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)
End	62,615,481 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	105,174,785 bp
RNA expression pattern
	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
	; ;
	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
	11011
	24086
	ENSG00000146872
	ENSMUSG00000020694
	Q86UE8
	O55047
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
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
	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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000146872 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020694 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^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.
^ ^a ^b "Entrez Gene: TLK2 tousled-like kinase 2".
^ 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.
^ ^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. Bibcode:2001CBio...11.1068S. doi:10.1016/S0960-9822(01)00298-6. PMID 11470414. S2CID 8866062.
^ 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.
^ 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.

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.

This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000146872 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9427565-5] 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.

[pmid10523312-6] 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.

[entrez-7] "Entrez Gene: TLK2 tousled-like kinase 2".

[pmid17353931-8] 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.

[pmid11470414-9] 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.

[ReijndersMiller2018-10] 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.

[pmid32478280-11] 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.

[1]

Function

Interactions

Clinical significance

References

Further reading