P46095 (GPR6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor 6

Alternative name(s):
Sphingosine 1-phosphate receptor GPR6

Gene names

Name:

GPR6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	362 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan receptor with constitutive G(s) signaling activity that activate cyclic AMP. Promotes neurite outgrowth and blocks myelin inhibition in neurons By similarity. Ref.5 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein Probable. Note: Detected in the intracellular compartments. It is currently unclear whether this is a cell surface or intracellular receptor. Ref.6
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Caution	Was originally (Ref.5) thought to be a receptor for sphingosine 1-phosphate. It has been demonstrated that it is not the case (Ref.7).

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.1. Source: ProtInc sphingosine-1-phosphate receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 362	362	G-protein coupled receptor 6		PRO_0000069514
Regions
	Topological domain	1 – 74	74	Extracellular Potential
	Transmembrane	75 – 94	20	Helical; Name=1; Potential
	Topological domain	95 – 106	12	Cytoplasmic Potential
	Transmembrane	107 – 130	24	Helical; Name=2; Potential
	Topological domain	131 – 142	12	Extracellular Potential
	Transmembrane	143 – 164	22	Helical; Name=3; Potential
	Topological domain	165 – 185	21	Cytoplasmic Potential
	Transmembrane	186 – 205	20	Helical; Name=4; Potential
	Topological domain	206 – 230	25	Extracellular Potential
	Transmembrane	231 – 249	19	Helical; Name=5; Potential
	Topological domain	250 – 277	28	Cytoplasmic Potential
	Transmembrane	278 – 304	27	Helical; Name=6; Potential
	Topological domain	305 – 309	5	Extracellular Potential
	Transmembrane	310 – 331	22	Helical; Name=7; Potential
	Topological domain	332 – 362	31	Cytoplasmic Potential
	Compositional bias	13 – 16	4	Poly-Val
	Compositional bias	21 – 28	8	Poly-Ala
	Compositional bias	40 – 43	4	Poly-Ala
Amino acid modifications
	Modified residue	356	1	Phosphoserine Potential
	Modified residue	358	1	Phosphoserine Potential
	Modified residue	360	1	Phosphoserine Potential
	Lipidation	345	1	S-palmitoyl cysteine By similarity
	Glycosylation	2	1	N-linked (GlcNAc...) Potential
	Glycosylation	9	1	N-linked (GlcNAc...) Potential
	Glycosylation	51	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P46095 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: AF8C6075603337AD	FASTA	362	37,881
	10 20 30 40 50 60 MNASAASLND SQVVVVAAEG AAAAATAAGG PDTGEWGPPA AAALGAGGGA NGSLELSSQL 70 80 90 100 110 120 SAGPPGLLLP AVNPWDVLLC VSGTVIAGEN ALVVALIAST PALRTPMFVL VGSLATADLL 130 140 150 160 170 180 AGCGLILHFV FQYLVPSETV SLLTVGFLVA SFAASVSSLL AITVDRYLSL YNALTYYSRR 190 200 210 220 230 240 TLLGVHLLLA ATWTVSLGLG LLPVLGWNCL AERAACSVVR PLARSHVALL SAAFFMVFGI 250 260 270 280 290 300 MLHLYVRICQ VVWRHAHQIA LQQHCLAPPH LAATRKGVGT LAVVLGTFGA SWLPFAIYCV 310 320 330 340 350 360 VGSHEDPAVY TYATLLPATY NSMINPIIYA FRNQEIQRAL WLLLCGCFQS KVPFRSRSPS EV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of three novel human genes encoding G protein-coupled receptors." Heiber M., Docherty J.M., Shah G., Nguyen T., Cheng R., Heng H.H.Q., Marchese A., Tsui L.-C., Shi X., George S.R., O'Dowd B.F. DNA Cell Biol. 14:25-35(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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].
[3]	"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].
[4]	"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]. Tissue: Brain.
[5]	"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.
[6]	"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.
[7]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L36150 Genomic DNA. Translation: AAA63181.1. U18549 Genomic DNA. Translation: AAA91631.1. AL591076 Genomic DNA. Translation: CAI17125.1. BC043414 mRNA. Translation: AAH43414.1. BC117298 mRNA. Translation: AAI17299.1. BC126301 mRNA. Translation: AAI26302.1.
IPI	IPI00942047.
PIR	I65990.
RefSeq	NP_005275.1. NM_005284.3.
UniGene	Hs.46332.
3D structure databases
ProteinModelPortal	P46095.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000275169.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	1170009.
Proteomic databases
PaxDb	P46095.
PRIDE	P46095.
Protocols and materials databases
DNASU	2830.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000275169; ENSP00000275169; ENSG00000146360.
GeneID	2830.
KEGG	hsa:2830.
UCSC	uc003ptu.3. human.
Organism-specific databases
CTD	2830.
GeneCards	GC06P110345.
HGNC	HGNC:4515. GPR6.
MIM	600553. gene.
neXtProt	NX_P46095.
PharmGKB	PA28904.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG327877.
HOGENOM	HOG000294075.
HOVERGEN	HBG079561.
InParanoid	P46095.
KO	K04313.
OrthoDB	EOG4MSD02.
PhylomeDB	P46095.
Gene expression databases
ArrayExpress	P46095.
Bgee	P46095.
CleanEx	HS_GPR6.
Genevestigator	P46095.
GermOnline	ENSG00000146360. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR001151. GPR6. IPR000723. GPR_3/6/12_orphan. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR00649. GPR6ORPHANR. PR00644. GPRORPHANR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2830.
NextBio	11169.
SOURCE	Search...

Entry information

Entry name

GPR6_HUMAN

Accession

Primary (citable) accession number: P46095
Secondary accession number(s): Q17RJ7, Q5SYL0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.