Details of Drug Off-Target (DOT)

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

• DOT Name: DNA repair and recombination protein RAD54-like (RAD54L)
• Synonyms: EC 3.6.4.12; RAD54 homolog; hHR54; hRAD54
• Gene Name: RAD54L
• Related Disease:
  Hepatocellular carcinoma
  Adult glioblastoma
  Carcinoma
  Glioblastoma multiforme
  Glioma
  Meningioma tumour
  Neoplasm
  Pancreatic cancer
  Bloom syndrome
  Breast neoplasm
  Urinary bladder cancer
  Werner syndrome
  Xeroderma pigmentosum
  Choroid plexus carcinoma
  Small lymphocytic lymphoma
• UniProt ID: RAD54_HUMAN
• EC Number: 3.6.4.12
• Pfam ID: PF00271 ; PF00176
• Sequence:
  MRRSLAPSQLAKRKPEGRSCDDEDWQPGLVTPRKRKSSSETQIQECFLSPFRKPLSQLTN
  QPPCLDSSQHEAFIRSILSKPFKVPIPNYQGPLGSRALGLKRAGVRRALHDPLEKDALVL
  YEPPPLSAHDQLKLDKEKLPVHVVVDPILSKVLRPHQREGVKFLWECVTSRRIPGSHGCI
  MADEMGLGKTLQCITLMWTLLRQSPECKPEIDKAVVVSPSSLVKNWYNEVGKWLGGRIQP
  LAIDGGSKDEIDQKLEGFMNQRGARVSSPILIISYETFRLHVGVLQKGSVGLVICDEGHR
  LKNSENQTYQALDSLNTSRRVLISGTPIQNDLLEYFSLVHFVNSGILGTAHEFKKHFELP
  ILKGRDAAASEADRQLGEERLRELTSIVNRCLIRRTSDILSKYLPVKIEQVVCCRLTPLQ
  TELYKRFLRQAKPAEELLEGKMSVSSLSSITSLKKLCNHPALIYDKCVEEEDGFVGALDL
  FPPGYSSKALEPQLSGKMLVLDYILAVTRSRSSDKVVLVSNYTQTLDLFEKLCRARRYLY
  VRLDGTMSIKKRAKVVERFNSPSSPDFVFMLSSKAGGCGLNLIGANRLVMFDPDWNPAND
  EQAMARVWRDGQKKTCYIYRLLSAGTIEEKIFQRQSHKKALSSCVVDEEQDVERHFSLGE
  LKELFILDEASLSDTHDRLHCRRCVNSRQIRPPPDGSDCTSDLAGWNHCTDKWGLRDEVL
  QAAWDAASTAITFVFHQRSHEEQRGLR
• Function: Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Also plays an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA.
• KEGG Pathway: Homologous recombi.tion (hsa03440)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
Meningioma tumour	DISOZOR8	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[7]
Bloom syndrome	DISKXQ7J	moderate	Genetic Variation	[8]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[9]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[10]
Werner syndrome	DISZY45W	moderate	Genetic Variation	[8]
Xeroderma pigmentosum	DISQ9H19	moderate	Genetic Variation	[8]
Choroid plexus carcinoma	DISQ04MQ	Limited	Biomarker	[11]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[12]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[15]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[18]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[18]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[1]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[21]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[22]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[29]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[30]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of DNA repair and recombination protein RAD54-like (RAD54L).	[31]

1 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 DNA repair and recombination protein RAD54-like (RAD54L).	[16]

References

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• [3] Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker.BMC Cancer. 2003 Mar 4;3:6. doi: 10.1186/1471-2407-3-6. Epub 2003 Mar 4.
• [4] Genetic variations in the homologous recombination repair pathway genes modify risk of glioma.J Neurooncol. 2016 Jan;126(1):11-17. doi: 10.1007/s11060-015-1892-0. Epub 2015 Oct 29.
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• [9] Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors.Cancer Res. 1997 Jun 15;57(12):2378-83.
• [10] Identification of Hub Genes Associated With Progression and Prognosis in Patients With Bladder Cancer.Front Genet. 2019 May 7;10:408. doi: 10.3389/fgene.2019.00408. eCollection 2019.
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• [12] Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.Leuk Lymphoma. 2008 Jan;49(1):130-3. doi: 10.1080/10428190701606800.
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• [18] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [19] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [20] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
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• [30] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
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