Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3P7JF1)

DOT Name Cyclin-dependent kinase 13 (CDK13)
Synonyms EC 2.7.11.22; EC 2.7.11.23; CDC2-related protein kinase 5; Cell division cycle 2-like protein kinase 5; Cell division protein kinase 13; hCDK13; Cholinesterase-related cell division controller
Gene Name CDK13
Related Disease
Syndromic intellectual disability ( )
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder ( )
UniProt ID
CDK13_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5EFQ; 7NXJ
EC Number
2.7.11.22; 2.7.11.23
Pfam ID
PF12330 ; PF00069
Sequence
MPSSSDTALGGGGGLSWAEKKLEERRKRRRFLSPQQPPLLLPLLQPQLLQPPPPPPPLLF
LAAPGTAAAAAAAAAASSSCFSPGPPLEVKRLARGKRRAGGRQKRRRGPRAGQEAEKRRV
FSLPQPQQDGGGGASSGGGVTPLVEYEDVSSQSEQGLLLGGASAATAATAAGGTGGSGGS
PASSSGTQRRGEGSERRPRRDRRSSSGRSKERHREHRRRDGQRGGSEASKSRSRHSHSGE
ERAEVAKSGSSSSSGGRRKSASATSSSSSSRKDRDSKAHRSRTKSSKEPPSAYKEPPKAY
REDKTEPKAYRRRRSLSPLGGRDDSPVSHRASQSLRSRKSPSPAGGGSSPYSRRLPRSPS
PYSRRRSPSYSRHSSYERGGDVSPSPYSSSSWRRSRSPYSPVLRRSGKSRSRSPYSSRHS
RSRSRHRLSRSRSRHSSISPSTLTLKSSLAAELNKNKKARAAEAARAAEAAKAAEATKAA
EAAAKAAKASNTSTPTKGNTETSASASQTNHVKDVKKIKIEHAPSPSSGGTLKNDKAKTK
PPLQVTKVENNLIVDKATKKAVIVGKESKSAATKEESVSLKEKTKPLTPSIGAKEKEQHV
ALVTSTLPPLPLPPMLPEDKEADSLRGNISVKAVKKEVEKKLRCLLADLPLPPELPGGDD
LSKSPEEKKTATQLHSKRRPKICGPRYGETKEKDIDWGKRCVDKFDIIGIIGEGTYGQVY
KARDKDTGEMVALKKVRLDNEKEGFPITAIREIKILRQLTHQSIINMKEIVTDKEDALDF
KKDKGAFYLVFEYMDHDLMGLLESGLVHFNENHIKSFMRQLMEGLDYCHKKNFLHRDIKC
SNILLNNRGQIKLADFGLARLYSSEESRPYTNKVITLWYRPPELLLGEERYTPAIDVWSC
GCILGELFTKKPIFQANQELAQLELISRICGSPCPAVWPDVIKLPYFNTMKPKKQYRRKL
REEFVFIPAAALDLFDYMLALDPSKRCTAEQALQCEFLRDVEPSKMPPPDLPLWQDCHEL
WSKKRRRQKQMGMTDDVSTIKAPRKDLSLGLDDSRTNTPQGVLPSSQLKSQGSSNVAPVK
TGPGQHLNHSELAILLNLLQSKTSVNMADFVQVLNIKVNSETQQQLNKINLPAGILATGE
KQTDPSTPQQESSKPLGGIQPSSQTIQPKVETDAAQAAVQSAFAVLLTQLIKAQQSKQKD
VLLEERENGSGHEASLQLRPPPEPSTPVSGQDDLIQHQDMRILELTPEPDRPRILPPDQR
PPEPPEPPPVTEEDLDYRTENQHVPTTSSSLTDPHAGVKAALLQLLAQHQPQDDPKREGG
IDYQAGDTYVSTSDYKDNFGSSSFSSAPYVSNDGLGSSSAPPLERRSFIGNSDIQSLDNY
STASSHSGGPPQPSAFSESFPSSVAGYGDIYLNAGPMLFSGDKDHRFEYSHGPIAVLANS
SDPSTGPESTHPLPAKMHNYNYGGNLQENPSGPSLMHGQTWTSPAQGPGYSQGYRGHIST
STGRGRGRGLPY
Function
Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef.
Tissue Specificity Expressed in fetal brain, liver, muscle and in adult brain. Also expressed in neuroblastoma and glioblastoma tumors.
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Syndromic intellectual disability DISH7SDF Definitive Autosomal dominant [1]
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder DISV1Z21 Strong Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Cyclin-dependent kinase 13 (CDK13). [3]
Quercetin DM3NC4M Approved Quercetin affects the phosphorylation of Cyclin-dependent kinase 13 (CDK13). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Cyclin-dependent kinase 13 (CDK13). [6]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Cyclin-dependent kinase 13 (CDK13). [6]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Cyclin-dependent kinase 13 (CDK13). [4]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Cyclin-dependent kinase 13 (CDK13). [5]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Cyclin-dependent kinase 13 (CDK13). [7]
Nicotine DMWX5CO Approved Nicotine increases the expression of Cyclin-dependent kinase 13 (CDK13). [8]
Menthol DMG2KW7 Approved Menthol increases the expression of Cyclin-dependent kinase 13 (CDK13). [9]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Cyclin-dependent kinase 13 (CDK13). [10]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Cyclin-dependent kinase 13 (CDK13). [11]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Cyclin-dependent kinase 13 (CDK13). [12]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Cyclin-dependent kinase 13 (CDK13). [13]
EMODIN DMAEDQG Terminated EMODIN decreases the expression of Cyclin-dependent kinase 13 (CDK13). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Cyclin-dependent kinase 13 (CDK13). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Cyclin-dependent kinase 13 (CDK13). [16]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Cyclin-dependent kinase 13 (CDK13). [17]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Cyclin-dependent kinase 13 (CDK13). [18]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Cyclin-dependent kinase 13 (CDK13). [19]
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⏷ Show the Full List of 15 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review. Clin Genet. 2018 May;93(5):1000-1007. doi: 10.1111/cge.13225.
3 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
4 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
5 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
6 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
7 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
8 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
9 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
11 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
12 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
13 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
14 Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
15 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
16 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
18 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
19 Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.