TLK2

TLK2
Identifiers
Aliases	TLK2 , HsHPK, PKU-ALPHA, tousled like kinase 2, MRD57
External IDs	OMIM: 608439; MGI: 1346023; HomoloGene: 4993; GeneCards: TLK2; OMA:TLK2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q23.2 Start 62,458,658 bp [1] End 62,615,481 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 E1 Start 105,069,633 bp [2] End 105,174,785 bp [2]
RNA expression pattern Bgee Human Mouse (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 Species Human Mouse 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 Mb Chr 11: 105.07 – 105.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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. GRCh38: Ensembl release 89: ENSG00000146872 – Ensembl, May 2017
2. 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, et al. (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. 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. "Entrez Gene: TLK2 tousled-like kinase 2".
8. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (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. 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. Bibcode:2001CBio...11.1068S. doi: 10.1016/S0960-9822(01)00298-6 . PMID   11470414. S2CID   8866062.
10. Reijnders MR, Miller KA, Alvi M, Goos JA, Lees MM, de Burca A, et al. (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 (September 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 (August 1999). "Nuclear localization of protein kinase U-alpha is regulated by 14-3-3". The Journal of Biological Chemistry. 274 (35): 24865–24872. doi: 10.1074/jbc.274.35.24865 . PMID   10455159.
• Silljé HH, Nigg EA (July 2001). "Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases". Current Biology. 11 (13): 1068–1073. Bibcode:2001CBio...11.1068S. doi: 10.1016/S0960-9822(01)00298-6 . PMID   11470414. S2CID   8866062.
• Groth A, Lukas J, Nigg EA, Silljé HH, Wernstedt C, Bartek J, et al. (April 2003). "Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint". The EMBO Journal. 22 (7): 1676–1687. doi:10.1093/emboj/cdg151. PMC   152895 . PMID   12660173.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi: 10.1073/pnas.0404720101 . PMC   514446 . PMID   15302935.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (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.