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

    Gene ID: 1024, updated on 14-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
    mouse all
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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 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 Variation Viewer (GRCh37.p13)

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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