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

    Gene ID: 1024, updated on 20-Aug-2016
    Official Symbol
    CDK8provided by HGNC
    Official Full Name
    cyclin dependent kinase 8provided by HGNC
    Primary source
    HGNC:HGNC:1779
    See related
    Ensembl:ENSG00000132964 HPRD:04422; MIM:603184; Vega:OTTHUMG00000016617
    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
    Summary
    The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit cyclin C are components of the RNA polymerase II holoenzyme complex, which phosphorylates the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. This kinase has also been shown to regulate transcription by targeting the CDK7/cyclin H subunits of the general transcription initiation factor IIH (TFIIH), thus providing a link between the 'Mediator-like' protein complexes and the basal transcription machinery. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    13q12
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 13 NC_000013.11 (26254104..26405238)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (26828262..26979375)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ATPase phospholipid transporting 8A2 pseudogene 3 Neighboring gene ring finger protein 6 Neighboring gene THAP domain containing 12 pseudogene 6 Neighboring gene ribosomal protein S3a pseudogene 44 Neighboring gene WAS protein family member 3 Neighboring gene uncharacterized LOC107984597

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

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

    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

    • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystem (from REACTOME)
      Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystemWhen found in cis, HD and PEST domain mutations act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold, compared with up to ~10-fold and up to ~2-fold increase with HD mutatio...
    • Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystem (from REACTOME)
      Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystemAs NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signal...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
      Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
      Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • NOTCH1 Intracellular Domain Regulates Transcription, organism-specific biosystem (from REACTOME)
      NOTCH1 Intracellular Domain Regulates Transcription, organism-specific biosystemNICD1 produced by activation of NOTCH1 in response to Delta and Jagged ligands (DLL/JAG) presented in trans, traffics to the nucleus where it acts as a transcription regulator. In the nucleus, NICD1 ...
    • PPARA activates gene expression, organism-specific biosystem (from REACTOME)
      PPARA activates gene expression, organism-specific biosystemThe set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor e...
    • Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystem (from REACTOME)
      Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystemPeroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma ...
    • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystem (from REACTOME)
      SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystemAfter phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, lin...
    • SREBP signalling, organism-specific biosystem (from WikiPathways)
      SREBP signalling, organism-specific biosystemSterol regulatory element-binding proteins (SREBPs) are membrane-bound proteins that act as transcription factors. They regulate lipid, especially cholesterol, biosynthesis and uptake at a transcript...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
    • Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
    • Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystemMutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increas...
    • Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystemNOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prol...
    • Signaling by NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 in Cancer, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). This tra...
    • Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
      Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
    • Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystem (from REACTOME)
      Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystemIn the nucleus, SMAD2/3:SMAD4 heterotrimer complex acts as a transcriptional regulator. The activity of SMAD2/3 complex is regulated both positively and negatively by association with other transcrip...
    • Transcriptional regulation of white adipocyte differentiation, organism-specific biosystem (from REACTOME)
      Transcriptional regulation of white adipocyte differentiation, organism-specific biosystemAdipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develo...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC126074, MGC126075

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    RNA polymerase II carboxy-terminal domain kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    cyclin-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    positive regulation of transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
     
    protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    transcription initiation from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    mediator complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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

    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_001260.2NP_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 longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC094784, BC104492, BM021447
      Consensus CDS
      CCDS9317.1
      UniProtKB/Swiss-Prot
      P49336
      Related
      ENSP00000370938, OTTHUMP00000018158, ENST00000381527, OTTHUMT00000044250
      Conserved Domains (2) summary
      smart00220
      Location:22335
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd07868
      Location:3335
      STKc_CDK8; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8
    2. NM_001318368.1NP_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 one amino acid shorter than isoform 1.
      Source sequence(s)
      BC069634, BC094784, BM021447
      UniProtKB/Swiss-Prot
      P49336
      Conserved Domains (2) summary
      smart00220
      Location:22335
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd07868
      Location:3335
      STKc_CDK8; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p7 Primary Assembly

      Range
      26254104..26405238
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534864.1XP_011533166.1  

      See identical proteins and their annotated locations for XP_011533166.1

      Conserved Domains (1) summary
      cl21453
      Location:1162
      PKc_like; Protein Kinases, catalytic domain
    2. XM_017020317.1XP_016875806.1  

    3. XM_005266216.4XP_005266273.1  

      See identical proteins and their annotated locations for XP_005266273.1

      Conserved Domains (2) summary
      smart00220
      Location:2275
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:1275
      PKc_like; Protein Kinases, catalytic domain
    4. XM_017020318.1XP_016875807.1  

    5. XM_011534865.2XP_011533167.1  

      See identical proteins and their annotated locations for XP_011533167.1

      Conserved Domains (1) summary
      cl21453
      Location:1162
      PKc_like; Protein Kinases, catalytic domain

    Alternate CHM1_1.1

    Genomic

    1. NC_018924.2 Alternate CHM1_1.1

      Range
      26796281..26947427
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)