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 , Daniela Digles , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

microcephaly intellectual disability Alzheimer's disease Parkinson's disease Lewy body dementia Down syndrome

Pathway Ontology

cell cycle pathway signaling pathway pertinent to the brain and nervous system

Participants

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
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 = WDR68
binding 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
HES5 GeneProduct ensembl:ENSG00000197921
HES1 GeneProduct ensembl:ENSG00000114315
NEUROG2 GeneProduct ensembl:ENSG00000178403
CASP9 GeneProduct ensembl:ENSG00000132906
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
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
Microtubule-associated protein tau GeneProduct ensembl:ENSG00000186868
H3-3A GeneProduct ensembl:ENSG00000163041 maybe needs to be phosphorylated?
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

References

  1. 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
  2. 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
  3. 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
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  7. 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
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  11. 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
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  13. 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
  14. Sweet DREAMs for Hippo. Dick FA, Mymryk JS. Genes Dev. 2011 May 1;25(9):889–94. PubMed Europe PMC Scholia
  15. 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
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  19. 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
  20. 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
  21. Crosstalk of Hedgehog and mTORC1 Pathways. Larsen LJ, Møller LB. Cells. 2020 Oct 18;9(10):2316. PubMed Europe PMC Scholia