GP183_HUMAN
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 03-AUG-2022, entry version 184.
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 -!- 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}.
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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_004951.4.
DR RefSeq; XP_016875894.1; XM_017020405.1.
DR PDB; 7TUY; EM; 2.98 A; R=1-361.
DR PDB; 7TUZ; EM; 3.12 A; R=2-361.
DR PDBsum; 7TUY; -.
DR PDBsum; 7TUZ; -.
DR AlphaFoldDB; P32249; -.
DR SMR; P32249; -.
DR BioGRID; 108212; 37.
DR IntAct; P32249; 31.
DR STRING; 9606.ENSP00000365596; -.
DR BindingDB; P32249; -.
DR ChEMBL; CHEMBL3259470; -.
DR GuidetoPHARMACOLOGY; 81; -.
DR CarbonylDB; P32249; -.
DR iPTMnet; P32249; -.
DR PhosphoSitePlus; P32249; -.
DR SwissPalm; P32249; -.
DR BioMuta; GPR183; -.
DR DMDM; 205371788; -.
DR jPOST; P32249; -.
DR MassIVE; P32249; -.
DR MaxQB; P32249; -.
DR PaxDb; P32249; -.
DR PeptideAtlas; P32249; -.
DR PRIDE; P32249; -.
DR ProteomicsDB; 54857; -.
DR Antibodypedia; 10905; 236 antibodies from 32 providers.
DR DNASU; 1880; -.
DR Ensembl; ENST00000376414.5; ENSP00000365596.4; ENSG00000169508.7.
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 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 neXtProt; NX_P32249; -.
DR OpenTargets; ENSG00000169508; -.
DR PharmGKB; PA162390174; -.
DR VEuPathDB; HostDB:ENSG00000169508; -.
DR eggNOG; ENOG502QWD9; Eukaryota.
DR GeneTree; ENSGT01030000234518; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; P32249; -.
DR OMA; HYTVFLM; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; P32249; -.
DR TreeFam; TF350009; -.
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 BioGRID-ORCS; 1880; 10 hits in 1053 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 167 other tissues.
DR ExpressionAtlas; P32249; baseline and differential.
DR Genevisible; P32249; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Immunity; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; 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 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 agonist-
FT 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"
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
