GPR6_HUMAN
ID GPR6_HUMAN Reviewed; 362 AA.
AC P46095; B4DHS9; J3KQR3; Q17RJ7; Q5SYL0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=G-protein coupled receptor 6;
DE AltName: Full=Sphingosine 1-phosphate receptor GPR6;
GN Name=GPR6;
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] (ISOFORM 1).
RX PubMed=7832990; DOI=10.1089/dna.1995.14.25;
RA Heiber M., Docherty J.M., Shah G., Nguyen T., Cheng R., Heng H.H.Q.,
RA Marchese A., Tsui L.-C., Shi X., George S.R., O'Dowd B.F.;
RT "Isolation of three novel human genes encoding G protein-coupled
RT receptors.";
RL DNA Cell Biol. 14:25-35(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=8530049; DOI=10.1006/geno.1995.1154;
RA Song Z.-H., Modi W., Bonner T.I.;
RT "Molecular cloning and chromosomal localization of human genes encoding
RT three closely related G protein-coupled receptors.";
RL Genomics 28:347-349(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 PRELIMINARY FUNCTION.
RX PubMed=12220620; DOI=10.1016/s0898-6568(02)00041-4;
RA Uhlenbrock K., Gassenhuber J., Kostenis E.;
RT "Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12
RT family of constitutively active G protein-coupled receptors.";
RL Cell. Signal. 14:941-953(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=19059244; DOI=10.1016/j.febslet.2008.11.033;
RA Padmanabhan S., Myers A.G., Prasad B.M.;
RT "Constitutively active GPR6 is located in the intracellular compartments.";
RL FEBS Lett. 583:107-112(2009).
RN [8]
RP LACK OF FUNCTION AS A SPHINGOSINE 1-PHOSPHATE RECEPTOR.
RX PubMed=19286662; DOI=10.1074/jbc.m806516200;
RA Yin H., Chu A., Li W., Wang B., Shelton F., Otero F., Nguyen D.G.,
RA Caldwell J.S., Chen Y.A.;
RT "Lipid G protein-coupled receptor ligand identification using beta-arrestin
RT PathHunter assay.";
RL J. Biol. Chem. 284:12328-12338(2009).
CC -!- FUNCTION: Orphan receptor with constitutive G(s) signaling activity
CC that activate cyclic AMP. Promotes neurite outgrowth and blocks myelin
CC inhibition in neurons (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:19059244};
CC Multi-pass membrane protein {ECO:0000305|PubMed:19059244}.
CC Note=Detected in the intracellular compartments. It is currently
CC unclear whether this is a cell surface or intracellular receptor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P46095-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P46095-2; Sequence=VSP_055105;
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally (PubMed:12220620) thought to be a receptor for
CC sphingosine 1-phosphate. It has been demonstrated that it is not the
CC case (PubMed:19286662). {ECO:0000305|PubMed:12220620,
CC ECO:0000305|PubMed:19286662}.
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DR EMBL; L36150; AAA63181.1; -; Genomic_DNA.
DR EMBL; U18549; AAA91631.1; -; Genomic_DNA.
DR EMBL; AK295250; BAG58241.1; -; mRNA.
DR EMBL; AL591076; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043414; AAH43414.1; -; mRNA.
DR EMBL; BC117298; AAI17299.1; -; mRNA.
DR EMBL; BC126301; AAI26302.1; -; mRNA.
DR CCDS; CCDS5079.1; -. [P46095-1]
DR CCDS; CCDS69172.1; -. [P46095-2]
DR PIR; I65990; I65990.
DR RefSeq; NP_001273028.1; NM_001286099.1. [P46095-2]
DR RefSeq; NP_005275.1; NM_005284.4. [P46095-1]
DR AlphaFoldDB; P46095; -.
DR SMR; P46095; -.
DR BioGRID; 109091; 10.
DR IntAct; P46095; 2.
DR STRING; 9606.ENSP00000406986; -.
DR BindingDB; P46095; -.
DR ChEMBL; CHEMBL3714130; -.
DR GuidetoPHARMACOLOGY; 85; -.
DR GlyGen; P46095; 3 sites.
DR PhosphoSitePlus; P46095; -.
DR BioMuta; GPR6; -.
DR DMDM; 1170009; -.
DR PaxDb; P46095; -.
DR PeptideAtlas; P46095; -.
DR PRIDE; P46095; -.
DR Antibodypedia; 19237; 117 antibodies from 27 providers.
DR DNASU; 2830; -.
DR Ensembl; ENST00000275169.5; ENSP00000275169.3; ENSG00000146360.9. [P46095-1]
DR Ensembl; ENST00000414000.3; ENSP00000406986.2; ENSG00000146360.9. [P46095-2]
DR GeneID; 2830; -.
DR KEGG; hsa:2830; -.
DR MANE-Select; ENST00000275169.5; ENSP00000275169.3; NM_005284.5; NP_005275.1.
DR UCSC; uc011eav.4; human. [P46095-1]
DR CTD; 2830; -.
DR DisGeNET; 2830; -.
DR GeneCards; GPR6; -.
DR HGNC; HGNC:4515; GPR6.
DR HPA; ENSG00000146360; Tissue enriched (brain).
DR MIM; 600553; gene.
DR neXtProt; NX_P46095; -.
DR OpenTargets; ENSG00000146360; -.
DR PharmGKB; PA28904; -.
DR VEuPathDB; HostDB:ENSG00000146360; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01000000214392; -.
DR HOGENOM; CLU_065071_0_0_1; -.
DR InParanoid; P46095; -.
DR OMA; YCVVGDP; -.
DR OrthoDB; 903801at2759; -.
DR PhylomeDB; P46095; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; P46095; -.
DR SignaLink; P46095; -.
DR BioGRID-ORCS; 2830; 14 hits in 1064 CRISPR screens.
DR GeneWiki; GPR6; -.
DR GenomeRNAi; 2830; -.
DR Pharos; P46095; Tchem.
DR PRO; PR:P46095; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P46095; protein.
DR Bgee; ENSG00000146360; Expressed in nucleus accumbens and 35 other tissues.
DR ExpressionAtlas; P46095; baseline and differential.
DR Genevisible; P46095; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001151; GPR6.
DR InterPro; IPR000723; GPR_3/6/12_orphan.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00649; GPR6ORPHANR.
DR PRINTS; PR00644; GPRORPHANR.
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 Alternative splicing; Cell membrane; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..362
FT /note="G-protein coupled receptor 6"
FT /id="PRO_0000069514"
FT TOPO_DOM 1..74
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..94
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..130
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..164
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..205
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..230
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..249
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..304
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..309
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..331
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT LIPID 345
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 9
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MTLLAWCTRGANPAAM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055105"
FT CONFLICT 310
FT /note="Y -> H (in Ref. 3; BAG58241)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="S -> P (in Ref. 3; BAG58241)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 37881 MW; AF8C6075603337AD CRC64;
MNASAASLND SQVVVVAAEG AAAAATAAGG PDTGEWGPPA AAALGAGGGA NGSLELSSQL
SAGPPGLLLP AVNPWDVLLC VSGTVIAGEN ALVVALIAST PALRTPMFVL VGSLATADLL
AGCGLILHFV FQYLVPSETV SLLTVGFLVA SFAASVSSLL AITVDRYLSL YNALTYYSRR
TLLGVHLLLA ATWTVSLGLG LLPVLGWNCL AERAACSVVR PLARSHVALL SAAFFMVFGI
MLHLYVRICQ VVWRHAHQIA LQQHCLAPPH LAATRKGVGT LAVVLGTFGA SWLPFAIYCV
VGSHEDPAVY TYATLLPATY NSMINPIIYA FRNQEIQRAL WLLLCGCFQS KVPFRSRSPS
EV
