Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRAB1PN)

• DOT Name: Transcription factor Sp6 (SP6)
• Synonyms: Krueppel-like factor 14
• Gene Name: SP6
• Related Disease:
  Alzheimer disease
  Amelogenesis imperfecta, IIa 1K
  Arteriosclerosis
  Atherosclerosis
  Coronary atherosclerosis
  Coronary heart disease
  Non-insulin dependent diabetes
  Castration-resistant prostate carcinoma
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: SP6_HUMAN
• Pfam ID: PF00096
• Sequence:
  MLTAVCGSLGSQHTEAPHASPPRLDLQPLQTYQGHTSPEAGDYPSPLQPGELQSLPLGPE
  VDFSQGYELPGASSRVTCEDLESDSPLAPGPFSKLLQPDMSHHYESWFRPTHPGAEDGSW
  WDLHPGTSWMDLPHTQGALTSPGHPGALQAGLGGYVGDHQLCAPPPHPHAHHLLPAAGGQ
  HLLGPPDGAKALEVAAPESQGLDSSLDGAARPKGSRRSVPRSSGQTVCRCPNCLEAERLG
  APCGPDGGKKKHLHNCHIPGCGKAYAKTSHLKAHLRWHSGDRPFVCNWLFCGKRFTRSDE
  LQRHLQTHTGTKKFPCAVCSRVFMRSDHLAKHMKTHEGAKEEAAGAASGEGKAGGAVEPP
  GGKGKREAEGSVAPSN
• Function: Promotes cell proliferation. Plays a role in tooth germ growth. Plays a role in the control of enamel mineralization. Binds the AMBN promoter.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Amelogenesis imperfecta, IIa 1K	DISDA0ZL	Strong	Autosomal dominant	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transcription factor Sp6 (SP6).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor Sp6 (SP6).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor Sp6 (SP6).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor Sp6 (SP6).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transcription factor Sp6 (SP6).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor Sp6 (SP6).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor Sp6 (SP6).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor Sp6 (SP6).	[15]

References

• [1] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [2] The development of several organs and appendages is impaired in mice lacking Sp6. Dev Dyn. 2008 Apr;237(4):883-92. doi: 10.1002/dvdy.21355.
• [3] Krppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo.Atherosclerosis. 2019 Oct;289:143-161. doi: 10.1016/j.atherosclerosis.2019.08.012. Epub 2019 Aug 26.
• [4] Krppel-like factor 14, a coronary artery disease associated transcription factor, inhibits endothelial inflammation via NF-B signaling pathway.Atherosclerosis. 2018 Nov;278:39-48. doi: 10.1016/j.atherosclerosis.2018.09.018. Epub 2018 Sep 15.
• [5] A novel role for the Krppel-like factor 14 on macrophage inflammatory response and atherosclerosis development.Cardiovasc Pathol. 2017 Mar-Apr;27:1-8. doi: 10.1016/j.carpath.2016.11.003. Epub 2016 Nov 14.
• [6] KLF14 potentiates oxidative adaptation via modulating HO-1 signaling in castrate-resistant prostate cancer.Endocr Relat Cancer. 2019 Jan 1;26(1):181-195. doi: 10.1530/ERC-18-0383.
• [7] LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR-346/KLF14 axis.J Cell Physiol. 2018 Jan;234(1):572-580. doi: 10.1002/jcp.26779. Epub 2018 Sep 14.
• [8] 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.
• [9] 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.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.