Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSOUTE1)

• DOT Name: Phospholipid-transporting ATPase VB (ATP10B)
• Synonyms: EC 7.6.2.1; ATPase class V type 10B; P4-ATPase flippase complex alpha subunit ATP10B
• Gene Name: ATP10B
• UniProt ID: AT10B_HUMAN
• EC Number: 7.6.2.1
• Pfam ID: PF13246 ; PF16212 ; PF16209
• Sequence:
  MALSVDSSWHRWQWRVRDGFPHCPSETTPLLSPEKGRQSYNLTQQRVVFPNNSIFHQDWE
  EVSRRYPGNRTCTTKYTLFTFLPRNLFEQFHRWANLYFLFLVILNWMPSMEVFHREITML
  PLAIVLFVIMIKDGMEDFKRHRFDKAINCSNIRIYERKEQTYVQKCWKDVRVGDFIQMKC
  NEIVPADILLLFSSDPNGICHLETASLDGETNLKQRCVVKGFSQQEVQFEPELFHNTIVC
  EKPNNHLNKFKGYMEHPDQTRTGFGCESLLLRGCTIRNTEMAVGIVIYAGHETKAMLNNS
  GPRYKRSKIERRMNIDIFFCIGILILMCLIGAVGHSIWNGTFEEHPPFDVPDANGSFLPS
  ALGGFYMFLTMIILLQVLIPISLYVSIELVKLGQVFFLSNDLDLYDEETDLSIQCRALNI
  AEDLGQIQYIFSDKTGTLTENKMVFRRCTIMGSEYSHQENAKRLETPKELDSDGEEWTQY
  QCLSFSARWAQDPATMRSQKGAQPLRRSQSARVPIQGHYRQRSMGHRESSQPPVAFSSSI
  EKDVTPDKNLLTKVRDAALWLETLSDSRPAKASLSTTSSIADFFLALTICNSVMVSTTTE
  PRQRVTIKPSSKALGTSLEKIQQLFQKLKLLSLSQSFSSTAPSDTDLGESLGANVATTDS
  DERDDASVCSGGDSTDDGGYRSSMWDQGDILESGSGTSLEEALEAPATDLARPEFCYEAE
  SPDEAALVHAAHAYSFTLVSRTPEQVTVRLPQGTCLTFSLLCTLGFDSVRKRMSVVVRHP
  LTGEIVVYTKGADSVIMDLLEDPACVPDINMEKKLRKIRARTQKHLDLYARDGLRTLCIA
  KKVVSEEDFRRWASFRREAEASLDNRDELLMETAQHLENQLTLLGATGIEDRLQEGVPDT
  IATLREAGIQLWVLTGDKQETAVNIAHSCRLLNQTDTVYTINTENQETCESILNCALEEL
  KQFRELQKPDRKLFGFRLPSKTPSITSEAVVPEAGLVIDGKTLNAIFQGKLEKKFLELTQ
  YCRSVLCCRSTPLQKSMIVKLVRDKLRVMTLSIGDGANDVSMIQAADIGIGISGQEGMQA
  VMSSDFAITRFKHLKKLLLVHGHWCYSRLARMVVYYLYKNVCYVNLLFWYQFFCGFSSST
  MIDYWQMIFFNLFFTSLPPLVFGVLDKDISAETLLALPELYKSGQNSECYNLSTFWISMV
  DAFYQSLICFFIPYLAYKGSDIDVFTFGTPINTISLTTILLHQAMEMKTWTIFHGVVLLG
  SFLMYFLVSLLYNATCVICNSPTNPYWVMEGQLSNPTFYLVCFLTPVVALLPRYFFLSLQ
  GTCGKSLISKAQKIDKLPPDKRNLEIQSWRSRQRPAPVPEVARPTHHPVSSITGQDFSAS
  TPKSSNPPKRKHVEESVLHEQRCGTECMRDDSCSGDSSAQLSSGEHLLGPNRIMAYSRGQ
  TDMCRCSKRSSHRRSQSSLTI
• 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 lysosome membranes. Plays an important role in the maintenance of lysosome membrane integrity and function in cortical neurons.
• Tissue Specificity: Expressed in predominantly in brain structures including medulla oblongata, substantia nigra and basal ganglia. Expressed in the gastrointestinal system with highest levels in the small intestine and colon. Also expressed at low levels in testis and thymus.
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

8 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 VB (ATP10B).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[2]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[4]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phospholipid-transporting ATPase VB (ATP10B).	[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 Phospholipid-transporting ATPase VB (ATP10B).	[7]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] 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.
• [3] 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.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [9] 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.