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Protein

Cyclin-dependent kinase 8

Gene

CDK8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.1 Publication

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei52ATPPROSITE-ProRule annotation1
Active sitei151Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi27 – 35ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Kinase, Repressor, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05713-MONOMER.
BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-212436. Generic Transcription Pathway.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiP49336.
SIGNORiP49336.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 8 (EC:2.7.11.22, EC:2.7.11.23)
Alternative name(s):
Cell division protein kinase 8
Mediator complex subunit CDK8
Mediator of RNA polymerase II transcription subunit CDK8
Protein kinase K35
Gene namesi
Name:CDK8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:1779. CDK8.

Subcellular locationi

GO - Cellular componenti

  • mediator complex Source: MGI
  • nucleolus Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi173D → A: Abrogates kinase activity and TFIIH-dependent transcriptional repression. 1 Publication1

Organism-specific databases

DisGeNETi1024.
OpenTargetsiENSG00000132964.
PharmGKBiPA26315.

Chemistry databases

ChEMBLiCHEMBL5719.
GuidetoPHARMACOLOGYi1980.

Polymorphism and mutation databases

BioMutaiCDK8.
DMDMi1345718.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000857971 – 464Cyclin-dependent kinase 8Add BLAST464

Proteomic databases

EPDiP49336.
MaxQBiP49336.
PaxDbiP49336.
PeptideAtlasiP49336.
PRIDEiP49336.

PTM databases

iPTMnetiP49336.
PhosphoSitePlusiP49336.

Expressioni

Gene expression databases

BgeeiENSG00000132964.
CleanExiHS_CDK8.
ExpressionAtlasiP49336. baseline and differential.
GenevisibleiP49336. HS.

Interactioni

Subunit structurei

Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Interacts with CTNNB1, GLI3 and MAML1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCNCP2486324EBI-394377,EBI-395261

Protein-protein interaction databases

BioGridi107458. 107 interactors.
DIPiDIP-32595N.
IntActiP49336. 78 interactors.
MINTiMINT-3017285.
STRINGi9606.ENSP00000370938.

Chemistry databases

BindingDBiP49336.

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 12Combined sources10
Helixi16 – 19Combined sources4
Beta strandi26 – 42Combined sources17
Beta strandi49 – 58Combined sources10
Helixi61 – 72Combined sources12
Beta strandi83 – 87Combined sources5
Turni88 – 91Combined sources4
Beta strandi92 – 98Combined sources7
Beta strandi101 – 103Combined sources3
Helixi104 – 113Combined sources10
Helixi125 – 144Combined sources20
Helixi154 – 156Combined sources3
Beta strandi157 – 159Combined sources3
Turni164 – 167Combined sources4
Beta strandi169 – 171Combined sources3
Helixi179 – 181Combined sources3
Helixi202 – 205Combined sources4
Helixi213 – 229Combined sources17
Helixi249 – 259Combined sources11
Helixi264 – 266Combined sources3
Helixi268 – 272Combined sources5
Helixi276 – 282Combined sources7
Helixi285 – 288Combined sources4
Helixi293 – 299Combined sources7
Helixi307 – 315Combined sources9
Helixi320 – 322Combined sources3
Helixi326 – 330Combined sources5
Helixi333 – 335Combined sources3
Beta strandi337 – 339Combined sources3
Turni345 – 348Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RGFX-ray2.20A1-403[»]
4CRLX-ray2.40A1-403[»]
4F6SX-ray2.60A1-403[»]
4F6UX-ray2.10A1-403[»]
4F6WX-ray2.39A1-403[»]
4F70X-ray3.00A1-403[»]
4F7JX-ray2.60A1-403[»]
4F7LX-ray2.90A1-403[»]
4F7NX-ray2.65A1-403[»]
4F7SX-ray2.20A1-403[»]
4G6LX-ray2.70A1-403[»]
5BNJX-ray2.64A1-403[»]
5CEIX-ray2.24A1-403[»]
5FGKX-ray2.36A1-362[»]
5HBEX-ray2.38A1-362[»]
5HBHX-ray2.50A1-362[»]
5HBJX-ray3.00A1-362[»]
5HNBX-ray2.35A1-362[»]
5HVYX-ray2.39A1-403[»]
5I5ZX-ray2.60A1-362[»]
ProteinModelPortaliP49336.
SMRiP49336.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 335Protein kinasePROSITE-ProRule annotationAdd BLAST315

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 15Interaction with CCNCAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi373 – 377Poly-Gln5

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0666. Eukaryota.
ENOG410XPPA. LUCA.
GeneTreeiENSGT00530000064012.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49336.
KOiK02208.
OMAiKHVNVIT.
OrthoDBiEOG091G0812.
PhylomeDBiP49336.
TreeFamiTF101025.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49336-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA
60 70 80 90 100
LKQIEGTGIS MSACREIALL RELKHPNVIS LQKVFLSHAD RKVWLLFDYA
110 120 130 140 150
EHDLWHIIKF HRASKANKKP VQLPRGMVKS LLYQILDGIH YLHANWVLHR
160 170 180 190 200
DLKPANILVM GEGPERGRVK IADMGFARLF NSPLKPLADL DPVVVTFWYR
210 220 230 240 250
APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED IKTSNPYHHD
260 270 280 290 300
QLDRIFNVMG FPADKDWEDI KKMPEHSTLM KDFRRNTYTN CSLIKYMEKH
310 320 330 340 350
KVKPDSKAFH LLQKLLTMDP IKRITSEQAM QDPYFLEDPL PTSDVFAGCQ
360 370 380 390 400
IPYPKREFLT EEEPDDKGDK KNQQQQQGNN HTNGTGHPGN QDSSHTQGPP
410 420 430 440 450
LKKVRVVPPT TTSGGLIMTS DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT
460
SQQPPQYSHQ THRY
Length:464
Mass (Da):53,284
Last modified:February 1, 1996 - v1
Checksum:i00CBAB6CE354605F
GO
Isoform 2 (identifier: P49336-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     370-370: Missing.

Show »
Length:463
Mass (Da):53,156
Checksum:i8C74EEBD24CBA5DB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041980189D → N in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041981424R → C in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029970370Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85753 mRNA. Translation: CAA59754.1.
AL590108, AL159159 Genomic DNA. Translation: CAH72300.1.
AL159159, AL590108 Genomic DNA. Translation: CAI16960.1.
CH471075 Genomic DNA. Translation: EAX08386.1.
CH471075 Genomic DNA. Translation: EAX08387.1.
BC069634 mRNA. Translation: AAH69634.1.
BC104492 mRNA. Translation: AAI04493.1.
BC105950 mRNA. Translation: AAI05951.1.
BC107601 mRNA. Translation: AAI07602.1.
CCDSiCCDS9317.1. [P49336-1]
PIRiI37227.
RefSeqiNP_001251.1. NM_001260.2. [P49336-1]
NP_001305297.1. NM_001318368.1. [P49336-2]
UniGeneiHs.382306.
Hs.695166.

Genome annotation databases

EnsembliENST00000381527; ENSP00000370938; ENSG00000132964. [P49336-1]
GeneIDi1024.
KEGGihsa:1024.
UCSCiuc001uqr.2. human. [P49336-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85753 mRNA. Translation: CAA59754.1.
AL590108, AL159159 Genomic DNA. Translation: CAH72300.1.
AL159159, AL590108 Genomic DNA. Translation: CAI16960.1.
CH471075 Genomic DNA. Translation: EAX08386.1.
CH471075 Genomic DNA. Translation: EAX08387.1.
BC069634 mRNA. Translation: AAH69634.1.
BC104492 mRNA. Translation: AAI04493.1.
BC105950 mRNA. Translation: AAI05951.1.
BC107601 mRNA. Translation: AAI07602.1.
CCDSiCCDS9317.1. [P49336-1]
PIRiI37227.
RefSeqiNP_001251.1. NM_001260.2. [P49336-1]
NP_001305297.1. NM_001318368.1. [P49336-2]
UniGeneiHs.382306.
Hs.695166.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RGFX-ray2.20A1-403[»]
4CRLX-ray2.40A1-403[»]
4F6SX-ray2.60A1-403[»]
4F6UX-ray2.10A1-403[»]
4F6WX-ray2.39A1-403[»]
4F70X-ray3.00A1-403[»]
4F7JX-ray2.60A1-403[»]
4F7LX-ray2.90A1-403[»]
4F7NX-ray2.65A1-403[»]
4F7SX-ray2.20A1-403[»]
4G6LX-ray2.70A1-403[»]
5BNJX-ray2.64A1-403[»]
5CEIX-ray2.24A1-403[»]
5FGKX-ray2.36A1-362[»]
5HBEX-ray2.38A1-362[»]
5HBHX-ray2.50A1-362[»]
5HBJX-ray3.00A1-362[»]
5HNBX-ray2.35A1-362[»]
5HVYX-ray2.39A1-403[»]
5I5ZX-ray2.60A1-362[»]
ProteinModelPortaliP49336.
SMRiP49336.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107458. 107 interactors.
DIPiDIP-32595N.
IntActiP49336. 78 interactors.
MINTiMINT-3017285.
STRINGi9606.ENSP00000370938.

Chemistry databases

BindingDBiP49336.
ChEMBLiCHEMBL5719.
GuidetoPHARMACOLOGYi1980.

PTM databases

iPTMnetiP49336.
PhosphoSitePlusiP49336.

Polymorphism and mutation databases

BioMutaiCDK8.
DMDMi1345718.

Proteomic databases

EPDiP49336.
MaxQBiP49336.
PaxDbiP49336.
PeptideAtlasiP49336.
PRIDEiP49336.

Protocols and materials databases

DNASUi1024.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381527; ENSP00000370938; ENSG00000132964. [P49336-1]
GeneIDi1024.
KEGGihsa:1024.
UCSCiuc001uqr.2. human. [P49336-1]

Organism-specific databases

CTDi1024.
DisGeNETi1024.
GeneCardsiCDK8.
HGNCiHGNC:1779. CDK8.
MIMi603184. gene.
neXtProtiNX_P49336.
OpenTargetsiENSG00000132964.
PharmGKBiPA26315.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0666. Eukaryota.
ENOG410XPPA. LUCA.
GeneTreeiENSGT00530000064012.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP49336.
KOiK02208.
OMAiKHVNVIT.
OrthoDBiEOG091G0812.
PhylomeDBiP49336.
TreeFamiTF101025.

Enzyme and pathway databases

BioCyciZFISH:HS05713-MONOMER.
BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-212436. Generic Transcription Pathway.
R-HSA-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiP49336.
SIGNORiP49336.

Miscellaneous databases

ChiTaRSiCDK8. human.
GeneWikiiCyclin-dependent_kinase_8.
GenomeRNAii1024.
PROiP49336.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132964.
CleanExiHS_CDK8.
ExpressionAtlasiP49336. baseline and differential.
GenevisibleiP49336. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK8_HUMAN
AccessioniPrimary (citable) accession number: P49336
Secondary accession number(s): Q5VUF3, Q6ISB5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.