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Q8R3L8 (CDK8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cdk8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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

Cofactor

Magnesium By similarity.

Subunit structure

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.

Subcellular location

Nucleus Probable.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8R3L8-1)

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.
Isoform 2 (identifier: Q8R3L8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: Missing.
     260-263: GFPA → MYFT
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8R3L8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     216-220: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464Cyclin-dependent kinase 8
PRO_0000280443

Regions

Domain21 – 335315Protein kinase
Nucleotide binding27 – 359ATP By similarity
Region1 – 1515Interaction with CCNC By similarity
Compositional bias373 – 3775Poly-Gln

Sites

Active site1511Proton acceptor By similarity
Binding site521ATP By similarity

Natural variations

Alternative sequence1 – 259259Missing in isoform 2.
VSP_023673
Alternative sequence216 – 2205Missing in isoform 3.
VSP_023675
Alternative sequence260 – 2634GFPA → MYFT in isoform 2.
VSP_023674

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 20, 2007. Version 3.
Checksum: D8E350486ADA3F8D

FASTA46453,210
        10         20         30         40         50         60 
MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS 

        70         80         90        100        110        120 
MSACREIALL RELKHPNVIS LLKVFLSHAD RKVWLLFDYA EHDLWHIIKF HRASKANKKP 

       130        140        150        160        170        180 
VQLPRGMVKS LLYQILDGIH YLHANWVLHR DLKPANILVM GEGPERGRVK IADMGFARLF 

       190        200        210        220        230        240 
NSPLKPLADL DPVVVTFWYR APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED 

       250        260        270        280        290        300 
IKTSNPYHHD QLDRIFNVMG FPADKDWEDI KKMPEHSTLM KDFRRNTYTN CSLIKYMEKH 

       310        320        330        340        350        360 
KVKPDSKAFH LLQKLLTMDP IKRITSEQAM QDPYFLEDPL PTSDVFAGCQ IPYPKREFLT 

       370        380        390        400        410        420 
EEEPDEKGDK KTQQQQQGNN HTNGTGHPGN QDSGHAQGPP LKKVRVVPPT TTSGGLIMTS 

       430        440        450        460 
DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT SQQPPQYSHQ THRY 

« Hide

Isoform 2 [UniParc].

Checksum: 13AF28272E4E7ACC
Show »

FASTA20523,342
Isoform 3 [UniParc].

Checksum: 32239BFC79E785B7
Show »

FASTA45952,611

References

[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS19869.1. [Q8R3L8-1]
RefSeqNP_705827.2. NM_153599.3. [Q8R3L8-1]
XP_006504899.1. XM_006504836.1. [Q8R3L8-3]
UniGeneMm.260576.

3D structure databases

ProteinModelPortalQ8R3L8.
SMRQ8R3L8. Positions 1-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid234457. 1 interaction.
DIPDIP-59235N.
IntActQ8R3L8. 1 interaction.

PTM databases

PhosphoSiteQ8R3L8.

Proteomic databases

PaxDbQ8R3L8.
PRIDEQ8R3L8.

Protocols and materials databases

DNASU264064.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031640; ENSMUSP00000031640; ENSMUSG00000029635. [Q8R3L8-1]
GeneID264064.
KEGGmmu:264064.
UCSCuc009and.1. mouse. [Q8R3L8-1]
uc009ane.1. mouse. [Q8R3L8-2]

Organism-specific databases

CTD1024.
MGIMGI:1196224. Cdk8.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000064012.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ8R3L8.
KOK02208.
OMANVITLIR.
PhylomeDBQ8R3L8.
TreeFamTF101025.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_200794. Mus musculus biological processes.

Gene expression databases

ArrayExpressQ8R3L8.
BgeeQ8R3L8.
CleanExMM_CDK8.
GenevestigatorQ8R3L8.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDK8. mouse.
NextBio392145.
PROQ8R3L8.
SOURCESearch...

Entry information

Entry nameCDK8_MOUSE
AccessionPrimary (citable) accession number: Q8R3L8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 98 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot