Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5TSGQ)

DOT Name Cyclin-dependent kinase 11A (CDK11A)
Synonyms EC 2.7.11.22; Cell division cycle 2-like protein kinase 2; Cell division protein kinase 11A; Galactosyltransferase-associated protein kinase p58/GTA; PITSLRE serine/threonine-protein kinase CDC2L2
Gene Name CDK11A
Related Disease
Bone osteosarcoma ( )
Hepatocellular carcinoma ( )
Neoplasm ( )
Neuroblastoma ( )
Osteosarcoma ( )
Melanoma ( )
Non-insulin dependent diabetes ( )
UniProt ID
CD11A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.22
Pfam ID
PF00069
Sequence
MGDEKDSWKVKTLDEILQEKKRRKEQEEKAEIKRLKNSDDRDSKRDSLEEGELRDHCMEI
TIRNSPYRREDSMEDRGEEDDSLAIKPPQQMSRKEKVHHRKDEKRKEKWKHARVKEREHE
RRKRHREEQDKARREWERQKRREMAREHSRRERDRLEQLERKRERERKMREQQKEQREQK
ERERRAEERRKEREARREVSAHHRTMREDYSDKVKASHWSRSPPRPPRERFELGDGRKPG
EARPAPAQKPAQLKEEKMEERDLLSDLQDISDSERKTSSAESSSAESGSGSEEEEEEEEE
EEEEGSTSEESEEEEEEEEEEEEETGSNSEEASEQSAEEVSEEEMSEDEERENENHLLVV
PESRFDRDSGESEEAEEEVGEGTPQSSALTEGDYVPDSPALLPIELKQELPKYLPALQGC
RSVEEFQCLNRIEEGTYGVVYRAKDKKTDEIVALKRLKMEKEKEGFPITSLREINTILKA
QHPNIVTVREIVVGSNMDKIYIVMNYVEHDLKSLMETMKQPFLPGEVKTLMIQLLRGVKH
LHDNWILHRDLKTSNLLLSHAGILKVGDFGLAREYGSPLKAYTPVVVTQWYRAPELLLGA
KEYSTAVDMWSVGCIFGELLTQKPLFPGNSEIDQINKVFKELGTPSEKIWPGYSELPVVK
KMTFSEHPYNNLRKRFGALLSDQGFDLMNKFLTYFPGRRISAEDGLKHEYFRETPLPIDP
SMFPTWPAKSEQQRVKRGTSPRPPEGGLGYSQLGDDDLKETGFHLTTTNQGASAAGPGFS
LKF
Function
Appears to play multiple roles in cell cycle progression, cytokinesis and apoptosis. The p110 isoforms have been suggested to be involved in pre-mRNA splicing, potentially by phosphorylating the splicing protein SFRS7. The p58 isoform may act as a negative regulator of normal cell cycle progression.
Tissue Specificity Expressed ubiquitously. Some evidence of isoform-specific tissue distribution.
Reactome Pathway
Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bone osteosarcoma DIST1004 Strong Altered Expression [1]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [2]
Neoplasm DISZKGEW Strong Genetic Variation [3]
Neuroblastoma DISVZBI4 Strong Genetic Variation [3]
Osteosarcoma DISLQ7E2 Strong Altered Expression [1]
Melanoma DIS1RRCY moderate Biomarker [4]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 11A (CDK11A). [6]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Cyclin-dependent kinase 11A (CDK11A). [9]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cyclin-dependent kinase 11A (CDK11A). [7]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Cyclin-dependent kinase 11A (CDK11A). [8]
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References

1 Systematic kinome shRNA screening identifies CDK11 (PITSLRE) kinase expression is critical for osteosarcoma cell growth and proliferation.Clin Cancer Res. 2012 Sep 1;18(17):4580-8. doi: 10.1158/1078-0432.CCR-12-1157. Epub 2012 Jul 12.
2 Effect of p58GTA on beta-1,4-galactosyltransferase 1 activity and cell-cycle in human hepatocarcinoma cells.Mol Cell Biochem. 2001 May;221(1-2):161-8. doi: 10.1023/a:1010932211745.
3 Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma.Nat Genet. 1994 Jul;7(3):370-5. doi: 10.1038/ng0794-370.
4 Death-signal-induced relocalization of cyclin-dependent kinase 11 to mitochondria.Biochem J. 2005 Nov 15;392(Pt 1):65-73. doi: 10.1042/BJ20050195.
5 Genetic variations of the CDC2L2 gene are associated with type 2 diabetes in a Han Chinese cohort.Diabetes Metab Res Rev. 2007 Sep;23(6):455-61. doi: 10.1002/dmrr.705.
6 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.
7 Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
8 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
9 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.