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

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1314DREAM complex1319225215454719115141911422451751243, 164Change in recruitment of endophilin at endocytic sitesGlucocorticoid receptor-dependenttranscriptionMuvB TF complexCyclin-dependent kinase 6AMPH1CASP3FOXO1SMARCB1CDK4 proteinFGF2LATS, large tumor suppressor, homolog 2 (Drosophila), isoform CRA_aBeta-secretase 1E2F geneHIP1Salvador-Warts-Hippo Signalling PathwaymTORC1RESTDynamin-1CREB1EtoposideAMPH1Protein lin-52 homologDual specificity tyrosine-phosphorylation-regulated kinase 1AARIP4GSK3B protein15151515131510, 171518Casein kinase 1MTORHedgehog signaling pathwayMLST8Zinc finger protein GLI1TSC1AKT1S1RPTORGLI1TSC2DCAF7DEPTOR1313139139CDKN1B proteinDelta-like protein 1Cell CycleG2DLL1HES5Notch Intracellular Domain (NICD)HES1Neurogenin-2QuiescenceSenescenceChemoresistance20Caspase-9Cell cycle exitMSG1G0CDKN1B protein6136Cryptochrome-2Protein sprouty homolog 2Delta and Notch-like epidermal growth factor-related receptorCCND1 proteinNAD-dependent protein deacetylase sirtuin-1Amyloid-beta precursor proteinTFAP4Dual specificity tyrosine-phosphorylation-regulated kinase 1AHistone H3Cellular tumor antigen p53NOTCH1Nuclear factor of activated T-cells, cytoplasmic 1GemininDelta-like protein 1TSC1TSC215GSK3B proteinCryptochrome-213Caspase-9Nuclear factor of activated T-cells, cytoplasmic 113Microtubule-associated protein tauMicrotubule-associated protein tau131313 Loss of axonal transport and promotion of tau self-aggregation and fibrillisationNFAT translocation back to the cytosol,inhibiting NFAT-dependent transcription8, 13Co-localization of CASP9 to the nucleus;inhibiting apopotic pathwayCell survival12, 20E2F protein(Neuronal) cell differentiationAmyloid-beta precursor protein13 Aβ42 and Aβ40 peptides form interlaced amyloid fibrilsGamma-secretase Histone H313Androgen receptor-dependenttranscriptionDynamin-1FOXO1HIP1Neuronal cell deathNeurite outgrowthCell deathSMARCB1RESTImpairment of dendritic lengthand complexityRetinoblastoma-like protein 1Retinoblastoma-like protein 2Transcription factor E2F4Transcription factor Dp-2Transcraiption factor E2F5Transcription factor Dp family member 3Transcription factor Dp-1Histone-binding protein RBBP4Protein lin-9 homologProtein lin-37 homologProtein lin-54 homologProtein lin-52 homolog


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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  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
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
Aβ42 and Aβ40 peptides form interlaced amyloid fibrilsQ37028176 (Wikidata)
Loss of axonal transport and promotion of tau self-aggregation and fibrillisation
(Neuronal) cell differentiation
AKT1S1GeneProductENSG00000204673 (Ensembl)
AMPH1GeneProduct121585 (HomoloGene)
ARIP4ProteinQ9Y4B4 (Uniprot-SwissProt)
Amyloid-beta precursor protein ProteinP05067 (Uniprot-TrEMBL) Located on chromosome 21
Beta-secretase 1ProteinP56817 (Uniprot-TrEMBL)
CASP3GeneProductENSG00000164305 (Ensembl)
CCND1 proteinProteinQ6FI00 (Uniprot-TrEMBL) Cyclin D1
CDK4 proteinProteinQ96BE9 (Uniprot-TrEMBL)
CDKN1B proteinProteinQ6I9V6 (Uniprot-TrEMBL) =p27Kip1

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

Earlier differentiation
CREB1GeneProductENSG00000118260 (Ensembl)
Casein kinase 1Protein
Caspase-9ProteinP55211 (Uniprot-TrEMBL)
Cell Cycle
Cell cycle exit
Cell survival
Cellular tumor antigen p53ProteinP04637 (Uniprot-TrEMBL) Not humans
Co-localization of CASP9 to the nucleus; inhibiting apopotic pathway
Cryptochrome-2ProteinQ49AN0 (Uniprot-TrEMBL)
Cyclin-dependent kinase 6ProteinQ00534 (Uniprot-TrEMBL)
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
DEPTORGeneProductENSG00000155792 (Ensembl)
DLL1GeneProductENSG00000198719 (Ensembl)
DREAM complex
Delta and Notch-like epidermal growth factor-related receptorPathwayQ8NFT8 (Uniprot-TrEMBL)
Delta-like protein 1ProteinO00548 (Uniprot-TrEMBL)
Dual specificity tyrosine-phosphorylation-regulated kinase 1AProteinQ13627 (Uniprot-TrEMBL)
Dynamin-1ProteinQ05193 (Uniprot-SwissProt)
E2F geneGeneProduct
E2F proteinGeneProduct
EtoposideMetaboliteHMDB14911 (HMDB)
FGF2GeneProductENSG00000138685 (Ensembl)
FOXO1GeneProductENSG00000150907 (Ensembl)
G0
G1
G2
GLI1GeneProductENSG00000111087 (Ensembl)
GSK3B proteinProteinQ6FI27 (Uniprot-TrEMBL) idk if this is right
Gamma-secretase Protein
GemininProteinO75496 (Uniprot-TrEMBL)
HES1GeneProductENSG00000114315 (Ensembl)
HES5GeneProductENSG00000197921 (Ensembl)
HIP1GeneProductENSG00000127946 (Ensembl)
Hedgehog signaling pathwayPathway
  • dyrk1a both positively and negatively regulates hh
  • add reference
Histone H3ProteinB2R4P9 (Uniprot-TrEMBL) maybe needs to be phosphorylated?
Histone-binding protein RBBP4ProteinQ09028 (Uniprot-TrEMBL)
LATS, large tumor suppressor, homolog 2 (Drosophila), isoform CRA_aProteinA0A024RDM3 (Uniprot-TrEMBL)
M
MLST8GeneProductENSG00000167965 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
Microtubule-associated protein tauProteinI3L2Z2 (Uniprot-TrEMBL)
Microtubule-associated protein tauProteinP10636 (Uniprot-TrEMBL)
MuvB TF complex
NAD-dependent protein deacetylase sirtuin-1ProteinQ96EB6 (Uniprot-TrEMBL) Not humans
NFAT translocation back to the cytosol, inhibiting NFAT-dependent transcription
NOTCH1GeneProductENSG00000148400 (Ensembl)
Neurogenin-2ProteinQ9H2A3 (Uniprot-TrEMBL)
Notch Intracellular Domain (NICD)
Nuclear factor of activated T-cells, cytoplasmic 1ProteinO95644 (Uniprot-TrEMBL) idk if this is right
Protein lin-37 homologProteinQ96GY3 (Uniprot-TrEMBL)
Protein lin-52 homologProteinQ52LA3 (Uniprot-TrEMBL)
Protein lin-54 homologProteinQ6MZP7 (Uniprot-TrEMBL)
Protein lin-9 homologProteinQ5TKA1 (Uniprot-TrEMBL)
Protein sprouty homolog 2ProteinO43597 (Uniprot-TrEMBL)
Quiescence

Senescence

Chemoresistance
RESTGeneProductENSG00000084093 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)
Retinoblastoma-like protein 1ProteinP28749 (Uniprot-TrEMBL)
Retinoblastoma-like protein 2ProteinQ08999 (Uniprot-TrEMBL)
S
SMARCB1GeneProductENSG00000099956 (Ensembl) Human ortholog of drosophila melanogaster SNR1 gene, which is described in the literature
Salvador-Warts-Hippo Signalling PathwayPathway
TFAP4GeneProductENSG00000090447 (Ensembl)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
Transcraiption factor E2F5ProteinQ15329 (Uniprot-TrEMBL)
Transcription factor Dp family member 3ProteinQ5H9I0 (Uniprot-TrEMBL)
Transcription factor Dp-1ProteinQ14186 (Uniprot-TrEMBL)
Transcription factor Dp-2ProteinQ14188 (Uniprot-TrEMBL)
Transcription factor E2F4ProteinQ16254 (Uniprot-TrEMBL)
Zinc finger protein GLI1ProteinP08151 (Uniprot-TrEMBL)
mTORC1ComplexR-HSA-377400

Annotated Interactions

No annotated interactions

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