Details of Drug Off-Target (DOT)

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

DOT Name Autophagy-related protein 2 homolog A (ATG2A)
Gene Name ATG2A
Related Disease
Chronic kidney disease ( )
UniProt ID
ATG2A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6KLR
Pfam ID
PF09333 ; PF12624
Sequence
MSRWLWPWSNCVKERVCRYLLHHYLGHFFQEHLSLDQLSLDLYKGSVALRDIHLEIWSVN
EVLESMESPLELVEGFVGSIEVAVPWAALLTDHCTVRVSGLQLTLQPRRGPAPGAADSQS
WASCMTTSLQLAQECLRDGLPEPSEPPQPLEGLEMFAQTIETVLRRIKVTFLDTVVRVEH
SPGDGERGVAVEVRVQRLEYCDEAVRDPSQAPPVDVHQPPAFLHKLLQLAGVRLHYEELP
AQEEPPEPPLQIGSCSGYMELMVKLKQNEAFPGPKLEVAGQLGSLHLLLTPRQLQQLQEL
LSAVSLTDHEGLADKLNKSRPLGAEDLWLIEQDLNQQLQAGAVAEPLSPDPLTNPLLNLD
NTDLFFSMAGLTSSVASALSELSLSDVDLASSVRSDMASRRLSAQAHPAGKMAPNPLLDT
MRPDSLLKMTLGGVTLTLLQTSAPSSGPPDLATHFFTEFDATKDGPFGSRDFHHLRPRFQ
RACPCSHVRLTGTAVQLSWELRTGSRGRRTTSMEVHFGQLEVLECLWPRGTSEPEYTEIL
TFPGTLGSQASARPCAHLRHTQILRRVPKSRPRRSVACHCHSELALDLANFQADVELGAL
DRLAALLRLATVPAEPPAGLLTEPLPAMEQQTVFRLSAPRATLRLRFPIADLRPEPDPWA
GQAVRAEQLRLELSEPQFRSELSSGPGPPVPTHLELTCSDLHGIYEDGGKPPVPCLRVSK
ALDPKSTGRKYFLPQVVVTVNPQSSSTQWEVAPEKGEELELSVESPCELREPEPSPFSSK
RTMYETEEMVIPGDPEEMRTFQSRTLALSRCSLEVILPSVHIFLPSKEVYESIYNRINND
LLMWEPADLLPTPDPAAQPSGFPGPSGFWHDSFKMCKSAFKLANCFDLTPDSDSDDEDAH
FFSVGASGGPQAAAPEAPSLHLQSTFSTLVTVLKGRITALCETKDEGGKRLEAVHGELVL
DMEHGTLFSVSQYCGQPGLGYFCLEAEKATLYHRAAVDDYPLPSHLDLPSFAPPAQLAPT
IYPSEEGVTERGASGRKGQGRGPHMLSTAVRIHLDPHKNVKEFLVTLRLHKATLRHYMAL
PEQSWHSQLLEFLDVLDDPVLGYLPPTVITILHTHLFSCSVDYRPLYLPVRVLITAETFT
LSSNIIMDTSTFLLRFILDDSALYLSDKCEVETLDLRRDYVCVLDVDLLELVIKTWKGST
EGKLSQPLFELRCSNNVVHVHSCADSCALLVNLLQYVMSTGDLHPPPRPPSPTEIAGQKL
SESPASLPSCPPVETALINQRDLADALLDTERSLRELAQPSGGHLPQASPISVYLFPGER
SGAPPPSPPVGGPAGSLGSCSEEKEDEREEEGDGDTLDSDEFCILDAPGLGIPPRDGEPV
VTQLHPGPIVVRDGYFSRPIGSTDLLRAPAHFPVPSTRVVLREVSLVWHLYGGRDFGPHP
GHRARTGLSGPRSSPSRCSGPNRPQNSWRTQGGSGRQHHVLMEIQLSKVSFQHEVYPAEP
ATGPAAPSQELEERPLSRQVFIVQELEVRDRLASSQINKFLYLHTSERMPRRAHSNMLTI
KALHVAPTTNLGGPECCLRVSLMPLRLNVDQDALFFLKDFFTSLVAGINPVVPGETSAEA
RPETRAQPSSPLEGQAEGVETTGSQEAPGGGHSPSPPDQQPIYFREFRFTSEVPIWLDYH
GKHVTMDQVGTFAGLLIGLAQLNCSELKLKRLCCRHGLLGVDKVLGYALNEWLQDIRKNQ
LPGLLGGVGPMHSVVQLFQGFRDLLWLPIEQYRKDGRLMRGLQRGAASFGSSTASAALEL
SNRLVQAIQATAETVYDILSPAAPVSRSLQDKRSARRLRRGQQPADLREGVAKAYDTVRE
GILDTAQTICDVASRGHEQKGLTGAVGGVIRQLPPTVVKPLILATEATSSLLGGMRNQIV
PDAHKDHALKWRSDSAQD
Function
Lipid transfer protein involved in autophagosome assembly. Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion. Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to ATG9 (ATG9A or ATG9B) to the IM for membrane expansion. Lipid transfer activity is enhanced by WIPI1 and WDR45/WIPI4, which promote ATG2A-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Also regulates lipid droplets morphology and distribution within the cell.
KEGG Pathway
Autophagy - other (hsa04136 )
Autophagy - animal (hsa04140 )
Alzheimer disease (hsa05010 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Spinocerebellar ataxia (hsa05017 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic kidney disease DISW82R7 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Autophagy-related protein 2 homolog A (ATG2A). [2]
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Autophagy-related protein 2 homolog A (ATG2A). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Autophagy-related protein 2 homolog A (ATG2A). [11]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Autophagy-related protein 2 homolog A (ATG2A). [5]
Quercetin DM3NC4M Approved Quercetin increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [7]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [8]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [9]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Autophagy-related protein 2 homolog A (ATG2A). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Autophagy-related protein 2 homolog A (ATG2A). [12]
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⏷ Show the Full List of 8 Drug(s)

References

1 Identification of C21orf59 and ATG2A as novel determinants of renal function-related traits in Japanese by exome-wide association studies.Oncotarget. 2017 Jul 11;8(28):45259-45273. doi: 10.18632/oncotarget.16696.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
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 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.
6 Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
9 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
11 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
12 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.