk D.L.,
RA Smith R.G., Howard A.D., van der Ploeg L.H.T.;
RT "Cloning and characterization of two human G protein-coupled receptor genes
RT (GPR38 and GPR39) related to the growth hormone secretagogue and
RT neurotensin receptors.";
RL Genomics 46:426-434(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for Homo sapiens G protein-coupled receptor 39
RT (GPR39).";
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-50.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP DISULFIDE BONDS.
RX PubMed=18693759; DOI=10.1021/bi8005016;
RA Storjohann L., Holst B., Schwartz T.W.;
RT "A second disulfide bridge from the N-terminal domain to extracellular loop
RT 2 dampens receptor activity in GPR39.";
RL Biochemistry 47:9198-9207(2008).
RN [7]
RP ZINC-BINDING SITES, AND MUTAGENESIS OF HIS-17; HIS-19; HIS-312 AND ASP-313.
RX PubMed=18588883; DOI=10.1016/j.febslet.2008.06.030;
RA Storjohann L., Holst B., Schwartz T.W.;
RT "Molecular mechanism of Zn2+ agonism in the extracellular domain of
RT GPR39.";
RL FEBS Lett. 582:2583-2588(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-396, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Zn(2+) acts as an agonist. This receptor mediates its action
CC by association with G proteins that activate a phosphatidylinositol-
CC calcium second messenger system. Its effect is mediated mainly through
CC G(q)-alpha and G(12)/G(13) proteins. Involved in regulation of body
CC weight, gastrointestinal mobility, hormone secretion and cell death (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O43194; P08908: HTR1A; NbExp=4; IntAct=EBI-7165599, EBI-6570214;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, including the stomach,
CC intestine and hypothalamus. {ECO:0000269|PubMed:9441746}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF034633; AAC26082.1; -; mRNA.
DR EMBL; FJ348258; ACI96302.1; -; mRNA.
DR EMBL; AK314895; BAG37409.1; -; mRNA.
DR EMBL; AC098800; AAY24154.1; -; Genomic_DNA.
DR EMBL; AC079773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC125046; AAI25047.1; -; mRNA.
DR CCDS; CCDS2170.1; -.
DR RefSeq; NP_001499.1; NM_001508.2.
DR AlphaFoldDB; O43194; -.
DR SMR; O43194; -.
DR BioGRID; 109121; 4.
DR IntAct; O43194; 4.
DR MINT; O43194; -.
DR STRING; 9606.ENSP00000327417; -.
DR BindingDB; O43194; -.
DR ChEMBL; CHEMBL3091266; -.
DR DrugCentral; O43194; -.
DR GuidetoPHARMACOLOGY; 105; -.
DR TCDB; 9.A.14.1.15; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; O43194; 3 sites.
DR iPTMnet; O43194; -.
DR PhosphoSitePlus; O43194; -.
DR SwissPalm; O43194; -.
DR BioMuta; GPR39; -.
DR EPD; O43194; -.
DR jPOST; O43194; -.
DR MassIVE; O43194; -.
DR MaxQB; O43194; -.
DR PaxDb; O43194; -.
DR PeptideAtlas; O43194; -.
DR PRIDE; O43194; -.
DR ProteomicsDB; 48809; -.
DR Antibodypedia; 18657; 371 antibodies from 34 providers.
DR DNASU; 2863; -.
DR Ensembl; ENST00000329321.4; ENSP00000327417.3; ENSG00000183840.7.
DR GeneID; 2863; -.
DR KEGG; hsa:2863; -.
DR MANE-Select; ENST00000329321.4; ENSP00000327417.3; NM_001508.3; NP_001499.1.
DR UCSC; uc002ttl.4; human.
DR CTD; 2863; -.
DR DisGeNET; 2863; -.
DR GeneCards; GPR39; -.
DR HGNC; HGNC:4496; GPR39.
DR HPA; ENSG00000183840; Tissue enhanced (intestine).
DR MIM; 602886; gene.
DR neXtProt; NX_O43194; -.
DR OpenTargets; ENSG00000183840; -.
DR PharmGKB; PA28885; -.
DR VEuPathDB; HostDB:ENSG00000183840; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244813; -.
DR HOGENOM; CLU_009579_6_5_1; -.
DR InParanoid; O43194; -.
DR OMA; AFVWVTS; -.
DR OrthoDB; 890529at2759; -.
DR PhylomeDB; O43194; -.
DR TreeFam; TF331140; -.
DR PathwayCommons; O43194; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; O43194; -.
DR BioGRID-ORCS; 2863; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; GPR39; human.
DR GeneWiki; GPR39; -.
DR GenomeRNAi; 2863; -.
DR Pharos; O43194; Tchem.
DR PRO; PR:O43194; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43194; protein.
DR Bgee; ENSG00000183840; Expressed in oocyte and 134 other tissues.
DR ExpressionAtlas; O43194; baseline and differential.
DR Genevisible; O43194; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
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; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Metal-binding; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..453
FT /note="G-protein coupled receptor 39"
FT /id="PRO_0000069565"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 35..55
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 56..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 70..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 90..109
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 110..131
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 132..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 152..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 173..217
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 218..242
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 243..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 284..305
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 306..323
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 324..344
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 345..453
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT REGION 255..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..442
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 17
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18588883"
FT BINDING 19
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18588883"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 11..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:18693759"
FT DISULFID 108..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:18693759"
FT VARIANT 50
FT /note="A -> V (in dbSNP:rs2241764)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_022067"
FT VARIANT 390
FT /note="R -> C (in dbSNP:rs16838944)"
FT /id="VAR_049393"
FT MUTAGEN 17
FT /note="H->A: Decreases activation by Zn(2+). Abolishes
FT activation by Zn(2+); when associated with A-19."
FT /evidence="ECO:0000269|PubMed:18588883"
FT MUTAGEN 19
FT /note="H->A: Decreases activation by Zn(2+). Abolishes
FT activation by Zn(2+); when associated with A-17."
FT /evidence="ECO:0000269|PubMed:18588883"
FT MUTAGEN 312
FT /note="H->A: Not affect constitutive or Zn(2+)-induced
FT activation."
FT /evidence="ECO:0000269|PubMed:18588883"
FT MUTAGEN 313
FT /note="D->A: Induces very high constitutive activity and
FT eliminates Zn(2+)-induced activation."
FT /evidence="ECO:0000269|PubMed:18588883"
SQ SEQUENCE 453 AA; 51329 MW; 8E3A233420D9021E CRC64;
MASPSLPGSD CSQIIDHSHV PEFEVATWIK ITLILVYLII FVMGLLGNSA TIRVTQVLQK
KGYLQKEVTD HMVSLACSDI LVFLIGMPME FYSIIWNPLT TSSYTLSCKL HTFLFEACSY
ATLLHVLTLS FERYIAICHP FRYKAVSGPC QVKLLIGFVW VTSALVALPL LFAMGTEYPL
VNVPSHRGLT CNRSSTRHHE QPETSNMSIC TNLSSRWTVF QSSIFGAFVV YLVVLLSVAF
MCWNMMQVLM KSQKGSLAGG TRPPQLRKSE SEESRTARRQ TIIFLRLIVV TLAVCWMPNQ
IRRIMAAAKP KHDWTRSYFR AYMILLPFSE TFFYLSSVIN PLLYTVSSQQ FRRVFVQVLC
CRLSLQHANH EKRLRVHAHS TTDSARFVQR PLLFASRRQS SARRTEKIFL STFQSEAEPQ
SKSQSLSLES LEPNSGAKPA NSAAENGFQE HEV
