ID:CDK12_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase 12; EC=2.7.11.22; EC=2.7.11.23; AltName: Full=Cdc2-related kinase, arginine/serine-rich; Short=CrkRS; AltName: Full=Cell division cycle 2-related protein kinase 7; Short=CDC2-related protein kinase 7; AltName: Full=Cell division protein kinase 12; Short=hCDK12; FUNCTION: Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogn inhibitors. CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Interacts with CCNL1 and CCNL2 (By similarity). SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Colocalized with nuclear speckles throughout interphase. TISSUE SPECIFICITY: Ubiquitously expressed. 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. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAA74927.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NYV4
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0004693 cyclin-dependent protein serine/threonine kinase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0008134 transcription factor binding GO:0008353 RNA polymerase II carboxy-terminal domain kinase activity GO:0016301 kinase activity GO:0016740 transferase activity GO:0019901 protein kinase binding GO:0030332 cyclin binding GO:0044212 transcription regulatory region DNA binding
Biological Process: GO:0006368 transcription elongation from RNA polymerase II promoter GO:0006397 mRNA processing GO:0006468 protein phosphorylation GO:0008380 RNA splicing GO:0016310 phosphorylation GO:0043405 regulation of MAP kinase activity GO:0043484 regulation of RNA splicing GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046777 protein autophosphorylation GO:0051726 regulation of cell cycle GO:0070816 phosphorylation of RNA polymerase II C-terminal domain GO:2000737 negative regulation of stem cell differentiation
LF209308 - JP 2014500723-A/16811: Polycomb-Associated Non-Coding RNAs. MA444885 - JP 2018138019-A/16811: Polycomb-Associated Non-Coding RNAs. AK302645 - Homo sapiens cDNA FLJ60980 complete cds, highly similar to Cell division cycle 2-related protein kinase 7 (EC 2.7.11.22). AB020711 - Homo sapiens KIAA0904 mRNA for KIAA0904 protein. BC150265 - Homo sapiens Cdc2-related kinase, arginine/serine-rich, mRNA (cDNA clone MGC:166847 IMAGE:9007217), complete cds. AF227198 - Homo sapiens CrkRS mRNA, complete cds. BC140854 - Homo sapiens Cdc2-related kinase, arginine/serine-rich, mRNA (cDNA clone MGC:176531 IMAGE:9021722), complete cds. AB462974 - Synthetic construct DNA, clone: pF1KA0904, Homo sapiens CRKRS gene for Cdc2-related kinase, arginine/serine-rich, without stop codon, in Flexi system. JD348267 - Sequence 329291 from Patent EP1572962. JD254517 - Sequence 235541 from Patent EP1572962. JD038272 - Sequence 19296 from Patent EP1572962. JD309228 - Sequence 290252 from Patent EP1572962. JD486205 - Sequence 467229 from Patent EP1572962. JD431799 - Sequence 412823 from Patent EP1572962. LP866598 - Sequence 6 from Patent WO2017163076. JD381992 - Sequence 363016 from Patent EP1572962. JD250527 - Sequence 231551 from Patent EP1572962. JD060839 - Sequence 41863 from Patent EP1572962. JD037740 - Sequence 18764 from Patent EP1572962. JD219110 - Sequence 200134 from Patent EP1572962. JD146632 - Sequence 127656 from Patent EP1572962. BC012428 - Homo sapiens, clone IMAGE:3862468, mRNA. JD297862 - Sequence 278886 from Patent EP1572962. JD360096 - Sequence 341120 from Patent EP1572962. JD525597 - Sequence 506621 from Patent EP1572962. MB124331 - JP 2019512554-A/5: INHIBITORS AND THEIR USES.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9NYV4 (Reactome details) participates in the following event(s):
R-HSA-6797090 CCNK binds CDK12 R-HSA-6797616 CCNK:CDK12 binds RNA Pol II at DNA repair genes R-HSA-6797606 CDK12 phosphorylates RNA Pol II CTD at DNA repair genes R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
