Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT68PVSD)

DOT Name DNA cross-link repair 1A protein (DCLRE1A)
Synonyms Beta-lactamase DCLRE1A; EC 3.5.2.6; SNM1 homolog A; hSNM1; hSNM1A
Gene Name DCLRE1A
Related Disease
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Peripheral neuropathy ( )
Severe combined immunodeficiency ( )
Colorectal carcinoma ( )
Small-cell lung cancer ( )
UniProt ID
DCR1A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4B87 ; 5AHR ; 5NZW ; 5NZX ; 5NZY ; 5Q1J ; 5Q1K ; 5Q1L ; 5Q1M ; 5Q1N ; 5Q1O ; 5Q1P ; 5Q1Q ; 5Q1R ; 5Q1S ; 5Q1T ; 5Q1U ; 5Q1V ; 5Q1W ; 5Q1X ; 5Q1Y ; 5Q1Z ; 5Q20 ; 5Q22 ; 5Q23 ; 5Q24 ; 5Q25 ; 5Q26 ; 5Q27 ; 5Q28 ; 5Q29 ; 5Q2A ; 5Q2B ; 5Q2C ; 5Q2D ; 5Q2E ; 5Q2F ; 5Q2G ; 5Q2H ; 5Q2I ; 5Q2J ; 5Q2K ; 5Q2L ; 5Q2M ; 5Q2N ; 5Q2O ; 5Q2P ; 5Q2Q ; 5Q2R ; 5Q2S ; 5Q2T ; 5Q2U ; 5Q2V ; 5Q2W ; 5Q2X ; 5Q2Y ; 5Q2Z ; 5Q30 ; 5Q31 ; 5Q32 ; 5Q33 ; 5Q34 ; 5Q35 ; 5Q36 ; 5Q37 ; 5Q38 ; 5Q39 ; 5Q3A ; 5Q3B ; 5Q3C ; 5Q3D ; 5Q3E ; 5Q3F ; 5Q3G ; 5Q3H ; 5Q3I ; 5Q3J ; 5Q3K ; 5Q3L ; 5Q3M ; 5Q3N ; 5Q3O ; 5Q3P ; 5Q3Q ; 5Q3R ; 5Q3S ; 5Q3T ; 5Q3U ; 5Q3V ; 5Q3W ; 5Q3X ; 5Q3Y ; 5Q3Z ; 5Q40 ; 5Q41 ; 5Q42 ; 5Q43 ; 5Q44 ; 5Q45 ; 5Q46 ; 5Q47 ; 5Q48 ; 5Q49 ; 5Q4A ; 5Q4B ; 5Q4C ; 5Q4D ; 5Q4E ; 5Q4F ; 5Q4G ; 5Q4H ; 5Q4I ; 5Q4J ; 5Q4K ; 5Q4L ; 5Q4M ; 5Q4N ; 5Q4O ; 5Q4P ; 5Q4Q ; 5Q4R ; 5Q4S ; 5Q4T ; 5Q4U ; 5Q4V ; 5Q4W ; 5Q4X ; 5Q4Y ; 5Q4Z ; 5Q50 ; 5Q51 ; 5Q52 ; 5Q53 ; 5Q54 ; 5Q55 ; 5Q56 ; 5Q57 ; 5Q58 ; 5Q59 ; 5Q5A ; 5Q5B ; 5Q5C ; 5Q5D ; 5Q5E ; 5Q5F ; 5Q5G ; 5Q5H ; 5Q5I ; 5Q5J ; 5Q5K ; 5Q5L ; 5Q5M ; 5Q5N ; 5Q5O ; 5Q5P ; 5Q5Q ; 5Q5R ; 5Q5S ; 5Q5T ; 5Q5U ; 5Q5V ; 5Q5W ; 5Q5X ; 5Q5Y ; 5Q5Z ; 5Q60 ; 5Q61 ; 5Q62 ; 5Q63 ; 5Q64 ; 5Q65 ; 5Q66 ; 5Q67 ; 5Q68 ; 5Q69 ; 5Q6A ; 5Q6B ; 5Q6C ; 5Q6D ; 5Q6E ; 5Q6F ; 5Q6G ; 5Q6H ; 5Q6I ; 5Q6J ; 5Q6K ; 5Q6L ; 5Q6M ; 5Q6N ; 5Q6O ; 5Q6P ; 5Q6Q ; 5Q6R ; 5Q6S ; 5Q6T ; 5Q6U ; 5Q6V ; 5Q6W ; 5Q6X ; 5Q6Y ; 5Q6Z ; 5Q70 ; 5Q71 ; 5Q72 ; 5Q73 ; 5Q74 ; 5Q75 ; 5Q76 ; 5Q77 ; 5Q78 ; 5Q79 ; 5Q7A ; 5Q7B ; 5Q7C ; 5Q7D ; 5Q7E ; 5Q7F ; 5Q7G ; 5Q7H ; 5Q7I ; 5Q7J ; 5Q7K ; 5Q7L ; 5Q7M ; 5Q7N ; 5Q7O ; 5Q7P ; 5Q7Q ; 5Q7R ; 5Q7S ; 5Q7T ; 5Q7U ; 5Q7V ; 5Q7W ; 5Q7X ; 5Q7Y ; 5Q7Z ; 5Q80 ; 5Q81 ; 5Q82 ; 5Q83 ; 5Q84 ; 5Q85 ; 5Q86 ; 5Q87 ; 5Q88 ; 5Q89 ; 5Q8A ; 5Q8B ; 5Q8C ; 5Q8D ; 5Q8E ; 5Q8F ; 5Q8G ; 5Q8H ; 5Q8I ; 5Q8J ; 5Q8K ; 5Q8L ; 5Q8M ; 5Q8N ; 5Q8O ; 5Q8P ; 5Q8Q ; 5Q8R ; 5Q8S ; 5Q8T ; 5Q8U ; 5Q8V ; 5Q8W ; 5Q8X ; 5Q8Y ; 5Q8Z ; 5Q90 ; 5Q91 ; 5Q92 ; 5Q93 ; 5Q94 ; 5Q95 ; 5Q96 ; 5Q97 ; 5Q98 ; 5Q99 ; 5Q9A ; 5Q9B ; 5Q9C ; 5Q9D ; 5Q9E ; 5Q9F ; 5Q9G ; 5Q9H ; 5Q9I ; 5Q9J ; 5Q9K ; 5Q9L ; 5Q9M ; 5Q9N ; 5Q9O ; 5Q9P ; 5Q9Q ; 5Q9R ; 5Q9S ; 5Q9T ; 5Q9U ; 5Q9V ; 5Q9W ; 5Q9X ; 5Q9Y ; 5Q9Z ; 5QA0 ; 5QA1 ; 5QA2
EC Number
3.5.2.6
Pfam ID
PF07522
Sequence
MLEDISEEDIWEYKSKRKPKRVDPNNGSKNILKSVEKATDGKYQSKRSRNRKRAAEAKEV
KDHEVPLGNAGCQTSVASSQNSSCGDGIQQTQDKETTPGKLCRTQKSQHVSPKIRPVYDG
YCPNCQMPFSSLIGQTPRWHVFECLDSPPRSETECPDGLLCTSTIPFHYKRYTHFLLAQS
RAGDHPFSSPSPASGGSFSETKSGVLCSLEERWSSYQNQTDNSVSNDPLLMTQYFKKSPS
LTEASEKISTHIQTSQQALQFTDFVENDKLVGVALRLANNSEHINLPLPENDFSDCEISY
SPLQSDEDTHDIDEKPDDSQEQLFFTESSKDGSLEEDDDSCGFFKKRHGPLLKDQDESCP
KVNSFLTRDKYDEGLYRFNSLNDLSQPISQNNESTLPYDLACTGGDFVLFPPALAGKLAA
SVHQATKAKPDEPEFHSAQSNKQKQVIEESSVYNQVSLPLVKSLMLKPFESQVEGYLSSQ
PTQNTIRKLSSENLNAKNNTNSACFCRKALEGVPVGKATILNTENLSSTPAPKYLKILPS
GLKYNARHPSTKVMKQMDIGVYFGLPPKRKEEKLLGESALEGINLNPVPSPNQKRSSQCK
RKAEKSLSDLEFDASTLHESQLSVELSSERSQRQKKRCRKSNSLQEGACQKRSDHLINTE
SEAVNLSKVKVFTKSAHGGLQRGNKKIPESSNVGGSRKKTCPFYKKIPGTGFTVDAFQYG
VVEGCTAYFLTHFHSDHYAGLSKHFTFPVYCSEITGNLLKNKLHVQEQYIHPLPLDTECI
VNGVKVVLLDANHCPGAVMILFYLPNGTVILHTGDFRADPSMERSLLADQKVHMLYLDTT
YCSPEYTFPSQQEVIRFAINTAFEAVTLNPHALVVCGTYSIGKEKVFLAIADVLGSKVGM
SQEKYKTLQCLNIPEINSLITTDMCSSLVHLLPMMQINFKGLQSHLKKCGGKYNQILAFR
PTGWTHSNKFTRIADVIPQTKGNISIYGIPYSEHSSYLEMKRFVQWLKPQKIIPTVNVGT
WKSRSTMEKYFREWKLEAGY
Function
May be required for DNA interstrand cross-link repair. Also required for checkpoint mediated cell cycle arrest in early prophase in response to mitotic spindle poisons. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin. Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem).
Tissue Specificity Expressed in brain, heart, kidney, liver, pancreas, placenta and skeletal muscle.
Reactome Pathway
Fanconi Anemia Pathway (R-HSA-6783310 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [1]
Fanconi's anemia DISGW6Q8 Strong Biomarker [1]
Peripheral neuropathy DIS7KN5G Strong Genetic Variation [2]
Severe combined immunodeficiency DIS6MF4Q Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [4]
Small-cell lung cancer DISK3LZD moderate Genetic Variation [5]
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⏷ Show the Full List of 6 Disease(s)
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 decreases the methylation of DNA cross-link repair 1A protein (DCLRE1A). [6]
TAK-243 DM4GKV2 Phase 1 TAK-243 affects the sumoylation of DNA cross-link repair 1A protein (DCLRE1A). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of DNA cross-link repair 1A protein (DCLRE1A). [15]
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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 decreases the expression of DNA cross-link repair 1A protein (DCLRE1A). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DNA cross-link repair 1A protein (DCLRE1A). [8]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of DNA cross-link repair 1A protein (DCLRE1A). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of DNA cross-link repair 1A protein (DCLRE1A). [10]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of DNA cross-link repair 1A protein (DCLRE1A). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of DNA cross-link repair 1A protein (DCLRE1A). [12]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of DNA cross-link repair 1A protein (DCLRE1A). [13]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of DNA cross-link repair 1A protein (DCLRE1A). [16]
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⏷ Show the Full List of 8 Drug(s)

References

1 Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.PLoS Genet. 2012;8(8):e1002884. doi: 10.1371/journal.pgen.1002884. Epub 2012 Aug 9.
2 Pharmacogenetic analyses of 2183 patients with advanced colorectal cancer; potential role for common dihydropyrimidine dehydrogenase variants in toxicity to chemotherapy.Eur J Cancer. 2018 Oct;102:31-39. doi: 10.1016/j.ejca.2018.07.009. Epub 2018 Aug 13.
3 A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J Immunol. 2002 Jun 15;168(12):6323-9. doi: 10.4049/jimmunol.168.12.6323.
4 The role of double-strand break repair, translesion synthesis, and interstrand crosslinks in colorectal cancer progression-clinicopathological data and survival.J Surg Oncol. 2020 Apr;121(5):906-916. doi: 10.1002/jso.25737. Epub 2019 Oct 25.
5 Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk.Carcinogenesis. 2006 Dec;27(12):2448-54. doi: 10.1093/carcin/bgl095. Epub 2006 Jun 14.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
10 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
11 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
14 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.
15 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.
16 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.