Details of Drug Off-Target (DOT)

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

• DOT Name: DNA excision repair protein ERCC-5 (ERCC5)
• Synonyms: EC 3.1.-.-; DNA repair protein complementing XP-G cells; Xeroderma pigmentosum group G-complementing protein
• Gene Name: ERCC5
• Related Disease:
  Chromosomal disorder
  Esophageal squamous cell carcinoma
  Xeroderma pigmentosum group G
  Adenocarcinoma
  B-cell lymphoma
  Bone osteosarcoma
  Cerebrooculofacioskeletal syndrome 3
  Cervical cancer
  Cockayne syndrome
  Cutaneous melanoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Lung neoplasm
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian neoplasm
  Prostate neoplasm
  Stomach cancer
  Xeroderma pigmentosum group D
  Adult lymphoma
  Arthrogryposis
  Cervical carcinoma
  Epithelial ovarian cancer
  leukaemia
  Leukemia
  Lymphoma
  Ovarian cancer
  Pediatric lymphoma
  Squamous cell carcinoma
  Stroke
  COFS syndrome
  Xeroderma pigmentosum
  Xeroderma pigmentosum-Cockayne syndrome complex
  Coronary heart disease
  Head-neck squamous cell carcinoma
  Laryngeal carcinoma
  Malignant soft tissue neoplasm
  Melanoma
  Multiple sclerosis
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Sarcoma
  Schizophrenia
• UniProt ID: ERCC5_HUMAN
• PDB ID: 5EKF; 5EKG; 6TUR; 6TUS; 6TUW; 6TUX; 6VBH
• EC Number: 3.1.-.-
• Pfam ID: PF00867 ; PF00752
• Sequence:
  MGVQGLWKLLECSGRQVSPEALEGKILAVDISIWLNQALKGVRDRHGNSIENPHLLTLFH
  RLCKLLFFRIRPIFVFDGDAPLLKKQTLVKRRQRKDLASSDSRKTTEKLLKTFLKRQAIK
  TAFRSKRDEALPSLTQVRRENDLYVLPPLQEEEKHSSEEEDEKEWQERMNQKQALQEEFF
  HNPQAIDIESEDFSSLPPEVKHEILTDMKEFTKRRRTLFEAMPEESDDFSQYQLKGLLKK
  NYLNQHIEHVQKEMNQQHSGHIRRQYEDEGGFLKEVESRRVVSEDTSHYILIKGIQAKTV
  AEVDSESLPSSSKMHGMSFDVKSSPCEKLKTEKEPDATPPSPRTLLAMQAALLGSSSEEE
  LESENRRQARGRNAPAAVDEGSISPRTLSAIKRALDDDEDVKVCAGDDVQTGGPGAEEMR
  INSSTENSDEGLKVRDGKGIPFTATLASSSVNSAEEHVASTNEGREPTDSVPKEQMSLVH
  VGTEAFPISDESMIKDRKDRLPLESAVVRHSDAPGLPNGRELTPASPTCTNSVSKNETHA
  EVLEQQNELCPYESKFDSSLLSSDDETKCKPNSASEVIGPVSLQETSSIVSVPSEAVDNV
  ENVVSFNAKEHENFLETIQEQQTTESAGQDLISIPKAVEPMEIDSEESESDGSFIEVQSV
  ISDEELQAEFPETSKPPSEQGEEELVGTREGEAPAESESLLRDNSERDDVDGEPQEAEKD
  AEDSLHEWQDINLEELETLESNLLAQQNSLKAQKQQQERIAATVTGQMFLESQELLRLFG
  IPYIQAPMEAEAQCAILDLTDQTSGTITDDSDIWLFGARHVYRNFFNKNKFVEYYQYVDF
  HNQLGLDRNKLINLAYLLGSDYTEGIPTVGCVTAMEILNEFPGHGLEPLLKFSEWWHEAQ
  KNPKIRPNPHDTKVKKKLRTLQLTPGFPNPAVAEAYLKPVVDDSKGSFLWGKPDLDKIRE
  FCQRYFGWNRTKTDESLFPVLKQLDAQQTQLRIDSFFRLAQQEKEDAKRIKSQRLNRAVT
  CMLRKEKEAAASEIEAVSVAMEKEFELLDKAKGKTQKRGITNTLEESSSLKRKRLSDSKG
  KNTCGGFLGETCLSESSDGSSSEDAESSSLMNVQRRTAAKEPKTSASDSQNSVKEAPVKN
  GGATTSSSSDSDDDGGKEKMVLVTARSVFGKKRRKLRRARGRKRKT
• Function: Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble. Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA. Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II. Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity. Required for DNA replication fork maintenance and preservation of genomic stability. Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site. During HRR, binds to the replication fork with high specificity and stabilizes it. Also, acts upstream of HRR, to promote the release of BRCA1 from DNA.
• KEGG Pathway: Nucleotide excision repair (hsa03420)
• Reactome Pathway:
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosomal disorder	DISM5BB5	Definitive	Genetic Variation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[2]
Xeroderma pigmentosum group G	DIS4PV33	Definitive	Autosomal recessive	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[6]
Cerebrooculofacioskeletal syndrome 3	DISGGZ1K	Strong	Autosomal recessive	[7]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[8]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[9]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[10]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Glioma	DIS5RPEH	Strong	Genetic Variation	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[13]
Lung neoplasm	DISVARNB	Strong	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[16]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[6]
Ovarian neoplasm	DISEAFTY	Strong	Posttranslational Modification	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[11]
Xeroderma pigmentosum group D	DISFFE93	Strong	Genetic Variation	[19]
Adult lymphoma	DISK8IZR	moderate	Genetic Variation	[20]
Arthrogryposis	DISC81CM	moderate	Genetic Variation	[21]
Cervical carcinoma	DIST4S00	moderate	Genetic Variation	[22]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[23]
leukaemia	DISS7D1V	moderate	Genetic Variation	[24]
Leukemia	DISNAKFL	moderate	Genetic Variation	[24]
Lymphoma	DISN6V4S	moderate	Genetic Variation	[20]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[23]
Pediatric lymphoma	DIS51BK2	moderate	Genetic Variation	[20]
Squamous cell carcinoma	DISQVIFL	moderate	Genetic Variation	[25]
Stroke	DISX6UHX	moderate	Genetic Variation	[26]
COFS syndrome	DISTEABI	Supportive	Autosomal recessive	[21]
Xeroderma pigmentosum	DISQ9H19	Supportive	Autosomal recessive	[27]
Xeroderma pigmentosum-Cockayne syndrome complex	DISJ0QRY	Supportive	Autosomal recessive	[27]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[28]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Genetic Variation	[29]
Laryngeal carcinoma	DISNHCIV	Limited	Genetic Variation	[30]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Altered Expression	[31]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[32]
Multiple sclerosis	DISB2WZI	Limited	Biomarker	[33]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[29]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[34]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[34]
Sarcoma	DISZDG3U	Limited	Altered Expression	[31]
Schizophrenia	DISSRV2N	Limited	Biomarker	[19]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	DNA excision repair protein ERCC-5 (ERCC5) decreases the response to substance of Cisplatin.	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[39]
Aspirin	DM672AH	Approved	Aspirin increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[40]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[40]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[41]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[42]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of DNA excision repair protein ERCC-5 (ERCC5).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[46]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[43]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[47]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of DNA excision repair protein ERCC-5 (ERCC5).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA excision repair protein ERCC-5 (ERCC5).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of DNA excision repair protein ERCC-5 (ERCC5).	[45]

References

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