Details of Drug Off-Target (DOT)

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

• DOT Name: ATPase family AAA domain-containing protein 2B (ATAD2B)
• Gene Name: ATAD2B
• Related Disease:
  Adult glioblastoma
  Breast carcinoma
  Glioblastoma multiforme
  Major depressive disorder
  Mood disorder
• UniProt ID: ATD2B_HUMAN
• PDB ID: 2DKW; 3LXJ; 6VEO
• Pfam ID: PF00004 ; PF17862 ; PF00439
• Sequence:
  MVNTRKSSLRLLGSKSPGPGPGPGAGAEPGATGGSSHFISSRTRSSKTRAASCPAAKAGG
  SGGAGVTLDEARKVEVDGSLSDSHVSPPAKRTLKQPDSVCKDKSKSRSTGQREEWNLSTG
  QARLTSQPGATLPNGHSGLSLRSHPLRGEKKGDGDLSCINGDMEVRKSCRSRKNRFESVN
  QSLLFDQLVNSTAEAVLQEMDNINIRRNRRSGEVERLRMWTDTEFENMDMYSRVKRRRKS
  LRRNSYGIQNHHEVSTEGEEEESQEEDGDIEVEEAEGEENDRPYNLRQRKTVDRYQAPPI
  VPAHQKKRENTLFDIHRSPARRSHIRRKKHAIHSSDTTSSDEERFERRKSKSMARARNRC
  LPMNFRAEDLASGILRERVKVGASLADVDPMNIDKSVRFDSIGGLSHHIHALKEMVVFPL
  LYPEIFEKFKIQPPRGCLFYGPPGTGKTLVARALANECSQGDKKVAFFMRKGADCLSKWV
  GESERQLRLLFDQAYLMRPSIIFFDEIDGLAPVRSSRQDQIHSSIVSTLLALMDGLDNRG
  EIVVIGATNRLDSIDPALRRPGRFDREFLFNLPDQKARKHILQIHTRDWNPKLSDAFLGE
  LAEKCVGYCGADIKALCTEAALIALRRRYPQIYASSHKLQLDVSSIVLSAQDFYHAMQNI
  VPASQRAVMSSGHALSPIIRPLLERSFNNILAVLQKVFPHAEISQSDKKEDIETLILEDS
  EDENALSIFETNCHSGSPKKQSSSAAIHKPYLHFTMSPYHQPTSYRPRLLLSGERGSGQT
  SHLAPALLHTLERFSVHRLDLPALYSVSAKTPEESCAQIFREARRTVPSIVYMPHIGDWW
  EAVSETVRATFLTLLQDIPSFSPIFLLSTSETMYSELPEEVKCIFRIQYEEVLYIQRPIE
  EDRRKFFQELILNQASMAPPRRKHAALCAMEVLPLALPSPPRQLSESEKSRMEDQEENTL
  RELRLFLRDVTKRLATDKRFNIFSKPVDIEEVSDYLEVIKEPMDLSTVITKIDKHNYLTA
  KDFLKDIDLICSNALEYNPDKDPGDKIIRHRACTLKDTAHAIIAAELDPEFNKLCEEIKE
  ARIKRGLSVTSEQINPHSTGARKTETRVEEAFRHKQRNPMDVWHNSANKCAFRVRRKSRR
  RSQWGKGIIKKRKVNNLKKDEEDTKFADYENHTEDRKLLENGEFEVSTDCHEENGEETGD
  LSMTNDESSCDIMDLDQGQRLNNGAGTKENFASTEEESSNESLLVNSSSSLNPEQTSRKE
  TFLKGNCLNGEASTDSFEGIPVLECQNGKLEVVSFCDSGDKCSSEQKILLEDQSKEKPET
  STENHGDDLEKLEALECSNNEKLEPGSDVEVKDAELDKEGASKVKKYRKLILEQAKTTSL
  ELVPEEPSEPVPPLIVDRERLKKLLDLLVDKSNNLAVDQLERLYSLLSQCIYRHRKDYDK
  SQLVEEMERTVHMFETFL

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[2]

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 ATPase family AAA domain-containing protein 2B (ATAD2B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[5]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATPase family AAA domain-containing protein 2B (ATAD2B).	[12]

3 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 increases the phosphorylation of ATPase family AAA domain-containing protein 2B (ATAD2B).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ATPase family AAA domain-containing protein 2B (ATAD2B).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of ATPase family AAA domain-containing protein 2B (ATAD2B).	[9]

References

• [1] ATAD2B is a phylogenetically conserved nuclear protein expressed during neuronal differentiation and tumorigenesis.Dev Growth Differ. 2010 Dec;52(9):747-55. doi: 10.1111/j.1440-169X.2010.01211.x.
• [2] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.