Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFIOPG1)

• DOT Name: DNA repair endonuclease XPF (ERCC4)
• Synonyms: EC 3.1.-.-; DNA excision repair protein ERCC-4; DNA repair protein complementing XP-F cells; Xeroderma pigmentosum group F-complementing protein
• Gene Name: ERCC4
• Related Disease:
  Embryonal neoplasm
  Germ cell tumor
  Xeroderma pigmentosum group F
  Acute monocytic leukemia
  Bone osteosarcoma
  Breast neoplasm
  Cerebellar ataxia
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Cockayne syndrome
  Cockayne syndrome type 1
  Colorectal carcinoma
  Cutaneous melanoma
  Endometrial carcinoma
  Fanconi anemia complementation group Q
  Gastric cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hutchinson-Gilford progeria syndrome
  Leukopenia
  Lung neoplasm
  Neoplasm
  Neoplasm of testis
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Testicular cancer
  Triple negative breast cancer
  Vulvar squamous intraepithelial lesion
  Xeroderma pigmentosum group A
  XFE progeroid syndrome
  Lung cancer
  Lung carcinoma
  Stomach cancer
  Fanconi's anemia
  Xeroderma pigmentosum
  Xeroderma pigmentosum-Cockayne syndrome complex
  Xeroderma pigmentosum group G
  Adenocarcinoma
  Chromosomal disorder
  Melanoma
  Neuroblastoma
  Squamous cell carcinoma
• UniProt ID: XPF_HUMAN
• PDB ID: 1Z00; 2A1J; 2AQ0; 2KN7; 2MUT; 6SXA; 6SXB
• EC Number: 3.1.-.-
• Pfam ID: PF02732
• Sequence:
  MESGQPARRIAMAPLLEYERQLVLELLDTDGLVVCARGLGADRLLYHFLQLHCHPACLVL
  VLNTQPAEEEYFINQLKIEGVEHLPRRVTNEITSNSRYEVYTQGGVIFATSRILVVDFLT
  DRIPSDLITGILVYRAHRIIESCQEAFILRLFRQKNKRGFIKAFTDNAVAFDTGFCHVER
  VMRNLFVRKLYLWPRFHVAVNSFLEQHKPEVVEIHVSMTPTMLAIQTAILDILNACLKEL
  KCHNPSLEVEDLSLENAIGKPFDKTIRHYLDPLWHQLGAKTKSLVQDLKILRTLLQYLSQ
  YDCVTFLNLLESLRATEKAFGQNSGWLFLDSSTSMFINARARVYHLPDAKMSKKEKISEK
  MEIKEGEETKKELVLESNPKWEALTEVLKEIEAENKESEALGGPGQVLICASDDRTCSQL
  RDYITLGAEAFLLRLYRKTFEKDSKAEEVWMKFRKEDSSKRIRKSHKRPKDPQNKERAST
  KERTLKKKKRKLTLTQMVGKPEELEEEGDVEEGYRREISSSPESCPEEIKHEEFDVNLSS
  DAAFGILKEPLTIIHPLLGCSDPYALTRVLHEVEPRYVVLYDAELTFVRQLEIYRASRPG
  KPLRVYFLIYGGSTEEQRYLTALRKEKEAFEKLIREKASMVVPEEREGRDETNLDLVRGT
  ASADVSTDTRKAGGQEQNGTQQSIVVDMREFRSELPSLIHRRGIDIEPVTLEVGDYILTP
  EMCVERKSISDLIGSLNNGRLYSQCISMSRYYKRPVLLIEFDPSKPFSLTSRGALFQEIS
  SNDISSKLTLLTLHFPRLRILWCPSPHATAELFEELKQSKPQPDAATALAITADSETLPE
  SEKYNPGPQDFLLKMPGVNAKNCRSLMHHVKNIAELAALSQDELTSILGNAANAKQLYDF
  IHTSFAEVVSKGKGKK
• Function: Catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair, and which is essential for nucleotide excision repair (NER) and interstrand cross-link (ICL) repair.
• KEGG Pathway:
  Nucleotide excision repair (hsa03420)
  Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Fanconi Anemia Pathway (R-HSA-6783310)
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Embryonal neoplasm	DIS5MQSB	Definitive	Biomarker	[1]
Germ cell tumor	DIS62070	Definitive	Biomarker	[1]
Xeroderma pigmentosum group F	DISRKRYY	Definitive	Autosomal recessive	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[9]
Cockayne syndrome type 1	DIS9JFVY	Strong	GermlineCausalMutation	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[11]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[13]
Fanconi anemia complementation group Q	DISHYVNK	Strong	Autosomal recessive	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Genetic Variation	[16]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[17]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Genetic Variation	[18]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[19]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Neoplasm of testis	DISK4XHT	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[22]
Obesity	DIS47Y1K	Strong	Genetic Variation	[23]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[4]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[24]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[25]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[8]
Triple negative breast cancer	DISAMG6N	Strong	Genetic Variation	[26]
Vulvar squamous intraepithelial lesion	DISULIZR	Strong	Biomarker	[27]
Xeroderma pigmentosum group A	DIS38HWC	Strong	Genetic Variation	[28]
XFE progeroid syndrome	DISVZ5JW	Strong	Autosomal recessive	[29]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[30]
Lung carcinoma	DISTR26C	moderate	Genetic Variation	[30]
Stomach cancer	DISKIJSX	moderate	Biomarker	[15]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[31]
Xeroderma pigmentosum	DISQ9H19	Supportive	Autosomal recessive	[32]
Xeroderma pigmentosum-Cockayne syndrome complex	DISJ0QRY	Supportive	Autosomal recessive	[32]
Xeroderma pigmentosum group G	DIS4PV33	Disputed	Biomarker	[33]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[34]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[35]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[12]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[36]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[27]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	DNA repair endonuclease XPF (ERCC4) increases the response to substance of Bortezomib.	[51]
Camptothecin	DM6CHNJ	Phase 3	DNA repair endonuclease XPF (ERCC4) decreases the response to substance of Camptothecin.	[52]

17 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 DNA repair endonuclease XPF (ERCC4).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA repair endonuclease XPF (ERCC4).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA repair endonuclease XPF (ERCC4).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA repair endonuclease XPF (ERCC4).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA repair endonuclease XPF (ERCC4).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA repair endonuclease XPF (ERCC4).	[42]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA repair endonuclease XPF (ERCC4).	[43]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of DNA repair endonuclease XPF (ERCC4).	[44]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA repair endonuclease XPF (ERCC4).	[45]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of DNA repair endonuclease XPF (ERCC4).	[46]
PD-0325901	DM27D4J	Phase 2	PD-0325901 increases the expression of DNA repair endonuclease XPF (ERCC4).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA repair endonuclease XPF (ERCC4).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of DNA repair endonuclease XPF (ERCC4).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA repair endonuclease XPF (ERCC4).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of DNA repair endonuclease XPF (ERCC4).	[46]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of DNA repair endonuclease XPF (ERCC4).	[45]
3-aminobenzamide	DM7P3IZ	Investigative	3-aminobenzamide decreases the expression of DNA repair endonuclease XPF (ERCC4).	[45]

3 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 DNA repair endonuclease XPF (ERCC4).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA repair endonuclease XPF (ERCC4).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of DNA repair endonuclease XPF (ERCC4).	[50]

References

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