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Protein

G-protein coupled receptor 183

Gene

GPR183

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (By similarity). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796212, PubMed:22875855, PubMed:22930711). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (By similarity). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (By similarity). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (By similarity). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (By similarity). Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5 (PubMed:22913878). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (By similarity). Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand (By similarity). Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4+ dendritic cells in bridging channels (By similarity). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897). Promotes osteoclast precursor migration to bone surfaces (By similarity). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (PubMed:21673108, PubMed:25297897). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).By similarity7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei87 – 871Oxysterol agonist1 Publication
Binding sitei112 – 1121Oxysterol agonist1 Publication
Binding sitei116 – 1161Oxysterol agonist1 Publication
Binding sitei260 – 2601Oxysterol agonist1 Publication

GO - Molecular functioni

  • G-protein coupled receptor activity Source: ProtInc
  • oxysterol binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • B cell activation involved in immune response Source: GO_Central
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • immune response Source: ProtInc
  • mature B cell differentiation involved in immune response Source: UniProtKB
  • positive regulation of B cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Adaptive immunity, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein coupled receptor 183Curated
Alternative name(s):
Epstein-Barr virus-induced G-protein coupled receptor 21 Publication
Short name:
EBI21 Publication
Short name:
EBV-induced G-protein coupled receptor 21 Publication
Short name:
hEBI21 Publication
Gene namesi
Name:GPR183Imported
Synonyms:EBI21 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:3128. GPR183.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3131ExtracellularSequence analysisAdd
BLAST
Transmembranei32 – 5726Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini58 – 7720CytoplasmicSequence analysisAdd
BLAST
Transmembranei78 – 9518Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini96 – 10510ExtracellularSequence analysis
Transmembranei106 – 12722Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini128 – 14922CytoplasmicSequence analysisAdd
BLAST
Transmembranei150 – 16819Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini169 – 19224ExtracellularSequence analysisAdd
BLAST
Transmembranei193 – 21523Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini216 – 24126CytoplasmicSequence analysisAdd
BLAST
Transmembranei242 – 26524Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini266 – 28722ExtracellularSequence analysisAdd
BLAST
Transmembranei288 – 31225Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini313 – 36149CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi21 – 211C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication
Mutagenesisi77 – 771D → A: Loss of receptor activation without affecting oxysterol agonist-binding. 2 Publications
Mutagenesisi77 – 771D → R: Strong decrease in oxysterol agonist-binding and receptor activation. 1 Publication
Mutagenesisi85 – 851P → A: Strongly reduced localization to the cell membrane. 1 Publication
Mutagenesisi87 – 871R → A: Strong decrease in oxysterol agonist-binding and receptor activation. 3 Publications
Mutagenesisi87 – 871R → K: Slight decrease in oxysterol agonist-binding and receptor activation. 2 Publications
Mutagenesisi87 – 871R → W: Slight decrease in oxysterol agonist-binding and receptor activation. 1 Publication
Mutagenesisi90 – 901Y → A: 10-fold reduction in receptor activation. Strongly reduced localization to the cell membrane. 2 Publications
Mutagenesisi104 – 1041C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication
Mutagenesisi111 – 1111F → A or Y: 500-fold decrease of IC(50) for GSK682753A. No effect on oxysterol agonist-binding and receptor activation. 2 Publications
Mutagenesisi112 – 1121Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications
Mutagenesisi114 – 1141N → A: Strongly reduced localization to the cell membrane. 1 Publication
Mutagenesisi115 – 1151T → A or F: No effect. 1 Publication
Mutagenesisi116 – 1161Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications
Mutagenesisi181 – 1811C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication
Mutagenesisi183 – 1831E → A: Strong reduction in ligand potency. 1 Publication
Mutagenesisi197 – 1971L → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication
Mutagenesisi205 – 2051Y → A or F: No effect. 1 Publication
Mutagenesisi256 – 2561C → A: Increased receptor activation. 1 Publication
Mutagenesisi257 – 2571F → A: Increased receptor activation. Strongly reduced localization to the cell membrane. 2 Publications
Mutagenesisi260 – 2601Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications
Mutagenesisi261 – 2611H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication
Mutagenesisi264 – 2641I → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication
Mutagenesisi280 – 2801C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication
Mutagenesisi287 – 2871Q → A: 10-fold reduction in receptor activation. 1 Publication
Mutagenesisi291 – 2911H → A: 10-fold reduction in receptor activation. 1 Publication
Mutagenesisi291 – 2911H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication
Mutagenesisi294 – 2941V → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication
Mutagenesisi297 – 2971M → A: Reduced localization to the cell membrane and reduced receptor function, without affecting oxysterol agonist-binding. 1 Publication
Mutagenesisi297 – 2971M → I: Reduced localization to the cell membrane and reduced receptor function. Reduced oxysterol agonist-binding. 1 Publication

Organism-specific databases

PharmGKBiPA162390174.

Chemistry

ChEMBLiCHEMBL3259470.
GuidetoPHARMACOLOGYi81.

Polymorphism and mutation databases

BioMutaiGPR183.
DMDMi205371788.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 361361G-protein coupled receptor 183PRO_0000069411Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi104 ↔ 181PROSITE-ProRule annotation
Modified residuei328 – 3281PhosphoserineBy similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiP32249.
PaxDbiP32249.
PeptideAtlasiP32249.
PRIDEiP32249.

PTM databases

iPTMnetiP32249.
PhosphoSiteiP32249.
SwissPalmiP32249.

Expressioni

Tissue specificityi

Expressed abundantly in lymphoid tissues such as spleen and lymph node, and in B- and T-lymphocytes (PubMed:16540462, PubMed:8383238). Also highly expressed in lung, heart and gastrointestinal tract, and weakly expressed in the urogenital system and brain (PubMed:16540462, PubMed:8383238). Expressed in astrocytes (PubMed:25297897).3 Publications

Inductioni

Induced following Epstein-Barr virus (EBV) infection (PubMed:8383238).1 Publication

Gene expression databases

BgeeiENSG00000169508.
CleanExiHS_GPR183.
ExpressionAtlasiP32249. baseline and differential.
GenevisibleiP32249. HS.

Organism-specific databases

HPAiCAB033690.
HPA028847.

Interactioni

Subunit structurei

Homodimer and heterodimer (PubMed:22913878). Heterodimerizes with CXCR5; leading to modulate the interaction between of CXCL13 and CXCR5 (PubMed:22913878).1 Publication

Protein-protein interaction databases

BioGridi108212. 35 interactions.
IntActiP32249. 2 interactions.
MINTiMINT-1427405.
STRINGi9606.ENSP00000365596.

Chemistry

BindingDBiP32249.

Structurei

3D structure databases

ProteinModelPortaliP32249.
SMRiP32249. Positions 19-323.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni126 – 1349Interaction with G proteins

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEQQ. Eukaryota.
ENOG4110QC8. LUCA.
GeneTreeiENSGT00760000118784.
HOGENOMiHOG000043070.
HOVERGENiHBG101355.
InParanoidiP32249.
KOiK04305.
OMAiRSAPEEN.
OrthoDBiEOG091G0B23.
PhylomeDBiP32249.
TreeFamiTF350009.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P32249-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDIQMANNFT PPSATPQGND CDLYAHHSTA RIVMPLHYSL VFIIGLVGNL
60 70 80 90 100
LALVVIVQNR KKINSTTLYS TNLVISDILF TTALPTRIAY YAMGFDWRIG
110 120 130 140 150
DALCRITALV FYINTYAGVN FMTCLSIDRF IAVVHPLRYN KIKRIEHAKG
160 170 180 190 200
VCIFVWILVF AQTLPLLINP MSKQEAERIT CMEYPNFEET KSLPWILLGA
210 220 230 240 250
CFIGYVLPLI IILICYSQIC CKLFRTAKQN PLTEKSGVNK KALNTIILII
260 270 280 290 300
VVFVLCFTPY HVAIIQHMIK KLRFSNFLEC SQRHSFQISL HFTVCLMNFN
310 320 330 340 350
CCMDPFIYFF ACKGYKRKVM RMLKRQVSVS ISSAVKSAPE ENSREMTETQ
360
MMIHSKSSNG K
Length:361
Mass (Da):41,224
Last modified:September 2, 2008 - v3
Checksum:iB5A2171F34C9C67B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61A → V in BAD97110 (Ref. 3) Curated
Sequence conflicti179 – 1791I → N in BAG36232 (PubMed:14702039).Curated
Sequence conflicti325 – 3251R → Q in BAG36232 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti338 – 3381A → V in an acute myeloid leukemia sample; somatic mutation. 1 Publication
VAR_054147

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9492.1.
PIRiB45680.
RefSeqiNP_004942.1. NM_004951.4.
UniGeneiHs.784.

Genome annotation databases

EnsembliENST00000376414; ENSP00000365596; ENSG00000169508.
GeneIDi1880.
KEGGihsa:1880.
UCSCiuc001vog.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9492.1.
PIRiB45680.
RefSeqiNP_004942.1. NM_004951.4.
UniGeneiHs.784.

3D structure databases

ProteinModelPortaliP32249.
SMRiP32249. Positions 19-323.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108212. 35 interactions.
IntActiP32249. 2 interactions.
MINTiMINT-1427405.
STRINGi9606.ENSP00000365596.

Chemistry

BindingDBiP32249.
ChEMBLiCHEMBL3259470.
GuidetoPHARMACOLOGYi81.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP32249.
PhosphoSiteiP32249.
SwissPalmiP32249.

Polymorphism and mutation databases

BioMutaiGPR183.
DMDMi205371788.

Proteomic databases

MaxQBiP32249.
PaxDbiP32249.
PeptideAtlasiP32249.
PRIDEiP32249.

Protocols and materials databases

DNASUi1880.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376414; ENSP00000365596; ENSG00000169508.
GeneIDi1880.
KEGGihsa:1880.
UCSCiuc001vog.4. human.

Organism-specific databases

CTDi1880.
GeneCardsiGPR183.
HGNCiHGNC:3128. GPR183.
HPAiCAB033690.
HPA028847.
MIMi605741. gene.
neXtProtiNX_P32249.
PharmGKBiPA162390174.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEQQ. Eukaryota.
ENOG4110QC8. LUCA.
GeneTreeiENSGT00760000118784.
HOGENOMiHOG000043070.
HOVERGENiHBG101355.
InParanoidiP32249.
KOiK04305.
OMAiRSAPEEN.
OrthoDBiEOG091G0B23.
PhylomeDBiP32249.
TreeFamiTF350009.

Miscellaneous databases

GeneWikiiGPR183.
GenomeRNAii1880.
PROiP32249.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169508.
CleanExiHS_GPR183.
ExpressionAtlasiP32249. baseline and differential.
GenevisibleiP32249. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGP183_HUMAN
AccessioniPrimary (citable) accession number: P32249
Secondary accession number(s): B2R8N5, Q53F99, Q5JUH7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: September 2, 2008
Last modified: September 7, 2016
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

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 (PubMed:21673108, PubMed:23772388). Specifically inhibited by NIBR189 ((2E)-3-(4-Bromophenyl)-1-[4-(4-methoxybenzoyl)-1-piperazinyl]-2-propene-1-one).2 Publications

Caution

It is uncertain whether Met-1 or Met-5 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.