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

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Gamma-secretase13DREAM complex13122312812518535322231651723101783510225431, 73Change in recruitment of endophilin at endocytic sitesGlucocorticoid receptor-dependenttranscriptionCo-localization of CASP9 to the nucleus;inhibiting apopotic pathwayAPH1APSENENPSEN1CREB1MuvB TF complexNCSTNEIF2B5Cyclin-dependent kinase 6AMPHCASP3FOXO1SMARCB1CDK4 proteinFGF2LATS2BACE1E2FHIP1Salvador-Warts-Hippo Signalling PathwaymTORC1RESTDNM1CREB1EtoposideAMPHLIN52Dual-specificity tyrosine phosphorylation regulated kinase 1AARIP4GSK3B666613615, 21619Casein kinase 1 alpha 1MTORHedgehog signaling pathwayMLST8Zinc finger protein GLI1TSC1AKT1S1RPTORGLI1TSC2DCAF7DEPTOR1313139139CDKN1BDLL1Cell CycleG2DLL1HES5Notch Intracellular Domain (NICD)HES1NEUROG2CASP9MSG1G0CDKN1B141314CRY2SPRY2Delta and Notch-like epidermal growth factor-related receptorCCND1NAD-dependent protein deacetylase sirtuin-1Amyloid-beta precursor proteinTFAP4Dual-specificity tyrosine phosphorylation regulated kinase 1AH3-3ATP53NOTCH1NFATC1GMNNDLL1TSC1TSC26GSK3BCRY213CASP9NFATC113Microtubule-associated protein tauMicrotubule-associated protein tau13131311, 132, 4E2FAmyloid-beta precursor protein13H3-3A13Androgen 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 exit


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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  9. Yang EJ, Ahn YS, Chung KC; ''Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  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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  22. Lepagnol-Bestel AM, Zvara A, Maussion G, Quignon F, Ngimbous B, Ramoz N, Imbeaud S, Loe-Mie Y, Benihoud K, Agier N, Salin PA, Cardona A, Khung-Savatovsky S, Kallunki P, Delabar JM, Puskas LG, Delacroix H, Aggerbeck L, Delezoide AL, Delattre O, Gorwood P, Moalic JM, Simonneau M; ''DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome.''; Hum Mol Genet, 2009 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
AKT1S1ProteinENSG00000204673 (Ensembl)
AMPHProteinENSG00000078053 (Ensembl)
APH1AProteinENSG00000117362 (Ensembl) identifier is for the c. elegans homolog of this gene
ARIP4ProteinENSG00000164080 (Ensembl)
Amyloid-beta precursor protein ProteinENSG00000142192 (Ensembl) Located on chromosome 21
BACE1ProteinENSG00000186318 (Ensembl)
CASP3ProteinENSG00000164305 (Ensembl)
CASP9ProteinENSG00000132906 (Ensembl)
CCND1ProteinENSG00000110092 (Ensembl) Cyclin D1
CDK4 proteinProteinENSG00000135446 (Ensembl)
CDKN1BProteinENSG00000111276 (Ensembl) =p27Kip1

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

Earlier differentiation
CREB1ProteinENSG00000118260 (Ensembl)
CRY2ProteinENSG00000121671 (Ensembl)
Casein kinase 1 alpha 1ProteinENSG00000113712 (Ensembl) lacks reference; which casein kinase is it specifically?
Cell Cycle
Cyclin-dependent kinase 6ProteinENSG00000105810 (Ensembl)
DCAF7ProteinENSG00000136485 (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
DEPTORProteinENSG00000155792 (Ensembl)
DLL1ProteinENSG00000198719 (Ensembl)
DNM1ProteinENSG00000106976 (Ensembl)
DREAM complex
Delta and Notch-like epidermal growth factor-related receptorProteinENSG00000187957 (Ensembl)
Dual-specificity tyrosine phosphorylation regulated kinase 1AProteinENSG00000157540 (Ensembl)
E2FProtein
E2F GeneProduct
E2F4ProteinENSG00000205250 (Ensembl)
E2F5ProteinENSG00000133740 (Ensembl)
EIF2B5ProteinENSG00000145191 (Ensembl)
EtoposideMetaboliteHMDB14911 (HMDB)
FGF2ProteinENSG00000138685 (Ensembl)
FOXO1ProteinENSG00000150907 (Ensembl)
G0
G1
G2
GLI1GeneProductENSG00000111087 (Ensembl)
GMNNProteinENSG00000112312 (Ensembl)
GSK3BProteinENSG00000082701 (Ensembl) idk if this is right
Gamma-secretaseComplexCPX-2176 (Other)
H3-3AProteinENSG00000163041 (Ensembl) maybe needs to be phosphorylated?
HES1ProteinENSG00000114315 (Ensembl)
HES5ProteinENSG00000197921 (Ensembl)
HIP1ProteinENSG00000127946 (Ensembl)
Hedgehog signaling pathwayPathway
  • dyrk1a both positively and negatively regulates hh
  • add reference
LATS2ProteinENSG00000150457 (Ensembl)
LIN37ProteinENSG00000267796 (Ensembl)
LIN52ProteinENSG00000205659 (Ensembl)
LIN54ProteinENSG00000189308 (Ensembl)
LIN9ProteinENSG00000183814 (Ensembl)
M
MLST8ProteinENSG00000167965 (Ensembl)
MTORProteinENSG00000198793 (Ensembl)
Microtubule-associated protein tauProteinENSG00000186868 (Ensembl)
MuvB TF complex
NAD-dependent protein deacetylase sirtuin-1ProteinENSG00000096717 (Ensembl) Not humans
NCSTNProteinENSG00000162736 (Ensembl)
NEUROG2ProteinENSG00000178403 (Ensembl)
NFATC1ProteinENSG00000131196 (Ensembl) idk if this is right
NOTCH1ProteinENSG00000148400 (Ensembl)
Notch Intracellular Domain (NICD)Protein
PSEN1ProteinENSG00000080815 (Ensembl)
PSENENProteinENSG00000205155 (Ensembl)
RBBP4ProteinENSG00000162521 (Ensembl)
RBL1ProteinENSG00000080839 (Ensembl)
RBL2ProteinENSG00000103479 (Ensembl)
RESTProteinENSG00000084093 (Ensembl)
RPTORProteinENSG00000141564 (Ensembl)
S
SMARCB1ProteinENSG00000099956 (Ensembl) Human ortholog of drosophila melanogaster SNR1 gene, which is described in the literature
SPRY2ProteinENSG00000136158 (Ensembl)
Salvador-Warts-Hippo Signalling PathwayPathway
TFAP4ProteinENSG00000090447 (Ensembl)
TP53ProteinENSG00000141510 (Ensembl) Not humans
TSC1ProteinENSG00000165699 (Ensembl)
TSC2ProteinENSG00000103197 (Ensembl)
Transcription factor Dp family member 3ProteinENSG00000183434 (Ensembl)
Transcription factor Dp-1ProteinENSG00000198176 (Ensembl)
Transcription factor Dp-2ProteinENSG00000114126 (Ensembl)
Zinc finger protein GLI1ProteinENSG00000111087 (Ensembl)
mTORC1ComplexR-HSA-377400

Annotated Interactions

No annotated interactions

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