Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKDU3SR)

• DOT Name: Cyclin-H (CCNH)
• Synonyms: MO15-associated protein; p34; p37
• Gene Name: CCNH
• Related Disease:
  Prostate carcinoma
  Advanced cancer
  Ataxia-telangiectasia
  B-cell lymphoma
  B-cell neoplasm
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Cowden disease
  Familial adenomatous polyposis
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Lung neoplasm
  Melanoma
  Myelodysplastic syndrome
  Oral cancer
  Peripheral neuropathy
  Prostate cancer
  Skin disease
  Small lymphocytic lymphoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Xeroderma pigmentosum
  Gastrointestinal stromal tumour
  Lyme disease
  Squamous cell carcinoma
  Carcinoma
  Undifferentiated carcinoma
  Capillary malformation-arteriovenous malformation syndrome
  Colonic neoplasm
  Esophageal cancer
  Glioblastoma multiforme
  Liver cancer
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate neoplasm
  Schizophrenia
• UniProt ID: CCNH_HUMAN
• PDB ID: 1JKW; 1KXU; 6O9L; 6XBZ; 6XD3; 7B5O; 7B5Q; 7EGB; 7EGC; 7ENA; 7ENC; 7LBM; 7NVR; 8BVW; 8BYQ; 8GXQ; 8GXS; 8ORM; 8P6V; 8P6Y
• Pfam ID: PF16899 ; PF00134
• Sequence:
  MYHNSSQKRHWTFSSEEQLARLRADANRKFRCKAVANGKVLPNDPVFLEPHEEMTLCKYY
  EKRLLEFCSVFKPAMPRSVVGTACMYFKRFYLNNSVMEYHPRIIMLTCAFLACKVDEFNV
  SSPQFVGNLRESPLGQEKALEQILEYELLLIQQLNFHLIVHNPYRPFEGFLIDLKTRYPI
  LENPEILRKTADDFLNRIALTDAYLLYTPSQIALTAILSSASRAGITMESYLSESLMLKE
  NRTCLSQLLDIMKSMRNLVKKYEPPRSEEVAVLKQKLERCHSAELALNVITKKRKGYEDD
  DYVSKKSKHEEEEWTDDDLVESL
• Function: Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Nucleotide excision repair (hsa03420)
  Cell cycle (hsa04110)
• Reactome Pathway:
  Formation of the Early Elongation Complex (R-HSA-113418)
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of the HIV-1 Early Elongation Complex (R-HSA-167158)
  RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160)
  HIV Transcription Initiation (R-HSA-167161)
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A/B1/B2 associated events during G2/M transition (R-HSA-69273)
  Cyclin A (R-HSA-69656)
  mRNA Capping (R-HSA-72086)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  RNA Polymerase I Promoter Escape (R-HSA-73772)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase I Transcription Termination (R-HSA-73863)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[4]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[7]
Cowden disease	DISMYKCE	Strong	Biomarker	[8]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Genetic Variation	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[13]
Melanoma	DIS1RRCY	Strong	Altered Expression	[14]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[15]
Oral cancer	DISLD42D	Strong	Genetic Variation	[16]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[17]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Skin disease	DISDW8R6	Strong	Genetic Variation	[18]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[20]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[21]
Lyme disease	DISO70G5	moderate	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	moderate	Genetic Variation	[23]
Carcinoma	DISH9F1N	Disputed	Biomarker	[24]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[24]
Capillary malformation-arteriovenous malformation syndrome	DISMN03Q	Limited	CausalMutation	[25]
Colonic neoplasm	DISSZ04P	Limited	Biomarker	[6]
Esophageal cancer	DISGB2VN	Limited	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[6]
Liver cancer	DISDE4BI	Limited	Biomarker	[6]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[6]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[6]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[6]
Schizophrenia	DISSRV2N	Limited	Biomarker	[26]

14 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 Cyclin-H (CCNH).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-H (CCNH).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the activity of Cyclin-H (CCNH).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-H (CCNH).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-H (CCNH).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-H (CCNH).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-H (CCNH).	[33]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Cyclin-H (CCNH).	[34]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cyclin-H (CCNH).	[33]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cyclin-H (CCNH).	[36]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the expression of Cyclin-H (CCNH).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cyclin-H (CCNH).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cyclin-H (CCNH).	[40]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Cyclin-H (CCNH).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cyclin-H (CCNH).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Cyclin-H (CCNH).	[38]

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