Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLKFB3)

• DTT Name: MHC class I antigen G (HLA-G)
• Synonyms: HLA G antigen; MHC class I antigen G
• Gene Name: HLA-G
• DTT Type: Clinical trial target; [1]
• UniProt ID: HLAG_HUMAN
• TTD ID: T95108
• Sequence:
  MVVMAPRTLFLLLSGALTLTETWAGSHSMRYFSAAVSRPGRGEPRFIAMGYVDDTQFVRF
  DSDSACPRMEPRAPWVEQEGPEYWEEETRNTKAHAQTDRMNLQTLRGYYNQSEASSHTLQ
  WMIGCDLGSDGRLLRGYEQYAYDGKDYLALNEDLRSWTAADTAAQISKRKCEAANVAEQR
  RAYLEGTCVEWLHRYLENGKEMLQRADPPKTHVTHHPVFDYEATLRCWALGFYPAEIILT
  WQRDGEDQTQDVELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPEPLMLRWKQ
  SSLPTIPIMGIVAGLVVLAAVVTGAAVAAVLWRKKSSD
• Function: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface. In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins. Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal-fetal tolerance. Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy. Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling. Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD8+ T cells and B cells. Reprograms B cells toward an immune suppressive phenotype via LILRB1. May induce immune activation/suppression via intercellular membrane transfer (trogocytosis), likely enabling interaction with KIR2DL4, which resides mostly in endosomes. Through interaction with the inhibitory receptor CD160 on endothelial cells may control angiogenesis in immune privileged sites.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Phagosome (hsa04145)
  Cellular senescence (hsa04218)
  Cell adhesion molecules (hsa04514)
  Antigen processing and presentation (hsa04612)
  Natural killer cell mediated cytotoxicity (hsa04650)
  Type I diabetes mellitus (hsa04940)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Viral carcinogenesis (hsa05203)
  Autoimmune thyroid disease (hsa05320)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Endosomal/Vacuolar pathway (R-HSA-1236977)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Interferon gamma signaling (R-HSA-877300)
  Interferon alpha/beta signaling (R-HSA-909733)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Antigen Presentation (R-HSA-983170)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TTX-080	DM6GKYF	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

References

• [1] Clinical pipeline report, company report or official report of Tizona Therapeutics.