Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN74LE)

• DTT Name: Direct IAP-binding protein with low pI (DIABLO)
• Synonyms: Smac protein; Smac; Second mitochondria-derived activator of caspase; Direct IAP binding protein with low pI; Diablo homolog, mitochondrial
• Gene Name: DIABLO
• DTT Type: Literature-reported target; [1]
• UniProt ID: DBLOH_HUMAN
• TTD ID: T78150
• Sequence:
  MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGVTLCAVPIA
  QKSEPHSLSSEALMRRAVSLVTDSTSTFLSQTTYALIEAITEYTKAVYTLTSLYRQYTSL
  LGKMNSEEEDEVWQVIIGARAEMTSKHQEYLKLETTWMTAVGLSEMAAEAAYQTGADQAS
  ITARNHIQLVKLQVEEVHQLSRKAETKLAEAQIEELRQKTQEEGEERAESEQEAYLRED
• Function: Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance. Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway.
• KEGG Pathway:
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
• Reactome Pathway:
  SMAC (DIABLO) binds to IAPs (R-HSA-111463)
  SMAC(DIABLO)-mediated dissociation of IAP (R-HSA-111464)
  SMAC, XIAP-regulated apoptotic response (R-HSA-111469)
  Regulation of the apoptosome activity (R-HSA-9627069)
  Release of apoptotic factors from the mitochondria (R-HSA-111457)

References

• [1] Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-x(L) in a strictly caspase-3-dependent manner in human carcinoma cells. Oncogene. 2004 Jun 3;23(26):4523-35.