Details of Drug Off-Target (DOT)

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

• DOT Name: SET domain-containing protein 4 (SETD4)
• Synonyms: EC 2.1.1.-; EC 2.1.1.364
• Gene Name: SETD4
• Related Disease:
  Cognitive impairment
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Lung cancer
  Neoplasm
  Thymus lymphoma
• UniProt ID: SETD4_HUMAN
• EC Number: 2.1.1.-; 2.1.1.364
• Pfam ID: PF09273 ; PF00856
• Sequence:
  MQKGKGRTSRIRRRKLCGSSESRGVNESHKSEFIELRKWLKARKFQDSNLAPACFPGTGR
  GLMSQTSLQEGQMIISLPESCLLTTDTVIRSYLGAYITKWKPPPSPLLALCTFLVSEKHA
  GHRSLWKPYLEILPKAYTCPVCLEPEVVNLLPKSLKAKAEEQRAHVQEFFASSRDFFSSL
  QPLFAEAVDSIFSYSALLWAWCTVNTRAVYLRPRQRECLSAEPDTCALAPYLDLLNHSPH
  VQVKAAFNEETHSYEIRTTSRWRKHEEVFICYGPHDNQRLFLEYGFVSVHNPHACVYVSR
  EILVKYLPSTDKQMDKKISILKDHGYIENLTFGWDGPSWRLLTALKLLCLEAEKFTCWKK
  VLLGEVISDTNEKTSLDIAQKICYYFIEETNAVLQKVSHMKDEKEALINQLTLVESLWTE
  ELKILRASAETLHSLQTAFT
• Function: Histone-lysine N-methyltransferase that acts as a regulator of cell proliferation, cell differentiation and inflammatory response. Regulates the inflammatory response by mediating mono- and dimethylation of 'Lys-4' of histone H3 (H3K4me1 and H3K4me2, respectively), leading to activate the transcription of pro-inflammatory cytokines IL6 and TNF-alpha. Also involved in the regulation of stem cell quiescence by catalyzing the trimethylation of 'Lys-20' of histone H4 (H4K20me3), thereby promoting heterochromatin formation. Involved in proliferation, migration, paracrine and myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Thymus lymphoma	DISJ17C5	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SET domain-containing protein 4 (SETD4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SET domain-containing protein 4 (SETD4).	[5]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SET domain-containing protein 4 (SETD4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SET domain-containing protein 4 (SETD4).	[6]

References

• [1] Genetic dissection of the Down syndrome critical region.Hum Mol Genet. 2015 Nov 15;24(22):6540-51. doi: 10.1093/hmg/ddv364. Epub 2015 Sep 15.
• [2] SET Domain-Containing Protein 4 Epigenetically Controls Breast Cancer Stem Cell Quiescence.Cancer Res. 2019 Sep 15;79(18):4729-4743. doi: 10.1158/0008-5472.CAN-19-1084. Epub 2019 Jul 15.
• [3] Loss of Setd4 delays radiation-induced thymic lymphoma in mice.DNA Repair (Amst). 2020 Feb;86:102754. doi: 10.1016/j.dnarep.2019.102754. Epub 2019 Nov 25.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.