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P46095

- GPR6_HUMAN

UniProt

P46095 - GPR6_HUMAN

Protein

G-protein coupled receptor 6

Gene

GPR6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Orphan receptor with constitutive G(s) signaling activity that activate cyclic AMP. Promotes neurite outgrowth and blocks myelin inhibition in neurons By similarity.By similarity

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: ProtInc
    2. sphingosine-1-phosphate receptor activity Source: Ensembl

    GO - Biological processi

    1. G-protein coupled receptor signaling pathway Source: ProtInc
    2. positive regulation of cytosolic calcium ion concentration Source: Ensembl

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    G-protein coupled receptor 6
    Alternative name(s):
    Sphingosine 1-phosphate receptor GPR6
    Gene namesi
    Name:GPR6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:4515. GPR6.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
    Note: Detected in the intracellular compartments. It is currently unclear whether this is a cell surface or intracellular receptor.

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28904.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 362362G-protein coupled receptor 6PRO_0000069514Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi2 – 21N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi9 – 91N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi51 – 511N-linked (GlcNAc...)Sequence Analysis
    Lipidationi345 – 3451S-palmitoyl cysteineBy similarity
    Modified residuei356 – 3561PhosphoserineSequence Analysis
    Modified residuei358 – 3581PhosphoserineSequence Analysis
    Modified residuei360 – 3601PhosphoserineSequence Analysis

    Keywords - PTMi

    Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiP46095.
    PRIDEiP46095.

    Expressioni

    Gene expression databases

    ArrayExpressiP46095.
    BgeeiP46095.
    CleanExiHS_GPR6.
    GenevestigatoriP46095.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000275169.

    Structurei

    3D structure databases

    ProteinModelPortaliP46095.
    SMRiP46095. Positions 56-344.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 7474ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini95 – 10612CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini131 – 14212ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini165 – 18521CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini206 – 23025ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini250 – 27728CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini305 – 3095ExtracellularSequence Analysis
    Topological domaini332 – 36231CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei75 – 9420Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei107 – 13024Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei143 – 16422Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei186 – 20520Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei231 – 24919Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei278 – 30427Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei310 – 33122Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi13 – 164Poly-Val
    Compositional biasi21 – 288Poly-Ala
    Compositional biasi40 – 434Poly-Ala

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG327877.
    HOGENOMiHOG000294075.
    HOVERGENiHBG079561.
    InParanoidiP46095.
    KOiK04313.
    PhylomeDBiP46095.
    TreeFamiTF330052.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR001151. GPR6.
    IPR000723. GPR_3/6/12_orphan.
    [Graphical view]
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00237. GPCRRHODOPSN.
    PR00649. GPR6ORPHANR.
    PR00644. GPRORPHANR.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P46095-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MNASAASLND SQVVVVAAEG AAAAATAAGG PDTGEWGPPA AAALGAGGGA    50
    NGSLELSSQL SAGPPGLLLP AVNPWDVLLC VSGTVIAGEN ALVVALIAST 100
    PALRTPMFVL VGSLATADLL AGCGLILHFV FQYLVPSETV SLLTVGFLVA 150
    SFAASVSSLL AITVDRYLSL YNALTYYSRR TLLGVHLLLA ATWTVSLGLG 200
    LLPVLGWNCL AERAACSVVR PLARSHVALL SAAFFMVFGI MLHLYVRICQ 250
    VVWRHAHQIA LQQHCLAPPH LAATRKGVGT LAVVLGTFGA SWLPFAIYCV 300
    VGSHEDPAVY TYATLLPATY NSMINPIIYA FRNQEIQRAL WLLLCGCFQS 350
    KVPFRSRSPS EV 362
    Length:362
    Mass (Da):37,881
    Last modified:November 1, 1995 - v1
    Checksum:iAF8C6075603337AD
    GO
    Isoform 2 (identifier: P46095-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MTLLAWCTRGANPAAM

    Show »
    Length:377
    Mass (Da):39,439
    Checksum:iE4C69B2CF3E77D89
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti310 – 3101Y → H in BAG58241. (PubMed:14702039)Curated
    Sequence conflicti358 – 3581S → P in BAG58241. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MTLLAWCTRGANPAAM in isoform 2. 1 PublicationVSP_055105

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36150 Genomic DNA. Translation: AAA63181.1.
    U18549 Genomic DNA. Translation: AAA91631.1.
    AK295250 mRNA. Translation: BAG58241.1.
    AL591076 Genomic DNA. Translation: CAI17125.1.
    BC043414 mRNA. Translation: AAH43414.1.
    BC117298 mRNA. Translation: AAI17299.1.
    BC126301 mRNA. Translation: AAI26302.1.
    CCDSiCCDS5079.1. [P46095-1]
    CCDS69172.1. [P46095-2]
    PIRiI65990.
    RefSeqiNP_001273028.1. NM_001286099.1.
    NP_005275.1. NM_005284.4.
    UniGeneiHs.46332.

    Genome annotation databases

    EnsembliENST00000275169; ENSP00000275169; ENSG00000146360. [P46095-1]
    ENST00000414000; ENSP00000406986; ENSG00000146360. [P46095-2]
    GeneIDi2830.
    KEGGihsa:2830.
    UCSCiuc003ptu.3. human. [P46095-1]

    Polymorphism databases

    DMDMi1170009.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36150 Genomic DNA. Translation: AAA63181.1 .
    U18549 Genomic DNA. Translation: AAA91631.1 .
    AK295250 mRNA. Translation: BAG58241.1 .
    AL591076 Genomic DNA. Translation: CAI17125.1 .
    BC043414 mRNA. Translation: AAH43414.1 .
    BC117298 mRNA. Translation: AAI17299.1 .
    BC126301 mRNA. Translation: AAI26302.1 .
    CCDSi CCDS5079.1. [P46095-1 ]
    CCDS69172.1. [P46095-2 ]
    PIRi I65990.
    RefSeqi NP_001273028.1. NM_001286099.1.
    NP_005275.1. NM_005284.4.
    UniGenei Hs.46332.

    3D structure databases

    ProteinModelPortali P46095.
    SMRi P46095. Positions 56-344.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000275169.

    Chemistry

    GuidetoPHARMACOLOGYi 85.

    Protein family/group databases

    GPCRDBi Search...

    Polymorphism databases

    DMDMi 1170009.

    Proteomic databases

    PaxDbi P46095.
    PRIDEi P46095.

    Protocols and materials databases

    DNASUi 2830.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000275169 ; ENSP00000275169 ; ENSG00000146360 . [P46095-1 ]
    ENST00000414000 ; ENSP00000406986 ; ENSG00000146360 . [P46095-2 ]
    GeneIDi 2830.
    KEGGi hsa:2830.
    UCSCi uc003ptu.3. human. [P46095-1 ]

    Organism-specific databases

    CTDi 2830.
    GeneCardsi GC06P110345.
    HGNCi HGNC:4515. GPR6.
    MIMi 600553. gene.
    neXtProti NX_P46095.
    PharmGKBi PA28904.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG327877.
    HOGENOMi HOG000294075.
    HOVERGENi HBG079561.
    InParanoidi P46095.
    KOi K04313.
    PhylomeDBi P46095.
    TreeFami TF330052.

    Miscellaneous databases

    GeneWikii GPR6.
    GenomeRNAii 2830.
    NextBioi 11169.
    PROi P46095.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P46095.
    Bgeei P46095.
    CleanExi HS_GPR6.
    Genevestigatori P46095.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR001151. GPR6.
    IPR000723. GPR_3/6/12_orphan.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR00649. GPR6ORPHANR.
    PR00644. GPRORPHANR.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    2. "Molecular cloning and chromosomal localization of human genes encoding three closely related G protein-coupled receptors."
      Song Z.-H., Modi W., Bonner T.I.
      Genomics 28:347-349(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    4. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    6. "Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors."
      Uhlenbrock K., Gassenhuber J., Kostenis E.
      Cell. Signal. 14:941-953(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PRELIMINARY FUNCTION.
    7. "Constitutively active GPR6 is located in the intracellular compartments."
      Padmanabhan S., Myers A.G., Prasad B.M.
      FEBS Lett. 583:107-112(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    8. "Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay."
      Yin H., Chu A., Li W., Wang B., Shelton F., Otero F., Nguyen D.G., Caldwell J.S., Chen Y.A.
      J. Biol. Chem. 284:12328-12338(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: LACK OF FUNCTION AS A SPHINGOSINE 1-PHOSPHATE RECEPTOR.

    Entry informationi

    Entry nameiGPR6_HUMAN
    AccessioniPrimary (citable) accession number: P46095
    Secondary accession number(s): B4DHS9
    , J3KQR3, Q17RJ7, Q5SYL0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [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

    Caution

    Was originally (PubMed:12220620) thought to be a receptor for sphingosine 1-phosphate. It has been demonstrated that it is not the case (PubMed:19286662).2 Publications

    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 6
      Human chromosome 6: 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

    External Data

    Dasty 3