CDK8
Cyclin-dependent kinase 8
Also known as: CDK8_HUMAN, K35
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P49336
- Gene
- CDK8
- Ensembl
- ENSG00000132964
- Chromosome
- 13
- Canonical length
- 464 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
464 residues, UniProt reviewed canonical sequence.
>P49336|CDK8
1 MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS
61 MSACREIALL RELKHPNVIS LQKVFLSHAD RKVWLLFDYA EHDLWHIIKF HRASKANKKP
121 VQLPRGMVKS LLYQILDGIH YLHANWVLHR DLKPANILVM GEGPERGRVK IADMGFARLF
181 NSPLKPLADL DPVVVTFWYR APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED
241 IKTSNPYHHD QLDRIFNVMG FPADKDWEDI KKMPEHSTLM KDFRRNTYTN CSLIKYMEKH
301 KVKPDSKAFH LLQKLLTMDP IKRITSEQAM QDPYFLEDPL PTSDVFAGCQ IPYPKREFLT
361 EEEPDDKGDK KNQQQQQGNN HTNGTGHPGN QDSSHTQGPP LKKVRVVPPT TTSGGLIMTS
421 DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT SQQPPQYSHQ THRYLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CDK8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.38
- Highest tissue expression
- 9.5 nTPM
Expression across tissuesHPA
Tissue
- colon: 9.5 nTPM
- small intestine: 6.4 nTPM
- duodenum: 5.6 nTPM
- urinary bladder: 4.8 nTPM
- testis: 4.5 nTPM
- stomach: 4.1 nTPM
Single-cell type
- myosatellite cells: 478 nCPM
- myonuclei: 427 nCPM
- prostatic club cells: 340 nCPM
- thyrotrophs: 270 nCPM
- cone photoreceptor cells: 261 nCPM
- oligodendrocyte progenitor cells: 243 nCPM
Immune cell
- eosinophil: 0.8 nTPM
- intermediate monocyte: 0.4 nTPM
- MAIT T-cell: 0.3 nTPM
- naive CD4 T-cell: 0.3 nTPM
- gdT-cell: 0.2 nTPM
- memory CD8 T-cell: 0.2 nTPM
Brain region
- cerebellum: 14 nTPM
- cerebral cortex: 12 nTPM
- midbrain: 11 nTPM
- basal ganglia: 10 nTPM
- medulla oblongata: 10 nTPM
- pons: 10 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CDK8.
Disease | AllUniProt
Conditions CDK8 is implicated in, by any mechanism.
- Intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA) MIM:618748
Disease | GeneticClinVar
20 pathogenic / likely-pathogenic of 117 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Intellectual developmental disorder with hypotonia and behavioral abnormalities
- 7 conditions
- Complex neurodevelopmental disorder with or without congenital anomalies
- NAD(P)HX dehydratase deficiency
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.42
- gnomAD pLI
- 0.41
- gnomAD missense Z
- 3.68
- DepMap mean gene effect
- -0.06
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
- ATP binding
- cyclin-dependent protein serine/threonine kinase activity
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- RNA polymerase II CTD heptapeptide repeat kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CDK8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CDK8 as an antibody target. Whether an autoantibody or antibody against CDK8 could matter depends on whether native CDK8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CDK8 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CDK8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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