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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

Ubiquitously expressed.

Cellular localization

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

Alternative names

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

Target type

Proteins

Molecular weight

164155Da