Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSIAM08)

• DOT Name: Caytaxin (ATCAY)
• Synonyms: Ataxia cayman type protein; BNIP-2-homology; BNIP-H
• Gene Name: ATCAY
• Related Disease:
  Cerebellar ataxia
  Alzheimer disease
  Cayman type cerebellar ataxia
  Dystonia
  Mental disorder
  Schizophrenia
• UniProt ID: ATCAY_HUMAN
• Pfam ID: PF12496 ; PF13716
• Sequence:
  MGTTEATLRMENVDVKEEWQDEDLPRPLPEETGVELLGSPVEDTSSPPNTLNFNGAHRKR
  KTLVAPEINISLDQSEGSLLSDDFLDTPDDLDINVDDIETPDETDSLEFLGNGNELEWED
  DTPVATAKNMPGDSADLFGDGTTEDGSAANGRLWRTVIIGEQEHRIDLHMIRPYMKVVTH
  GGYYGEGLNAIIVFAACFLPDSSLPDYHYIMENLFLYVISSLELLVAEDYMIVYLNGATP
  RRRMPGIGWLKKCYQMIDRRLRKNLKSLIIVHPSWFIRTVLAISRPFISVKFINKIQYVH
  SLEDLEQLIPMEHVQIPDCVLQYEEERLKARRESARPQPEFVLPRSEEKPEVAPVENRSA
  LVSEDQETSMS
• Function: Functions in the development of neural tissues, particularly the postnatal maturation of the cerebellar cortex. May play a role in neurotransmission through regulation of glutaminase/GLS, an enzyme responsible for the production in neurons of the glutamate neurotransmitter. Alternatively, may regulate the localization of mitochondria within axons and dendrites.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Definitive	Autosomal recessive	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Cayman type cerebellar ataxia	DISN1RNS	Strong	Autosomal recessive	[3]
Dystonia	DISJLFGW	Strong	Biomarker	[4]
Mental disorder	DIS3J5R8	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[6]

6 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 Caytaxin (ATCAY).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Caytaxin (ATCAY).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Caytaxin (ATCAY).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caytaxin (ATCAY).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Caytaxin (ATCAY).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Caytaxin (ATCAY).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Caytaxin (ATCAY).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Caytaxin (ATCAY).	[13]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease.Neurobiol Aging. 2010 Mar;31(3):409-15. doi: 10.1016/j.neurobiolaging.2008.04.009. Epub 2008 May 22.
• [3] Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Nat Genet. 2003 Nov;35(3):264-9. doi: 10.1038/ng1255. Epub 2003 Oct 12.
• [4] Expression of Caytaxin protein in Cayman Ataxia mouse models correlates with phenotype severity.PLoS One. 2012;7(11):e50570. doi: 10.1371/journal.pone.0050570. Epub 2012 Nov 30.
• [5] Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner.Brain Res. 2007 Jan 19;1129(1):100-9. doi: 10.1016/j.brainres.2006.10.068. Epub 2006 Dec 8.
• [6] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] 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.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] 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.
• [13] 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.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.