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Protein

Cyclin-dependent kinase 8

Gene

Cdk8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei52 – 521ATPPROSITE-ProRule annotation
Active sitei151 – 1511Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi27 – 359ATPPROSITE-ProRule annotation

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

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_275829. Generic Transcription Pathway.
REACT_302128. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.

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
Gene namesi
Name:Cdk8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1196224. Cdk8.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 464464Cyclin-dependent kinase 8PRO_0000280443Add
BLAST

Proteomic databases

MaxQBiQ8R3L8.
PaxDbiQ8R3L8.
PRIDEiQ8R3L8.

PTM databases

PhosphoSiteiQ8R3L8.

Expressioni

Gene expression databases

BgeeiQ8R3L8.
CleanExiMM_CDK8.
ExpressionAtlasiQ8R3L8. baseline and differential.
GenevisibleiQ8R3L8. MM.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi234457. 1 interaction.
DIPiDIP-59235N.
IntActiQ8R3L8. 1 interaction.
STRINGi10090.ENSMUSP00000031640.

Structurei

3D structure databases

ProteinModelPortaliQ8R3L8.
SMRiQ8R3L8. Positions 1-359.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 335315Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 1515Interaction with CCNCBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi373 – 3775Poly-Gln

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000064012.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ8R3L8.
KOiK02208.
OMAiQDVFAGC.
PhylomeDBiQ8R3L8.
TreeFamiTF101025.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R3L8-1) [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 LLKVFLSHAD 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 EEEPDEKGDK KTQQQQQGNN HTNGTGHPGN QDSGHAQGPP
410 420 430 440 450
LKKVRVVPPT TTSGGLIMTS DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT
460
SQQPPQYSHQ THRY
Length:464
Mass (Da):53,210
Last modified:March 20, 2007 - v3
Checksum:iD8E350486ADA3F8D
GO
Isoform 2 (identifier: Q8R3L8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: Missing.
     260-263: GFPA → MYFT

Note: No experimental confirmation available.
Show »
Length:205
Mass (Da):23,342
Checksum:i13AF28272E4E7ACC
GO
Isoform 3 (identifier: Q8R3L8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     216-220: Missing.

Note: No experimental confirmation available.
Show »
Length:459
Mass (Da):52,611
Checksum:i32239BFC79E785B7
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 259259Missing in isoform 2. 1 PublicationVSP_023673Add
BLAST
Alternative sequencei216 – 2205Missing in isoform 3. 1 PublicationVSP_023675
Alternative sequencei260 – 2634GFPA → MYFT in isoform 2. 1 PublicationVSP_023674

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC113316 Genomic DNA. No translation available.
BC025046 mRNA. No translation available.
BC132551 mRNA. Translation: AAI32552.1.
BC132553 mRNA. Translation: AAI32554.1.
AK131948 mRNA. No translation available.
CCDSiCCDS19869.1. [Q8R3L8-1]
RefSeqiNP_705827.2. NM_153599.3. [Q8R3L8-1]
XP_006504899.1. XM_006504836.2. [Q8R3L8-3]
UniGeneiMm.260576.

Genome annotation databases

EnsembliENSMUST00000031640; ENSMUSP00000031640; ENSMUSG00000029635. [Q8R3L8-1]
GeneIDi264064.
KEGGimmu:264064.
UCSCiuc009and.1. mouse. [Q8R3L8-1]
uc009ane.1. mouse. [Q8R3L8-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC113316 Genomic DNA. No translation available.
BC025046 mRNA. No translation available.
BC132551 mRNA. Translation: AAI32552.1.
BC132553 mRNA. Translation: AAI32554.1.
AK131948 mRNA. No translation available.
CCDSiCCDS19869.1. [Q8R3L8-1]
RefSeqiNP_705827.2. NM_153599.3. [Q8R3L8-1]
XP_006504899.1. XM_006504836.2. [Q8R3L8-3]
UniGeneiMm.260576.

3D structure databases

ProteinModelPortaliQ8R3L8.
SMRiQ8R3L8. Positions 1-359.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi234457. 1 interaction.
DIPiDIP-59235N.
IntActiQ8R3L8. 1 interaction.
STRINGi10090.ENSMUSP00000031640.

PTM databases

PhosphoSiteiQ8R3L8.

Proteomic databases

MaxQBiQ8R3L8.
PaxDbiQ8R3L8.
PRIDEiQ8R3L8.

Protocols and materials databases

DNASUi264064.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000031640; ENSMUSP00000031640; ENSMUSG00000029635. [Q8R3L8-1]
GeneIDi264064.
KEGGimmu:264064.
UCSCiuc009and.1. mouse. [Q8R3L8-1]
uc009ane.1. mouse. [Q8R3L8-2]

Organism-specific databases

CTDi1024.
MGIiMGI:1196224. Cdk8.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000064012.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ8R3L8.
KOiK02208.
OMAiQDVFAGC.
PhylomeDBiQ8R3L8.
TreeFamiTF101025.

Enzyme and pathway databases

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_275829. Generic Transcription Pathway.
REACT_302128. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.

Miscellaneous databases

ChiTaRSiCdk8. mouse.
NextBioi392145.
PROiQ8R3L8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R3L8.
CleanExiMM_CDK8.
ExpressionAtlasiQ8R3L8. baseline and differential.
GenevisibleiQ8R3L8. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: FVB/N.
    Tissue: Brain and Mammary tumor.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-464 (ISOFORM 3).

Entry informationi

Entry nameiCDK8_MOUSE
AccessioniPrimary (citable) accession number: Q8R3L8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: June 24, 2015
This is version 106 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.