Details of Drug Off-Target (DOT)

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

• DOT Name: CDK-activating kinase assembly factor MAT1 (MNAT1)
• Synonyms: CDK7/cyclin-H assembly factor; Cyclin-G1-interacting protein; Menage a trois; RING finger protein 66; RING finger protein MAT1; p35; p36
• Gene Name: MNAT1
• Related Disease:
  Alzheimer disease
  Astrocytoma
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Endometriosis
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Huntington disease
  Immunodeficiency
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Lyme disease
  Malaria
  Mycobacterium infection
  Neoplasm
  Osteosarcoma
  Prostate cancer
  Psoriasis
  Rheumatoid arthritis
  Schizophrenia
  Stroke
  Systemic lupus erythematosus
  Systemic sclerosis
  Crohn disease
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
  Type-1/2 diabetes
  Acute myelogenous leukaemia
  Advanced cancer
  Epithelial ovarian cancer
  Hepatitis C virus infection
  Inflammatory bowel disease
  Intellectual disability
  Nervous system disease
  Neuroblastoma
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Prostate carcinoma
  Tuberculosis
  Type-1 diabetes
  Ulcerative colitis
• UniProt ID: MAT1_HUMAN
• PDB ID: 1G25 ; 6NMI ; 6O9L ; 6O9M ; 6TUN ; 6XBZ ; 6XD3 ; 7B5O ; 7B5Q ; 7EGB ; 7EGC ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVW ; 7NVX ; 7NVY ; 7NVZ ; 7NW0 ; 8BVW ; 8BYQ ; 8GXQ ; 8GXS ; 8ORM ; 8P6V ; 8P6Y ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
• Pfam ID: PF06391 ; PF17121
• Sequence:
  MDDQGCPRCKTTKYRNPSLKLMVNVCGHTLCESCVDLLFVRGAGNCPECGTPLRKSNFRV
  QLFEDPTVDKEVEIRKKVLKIYNKREEDFPSLREYNDFLEEVEEIVFNLTNNVDLDNTKK
  KMEIYQKENKDVIQKNKLKLTREQEELEEALEVERQENEQRRLFIQKEEQLQQILKRKNK
  QAFLDELESSDLPVALLLAQHKDRSTQLEMQLEKPKPVKPVTFSTGIKMGQHISLAPIHK
  LEEALYEYQPLQIETYGPHVPELEMLGRLGYLNHVRAASPQDLAGGYTSSLACHRALQDA
  FSGLFWQPS
• Function: Stabilizes the cyclin H-CDK7 complex to form a functional 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.
• Tissue Specificity: Highest levels in colon and testis. Moderate levels are present thymus, prostate, ovary, and small intestine. The lowest levels are found in spleen and leukocytes.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Nucleotide excision repair (hsa03420)
• 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

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Endometriosis	DISX1AG8	Strong	Biomarker	[7]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Huntington disease	DISQPLA4	Strong	Biomarker	[10]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[11]
leukaemia	DISS7D1V	Strong	Biomarker	[12]
Leukemia	DISNAKFL	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Lung neoplasm	DISVARNB	Strong	Biomarker	[3]
Lyme disease	DISO70G5	Strong	Altered Expression	[14]
Malaria	DISQ9Y50	Strong	Biomarker	[15]
Mycobacterium infection	DISNSMUD	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[17]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[19]
Schizophrenia	DISSRV2N	Strong	Biomarker	[20]
Stroke	DISX6UHX	Strong	Biomarker	[21]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[22]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[23]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[24]
Matthew-Wood syndrome	DISA7HR7	moderate	Genetic Variation	[25]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[26]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[27]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[28]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[29]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[30]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[31]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[32]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[33]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[34]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[29]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[29]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[35]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[36]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[31]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[37]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[31]

8 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 CDK-activating kinase assembly factor MAT1 (MNAT1).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[41]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CDK-activating kinase assembly factor MAT1 (MNAT1).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CDK-activating kinase assembly factor MAT1 (MNAT1).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of CDK-activating kinase assembly factor MAT1 (MNAT1).	[47]

References

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