CDK12

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.

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.

Post-translational modifications

Phosphorylation at Thr-893 increases kinase activity.

Sequence Similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Tissue Specificity

Widely expressed.

Cellular localization

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

Alternative names

CRK7, CRKRS, KIAA0904, CDK12, Cyclin-dependent kinase 12, Cell division cycle 2-related protein kinase 7, Cell division protein kinase 12, CrkRS, CDC2-related protein kinase 7, hCDK12

Database links

swissprot:Q9NYV4 entrezGene:51755 swissprot:O75909 omim:615514