Dual specificity protein kinase TTK

Details

Name

Dual specificity protein kinase TTK

Synonyms

• 2.7.12.1
• MPS1
• MPS1L1
• Phosphotyrosine picked threonine-protein kinase
• PYT

Gene Name

TTK

Organism

Humans

Amino acid sequence

>lcl|BSEQ0007272|Dual specificity protein kinase TTK
MESEDLSGRELTIDSIMNKVRDIKNKFKNEDLTDELSLNKISADTTDNSGTVNQIMMMAN
NPEDWLSLLLKLEKNSVPLSDALLNKLIGRYSQAIEALPPDKYGQNESFARIQVRFAELK
AIQEPDDARDYFQMARANCKKFAFVHISFAQFELSQGNVKKSKQLLQKAVERGAVPLEML
EIALRNLNLQKKQLLSEEEKKNLSASTVLTAQESFSGSLGHLQNRNNSCDSRGQTTKARF
LYGENMPPQDAEIGYRNSLRQTNKTKQSCPFGRVPVNLLNSPDCDVKTDDSVVPCFMKRQ
TSRSECRDLVVPGSKPSGNDSCELRNLKSVQNSHFKEPLVSDEKSSELIITDSITLKNKT
ESSLLAKLEETKEYQEPEVPESNQKQWQSKRKSECINQNPAASSNHWQIPELARKVNTEQ
KHTTFEQPVFSVSKQSPPISTSKWFDPKSICKTPSSNTLDDYMSCFRTPVVKNDFPPACQ
LSTPYGQPACFQQQQHQILATPLQNLQVLASSSANECISVKGRIYSILKQIGSGGSSKVF
QVLNEKKQIYAIKYVNLEEADNQTLDSYRNEIAYLNKLQQHSDKIIRLYDYEITDQYIYM
VMECGNIDLNSWLKKKKSIDPWERKSYWKNMLEAVHTIHQHGIVHSDLKPANFLIVDGML
KLIDFGIANQMQPDTTSVVKDSQVGTVNYMPPEAIKDMSSSRENGKSKSKISPKSDVWSL
GCILYYMTYGKTPFQQIINQISKLHAIIDPNHEIEFPDIPEKDLQDVLKCCLKRDPKQRI
SIPELLAHPYVQIQTHPVNQMAKGTTEEMKYVLGQLVGLNSPNSILKAAKTLYEHYSGGE
SHNSSSSKTFEKKRGKK

Number of residues

857

Molecular Weight

97071.5

Theoretical pI

8.27

GO Classification

Functions

ATP binding / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / protein tyrosine kinase activity

Processes

chromosome separation / mitotic spindle assembly checkpoint / mitotic spindle organization / peptidyl-tyrosine phosphorylation / positive regulation of cell proliferation / positive regulation of pathway-restricted SMAD protein phosphorylation / spindle organization

Components

membrane / spindle

General Function

Protein tyrosine kinase activity

Specific Function

Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Not Available

Gene sequence

>lcl|BSEQ0017226|Dual specificity protein kinase TTK (TTK)
ATGGAATCCGAGGATTTAAGTGGCAGAGAATTGACAATTGATTCCATAATGAACAAAGTG
AGAGACATTAAAAATAAGTTTAAAAATGAAGACCTTACTGATGAACTAAGCTTGAATAAA
ATTTCTGCTGATACTACAGATAACTCGGGAACTGTTAACCAAATTATGATGATGGCAAAC
AACCCAGAGGACTGGTTGAGTTTGTTGCTCAAACTAGAGAAAAACAGTGTTCCGCTAAGT
GATGCTCTTTTAAATAAATTGATTGGTCGTTACAGTCAAGCAATTGAAGCGCTTCCCCCA
GATAAATATGGCCAAAATGAGAGTTTTGCTAGAATTCAAGTGAGATTTGCTGAATTAAAA
GCTATTCAAGAGCCAGATGATGCACGTGACTACTTTCAAATGGCCAGAGCAAACTGCAAG
AAATTTGCTTTTGTTCATATATCTTTTGCACAATTTGAACTGTCACAAGGTAATGTCAAA
AAAAGTAAACAACTTCTTCAAAAAGCTGTAGAACGTGGAGCAGTACCACTAGAAATGCTG
GAAATTGCCCTGCGGAATTTAAACCTCCAAAAAAAGCAGCTGCTTTCAGAGGAGGAAAAG
AAGAATTTATCAGCATCTACGGTATTAACTGCCCAAGAATCATTTTCCGGTTCACTTGGG
CATTTACAGAATAGGAACAACAGTTGTGATTCCAGAGGACAGACTACTAAAGCCAGGTTT
TTATATGGAGAGAACATGCCACCACAAGATGCAGAAATAGGTTACCGGAATTCATTGAGA
CAAACTAACAAAACTAAACAGTCATGCCCATTTGGAAGAGTCCCAGTTAACCTTCTAAAT
AGCCCAGATTGTGATGTGAAGACAGATGATTCAGTTGTACCTTGTTTTATGAAAAGACAA
ACCTCTAGATCAGAATGCCGAGATTTGGTTGTGCCTGGATCTAAACCAAGTGGAAATGAT
TCCTGTGAATTAAGAAATTTAAAGTCTGTTCAAAATAGTCATTTCAAGGAACCTCTGGTG
TCAGATGAAAAGAGTTCTGAACTTATTATTACTGATTCAATAACCCTGAAGAATAAAACG
GAATCAAGTCTTCTAGCTAAATTAGAAGAAACTAAAGAGTATCAAGAACCAGAGGTTCCA
GAGAGTAACCAGAAACAGTGGCAATCTAAGAGAAAGTCAGAGTGTATTAACCAGAATCCT
GCTGCATCTTCAAATCACTGGCAGATTCCGGAGTTAGCCCGAAAAGTTAATACAGAGAAA
CATACCACTTTTGAGCAACCTGTCTTTTCAGTTTCAAAACAGTCACCACCAATATCAACA
TCTAAATGGTTTGACCCAAAATCTATTTGTAAGACACCAAGCAGCAATACCTTGGATGAT
TACATGAGCTGTTTTAGAACTCCAGTTGTAAAGAATGACTTTCCACCTGCTTGTCAGTTG
TCAACACCTTATGGCCAACCTGCCTGTTTCCAGCAGCAACAGCATCAAATACTTGCCACT
CCACTTCAAAATTTACAGGTTTTAGCATCTTCTTCAGCAAATGAATGCATTTCGGTTAAA
GGAAGAATTTATTCCATATTAAAGCAGATAGGAAGTGGAGGTTCAAGCAAGGTATTTCAG
GTGTTAAATGAAAAGAAACAGATATATGCTATAAAATATGTGAACTTAGAAGAAGCAGAT
AACCAAACTCTTGATAGTTACCGGAACGAAATAGCTTATTTGAATAAACTACAACAACAC
AGTGATAAGATCATCCGACTTTATGATTATGAAATCACGGACCAGTACATCTACATGGTA
ATGGAGTGTGGAAATATTGATCTTAATAGTTGGCTTAAAAAGAAAAAATCCATTGATCCA
TGGGAACGCAAGAGTTACTGGAAAAATATGTTAGAGGCAGTTCACACAATCCATCAACAT
GGCATTGTTCACAGTGATCTTAAACCAGCTAACTTTCTGATAGTTGATGGAATGCTAAAG
CTAATTGATTTTGGGATTGCAAACCAAATGCAACCAGATACAACAAGTGTTGTTAAAGAT
TCTCAGGTTGGCACAGTTAATTATATGCCACCAGAAGCAATCAAAGATATGTCTTCCTCC
AGAGAGAATGGGAAATCTAAGTCAAAGATAAGCCCCAAAAGTGATGTTTGGTCCTTAGGA
TGTATTTTGTACTATATGACTTACGGGAAAACACCATTTCAGCAGATAATTAATCAGATT
TCTAAATTACATGCCATAATTGATCCTAATCATGAAATTGAATTTCCCGATATTCCAGAG
AAAGATCTTCAAGATGTGTTAAAGTGTTGTTTAAAAAGGGACCCAAAACAGAGGATATCC
ATTCCTGAGCTCCTGGCTCATCCATATGTTCAAATTCAAACTCATCCAGTTAACCAAATG
GCCAAGGGAACCACTGAAGAAATGAAATATGTTCTGGGCCAACTTGTTGGTCTGAATTCT
CCTAACTCCATTTTGAAAGCTGCTAAAACTTTATATGAACACTATAGTGGTGGTGAAAGT
CATAATTCTTCATCCTCCAAGACTTTTGAAAAAAAAAGGGGAAAAAAATGA

Chromosome Location

6

Locus

6q13-q21

External Identifiers

Resource	Link
UniProtKB ID	P33981
UniProtKB Entry Name	TTK_HUMAN
GenBank Protein ID	340011
GenBank Gene ID	M86699
HGNC ID	HGNC:12401

General References

1. Mills GB, Schmandt R, McGill M, Amendola A, Hill M, Jacobs K, May C, Rodricks AM, Campbell S, Hogg D: Expression of TTK, a novel human protein kinase, is associated with cell proliferation. J Biol Chem. 1992 Aug 5;267(22):16000-6. [Article]
2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
3. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
4. 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. [Article]
5. Lindberg RA, Fischer WH, Hunter T: Characterization of a human protein threonine kinase isolated by screening an expression library with antibodies to phosphotyrosine. Oncogene. 1993 Feb;8(2):351-9. [Article]
6. Hanks SK, Quinn AM: Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. Methods Enzymol. 1991;200:38-62. [Article]
7. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [Article]
8. Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ: Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. [Article]
9. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
10. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
11. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
12. Lince-Faria M, Maffini S, Orr B, Ding Y, Claudia Florindo, Sunkel CE, Tavares A, Johansen J, Johansen KM, Maiato H: Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J Cell Biol. 2009 Mar 9;184(5):647-57. doi: 10.1083/jcb.200811012. [Article]
13. 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. [Article]
14. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
15. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
17. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
18. Chu ML, Chavas LM, Douglas KT, Eyers PA, Tabernero L: Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125. J Biol Chem. 2008 Aug 1;283(31):21495-500. doi: 10.1074/jbc.M803026200. Epub 2008 May 14. [Article]
19. Wang W, Yang Y, Gao Y, Xu Q, Wang F, Zhu S, Old W, Resing K, Ahn N, Lei M, Liu X: Structural and mechanistic insights into Mps1 kinase activation. J Cell Mol Med. 2009 Aug;13(8B):1679-94. doi: 10.1111/j.1582-4934.2008.00605.x. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB01782	Pyrazolanthrone	experimental	unknown		Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details
DB15498	BOS172722	experimental	yes	inhibitor	Details