DYRK1A involvement regarding cell proliferation in brain development (WP5180)
Homo sapiens
DYRK1A (Dual-specificity tyrosine phosphorylation-regulated kinase 1A)(OMIM 600855) is a kinase whose gene is located at 21q22.13 and is highly conserved.It is composed of a nuclear targeting sequence, a protein kinase domain, a leucine zipper motif and a 13-consecutive-histidine repeat. The gene is located in the so-called "Down syndrome critical region" (DSCR), a region on chromosome 21 thought responsible for most phenotypic manifestations of Down syndrome. DYRK1A is involved in signaling pathways regulating cell proliferation in brain development. Amongst others, haploinsufficiency of DYRK1A, DYRK1A overexpression and interactions with alpha-synuclein are thought to be the main factors for the clinical phenotype.
Authors
Veerle Horsting , Pierre Klemmer , Alex Pico , Lars Willighagen , Denise Slenter , Egon Willighagen , and Daniela DiglesActivity
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
intellectual disability Down syndrome Lewy body dementia Parkinson's disease Alzheimer's disease microcephalyPathway Ontology
signaling pathway pertinent to the brain and nervous system| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Etoposide | Metabolite | hmdb:HMDB14911 | |
| NCSTN | GeneProduct | ensembl:ENSG00000162736 | |
| PSEN1 | GeneProduct | ensembl:ENSG00000080815 | |
| PSENEN | GeneProduct | ensembl:ENSG00000205155 | |
| EIF2B5 | GeneProduct | ensembl:ENSG00000145191 | |
| APH1A | GeneProduct | ensembl:ENSG00000117362 | identifier is for the c. elegans homolog of this gene |
| CREB1 | GeneProduct | ensembl:ENSG00000118260 | |
| Cyclin-dependent kinase 6 | GeneProduct | ensembl:ENSG00000105810 | |
| AMPH | GeneProduct | ensembl:ENSG00000078053 | |
| CASP3 | GeneProduct | ensembl:ENSG00000164305 | |
| FOXO1 | GeneProduct | ensembl:ENSG00000150907 | |
| SMARCB1 | GeneProduct | ensembl:ENSG00000099956 | Human ortholog of drosophila melanogaster SNR1 gene, which is described in the literature |
| CDK4 protein | GeneProduct | ensembl:ENSG00000135446 | |
| FGF2 | GeneProduct | ensembl:ENSG00000138685 | |
| LATS2 | GeneProduct | ensembl:ENSG00000150457 | |
| BACE1 | GeneProduct | ensembl:ENSG00000186318 | |
| HIP1 | GeneProduct | ensembl:ENSG00000127946 | |
| REST | GeneProduct | ensembl:ENSG00000084093 | |
| DNM1 | GeneProduct | ensembl:ENSG00000106976 | |
| CREB1 | GeneProduct | ensembl:ENSG00000118260 | |
| AMPH | GeneProduct | ensembl:ENSG00000078053 | |
| LIN52 | GeneProduct | ensembl:ENSG00000205659 | |
| Dual-specificity tyrosine phosphorylation regulated kinase 1A | GeneProduct | ensembl:ENSG00000157540 | |
| ARIP4 | GeneProduct | ensembl:ENSG00000164080 | |
| GSK3B | GeneProduct | ensembl:ENSG00000082701 | idk if this is right |
| Casein kinase 1 alpha 1 | GeneProduct | ensembl:ENSG00000113712 | lacks reference; which casein kinase is it specifically? |
| MTOR | GeneProduct | ensembl:ENSG00000198793 | |
| MLST8 | GeneProduct | ensembl:ENSG00000167965 | |
| Zinc finger protein GLI1 | GeneProduct | ensembl:ENSG00000111087 | |
| TSC1 | GeneProduct | ensembl:ENSG00000165699 | |
| AKT1S1 | GeneProduct | ensembl:ENSG00000204673 | |
| RPTOR | GeneProduct | ensembl:ENSG00000141564 | |
| GLI1 | GeneProduct | ensembl:ENSG00000111087 | |
| TSC2 | GeneProduct | ensembl:ENSG00000103197 | |
| DCAF7 | GeneProduct | ensembl:ENSG00000136485 | DCAF7 = AN11 = HAN11 = WDR68binding of DYRK1A to DCAF7 leads to DCAF7 migrating into cell nucleus, where it might induce aberrant gene expresion = could be part of mechanism that induces Down syndrome phenotypes |
| DEPTOR | GeneProduct | ensembl:ENSG00000155792 | |
| CDKN1B | GeneProduct | ensembl:ENSG00000111276 | =p27Kip1 Promotes exit of cell cylce; prevents progression through G1 checkpoint; Earlier differentiation |
| DLL1 | GeneProduct | ensembl:ENSG00000198719 | |
| DLL1 | GeneProduct | ensembl:ENSG00000198719 | |
| HES5 | GeneProduct | ensembl:ENSG00000197921 | |
| HES1 | GeneProduct | ensembl:ENSG00000114315 | |
| NEUROG2 | GeneProduct | ensembl:ENSG00000178403 | |
| CASP9 | GeneProduct | ensembl:ENSG00000132906 | |
| CDKN1B | GeneProduct | ensembl:ENSG00000111276 | =p27Kip1 Promotes exit of cell cylce; prevents progression through G1 checkpoint; Earlier differentiation |
| CRY2 | GeneProduct | ensembl:ENSG00000121671 | |
| SPRY2 | GeneProduct | ensembl:ENSG00000136158 | |
| Delta and Notch-like epidermal growth factor-related receptor | GeneProduct | ensembl:ENSG00000187957 | |
| CCND1 | GeneProduct | ensembl:ENSG00000110092 | Cyclin D1 |
| NAD-dependent protein deacetylase sirtuin-1 | GeneProduct | ensembl:ENSG00000096717 | Not humans |
| Amyloid-beta precursor protein | GeneProduct | ensembl:ENSG00000142192 | Located on chromosome 21 |
| TFAP4 | GeneProduct | ensembl:ENSG00000090447 | |
| Dual-specificity tyrosine phosphorylation regulated kinase 1A | GeneProduct | ensembl:ENSG00000157540 | |
| H3-3A | GeneProduct | ensembl:ENSG00000163041 | |
| TP53 | GeneProduct | ensembl:ENSG00000141510 | Not humans |
| NOTCH1 | GeneProduct | ensembl:ENSG00000148400 | |
| NFATC1 | GeneProduct | ensembl:ENSG00000131196 | idk if this is right |
| GMNN | GeneProduct | ensembl:ENSG00000112312 | |
| DLL1 | GeneProduct | ensembl:ENSG00000198719 | |
| TSC1 | GeneProduct | ensembl:ENSG00000165699 | |
| TSC2 | GeneProduct | ensembl:ENSG00000103197 | |
| GSK3B | GeneProduct | ensembl:ENSG00000082701 | idk if this is right |
| CRY2 | GeneProduct | ensembl:ENSG00000121671 | |
| CASP9 | GeneProduct | ensembl:ENSG00000132906 | |
| NFATC1 | GeneProduct | ensembl:ENSG00000131196 | idk if this is right |
| Microtubule-associated protein tau | GeneProduct | ensembl:ENSG00000186868 | |
| Microtubule-associated protein tau | GeneProduct | ensembl:ENSG00000186868 | |
| Amyloid-beta precursor protein | GeneProduct | ensembl:ENSG00000142192 | Located on chromosome 21 |
| H3-3A | GeneProduct | ensembl:ENSG00000163041 | maybe needs to be phosphorylated? |
| DNM1 | GeneProduct | ensembl:ENSG00000106976 | |
| FOXO1 | GeneProduct | ensembl:ENSG00000150907 | |
| HIP1 | GeneProduct | ensembl:ENSG00000127946 | |
| SMARCB1 | GeneProduct | ensembl:ENSG00000099956 | Human ortholog of drosophila melanogaster SNR1 gene, which is described in the literature |
| REST | GeneProduct | ensembl:ENSG00000084093 | |
| RBL1 | GeneProduct | ensembl:ENSG00000080839 | |
| RBL2 | GeneProduct | ensembl:ENSG00000103479 | |
| E2F4 | GeneProduct | ensembl:ENSG00000205250 | |
| Transcription factor Dp-2 | GeneProduct | ensembl:ENSG00000114126 | |
| E2F5 | GeneProduct | ensembl:ENSG00000133740 | |
| Transcription factor Dp family member 3 | GeneProduct | ensembl:ENSG00000183434 | |
| Transcription factor Dp-1 | GeneProduct | ensembl:ENSG00000198176 | |
| RBBP4 | GeneProduct | ensembl:ENSG00000162521 | |
| LIN9 | GeneProduct | ensembl:ENSG00000183814 | |
| LIN37 | GeneProduct | ensembl:ENSG00000267796 | |
| LIN54 | GeneProduct | ensembl:ENSG00000189308 | |
| LIN52 | GeneProduct | ensembl:ENSG00000205659 | |
| EIF2B5 | GeneProduct | ensembl:ENSG00000145191 |
References
- The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site. Woods YL, Rena G, Morrice N, Barthel A, Becker W, Guo S, et al. Biochem J. 2001 May 1;355(Pt 3):597–607. PubMed Europe PMC Scholia
- Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells. Yang EJ, Ahn YS, Chung KC. J Biol Chem. 2001 Oct 26;276(43):39819–24. PubMed Europe PMC Scholia
- Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1. Mao J, Maye P, Kogerman P, Tejedor FJ, Toftgard R, Xie W, et al. J Biol Chem. 2002 Sep 20;277(38):35156–61. PubMed Europe PMC Scholia
- Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases. Skurat AV, Dietrich AD. J Biol Chem. 2004 Jan 23;279(4):2490–8. PubMed Europe PMC Scholia
- Dyrk1A potentiates steroid hormone-induced transcription via the chromatin remodeling factor Arip4. Sitz JH, Tigges M, Baumgärtel K, Khaspekov LG, Lutz B. Mol Cell Biol. 2004 Jul;24(13):5821–34. PubMed Europe PMC Scholia
- Mnb/Dyrk1A phosphorylation regulates the interaction of dynamin 1 with SH3 domain-containing proteins. Huang Y, Chen-Hwang MC, Dolios G, Murakami N, Padovan JC, Wang R, et al. Biochemistry. 2004 Aug 10;43(31):10173–85. PubMed Europe PMC Scholia
- Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) interacts with the phytanoyl-CoA alpha-hydroxylase associated protein 1 (PAHX-AP1), a brain specific protein. Bescond M, Rahmani Z. Int J Biochem Cell Biol. 2005 Apr;37(4):775–83. PubMed Europe PMC Scholia
- Regulation of the proapoptotic activity of huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells. Kang JE, Choi SA, Park JB, Chung KC. J Neurosci Res. 2005 Jul 1;81(1):62–72. PubMed Europe PMC Scholia
- dDYRK2 and Minibrain interact with the chromatin remodelling factors SNR1 and TRX. Kinstrie R, Lochhead PA, Sibbet G, Morrice N, Cleghon V. Biochem J. 2006 Aug 15;398(1):45–54. PubMed Europe PMC Scholia
- Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome. Murakami N, Xie W, Lu RC, Chen-Hwang MC, Wieraszko A, Hwang YW. J Biol Chem. 2006 Aug 18;281(33):23712–24. PubMed Europe PMC Scholia
- DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome. Lepagnol-Bestel AM, Zvara A, Maussion G, Quignon F, Ngimbous B, Ramoz N, et al. Hum Mol Genet. 2009 Apr 15;18(8):1405–14. PubMed Europe PMC Scholia
- Dynamic regulation of Notch signaling in neural progenitor cells. Kageyama R, Ohtsuka T, Shimojo H, Imayoshi I. Curr Opin Cell Biol. 2009 Dec;21(6):733–40. PubMed Europe PMC Scholia
- DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. Guo X, Williams JG, Schug TT, Li X. J Biol Chem. 2010 Apr 23;285(17):13223–32. PubMed Europe PMC Scholia
- Sweet DREAMs for Hippo. Dick FA, Mymryk JS. Genes Dev. 2011 May 1;25(9):889–94. PubMed Europe PMC Scholia
- DYRK1A binds to an evolutionarily conserved WD40-repeat protein WDR68 and induces its nuclear translocation. Miyata Y, Nishida E. Biochim Biophys Acta. 2011 Oct;1813(10):1728–39. PubMed Europe PMC Scholia
- Alzheimer’s Aβ42 and Aβ40 peptides form interlaced amyloid fibrils. Gu L, Guo Z. J Neurochem. 2013 Aug;126(3):305–11. PubMed Europe PMC Scholia
- The role of the hippo pathway in melanocytes and melanoma. Kim JE, Finlay GJ, Baguley BC. Front Oncol. 2013 May 16;3:123. PubMed Europe PMC Scholia
- The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis. Knippschild U, Krüger M, Richter J, Xu P, García-Reyes B, Peifer C, et al. Front Oncol. 2014 May 19;4:96. PubMed Europe PMC Scholia
- DYRK1A in neurodegeneration and cancer: Molecular basis and clinical implications. Abbassi R, Johns TG, Kassiou M, Munoz L. Pharmacol Ther. 2015 Jul;151:87–98. PubMed Europe PMC Scholia
- DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis. Fernández-Martínez P, Zahonero C, Sánchez-Gómez P. Mol Cell Oncol. 2015 Jan 30;2(1):e970048. PubMed Europe PMC Scholia
- Crosstalk of Hedgehog and mTORC1 Pathways. Larsen LJ, Møller LB. Cells. 2020 Oct 18;9(10):2316. PubMed Europe PMC Scholia