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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.2 Publications

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW
  2. sphingosine-1-phosphate receptor activity Source: Ensembl
Complete GO annotation...

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: ProtInc
  2. positive regulation of cytosolic calcium ion concentration Source: Ensembl
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; Multi-pass membrane protein Inferred
Note: Detected in the intracellular compartments. It is currently unclear whether this is a cell surface or intracellular receptor.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7474Extracellular Reviewed prediction
Add
BLAST
Transmembranei75 – 9420Helical; Name=1; Reviewed prediction
Add
BLAST
Topological domaini95 – 10612Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei107 – 13024Helical; Name=2; Reviewed prediction
Add
BLAST
Topological domaini131 – 14212Extracellular Reviewed prediction
Add
BLAST
Transmembranei143 – 16422Helical; Name=3; Reviewed prediction
Add
BLAST
Topological domaini165 – 18521Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei186 – 20520Helical; Name=4; Reviewed prediction
Add
BLAST
Topological domaini206 – 23025Extracellular Reviewed prediction
Add
BLAST
Transmembranei231 – 24919Helical; Name=5; Reviewed prediction
Add
BLAST
Topological domaini250 – 27728Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei278 – 30427Helical; Name=6; Reviewed prediction
Add
BLAST
Topological domaini305 – 3095Extracellular Reviewed prediction
Transmembranei310 – 33122Helical; Name=7; Reviewed prediction
Add
BLAST
Topological domaini332 – 36231Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. 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 6
PRO_0000069514Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...) Reviewed prediction
Glycosylationi9 – 91N-linked (GlcNAc...) Reviewed prediction
Glycosylationi51 – 511N-linked (GlcNAc...) Reviewed prediction
Lipidationi345 – 3451S-palmitoyl cysteine By similarity
Modified residuei356 – 3561Phosphoserine Reviewed prediction
Modified residuei358 – 3581Phosphoserine Reviewed prediction
Modified residuei360 – 3601Phosphoserine Reviewed prediction

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.

Family & Domainsi

Compositional bias

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

Sequence similaritiesi

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MTLLAWCTRGANPAAM in isoform 2.
VSP_055105

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti310 – 3101Y → H in BAG58241. 1 Publication
Sequence conflicti358 – 3581S → P in BAG58241. 1 Publication

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]
PIRiI65990.
RefSeqiNP_001273028.1. NM_001286099.1.
NP_005275.1. NM_005284.4.
UniGeneiHs.46332.

Genome annotation databases

EnsembliENST00000275169; ENSP00000275169; ENSG00000146360.
ENST00000414000; ENSP00000406986; ENSG00000146360.
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 ]
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...

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 .
ENST00000414000 ; ENSP00000406986 ; ENSG00000146360 .
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

« 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: September 3, 2014
This is version 120 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 (1 Publication) thought to be a receptor for sphingosine 1-phosphate. It has been demonstrated that it is not the case (1 Publication).

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

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