Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJYVW1I)

• DOT Name: Probable cation-transporting ATPase 13A4 (ATP13A4)
• Synonyms: EC 7.2.2.-; P5-ATPase isoform 4
• Gene Name: ATP13A4
• Related Disease:
  Autism
  Autism spectrum disorder
  Parkinson disease
  Schizophrenia
• UniProt ID: AT134_HUMAN
• EC Number: 7.2.2.-
• Pfam ID: PF13246 ; PF00690 ; PF00122 ; PF12409
• Sequence:
  MGHFEKGQHALLNEGEENEMEIFGYRTQGCRKSLCLAGSIFSFGILPLVFYWRPAWHVWA
  HCVPCSLQEADTVLLRTTDEFQIYSWKKVIWIYLSALNSAFGLTPDHPLMTDEEYIINRA
  IRKPDLKVRCIKVQKIRYVWNYLEGQFQKIGSLEDWLSSAKIHQKFGSGLTREEQEIRRL
  ICGPNTIDVEVTPIWKLLIKEVLNPFYIFQLFSVCLWFSEDYKEYAFAIIIMSIISISLT
  VYDLREQSVKLHHLVESHNSITVSVCGRKAGVQELESRVLVPGDLLILTGNKVLMPCDAV
  LIEGSCVVDEGMLTGESIPVTKTPLPKMDSSVPWKTQSEADYKRHVLFCGTEVIQAKAAC
  SGTVRAVVLQTGFNTAKGDLVRSILYPKPVNFQLYRDAIRFLLCLVGTATIGMIYTLCVY
  VLSGEPPEEVVRKALDVITIAVPPALPAALTTGIIYAQRRLKKRGIFCISPQRINVCGQL
  NLVCFDKTGTLTRDGLDLWGVVSCDRNGFQEVHSFASGQALPWGPLCAAMASCHSLILLD
  GTIQGDPLDLKMFEATTWEMAFSGDDFHIKGVPAHAMVVKPCRTASQVPVEGIAILHQFP
  FSSALQRMTVIVQEMGGDRLAFMKGAPERVASFCQPETVPTSFVSELQIYTTQGFRVIAL
  AYKKLENDHHATTLTRETVESDLIFLGLLILENRLKEETKPVLEELISARIRTVMITGDN
  LQTAITVARKSGMVSESQKVILIEANETTGSSSASISWTLVEEKKHIMYGNQDNYINIRD
  EVSDKGREGSYHFALTGKSFHVISQHFSSLLPKILINGTIFARMSPGQKSSLVEEFQKLD
  YFVGMCGDGANDCGALKMAHVGISLSEQEASVASPFTSKTPNIECVPHLIKEGRAALVTS
  FCMFKYMALYSMIQYVGVLLLYWETNSLSNYQFLFQDLAITTLIGVTMNLNGAYPKLVPF
  RPAGRLISPPLLLSVIFNILLSLAMHIAGFILVQRQPWYSVEIHSACTVQNESISELTMS
  PTAPEKMESNSTFTSFENTTVWFLGTINCITVALVFSKGKPFRQPTYTNYIFVLVLIIQL
  GVCLFILFADIPELYRRLDLLCTPVLWRASIVIMLSLNFIVSLVAEEAVIENRALWMMIK
  RCFGYQSKSQYRIWQRDLANDPSWPPLNQTSHSDMPECGRGVSYSNPVFESNEEQL
• Tissue Specificity: Expressed in heart, placenta, liver, skeletal muscles, and pancreas. Lower levels of expression are also detected in brain, lung and kidney. Weakly expressed in the adult brain. Expression in fetal brain is higher than in adult brain, with levels similar to several other fetal tissues including spleen and skeletal muscle. In adult brain expressed at low levels in all tissues examined, including the temporal lobe and putamen . Highly expressed in the respiratory and integumentary systems .
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Probable cation-transporting ATPase 13A4 (ATP13A4).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Probable cation-transporting ATPase 13A4 (ATP13A4).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Probable cation-transporting ATPase 13A4 (ATP13A4).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Probable cation-transporting ATPase 13A4 (ATP13A4).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Probable cation-transporting ATPase 13A4 (ATP13A4).	[9]

1 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 increases the methylation of Probable cation-transporting ATPase 13A4 (ATP13A4).	[7]

References

• [1] The E646D-ATP13A4 mutation associated with autism reveals a defect in calcium regulation.Cell Mol Neurobiol. 2010 Mar;30(2):233-46. doi: 10.1007/s10571-009-9445-8.
• [2] Parkinson disease related ATP13A2 evolved early in animal evolution.PLoS One. 2018 Mar 5;13(3):e0193228. doi: 10.1371/journal.pone.0193228. eCollection 2018.
• [3] mRNA expression of the P5 ATPase ATP13A4 is increased in Broca's area from subjects with schizophrenia.World J Biol Psychiatry. 2020 Jun;21(5):402-408. doi: 10.1080/15622975.2018.1548781. Epub 2019 Jan 14.
• [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] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.