Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTW30FR)

• DTT Name: Small ubiquitin-related modifier (SUMO)
• Synonyms: Ubiquitin-like protein; SUMO; SMT3 homolog 1
• Gene Name: SUMO1
• DTT Type: Preclinical target; [1]
• UniProt ID: SUMO1_HUMAN ; SUMO2_HUMAN ; SUMO3_HUMAN ; SUMO4_HUMAN ; SUMO5_HUMAN
• TTD ID: T99765
• Sequence:
  MSDQEAKPSTEDLGDKKEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMN
  SLRFLFEGQRIADNHTPKELGMEEEDVIEVYQEQTGGHSTV
• Function: Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  SUMO is transferred from E1 to E2 (UBE2I, UBC9) (R-HSA-3065678)
  SUMO is proteolytically processed (R-HSA-3065679)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMO E3 ligases SUMOylate target proteins (R-HSA-3108232)
  SUMOylation of transcription factors (R-HSA-3232118)
  SUMOylation of ubiquitinylation proteins (R-HSA-3232142)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  SUMOylation of SUMOylation proteins (R-HSA-4085377)
  SUMOylation of intracellular receptors (R-HSA-4090294)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  SUMOylation of DNA methylation proteins (R-HSA-4655427)
  SUMOylation of immune response proteins (R-HSA-4755510)
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Regulation of IFNG signaling (R-HSA-877312)
  Negative regulation of activity of TFAP2 (AP-2) family transcription factors (R-HSA-8866904)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  Maturation of nucleoprotein (R-HSA-9683610)
  Maturation of nucleoprotein (R-HSA-9694631)
  SUMO is conjugated to E1 (UBA2 (R-HSA-3065676)
• BioCyc Pathway: MetaCyc:ENSG00000116030-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-D08	DMRDQPT	Acute myeloid leukaemia	2A60	Preclinical	[2]

References

• [1] Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem. 2013;82:357-85.
• [2] Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1. J Cell Sci. 2019 Oct 22;132(20):jcs234120.