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Identification
HMDB Protein ID HMDBP01191
Secondary Accession Numbers
  • 6487
Name Cell division protein kinase 8
Synonyms
  1. Cyclin-dependent kinase 8
  2. Mediator complex subunit CDK8
  3. Mediator of RNA polymerase II transcription subunit CDK8
  4. Protein kinase K35
Gene Name CDK8
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus (Probable)
Gene Properties
Chromosome Location Chromosome:1
Locus 13q12
SNPs CDK8
Gene Sequence
>1395 bp
ATGGACTATGACTTTAAAGTGAAGCTGAGCAGCGAGCGGGAGCGGGTCGAGGACCTGTTT
GAATACGAGGGCTGCAAAGTTGGCCGAGGCACTTATGGTCACGTCTACAAAGCCAAGAGG
AAAGATGGGAAGGATGATAAAGACTATGCTTTAAAACAAATAGAAGGAACTGGGATCTCT
ATGTCGGCATGTAGAGAAATAGCATTACTTCGAGAGCTTAAGCATCCAAACGTCATTTCT
CTTCAAAAGGTGTTTCTGTCTCATGCTGATAGGAAGGTGTGGCTTCTGTTTGACTATGCT
GAACATGACCTCTGGCATATAATCAAGTTTCACAGAGCTTCTAAAGCAAACAAGAAGCCA
GTTCAGTTACCTCGGGGAATGGTGAAGTCACTATTATATCAGATCCTAGATGGTATTCAC
TACCTGCATGCTAACTGGGTGTTGCACAGAGATTTGAAACCTGCTAATATTTTAGTTATG
GGTGAAGGTCCTGAGCGAGGAAGAGTAAAAATTGCTGACATGGGCTTTGCCCGATTATTT
AATTCACCTTTGAAGCCTTTAGCAGATTTGGATCCAGTGGTTGTTACATTCTGGTACCGA
GCCCCTGAACTACTTCTTGGAGCAAGGCATTATACCAAAGCTATTGATATTTGGGCTATA
GGGTGTATATTTGCAGAACTACTAACGTCAGAACCAATATTTCACTGTCGACAAGAGGAC
ATCAAAACTAGTAATCCTTATCACCATGACCAGCTGGACAGAATATTCAATGTAATGGGA
TTTCCTGCAGATAAAGATTGGGAAGATATAAAAAAGATGCCTGAACATTCAACATTAATG
AAAGATTTCAGAAGAAATACGTATACCAACTGCAGCCTTATCAAGTATATGGAAAAACAT
AAAGTTAAACCAGATAGTAAAGCATTCCACTTGCTTCAGAAGCTGCTTACCATGGACCCA
ATAAAGCGAATTACCTCAGAACAGGCTATGCAGGACCCCTATTTCTTAGAAGACCCACTT
CCTACATCAGACGTTTTTGCCGGTTGTCAAATCCCTTACCCAAAACGAGAATTTTTAACG
GAAGAAGAACCTGATGACAAAGGAGACAAAAAGAACCAGCAGCAGCAGCAGGGCAATAAC
CACACTAATGGAACTGGCCACCCAGGGAATCAAGACAGCAGTCACACACAGGGACCCCCG
TTGAAGAAAGTGAGAGTTGTTCCTCCTACCACTACCTCAGGTGGACTTATCATGACCTCA
GACTATCAGCGTTCCAATCCACATGCTGCCTATCCCAACCCTGGACCAAGCACATCACAG
CCGCAGAGCAGCATGGGATACTCAGCTACCTCCCAGCAGCCTCCACAGTACTCACATCAG
ACACATCGGTACTGA
Protein Properties
Number of Residues 464
Molecular Weight 53283.3
Theoretical pI 8.82
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Cell division protein kinase 8
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGIS
MSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKP
VQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLF
NSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQED
IKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKH
KVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLT
EEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTS
DYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY
GenBank ID Protein 1000491
UniProtKB/Swiss-Prot ID P49336
UniProtKB/Swiss-Prot Entry Name CDK8_HUMAN
PDB IDs Not Available
GenBank Gene ID X85753
GeneCard ID CDK8
GenAtlas ID CDK8
HGNC ID HGNC:1779
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  3. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. [PubMed:15057823 ]
  4. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  5. Tassan JP, Jaquenoud M, Leopold P, Schultz SJ, Nigg EA: Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8871-5. [PubMed:7568034 ]
  6. Sun X, Zhang Y, Cho H, Rickert P, Lees E, Lane W, Reinberg D: NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription. Mol Cell. 1998 Aug;2(2):213-22. [PubMed:9734358 ]
  7. Gu W, Malik S, Ito M, Yuan CX, Fondell JD, Zhang X, Martinez E, Qin J, Roeder RG: A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol Cell. 1999 Jan;3(1):97-108. [PubMed:10024883 ]
  8. Akoulitchev S, Chuikov S, Reinberg D: TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature. 2000 Sep 7;407(6800):102-6. [PubMed:10993082 ]
  9. Fryer CJ, White JB, Jones KA: Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell. 2004 Nov 19;16(4):509-20. [PubMed:15546612 ]
  10. Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway JW, Conaway RC: A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Mol Cell. 2004 Jun 4;14(5):685-91. [PubMed:15175163 ]
  11. Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT, Roeder RG: MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell. 2005 Jul 1;19(1):89-100. [PubMed:15989967 ]
  12. Zhou H, Kim S, Ishii S, Boyer TG: Mediator modulates Gli3-dependent Sonic hedgehog signaling. Mol Cell Biol. 2006 Dec;26(23):8667-82. Epub 2006 Sep 25. [PubMed:17000779 ]