Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1DBIM)

• DOT Name: Divergent protein kinase domain 2A (DIPK2A)
• Synonyms: Deleted in autism protein 1; Golgi Protein of 49 kDa; GoPro49; Hypoxia and AKT-induced stem cell factor; HASF
• Gene Name: DIPK2A
• Related Disease:
  Advanced cancer
  Myocardial infarction
  Cognitive impairment
  Intellectual disability
  Autism
  Autism spectrum disorder
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: DIK2A_HUMAN
• Pfam ID: PF12260
• Sequence:
  MWRLVPPKLGRLSRSLKLAALGSLLVLMVLHSPSLLASWQRNELTDRRFLQLNKCPACFG
  TSWCRRFLNGQVVFEAWGRLRLLDFLNVKNVYFAQYGEPREGGRRRVVLKRLGSQRELAQ
  LDQSICKRATGRPRCDLLQAMPRTEFARLNGDVRLLTPEAVEGWSDLVHCPSQRLLDRLV
  RRYAETKDSGSFLLRNLKDSERMQLLLTLAFNPEPLVLQSFPSDEGWPFAKYLGACGRMV
  AVNYVGEELWSYFNAPWEKRVDLAWQLMEIAEQLTNNDFEFALYLLDVSFDNFAVGPRDG
  KVIIVDAENVLVADKRLIRQNKPENWDVWYESKFDDCDKEACLSFSKEILCARATVDHNY
  YAVCQNLLSRHATWRGTSGGLLHDPPSEIAKDGRLEALLDECANPKKRYGRFQAAKELRE
  YLAQLSNNVR
• Function: May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Myocardial infarction	DIS655KI	Strong	Biomarker	[2]
Cognitive impairment	DISH2ERD	Disputed	Biomarker	[3]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[3]
Autism	DISV4V1Z	Limited	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[3]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[5]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[5]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Divergent protein kinase domain 2A (DIPK2A).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Divergent protein kinase domain 2A (DIPK2A).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Divergent protein kinase domain 2A (DIPK2A).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Divergent protein kinase domain 2A (DIPK2A).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Divergent protein kinase domain 2A (DIPK2A).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Divergent protein kinase domain 2A (DIPK2A).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Divergent protein kinase domain 2A (DIPK2A).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Divergent protein kinase domain 2A (DIPK2A).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Divergent protein kinase domain 2A (DIPK2A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Divergent protein kinase domain 2A (DIPK2A).	[12]

References

• [1] Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion.Genes Dev. 2007 Jun 15;21(12):1478-83. doi: 10.1101/gad.424807.
• [2] HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection.J Mol Cell Cardiol. 2014 Jan;66:157-64. doi: 10.1016/j.yjmcc.2013.11.010. Epub 2013 Nov 20.
• [3] Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.PLoS One. 2011 Jan 19;6(1):e14547. doi: 10.1371/journal.pone.0014547.
• [4] DIA1R is an X-linked gene related to Deleted In Autism-1.PLoS One. 2011 Jan 17;6(1):e14534. doi: 10.1371/journal.pone.0014534.
• [5] RAGE Mediates the Pro-Migratory Response of Extracellular S100A4 in Human Thyroid Cancer Cells.Thyroid. 2015 May;25(5):514-27. doi: 10.1089/thy.2014.0257. Epub 2015 Apr 3.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.