Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWQYB7)

• DTT Name: High mobility group protein B1 (HMGB1)
• Synonyms: High mobility group protein 1; High mobility group box chromosomal protein 1; HMG1; HMG-1
• Gene Name: HMGB1
• DTT Type: Literature-reported target; [1]
• UniProt ID: HMGB1_HUMAN
• TTD ID: T63595
• Sequence:
  MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKF
  EDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGL
  SIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEK
  SKKKKEEEEDEEDEEDEEEEEDEEDEDEEEDDDDE
• Function: In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance. Has proangiogdenic activity. May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates signaling for neuronal outgrowth. May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP. Multifunctional redox sensitive protein with various roles in different cellular compartments.
• KEGG Pathway: Base excision repair (hsa03410)
• Reactome Pathway:
  Activation of DNA fragmentation factor (R-HSA-211227)
  DEx/H-box helicases activate type I IFN and inflammatory cytokines production (R-HSA-3134963)
  TAK1 activates NFkB by phosphorylation and activation of IKKs complex (R-HSA-445989)
  Advanced glycosylation endproduct receptor signaling (R-HSA-879415)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[1]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.