Details of Drug Off-Target (DOT)

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

DOT Name DNA excision repair protein ERCC-6-like 2 (ERCC6L2)
Synonyms EC 3.6.4.-; DNA repair and recombination protein RAD26-like
Gene Name ERCC6L2
Related Disease
Amyotrophic lateral sclerosis ( )
Pancytopenia-developmental delay syndrome ( )
Anxiety ( )
Major depressive disorder ( )
Parkinson disease ( )
UniProt ID
ER6L2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6HQ9; 8COB
EC Number
3.6.4.-
Pfam ID
PF00271 ; PF00176 ; PF14773
Sequence
MDPSAPQPRAETSGKDIWHPGERCLAPSPDNGKLCEASIKSITVDENGKSFAVVLYADFQ
ERKIPLKQLQEVKFVKDCPRNLIFDDEDLEKPYFPNRKFPSSSVAFKLSDNGDSIPYTIN
RYLRDYQREGTRFLYGHYIHGGGCILGDDMGLGKTVQVISFLAAVLHKKGTREDIENNMP
EFLLRSMKKEPLSSTAKKMFLIVAPLSVLYNWKDELDTWGYFRVTVLHGNRKDNELIRVK
QRKCEIALTTYETLRLCLDELNSLEWSAVIVDEAHRIKNPKARVTEVMKALKCNVRIGLT
GTILQNNMKELWCVMDWAVPGLLGSGTYFKKQFSDPVEHGQRHTATKRELATGRKAMQRL
AKKMSGWFLRRTKTLIKDQLPKKEDRMVYCSLTDFQKAVYQTVLETEDVTLILQSSEPCT
CRSGQKRRNCCYKTNSHGETVKTLYLSYLTVLQKVANHVALLQAASTSKQQETLIKRICD
QVFSRFPDFVQKSKDAAFETLSDPKYSGKMKVLQQLLNHCRKNRDKVLLFSFSTKLLDVL
QQYCMASGLDYRRLDGSTKSEERLKIVKEFNSTQDVNICLVSTMAGGLGLNFVGANVVVL
FDPTWNPANDLQAIDRAYRIGQCRDVKVLRLISLGTVEEIMYLRQIYKQQLHCVVVGSEN
AKRYFEAVQGSKEHQGELFGIHNLFKFRSQGSCLTKDILEREGQVEAGIMTATTWLKEGP
PAHKLEMPRQPDCQECRGTEQAAEPLAKEACDLCSDFSDEEPVGATGIKTAKNKAPDSSK
ASSSPGQLTLLQCGFSKLLETKCKAVEDSDGNTASDDESSDEQPTCLSTEAKDAGCEKNQ
DSLGTSKHQKLDNILNPKEKHIFYKSEKILEQNISSKSDEKKIKNTDKHCILQNVTESED
SDVICPTQYTTERFPDNSIRFKPPLEGSEDSETEHTVKTRNNDNSRNTDDKRNGIISKKL
SPENTTLKSILKRKGTSDISDESDDIEISSKSRVRKRASSLRFKRIKETKKELHNSPKTM
NKTNQVYAANEDHNSQFIDDYSSSDESLSVSHFSFSKQSHRPRTIRDRTSFSSKLPSHNK
KNSTFIPRKPMKCSNEKVVNQEQSYESMDKFLDGVQEVAYIHSNQNVIGSSKAENHMSRW
AAHDVFELKQFSQLPANIAVCSSKTYKEKVDADTLPHTKKGQQPSEGSISLPLYISNPVN
QKKKKVYHTNQTTFIIGETPKGIRRKQFEEMASYFNSSSVNEFAKHITNATSEERQKMLR
DFYASQYPEVKEFFVDSVSQFNNSSFEKGEQRTRKKSDKRESLIKPRLSDSETLSFKDST
NKISQVCSLKTYKRKSVKFQNHISYREEVFFNDAETKKSPVSSTQEIDSGKNSQASEDTV
TSRSLNSESETRERRLENTMKDQQDLTRTGISRKEPLLKLENKKIENPVLENTSVISLLG
DTSILDDLFKSHGNSPTQLPKKVLSGPMEKAKQRPKDFWDILNEQNDESLSKLTDLAVIE
TLCEKAPLAAPFKRREEPATSLWKSNEKFLWKKFSPSDTDENATNTQSTT
Function May be involved in early DNA damage response.
Tissue Specificity Expressed in bone marrow (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis DISF7HVM Definitive Genetic Variation [1]
Pancytopenia-developmental delay syndrome DIS3J2EY Definitive Autosomal recessive [2]
Anxiety DISIJDBA Strong Genetic Variation [3]
Major depressive disorder DIS4CL3X Strong Genetic Variation [3]
Parkinson disease DISQVHKL moderate Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [4]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [5]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [9]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Temozolomide increases the expression of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [6]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [7]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of DNA excision repair protein ERCC-6-like 2 (ERCC6L2). [11]
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References

1 ERCC6L2 rs591486 polymorphism and risk for amyotrophic lateral sclerosis in Greek population.Neurol Sci. 2019 Jun;40(6):1237-1244. doi: 10.1007/s10072-019-03825-3. Epub 2019 Mar 16.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 Genome-wide association study of co-occurring anxiety in major depression.World J Biol Psychiatry. 2013 Dec;14(8):611-21. doi: 10.3109/15622975.2013.782107. Epub 2013 Sep 19.
4 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.
5 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.
6 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.
7 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
8 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
9 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.
10 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.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.