Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYZP3MP)

• DOT Name: Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A)
• Synonyms: Odin
• Gene Name: ANKS1A
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
  Systemic sclerosis
  Type-1 diabetes
  Systemic lupus erythematosus
• UniProt ID: ANS1A_HUMAN
• PDB ID: 2LMR; 2MYQ; 6F7O
• Pfam ID: PF12796 ; PF00640 ; PF00536
• Sequence:
  MGKEQELLEAARTGHLPAVEKLLSGKRLSSGFGGGGGGGSGGGGGGSGGGGGGLGSSSHP
  LSSLLSMWRGPNVNCVDSTGYTPLHHAALNGHKDVVEVLLRNDALTNVADSKGCYPLHLA
  AWKGDAQIVRLLIHQGPSHTRVNEQNNDNETALHCAAQYGHTEVVKVLLEELTDPTMRNN
  KFETPLDLAALYGRLEVVKMLLNAHPNLLSCNTKKHTPLHLAARNGHKAVVQVLLDAGMD
  SNYQTEMGSALHEAALFGKTDVVQILLAAGTDVNIKDNHGLTALDTVRELPSQKSQQIAA
  LIEDHMTGKRSTKEVDKTPPPQPPLISSMDSISQKSQGDVEKAVTELIIDFDANAEEEGP
  YEALYNAISCHSLDSMASGRSSDQDSTNKEAEAAGVKPAGVRPRERPPPPAKPPPDEEEE
  DHIDKKYFPLTASEVLSMRPRIHGSAAREEDEHPYELLLTAETKKVVLVDGKTKDHRRSS
  SSRSQDSAEGQDGQVPEQFSGLLHGSSPVCEVGQDPFQLLCTAGQSHPDGSPQQGACHKA
  SMQLEETGVHAPGASQPSALDQSKRVGYLTGLPTTNSRSHPETLTHTASPHPGGAEEGDR
  SGARSRAPPTSKPKAELKLSRSLSKSDSDLLTCSPTEDATMGSRSESLSNCSIGKKRLEK
  SPSFASEWDEIEKIMSSIGEGIDFSQERQKISGLRTLEQSVGEWLESIGLQQYESKLLLN
  GFDDVHFLGSNVMEEQDLRDIGISDPQHRRKLLQAARSLPKVKALGYDGNSPPSVPSWLD
  SLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVLKVQLLGHRKRIIASLADRPYEEPPQK
  PPRFSQLRCQDLLSQTSSPLSQNDSCTGRSADLLLPPGDTGRRRHDSLHDPAAPSRAERF
  RIQEEHREAKLTLRPPSLAAPYAPVQSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTES
  TQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPEDLC
  TFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKSRATGASAAE
  MIETKSSKPVPKPRVGVRKSALEPPDMDQDAQSHASVSWVVDPKPDSKRSLSTN
• Function: Regulator of different signaling pathways. Regulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction.
• Tissue Specificity: Widely expressed (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[1]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[2]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[1]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A).	[11]

References

• [1] Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes.Cardiovasc Diabetol. 2018 Apr 25;17(1):61. doi: 10.1186/s12933-018-0705-0.
• [2] A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.
• [3] Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.Nat Genet. 2015 Dec;47(12):1457-1464. doi: 10.1038/ng.3434. Epub 2015 Oct 26.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.