Serine/threonine-protein kinase tousled-like 2

Details

Name

Serine/threonine-protein kinase tousled-like 2

Synonyms

• 2.7.11.1
• HsHPK
• PKU-alpha
• Tousled-like kinase 2

Gene Name

TLK2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051674|Serine/threonine-protein kinase tousled-like 2
MMEELHSLDPRRQELLEARFTGVGVSKGPLNSESSNQSLCSVGSLSDKEVETPEKKQNDQ
RNRKRKAEPYETSQGKGTPRGHKISDYFEFAGGSAPGTSPGRSVPPVARSSPQHSLSNPL
PRRVEQPLYGLDGSAAKEATEEQSALPTLMSVMLAKPRLDTEQLAQRGAGLCFTFVSAQQ
NSPSSTGSGNTEHSCSSQKQISIQHRQTQSDLTIEKISALENSKNSDLEKKEGRIDDLLR
ANCDLRRQIDEQQKMLEKYKERLNRCVTMSKKLLIEKSKQEKMACRDKSMQDRLRLGHFT
TVRHGASFTEQWTDGYAFQNLIKQQERINSQREEIERQRKMLAKRKPPAMGQAPPATNEQ
KQRKSKTNGAENETPSSGNTELKDTAPALGAHSLLRLTLAEYHEQEEIFKLRLGHLKKEE
AEIQAELERLERVRNLHIRELKRIHNEDNSQFKDHPTLNDRYLLLHLLGRGGFSEVYKAF
DLTEQRYVAVKIHQLNKNWRDEKKENYHKHACREYRIHKELDHPRIVKLYDYFSLDTDSF
CTVLEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKPPIIHYDLKPGNILL
VNGTACGEIKITDFGLSKIMDDDSYNSVDGMELTSQGAGTYWYLPPECFVVGKEPPKISN
KVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQENTILKATEVQFPPKPVVTPEAKAFIRR
CLAYRKEDRIDVQQLACDPYLLPHIRKSVSTSSPAGAAIASTSGASNNSSSN

Number of residues

772

Molecular Weight

87660.305

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / protein serine/threonine kinase activity

Processes

cell cycle / cellular response to DNA damage stimulus / cellular response to gamma radiation / chromatin organization / chromosome segregation / intracellular signal transduction / negative regulation of autophagy / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / peptidyl-serine phosphorylation / protein phosphorylation / regulation of chromatin assembly or disassembly

Components

intermediate filament / nucleus / perinuclear region of cytoplasm

General Function

Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. Negative regulator of amino acid starvation-induced autophagy.

Specific Function

Atp binding

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0051675|Serine/threonine-protein kinase tousled-like 2 (TLK2)
ATGATGGAAGAATTGCATAGCCTGGACCCACGACGGCAGGAATTATTGGAGGCCAGGTTT
ACTGGAGTAGGTGTTAGTAAGGGACCACTTAATAGTGAGTCTTCCAACCAGAGCTTGTGC
AGCGTCGGATCCTTGAGTGATAAAGAAGTAGAGACTCCCGAGAAAAAGCAGAATGACCAG
CGAAATCGGAAAAGAAAAGCTGAACCATATGAAACTAGCCAAGGGAAAGGCACTCCTAGG
GGACATAAAATTAGTGATTACTTTGAGTTTGCTGGGGGAAGCGCGCCAGGAACCAGCCCT
GGCAGAAGTGTTCCACCAGTTGCACGATCCTCACCGCAACATTCCTTATCCAATCCCTTA
CCGCGACGAGTAGAACAGCCCCTCTATGGTTTAGATGGCAGTGCTGCAAAGGAGGCAACG
GAGGAGCAGTCTGCTCTGCCAACCCTCATGTCAGTGATGCTAGCAAAACCTCGGCTTGAC
ACAGAGCAGCTGGCGCAAAGGGGAGCTGGCCTCTGCTTCACTTTTGTTTCAGCTCAGCAA
AACAGTCCCTCATCTACGGGATCTGGCAACACAGAGCATTCCTGCAGCTCCCAAAAACAG
ATCTCCATCCAGCACAGACAGACCCAGTCCGACCTCACAATAGAAAAAATATCTGCACTA
GAAAACAGTAAGAATTCTGACTTAGAGAAGAAGGAGGGAAGAATAGATGATTTATTAAGA
GCCAACTGTGATTTGAGACGGCAGATTGATGAACAGCAAAAGATGCTAGAGAAATACAAG
GAACGATTAAATAGATGTGTGACAATGAGCAAGAAACTCCTTATAGAAAAGTCAAAACAA
GAGAAGATGGCGTGTAGAGATAAGAGCATGCAAGACCGCTTGAGACTGGGCCACTTTACT
ACTGTCCGACACGGAGCCTCATTTACTGAACAGTGGACAGATGGTTATGCTTTTCAGAAT
CTTATCAAGCAACAGGAAAGGATAAATTCACAGAGGGAAGAGATAGAAAGACAACGGAAA
ATGTTAGCAAAGCGGAAACCTCCTGCCATGGGTCAGGCCCCTCCTGCAACCAATGAGCAG
AAACAGCGGAAAAGCAAGACCAATGGAGCTGAAAATGAAACGCCCTCTTCTGGGAATACA
GAGCTAAAGGATACAGCCCCAGCCTTAGGAGCCCACAGTTTACTTAGGTTAACGTTAGCA
GAATACCATGAACAAGAAGAAATCTTCAAACTCAGATTAGGTCATCTTAAAAAGGAGGAA
GCAGAGATCCAGGCAGAGCTGGAGAGACTAGAAAGGGTTAGAAATCTACATATCAGGGAA
CTAAAAAGGATACATAATGAAGATAATTCACAATTTAAAGATCATCCAACGCTAAATGAC
AGATATTTGTTGTTACATCTTTTGGGTAGAGGAGGTTTCAGTGAAGTTTACAAGGCATTT
GATCTAACAGAGCAAAGATACGTAGCTGTGAAAATTCACCAGTTAAATAAAAACTGGAGA
GATGAGAAAAAGGAGAATTACCACAAGCATGCATGTAGGGAATACCGGATTCATAAAGAG
CTGGATCATCCCAGAATAGTTAAGCTGTATGATTACTTTTCACTGGATACTGACTCGTTT
TGTACAGTATTAGAATACTGTGAGGGAAATGATCTGGACTTCTACCTGAAACAGCACAAA
TTAATGTCGGAGAAAGAGGCCCGGTCCATTATCATGCAGATTGTGAATGCTTTAAAGTAC
TTAAATGAAATAAAACCTCCCATCATACACTATGACCTCAAACCAGGTAATATTCTTTTA
GTAAATGGTACAGCGTGTGGAGAGATAAAAATTACAGATTTTGGTCTTTCGAAGATCATG
GATGATGATAGCTACAATTCAGTGGATGGCATGGAGCTAACATCACAAGGTGCTGGTACT
TATTGGTATTTACCACCAGAGTGTTTTGTGGTTGGGAAAGAACCACCAAAGATCTCAAAT
AAAGTTGATGTGTGGTCGGTGGGTGTGATCTTCTATCAGTGTCTTTATGGAAGGAAGCCT
TTTGGCCATAACCAGTCTCAGCAAGACATCCTACAAGAGAATACGATTCTTAAAGCTACT
GAAGTGCAGTTCCCGCCAAAGCCAGTAGTAACACCTGAAGCAAAGGCGTTTATTCGACGA
TGCTTGGCCTACCGAAAGGAGGACCGCATTGATGTCCAGCAGCTGGCCTGTGATCCCTAC
TTGTTGCCTCACATCCGAAAGTCAGTCTCTACAAGTAGCCCTGCTGGAGCTGCTATTGCA
TCAACCTCTGGGGCGTCCAATAACAGTTCTTCTAATTGA

Chromosome Location

17

Locus

17q23.2

External Identifiers

Resource	Link
UniProtKB ID	Q86UE8
UniProtKB Entry Name	TLK2_HUMAN
HGNC ID	HGNC:11842

General References

1. Yamakawa A, Kameoka Y, Hashimoto K, Yoshitake Y, Nishikawa K, Tanihara K, Date T: cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal. Gene. 1997 Nov 20;202(1-2):193-201. [Article]
2. Sillje HH, Takahashi K, Tanaka K, Van Houwe G, Nigg EA: Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated kinases with maximal activities linked to ongoing DNA replication. EMBO J. 1999 Oct 15;18(20):5691-702. [Article]
3. 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]
4. Huang AM, Chang TJ, Cho WL, Chou CK: From mosquito to man: identification of a novel protein kinase, HsHPK, which is highly expressed in human hepatoma tissues. J Biomed Sci. 1998;5(2):135-40. [Article]
5. Zhang S, Xing H, Muslin AJ: Nuclear localization of protein kinase U-alpha is regulated by 14-3-3. J Biol Chem. 1999 Aug 27;274(35):24865-72. [Article]
6. Sillje HH, Nigg EA: Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases. Curr Biol. 2001 Jul 10;11(13):1068-73. [Article]
7. Groth A, Lukas J, Nigg EA, Sillje HH, Wernstedt C, Bartek J, Hansen K: Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint. EMBO J. 2003 Apr 1;22(7):1676-87. [Article]
8. Krause DR, Jonnalagadda JC, Gatei MH, Sillje HH, Zhou BB, Nigg EA, Khanna K: Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1. Oncogene. 2003 Sep 4;22(38):5927-37. [Article]
9. Assmann EM, Alborghetti MR, Camargo ME, Kobarg J: FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region. J Biol Chem. 2006 Apr 14;281(15):9869-81. Epub 2006 Feb 16. [Article]
10. 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]
11. 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]
12. 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]
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. Pilyugin M, Demmers J, Verrijzer CP, Karch F, Moshkin YM: Phosphorylation-mediated control of histone chaperone ASF1 levels by Tousled-like kinases. PLoS One. 2009 Dec 16;4(12):e8328. doi: 10.1371/journal.pone.0008328. [Article]
15. 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]
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. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
18. McKnight NC, Jefferies HB, Alemu EA, Saunders RE, Howell M, Johansen T, Tooze SA: Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J. 2012 Apr 18;31(8):1931-46. doi: 10.1038/emboj.2012.36. Epub 2012 Feb 21. [Article]
19. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
20. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
21. 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. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details