Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T59577
(Former ID: TTDI03237)
|
|||||
Target Name |
EBV-induced G-protein coupled receptor 2 (GPR183)
|
|||||
Synonyms |
hEBI2; G-protein coupled receptor 183; Epstein-Barr virus-induced G-protein coupled receptor 2; EBI2
Click to Show/Hide
|
|||||
Gene Name |
GPR183
|
|||||
Target Type |
Literature-reported target
|
[1] | ||||
Function |
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. 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. 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. Promotes osteoclast precursor migration to bone surfaces (By similarity). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha. Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).
Click to Show/Hide
|
|||||
UniProt ID | ||||||
Sequence |
MDIQMANNFTPPSATPQGNDCDLYAHHSTARIVMPLHYSLVFIIGLVGNLLALVVIVQNR
KKINSTTLYSTNLVISDILFTTALPTRIAYYAMGFDWRIGDALCRITALVFYINTYAGVN FMTCLSIDRFIAVVHPLRYNKIKRIEHAKGVCIFVWILVFAQTLPLLINPMSKQEAERIT CMEYPNFEETKSLPWILLGACFIGYVLPLIIILICYSQICCKLFRTAKQNPLTEKSGVNK KALNTIILIIVVFVLCFTPYHVAIIQHMIKKLRFSNFLECSQRHSFQISLHFTVCLMNFN CCMDPFIYFFACKGYKRKVMRMLKRQVSVSISSAVKSAPEENSREMTETQMMIHSKSSNG K Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
---|---|---|---|---|---|---|
Ligand Name: 7alpha,25-dihydroxycholesterol | Ligand Info | |||||
Structure Description | Cryo-EM structure of 7alpha,25-dihydroxycholesterol-bound EBI2/GPR183 in complex with Gi protein | PDB:7TUZ | ||||
Method | Electron microscopy | Resolution | 3.12 Å | Mutation | No | [3] |
PDB Sequence |
DLYAHHSTAR
31 IVMPLHYSLV41 FIIGLVGNLL51 ALVVIVQNRK61 KINSTTLYST71 NLVISDILFT 81 TALPTRIAYY91 AMGDALCRIT107 ALVFYINTYA117 GVNFMTCLSI127 DRFIAVVHPL 137 RYNKIKRIEH147 AKGVCIFVWI157 LVFAQTLPLL167 INPMSKITCM182 EYPNFEETKS 192 LPWILLGACF202 IGYVLPLIII212 LICYSQICCK222 LFRTAKQNPL232 TEKSGVNKKA 242 LNTIILIIVV252 FVLCFTPYHV262 AIIQHMIKKL272 RFSNFLECSQ282 RHSFQISLHF 292 TVCLMNFNCC302 MDPFIYFFAC312 KGYK
|
|||||
|
||||||
Ligand Name: 8-[(E)-3-(4-Chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one | Ligand Info | |||||
Structure Description | Cryo-EM structure of GSK682753A-bound EBI2/GPR183 | PDB:7TUY | ||||
Method | Electron microscopy | Resolution | 2.98 Å | Mutation | No | [3] |
PDB Sequence |
YAHHSTARIV
33 MPLHYSLVFI43 IGLVGNLLAL53 VVIVQNRKKI63 NSTTLYSTNL73 VISDILFTTA 83 LPTRIAYYAM93 GDALCRITAL109 VFYINTYAGV119 NFMTCLSIDR129 FIAVVHPLRY 139 NKIKRIEHAK149 GVCIFVWILV159 FAQTLPLLIN169 PMSKQTCMEY184 PNLPWILLGA 200 CFIGYVLPLI210 IILICYSQIC220 CKLFRARRQL1005 ADLEDNWETL1015 NDNLKVIEKA 1025 DNAAQVKDAL1035 TKMRAAALDA1045 QKASPEMKDF1066 RHGFDILVGQ1076 IDDALKLANE 1086 GKVKEAQAAA1096 EQLKTTRNAY1106 IQKYLERARS1116 TLSGVNKKAL233 NTIILIIVVF 243 VLCFTPYHVA253 IIQHMIKKLR263 FSQRHSFQIS279 LHFTVCLMNF289 NCCMDPFIYF 299 FACKGYKRKV309 M
|
|||||
|
||||||
Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
---|---|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
|
Chemical Structure based Activity Landscape of Target | Top |
---|---|
Drug Property Profile of Target | Top | |
---|---|---|
(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
||
(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
||
(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
||
"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Oxysterols direct immune cell migration via EBI2. Nature. 2011 Jul 27;475(7357):524-7. | |||||
REF 2 | Oxysterols direct B-cell migration through EBI2. Nature. 2011 Jul 27;475(7357):519-23. | |||||
REF 3 | Structures of oxysterol sensor EBI2/GPR183, a key regulator of the immune response. Structure. 2022 Jul 7;30(7):1016-1024.e5. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.