Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Survivin messenger RNA (Survivin mRNA)
• Synonyms: Survivin (mRNA); IAP4 (mRNA); Baculoviral IAP repeat-containing protein 5 (mRNA); Apoptosis inhibitor survivin (mRNA); Apoptosis inhibitor 4 (mRNA); API4 (mRNA)
• Gene Name: BIRC5
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: BIRC5_HUMAN
• TTD ID: T60688
• Sequence:
  MGAPTLPPAWQPFLKDHRISTFKNWPFLEGCACTPERMAEAGFIHCPTENEPDLAQCFFC
  FKELEGWEPDDDPIEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIAKETNNK
  KKEFEETAKKVRRAIEQLAAMD
• Function: Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform. Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Hippo signaling pathway (hsa04390)
  Hepatitis B (hsa05161)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Colorectal cancer (hsa05210)
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)
  Mitotic Prometaphase (R-HSA-68877)
  Neddylation (R-HSA-8951664)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DTT

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 23705	DM5LBQM	Discovery agent	N.A.	Investigative	[1]
ISIS 23707	DMIK0GR	Discovery agent	N.A.	Investigative	[1]
ISIS 23718	DM1SDN3	Discovery agent	N.A.	Investigative	[1]
ISIS 341881	DMOYBFQ	Discovery agent	N.A.	Investigative	[2]
ISIS 343867	DMO7492	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
Lung cancer	2C82	Lung tissue	1.67E-190	1.63	5.29

References

• [1] US patent application no. 6,165,788, Antisense modulation of Survivin expression.
• [2] US patent application no. 7,541,344, Modulation of survivin expression.