CDK12

CDK12 (Cyclin Dependent Kinase 12) is a Protein Coding gene. Diseases associated with CDK12 include Corneal Endothelial Dystrophy. Among its related pathways are Gene Expression and DNA Damage. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDK13.

Full Name

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.

Biological Process

mRNA processing Source: UniProtKB-KW
Negative regulation of stem cell differentiation Source: Ensembl
Phosphorylation of RNA polymerase II C-terminal domain Source: UniProtKB
Positive regulation of transcription elongation from RNA polymerase II promoter Source: GO_Central
Protein autophosphorylation Source: HGNC-UCL
Protein phosphorylation Source: GO_Central
Regulation of MAP kinase activity Source: UniProtKB
Regulation of RNA splicing Source: Ensembl
RNA splicing Source: UniProtKB
Transcription elongation from RNA polymerase II promoter Source: GO_Central

Cellular Location

Nucleus; Nucleus speckle. Colocalized with nuclear speckles throughout interphase.

Involvement in disease

Chromosomal aberrations involving CDK12 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to trunctated CDK12 protein not in-frame with ERBB2.

PTM

Phosphorylation at Thr-893 increases kinase activity.