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UniProt functional annotation for Q9NYV4 | ||
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| UniProt code: Q9NYV4. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| 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. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
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| Catalytic activity: | |
Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho- [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA- COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216; EC=2.7.11.23; |
| Catalytic activity: | |
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; |
| Catalytic activity: | |
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22; |
| Activity regulation: | |
Inhibited by the ATP analog flavopiridol, purvalanol A, purvalanol B, staurosporine and CR8. {ECO:0000269|PubMed:24662513}. |
| Subunit: | |
Interacts with CCNL1 and CCNL2 (By similarity). Interacts with CCNK. {ECO:0000250, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Subcellular location: | |
Nucleus. Nucleus speckle. Note=Colocalized with nuclear speckles throughout interphase. |
| Tissue specificity: | |
Ubiquitously expressed. {ECO:0000269|PubMed:11683387}. |
| Ptm: | |
Phosphorylation at Thr-893 increases kinase activity. {ECO:0000269|PubMed:24662513}. |
| Disease: | |
Note=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. |
| Similarity: | |
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. |
| Sequence caution: | |
Sequence=BAA74927.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.