DYRK1A involvement regarding cell proliferation in brain development (Homo sapiens)

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Gamma-secretase44121222212182018101810621518162916221018961881017, 2310Change in recruitment of endophilin at endocytic sitesGlucocorticoid receptor-dependenttranscriptionMuvB TF complexG2Co-localization of CASP9 to the nucleus;inhibiting apopotic pathwaySAPH1ACREB1EIF2B5PSEN1PSENENNCSTNCyclin-dependent kinase 6AMPHCASP3FOXO1SMARCB1CDK4 proteinFGF2LATS2BACE1E2FHIP1Salvador-Warts-Hippo Signalling PathwaymTORC1RESTDNM1CREB1EtoposideAMPHLIN52Dual-specificity tyrosine phosphorylation regulated kinase 1AARIP4GSK3B111111114117, 211114Casein kinase 1 alpha 1MTORHedgehog signaling pathwayMLST8Zinc finger protein GLI1TSC1AKT1S1RPTORGLI1TSC2DCAF7DEPTOR444141CDKN1BDLL1DLL1HES5Notch Intracellular Domain (NICD)HES1NEUROG2CASP9CDKN1B545CRY2SPRY2Delta and Notch-like epidermal growth factor-related receptorCCND1NAD-dependent protein deacetylase sirtuin-1Amyloid-beta precursor proteinTFAP4Dual-specificity tyrosine phosphorylation regulated kinase 1AH3-3ATP53NOTCH1NFATC1GMNNDLL1TSC1TSC211GSK3BCRY24CASP9NFATC14Microtubule-associated protein tauMicrotubule-associated protein tau4444, 198, 13E2FAmyloid-beta precursor protein4H3-3A4Androgen receptor-dependenttranscriptionDNM1FOXO1HIP1Neuronal cell deathNeurite outgrowthCell deathSMARCB1RESTImpairment of dendritic lengthand complexityRBL1RBL2E2F4Transcription factor Dp-2E2F5Transcription factor Dp family member 3Transcription factor Dp-1RBBP4LIN9LIN37LIN54LIN52EIF2B5Gene transcription inhippocampal cellsAβ42 and Aβ40 peptides form interlaced amyloid fibrilsCell survivalNFAT translocation back to the cytosol,inhibiting NFAT-dependent transcription Loss of axonal transport and promotion of tau self-aggregation and fibrillisation(Neuronal) cell differentiationQuiescenceSenescenceChemoresistanceCell cycle exitCell CycleG1G0MDREAM complex


Description

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.

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Bibliography

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  4. Abbassi R, Johns TG, Kassiou M, Munoz L; ''DYRK1A in neurodegeneration and cancer: Molecular basis and clinical implications.''; Pharmacol Ther, 2015 PubMed Europe PMC Scholia
  5. Guo X, Williams JG, Schug TT, Li X; ''DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  6. Murakami N, Xie W, Lu RC, Chen-Hwang MC, Wieraszko A, Hwang YW; ''Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome.''; J Biol Chem, 2006 PubMed Europe PMC Scholia
  7. Skurat AV, Dietrich AD; ''Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
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  10. Huang Y, Chen-Hwang MC, Dolios G, Murakami N, Padovan JC, Wang R, Hwang YW; ''Mnb/Dyrk1A phosphorylation regulates the interaction of dynamin 1 with SH3 domain-containing proteins.''; Biochemistry, 2004 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
134649view09:03, 24 July 2024EgonwAdded the datasource of a Reactome identifier
134568view22:52, 22 July 2024EweitzOntology Term : 'cell cycle pathway' added !
126955view14:19, 7 July 2023DdiglesOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
126860view04:33, 28 June 2023EgonwSet the data source for the Complex Portal identifier
125980view16:10, 23 March 2023DeSlchanged "complex titles" to textLabels as well
125979view16:07, 23 March 2023DeSlConverted unknowns to textLabels
125978view16:04, 23 March 2023DeSlUpdated title
125328view22:20, 31 January 2023LarsgwFix references
122423view22:28, 1 April 2022AlexanderPicoSwitched back to GeneProducts. Though they represent protein functions, Ensembl IDs are for genes, so the more generic type is correct.
122393view15:28, 28 March 2022PklemmerUpdated data node type of several nodes from gene product to protein
122391view12:55, 28 March 2022PklemmerAdjusted several nodes from 'Data Node' to 'Label' if applicable.

Updated some identifiers from canonical transcript (ENST) to Ensembl gene (ENSG).

Minor layout changes.
122347view17:37, 21 March 2022PklemmerFixed missing connection between interaction and data node.
122346view17:30, 21 March 2022PklemmerUpdated descriptions of several proteins and gene products - replaced non-Ensembl identifiers with Ensembl identifiers for Cytoscape dataset compatibility
122342view11:15, 21 March 2022PklemmerUpdated descriptions of several proteins and gene products - replaced non-Ensembl identifiers with Ensembl identifiers for Cytoscsape dataset compatibility.
122318view19:43, 17 March 2022PklemmerUpdated identifiers for ARIP4, caseein kinase 1 alpha 1, Dynamin-1.
122134view16:04, 13 March 2022PklemmerAdjusted 'Biological type' of several nodes from generic 'Gene product' to 'Protein'
122091view18:00, 10 March 2022PklemmerAdded EIF2B interaction

Added to CREB1 interaction

Minor layout changes
122072view19:55, 9 March 2022PklemmerModified description
122071view19:44, 9 March 2022PklemmerAdded SMARCB1 interaction Added REST interaction
121972view17:38, 8 March 2022PklemmerAdded ARIP4 interaction

Added FOXO1 interaction Added Dynamin-1 interaction Added HIP1 interaction Added AMPH1 interaction Added CREB1 interaction

Small layout changes
121508view16:54, 19 February 2022VeerleHorstingEdited APP part
121507view15:27, 19 February 2022VeerleHorstingAdjusted geneproducts to proteins
121500view13:40, 18 February 2022PklemmerIncorporated some changes based on feedback from supervisor.
121464view15:42, 17 February 2022VeerleHorsting
121444view14:05, 17 February 2022VeerleHorstingDREAM complex
121422view11:27, 17 February 2022VeerleHorsting
121421view11:25, 17 February 2022VeerleHorstingReverted to version '20:43, 16 February 2022' by VeerleHorsting
121388view09:35, 17 February 2022VeerleHorstingReverted to version '09:32, 10 February 2022' by VeerleHorsting
121375view20:43, 16 February 2022PklemmerAdded GL1 interaction.

Added DCAF7 interaction. Added mTORC1 interaction. Added Hh interaction.

Added TSC1 and TSC2 interaction.
121343view15:10, 15 February 2022PklemmerUpdated layout. Added references to interactions instead of gene products.
121312view17:46, 14 February 2022PklemmerOntology Term : 'microcephaly' added !
121311view17:43, 14 February 2022PklemmerOntology Term : 'Lewy body dementia' added !
121310view17:43, 14 February 2022PklemmerOntology Term : 'Parkinson's disease' added !
121309view17:43, 14 February 2022PklemmerOntology Term : 'Alzheimer's disease' added !
121308view17:43, 14 February 2022PklemmerOntology Term : 'Down syndrome' added !
121307view17:43, 14 February 2022PklemmerOntology Term : 'intellectual disability' added !
121306view17:41, 14 February 2022PklemmerModified title
121157view09:32, 10 February 2022VeerleHorstingNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1S1GeneProductENSG00000204673 (Ensembl)
AMPHGeneProductENSG00000078053 (Ensembl)
APH1AGeneProductENSG00000117362 (Ensembl) identifier is for the c. elegans homolog of this gene
ARIP4GeneProductENSG00000164080 (Ensembl)
Amyloid-beta precursor protein GeneProductENSG00000142192 (Ensembl) Located on chromosome 21
BACE1GeneProductENSG00000186318 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl) Cyclin D1
CDK4 proteinGeneProductENSG00000135446 (Ensembl)
CDKN1BGeneProductENSG00000111276 (Ensembl) =p27Kip1

Promotes exit of cell cylce; prevents progression through G1 checkpoint;

Earlier differentiation
CREB1GeneProductENSG00000118260 (Ensembl)
CRY2GeneProductENSG00000121671 (Ensembl)
Casein kinase 1 alpha 1GeneProductENSG00000113712 (Ensembl) lacks reference; which casein kinase is it specifically?
Cyclin-dependent kinase 6GeneProductENSG00000105810 (Ensembl)
DCAF7GeneProductENSG00000136485 (Ensembl)
  • 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
DEPTORGeneProductENSG00000155792 (Ensembl)
DLL1GeneProductENSG00000198719 (Ensembl)
DNM1GeneProductENSG00000106976 (Ensembl)
Delta and Notch-like epidermal growth factor-related receptorGeneProductENSG00000187957 (Ensembl)
Dual-specificity tyrosine phosphorylation regulated kinase 1AGeneProductENSG00000157540 (Ensembl)
E2FGeneProduct
E2F GeneProduct
E2F4GeneProductENSG00000205250 (Ensembl)
E2F5GeneProductENSG00000133740 (Ensembl)
EIF2B5GeneProductENSG00000145191 (Ensembl)
EtoposideMetaboliteHMDB14911 (HMDB)
FGF2GeneProductENSG00000138685 (Ensembl)
FOXO1GeneProductENSG00000150907 (Ensembl)
GLI1GeneProductENSG00000111087 (Ensembl)
GMNNGeneProductENSG00000112312 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl) idk if this is right
Gamma-secretaseComplexCPX-2176 (Complex Portal)
H3-3AGeneProductENSG00000163041 (Ensembl) maybe needs to be phosphorylated?
HES1GeneProductENSG00000114315 (Ensembl)
HES5GeneProductENSG00000197921 (Ensembl)
HIP1GeneProductENSG00000127946 (Ensembl)
Hedgehog signaling pathwayPathway
  • dyrk1a both positively and negatively regulates hh
  • add reference
LATS2GeneProductENSG00000150457 (Ensembl)
LIN37GeneProductENSG00000267796 (Ensembl)
LIN52GeneProductENSG00000205659 (Ensembl)
LIN54GeneProductENSG00000189308 (Ensembl)
LIN9GeneProductENSG00000183814 (Ensembl)
MLST8GeneProductENSG00000167965 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
Microtubule-associated protein tauGeneProductENSG00000186868 (Ensembl)
NAD-dependent protein deacetylase sirtuin-1GeneProductENSG00000096717 (Ensembl) Not humans
NCSTNGeneProductENSG00000162736 (Ensembl)
NEUROG2GeneProductENSG00000178403 (Ensembl)
NFATC1GeneProductENSG00000131196 (Ensembl) idk if this is right
NOTCH1GeneProductENSG00000148400 (Ensembl)
Notch Intracellular Domain (NICD)GeneProduct
PSEN1GeneProductENSG00000080815 (Ensembl)
PSENENGeneProductENSG00000205155 (Ensembl)
RBBP4GeneProductENSG00000162521 (Ensembl)
RBL1GeneProductENSG00000080839 (Ensembl)
RBL2GeneProductENSG00000103479 (Ensembl)
RESTGeneProductENSG00000084093 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)
SMARCB1GeneProductENSG00000099956 (Ensembl) Human ortholog of drosophila melanogaster SNR1 gene, which is described in the literature
SPRY2GeneProductENSG00000136158 (Ensembl)
Salvador-Warts-Hippo Signalling PathwayPathway
TFAP4GeneProductENSG00000090447 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl) Not humans
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
Transcription factor Dp family member 3GeneProductENSG00000183434 (Ensembl)
Transcription factor Dp-1GeneProductENSG00000198176 (Ensembl)
Transcription factor Dp-2GeneProductENSG00000114126 (Ensembl)
Zinc finger protein GLI1GeneProductENSG00000111087 (Ensembl)
mTORC1ComplexR-HSA-377400 (Reactome)

Annotated Interactions

No annotated interactions

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