Cyclin-dependent kinase 12 (CDK12) phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. CDK12 regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. It preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. CDK12 is required for RNA splicing, possibly by phosphorylating SRSF1/SF2 and is involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804