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Aliases for CDK8 Gene

Aliases for CDK8 Gene

  • Cyclin Dependent Kinase 8 2 3 5
  • Mediator Of RNA Polymerase II Transcription Subunit CDK8 3 4
  • Cell Division Protein Kinase 8 3 4
  • Mediator Complex Subunit CDK8 3 4
  • Cyclin-Dependent Kinase 8 2 3
  • Protein Kinase K35 3 4
  • CDK8 Protein Kinase 3
  • EC 2.7.11.22 4
  • EC 2.7.11.23 4
  • K35 3

External Ids for CDK8 Gene

Previous GeneCards Identifiers for CDK8 Gene

  • GC13P024808
  • GC13P020808
  • GC13P025758
  • GC13P024626
  • GC13P025726
  • GC13P026828
  • GC13P007646

Summaries for CDK8 Gene

Entrez Gene Summary for CDK8 Gene

  • 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]

GeneCards Summary for CDK8 Gene

CDK8 (Cyclin Dependent Kinase 8) is a Protein Coding gene. Diseases associated with CDK8 include Colorectal Adenocarcinoma and Hemophagocytic Lymphohistiocytosis, Familial, 3. Among its related pathways are Gene Expression and HIV Life Cycle. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDK19.

UniProtKB/Swiss-Prot for CDK8 Gene

  • 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.

Gene Wiki entry for CDK8 Gene

Additional gene information for CDK8 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CDK8 Gene

Genomics for CDK8 Gene

GeneHancer (GH) Regulatory Elements for CDK8 Gene

Promoters and enhancers for CDK8 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J026253 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 650.7 +0.9 870 3.1 HDGF PKNOX1 FOXA2 ARID4B SIN3A DMAP1 YY1 POLR2B ZNF766 E2F8 CDK8 RNF6 ENSG00000278413
GH13J025300 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 10.4 -952.2 -952231 2.6 MLX ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 POLR2B E2F8 ZNF143 NUP58 GC13P025300 ENSG00000260509 CDK8 MTMR6 GC13P025348
GH13J026961 Enhancer 1.4 Ensembl ENCODE dbSUPER 10.4 +712.8 712814 11.8 PKNOX1 FOXA2 MLX ZFP64 ARID4B FEZF1 DMAP1 YY1 SLC30A9 ZNF143 RNU6-70P CDK8 MTIF3 POLR1D RPS21P8 ENSG00000283579 FGFR1OP2P1
GH13J025900 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 5.3 -351.7 -351663 3.3 MEIS2 PKNOX1 BMI1 BATF IRF4 EED ATF7 ETV6 FOS IKZF2 CDK8 GC13P025866 PIR50437 RN7SL741P ATP8A2
GH13J026422 Enhancer 0.9 Ensembl ENCODE dbSUPER 8.2 +170.8 170754 4.1 ATF4 HLF PRDM10 BCL6 NR2F2 CDK8 GC13P026404 WASF3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CDK8 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CDK8 gene promoter:

Genomic Locations for CDK8 Gene

Genomic Locations for CDK8 Gene
chr13:26,254,104-26,405,238
(GRCh38/hg38)
Size:
151,135 bases
Orientation:
Plus strand
chr13:26,828,276-26,979,375
(GRCh37/hg19)

Genomic View for CDK8 Gene

Genes around CDK8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CDK8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CDK8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CDK8 Gene

Proteins for CDK8 Gene

  • Protein details for CDK8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49336-CDK8_HUMAN
    Recommended name:
    Cyclin-dependent kinase 8
    Protein Accession:
    P49336
    Secondary Accessions:
    • Q5VUF3
    • Q6ISB5

    Protein attributes for CDK8 Gene

    Size:
    464 amino acids
    Molecular mass:
    53284 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for CDK8 Gene

    Alternative splice isoforms for CDK8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CDK8 Gene

Post-translational modifications for CDK8 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for CDK8 Gene

Domains & Families for CDK8 Gene

Gene Families for CDK8 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CDK8 Gene

Suggested Antigen Peptide Sequences for CDK8 Gene

Graphical View of Domain Structure for InterPro Entry

P49336

UniProtKB/Swiss-Prot:

CDK8_HUMAN :
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
genes like me logo Genes that share domains with CDK8: view

Function for CDK8 Gene

Molecular function for CDK8 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

Enzyme Numbers (IUBMB) for CDK8 Gene

Phenotypes From GWAS Catalog for CDK8 Gene

Gene Ontology (GO) - Molecular Function for CDK8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA,TAS 7568034
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004693 cyclin-dependent protein serine/threonine kinase activity IBA --
GO:0005515 protein binding IPI 7568034
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with CDK8: view
genes like me logo Genes that share phenotypes with CDK8: view

Animal Models for CDK8 Gene

MGI Knock Outs for CDK8:
  • Cdk8 Cdk8<tm1b(EUCOMM)Hmgu>

Animal Model Products

  • Taconic Biosciences Mouse Models for CDK8

Clone Products

  • Addgene plasmids for CDK8

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CDK8 Gene

Localization for CDK8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CDK8 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CDK8 gene
Compartment Confidence
nucleus 5
cytosol 2
plasma membrane 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CDK8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 16109376
GO:0005654 nucleoplasm TAS --
GO:0005730 nucleolus IDA 22869755
GO:0016592 mediator complex IEA,IDA 14638676
GO:0032991 protein-containing complex IDA 22869755
genes like me logo Genes that share ontologies with CDK8: view

Pathways & Interactions for CDK8 Gene

genes like me logo Genes that share pathways with CDK8: view

Pathways by source for CDK8 Gene

1 GeneGo (Thomson Reuters) pathway for CDK8 Gene
1 R&D Systems pathway for CDK8 Gene
1 Cell Signaling Technology pathway for CDK8 Gene

SIGNOR curated interactions for CDK8 Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for CDK8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0006468 protein phosphorylation IEA --
GO:0007346 regulation of mitotic cell cycle IBA --
genes like me logo Genes that share ontologies with CDK8: view

Drugs & Compounds for CDK8 Gene

(5) Drugs for CDK8 Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved Nutra 0
Alvocidib Experimental, Investigational Pharma inhibitor, Target Pan-cdk inhibitor, Kinase Inhibitors 60
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0
Senexin A Pharma CDK8 inhibitor 0

(1) Additional Compounds for CDK8 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0

(1) ApexBio Compounds for CDK8 Gene

Compound Action Cas Number
Senexin A CDK8 inhibitor 1366002-50-7
genes like me logo Genes that share compounds with CDK8: view

Drug Products

Transcripts for CDK8 Gene

Unigene Clusters for CDK8 Gene

Cyclin-dependent kinase 8:
Representative Sequences:

Clone Products

  • Addgene plasmids for CDK8

Alternative Splicing Database (ASD) splice patterns (SP) for CDK8 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c
SP1:
SP2:
SP3: -

Relevant External Links for CDK8 Gene

GeneLoc Exon Structure for
CDK8
ECgene alternative splicing isoforms for
CDK8

Expression for CDK8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CDK8 Gene

Protein differential expression in normal tissues from HIPED for CDK8 Gene

This gene is overexpressed in Adrenal (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CDK8 Gene



Protein tissue co-expression partners for CDK8 Gene

NURSA nuclear receptor signaling pathways regulating expression of CDK8 Gene:

CDK8

SOURCE GeneReport for Unigene cluster for CDK8 Gene:

Hs.382306

Evidence on tissue expression from TISSUES for CDK8 Gene

  • Intestine(2.2)
  • Nervous system(2)
genes like me logo Genes that share expression patterns with CDK8: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CDK8 Gene

Orthologs for CDK8 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CDK8 Gene

Organism Taxonomy Gene Similarity Type Details
oppossum
(Monodelphis domestica)
Mammalia CDK8 34
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CDK8 34 33
  • 99.71 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CDK8 34 33
  • 97.05 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CDK8 34
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CDK8 34 33
  • 95.99 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Cdk8 16 34 33
  • 93.97 (n)
rat
(Rattus norvegicus)
Mammalia Cdk8 33
  • 93.68 (n)
chicken
(Gallus gallus)
Aves CDK8 34 33
  • 91.72 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CDK8 34
  • 100 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cdk8 33
  • 85.99 (n)
MGC76204 33
zebrafish
(Danio rerio)
Actinopterygii cdk8 34 33 33
  • 79.96 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009936 33
  • 71.04 (n)
fruit fly
(Drosophila melanogaster)
Insecta Cdk8 34 35 33
  • 69.58 (n)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea cdk-8 34 33
  • 62.99 (n)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SSN3 36 34
  • 28 (a)
rice
(Oryza sativa)
Liliopsida Os.2989 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 81 (a)
OneToMany
Cin.10765 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10765 33
Species where no ortholog for CDK8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CDK8 Gene

ENSEMBL:
Gene Tree for CDK8 (if available)
TreeFam:
Gene Tree for CDK8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CDK8: view image

Paralogs for CDK8 Gene

Paralogs for CDK8 Gene

(23) SIMAP similar genes for CDK8 Gene using alignment to 4 proteins:

  • CDK8_HUMAN
  • F5H6D4_HUMAN
  • Q64FY6_HUMAN
  • U4PPA3_HUMAN

Pseudogenes.org Pseudogenes for CDK8 Gene

genes like me logo Genes that share paralogs with CDK8: view

Variants for CDK8 Gene

Sequence variations from dbSNP and Humsavar for CDK8 Gene

SNP ID Clin Chr 13 pos Variation AA Info Type
VAR_041980 A lung neuroendocrine carcinoma sample p.Asp189Asn
VAR_041981 A colorectal adenocarcinoma sample p.Arg424Cys
rs1000009077 -- 26,269,693(+) T/C genic_upstream_transcript_variant, intron_variant
rs1000029689 -- 26,363,576(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000030007 -- 26,279,317(+) C/T genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CDK8 Gene

Variant ID Type Subtype PubMed ID
esv3304269 CNV mobile element insertion 20981092
esv3360510 CNV insertion 20981092
esv3361608 CNV insertion 20981092
esv3631600 CNV loss 21293372
nsv1138203 CNV deletion 24896259
nsv561357 CNV gain 21841781

Variation tolerance for CDK8 Gene

Residual Variation Intolerance Score: 20.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.25; 5.53% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CDK8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CDK8

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CDK8 Gene

Disorders for CDK8 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CDK8 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
colorectal adenocarcinoma
  • adenocarcinoma of large intestine
hemophagocytic lymphohistiocytosis, familial, 3
  • fhl3
- elite association - COSMIC cancer census association via MalaCards
Search CDK8 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CDK8

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CDK8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CDK8 Gene

Publications for CDK8 Gene

  1. Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. (PMID: 7568034) Tassan JP … Nigg EA (Proceedings of the National Academy of Sciences of the United States of America 1995) 2 3 4 22 58
  2. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. (PMID: 15546612) Fryer CJ … Jones KA (Molecular cell 2004) 3 4 22 58
  3. The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. (PMID: 21806996) Schneider EV … Maskos K (Journal of molecular biology 2011) 3 4 58
  4. CDK8 is a positive regulator of transcriptional elongation within the serum response network. (PMID: 20098423) Donner AJ … Espinosa JM (Nature structural & molecular biology 2010) 3 22 58
  5. CDK8 expression in 470 colorectal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. (PMID: 19790197) Firestein R … Ogino S (International journal of cancer 2010) 3 22 58

Products for CDK8 Gene

Sources for CDK8 Gene

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