TLK2

Protein-coding gene in the species Homo sapiens
TLK2
Identifiers
AliasesTLK2, HsHPK, PKU-ALPHA, tousled like kinase 2, MRD57
External IDsOMIM: 608439; MGI: 1346023; HomoloGene: 4993; GeneCards: TLK2; OMA:TLK2 - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for TLK2
Genomic location for TLK2
Band17q23.2Start62,458,658 bp[1]
End62,615,481 bp[1]
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)[2]
Chromosome 11 (mouse)
Genomic location for TLK2
Genomic location for TLK2
Band11|11 E1Start105,069,633 bp[2]
End105,174,785 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • Achilles tendon

  • sural nerve

  • epithelium of colon

  • bone marrow cells

  • ventricular zone

  • gonad

  • ganglionic eminence

  • left testis

  • right testis

  • stromal cell of endometrium
Top expressed in
  • genital tubercle

  • tail of embryo

  • spermatocyte

  • neural layer of retina

  • zygote

  • secondary oocyte

  • seminiferous tubule

  • spermatid

  • ureter

  • ventricular zone
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • transferase activity
  • nucleotide binding
  • protein kinase activity
  • kinase activity
  • protein serine/threonine kinase activity
  • protein binding
  • ATP binding
Cellular component
  • cytoplasm
  • perinuclear region of cytoplasm
  • cytoskeleton
  • intermediate filament
  • nucleus
Biological process
  • intracellular signal transduction
  • phosphorylation
  • chromosome segregation
  • cellular response to DNA damage stimulus
  • protein phosphorylation
  • peptidyl-serine phosphorylation
  • cellular response to gamma radiation
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process
  • cell cycle
  • negative regulation of autophagy
  • chromatin organization
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

11011

24086

Ensembl

ENSG00000146872

ENSMUSG00000020694

UniProt

Q86UE8

O55047

RefSeq (mRNA)
NM_001112707
NM_001284333
NM_001284363
NM_006852
NM_001330418

NM_001375269
NM_001375270
NM_001375271
NM_001375272
NM_001375273

NM_001112705
NM_001294329
NM_001294330
NM_001294331
NM_001294334

NM_011903
NM_001361996

RefSeq (protein)
NP_001271262
NP_001271292
NP_001317347
NP_006843
NP_001362198

NP_001362199
NP_001362200
NP_001362201
NP_001362202

NP_001106176
NP_001281258
NP_001281259
NP_001281260
NP_001281263

NP_001348925

Location (UCSC)Chr 17: 62.46 – 62.62 MbChr 11: 105.07 – 105.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Serine/threonine-protein kinase tousled-like 2 is an enzyme that in humans is encoded by the TLK2 gene.[5][6][7]

Function

The Tousled-like kinases, first described in Arabidopsis, are nuclear serine/threonine kinases that are potentially involved in the regulation of chromatin assembly. These are different from other "tousled" varieties, such as flock-of-seagulls, post-coitus, or the-Sean-Bean.[supplied by OMIM][7]

Interactions

TLK2 has been shown to interact with TLK1,[6] ASF1B[8][9] and ASF1A.[9]

Clinical significance

Mutations in this gene have been linked to a specific form of autism spectrum disorder with unique facial features.[10] Amplifications of the nuclear localization sequence-encoding part of this gene have been linked to glioblastoma and lower-grade astrocytoma survival.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146872 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020694 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Yamakawa A, Kameoka Y, Hashimoto K, Yoshitake Y, Nishikawa K, Tanihara K, Date T (Nov 1997). "cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal". Gene. 202 (1–2): 193–201. doi:10.1016/S0378-1119(97)00495-2. PMID 9427565.
  6. ^ a b Silljé HH, Takahashi K, Tanaka K, Van Houwe G, Nigg EA (Oct 1999). "Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated kinases with maximal activities linked to ongoing DNA replication". The EMBO Journal. 18 (20): 5691–702. doi:10.1093/emboj/18.20.5691. PMC 1171636. PMID 10523312.
  7. ^ a b "Entrez Gene: TLK2 tousled-like kinase 2".
  8. ^ 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  9. ^ a b Silljé HH, Nigg EA (Jul 2001). "Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases". Current Biology. 11 (13): 1068–73. doi:10.1016/S0960-9822(01)00298-6. PMID 11470414. S2CID 8866062.
  10. ^ Reijnders, Margot R.F.; Miller, Kerry A.; Alvi, Mohsan; Goos, Jacqueline A.C.; Lees, Melissa M.; de Burca, Anna; Henderson, Alex; Kraus, Alison; Mikat, Barbara; de Vries, Bert B.A.; Isidor, Bertrand; Kerr, Bronwyn; Marcelis, Carlo; Schluth-Bolard, Caroline; Deshpande, Charu; Ruivenkamp, Claudia A.L.; Wieczorek, Dagmar; Baralle, Diana; Blair, Edward M.; Engels, Hartmut; Lüdecke, Hermann-Josef; Eason, Jacqueline; Santen, Gijs W.E.; Clayton-Smith, Jill; Chandler, Kate; Tatton-Brown, Katrina; Payne, Katelyn; Helbig, Katherine; Radtke, Kelly; Nugent, Kimberly M.; Cremer, Kirsten; Strom, Tim M.; Bird, Lynne M.; Sinnema, Margje; Bitner-Glindzicz, Maria; van Dooren, Marieke F.; Alders, Marielle; Koopmans, Marije; Brick, Lauren; Kozenko, Mariya; Harline, Megan L.; Klaassens, Merel; Steinraths, Michelle; Cooper, Nicola S.; Edery, Patrick; Yap, Patrick; Terhal, Paulien A.; van der Spek, Peter J.; Lakeman, Phillis; Taylor, Rachel L.; Littlejohn, Rebecca O.; Pfundt, Rolph; Mercimek-Andrews, Saadet; Stegmann, Alexander P.A.; Kant, Sarina G.; McLean, Scott; Joss, Shelagh; Swagemakers, Sigrid M.A.; Douzgou, Sofia; Wall, Steven A.; Küry, Sébastien; Calpena, Eduardo; Koelling, Nils; McGowan, Simon J.; Twigg, Stephen R.F.; Mathijssen, Irene M.J.; Nellaker, Christoffer; Brunner, Han G.; Wilkie, Andrew O.M. (2018). "De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder". The American Journal of Human Genetics. 102 (6): 1195–1203. doi:10.1016/j.ajhg.2018.04.014. ISSN 0002-9297. PMC 5992133. PMID 29861108.
  11. ^ Ponnapalli S.P., et int.; Alter O. (May 2020). "Retrospective clinical trial experimentally validates glioblastoma genome-wide pattern of DNA copy-number alterations predictor of survival". APL Bioengineering. 4 (2): 026106. doi:10.1063/1.5142559. PMC 7229984. PMID 32478280.

Further reading

  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Zhang S, Xing H, Muslin AJ (Aug 1999). "Nuclear localization of protein kinase U-alpha is regulated by 14-3-3". The Journal of Biological Chemistry. 274 (35): 24865–72. doi:10.1074/jbc.274.35.24865. PMID 10455159.
  • Silljé HH, Nigg EA (Jul 2001). "Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases". Current Biology. 11 (13): 1068–73. doi:10.1016/S0960-9822(01)00298-6. PMID 11470414. S2CID 8866062.
  • Groth A, Lukas J, Nigg EA, Silljé HH, Wernstedt C, Bartek J, Hansen K (Apr 2003). "Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint". The EMBO Journal. 22 (7): 1676–87. doi:10.1093/emboj/cdg151. PMC 152895. PMID 12660173.
  • Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
  • 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
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