Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH6MSKQ)

DOT Name Phospholipid-transporting ATPase ABCA3 (ABCA3)
Synonyms EC 7.6.2.1; ABC-C transporter; ATP-binding cassette sub-family A member 3; ATP-binding cassette transporter 3; ATP-binding cassette 3; Xenobiotic-transporting ATPase ABCA3; EC 7.6.2.2
Gene Name ABCA3
Related Disease
Interstitial lung disease due to ABCA3 deficiency ( )
UniProt ID
ABCA3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7W01; 7W02
EC Number
7.6.2.1; 7.6.2.2
Pfam ID
PF12698 ; PF00005
Sequence
MAVLRQLALLLWKNYTLQKRKVLVTVLELFLPLLFSGILIWLRLKIQSENVPNATIYPGQ
SIQELPLFFTFPPPGDTWELAYIPSHSDAAKTVTETVRRALVINMRVRGFPSEKDFEDYI
RYDNCSSSVLAAVVFEHPFNHSKEPLPLAVKYHLRFSYTRRNYMWTQTGSFFLKETEGWH
TTSLFPLFPNPGPREPTSPDGGEPGYIREGFLAVQHAVDRAIMEYHADAATRQLFQRLTV
TIKRFPYPPFIADPFLVAIQYQLPLLLLLSFTYTALTIARAVVQEKERRLKEYMRMMGLS
SWLHWSAWFLLFFLFLLIAASFMTLLFCVKVKPNVAVLSRSDPSLVLAFLLCFAISTISF
SFMVSTFFSKANMAAAFGGFLYFFTYIPYFFVAPRYNWMTLSQKLCSCLLSNVAMAMGAQ
LIGKFEAKGMGIQWRDLLSPVNVDDDFCFGQVLGMLLLDSVLYGLVTWYMEAVFPGQFGV
PQPWYFFIMPSYWCGKPRAVAGKEEEDSDPEKALRNEYFEAEPEDLVAGIKIKHLSKVFR
VGNKDRAAVRDLNLNLYEGQITVLLGHNGAGKTTTLSMLTGLFPPTSGRAYISGYEISQD
MVQIRKSLGLCPQHDILFDNLTVAEHLYFYAQLKGLSRQKCPEEVKQMLHIIGLEDKWNS
RSRFLSGGMRRKLSIGIALIAGSKVLILDEPTSGMDAISRRAIWDLLQRQKSDRTIVLTT
HFMDEADLLGDRIAIMAKGELQCCGSSLFLKQKYGAGYHMTLVKEPHCNPEDISQLVHHH
VPNATLESSAGAELSFILPRESTHRFEGLFAKLEKKQKELGIASFGASITTMEEVFLRVG
KLVDSSMDIQAIQLPALQYQHERRASDWAVDSNLCGAMDPSDGIGALIEEERTAVKLNTG
LALHCQQFWAMFLKKAAYSWREWKMVAAQVLVPLTCVTLALLAINYSSELFDDPMLRLTL
GEYGRTVVPFSVPGTSQLGQQLSEHLKDALQAEGQEPREVLGDLEEFLIFRASVEGGGFN
ERCLVAASFRDVGERTVVNALFNNQAYHSPATALAVVDNLLFKLLCGPHASIVVSNFPQP
RSALQAAKDQFNEGRKGFDIALNLLFAMAFLASTFSILAVSERAVQAKHVQFVSGVHVAS
FWLSALLWDLISFLIPSLLLLVVFKAFDVRAFTRDGHMADTLLLLLLYGWAIIPLMYLMN
FFFLGAATAYTRLTIFNILSGIATFLMVTIMRIPAVKLEELSKTLDHVFLVLPNHCLGMA
VSSFYENYETRRYCTSSEVAAHYCKKYNIQYQENFYAWSAPGVGRFVASMAASGCAYLIL
LFLIETNLLQRLRGILCALRRRRTLTELYTRMPVLPEDQDVADERTRILAPSPDSLLHTP
LIIKELSKVYEQRVPLLAVDRLSLAVQKGECFGLLGFNGAGKTTTFKMLTGEESLTSGDA
FVGGHRISSDVGKVRQRIGYCPQFDALLDHMTGREMLVMYARLRGIPERHIGACVENTLR
GLLLEPHANKLVRTYSGGNKRKLSTGIALIGEPAVIFLDEPSTGMDPVARRLLWDTVARA
RESGKAIIITSHSMEECEALCTRLAIMVQGQFKCLGSPQHLKSKFGSGYSLRAKVQSEGQ
QEALEEFKAFVDLTFPGSVLEDEHQGMVHYHLPGRDLSWAKVFGILEKAKEKYGVDDYSV
SQISLEQVFLSFAHLQPPTAEEGR
Function
Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant. Transports preferentially phosphatidylcholine containing short acyl chains. In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity.
Tissue Specificity
Expressed in brain, pancreas, skeletal muscle and heart . Highly expressed in the lung in an AT2-cell-specific manner . Weakly expressed in placenta, kidney and liver . Also expressed in medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma .
KEGG Pathway
ABC transporters (hsa02010 )
Reactome Pathway
Defective ABCA3 causes SMDP3 (R-HSA-5683678 )
Surfactant metabolism (R-HSA-5683826 )
Defective ABCA3 causes SMDP3 (R-HSA-5688399 )
ABC transporters in lipid homeostasis (R-HSA-1369062 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Interstitial lung disease due to ABCA3 deficiency DISLI77R Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Phospholipid-transporting ATPase ABCA3 (ABCA3) decreases the response to substance of Doxorubicin. [18]
Methotrexate DM2TEOL Approved Phospholipid-transporting ATPase ABCA3 (ABCA3) decreases the response to substance of Methotrexate. [18]
Vinblastine DM5TVS3 Approved Phospholipid-transporting ATPase ABCA3 (ABCA3) decreases the response to substance of Vinblastine. [18]
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14 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 ABCA3 (ABCA3). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [10]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [11]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [12]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Phospholipid-transporting ATPase ABCA3 (ABCA3). [16]
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⏷ Show the Full List of 14 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Phospholipid-transporting ATPase ABCA3 (ABCA3). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Phospholipid-transporting ATPase ABCA3 (ABCA3). [17]
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References

1 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 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.
6 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
7 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.
8 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
9 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
10 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
11 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
12 Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin. Int J Oncol. 2008 Apr;32(4):931-6.
13 Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
14 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
15 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
16 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.
17 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.
18 Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Mol Cancer Ther. 2006 Aug;5(8):1986-94.