Human Gene CDK8 (uc001uqr.1) Description and Page Index
  Description: Homo sapiens cyclin-dependent kinase 8 (CDK8), mRNA.
RefSeq Summary (NM_001260): This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016].
Transcript (Including UTRs)
   Position: hg19 chr13:26,828,756-26,978,569 Size: 149,814 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr13:26,828,779-26,978,218 Size: 149,440 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr13:26,828,756-26,978,569)mRNA (may differ from genome)Protein (464 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  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.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CDK8
CDC HuGE Published Literature: CDK8
Positive Disease Associations: Body Fat Distribution , Exercise Test , Hippocampus , Lipoproteins, VLDL , Mental Competency
Related Studies:
  1. Body Fat Distribution
    , , . [PubMed 0]
  2. Body Fat Distribution
    , , . [PubMed 0]
  3. Body Fat Distribution
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CDK8
Diseases sorted by gene-association score: colorectal adenocarcinoma (4), hemophagocytic lymphohistiocytosis, familial, 3 (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.81 RPKM in Colon - Sigmoid
Total median expression: 244.12 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.3023-0.361 Picture PostScript Text
3' UTR -114.70351-0.327 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

3RGF
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P49336
FrontTopSide
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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details  Gene Details  
Gene Sorter  Gene Sorter  
  EnsemblFlyBase  
  Protein SequenceProtein Sequence  
  AlignmentAlignment  

-  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

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0016592 mediator complex
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  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.

-  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

-  Other Names for This Gene
  Alternate Gene Symbols: CDK8_HUMAN, NM_001260, NP_001251, P49336, Q5VUF3, Q6ISB5
UCSC ID: uc001uqr.1
RefSeq Accession: NM_001260
Protein: P49336 (aka CDK8_HUMAN)
CCDS: CCDS9317.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001260.1
exon count: 13CDS single in 3' UTR: no RNA size: 1772
ORF size: 1395CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2990.00frame shift in genome: no % Coverage: 99.83
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.