Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7B6FRO)

• DOT Name: Transcription initiation protein SPT3 homolog (SUPT3H)
• Synonyms: SPT3-like protein
• Gene Name: SUPT3H
• Related Disease:
  Head-neck squamous cell carcinoma
  Knee osteoarthritis
  Osteoarthritis
  Autosomal dominant cerebellar ataxia type II
• UniProt ID: SUPT3_HUMAN
• PDB ID: 7KTR; 7KTS; 8H7G
• Pfam ID: PF02269
• Sequence:
  MNNTAASPMSTATSSSGRSTGKSISFATELQSMMYSLGDARRPLHETAVLVEDVVHTQLI
  NLLQQAAEVSQLRGARVITPEDLLFLMRKDKKKLRRLLKYMFIRDYKSKIVKGIDEDDLL
  EDKLSGSNNANKRQKIAQDFLNSIDQTGELLAMFEDDEIDEVKQERMERAERQTRIMDSA
  QYAEFCESRQLSFSKKASKFRDWLDCSSMEIKPNVVAMEILAYLAYETVAQLVDLALLVR
  QDMVTKAGDPFSHAISATFIQYHNSAESTAACGVEAHSDAIQPCHIREAIRRYSHRIGPL
  SPFTNAYRRNGMAFLAC
• Function: Probable transcriptional activator.
• Tissue Specificity: Expressed in all tissues tested including pancreas, kidney, skeletal muscle, liver, lung, placenta, brain and heart.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[1]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[2]
Osteoarthritis	DIS05URM	moderate	Genetic Variation	[3]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transcription initiation protein SPT3 homolog (SUPT3H).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Transcription initiation protein SPT3 homolog (SUPT3H).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription initiation protein SPT3 homolog (SUPT3H).	[15]

References

• [1] p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.Oral Oncol. 2016 Sep;60:81-9. doi: 10.1016/j.oraloncology.2016.06.010. Epub 2016 Jul 15.
• [2] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [3] Identification of a novel, methylation-dependent, RUNX2 regulatory region associated with osteoarthritis risk.Hum Mol Genet. 2018 Oct 1;27(19):3464-3474. doi: 10.1093/hmg/ddy257.
• [4] Posttranslational modification of ataxin-7 at lysine 257 prevents autophagy-mediated turnover of an N-terminal caspase-7 cleavage fragment.J Neurosci. 2009 Dec 2;29(48):15134-44. doi: 10.1523/JNEUROSCI.4720-09.2009.
• [5] 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.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.