Details of Drug Off-Target (DOT)

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

• DOT Name: ATPase family gene 2 protein homolog B (AFG2B)
• Synonyms: EC 3.6.4.10; AFG2 AAA ATPase homolog B; Ribosome biogenesis protein SPATA5L1; Spermatogenesis-associated protein 5-like protein 1
• Gene Name: AFG2B
• Related Disease:
  Hearing loss, autosomal recessive 119
  Neurodevelopmental disorder with hearing loss and spasticity
• UniProt ID: AFG2B_HUMAN
• EC Number: 3.6.4.10
• Pfam ID: PF00004 ; PF17862
• Sequence:
  MAPDSDPFPEGPLLKLLPLDARDRGTQRCRLGPAALHALGARLGSAVKISLPDGGSCLCT
  AWPRRDGADGFVQLDPLCASPGAAVGASRSRRSLSLNRLLLVPCPPLRRVAVWPVLRERA
  GAPGARNTAAVLEAAQELLRNRPISLGHVVVAPPGAPGLVAALHIVGGTPSPDPAGLVTP
  RTRVSLGGEPPSEAQPQPEVPLGGLSEAADSLRELLRLPLRYPRALTALGLAVPRGVLLA
  GPPGVGKTQLVRAVAREAGAELLAVSAPALQGSRPGETEENVRRVFQRARELASRGPSLL
  FLDEMDALCPQRGSRAPESRVVAQVLTLLDGASGDREVVVVGATNRPDALDPALRRPGRF
  DREVVIGTPTLKQRKEILQVITSKMPISSHVDLGLLAEMTVGYVGADLTALCREAAMHAL
  LHSEKNQDNPVIDEIDFLEAFKNIQPSSFRSVIGLMDIKPVDWEEIGGLEDVKLKLKQSI
  EWPLKFPWEFVRMGLTQPKGVLLYGPPGCAKTTLVRALATSCHCSFVSVSGADLFSPFVG
  DSEKVLSQIFRQARASTPAILFLDEIDSILGARSASKTGCDVQERVLSVLLNELDGVGLK
  TIERRGSKSSQQEFQEVFNRSVMIIAATNRPDVLDTALLRPGRLDKIIYIPPPDHKGRLS
  ILKVCTKTMPIGPDVSLENLAAETCFFSGADLRNLCTEAALLALQENGLDATTVKQEHFL
  KSLKTVKPSLSCKDLALYENLFKKEGFSNVEGI
• Function: ATP-dependent chaperone, which plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with AFG2A, AIRIM and CINP.
• Tissue Specificity: Expressed in both neurons and glia during embryonic and adult stages of brain development.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hearing loss, autosomal recessive 119	DIS9Y6F2	Strong	Autosomal recessive	[1]
Neurodevelopmental disorder with hearing loss and spasticity	DISOFESB	Moderate	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATPase family gene 2 protein homolog B (AFG2B).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATPase family gene 2 protein homolog B (AFG2B).	[14]

3 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 ATPase family gene 2 protein homolog B (AFG2B).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of ATPase family gene 2 protein homolog B (AFG2B).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of ATPase family gene 2 protein homolog B (AFG2B).	[13]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ATPase family gene 2 protein homolog B (AFG2B).	[10]

References

• [1] Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss. Am J Hum Genet. 2021 Oct 7;108(10):2006-2016. doi: 10.1016/j.ajhg.2021.08.003.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] 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.
• [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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.