Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
• Synonyms: Peptidyl-cysteine S-nitrosylase GAPDH; OK/SW-cl.12; GAPD; D-glyceraldehyde-3-phosphate dehydrogenase; CDABP0047
• Gene Name: GAPDH
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Aldehyde/oxo donor oxidoreductase
• UniProt ID: G3P_HUMAN
• TTD ID: T39321
• EC Number: EC 1.2.1.12
• Sequence:
  MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVYMFQYDSTHGKFHGTV
  KAENGKLVINGNPITIFQERDPSKIKWGDAGAEYVVESTGVFTTMEKAGAHLQGGAKRVI
  ISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHA
  ITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTANV
  SVVDLTCRLEKPAKYDDIKKVVKQASEGPLKGILGYTEHQVVSSDFNSDTHSSTFDAGAG
  IALNDHFVKLISWYDNEFGYSNRVVDLMAHMASKE
• Function: Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  HIF-1 signaling pathway (hsa04066)
  Alzheimer's disease (hsa05010)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS03433-MON

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
Omigapil	DMH9RTV	Lateral sclerosis	8B61	Phase 2	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Saframycin A	DMZWGVP	Discovery agent	N.A.	Investigative	[2]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lateral sclerosis	8A00.0	Cervical spinal cord	5.24E-01	-0.21	-0.24

References

• [1] Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3887-9.
• [2] Identification of GAPDH as a protein target of the saframycin antiproliferative agents. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5862-6.