General Information of Drug Off-Target (DOT) (ID: OTL1STJT)

DOT Name Helicase POLQ-like (HELQ)
Synonyms EC 3.6.4.12; Mus308-like helicase; POLQ-like helicase
Gene Name HELQ
Related Disease
Bone osteosarcoma ( )
Osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Head and neck neoplasm ( )
Head-neck squamous cell carcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pharynx cancer ( )
Advanced cancer ( )
UniProt ID
HELQ_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.6.4.12
Pfam ID
PF00270 ; PF00271 ; PF20470 ; PF21099
Sequence
MDECGSRIRRRVSLPKRNRPSLGCIFGAPTAAELVPGDEGKEEEEMVAENRRRKTAGVLP
VEVQPLLLSDSPECLVLGGGDTNPDLLRHMPTDRGVGDQPNDSEVDMFGDYDSFTENSFI
AQVDDLEQKYMQLPEHKKHATDFATENLCSESIKNKLSITTIGNLTELQTDKHTENQSGY
EGVTIEPGADLLYDVPSSQAIYFENLQNSSNDLGDHSMKERDWKSSSHNTVNEELPHNCI
EQPQQNDESSSKVRTSSDMNRRKSIKDHLKNAMTGNAKAQTPIFSRSKQLKDTLLSEEIN
VAKKTVESSSNDLGPFYSLPSKVRDLYAQFKGIEKLYEWQHTCLTLNSVQERKNLIYSLP
TSGGKTLVAEILMLQELLCCRKDVLMILPYVAIVQEKISGLSSFGIELGFFVEEYAGSKG
RFPPTKRREKKSLYIATIEKGHSLVNSLIETGRIDSLGLVVVDELHMIGEGSRGATLEMT
LAKILYTSKTTQIIGMSATLNNVEDLQKFLQAEYYTSQFRPVELKEYLKINDTIYEVDSK
AENGMTFSRLLNYKYSDTLKKMDPDHLVALVTEVIPNYSCLVFCPSKKNCENVAEMICKF
LSKEYLKHKEKEKCEVIKNLKNIGNGNLCPVLKRTIPFGVAYHHSGLTSDERKLLEEAYS
TGVLCLFTCTSTLAAGVNLPARRVILRAPYVAKEFLKRNQYKQMIGRAGRAGIDTIGESI
LILQEKDKQQVLELITKPLENCYSHLVQEFTKGIQTLFLSLIGLKIATNLDDIYHFMNGT
FFGVQQKVLLKEKSLWEITVESLRYLTEKGLLQKDTIYKSEEEVQYNFHITKLGRASFKG
TIDLAYCDILYRDLKKGLEGLVLESLLHLIYLTTPYDLVSQCNPDWMIYFRQFSQLSPAE
QNVAAILGVSESFIGKKASGQAIGKKVDKNVVNRLYLSFVLYTLLKETNIWTVSEKFNMP
RGYIQNLLTGTASFSSCVLHFCEELEEFWVYRALLVELTKKLTYCVKAELIPLMEVTGVL
EGRAKQLYSAGYKSLMHLANANPEVLVRTIDHLSRRQAKQIVSSAKMLLHEKAEALQEEV
EELLRLPSDFPGAVASSTDKA
Function
Single-stranded 3'-5' DNA helicase that plays a key role in homology-driven double-strand break (DSB) repair. Involved in different DSB repair mechanisms that are guided by annealing of extensive stretches of complementary bases at break ends, such as microhomology-mediated end-joining (MMEJ), single-strand annealing (SSA) or synthesis-dependent strand annealing (SDSA). Possesses both DNA unwinding and annealing activities. Forms a complex with RAD51, stimulating HELQ DNA helicase activity and ability to unwing DNA. Efficiently unwinds substrates containing 3' overhangs or a D-loop. In contrast, interaction with the replication protein A (RPA/RP-A) complex inhibits DNA unwinding by HELQ but strongly stimulates DNA strand annealing. Triggers displacement of RPA from single-stranded DNA to facilitate annealing of complementary sequences.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bone osteosarcoma DIST1004 Definitive Biomarker [1]
Osteosarcoma DISLQ7E2 Definitive Biomarker [1]
Breast cancer DIS7DPX1 Strong Genetic Variation [2]
Breast carcinoma DIS2UE88 Strong Genetic Variation [2]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [3]
Esophageal squamous cell carcinoma DIS5N2GV Strong Genetic Variation [4]
Head and neck neoplasm DIS1OB2G Strong Genetic Variation [5]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [6]
Ovarian cancer DISZJHAP Strong Biomarker [7]
Ovarian neoplasm DISEAFTY Strong Biomarker [7]
Pharynx cancer DISXLF8Z Strong Genetic Variation [8]
Advanced cancer DISAT1Z9 moderate Biomarker [1]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Helicase POLQ-like (HELQ). [9]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Helicase POLQ-like (HELQ). [16]
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6 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 Helicase POLQ-like (HELQ). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Helicase POLQ-like (HELQ). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Helicase POLQ-like (HELQ). [12]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Helicase POLQ-like (HELQ). [13]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Helicase POLQ-like (HELQ). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Helicase POLQ-like (HELQ). [15]
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⏷ Show the Full List of 6 Drug(s)

References

1 HELQ reverses the malignant phenotype of osteosarcoma cells via CHK1-RAD51 signaling pathway.Oncol Rep. 2017 Feb;37(2):1107-1113. doi: 10.3892/or.2016.5329. Epub 2016 Dec 20.
2 Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.Oncotarget. 2016 Dec 6;7(49):80140-80163. doi: 10.18632/oncotarget.12818.
3 Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer.Gynecol Oncol. 2018 May;149(2):341-349. doi: 10.1016/j.ygyno.2018.03.006. Epub 2018 Mar 21.
4 Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population.Hum Genet. 2013 Jun;132(6):649-56. doi: 10.1007/s00439-013-1276-5. Epub 2013 Feb 22.
5 A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.PLoS Genet. 2011 Mar;7(3):e1001333. doi: 10.1371/journal.pgen.1001333. Epub 2011 Mar 17.
6 Gene-environment interactions of novel variants associated with head and neck cancer.Head Neck. 2012 Aug;34(8):1111-8. doi: 10.1002/hed.21867. Epub 2011 Nov 2.
7 Screening of HELQ in breast and ovarian cancer families.Fam Cancer. 2016 Jan;15(1):19-23. doi: 10.1007/s10689-015-9838-4.
8 Genetic variants in DNA repair pathways and risk of upper aerodigestive tract cancers: combined analysis of data from two genome-wide association studies in European populations.Carcinogenesis. 2014 Jul;35(7):1523-7. doi: 10.1093/carcin/bgu075. Epub 2014 Mar 21.
9 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.
10 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.
11 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.
12 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
13 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
14 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.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 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.