Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Transforming protein RhoA (RHOA)
• Synonyms: h12; Rho cDNA clone 12; RHO12; ARHA; ARH12
• Gene Name: RHOA
• DTT Type: Discontinued target; [1]
• BioChemical Class: Small GTPase
• UniProt ID: RHOA_HUMAN
• TTD ID: T96736
• EC Number: EC 3.6.5.2
• Sequence:
  MAAIRKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDT
  AGQEDYDRLRPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKD
  LRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTKDGVREVFEMATRAALQ
  ARRGKKKSGCLVL
• Function: Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Chemokine signaling pathway (hsa04062)
  Sphingolipid signaling pathway (hsa04071)
  Endocytosis (hsa04144)
  Vascular smooth muscle contraction (hsa04270)
  Wnt signaling pathway (hsa04310)
  TGF-beta signaling pathway (hsa04350)
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Platelet activation (hsa04611)
  T cell receptor signaling pathway (hsa04660)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin signaling pathway (hsa04722)
  Regulation of actin cytoskeleton (hsa04810)
  Oxytocin signaling pathway (hsa04921)
  Pancreatic secretion (hsa04972)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  Pertussis (hsa05133)
  Tuberculosis (hsa05152)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Colorectal cancer (hsa05210)
• Reactome Pathway:
  Axonal growth inhibition (RHOA activation) (R-HSA-193634)
  Rho GTPase cycle (R-HSA-194840)
  PI3K/AKT activation (R-HSA-198203)
  Axonal growth stimulation (R-HSA-209563)
  TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791)
  G beta (R-HSA-392451)
  EPHB-mediated forward signaling (R-HSA-3928662)
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  PCP/CE pathway (R-HSA-4086400)
  G alpha (12/13) signalling events (R-HSA-416482)
  Sema4D mediated inhibition of cell attachment and migration (R-HSA-416550)
  Sema4D induced cell migration and growth-cone collapse (R-HSA-416572)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases activate PKNs (R-HSA-5625740)
  RHO GTPases activate CIT (R-HSA-5625900)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  RHO GTPases Activate Formins (R-HSA-5663220)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ES-285	DMW9LHG	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[1]

References

• [1] Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCzeta activation. Eur J Pharmacol. 2008 Apr 28;584(2-3):237-45.