Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWRV4S2)

• DOT Name: DNA repair protein XRCC1
• Synonyms: X-ray repair cross-complementing protein 1
• Gene Name: XRCC1
• Related Disease:
  Head and neck cancer
  Spinocerebellar ataxia, autosomal recessive 26
• UniProt ID: XRCC1_HUMAN
• PDB ID: 1CDZ; 1XNA; 1XNT; 2D8M; 2W3O; 3K75; 3K77; 3LQC; 5E6Q; 5W7X; 5W7Y; 6WH1; 6WH2
• Pfam ID: PF00533 ; PF16589 ; PF01834
• Sequence:
  MPEIRLRHVVSCSSQDSTHCAENLLKADTYRKWRAAKAGEKTISVVLQLEKEEQIHSVDI
  GNDGSAFVEVLVGSSAGGAGEQDYEVLLVTSSFMSPSESRSGSNPNRVRMFGPDKLVRAA
  AEKRWDRVKIVCSQPYSKDSPFGLSFVRFHSPPDKDEAEAPSQKVTVTKLGQFRVKEEDE
  SANSLRPGALFFSRINKTSPVTASDPAGPSYAAATLQASSAASSASPVSRAIGSTSKPQE
  SPKGKRKLDLNQEEKKTPSKPPAQLSPSVPKRPKLPAPTRTPATAPVPARAQGAVTGKPR
  GEGTEPRRPRAGPEELGKILQGVVVVLSGFQNPFRSELRDKALELGAKYRPDWTRDSTHL
  ICAFANTPKYSQVLGLGGRIVRKEWVLDCHRMRRRLPSQRYLMAGPGSSSEEDEASHSGG
  SGDEAPKLPQKQPQTKTKPTQAAGPSSPQKPPTPEETKAASPVLQEDIDIEGVQSEGQDN
  GAEDSGDTEDELRRVAEQKEHRLPPGQEENGEDPYAGSTDENTDSEEHQEPPDLPVPELP
  DFFQGKHFFLYGEFPGDERRKLIRYVTAFNGELEDYMSDRVQFVITAQEWDPSFEEALMD
  NPSLAFVRPRWIYSCNEKQKLLPHQLYGVVPQA
• Function: Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity. Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity.
• Tissue Specificity: Expressed in fibroblasts, retinal pigmented epithelial cells and lymphoblastoid cells (at protein level).
• KEGG Pathway: Base excision repair (hsa03410)
• Reactome Pathway:
  APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway (R-HSA-5649702)
  HDR through MMEJ (alt-NHEJ) (R-HSA-5685939)
  Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  Resolution of AP sites via the single-nucleotide replacement pathway (R-HSA-110381)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head and neck cancer	DISBPSQZ	Limited	Autosomal dominant	[1]
Spinocerebellar ataxia, autosomal recessive 26	DISL5KY2	Limited	Unknown	[2]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	DNA repair protein XRCC1 decreases the response to substance of Hydrogen peroxide.	[28]
Gefitinib	DM15F0X	Approved	DNA repair protein XRCC1 affects the response to substance of Gefitinib.	[29]
Bleomycin	DMNER5S	Approved	DNA repair protein XRCC1 decreases the response to substance of Bleomycin.	[28]
Floxuridine	DM04LR2	Approved	DNA repair protein XRCC1 decreases the response to substance of Floxuridine.	[30]
Camptothecin	DM6CHNJ	Phase 3	DNA repair protein XRCC1 affects the response to substance of Camptothecin.	[31]
Formaldehyde	DM7Q6M0	Investigative	DNA repair protein XRCC1 affects the response to substance of Formaldehyde.	[32]
Aminohippuric acid	DMUN54G	Investigative	DNA repair protein XRCC1 increases the response to substance of Aminohippuric acid.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA repair protein XRCC1.	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA repair protein XRCC1.	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DNA repair protein XRCC1.	[22]

24 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 protein XRCC1.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA repair protein XRCC1.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA repair protein XRCC1.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA repair protein XRCC1.	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA repair protein XRCC1.	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA repair protein XRCC1.	[9]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA repair protein XRCC1.	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA repair protein XRCC1.	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA repair protein XRCC1.	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA repair protein XRCC1.	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA repair protein XRCC1.	[14]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of DNA repair protein XRCC1.	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of DNA repair protein XRCC1.	[16]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of DNA repair protein XRCC1.	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of DNA repair protein XRCC1.	[15]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of DNA repair protein XRCC1.	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA repair protein XRCC1.	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA repair protein XRCC1.	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA repair protein XRCC1.	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA repair protein XRCC1.	[23]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of DNA repair protein XRCC1.	[24]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of DNA repair protein XRCC1.	[25]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of DNA repair protein XRCC1.	[26]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of DNA repair protein XRCC1.	[27]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
LY294002	DMY1AFS	Phase 1	LY294002 decreases the stability of DNA repair protein XRCC1.	[17]
U0126	DM31OGF	Investigative	U0126 decreases the stability of DNA repair protein XRCC1.	[17]

References

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