Cyclin-dependent kinase 12

Function

Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors.

Classification

Family (Pfam)

PF00069 Pkinase

InterPro

CDK, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 39

• 4CXA X-ray 3.15A
• 4NST X-ray 2.20A
• 4UN0 X-ray 3.15A
• 5ACB X-ray 2.70A
• 6B3E X-ray 3.06A
• 6CKX X-ray 2.80A
• 6TD3 X-ray 3.46A
• 7NXK X-ray 3.00A
• 8BU1 X-ray 2.98A
• 8BU2 X-ray 3.13A
• 8BU3 X-ray 3.42A
• 8BU4 X-ray 3.09A
• … and 27 more

A predicted model is available from AlphaFold.

Gene Ontology · 22

• GO:0002944 cyclin K-CDK12 complex
• GO:0008024 cyclin/CDK positive transcription elongation factor complex
• GO:0019908 nuclear cyclin-dependent protein kinase holoenzyme complex
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005524 ATP binding
• GO:0030332 cyclin binding
• GO:0004693 cyclin-dependent protein serine/threonine kinase activity
• GO:0004672 protein kinase activity
• GO:0019901 protein kinase binding
• GO:0106310 protein serine kinase activity
• GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
• GO:0071391 cellular response to estrogen stimulus
• GO:0006397 mRNA processing
• GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway
• GO:0043409 negative regulation of MAPK cascade
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0032968 positive regulation of transcription elongation by RNA polymerase II
• GO:0043405 regulation of MAP kinase activity
• GO:0008380 RNA splicing
• GO:0006366 transcription by RNA polymerase II

Drugs targeting this protein · 4

• PHA-793887 inhibitor
• RONICICLIB inhibitor
• AT-7519 inhibitor
• AZD-5438 inhibitor

Related proteins · sequence + function similarity

• Cyclin-dependent kinase 12 1.00
• Cyclin-dependent kinase 12 0.99
• Cyclin-dependent kinase 12 0.99
• Cyclin-dependent kinase 12 0.99
• Cyclin-dependent kinase 12 0.98
• Cyclin-dependent kinase 13 0.83
• Cyclin-dependent kinase 13 0.82
• Cyclin-dependent kinase 13 0.82
• NK-tumor recognition protein 0.81
• NK-tumor recognition protein 0.81
• Cyclin-dependent kinase 12 0.79
• Serine/arginine repetitive matrix protein 1 0.78

Co-cited proteins · studied together in the literature

• Cyclin-K 3 shared papers
• Cyclin-dependent kinase 12 1 shared papers
• Cyclin-dependent kinase 13 3 shared papers
• Receptor tyrosine-protein kinase erbB-2 1 shared papers
• Cyclin-dependent kinase 12 1 shared papers
• Cyclin-dependent kinase 13 1 shared papers
• Cyclin-K 1 shared papers
• Cyclin-L1 1 shared papers
• Transcriptional regulator ICP22 1 shared papers
• Tegument protein VP16 1 shared papers
• Cyclin-T1 1 shared papers
• Cyclin-dependent kinase 11B 1 shared papers

Literature · 26 cited papers

• HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation. Vaccines (Basel) · 2021
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• The structure and substrate specificity of human Cdk12/Cyclin K. Nat. Commun. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res. · 2011
• CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev. · 2010
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• … and 14 more in the literature graph