Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2B7XBT)

DOT Name Phospholipid-transporting ATPase IA (ATP8A1)
Synonyms EC 7.6.2.1; ATPase class I type 8A member 1; Chromaffin granule ATPase II; P4-ATPase flippase complex alpha subunit ATP8A1
Gene Name ATP8A1
Related Disease
Angelman syndrome ( )
Autism ( )
Autism spectrum disorder ( )
Cholestasis ( )
Non-small-cell lung cancer ( )
Non-insulin dependent diabetes ( )
UniProt ID
AT8A1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6K7G; 6K7H; 6K7I; 6K7J; 6K7K; 6K7L; 6K7M; 6K7N
EC Number
7.6.2.1
Pfam ID
PF13246 ; PF00122 ; PF16212 ; PF16209
Sequence
MPTMRRTVSEIRSRAEGYEKTDDVSEKTSLADQEEVRTIFINQPQLTKFCNNHVSTAKYN
IITFLPRFLYSQFRRAANSFFLFIALLQQIPDVSPTGRYTTLVPLLFILAVAAIKEIIED
IKRHKADNAVNKKQTQVLRNGAWEIVHWEKVAVGEIVKVTNGEHLPADLISLSSSEPQAM
CYIETSNLDGETNLKIRQGLPATSDIKDVDSLMRISGRIECESPNRHLYDFVGNIRLDGH
GTVPLGADQILLRGAQLRNTQWVHGIVVYTGHDTKLMQNSTSPPLKLSNVERITNVQILI
LFCILIAMSLVCSVGSAIWNRRHSGKDWYLNLNYGGASNFGLNFLTFIILFNNLIPISLL
VTLEVVKFTQAYFINWDLDMHYEPTDTAAMARTSNLNEELGQVKYIFSDKTGTLTCNVMQ
FKKCTIAGVAYGHVPEPEDYGCSPDEWQNSQFGDEKTFSDSSLLENLQNNHPTAPIICEF
LTMMAVCHTAVPEREGDKIIYQAASPDEGALVRAAKQLNFVFTGRTPDSVIIDSLGQEER
YELLNVLEFTSARKRMSVIVRTPSGKLRLYCKGADTVIYDRLAETSKYKEITLKHLEQFA
TEGLRTLCFAVAEISESDFQEWRAVYQRASTSVQNRLLKLEESYELIEKNLQLLGATAIE
DKLQDQVPETIETLMKADIKIWILTGDKQETAINIGHSCKLLKKNMGMIVINEGSLDGTR
ETLSRHCTTLGDALRKENDFALIIDGKTLKYALTFGVRQYFLDLALSCKAVICCRVSPLQ
KSEVVEMVKKQVKVVTLAIGDGANDVSMIQTAHVGVGISGNEGLQAANSSDYSIAQFKYL
KNLLMIHGAWNYNRVSKCILYCFYKNIVLYIIEIWFAFVNGFSGQILFERWCIGLYNVMF
TAMPPLTLGIFERSCRKENMLKYPELYKTSQNALDFNTKVFWVHCLNGLFHSVILFWFPL
KALQYGTAFGNGKTSDYLLLGNFVYTFVVITVCLKAGLETSYWTWFSHIAIWGSIALWVV
FFGIYSSLWPAIPMAPDMSGEAAMLFSSGVFWMGLLFIPVASLLLDVVYKVIKRTAFKTL
VDEVQELEAKSQDPGAVVLGKSLTERAQLLKNVFKKNHVNLYRSESLQQNLLHGYAFSQD
ENGIVSQSEVIRAYDTTKQRPDEW
Function
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the cell membrane. Acts as aminophospholipid translocase at the cell membrane in neuronal cells.
Tissue Specificity
Found in most adult tissues except liver, testis and placenta. Most abundant in heart, brain and skeletal muscle. Also detected in fetal tissues. Isoform 1 is only detected in brain, skeletal muscle and heart and is the most abundant form in skeletal muscle. Highly expressed in platelets .
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

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Angelman syndrome DIS4QVXO Definitive Genetic Variation [1]
Autism DISV4V1Z Strong Altered Expression [2]
Autism spectrum disorder DISXK8NV Strong Biomarker [3]
Cholestasis DISDJJWE Strong Altered Expression [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [5]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 IA (ATP8A1). [7]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [9]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [12]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [13]
Testosterone DM7HUNW Approved Testosterone increases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [13]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [14]
Epanova DMHEAGL Approved Epanova decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [15]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [7]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [14]
Manganese DMKT129 Investigative Manganese decreases the expression of Phospholipid-transporting ATPase IA (ATP8A1). [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 Drug(s)

References

1 A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome.Nat Genet. 2001 May;28(1):19-20. doi: 10.1038/ng0501-19.
2 Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior.Biochim Biophys Acta. 2016 Sep;1862(9):1755-65. doi: 10.1016/j.bbadis.2016.06.005. Epub 2016 Jun 7.
3 Oxidative Stress in Autistic Children Alters Erythrocyte Shape in the Absence of Quantitative Protein Alterations and of Loss of Membrane Phospholipid Asymmetry.Oxid Med Cell Longev. 2018 Nov 11;2018:6430601. doi: 10.1155/2018/6430601. eCollection 2018.
4 A flippase-independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells.Hepatology. 2010 Jun;51(6):2049-60. doi: 10.1002/hep.23586.
5 MiR-140-3p suppressed cell growth and invasion by downregulating the expression of ATP8A1 in non-small cell lung cancer.Tumour Biol. 2016 Mar;37(3):2973-85. doi: 10.1007/s13277-015-3452-9. Epub 2015 Sep 28.
6 An aminophospholipid translocase associated with body fat and type 2 diabetes phenotypes.Obes Res. 2002 Jul;10(7):695-702. doi: 10.1038/oby.2002.94.
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 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
9 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.
10 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.
11 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
12 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
15 Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
16 BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. Oncotarget. 2013 Nov;4(11):2080-95.
17 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
18 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.