Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQOXTH2)

DOT Name Phospholipid-transporting ATPase IF (ATP11B)
Synonyms EC 7.6.2.1; ATPase IR; ATPase class VI type 11B; P4-ATPase flippase complex alpha subunit ATP11B
Gene Name ATP11B
Related Disease
Advanced cancer ( )
Epithelial ovarian cancer ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
UniProt ID
AT11B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
7.6.2.1
Pfam ID
PF13246 ; PF00122 ; PF00702 ; PF16212 ; PF16209
Sequence
MWRWIRQQLGFDPPHQSDTRTIYVANRFPQNGLYTPQKFIDNRIISSKYTVWNFVPKNLF
EQFRRVANFYFLIIFLVQLMIDTPTSPVTSGLPLFFVITVTAIKQGYEDWLRHNSDNEVN
GAPVYVVRSGGLVKTRSKNIRVGDIVRIAKDEIFPADLVLLSSDRLDGSCHVTTASLDGE
TNLKTHVAVPETALLQTVANLDTLVAVIECQQPEADLYRFMGRMIITQQMEEIVRPLGPE
SLLLRGARLKNTKEIFGVAVYTGMETKMALNYKSKSQKRSAVEKSMNTFLIIYLVILISE
AVISTILKYTWQAEEKWDEPWYNQKTEHQRNSSKILRFISDFLAFLVLYNFIIPISLYVT
VEMQKFLGSFFIGWDLDLYHEESDQKAQVNTSDLNEELGQVEYVFTDKTGTLTENEMQFR
ECSINGMKYQEINGRLVPEGPTPDSSEGNLSYLSSLSHLNNLSHLTTSSSFRTSPENETE
LIKEHDLFFKAVSLCHTVQISNVQTDCTGDGPWQSNLAPSQLEYYASSPDEKALVEAAAR
IGIVFIGNSEETMEVKTLGKLERYKLLHILEFDSDRRRMSVIVQAPSGEKLLFAKGAESS
ILPKCIGGEIEKTRIHVDEFALKGLRTLCIAYRKFTSKEYEEIDKRIFEARTALQQREEK
LAAVFQFIEKDLILLGATAVEDRLQDKVRETIEALRMAGIKVWVLTGDKHETAVSVSLSC
GHFHRTMNILELINQKSDSECAEQLRQLARRITEDHVIQHGLVVDGTSLSLALREHEKLF
MEVCRNCSAVLCCRMAPLQKAKVIRLIKISPEKPITLAVGDGANDVSMIQEAHVGIGIMG
KEGRQAARNSDYAIARFKFLSKLLFVHGHFYYIRIATLVQYFFYKNVCFITPQFLYQFYC
LFSQQTLYDSVYLTLYNICFTSLPILIYSLLEQHVDPHVLQNKPTLYRDISKNRLLSIKT
FLYWTILGFSHAFIFFFGSYLLIGKDTSLLGNGQMFGNWTFGTLVFTVMVITVTVKMALE
THFWTWINHLVTWGSIIFYFVFSLFYGGILWPFLGSQNMYFVFIQLLSSGSAWFAIILMV
VTCLFLDIIKKVFDRHLHPTSTEKAQLTETNAGIKCLDSMCCFPEGEAACASVGRMLERV
IGRCSPTHISRSWSASDPFYTNDRSILTLSTMDSSTC
Function
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of intracellular membranes. May contribute to the maintenance of membrane lipid asymmetry in endosome compartment.
KEGG Pathway
Efferocytosis (hsa04148 )
Reactome Pathway
Ion transport by P-type ATPases (R-HSA-936837 )
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Limited Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [1]
Neoplasm DISZKGEW Limited Altered Expression [1]
Ovarian cancer DISZJHAP Limited Biomarker [1]
Ovarian neoplasm DISEAFTY Limited Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 IF (ATP11B). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phospholipid-transporting ATPase IF (ATP11B). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Phospholipid-transporting ATPase IF (ATP11B). [7]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [8]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [9]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [10]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Phospholipid-transporting ATPase IF (ATP11B). [11]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Phospholipid-transporting ATPase IF (ATP11B). [13]
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⏷ Show the Full List of 11 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Phospholipid-transporting ATPase IF (ATP11B). [12]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Phospholipid-transporting ATPase IF (ATP11B). [14]
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References

1 ATP11B mediates platinum resistance in ovarian cancer.J Clin Invest. 2013 May;123(5):2119-30. doi: 10.1172/JCI65425. Epub 2013 Apr 15.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
5 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.
6 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.
7 Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
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 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
11 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
12 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.
13 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
14 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.