Q8R3L8 (CDK8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Cdk8

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	464 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Activator Kinase Repressor Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mediator complex Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II carboxy-terminal domain kinase activity Inferred from electronic annotation. Source: EC cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 464	464	Cyclin-dependent kinase 8		PRO_0000280443
Regions
	Domain	21 – 335	315	Protein kinase
	Nucleotide binding	27 – 35	9	ATP By similarity
	Compositional bias	373 – 377	5	Poly-Gln
Sites
	Active site	151	1	Proton acceptor By similarity
	Binding site	52	1	ATP By similarity
Amino acid modifications
	Modified residue	410	1	Phosphothreonine By similarity
	Modified residue	413	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 259	259	Missing in isoform 2.		VSP_023673
	Alternative sequence	216 – 220	5	Missing in isoform 3.		VSP_023675
	Alternative sequence	260 – 263	4	GFPA → MYFT in isoform 2.		VSP_023674

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 3. Checksum: D8E350486ADA3F8D	FASTA	464	53,210
	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
	Isoform 2 [UniParc]. Checksum: 13AF28272E4E7ACC	FASTA	205	23,342
	10 20 30 40 50 60 MYFTDKDWED IKKMPEHSTL MKDFRRNTYT NCSLIKYMEK HKVKPDSKAF HLLQKLLTMD 70 80 90 100 110 120 PIKRITSEQA MQDPYFLEDP LPTSDVFAGC QIPYPKREFL TEEEPDEKGD KKTQQQQQGN 130 140 150 160 170 180 NHTNGTGHPG NQDSGHAQGP PLKKVRVVPP TTTSGGLIMT SDYQRSNPHA AYPNPGPSTS 190 200 QPQSSMGYSA TSQQPPQYSH QTHRY
	Isoform 3 [UniParc]. Checksum: 32239BFC79E785B7	FASTA	459	52,611
	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 YTKAIGCIFA ELLTSEPIFH CRQEDIKTSN 250 260 270 280 290 300 PYHHDQLDRI FNVMGFPADK DWEDIKKMPE HSTLMKDFRR NTYTNCSLIK YMEKHKVKPD 310 320 330 340 350 360 SKAFHLLQKL LTMDPIKRIT SEQAMQDPYF LEDPLPTSDV FAGCQIPYPK REFLTEEEPD 370 380 390 400 410 420 EKGDKKTQQQ QQGNNHTNGT GHPGNQDSGH AQGPPLKKVR VVPPTTTSGG LIMTSDYQRS 430 440 450 NPHAAYPNPG PSTSQPQSSM GYSATSQQPP QYSHQTHRY

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. , 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: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[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: 15489334] [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: 16141072] [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.
IPI	IPI00405475. IPI00830288. IPI00830408.
RefSeq	NP_705827.2. NM_153599.3.
UniGene	Mm.260576.
3D structure databases
ProteinModelPortal	Q8R3L8.
SMR	Q8R3L8. Positions 1-353.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8R3L8.
PTM databases
PhosphoSite	Q8R3L8.
Proteomic databases
PRIDE	Q8R3L8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031640; ENSMUSP00000031640; ENSMUSG00000029635.
GeneID	264064.
KEGG	mmu:264064.
UCSC	uc007eww.2. mouse. uc009ane.1. mouse.
Organism-specific databases
CTD	1024.
MGI	MGI:1196224. Cdk8.
Phylogenomic databases
GeneTree	ENSGT00530000064012.
HOGENOM	HBG755340.
HOVERGEN	HBG014652.
InParanoid	Q8R3L8.
OMA	QDVFAGC.
OrthoDB	EOG48D0V7.
PhylomeDB	Q8R3L8.
Enzyme and pathway databases
Reactome	REACT_115492. Developmental Biology. REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
Gene expression databases
ArrayExpress	Q8R3L8.
Bgee	Q8R3L8.
CleanEx	MM_CDK8.
Genevestigator	Q8R3L8.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K02208.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	392145.
SOURCE	Search...

Entry information

Entry name

CDK8_MOUSE

Accession

Primary (citable) accession number: Q8R3L8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 20, 2007
Last modified:	November 16, 2011
This is version 76 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program