Cyclin-dependent kinase 11B

Function

Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing. Acts as a key regulator of pre-mRNA splicing by mediating phosphorylation of SF3B1, enabling the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, thereby promoting spliceosome assembly. Also acts as a regulator of transcription by phosphorylating 'Ser-2' of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A. Involved in replication-dependent transcription of histone genes: binds to histone genes and phosphorylates POLR2A at 'Ser-2' of the CTD to specifically control transcriptional elongation of histones and recruitment of 3'-end processing factors. Part of a transcription checkpoint upstream of CDK9, which regulates promoter-proximal pausing by RNA polymerase II, a transcription halt following transcription initiation, but prior to elongation. Probably regulates promoter-proximal pausing by mediating phosphorylation of POLR2A at 'Ser-2' of the CTD. Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity.

Classification

Family (Pfam)

PF00069 Pkinase

InterPro

CDK, CDK11/PITSLRE_STKc, Kinase-like_dom_sf, Prot_kinase_dom, Ser/Thr_kinase_AS

Functional cluster

RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 2

• 7UKZ X-ray 2.60A
• 9I9I EM 3.50A

A predicted model is available from AlphaFold.

Gene Ontology · 29

• GO:0005694 chromosome
• GO:0000775 chromosome, centromeric region
• GO:0180038 cyclin L-CDK11 complex
• GO:0000307 cyclin-dependent protein kinase holoenzyme complex
• GO:0005737 cytoplasm
• GO:0016607 nuclear speck
• GO:0005634 nucleus
• GO:0005524 ATP binding
• GO:0004693 cyclin-dependent protein serine/threonine kinase activity
• GO:0004672 protein kinase activity
• GO:0106310 protein serine kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0003723 RNA binding
• GO:0140834 RNA polymerase II CTD heptapeptide repeat S2 kinase activity
• GO:0140836 RNA polymerase II CTD heptapeptide repeat S5 kinase activity
• GO:0006915 apoptotic process
• GO:0000278 mitotic cell cycle
• GO:0071962 mitotic sister chromatid cohesion, centromeric
• GO:0006397 mRNA processing
• GO:0006468 protein phosphorylation
• GO:0042981 regulation of apoptotic process
• GO:0051726 regulation of cell cycle
• GO:0001558 regulation of cell growth
• GO:0046605 regulation of centrosome cycle
• GO:0006355 regulation of DNA-templated transcription
• GO:0050684 regulation of mRNA processing
• GO:0048024 regulation of mRNA splicing, via spliceosome
• GO:0001111 RNA polymerase II promoter clearance
• GO:0008380 RNA splicing

Drugs targeting this protein · 4

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

Related proteins · sequence + function similarity

• Cyclin-dependent kinase 11A 0.99
• Cyclin-dependent kinase 11B 0.99
• Serine/threonine-protein kinase PITSLRE 0.83
• Cyclin-dependent kinase 11.1 0.78
• Cyclin-dependent kinase 11.2 0.73
• Cyclin-dependent kinase G-2 0.73
• Cyclin-dependent kinase G-2 0.73
• Cyclin-dependent kinase G-1 0.70
• Serine/threonine-protein kinase PRP4 homolog 0.69
• Serine/threonine-protein kinase PRP4 homolog 0.69
• Serine/threonine-protein kinase PRP4 homolog 0.68
• Cyclin-dependent kinase G-1 0.68

Co-cited proteins · studied together in the literature

• Cyclin-dependent kinase 11A 15 shared papers
• Cyclin-L1 4 shared papers
• Cyclin-L2 3 shared papers
• RNA-binding protein with serine-rich domain 1 1 shared papers
• Ran-binding protein 9 1 shared papers
• CASP8-associated protein 2 1 shared papers
• Serine/arginine-rich splicing factor 7 1 shared papers
• G1/S-specific cyclin-D3 1 shared papers
• Pulmonary surfactant-associated protein A 1 shared papers
• Cyclin-dependent kinase 7 2 shared papers
• SAP30-binding protein 1 shared papers
• Cyclin-L1 1 shared papers

Literature · 39 cited papers

• Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase. Science · 2025
• A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation. Mol. Cell · 2025
• CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing. EMBO J. · 2023
• CDK11 facilitates centromeric transcription to maintain centromeric cohesion during mitosis. Mol. Biol. Cell · 2024
• Crystal structure of the CDK11 kinase domain bound to the small-molecule inhibitor OTS964. Structure · 2022
• CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1. Nature · 2022
• HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation. Vaccines (Basel) · 2021
• CDK11 is required for transcription of replication-dependent histone genes. Nat. Struct. Mol. Biol. · 2020
• Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med. · 2019
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• SP-R210 (Myo18A) isoforms as intrinsic modulators of macrophage priming and activation. PLoS ONE · 2015
• CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome Res. · 2014
• … and 27 more in the literature graph