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CDK8 cyclin dependent kinase 8 [ Homo sapiens (human) ]

Gene ID: 1024, updated on 27-Nov-2024

Summary

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Official Symbol
CDK8provided by HGNC
Official Full Name
cyclin dependent kinase 8provided by HGNC
Primary source
HGNC:HGNC:1779
See related
Ensembl:ENSG00000132964 MIM:603184; AllianceGenome:HGNC:1779
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
K35; IDDHBA
Summary
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]
Expression
Ubiquitous expression in testis (RPKM 6.1), duodenum (RPKM 3.9) and 25 other tissues See more
Orthologs
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Genomic context

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See CDK8 in Genome Data Viewer
Location:
13q12.13
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (26254129..26405238)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (25467904..25619002)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (26828266..26979375)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ATPase phospholipid transporting 8A2 pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7491 Neighboring gene ring finger protein 6 Neighboring gene Sharpr-MPRA regulatory region 3220 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:26795223-26796104 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:26796105-26796986 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5186 Neighboring gene THAP domain containing 12 pseudogene 6 Neighboring gene NANOG hESC enhancer GRCh37_chr13:26953049-26953564 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:26998629-26999154 Neighboring gene Sharpr-MPRA regulatory region 712 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:27059649-27060160 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5187 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:27075157-27075657 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5188 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5189 Neighboring gene WASP family member 3 Neighboring gene RPS3A pseudogene 44 Neighboring gene NANOG hESC enhancer GRCh37_chr13:27232594-27233188 Neighboring gene uncharacterized LOC107984597 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:27269807-27270328

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Expanding the phenotypic spectrum for CDK8-related disease: A case report. Comeau D, et al. Am J Med Genet A, 2024 May. PMID 38193604
  2. De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of the Mediator Complex, Cause a Syndromic Developmental Disorder. Calpena E, et al. Am J Hum Genet, 2019 Apr 4. PMID 30905399, Free PMC Article
  3. Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism. Rice S, et al. Viruses, 2020 Mar 13. PMID 32183180, Free PMC Article
  4. CDK8 expression in 470 colorectal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. Firestein R, et al. Int J Cancer, 2010 Jun 15. PMID 19790197, Free PMC Article
  5. CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-β-catenin-KLF2 signal axis. Wei R, et al. Exp Cell Res, 2018 Aug 15. PMID 29856990

See all (170) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Expanding the phenotypic spectrum for CDK8-related disease: A case report.
    Title: Expanding the phenotypic spectrum for CDK8-related disease: A case report.
  2. NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells.
    Title: NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells.
  3. Transcriptome-based chemical screens identify CDK8 as a common barrier in multiple cell reprogramming systems.
    Title: Transcriptome-based chemical screens identify CDK8 as a common barrier in multiple cell reprogramming systems.
  4. CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.
    Title: CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.
  5. Loss of miR-26b-5p promotes gastric cancer progression via miR-26b-5p-PDE4B/CDK8-STAT3 feedback loop.
    Title: Loss of miR-26b-5p promotes gastric cancer progression via miR-26b-5p-PDE4B/CDK8-STAT3 feedback loop.
  6. Identification of <i>Cdk8</i> and <i>Cdkn2d</i> as New Prame-Target Genes in 2C-like Embryonic Stem Cells.
    Title: Identification of Cdk8 and Cdkn2d as New Prame-Target Genes in 2C-like Embryonic Stem Cells.
  7. A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.
    Title: A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.
  8. CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF.
    Title: CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF.
  9. Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma.
    Title: Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma.
  10. Inhibition of Cyclin-Dependent Kinase 8/Cyclin-Dependent Kinase 19 Suppresses Its Pro-Oncogenic Effects in Prostate Cancer.
    Title: Inhibition of Cyclin-Dependent Kinase 8/Cyclin-Dependent Kinase 19 Suppresses Its Pro-Oncogenic Effects in Prostate Cancer.
Submit: New GeneRIF Correction See all GeneRIFs (83)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual developmental disorder with hypotonia and behavioral abnormalities
MedGen: C5231489 OMIM: 618748 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat interacts with the RNA polymerase II holoenzyme, which includes CDK8, during Tat-mediated transactivation of the HIV-1 LTR PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126074, MGC126075

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II CTD heptapeptide repeat S2 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II CTD heptapeptide repeat S5 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II CTD heptapeptide repeat S7 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II CTD heptapeptide repeat T4 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II CTD heptapeptide repeat Y1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cell cycle IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of CKM complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of cyclin-dependent protein kinase holoenzyme complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of mediator complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of mediator complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in nucleolus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
cyclin-dependent kinase 8
Names
CDK8 protein kinase
cell division protein kinase 8
mediator complex subunit CDK8
mediator of RNA polymerase II transcription subunit CDK8
protein kinase K35
NP_001251.1
NP_001305297.1
NP_001333430.1
XP_011533167.1
XP_047285989.1
XP_054229972.1
XP_054229973.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001260.3 → NP_001251.1  cyclin-dependent kinase 8 isoform 1

    See identical proteins and their annotated locations for NP_001251.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC094784, BC104492, BM021447
    Consensus CDS
    CCDS9317.1
    UniProtKB/Swiss-Prot
    P49336, Q5VUF3, Q6ISB5
    Related
    ENSP00000370938.3, ENST00000381527.8
    Conserved Domains (1) summary
    cd07868
    Location:3 → 335
    STKc_CDK8; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8

  2. NM_001318368.2 → NP_001305297.1  cyclin-dependent kinase 8 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, which results in a protein (isoform 2) that is shorter than isoform 1.
    Source sequence(s)
    BC069634, BC094784, BM021447
    UniProtKB/Swiss-Prot
    P49336
    Conserved Domains (1) summary
    cd07868
    Location:3 → 335
    STKc_CDK8; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8

  3. NM_001346501.2 → NP_001333430.1  cyclin-dependent kinase 8 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an exon in the 5' region and uses a downstream start codon, compared to variant 1. It encodes isoform 3 which has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    BC094784, BM021938
    UniProtKB/TrEMBL
    B4DJH7
    Conserved Domains (1) summary
    cl21453
    Location:1 → 162
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    26254129..26405238
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047430033.1 → XP_047285989.1  cyclin-dependent kinase 8 isoform X1

  2. XM_011534865.3 → XP_011533167.1  cyclin-dependent kinase 8 isoform X2

    See identical proteins and their annotated locations for XP_011533167.1

    UniProtKB/TrEMBL
    B4DJH7
    Conserved Domains (1) summary
    cl21453
    Location:1 → 162
    PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    25467904..25619002
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054373997.1 → XP_054229972.1  cyclin-dependent kinase 8 isoform X1

  2. XM_054373998.1 → XP_054229973.1  cyclin-dependent kinase 8 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49336.1 GenPept UniProtKB/Swiss-Prot:P49336

Gene LinkOut

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