# TLK2

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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
'''Serine/threonine-protein kinase tousled-like 2''' is an [enzyme](/source/enzyme) that in humans is encoded by the ''TLK2'' [gene](/source/gene).<ref name="pmid9427565">{{cite journal | vauthors = Yamakawa A, Kameoka Y, Hashimoto K, Yoshitake Y, Nishikawa K, Tanihara K, Date T | title = cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal | journal = Gene | volume = 202 | issue = 1–2 | pages = 193–201 | date = Nov 1997 | pmid = 9427565 | doi = 10.1016/S0378-1119(97)00495-2 }}</ref><ref name="pmid10523312">{{cite journal | vauthors = Silljé HH, Takahashi K, Tanaka K, Van Houwe G, Nigg EA | title = Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated kinases with maximal activities linked to ongoing DNA replication | journal = The EMBO Journal | volume = 18 | issue = 20 | pages = 5691–702 | date = Oct 1999 | pmid = 10523312 | pmc = 1171636 | doi = 10.1093/emboj/18.20.5691 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TLK2 tousled-like kinase 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=11011}}</ref>

== Function ==

The Tousled-like kinases, first described in [Arabidopsis](/source/Arabidopsis), are nuclear [serine/threonine kinases](/source/Serine%2Fthreonine-specific_protein_kinase) that are potentially involved in the regulation of [chromatin](/source/chromatin) assembly. These are different from other "tousled" varieties, such as flock-of-seagulls, post-coitus, or the-Sean-Bean.[supplied by OMIM]<ref name="entrez" />

== Interactions ==

TLK2 has been shown to [interact](/source/Protein-protein_interaction) with [TLK1](/source/TLK1),<ref name=pmid10523312 /> [ASF1B](/source/ASF1B)<ref name=pmid17353931>{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}</ref><ref name=pmid11470414>{{cite journal | vauthors = Silljé HH, Nigg EA | title = Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases | journal = Current Biology | volume = 11 | issue = 13 | pages = 1068–73 | date = Jul 2001 | pmid = 11470414 | doi = 10.1016/S0960-9822(01)00298-6 | s2cid = 8866062 | doi-access = free | bibcode = 2001CBio...11.1068S }}</ref> and [ASF1A](/source/ASF1A).<ref name=pmid11470414/>

==Clinical significance ==
Mutations in this gene have been linked to a specific form of [autism spectrum disorder](/source/autism_spectrum_disorder) with unique facial features.<ref name="ReijndersMiller2018">{{cite journal| vauthors = Reijnders MR, Miller KA, Alvi M, Goos JA, Lees MM, de Burca A, Henderson A, Kraus A, Mikat B, de Vries BB, Isidor B, Kerr B, Marcelis C, Schluth-Bolard C, Deshpande C, Ruivenkamp CA, Wieczorek D, Baralle D, Blair EM, Engels H, Lüdecke HJ, Eason J, Santen GW, Clayton-Smith J, Chandler K, Tatton-Brown K, Payne K, Helbig K, Radtke K, Nugent KM, Cremer K, Strom TM, Bird LM, Sinnema M, Bitner-Glindzicz M, van Dooren MF, Alders M, Koopmans M, Brick L, Kozenko M, Harline ML, Klaassens M, Steinraths M, Cooper NS, Edery P, Yap P, Terhal PA, van der Spek PJ, Lakeman P, Taylor RL, Littlejohn RO, Pfundt R, Mercimek-Andrews S, Stegmann AP, Kant SG, McLean S, Joss S, Swagemakers SM, Douzgou S, Wall SA, Küry S, Calpena E, Koelling N, McGowan SJ, Twigg SR, Mathijssen IM, Nellaker C, Brunner HG, Wilkie AO |title=De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder|journal=The American Journal of Human Genetics|volume=102|issue=6|year=2018|pages=1195–1203|issn=0002-9297|doi=10.1016/j.ajhg.2018.04.014|pmid=29861108|pmc=5992133}}</ref> Amplifications of the nuclear localization sequence-encoding part of this gene have been linked to [glioblastoma](/source/glioblastoma) and lower-grade [astrocytoma](/source/astrocytoma) survival.<ref name=pmid32478280>{{cite journal | author1= Ponnapalli S.P., et int. |author2=Alter O. | title = Retrospective clinical trial experimentally validates glioblastoma genome-wide pattern of DNA copy-number alterations predictor of survival | journal = APL Bioengineering | volume = 4 | issue = 2 | pages = 026106 | date = May 2020 | pmid = 32478280 | doi = 10.1063/1.5142559 |pmc=7229984 | doi-access = free }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
* {{cite journal | vauthors = Zhang S, Xing H, Muslin AJ | title = Nuclear localization of protein kinase U-alpha is regulated by 14-3-3 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 35 | pages = 24865–24872 | date = August 1999 | pmid = 10455159 | doi = 10.1074/jbc.274.35.24865 | doi-access = free }}
* {{cite journal | vauthors = Silljé HH, Nigg EA | title = Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases | journal = Current Biology | volume = 11 | issue = 13 | pages = 1068–1073 | date = July 2001 | pmid = 11470414 | doi = 10.1016/S0960-9822(01)00298-6 | s2cid = 8866062 | doi-access = free | bibcode = 2001CBio...11.1068S }}
* {{cite journal | vauthors = Groth A, Lukas J, Nigg EA, Silljé HH, Wernstedt C, Bartek J, Hansen K | title = Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint | journal = The EMBO Journal | volume = 22 | issue = 7 | pages = 1676–1687 | date = April 2003 | pmid = 12660173 | pmc = 152895 | doi = 10.1093/emboj/cdg151 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–12135 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | doi-access = free | bibcode = 2004PNAS..10112130B }}
* {{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}
{{Refend}}

{{Gene-17-stub}}

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Adapted from the Wikipedia article [TLK2](https://en.wikipedia.org/wiki/TLK2) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/TLK2?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.
