UniProtKB - P32249 (GP183_HUMAN)
Protein
G-protein coupled receptor 183
Gene
GPR183
Organism
Homo sapiens (Human)
Status
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
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
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 87 | Oxysterol agonist1 Publication | 1 | |
Binding sitei | 112 | Oxysterol agonist1 Publication | 1 | |
Binding sitei | 116 | Oxysterol agonist1 Publication | 1 | |
Binding sitei | 260 | Oxysterol agonist1 Publication | 1 |
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
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Biological process | Adaptive immunity, Immunity |
Enzyme and pathway databases
PathwayCommonsi | P32249 |
Reactomei | R-HSA-373076, Class A/1 (Rhodopsin-like receptors) R-HSA-418594, G alpha (i) signalling events |
SIGNORi | P32249 |
Names & Taxonomyi
Protein namesi | Recommended name: G-protein coupled receptor 183CuratedAlternative 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3128, GPR183 |
MIMi | 605741, gene |
neXtProti | NX_P32249 |
VEuPathDBi | HostDB:ENSG00000169508.6 |
Subcellular locationi
Plasma membrane
- Cell membrane 4 Publications; Multi-pass membrane protein Sequence analysis
Plasma Membrane
- integral component of plasma membrane Source: ProtInc
- plasma membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 31 | ExtracellularSequence analysisAdd BLAST | 31 | |
Transmembranei | 32 – 57 | Helical; Name=1Sequence analysisAdd BLAST | 26 | |
Topological domaini | 58 – 77 | CytoplasmicSequence analysisAdd BLAST | 20 | |
Transmembranei | 78 – 95 | Helical; Name=2Sequence analysisAdd BLAST | 18 | |
Topological domaini | 96 – 105 | ExtracellularSequence analysis | 10 | |
Transmembranei | 106 – 127 | Helical; Name=3Sequence analysisAdd BLAST | 22 | |
Topological domaini | 128 – 149 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 150 – 168 | Helical; Name=4Sequence analysisAdd BLAST | 19 | |
Topological domaini | 169 – 192 | ExtracellularSequence analysisAdd BLAST | 24 | |
Transmembranei | 193 – 215 | Helical; Name=5Sequence analysisAdd BLAST | 23 | |
Topological domaini | 216 – 241 | CytoplasmicSequence analysisAdd BLAST | 26 | |
Transmembranei | 242 – 265 | Helical; Name=6Sequence analysisAdd BLAST | 24 | |
Topological domaini | 266 – 287 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 288 – 312 | Helical; Name=7Sequence analysisAdd BLAST | 25 | |
Topological domaini | 313 – 361 | CytoplasmicSequence analysisAdd BLAST | 49 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 21 | C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication | 1 | |
Mutagenesisi | 77 | D → A: Loss of receptor activation without affecting oxysterol agonist-binding. 2 Publications | 1 | |
Mutagenesisi | 77 | D → R: Strong decrease in oxysterol agonist-binding and receptor activation. 1 Publication | 1 | |
Mutagenesisi | 85 | P → A: Strongly reduced localization to the cell membrane. 1 Publication | 1 | |
Mutagenesisi | 87 | R → A: Strong decrease in oxysterol agonist-binding and receptor activation. 3 Publications | 1 | |
Mutagenesisi | 87 | R → K: Slight decrease in oxysterol agonist-binding and receptor activation. 2 Publications | 1 | |
Mutagenesisi | 87 | R → W: Slight decrease in oxysterol agonist-binding and receptor activation. 1 Publication | 1 | |
Mutagenesisi | 90 | Y → A: 10-fold reduction in receptor activation. Strongly reduced localization to the cell membrane. 2 Publications | 1 | |
Mutagenesisi | 104 | C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication | 1 | |
Mutagenesisi | 111 | F → A or Y: 500-fold decrease of IC(50) for GSK682753A. No effect on oxysterol agonist-binding and receptor activation. 2 Publications | 1 | |
Mutagenesisi | 112 | Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications | 1 | |
Mutagenesisi | 114 | N → A: Strongly reduced localization to the cell membrane. 1 Publication | 1 | |
Mutagenesisi | 115 | T → A or F: No effect. 1 Publication | 1 | |
Mutagenesisi | 116 | Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications | 1 | |
Mutagenesisi | 181 | C → A: Abolishes localization to the cell membrane without affecting protein expression levels. 1 Publication | 1 | |
Mutagenesisi | 183 | E → A: Strong reduction in ligand potency. 1 Publication | 1 | |
Mutagenesisi | 197 | L → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication | 1 | |
Mutagenesisi | 205 | Y → A or F: No effect. 1 Publication | 1 | |
Mutagenesisi | 256 | C → A: Increased receptor activation. 1 Publication | 1 | |
Mutagenesisi | 257 | F → A: Increased receptor activation. Strongly reduced localization to the cell membrane. 2 Publications | 1 | |
Mutagenesisi | 260 | Y → A or F: Strong decrease in oxysterol agonist-binding and receptor activation. 2 Publications | 1 | |
Mutagenesisi | 261 | H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication | 1 | |
Mutagenesisi | 264 | I → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication | 1 | |
Mutagenesisi | 280 | C → A: Strongly reduced localization to the cell membrane and reduced protein expression levels. 1 Publication | 1 | |
Mutagenesisi | 287 | Q → A: 10-fold reduction in receptor activation. 1 Publication | 1 | |
Mutagenesisi | 291 | H → A: 10-fold reduction in receptor activation. 1 Publication | 1 | |
Mutagenesisi | 291 | H → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication | 1 | |
Mutagenesisi | 294 | V → A: Reduced localization to the cell membrane and reduced receptor function. 1 Publication | 1 | |
Mutagenesisi | 297 | M → A: Reduced localization to the cell membrane and reduced receptor function, without affecting oxysterol agonist-binding. 1 Publication | 1 | |
Mutagenesisi | 297 | M → I: Reduced localization to the cell membrane and reduced receptor function. Reduced oxysterol agonist-binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 1880 |
OpenTargetsi | ENSG00000169508 |
PharmGKBi | PA162390174 |
Miscellaneous databases
Pharosi | P32249, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3259470 |
GuidetoPHARMACOLOGYi | 81 |
Genetic variation databases
BioMutai | GPR183 |
DMDMi | 205371788 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069411 | 1 – 361 | G-protein coupled receptor 183Add BLAST | 361 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 104 ↔ 181 | PROSITE-ProRule annotation | ||
Modified residuei | 328 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Disulfide bond, PhosphoproteinProteomic databases
jPOSTi | P32249 |
MassIVEi | P32249 |
MaxQBi | P32249 |
PaxDbi | P32249 |
PeptideAtlasi | P32249 |
PRIDEi | P32249 |
ProteomicsDBi | 54857 |
PTM databases
CarbonylDBi | P32249 |
iPTMneti | P32249 |
PhosphoSitePlusi | P32249 |
SwissPalmi | P32249 |
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
Bgeei | ENSG00000169508, Expressed in vermiform appendix and 206 other tissues |
ExpressionAtlasi | P32249, baseline and differential |
Genevisiblei | P32249, HS |
Organism-specific databases
HPAi | ENSG00000169508, Tissue enhanced (blood) |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 108212, 36 interactors |
IntActi | P32249, 31 interactors |
STRINGi | 9606.ENSP00000365596 |
Chemistry databases
BindingDBi | P32249 |
Miscellaneous databases
RNActi | P32249, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 126 – 134 | Interaction with G proteins | 9 |
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QWD9, Eukaryota |
GeneTreei | ENSGT01010000222405 |
HOGENOMi | CLU_009579_8_2_1 |
InParanoidi | P32249 |
OMAi | HYTVFLM |
OrthoDBi | 543832at2759 |
PhylomeDBi | P32249 |
TreeFami | TF350009 |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P32249-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 6 | A → V in BAD97110 (Ref. 3) Curated | 1 | |
Sequence conflicti | 179 | I → N in BAG36232 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 325 | R → Q in BAG36232 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_054147 | 338 | A → V in an acute myeloid leukemia sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1466524306Ensembl. | 1 |
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 No translation available. CH471085 Genomic DNA Translation: EAX09018.1 BC020752 mRNA Translation: AAH20752.1 |
CCDSi | CCDS9492.1 |
PIRi | B45680 |
RefSeqi | NP_004942.1, NM_004951.4 XP_016875894.1, XM_017020405.1 |
Genome annotation databases
Ensembli | ENST00000376414; ENSP00000365596; ENSG00000169508 |
GeneIDi | 1880 |
KEGGi | hsa:1880 |
UCSCi | uc001vog.4, human |
Similar proteinsi
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 No translation available. CH471085 Genomic DNA Translation: EAX09018.1 BC020752 mRNA Translation: AAH20752.1 |
CCDSi | CCDS9492.1 |
PIRi | B45680 |
RefSeqi | NP_004942.1, NM_004951.4 XP_016875894.1, XM_017020405.1 |
3D structure databases
SMRi | P32249 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108212, 36 interactors |
IntActi | P32249, 31 interactors |
STRINGi | 9606.ENSP00000365596 |
Chemistry databases
BindingDBi | P32249 |
ChEMBLi | CHEMBL3259470 |
GuidetoPHARMACOLOGYi | 81 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
CarbonylDBi | P32249 |
iPTMneti | P32249 |
PhosphoSitePlusi | P32249 |
SwissPalmi | P32249 |
Genetic variation databases
BioMutai | GPR183 |
DMDMi | 205371788 |
Proteomic databases
jPOSTi | P32249 |
MassIVEi | P32249 |
MaxQBi | P32249 |
PaxDbi | P32249 |
PeptideAtlasi | P32249 |
PRIDEi | P32249 |
ProteomicsDBi | 54857 |
Protocols and materials databases
Antibodypediai | 10905, 205 antibodies |
DNASUi | 1880 |
Genome annotation databases
Ensembli | ENST00000376414; ENSP00000365596; ENSG00000169508 |
GeneIDi | 1880 |
KEGGi | hsa:1880 |
UCSCi | uc001vog.4, human |
Organism-specific databases
CTDi | 1880 |
DisGeNETi | 1880 |
GeneCardsi | GPR183 |
HGNCi | HGNC:3128, GPR183 |
HPAi | ENSG00000169508, Tissue enhanced (blood) |
MIMi | 605741, gene |
neXtProti | NX_P32249 |
OpenTargetsi | ENSG00000169508 |
PharmGKBi | PA162390174 |
VEuPathDBi | HostDB:ENSG00000169508.6 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QWD9, Eukaryota |
GeneTreei | ENSGT01010000222405 |
HOGENOMi | CLU_009579_8_2_1 |
InParanoidi | P32249 |
OMAi | HYTVFLM |
OrthoDBi | 543832at2759 |
PhylomeDBi | P32249 |
TreeFami | TF350009 |
Enzyme and pathway databases
PathwayCommonsi | P32249 |
Reactomei | R-HSA-373076, Class A/1 (Rhodopsin-like receptors) R-HSA-418594, G alpha (i) signalling events |
SIGNORi | P32249 |
Miscellaneous databases
BioGRID-ORCSi | 1880, 6 hits in 866 CRISPR screens |
GeneWikii | GPR183 |
GenomeRNAii | 1880 |
Pharosi | P32249, Tchem |
PROi | PR:P32249 |
RNActi | P32249, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000169508, Expressed in vermiform appendix and 206 other tissues |
ExpressionAtlasi | P32249, baseline and differential |
Genevisiblei | P32249, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GP183_HUMAN | |
Accessioni | P32249Primary (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: | February 10, 2021 | |
This is version 178 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries