ID GP183_HUMAN Reviewed; 361 AA. AC P32249; B2R8N5; Q53F99; Q5JUH7; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 3. DT 02-SEP-2026, entry version 202. DE RecName: Full=G protein-coupled receptor 183 {ECO:0000305}; DE AltName: Full=Epstein-Barr virus-induced G protein-coupled receptor 2 {ECO:0000303|PubMed:8383238}; DE Short=EBI2 {ECO:0000303|PubMed:8383238}; DE Short=EBV-induced G protein-coupled receptor 2 {ECO:0000303|PubMed:8383238}; DE Short=hEBI2 {ECO:0000303|PubMed:22875855}; GN Name=GPR183 {ECO:0000312|HGNC:HGNC:3128}; GN Synonyms=EBI2 {ECO:0000303|PubMed:8383238}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=8383238; DOI=10.1128/jvi.67.4.2209-2220.1993; RA Birkenbach M.P., Josefsen K., Yalamanchili R.R., Lenoir G.M., Kieff E.; RT "Epstein-Barr virus-induced genes: first lymphocyte-specific G protein- RT coupled peptide receptors."; RL J. Virol. 67:2209-2220(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Amygdala; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=16540462; DOI=10.1074/jbc.m602245200; RA Rosenkilde M.M., Benned-Jensen T., Andersen H., Holst P.J., Kledal T.N., RA Luttichau H.R., Larsen J.K., Christensen J.P., Schwartz T.W.; RT "Molecular pharmacological phenotyping of EBI2. An orphan seven- RT transmembrane receptor with constitutive activity."; RL J. Biol. Chem. 281:13199-13208(2006). RN [8] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-87; CYS-256 AND PHE-257. RX PubMed=18628402; DOI=10.1124/mol.108.049676; RA Benned-Jensen T., Rosenkilde M.M.; RT "Structural motifs of importance for the constitutive activity of the RT orphan 7TM receptor EBI2: analysis of receptor activation in the absence of RT an agonist."; RL Mol. Pharmacol. 74:1008-1021(2008). RN [9] RP IDENTIFICATION OF GSK682753A AS AN INVERSE AGONIST, SUBCELLULAR LOCATION, RP FUNCTION, AND MUTAGENESIS OF PHE-111. RX PubMed=21673108; DOI=10.1074/jbc.m110.196345; RA Benned-Jensen T., Smethurst C., Holst P.J., Page K.R., Sauls H., RA Sivertsen B., Schwartz T.W., Blanchard A., Jepras R., Rosenkilde M.M.; RT "Ligand modulation of the Epstein-Barr virus-induced seven-transmembrane RT receptor EBI2: identification of a potent and efficacious inverse RT agonist."; RL J. Biol. Chem. 286:29292-29302(2011). RN [10] RP FUNCTION. RX PubMed=21796212; DOI=10.1038/nature10280; RA Hannedouche S., Zhang J., Yi T., Shen W., Nguyen D., Pereira J.P., RA Guerini D., Baumgarten B.U., Roggo S., Wen B., Knochenmuss R., Noel S., RA Gessier F., Kelly L.M., Vanek M., Laurent S., Preuss I., Miault C., RA Christen I., Karuna R., Li W., Koo D.I., Suply T., Schmedt C., Peters E.C., RA Falchetto R., Katopodis A., Spanka C., Roy M.O., Detheux M., Chen Y.A., RA Schultz P.G., Cho C.Y., Seuwen K., Cyster J.G., Sailer A.W.; RT "Oxysterols direct immune cell migration via EBI2."; RL Nature 475:524-527(2011). RN [11] RP FUNCTION, SUBUNIT, AND INTERACTION WITH CXCR5. RX PubMed=22913878; DOI=10.1096/fj.12-208876; RA Barroso R., Martinez Munoz L., Barrondo S., Vega B., Holgado B.L., RA Lucas P., Baillo A., Salles J., Rodriguez-Frade J.M., Mellado M.; RT "EBI2 regulates CXCL13-mediated responses by heterodimerization with RT CXCR5."; RL FASEB J. 26:4841-4854(2012). RN [12] RP FUNCTION, AGONIST-BINDING, AND MUTAGENESIS OF ASP-77; ARG-87; TYR-90; RP PHE-111; TYR-112; THR-115; TYR-116; TYR-205 AND TYR-260. RX PubMed=22875855; DOI=10.1074/jbc.m112.387894; RA Benned-Jensen T., Norn C., Laurent S., Madsen C.M., Larsen H.M., RA Arfelt K.N., Wolf R.M., Frimurer T., Sailer A.W., Rosenkilde M.M.; RT "Molecular characterization of oxysterol binding to the Epstein-Barr virus- RT induced gene 2 (GPR183)."; RL J. Biol. Chem. 287:35470-35483(2012). RN [13] RP FUNCTION, AGONIST-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-21; RP ASP-77; PRO-85; ARG-87; TYR-90; CYS-104; TYR-112; ASN-114; TYR-116; RP CYS-181; GLU-183; LEU-197; PHE-257; TYR-260; HIS-261; ILE-264; CYS-280; RP HIS-291; VAL-294 AND MET-297. RX PubMed=22930711; DOI=10.1124/mol.112.080275; RA Zhang L., Shih A.Y., Yang X.V., Kuei C., Wu J., Deng X., Mani N.S., RA Mirzadegan T., Sun S., Lovenberg T.W., Liu C.; RT "Identification of structural motifs critical for epstein-barr virus- RT induced molecule 2 function and homology modeling of the ligand docking RT site."; RL Mol. Pharmacol. 82:1094-1103(2012). RN [14] RP IDENTIFICATION OF GSK682753A AS AN INVERSE AGONIST. RX PubMed=23772388; DOI=10.1016/j.fob.2013.02.003; RA Benned-Jensen T., Madsen C.M., Arfelt K.N., Smethurts C., Blanchard A., RA Jepras R., Rosenkilde M.M.; RT "Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced RT gene 2 (EBI2) activation."; RL FEBS Open Bio 3:156-160(2013). RN [15] RP IDENTIFICATION OF NIBR189 AS AN AGONIST. RX PubMed=24678947; DOI=10.1021/jm4019355; RA Gessier F., Preuss I., Yin H., Rosenkilde M.M., Laurent S., Endres R., RA Chen Y.A., Marsilje T.H., Seuwen K., Nguyen D.G., Sailer A.W.; RT "Identification and characterization of small molecule modulators of the RT Epstein-Barr virus-induced gene 2 (EBI2) receptor."; RL J. Med. Chem. 57:3358-3368(2014). RN [16] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=25297897; DOI=10.1002/glia.22757; RA Rutkowska A., Preuss I., Gessier F., Sailer A.W., Dev K.K.; RT "EBI2 regulates intracellular signaling and migration in human astrocyte."; RL Glia 63:341-351(2015). RN [17] RP VARIANT [LARGE SCALE ANALYSIS] VAL-338. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). CC -!- FUNCTION: G protein-coupled receptor expressed in lymphocytes that acts CC as a chemotactic receptor for B-cells, T-cells, splenic dendritic CC cells, monocytes/macrophages and astrocytes (By similarity). Receptor CC for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and CC other related oxysterols (PubMed:21796212, PubMed:22875855, CC PubMed:22930711). Mediates cell positioning and movement of a number of CC cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic CC gradient (By similarity). Binding of 7-alpha,25-OHC mediates the CC correct localization of B-cells during humoral immune responses (By CC similarity). Guides B-cell movement along the B-cell zone-T-cell zone CC boundary and later to interfollicular and outer follicular regions (By CC similarity). Its specific expression during B-cell maturation helps CC position B-cells appropriately for mounting T-dependent antibody CC responses (By similarity). Collaborates with CXCR5 to mediate B-cell CC migration; probably by forming a heterodimer with CXCR5 that affects CC the interaction between of CXCL13 and CXCR5 (PubMed:22913878). Also CC acts as a chemotactic receptor for some T-cells upon binding to 7- CC alpha,25-OHC ligand (By similarity). Promotes follicular helper T (Tfh) CC cells differentiation by positioning activated T-cells at the follicle- CC T-zone interface, promoting contact of newly activated CD4 T-cells with CC activated dendritic cells and exposing them to Tfh-cell-promoting CC inducible costimulator (ICOS) ligand (By similarity). Expression in CC splenic dendritic cells is required for their homeostasis, localization CC and ability to induce B- and T-cell responses: GPR183 acts as a CC chemotactic receptor in dendritic cells that mediates the accumulation CC of CD4(+) dendritic cells in bridging channels (By similarity). CC Regulates migration of astrocytes and is involved in communication CC between astrocytes and macrophages (PubMed:25297897). Promotes CC osteoclast precursor migration to bone surfaces (By similarity). CC Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)- CC alpha (PubMed:21673108, PubMed:25297897). Signals constitutively also CC via MAPK1/3 (ERK1/2) (By similarity). {ECO:0000250|UniProtKB:Q3U6B2, CC ECO:0000269|PubMed:16540462, ECO:0000269|PubMed:21673108, CC ECO:0000269|PubMed:21796212, ECO:0000269|PubMed:22875855, CC ECO:0000269|PubMed:22913878, ECO:0000269|PubMed:22930711, CC ECO:0000269|PubMed:25297897}. CC -!- SUBUNIT: Homodimer and heterodimer (PubMed:22913878). Heterodimerizes CC with CXCR5; leading to modulate the interaction between of CXCL13 and CC CXCR5 (PubMed:22913878). {ECO:0000269|PubMed:22913878}. CC -!- INTERACTION: CC P32249; O60894: RAMP1; NbExp=3; IntAct=EBI-715171, EBI-962893; CC P32249; O60895: RAMP2; NbExp=3; IntAct=EBI-715171, EBI-9009040; CC P32249; O60896: RAMP3; NbExp=3; IntAct=EBI-715171, EBI-720447; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16540462, CC ECO:0000269|PubMed:18628402, ECO:0000269|PubMed:21673108, CC ECO:0000269|PubMed:22930711}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Expressed abundantly in lymphoid tissues such as CC spleen and lymph node, and in B- and T-lymphocytes (PubMed:16540462, CC PubMed:8383238). Also highly expressed in lung, heart and CC gastrointestinal tract, and weakly expressed in the urogenital system CC and brain (PubMed:16540462, PubMed:8383238). Expressed in astrocytes CC (PubMed:25297897). {ECO:0000269|PubMed:16540462, CC ECO:0000269|PubMed:25297897, ECO:0000269|PubMed:8383238}. CC -!- INDUCTION: Induced following Epstein-Barr virus (EBV) infection CC (PubMed:8383238). {ECO:0000269|PubMed:8383238}. CC -!- MISCELLANEOUS: GSK682753A (8-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-3- CC [(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one), an CC inverse agonist, selectively inhibits the constitutive activity of CC GPR183 with high potency and efficacy (PubMed:21673108, CC PubMed:23772388). Specifically inhibited by NIBR189 ((2E)-3-(4- CC Bromophenyl)-1-[4-(4-methoxybenzoyl)-1-piperazinyl]-2-propene-1-one). CC {ECO:0000269|PubMed:21673108, ECO:0000269|PubMed:23772388}. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-5 is the initiator. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L08177; AAA35924.1; -; mRNA. DR EMBL; AK292091; BAF84780.1; -; mRNA. DR EMBL; AK313443; BAG36232.1; -; mRNA. DR EMBL; AK223390; BAD97110.1; -; mRNA. DR EMBL; AL160155; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471085; EAX09018.1; -; Genomic_DNA. DR EMBL; BC020752; AAH20752.1; -; mRNA. DR CCDS; CCDS9492.1; -. DR PIR; B45680; B45680. DR RefSeq; NP_004942.1; NM_004951.5. DR PDB; 7TUY; EM; 2.98 A; R=1-361. DR PDB; 7TUZ; EM; 3.12 A; R=2-361. DR AlphaFoldDB; P32249; -. DR EMDB; EMD-26135; -. DR EMDB; EMD-26136; -. DR SMR; P32249; -. DR BioGRID; 108212; 39. DR CORUM; P32249; -. DR FunCoup; P32249; 835. DR IntAct; P32249; 37. DR NDEx; IQUERY-CP-GPR183; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000365596; -. DR BindingDB; P32249; -. DR ChEMBL; CHEMBL3259470; -. DR GuidetoPHARMACOLOGY; 81; -. DR TCDB; 9.A.14.13.40; the g-protein-coupled receptor (gpcr) family. DR CarbonylDB; P32249; -. DR iPTMnet; P32249; -. DR PhosphoSitePlus; P32249; -. DR SwissPalm; P32249; -. DR BioMuta; GPR183; -. DR DMDM; 205371788; -. DR MassIVE; P32249; -. DR PaxDb; 9606-ENSP00000365596; -. DR PeptideAtlas; P32249; -. DR ProteomicsDB; 54857; -. DR Antibodypedia; 10905; 238 antibodies from 34 providers. DR DNASU; 1880; -. DR Ensembl; ENST00000376414.5; ENSP00000365596.4; ENSG00000169508.8. DR Ensembl; ENST00000858905.1; ENSP00000528964.1; ENSG00000169508.8. DR GeneID; 1880; -. DR KEGG; hsa:1880; -. DR MANE-Select; ENST00000376414.5; ENSP00000365596.4; NM_004951.5; NP_004942.1. DR UCSC; uc001vog.4; human. DR AGR; HGNC:3128; -. DR ClinPGx; PA162390174; -. DR CTD; 1880; -. DR DisGeNET; 1880; -. DR GeneCards; GPR183; -. DR HGNC; HGNC:3128; GPR183. DR HPA; ENSG00000169508; Tissue enhanced (bone marrow, lymphoid tissue). DR MIM; 605741; gene. DR OpenTargets; ENSG00000169508; -. DR VEuPathDB; HostDB:ENSG00000169508; -. DR eggNOG; ENOG502QWD9; Eukaryota. DR GeneTree; ENSGT01030000234518; -. DR HOGENOM; CLU_009579_8_2_1; -. DR InParanoid; P32249; -. DR OMA; NERTTCM; -. DR OrthoDB; 10021141at2759; -. DR PAN-GO; P32249; 2 GO annotations based on evolutionary models. DR PhylomeDB; P32249; -. DR PathwayCommons; P32249; -. DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors). DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SignaLink; P32249; -. DR SIGNOR; P32249; -. DR Agora; ENSG00000169508; -. DR BioGRID-ORCS; 1880; 11 hits in 1131 CRISPR screens. DR GeneWiki; GPR183; -. DR GenomeRNAi; 1880; -. DR Pharos; P32249; Tchem. DR PRO; PR:P32249; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P32249; protein. DR Bgee; ENSG00000169508; Expressed in vermiform appendix and 169 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB. DR GO; GO:0008142; F:oxysterol binding; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB. DR GO; GO:0002312; P:B cell activation involved in immune response; IBA:GO_Central. DR GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB. DR GO; GO:0036145; P:dendritic cell homeostasis; ISS:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0030595; P:leukocyte chemotaxis; IMP:UniProtKB. DR GO; GO:0002313; P:mature B cell differentiation involved in immune response; ISS:UniProtKB. DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:2000458; P:regulation of astrocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0010818; P:T cell chemotaxis; ISS:UniProtKB. DR GO; GO:0061470; P:T follicular helper cell differentiation; ISS:UniProtKB. DR CDD; cd15159; 7tmA_EBI2; 1. DR FunFam; 1.20.1070.10:FF:000017; lysophosphatidic acid receptor 4; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR047160; GP183-like. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24237; G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24237:SF7; G-PROTEIN COUPLED RECEPTOR 183; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01157; P2YPURNOCPTR. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR PDBsum; 7TUY; -. DR PDBsum; 7TUZ; -. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; KW G protein-coupled receptor; Immunity; Membrane; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..361 FT /note="G protein-coupled receptor 183" FT /id="PRO_0000069411" FT TOPO_DOM 1..31 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 32..57 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 58..77 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 78..95 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 96..105 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 106..127 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 128..149 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 150..168 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 169..192 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 193..215 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 216..241 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 242..265 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 266..287 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 288..312 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 313..361 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 126..134 FT /note="Interaction with G proteins" FT REGION 340..361 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 348..361 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 87 FT /ligand="7alpha,25-dihydroxycholesterol" FT /ligand_id="ChEBI:CHEBI:37623" FT /ligand_note="agonist" FT /evidence="ECO:0000305|PubMed:22875855" FT BINDING 112 FT /ligand="7alpha,25-dihydroxycholesterol" FT /ligand_id="ChEBI:CHEBI:37623" FT /ligand_note="agonist" FT /evidence="ECO:0000305|PubMed:22875855" FT BINDING 116 FT /ligand="7alpha,25-dihydroxycholesterol" FT /ligand_id="ChEBI:CHEBI:37623" FT /ligand_note="agonist" FT /evidence="ECO:0000305|PubMed:22875855" FT BINDING 260 FT /ligand="7alpha,25-dihydroxycholesterol" FT /ligand_id="ChEBI:CHEBI:37623" FT /ligand_note="agonist" FT /evidence="ECO:0000305|PubMed:22875855" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U6B2" FT DISULFID 104..181 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VARIANT 338 FT /note="A -> V (in an acute myeloid leukemia sample; somatic FT mutation; dbSNP:rs1466524306)" FT /evidence="ECO:0000269|PubMed:18987736" FT /id="VAR_054147" FT MUTAGEN 21 FT /note="C->A: Strongly reduced localization to the cell FT membrane and reduced protein expression levels." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 77 FT /note="D->A: Loss of receptor activation without affecting FT oxysterol agonist-binding." FT /evidence="ECO:0000269|PubMed:22875855, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 77 FT /note="D->R: Strong decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:22875855" FT MUTAGEN 85 FT /note="P->A: Strongly reduced localization to the cell FT membrane." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 87 FT /note="R->A: Strong decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:18628402, FT ECO:0000269|PubMed:22875855, ECO:0000269|PubMed:22930711" FT MUTAGEN 87 FT /note="R->K: Slight decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:18628402, FT ECO:0000269|PubMed:22875855" FT MUTAGEN 87 FT /note="R->W: Slight decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 90 FT /note="Y->A: 10-fold reduction in receptor activation. FT Strongly reduced localization to the cell membrane." FT /evidence="ECO:0000269|PubMed:22875855, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 104 FT /note="C->A: Abolishes localization to the cell membrane FT without affecting protein expression levels." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 111 FT /note="F->A,Y: 500-fold decrease of IC(50) for GSK682753A. FT No effect on oxysterol agonist-binding and receptor FT activation." FT /evidence="ECO:0000269|PubMed:21673108, FT ECO:0000269|PubMed:22875855" FT MUTAGEN 112 FT /note="Y->A,F: Strong decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:22875855, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 114 FT /note="N->A: Strongly reduced localization to the cell FT membrane." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 115 FT /note="T->A,F: No effect." FT /evidence="ECO:0000269|PubMed:22875855" FT MUTAGEN 116 FT /note="Y->A,F: Strong decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:22875855, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 181 FT /note="C->A: Abolishes localization to the cell membrane FT without affecting protein expression levels." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 183 FT /note="E->A: Strong reduction in ligand potency." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 197 FT /note="L->A: Reduced localization to the cell membrane and FT reduced receptor function." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 205 FT /note="Y->A,F: No effect." FT /evidence="ECO:0000269|PubMed:22875855" FT MUTAGEN 256 FT /note="C->A: Increased receptor activation." FT /evidence="ECO:0000269|PubMed:18628402" FT MUTAGEN 257 FT /note="F->A: Increased receptor activation. Strongly FT reduced localization to the cell membrane." FT /evidence="ECO:0000269|PubMed:18628402, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 260 FT /note="Y->A,F: Strong decrease in oxysterol agonist-binding FT and receptor activation." FT /evidence="ECO:0000269|PubMed:22875855, FT ECO:0000269|PubMed:22930711" FT MUTAGEN 261 FT /note="H->A: Reduced localization to the cell membrane and FT reduced receptor function." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 264 FT /note="I->A: Reduced localization to the cell membrane and FT reduced receptor function." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 280 FT /note="C->A: Strongly reduced localization to the cell FT membrane and reduced protein expression levels." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 287 FT /note="Q->A: 10-fold reduction in receptor activation." FT /evidence="ECO:0000269|PubMed:22875855" FT MUTAGEN 291 FT /note="H->A: 10-fold reduction in receptor activation." FT /evidence="ECO:0000269|PubMed:22875855" FT MUTAGEN 291 FT /note="H->A: Reduced localization to the cell membrane and FT reduced receptor function." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 294 FT /note="V->A: Reduced localization to the cell membrane and FT reduced receptor function." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 297 FT /note="M->A: Reduced localization to the cell membrane and FT reduced receptor function, without affecting oxysterol FT agonist-binding." FT /evidence="ECO:0000269|PubMed:22930711" FT MUTAGEN 297 FT /note="M->I: Reduced localization to the cell membrane and FT reduced receptor function. Reduced oxysterol FT agonist-binding." FT /evidence="ECO:0000269|PubMed:22930711" FT CONFLICT 6 FT /note="A -> V (in Ref. 3; BAD97110)" FT /evidence="ECO:0000305" FT CONFLICT 179 FT /note="I -> N (in Ref. 2; BAG36232)" FT /evidence="ECO:0000305" FT CONFLICT 325 FT /note="R -> Q (in Ref. 2; BAG36232)" FT /evidence="ECO:0000305" FT TURN 23..26 FT /evidence="ECO:0007829|PDB:7TUZ" FT HELIX 27..58 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 67..82 FT /evidence="ECO:0007829|PDB:7TUY" FT TURN 85..87 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 102..132 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 145..163 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 184..187 FT /evidence="ECO:0007829|PDB:7TUZ" FT TURN 190..192 FT /evidence="ECO:0007829|PDB:7TUZ" FT HELIX 196..201 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 202..206 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 207..224 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 231..236 FT /evidence="ECO:0007829|PDB:7TUZ" FT HELIX 238..256 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 258..269 FT /evidence="ECO:0007829|PDB:7TUY" FT TURN 270..273 FT /evidence="ECO:0007829|PDB:7TUY" FT TURN 279..281 FT /evidence="ECO:0007829|PDB:7TUZ" FT STRAND 284..286 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 287..310 FT /evidence="ECO:0007829|PDB:7TUY" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:7TUY" FT HELIX 316..319 FT /evidence="ECO:0007829|PDB:7TUY" SQ SEQUENCE 361 AA; 41224 MW; B5A2171F34C9C67B CRC64; MDIQMANNFT PPSATPQGND CDLYAHHSTA RIVMPLHYSL VFIIGLVGNL LALVVIVQNR KKINSTTLYS TNLVISDILF TTALPTRIAY YAMGFDWRIG DALCRITALV FYINTYAGVN FMTCLSIDRF IAVVHPLRYN KIKRIEHAKG VCIFVWILVF AQTLPLLINP MSKQEAERIT CMEYPNFEET KSLPWILLGA CFIGYVLPLI IILICYSQIC CKLFRTAKQN PLTEKSGVNK KALNTIILII VVFVLCFTPY HVAIIQHMIK KLRFSNFLEC SQRHSFQISL HFTVCLMNFN CCMDPFIYFF ACKGYKRKVM RMLKRQVSVS ISSAVKSAPE ENSREMTETQ MMIHSKSSNG K //