Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0PGOG3)

• DOT Name: UV excision repair protein RAD23 homolog B (RAD23B)
• Synonyms: HR23B; hHR23B; XP-C repair-complementing complex 58 kDa protein; p58
• Gene Name: RAD23B
• Related Disease:
  Bladder cancer
  Sweetener
  Synovial sarcoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Alzheimer disease 3
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Differentiated thyroid carcinoma
  Esophageal cancer
  Fragile X-associated tremor/ataxia syndrome
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Male infertility
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Pediatric lymphoma
  Plasma cell myeloma
  Primary cutaneous T-cell lymphoma
  Prostate carcinoma
  Prostate neoplasm
  Xeroderma pigmentosum
  Xeroderma pigmentosum group C
  Myotonic dystrophy type 2
  Follicular lymphoma
  Malignant mesothelioma
  Malignant pleural mesothelioma
  Prostate cancer
  Schistosomiasis
• UniProt ID: RD23B_HUMAN
• PDB ID: 1P1A; 1PVE; 1UEL; 8EBS; 8EBV; 8EBW
• Pfam ID: PF00627 ; PF00240 ; PF09280
• Sequence:
  MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALK
  EYKIDEKNFVVVMVTKPKAVSTPAPATTQQSAPASTTAVTSSTTTTVAQAPTPVPALAPT
  STPASITPASATASSEPAPASAAKQEKPAEKPAETPVATSPTATDSTSGDSSRSNLFEDA
  TSALVTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIPGDRESQAVVD
  PPQAASTGAPQSSAVAAAAATTTATTTTTSSGGHPLEFLRNQPQFQQMRQIIQQNPSLLP
  ALLQQIGRENPQLLQQISQHQEHFIQMLNEPVQEAGGQGGGGGGGSGGIAEAGSGHMNYI
  QVTPQEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQNFDED
• Function: Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.; Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with CETN2 appears to stabilize XPC. May protect XPC from proteasomal degradation.; The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.
• KEGG Pathway:
  Nucleotide excision repair (hsa03420)
  Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Josephin domain DUBs (R-HSA-5689877)
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Genetic Variation	[1]
Sweetener	DISDGALM	Definitive	Genetic Variation	[2]
Synovial sarcoma	DISEZJS7	Definitive	Genetic Variation	[2]
Urinary bladder cancer	DISDV4T7	Definitive	Genetic Variation	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Genetic Variation	[1]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[8]
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Genetic Variation	[9]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[8]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Laryngeal carcinoma	DISNHCIV	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[13]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[13]
Lymphoma	DISN6V4S	Strong	Altered Expression	[3]
Male infertility	DISY3YZZ	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[3]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[17]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Xeroderma pigmentosum	DISQ9H19	Strong	Altered Expression	[20]
Xeroderma pigmentosum group C	DIS8DQXS	Strong	Biomarker	[21]
Myotonic dystrophy type 2	DIS5ZWF1	moderate	Altered Expression	[22]
Follicular lymphoma	DISVEUR6	Disputed	Genetic Variation	[23]
Malignant mesothelioma	DISTHJGH	Limited	Biomarker	[24]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[24]
Prostate cancer	DISF190Y	Limited	Biomarker	[18]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[25]

17 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 UV excision repair protein RAD23 homolog B (RAD23B).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[30]
Selenium	DM25CGV	Approved	Selenium decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[32]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[33]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[34]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[35]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[31]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[42]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[43]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of UV excision repair protein RAD23 homolog B (RAD23B).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the binding of UV excision repair protein RAD23 homolog B (RAD23B).	[39]

3 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 decreases the phosphorylation of UV excision repair protein RAD23 homolog B (RAD23B).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of UV excision repair protein RAD23 homolog B (RAD23B).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of UV excision repair protein RAD23 homolog B (RAD23B).	[40]

References

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