Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXM7UTD)

• DOT Name: RAD51-associated protein 1 (RAD51AP1)
• Synonyms: HsRAD51AP1; RAD51-interacting protein
• Gene Name: RAD51AP1
• Related Disease:
  Cholangiocarcinoma
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Intrahepatic cholangiocarcinoma
  Lung cancer
  Lung carcinoma
  Mantle cell lymphoma
  Non-small-cell lung cancer
  Triple negative breast cancer
  Melanoma
• UniProt ID: R51A1_HUMAN
• Pfam ID: PF15696
• Sequence:
  MVRPVRHKKPVNYSQFDHSDSDDDFVSATVPLNKKSRTAPKELKQDKPKPNLNNLRKEEI
  PVQEKTPKKRLPEGTFSIPASAVPCTKMALDDKLYQRDLEVALALSVKELPTVTTNVQNS
  QDKSIEKHGSSKIETMNKSPHISNCSVASDYLDLDKITVEDDVGGVQGKRKAASKAAAQQ
  RKILLEGSDGDSANDTEPDFAPGEDSEDDSDFCESEDNDEDFSMRKSKVKEIKKKEVKVK
  SPVEKKEKKSKSKCNALVTSVDSAPAAVKSESQSLPKKVSLSSDTTRKPLEIRSPSAESK
  KPKWVPPAASGGSRSSSSPLVVVSVKSPNQSLRLGLSRLARVKPLHPNATST
• Function: Structure-specific DNA-binding protein involved in DNA repair by promoting RAD51-mediated homologous recombination. Acts by stimulating D-Loop formation by RAD51: specifically enhances joint molecule formation through its structure-specific DNA interaction and its interaction with RAD51. Binds single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures: has a strong preference for branched-DNA structures that are obligatory intermediates during joint molecule formation. Cooperates with WDR48/UAF1 to stimulate RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during homologous recombination and DNA repair. WDR48/UAF1 and RAD51AP1 also have a coordinated role in DNA-binding to promote USP1-mediated deubiquitination of FANCD2. Also involved in meiosis by promoting DMC1-mediated homologous meiotic recombination. Key mediator of alternative lengthening of telomeres (ALT) pathway, a homology-directed repair mechanism of telomere elongation that controls proliferation in aggressive cancers, by stimulating homologous recombination. May also bind RNA; additional evidences are however required to confirm RNA-binding in vivo.
• Tissue Specificity: Highly expressed in testis and thymus . Lower levels in colon and small intestine . Little or no expression in spleen, prostate, ovary and peripheral blood leukocytes .
• Reactome Pathway:
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568)
  Homologous DNA Pairing and Strand Exchange (R-HSA-5693579)
  Defective homologous recombination repair (HRR) due to BRCA1 loss of function (R-HSA-9701192)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function (R-HSA-9704331)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function (R-HSA-9704646)
  Impaired BRCA2 binding to PALB2 (R-HSA-9709603)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[8]
Melanoma	DIS1RRCY	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RAD51-associated protein 1 (RAD51AP1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RAD51-associated protein 1 (RAD51AP1).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RAD51-associated protein 1 (RAD51AP1).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[21]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[22]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[23]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[24]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[25]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[26]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[27]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[28]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of RAD51-associated protein 1 (RAD51AP1).	[17]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[30]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of RAD51-associated protein 1 (RAD51AP1).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RAD51-associated protein 1 (RAD51AP1).	[37]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of RAD51-associated protein 1 (RAD51AP1).	[38]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of RAD51-associated protein 1 (RAD51AP1).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RAD51-associated protein 1 (RAD51AP1).	[36]

References

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