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Protein

G-protein coupled receptor 183

Gene

Gpr183

Organism
Mus musculus (Mouse)
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 (PubMed:19597478, PubMed:19615922, PubMed:21844396, PubMed:21796211, PubMed:21796212, PubMed:27147029). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796211, PubMed:21796212). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (PubMed:21796211, PubMed:21796212, PubMed:27147029). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (PubMed:21796211, PubMed:21796212). 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:21948984, PubMed:22913878). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (PubMed:19615922, PubMed:19597478, PubMed:21844396). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (PubMed:19615922). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (PubMed:27147029). 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 (PubMed:27147029). 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 (PubMed:23682316, PubMed:23502855). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897, PubMed:27166278). Promotes osteoclast precursor migration to bone surfaces (PubMed:26438360). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (By similarity). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).By similarity13 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei83Oxysterol agonistBy similarity1
Binding sitei108Oxysterol agonistBy similarity1
Binding sitei112Oxysterol agonistBy similarity1
Binding sitei256Oxysterol agonistBy similarity1

GO - Molecular functioni

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

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • cell chemotaxis Source: UniProtKB
  • dendritic cell chemotaxis Source: UniProtKB
  • dendritic cell homeostasis Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • humoral immune response Source: UniProtKB
  • leukocyte chemotaxis Source: MGI
  • 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

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein coupled receptor 183Curated
Alternative name(s):
Epstein-Barr virus-induced G-protein coupled receptor 2 homologBy similarity
Short name:
EBI2By similarity
Short name:
EBV-induced G-protein coupled receptor 2 homologBy similarity
Gene namesi
Name:Gpr183Imported
Synonyms:Ebi2By similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:2442034. Gpr183.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 27ExtracellularSequence analysisAdd BLAST27
Transmembranei28 – 53Helical; Name=1Sequence analysisAdd BLAST26
Topological domaini54 – 73CytoplasmicSequence analysisAdd BLAST20
Transmembranei74 – 91Helical; Name=2Sequence analysisAdd BLAST18
Topological domaini92 – 101ExtracellularSequence analysis10
Transmembranei102 – 123Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini124 – 145CytoplasmicSequence analysisAdd BLAST22
Transmembranei146 – 164Helical; Name=4Sequence analysisAdd BLAST19
Topological domaini165 – 188ExtracellularSequence analysisAdd BLAST24
Transmembranei189 – 211Helical; Name=5Sequence analysisAdd BLAST23
Topological domaini212 – 237CytoplasmicSequence analysisAdd BLAST26
Transmembranei238 – 261Helical; Name=6Sequence analysisAdd BLAST24
Topological domaini262 – 283ExtracellularSequence analysisAdd BLAST22
Transmembranei284 – 308Helical; Name=7Sequence analysisAdd BLAST25
Topological domaini309 – 357CytoplasmicSequence analysisAdd BLAST49

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice display a reduction in the early antibody response to a T-dependent antigen (PubMed:19597478). B-cells fail to move to the outer follicle at day 2 of activation, and instead are found in the follicle center (PubMed:19615922). Mice have normal numbers of B- and T-cells and organized follicles and T-cell compartments are present (PubMed:19615922). Mice show a decreased number of splenic CD4+ dendritic cells and defective priming of T- and B-cell response (PubMed:23682316, PubMed:23502855). Reduced follicular helper T (Tfh) cells (PubMed:27147029). T-cells fail to accumulate in the outer T zone at either time point and instead remain dispersed throughout the T zone (PubMed:27147029).4 Publications

Chemistry databases

ChEMBLiCHEMBL3259471.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003032311 – 357G-protein coupled receptor 183Add BLAST357

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi4N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi100 ↔ 177PROSITE-ProRule annotation
Modified residuei324PhosphoserineCombined sources1
Modified residuei345PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ3U6B2.
PRIDEiQ3U6B2.

PTM databases

iPTMnetiQ3U6B2.
PhosphoSitePlusiQ3U6B2.

Expressioni

Tissue specificityi

Expressed in mature B-cells and increases in expression early after activation, before being down-regulated in germinal center B-cells (PubMed:19597478). Expressed in astrocytes (PubMed:25297897). Specifically expressed in CD4+ dendritic cells but not in CD8+ dendritic cells (PubMed:23682316, PubMed:23502855). Expressed in monocyte/osteoclasts precursors and mature osteoclasts (PubMed:26438360).5 Publications

Inductioni

Up-regulated during B-cell maturation in the bone marrow, and is expressed in mature recirculating B-cells in bone marrow, spleen and lymph nodes (PubMed:19597478). Up-regulated in B-cells after BCR and CD40 engagement (PubMed:19597478). Down-regulated by lipopolysaccharide (LPS) in astrocytes (PubMed:27166278). Expression is directly down-regulated by BCL6 (PubMed:25176650).3 Publications

Gene expression databases

BgeeiENSMUSG00000051212.
GenevisibleiQ3U6B2. MM.

Interactioni

Subunit structurei

Homodimer and heterodimer. Heterodimerizes with CXCR5; leading to modulate the interaction between of CXCL13 and CXCR5.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000052404.

Chemistry databases

BindingDBiQ3U6B2.

Structurei

3D structure databases

ProteinModelPortaliQ3U6B2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni122 – 130Interaction with G proteinsBy similarity9

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.
InParanoidiQ3U6B2.
KOiK04305.
OMAiRSAPEEN.
OrthoDBiEOG091G0B23.
PhylomeDBiQ3U6B2.
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.

Q3U6B2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANNFTTPLA TSHGNNCDLY AHHSTARVLM PLHYSLVFII GLVGNLLALV
60 70 80 90 100
VIVQNRKKIN STTLYSMNLV ISDILFTTAL PTRIAYYALG FDWRIGDALC
110 120 130 140 150
RVTALVFYIN TYAGVNFMTC LSIDRFFAVV HPLRYNKIKR IEYAKGVCLS
160 170 180 190 200
VWILVFAQTL PLLLTPMSKE EGDKTTCMEY PNFEGTASLP WILLGACLLG
210 220 230 240 250
YVLPITVILL CYSQICCKLF RTAKQNPLTE KSGVNKKALN TIILIIVVFI
260 270 280 290 300
LCFTPYHVAI IQHMIKMLCS PGALECGARH SFQISLHFTV CLMNFNCCMD
310 320 330 340 350
PFIYFFACKG YKRKVMKMLK RQVSVSISSA VRSAPEENSR EMTESQMMIH

SKASNGR
Length:357
Mass (Da):40,185
Last modified:October 11, 2005 - v1
Checksum:iD4B1C32C0C451993
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163L → F in AAH52868 (PubMed:15489334).Curated1
Sequence conflicti239L → P in BAE33542 (PubMed:16141072).Curated1
Sequence conflicti338N → S in AAH52868 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK138693 mRNA. Translation: BAE23750.1.
AK153216 mRNA. Translation: BAE31813.1.
AK156005 mRNA. Translation: BAE33542.1.
BC052868 mRNA. Translation: AAH52868.1.
AY255606 mRNA. Translation: AAO85118.1.
CCDSiCCDS27343.1.
RefSeqiNP_898852.2. NM_183031.2.
UniGeneiMm.265618.

Genome annotation databases

EnsembliENSMUST00000049872; ENSMUSP00000052404; ENSMUSG00000051212.
GeneIDi321019.
KEGGimmu:321019.
UCSCiuc007vaq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK138693 mRNA. Translation: BAE23750.1.
AK153216 mRNA. Translation: BAE31813.1.
AK156005 mRNA. Translation: BAE33542.1.
BC052868 mRNA. Translation: AAH52868.1.
AY255606 mRNA. Translation: AAO85118.1.
CCDSiCCDS27343.1.
RefSeqiNP_898852.2. NM_183031.2.
UniGeneiMm.265618.

3D structure databases

ProteinModelPortaliQ3U6B2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000052404.

Chemistry databases

BindingDBiQ3U6B2.
ChEMBLiCHEMBL3259471.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ3U6B2.
PhosphoSitePlusiQ3U6B2.

Proteomic databases

PaxDbiQ3U6B2.
PRIDEiQ3U6B2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049872; ENSMUSP00000052404; ENSMUSG00000051212.
GeneIDi321019.
KEGGimmu:321019.
UCSCiuc007vaq.1. mouse.

Organism-specific databases

CTDi1880.
MGIiMGI:2442034. Gpr183.

Phylogenomic databases

eggNOGiENOG410IEQQ. Eukaryota.
ENOG4110QC8. LUCA.
GeneTreeiENSGT00760000118784.
HOGENOMiHOG000043070.
HOVERGENiHBG101355.
InParanoidiQ3U6B2.
KOiK04305.
OMAiRSAPEEN.
OrthoDBiEOG091G0B23.
PhylomeDBiQ3U6B2.
TreeFamiTF350009.

Miscellaneous databases

PROiQ3U6B2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000051212.
GenevisibleiQ3U6B2. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q3U6B2
Secondary accession number(s): Q3U1F6, Q7TMV7, Q80T40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: October 11, 2005
Last modified: November 2, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.