Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTME5YJ)

• DTT 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
• Gene Name: GPR183
• DTT Type: Literature-reported target; [1]
• UniProt ID: GP183_HUMAN
• TTD ID: T59577
• Sequence:
  MDIQMANNFTPPSATPQGNDCDLYAHHSTARIVMPLHYSLVFIIGLVGNLLALVVIVQNR
  KKINSTTLYSTNLVISDILFTTALPTRIAYYAMGFDWRIGDALCRITALVFYINTYAGVN
  FMTCLSIDRFIAVVHPLRYNKIKRIEHAKGVCIFVWILVFAQTLPLLINPMSKQEAERIT
  CMEYPNFEETKSLPWILLGACFIGYVLPLIIILICYSQICCKLFRTAKQNPLTEKSGVNK
  KALNTIILIIVVFVLCFTPYHVAIIQHMIKKLRFSNFLECSQRHSFQISLHFTVCLMNFN
  CCMDPFIYFFACKGYKRKVMRMLKRQVSVSISSAVKSAPEENSREMTETQMMIHSKSSNG
  K
• 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).
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

Molecular Interaction Atlas (MIA) of This DTT

8 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
25-hydroxycholesterol	DMCHAQ7	Discovery agent	N.A.	Investigative	[2]
27-hydroxycholesterol	DM2L6OZ	Discovery agent	N.A.	Investigative	[2]
7alpha,25-dihydroxycholesterol	DM2N8TW	Discovery agent	N.A.	Investigative	[1]
7alpha,27-dihydroxycholesterol	DM52UOM	Discovery agent	N.A.	Investigative	[2]
7alpha-hydroxycholesterol	DMH6LD0	Discovery agent	N.A.	Investigative	[2]
7beta, 25-dihydroxycholesterol	DMYKXWE	Discovery agent	N.A.	Investigative	[2]
7beta, 27-dihydroxycholesterol	DMSDINR	Discovery agent	N.A.	Investigative	[2]
7beta-hydroxycholesterol	DMPHJZU	Discovery agent	N.A.	Investigative	[2]

References

• [1] Oxysterols direct immune cell migration via EBI2. Nature. 2011 Jul 27;475(7357):524-7.
• [2] Oxysterols direct B-cell migration through EBI2. Nature. 2011 Jul 27;475(7357):519-23.