Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1RY99Z)

• DOT Name: Protein SPT2 homolog (SPTY2D1)
• Synonyms: Protein KU002155; SPT2 domain-containing protein 1
• Gene Name: SPTY2D1
• Related Disease:
  Neoplasm
  Hepatocellular carcinoma
• UniProt ID: SPT2_HUMAN
• PDB ID: 5BS7; 5BSA
• Pfam ID: PF08243
• Sequence:
  MDFREILMIASKGQGVNNVPKRYSLAVGPPKKDPKVKGVQSAAVQAFLKRKEEELRRKAL
  EEKRRKEELVKKRIELKHDKKARAMAKRTKDNFHGYNGIPIEEKSKKRQATESHTSQGTD
  REYEMEEENEFLEYNHAESEQEYEEEQEPPKVESKPKVPLKSAPPPMNFTDLLRLAEKKQ
  FEPVEIKVVKKSEERPMTAEELREREFLERKHRRKKLETDGKLPPTVSKKAPSQKESVGT
  KLSKGSGDRHPSSKGMPLPHAEKKSRPSMANEKHLALSSSKSMPGERIKAGSGNSSQPSL
  REGHDKPVFNGAGKPHSSTSSPSVPKTSASRTQKSAVEHKAKKSLSHPSHSRPGPMVTPH
  NKAKSPGVRQPGSSSSSAPGQPSTGVARPTVSSGPVPRRQNGSSSSGPERSISGSKKPTN
  DSNPSRRTVSGTCGPGQPASSSGGPGRPISGSVSSARPLGSSRGPGRPVSSPHELRRPVS
  GLGPPGRSVSGPGRSISGSIPAGRTVSNSVPGRPVSSLGPGQTVSSSGPTIKPKCTVVSE
  TISSKNIISRSSNGQMNGMKPPLSGYRAAQGPQRLPFPTGYKRQREYEEEDDDDDEYDSE
  MEDFIEDEGEPQEEISKHIREIFGYDRKKYKDESDYALRYMESSWKEQQKEEAKSLRLGM
  QEDLEEMRREEEEMQRRRAKKLKRR
• Function: Histone chaperone that stabilizes pre-existing histone tetramers and regulates replication-independent histone exchange on chromatin. Required for normal chromatin refolding in the coding region of transcribed genes, and for the suppression of spurious transcription. Binds DNA and histones and promotes nucleosome assembly (in vitro). Facilitates formation of tetrameric histone complexes containing histone H3 and H4. Modulates RNA polymerase 1-mediated transcription. Binds DNA, with a preference for branched DNA species, such as Y-form DNA and Holliday junction DNA.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein SPT2 homolog (SPTY2D1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein SPT2 homolog (SPTY2D1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein SPT2 homolog (SPTY2D1).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein SPT2 homolog (SPTY2D1).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein SPT2 homolog (SPTY2D1).	[7]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Protein SPT2 homolog (SPTY2D1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein SPT2 homolog (SPTY2D1).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein SPT2 homolog (SPTY2D1).	[9]

References

• [1] Genetic relationship between multiple squamous cell carcinomas arising in the oral cavity.Head Neck. 2014 Jan;36(1):94-100. doi: 10.1002/hed.23259. Epub 2013 Apr 30.
• [2] Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays.Gut Liver. 2018 May 15;12(3):306-315. doi: 10.5009/gnl17277.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.