Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JPE4H)

• DOT Name: Phospholipid-transporting ATPase VD (ATP10D)
• Synonyms: EC 7.6.2.1; ATPase class V type 10D; P4-ATPase flippase complex alpha subunit ATP10D
• Gene Name: ATP10D
• Related Disease:
  Myocardial infarction
  Obesity
• UniProt ID: AT10D_HUMAN
• EC Number: 7.6.2.1
• Pfam ID: PF13246 ; PF16212 ; PF16209
• Sequence:
  MTEALQWARYHWRRLIRGATRDDDSGPYNYSSLLACGRKSSQTPKLSGRHRIVVPHIQPF
  KDEYEKFSGAYVNNRIRTTKYTLLNFVPRNLFEQFHRAANLYFLFLVVLNWVPLVEAFQK
  EITMLPLVVVLTIIAIKDGLEDYRKYKIDKQINNLITKVYSRKEKKYIDRCWKDVTVGDF
  IRLSCNEVIPADMVLLFSTDPDGICHIETSGLDGESNLKQRQVVRGYAEQDSEVDPEKFS
  SRIECESPNNDLSRFRGFLEHSNKERVGLSKENLLLRGCTIRNTEAVVGIVVYAGHETKA
  MLNNSGPRYKRSKLERRANTDVLWCVMLLVIMCLTGAVGHGIWLSRYEKMHFFNVPEPDG
  HIISPLLAGFYMFWTMIILLQVLIPISLYVSIEIVKLGQIYFIQSDVDFYNEKMDSIVQC
  RALNIAEDLGQIQYLFSDKTGTLTENKMVFRRCSVAGFDYCHEENARRLESYQEAVSEDE
  DFIDTVSGSLSNMAKPRAPSCRTVHNGPLGNKPSNHLAGSSFTLGSGEGASEVPHSRQAA
  FSSPIETDVVPDTRLLDKFSQITPRLFMPLDETIQNPPMETLYIIDFFIALAICNTVVVS
  APNQPRQKIRHPSLGGLPIKSLEEIKSLFQRWSVRRSSSPSLNSGKEPSSGVPNAFVSRL
  PLFSRMKPASPVEEEVSQVCESPQCSSSSACCTETEKQHGDAGLLNGKAESLPGQPLACN
  LCYEAESPDEAALVYAARAYQCTLRSRTPEQVMVDFAALGPLTFQLLHILPFDSVRKRMS
  VVVRHPLSNQVVVYTKGADSVIMELLSVASPDGASLEKQQMIVREKTQKHLDDYAKQGLR
  TLCIAKKVMSDTEYAEWLRNHFLAETSIDNREELLLESAMRLENKLTLLGATGIEDRLQE
  GVPESIEALHKAGIKIWMLTGDKQETAVNIAYACKLLEPDDKLFILNTQSKDACGMLMST
  ILKELQKKTQALPEQVSLSEDLLQPPVPRDSGLRAGLIITGKTLEFALQESLQKQFLELT
  SWCQAVVCCRATPLQKSEVVKLVRSHLQVMTLAIGDGANDVSMIQVADIGIGVSGQEGMQ
  AVMASDFAVSQFKHLSKLLLVHGHWCYTRLSNMILYFFYKNVAYVNLLFWYQFFCGFSGT
  SMTDYWVLIFFNLLFTSAPPVIYGVLEKDVSAETLMQLPELYRSGQKSEAYLPHTFWITL
  LDAFYQSLVCFFVPYFTYQGSDTDIFAFGNPLNTAALFIVLLHLVIESKSLTWIHLLVII
  GSILSYFLFAIVFGAMCVTCNPPSNPYWIMQEHMLDPVFYLVCILTTSIALLPRFVYRVL
  QGSLFPSPILRAKHFDRLTPEERTKALKKWRGAGKMNQVTSKYANQSAGKSGRRPMPGPS
  AVFAMKSASSCAIEQGNLSLCETALDQGYSETKAFEMAGPSKGKES
• Function: Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of the plasma membrane.
• Tissue Specificity: Expressed in placenta and, to a lesser extent, in kidney.
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]

15 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 Phospholipid-transporting ATPase VD (ATP10D).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[8]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Phospholipid-transporting ATPase VD (ATP10D).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phospholipid-transporting ATPase VD (ATP10D).	[16]

References

• [1] A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population.Atherosclerosis. 2013 Nov;231(1):158-62. doi: 10.1016/j.atherosclerosis.2013.08.034. Epub 2013 Sep 5.
• [2] Lipidomic and metabolic changes in the P4-type ATPase ATP10D deficient C57BL/6J wild type mice upon rescue of ATP10D function.PLoS One. 2017 May 25;12(5):e0178368. doi: 10.1371/journal.pone.0178368. eCollection 2017.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [13] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [14] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.