Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV2BIKK)

• DOT Name: Ankyrin repeat domain-containing protein 13A (ANKRD13A)
• Synonyms: Protein KE03
• Gene Name: ANKRD13A
• UniProt ID: AN13A_HUMAN
• Pfam ID: PF12796 ; PF11904
• Sequence:
  MSSACDAGDHYPLHLLVWKNDYRQLEKELQGQNVEAVDPRGRTLLHLAVSLGHLESARVL
  LRHKADVTKENRQGWTVLHEAVSTGDPEMVYTVLQHRDYHNTSMALEGVPELLQKILEAP
  DFYVQMKWEFTSWVPLVSRICPNDVCRIWKSGAKLRVDITLLGFENMSWIRGRRSFIFKG
  EDNWAELMEVNHDDKVVTTERFDLSQEMERLTLDLMKPKSREVERRLTSPVINTSLDTKN
  IAFERTKSGFWGWRTDKAEVVNGYEAKVYTVNNVNVITKIRTEHLTEEEKKRYKADRNPL
  ESLLGTVEHQFGAQGDLTTECATANNPTAITPDEYFNEEFDLKDRDIGRPKELTIRTQKF
  KAMLWMCEEFPLSLVEQVIPIIDLMARTSAHFARLRDFIKLEFPPGFPVKIEIPLFHVLN
  ARITFGNVNGCSTAEESVSQNVEGTQADSASHITNFEVDQSVFEIPESYYVQDNGRNVHL
  QDEDYEIMQFAIQQSLLESSRSQELSGPASNGGISQTNTYDAQYERAIQESLLTSTEGLC
  PSALSETSRFDNDLQLAMELSAKELEEWELRLQEEEAELQQVLQLSLTDK
• Function: Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[10]

1 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 decreases the phosphorylation of Ankyrin repeat domain-containing protein 13A (ANKRD13A).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.