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Q8R3L8

- CDK8_MOUSE

UniProt

Q8R3L8 - CDK8_MOUSE

Protein

Cyclin-dependent kinase 8

Gene

Cdk8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 3 (20 Mar 2007)
      Previous versions | rss
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    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

    Magnesium.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

    1. ATP binding Source: UniProtKB-KW
    2. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB-EC
    3. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. regulation of transcription, DNA-templated Source: UniProtKB-KW
    2. transcription, DNA-templated Source: UniProtKB-KW

    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_196464. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_196589. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_196591. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_198602. PPARA activates gene expression.
    REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_206529. Generic Transcription Pathway.
    REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

    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: Chromosome 5

    Organism-specific databases

    MGIiMGI:1196224. Cdk8.

    Subcellular locationi

    Nucleus Curated

    GO - Cellular componenti

    1. mediator complex Source: MGI
    2. nucleoplasm Source: Reactome
    3. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

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

    Proteomic databases

    PaxDbiQ8R3L8.
    PRIDEiQ8R3L8.

    PTM databases

    PhosphoSiteiQ8R3L8.

    Expressioni

    Gene expression databases

    ArrayExpressiQ8R3L8.
    BgeeiQ8R3L8.
    CleanExiMM_CDK8.
    GenevestigatoriQ8R3L8.

    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.

    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.
    OMAiNVITLIR.
    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_dom.
    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. Align

    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

    MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA    50
    LKQIEGTGIS MSACREIALL RELKHPNVIS LLKVFLSHAD RKVWLLFDYA 100
    EHDLWHIIKF HRASKANKKP VQLPRGMVKS LLYQILDGIH YLHANWVLHR 150
    DLKPANILVM GEGPERGRVK IADMGFARLF NSPLKPLADL DPVVVTFWYR 200
    APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED IKTSNPYHHD 250
    QLDRIFNVMG FPADKDWEDI KKMPEHSTLM KDFRRNTYTN CSLIKYMEKH 300
    KVKPDSKAFH LLQKLLTMDP IKRITSEQAM QDPYFLEDPL PTSDVFAGCQ 350
    IPYPKREFLT EEEPDEKGDK KTQQQQQGNN HTNGTGHPGN QDSGHAQGPP 400
    LKKVRVVPPT TTSGGLIMTS DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT 450
    SQQPPQYSHQ THRY 464
    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:
    EMBL
    GenBank
    DDBJ
    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_006504836.1. [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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS19869.1. [Q8R3L8-1 ]
    RefSeqi NP_705827.2. NM_153599.3. [Q8R3L8-1 ]
    XP_006504899.1. XM_006504836.1. [Q8R3L8-3 ]
    UniGenei Mm.260576.

    3D structure databases

    ProteinModelPortali Q8R3L8.
    SMRi Q8R3L8. Positions 1-359.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 234457. 1 interaction.
    DIPi DIP-59235N.
    IntActi Q8R3L8. 1 interaction.

    PTM databases

    PhosphoSitei Q8R3L8.

    Proteomic databases

    PaxDbi Q8R3L8.
    PRIDEi Q8R3L8.

    Protocols and materials databases

    DNASUi 264064.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031640 ; ENSMUSP00000031640 ; ENSMUSG00000029635 . [Q8R3L8-1 ]
    GeneIDi 264064.
    KEGGi mmu:264064.
    UCSCi uc009and.1. mouse. [Q8R3L8-1 ]
    uc009ane.1. mouse. [Q8R3L8-2 ]

    Organism-specific databases

    CTDi 1024.
    MGIi MGI:1196224. Cdk8.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00530000064012.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q8R3L8.
    KOi K02208.
    OMAi NVITLIR.
    PhylomeDBi Q8R3L8.
    TreeFami TF101025.

    Enzyme and pathway databases

    Reactomei REACT_196464. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_196589. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_196591. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_198602. PPARA activates gene expression.
    REACT_203903. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_206529. Generic Transcription Pathway.
    REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

    Miscellaneous databases

    ChiTaRSi CDK8. mouse.
    NextBioi 392145.
    PROi Q8R3L8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8R3L8.
    Bgeei Q8R3L8.
    CleanExi MM_CDK8.
    Genevestigatori Q8R3L8.

    Family and domain databases

    InterProi IPR011009. 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 100 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