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

Gene ID: 1024, updated on 15-Apr-2019

Summary

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
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
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

Genomic context

See CDK8 in Genome Data Viewer
Location:
13q12.13
Exon count:
14
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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 WASP family member 3 Neighboring gene ribosomal protein S3a pseudogene 44 Neighboring gene uncharacterized LOC107984597

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

HIV-1 interactions

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 BioSystems

  • 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...
  • 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 ...
  • Sterol Regulatory Element-Binding Proteins (SREBP) signalling, organism-specific biosystem (from WikiPathways)
    Sterol Regulatory Element-Binding Proteins (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...
  • 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 CTD heptapeptide repeat kinase activity IEA
Inferred from Electronic Annotation
more info
 
cyclin-dependent protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mediator complex IDA
Inferred from Direct Assay
more info
PubMed 
nucleolus IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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_016875806.1
XP_016875807.1

NCBI Reference Sequences (RefSeq)

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_001260.3NP_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
    Related
    ENSP00000370938.3, ENST00000381527.8
    Conserved Domains (1) summary
    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 shorter than isoform 1.
    Source sequence(s)
    BC069634, BC094784, BM021447
    UniProtKB/Swiss-Prot
    P49336
    Conserved Domains (1) summary
    cd07868
    Location:3335
    STKc_CDK8; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8
  3. NM_001346501.1NP_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
    Conserved Domains (1) summary
    cl21453
    Location:1162
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p12 Primary Assembly

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

mRNA and Protein(s)

  1. XM_017020317.2XP_016875806.1  cyclin-dependent kinase 8 isoform X1

    Conserved Domains (1) summary
    cl21453
    Location:1209
    PKc_like; Protein Kinases, catalytic domain
  2. XM_017020318.1XP_016875807.1  cyclin-dependent kinase 8 isoform X3

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

    See identical proteins and their annotated locations for XP_011533167.1

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