ID:CDK8_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase 8; EC=2.7.11.22; EC=2.7.11.23; AltName: Full=Cell division protein kinase 8; AltName: Full=Mediator complex subunit CDK8; AltName: Full=Mediator of RNA polymerase II transcription subunit CDK8; AltName: Full=Protein kinase K35; FUNCTION: Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. COFACTOR: Magnesium (By similarity). SUBUNIT: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Interacts with CTNNB1, GLI3 and MAML1. INTERACTION: P24863:CCNC; NbExp=3; IntAct=EBI-394377, EBI-395261; SUBCELLULAR LOCATION: Nucleus (Probable). SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain.
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 P49336
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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:0008353 RNA polymerase II carboxy-terminal domain kinase activity GO:0016301 kinase activity GO:0016740 transferase activity
Biological Process: GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0007346 regulation of mitotic cell cycle GO:0016310 phosphorylation GO:0045944 positive regulation of transcription from RNA polymerase II promoter
BC094784 - Homo sapiens cDNA clone IMAGE:30528795. BC069634 - Homo sapiens cyclin-dependent kinase 8, mRNA (cDNA clone MGC:97177 IMAGE:7262421), complete cds. BC104492 - Homo sapiens cyclin-dependent kinase 8, mRNA (cDNA clone MGC:126075 IMAGE:40032854), complete cds. BC105950 - Homo sapiens cyclin-dependent kinase 8, mRNA (cDNA clone MGC:126074 IMAGE:40032852), complete cds. BC107601 - Homo sapiens cyclin-dependent kinase 8, mRNA (cDNA clone MGC:126073 IMAGE:40032849), complete cds. X85753 - Homo sapiens mRNA for CDK8 protein kinase. CU686950 - Synthetic construct Homo sapiens gateway clone IMAGE:100022667 5' read CDK8 mRNA. KJ890887 - Synthetic construct Homo sapiens clone ccsbBroadEn_00281 CDK8 gene, encodes complete protein. KJ905168 - Synthetic construct Homo sapiens clone ccsbBroadEn_14578 CDK8 gene, encodes complete protein. AY702976 - Homo sapiens cyclin-dependent kinase 8 (CDK8) mRNA, complete cds, alternatively spliced. AK296875 - Homo sapiens cDNA FLJ56597 complete cds, highly similar to Cell division protein kinase 8 (EC 2.7.11.22). AK296084 - Homo sapiens cDNA FLJ56916 complete cds, highly similar to Cell division protein kinase 8 (EC 2.7.11.22). HG518164 - Homo sapiens mRNA for cyclin-dependent kinase 8 (CDK8 gene). L23208 - Human chromosome-specific mRNA. JD296829 - Sequence 277853 from Patent EP1572962. L23311 - Homo sapiens mRNA fragment.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth
Reactome (by CSHL, EBI, and GO)
Protein P49336 (Reactome details) participates in the following event(s):
R-HSA-212352 Formation of ARC coactivator complex R-HSA-212380 Formation of TRAP coactivator complex R-HSA-212432 Formation of DRIP coactivator complex R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-1912393 MAML in complex with NICD1 recruits CDK8 R-NUL-2064916 MAML recruits CDK8:CCNC to xNICD1 R-HSA-2220957 NOTCH1 PEST domain mutants coactivator complex binds CDK8:CCNC R-HSA-1912391 NICD1 is phosphorylated by CDK8 R-NUL-2065178 CDK8 phosphorylates xNICD1 R-HSA-2220971 CDK8 phosphorylates NICD1 PEST domain mutants R-HSA-2176475 Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9 R-HSA-212436 Generic Transcription Pathway R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-73857 RNA Polymerase II Transcription R-HSA-1266738 Developmental Biology R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-74160 Gene expression (Transcription) R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-1643685 Disease R-HSA-9006936 Signaling by TGF-beta family members
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
