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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)DescriptionActionsGraphical viewLength
Binding sitei87Oxysterol agonist1 Publication1
Binding sitei112Oxysterol agonist1 Publication1
Binding sitei116Oxysterol agonist1 Publication1
Binding sitei260Oxysterol agonist1 Publication1

GO - Molecular functioni

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

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • B cell activation involved in immune response Source: GO_Central
  • dendritic cell chemotaxis Source: UniProtKB
  • dendritic cell homeostasis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • immune response Source: ProtInc
  • leukocyte chemotaxis Source: UniProtKB
  • mature B cell differentiation involved in immune response Source: UniProtKB
  • osteoclast differentiation Source: UniProtKB
  • positive regulation of B cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of astrocyte chemotaxis Source: UniProtKB
  • T cell chemotaxis Source: UniProtKB
  • T follicular helper cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169508-MONOMER.

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)DescriptionActionsGraphical viewLength
Topological domaini1 – 31ExtracellularSequence analysisAdd BLAST31
Transmembranei32 – 57Helical; Name=1Sequence analysisAdd BLAST26
Topological domaini58 – 77CytoplasmicSequence analysisAdd BLAST20
Transmembranei78 – 95Helical; Name=2Sequence analysisAdd BLAST18
Topological domaini96 – 105ExtracellularSequence analysis10
Transmembranei106 – 127Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini128 – 149CytoplasmicSequence analysisAdd BLAST22
Transmembranei150 – 168Helical; Name=4Sequence analysisAdd BLAST19
Topological domaini169 – 192ExtracellularSequence analysisAdd BLAST24
Transmembranei193 – 215Helical; Name=5Sequence analysisAdd BLAST23
Topological domaini216 – 241CytoplasmicSequence analysisAdd BLAST26
Transmembranei242 – 265Helical; Name=6Sequence analysisAdd BLAST24
Topological domaini266 – 287ExtracellularSequence analysisAdd BLAST22
Transmembranei288 – 312Helical; Name=7Sequence analysisAdd BLAST25
Topological domaini313 – 361CytoplasmicSequence analysisAdd BLAST49

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)DescriptionActionsGraphical viewLength
Mutagenesisi21C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication1
Mutagenesisi77D → A: Loss of receptor activation without affecting oxysterol agonist-binding. 2 Publications1
Mutagenesisi77D → R: Strong decrease in oxysterol agonist-binding and receptor activation. 1 Publication1
Mutagenesisi85P → A: Strongly reduced localization to the cell membrane. 1 Publication1
Mutagenesisi87R → A: Strong decrease in oxysterol agonist-binding and receptor activation. 3 Publications1
Mutagenesisi87R → K: Slight decrease in oxysterol agonist-binding and receptor activation. 2 Publications1
Mutagenesisi87R → W: Slight decrease in oxysterol agonist-binding and receptor activation. 1 Publication1
Mutagenesisi90Y → A: 10-fold reduction in receptor activation. Strongly reduced localization to the cell membrane. 2 Publications1
Mutagenesisi104C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication1
Mutagenesisi111F → A or Y: 500-fold decrease of IC(50) for GSK682753A. No effect on oxysterol agonist-binding and receptor activation. 2 Publications1
Mutagenesisi112Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications1
Mutagenesisi114N → A: Strongly reduced localization to the cell membrane. 1 Publication1
Mutagenesisi115T → A or F: No effect. 1 Publication1
Mutagenesisi116Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications1
Mutagenesisi181C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication1
Mutagenesisi183E → A: Strong reduction in ligand potency. 1 Publication1
Mutagenesisi197L → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication1
Mutagenesisi205Y → A or F: No effect. 1 Publication1
Mutagenesisi256C → A: Increased receptor activation. 1 Publication1
Mutagenesisi257F → A: Increased receptor activation. Strongly reduced localization to the cell membrane. 2 Publications1
Mutagenesisi260Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications1
Mutagenesisi261H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication1
Mutagenesisi264I → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication1
Mutagenesisi280C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication1
Mutagenesisi287Q → A: 10-fold reduction in receptor activation. 1 Publication1
Mutagenesisi291H → A: 10-fold reduction in receptor activation. 1 Publication1
Mutagenesisi291H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication1
Mutagenesisi294V → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication1
Mutagenesisi297M → A: Reduced localization to the cell membrane and reduced receptor function, without affecting oxysterol agonist-binding. 1 Publication1
Mutagenesisi297M → I: Reduced localization to the cell membrane and reduced receptor function. Reduced oxysterol agonist-binding. 1 Publication1

Organism-specific databases

DisGeNETi1880.
OpenTargetsiENSG00000169508.
PharmGKBiPA162390174.

Chemistry databases

ChEMBLiCHEMBL3259470.
GuidetoPHARMACOLOGYi81.

Polymorphism and mutation databases

BioMutaiGPR183.
DMDMi205371788.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694111 – 361G-protein coupled receptor 183Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi104 ↔ 181PROSITE-ProRule annotation
Modified residuei328PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiP32249.
PaxDbiP32249.
PeptideAtlasiP32249.
PRIDEiP32249.

PTM databases

iPTMnetiP32249.
PhosphoSitePlusiP32249.
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 interactors.
IntActiP32249. 2 interactors.
MINTiMINT-1427405.
STRINGi9606.ENSP00000365596.

Chemistry databases

BindingDBiP32249.

Structurei

3D structure databases

ProteinModelPortaliP32249.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni126 – 134Interaction with G proteins9

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)DescriptionActionsGraphical viewLength
Sequence conflicti6A → V in BAD97110 (Ref. 3) Curated1
Sequence conflicti179I → N in BAG36232 (PubMed:14702039).Curated1
Sequence conflicti325R → Q in BAG36232 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054147338A → V in an acute myeloid leukemia sample; somatic mutation. 1 Publication1

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.
XP_016875894.1. XM_017020405.1.
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.
XP_016875894.1. XM_017020405.1.
UniGeneiHs.784.

3D structure databases

ProteinModelPortaliP32249.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP32249.
ChEMBLiCHEMBL3259470.
GuidetoPHARMACOLOGYi81.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP32249.
PhosphoSitePlusiP32249.
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.
DisGeNETi1880.
GeneCardsiGPR183.
HGNCiHGNC:3128. GPR183.
HPAiCAB033690.
HPA028847.
MIMi605741. gene.
neXtProtiNX_P32249.
OpenTargetsiENSG00000169508.
PharmGKBiPA162390174.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169508-MONOMER.

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: November 2, 2016
This is version 150 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.