P46089 (GPR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor 3

Alternative name(s):
ACCA orphan receptor

Gene names

Name:	GPR3
Synonyms:	ACCA

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	330 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. Has a potential role in modulating a number of brain functions, including behavioral responses to stress By similarity, amyloid-beta peptide generation in neurons and neurite outgrowth By similarity. Maintains also meiotic arrest in oocytes By similarity. Ref.9 Ref.11
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed predominantly in the central nervous system, and at low levels in the lung, kidney, testis, ovary and eye. Highly expressed in regions of the brain implicated in the Alzheimer disease.
Induction	Overexpression stimulates amyloid-beta production.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Caution	Was originally (Ref.9) thought to be a receptor for sphingosine 1-phosphate. Ref.10 demonstrated that it is not the case.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
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	adenylate cyclase-activating G-protein coupled receptor signaling pathway Traceable author statement Ref.3. Source: ProtInc regulation of meiosis Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	G-protein coupled receptor 3		PRO_0000069510
Regions
	Topological domain	1 – 42	42	Extracellular Potential
	Transmembrane	43 – 62	20	Helical; Name=1; Potential
	Topological domain	63 – 74	12	Cytoplasmic Potential
	Transmembrane	75 – 98	24	Helical; Name=2; Potential
	Topological domain	99 – 110	12	Extracellular Potential
	Transmembrane	111 – 132	22	Helical; Name=3; Potential
	Topological domain	133 – 153	21	Cytoplasmic Potential
	Transmembrane	154 – 173	20	Helical; Name=4; Potential
	Topological domain	174 – 198	25	Extracellular Potential
	Transmembrane	199 – 217	19	Helical; Name=5; Potential
	Topological domain	218 – 245	28	Cytoplasmic Potential
	Transmembrane	246 – 272	27	Helical; Name=6; Potential
	Topological domain	273 – 277	5	Extracellular Potential
	Transmembrane	278 – 299	22	Helical; Name=7; Potential
	Topological domain	300 – 330	31	Cytoplasmic Potential
Amino acid modifications
	Modified residue	324	1	Phosphoserine Potential
	Modified residue	326	1	Phosphoserine Potential
	Modified residue	328	1	Phosphoserine Potential
	Lipidation	313	1	S-palmitoyl cysteine By similarity
	Glycosylation	20	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	222	1	R → H. Corresponds to variant rs734852 [ dbSNP | Ensembl ].		VAR_011859

Sequences

	Sequence		Length	Mass (Da)
	P46089 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 0F82E89200968D1E	FASTA	330	35,010
	10 20 30 40 50 60 MMWGAGSPLA WLSAGSGNVN VSSVGPAEGP TGPAAPLPSP KAWDVVLCIS GTLVSCENAL 70 80 90 100 110 120 VVAIIVGTPA FRAPMFLLVG SLAVADLLAG LGLVLHFAAV FCIGSAEMSL VLVGVLAMAF 130 140 150 160 170 180 TASIGSLLAI TVDRYLSLYN ALTYYSETTV TRTYVMLALV WGGALGLGLL PVLAWNCLDG 190 200 210 220 230 240 LTTCGVVYPL SKNHLVVLAI AFFMVFGIML QLYAQICRIV CRHAQQIALQ RHLLPASHYV 250 260 270 280 290 300 ATRKGIATLA VVLGAFAACW LPFTVYCLLG DAHSPPLYTY LTLLPATYNS MINPIIYAFR 310 320 330 NQDVQKVLWA VCCCCSSSKI PFRSRSPSDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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].
[2]	"Isolation and chromosomal localization of a novel human G-protein-coupled receptor (GPR3) expressed predominantly in the central nervous system." Iismaa T.P., Kiefer J., Liu M.L., Baker E., Sutherland G.R., Shine J. Genomics 24:391-394(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase." Eggerickx D., Denef J.F., Labbe O., Hayashi Y., Refetoff S., Vassart G., Parmentier M., Libert F. Biochem. J. 309:837-843(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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].
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"Cloning of human genes encoding novel G protein-coupled receptors." Marchese A., Docherty J.M., Nguyen T., Heiber M., Cheng R., Heng H.H.Q., Tsui L.-C., Shi X., George S.R., O'Dowd B.F. Genomics 23:609-618(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-292.
[9]	"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.
[10]	"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: SHOWS THAT IT IS NOT A SPHINGOSINE 1-PHOSPHATE RECEPTOR.
[11]	"The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons." Thathiah A., Spittaels K., Hoffmann M., Staes M., Cohen A., Horre K., Vanbrabant M., Coun F., Baekelandt V., Delacourte A., Fischer D.F., Pollet D., De Strooper B., Merchiers P. Science 323:946-951(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U18550 Genomic DNA. Translation: AAB60402.1. L32831 Genomic DNA. Translation: AAA73560.1. X83956 Genomic DNA. Translation: CAA58787.1. AK291185 mRNA. Translation: BAF83874.1. AK314868 mRNA. Translation: BAG37383.1. AL096774 Genomic DNA. Translation: CAC18517.1. CH471059 Genomic DNA. Translation: EAX07754.1. BC032702 mRNA. Translation: AAH32702.1. U13668 Genomic DNA. Translation: AAA64594.1.
IPI	IPI00004334.
PIR	A55689.
RefSeq	NP_005272.1. NM_005281.3.
UniGene	Hs.66542.
3D structure databases
ProteinModelPortal	P46089.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46089. 3 interactions.
STRING	9606.ENSP00000363136.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	1170006.
Proteomic databases
PaxDb	P46089.
PRIDE	P46089.
Protocols and materials databases
DNASU	2827.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374024; ENSP00000363136; ENSG00000181773.
GeneID	2827.
KEGG	hsa:2827.
UCSC	uc001bod.3. human.
Organism-specific databases
CTD	2827.
GeneCards	GC01P027719.
H-InvDB	HIX0160062.
HGNC	HGNC:4484. GPR3.
HPA	CAB006254.
MIM	600241. gene.
neXtProt	NX_P46089.
PharmGKB	PA28872.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320944.
HOGENOM	HOG000294075.
HOVERGEN	HBG079561.
InParanoid	P46089.
KO	K04311.
OMA	LWAICCC.
OrthoDB	EOG4MSD02.
PhylomeDB	P46089.
Gene expression databases
ArrayExpress	P46089.
Bgee	P46089.
CleanEx	HS_GPR3.
Genevestigator	P46089.
GermOnline	ENSG00000181773. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR000984. GPR3. IPR000723. GPR_3/6/12_orphan. [Graphical view]
PANTHER	PTHR22750:SF9. PTHR22750:SF9. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR00648. GPR3ORPHANR. 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	2827.
NextBio	11155.
SOURCE	Search...

Entry information

Entry name

GPR3_HUMAN

Accession

Primary (citable) accession number: P46089
Secondary accession number(s): A8K570

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 115 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.