P32249 (GP183_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor 183

Alternative name(s):
Epstein-Barr virus-induced G-protein coupled receptor 2
Short name=EBI2
Short name=EBV-induced G-protein coupled receptor 2

Gene names

Name:	GPR183
Synonyms:	EBI2

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	361 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols. Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses. Promotes activated B-cell localization in the outer follicle and interfollicular regions. Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses By similarity. Signals constitutively through G(i)-alpha, but not through G(s)-alpha or G(q)-alpha. Signals constitutively also via MAPK1/3 (ERK1/2). Ref.7 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.7 Ref.8.
Tissue specificity	Expressed abundantly in lymphoid tissues such as spleen and lymph node, and in B- and T-lymphocytes. Also highly expressed in lung, heart and gastrointestinal tract, and weakly expressed in the urogenital system and brain. Ref.1 Ref.7
Induction	By Epstein-Barr virus (EBV). Ref.1
Miscellaneous	GSK682753A (8-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one), an inverse agonist, selectively inhibits the constitutive activity of GPR183 with high potency and efficacy (Ref.8).
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Caution	It is uncertain whether Met-1 or Met-5 is the initiator.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	humoral immune response Inferred from sequence or structural similarity. Source: UniProtKB mature B cell differentiation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of B cell proliferation Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.8. Source: UniProtKB
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled purinergic nucleotide receptor activity Inferred from electronic annotation. Source: InterPro G-protein coupled receptor activity Traceable author statement Ref.1. Source: ProtInc oxysterol binding Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 361	361	G-protein coupled receptor 183		PRO_0000069411
Regions
	Topological domain	1 – 31	31	Extracellular Potential
	Transmembrane	32 – 57	26	Helical; Name=1; Potential
	Topological domain	58 – 77	20	Cytoplasmic Potential
	Transmembrane	78 – 95	18	Helical; Name=2; Potential
	Topological domain	96 – 105	10	Extracellular Potential
	Transmembrane	106 – 127	22	Helical; Name=3; Potential
	Topological domain	128 – 149	22	Cytoplasmic Potential
	Transmembrane	150 – 168	19	Helical; Name=4; Potential
	Topological domain	169 – 192	24	Extracellular Potential
	Transmembrane	193 – 215	23	Helical; Name=5; Potential
	Topological domain	216 – 241	26	Cytoplasmic Potential
	Transmembrane	242 – 265	24	Helical; Name=6; Potential
	Topological domain	266 – 287	22	Extracellular Potential
	Transmembrane	288 – 312	25	Helical; Name=7; Potential
	Topological domain	313 – 361	49	Cytoplasmic Potential
	Region	126 – 134	9	Interaction with G proteins
Amino acid modifications
	Modified residue	328	1	Phosphoserine By similarity
	Disulfide bond	104 ↔ 181		By similarity
Natural variations
	Natural variant	338	1	A → V in an acute myeloid leukemia sample; somatic mutation. Ref.10		VAR_054147
Experimental info
	Mutagenesis	111	1	F → A: 500-fold decrease of IC(50) for GSK682753A. Ref.8
	Sequence conflict	6	1	A → V in BAD97110. Ref.3
	Sequence conflict	179	1	I → N in BAG36232. Ref.2
	Sequence conflict	325	1	R → Q in BAG36232. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P32249 [UniParc]. Last modified September 2, 2008. Version 3. Checksum: B5A2171F34C9C67B	FASTA	361	41,224
	10 20 30 40 50 60 MDIQMANNFT PPSATPQGND CDLYAHHSTA RIVMPLHYSL VFIIGLVGNL LALVVIVQNR 70 80 90 100 110 120 KKINSTTLYS TNLVISDILF TTALPTRIAY YAMGFDWRIG DALCRITALV FYINTYAGVN 130 140 150 160 170 180 FMTCLSIDRF IAVVHPLRYN KIKRIEHAKG VCIFVWILVF AQTLPLLINP MSKQEAERIT 190 200 210 220 230 240 CMEYPNFEET KSLPWILLGA CFIGYVLPLI IILICYSQIC CKLFRTAKQN PLTEKSGVNK 250 260 270 280 290 300 KALNTIILII VVFVLCFTPY HVAIIQHMIK KLRFSNFLEC SQRHSFQISL HFTVCLMNFN 310 320 330 340 350 360 CCMDPFIYFF ACKGYKRKVM RMLKRQVSVS ISSAVKSAPE ENSREMTETQ MMIHSKSSNG K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors." Birkenbach M.P., Josefsen K., Yalamanchili R.R., Lenoir G.M., Kieff E. J. Virol. 67:2209-2220(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
[2]	"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]. Tissue: Amygdala.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Placenta.
[7]	"Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity." Rosenkilde M.M., Benned-Jensen T., Andersen H., Holst P.J., Kledal T.N., Luttichau H.R., Larsen J.K., Christensen J.P., Schwartz T.W. J. Biol. Chem. 281:13199-13208(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"Ligand modulation of the Epstein-Barr virus-induced seven-transmembrane receptor EBI2: identification of a potent and efficacious inverse agonist." Benned-Jensen T., Smethurst C., Holst P.J., Page K.R., Sauls H., Sivertsen B., Schwartz T.W., Blanchard A., Jepras R., Rosenkilde M.M. J. Biol. Chem. 286:29292-29302(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF GSK682753A AS AN INVERSE AGONIST, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF PHE-111.
[9]	"Oxysterols direct immune cell migration via EBI2." Hannedouche S., Zhang J., Yi T., Shen W., Nguyen D., Pereira J.P., Guerini D., Baumgarten B.U., Roggo S., Wen B., Knochenmuss R., Noel S., Gessier F., Kelly L.M., Vanek M., Laurent S., Preuss I., Miault C. , Christen I., Karuna R., Li W., Koo D.I., Suply T., Schmedt C., Peters E.C., Falchetto R., Katopodis A., Spanka C., Roy M.O., Detheux M., Chen Y.A., Schultz P.G., Cho C.Y., Seuwen K., Cyster J.G., Sailer A.W. Nature 475:524-527(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF OXYSTEROLS AS ENDOGENOUS LIGANDS.
[10]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-338.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L08177 mRNA. Translation: AAA35924.1. AK292091 mRNA. Translation: BAF84780.1. AK313443 mRNA. Translation: BAG36232.1. AK223390 mRNA. Translation: BAD97110.1. AL160155 Genomic DNA. Translation: CAI14308.1. CH471085 Genomic DNA. Translation: EAX09018.1. BC020752 mRNA. Translation: AAH20752.1.
IPI	IPI00027688.
PIR	B45680.
RefSeq	NP_004942.1. NM_004951.4.
UniGene	Hs.784.
3D structure databases
ProteinModelPortal	P32249.
ModBase	Search...
Protein-protein interaction databases
IntAct	P32249. 2 interactions.
MINT	MINT-1427405.
STRING	9606.ENSP00000365596.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P32249.
Polymorphism databases
DMDM	205371788.
Proteomic databases
PaxDb	P32249.
PeptideAtlas	P32249.
PRIDE	P32249.
Protocols and materials databases
DNASU	1880.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376414; ENSP00000365596; ENSG00000169508.
GeneID	1880.
KEGG	hsa:1880.
UCSC	uc001vog.3. human.
Organism-specific databases
CTD	1880.
GeneCards	GC13M099946.
HGNC	HGNC:3128. GPR183.
HPA	CAB033690. HPA028847.
MIM	605741. gene.
neXtProt	NX_P32249.
PharmGKB	PA162390174.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG145860.
HOGENOM	HOG000043070.
HOVERGEN	HBG101355.
InParanoid	P32249.
KO	K04305.
OMA	LVFYINT.
OrthoDB	EOG4V437Z.
PhylomeDB	P32249.
Gene expression databases
Bgee	P32249.
CleanEx	HS_GPR183.
Genevestigator	P32249.
GermOnline	ENSG00000169508. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002286. P2_purnocptor. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01157. P2YPURNOCPTR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1880.
NextBio	7689.
SOURCE	Search...

Entry information

Entry name

GP183_HUMAN

Accession

Primary (citable) accession number: P32249
Secondary accession number(s): B2R8N5, Q53F99, Q5JUH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	September 2, 2008
Last modified:	May 1, 2013
This is version 120 of the entry and version 3 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.