Details of Drug Off-Target (DOT)

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

• DOT Name: Atlastin-3 (ATL3)
• Synonyms: EC 3.6.5.-
• Gene Name: ATL3
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Hereditary sensory and autonomic neuropathy
  Neuropathy, hereditary sensory, type 1F
  Peripheral sensory neuropathies
  T-cell leukaemia
  Hereditary sensory and autonomic neuropathy type 1
• UniProt ID: ATLA3_HUMAN
• PDB ID: 5VGR; 6XJO
• EC Number: 3.6.5.-
• Pfam ID: PF02263 ; PF02841
• Sequence:
  MLSPQRVAAAASRGADDAMESSKPGPVQVVLVQKDQHSFELDEKALASILLQDHIRDLDV
  VVVSVAGAFRKGKSFILDFMLRYLYSQKESGHSNWLGDPEEPLTGFSWRGGSDPETTGIQ
  IWSEVFTVEKPGGKKVAVVLMDTQGAFDSQSTVKDCATIFALSTMTSSVQIYNLSQNIQE
  DDLQQLQLFTEYGRLAMDEIFQKPFQTLMFLVRDWSFPYEYSYGLQGGMAFLDKRLQVKE
  HQHEEIQNVRNHIHSCFSDVTCFLLPHPGLQVATSPDFDGKLKDIAGEFKEQLQALIPYV
  LNPSKLMEKEINGSKVTCRGLLEYFKAYIKIYQGEDLPHPKSMLQATAEANNLAAAASAK
  DIYYNNMEEVCGGEKPYLSPDILEEKHCEFKQLALDHFKKTKKMGGKDFSFRYQQELEEE
  IKELYENFCKHNGSKNVFSTFRTPAVLFTGIVALYIASGLTGFIGLEVVAQLFNCMVGLL
  LIALLTWGYIRYSGQYRELGGAIDFGAAYVLEQASSHIGNSTQATVRDAVVGRPSMDKKA
  Q
• Function: GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis.
• Tissue Specificity: Expressed in the central nervous system and in dorsal root ganglia neurons. Expressed in peripheral tissues (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[1]
Hereditary sensory and autonomic neuropathy	DIS2VOAM	Strong	Genetic Variation	[2]
Neuropathy, hereditary sensory, type 1F	DISFP4J8	Strong	Autosomal dominant	[3]
Peripheral sensory neuropathies	DISYWI6M	Strong	Genetic Variation	[4]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[1]
Hereditary sensory and autonomic neuropathy type 1	DISLSPO4	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Atlastin-3 (ATL3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Atlastin-3 (ATL3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Atlastin-3 (ATL3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Atlastin-3 (ATL3).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Atlastin-3 (ATL3).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Atlastin-3 (ATL3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Atlastin-3 (ATL3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Atlastin-3 (ATL3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Atlastin-3 (ATL3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Atlastin-3 (ATL3).	[14]

References

• [1] Adult T-cell leukemia: structures and expression of the p53 gene.Int J Cancer. 1991 Dec 2;49(6):880-5. doi: 10.1002/ijc.2910490614.
• [2] ATL3, a cargo receptor for reticulophagy.Autophagy. 2019 Aug;15(8):1465-1466. doi: 10.1080/15548627.2019.1609862. Epub 2019 Apr 28.
• [3] Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. Brain. 2014 Mar;137(Pt 3):683-92. doi: 10.1093/brain/awt357. Epub 2014 Jan 22.
• [4] Sensory-Neuropathy-Causing Mutations in ATL3 Cause Aberrant ER Membrane Tethering.Cell Rep. 2018 May 15;23(7):2026-2038. doi: 10.1016/j.celrep.2018.04.071.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [10] 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.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] 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.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.