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P46095

- GPR6_HUMAN

UniProt

P46095 - GPR6_HUMAN

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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

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

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: ProtInc
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP46095.
CleanExiHS_GPR6.
ExpressionAtlasiP46095. baseline and differential.
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.
GeneTreeiENSGT00760000118804.
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

        10         20         30         40         50
MNASAASLND SQVVVVAAEG AAAAATAAGG PDTGEWGPPA AAALGAGGGA
60 70 80 90 100
NGSLELSSQL SAGPPGLLLP AVNPWDVLLC VSGTVIAGEN ALVVALIAST
110 120 130 140 150
PALRTPMFVL VGSLATADLL AGCGLILHFV FQYLVPSETV SLLTVGFLVA
160 170 180 190 200
SFAASVSSLL AITVDRYLSL YNALTYYSRR TLLGVHLLLA ATWTVSLGLG
210 220 230 240 250
LLPVLGWNCL AERAACSVVR PLARSHVALL SAAFFMVFGI MLHLYVRICQ
260 270 280 290 300
VVWRHAHQIA LQQHCLAPPH LAATRKGVGT LAVVLGTFGA SWLPFAIYCV
310 320 330 340 350
VGSHEDPAVY TYATLLPATY NSMINPIIYA FRNQEIQRAL WLLLCGCFQS
360
KVPFRSRSPS EV
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. [P46095-2]
NP_005275.1. NM_005284.4. [P46095-1]
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. [P46095-2 ]
NP_005275.1. NM_005284.4. [P46095-1 ]
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.
GeneTreei ENSGT00760000118804.
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

Bgeei P46095.
CleanExi HS_GPR6.
ExpressionAtlasi P46095. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 122 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