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  5. CMGC group
  6. DYRK family
  7. Dyrk2 subfamily
  8. Dual specificity tyrosine-phosphorylation-regulated kinase 3

Tchem Dual specificity tyrosine-phosphorylation-regulated kinase 3

Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Negative regulator of EPO-dependent erythropoiesis, may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). May act by regulating CREB/CRE signaling (By similarity). Stabilizes and prevents stress granule disassembly thereby regulating mTORC1 signaling during cellular stress. During stressful conditions, DYRK3 partitions to the stress granule from the cytosol, as well as mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol, and promotes the phosphorylation of the mTORC1 inhibitor, AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (PubMed:20167603).

This gene product belongs to the DYRK family of dual-specificity protein kinases that catalyze autophosphorylation on serine/threonine and tyrosine residues. The members of this family share structural similarity, however, differ in their substrate specificity, suggesting their involvement in different cellular functions. The encoded protein has been shown to autophosphorylate on tyrosine residue and catalyze phosphorylation of histones H3 and H2B in vitro. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

 Comments

Property Summary

Ligand Count 6
NCBI Gene PubMed Count 13
PubMed Score 29.13
PubTator Score 13.10

Knowledge Summary

Patent (1,347)

TINX Plot

  Disease (3)

Disease Target Count P-value
posterior fossa group B ependymoma 416 6.4e-08
malignant mesothelioma 3232 9.3e-07
lung adenocarcinoma 2716 4.2e-06
lung cancer 4740 6.8e-04
Disease Target Count Z-score Confidence
Carcinoma 11493 0.0 0.9
Kidney cancer 2613 0.0 0.5
Disease Target Count Z-score Confidence
Down syndrome 499 3.373 1.7

Expression

  Differential Expression (4)

Disease log2 FC p
lung adenocarcinoma 1.100 4.2e-06
lung cancer -1.200 6.8e-04
malignant mesothelioma -2.200 9.3e-07
posterior fossa group B ependymoma 1.200 6.4e-08

Synonym

Accession O43781 D3DT79 Q7Z752 Q9HBY6 Q9HBY7
Symbols RED
REDK
DYRK5
hYAK3-2

Gene

DYRK3

PANTHER Protein Class (4)

  Ortholog (10)

Species Source Disease
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA
Inparanoid OMA

 Collection (2)

 UniProt Keyword (14)

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 GO Function (6)

 GO Component (6)

 GO Process (7)

 Compartment GO Term (29)

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 MGI Phenotype (1)

 HCA RNA Cell Line (56)

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Pathway (1)

Ligand (6)

Structure of CHEMBL3730504

CHEMBL3730504
pIC50 8.00

Structure of CHEMBL3728543

CHEMBL3728543
pIC50 9.00

Structure of CHEMBL3728359

CHEMBL3728359
pIC50 9.00

Structure of compound 1a [PMID: 24900749]

compound 1a [PMID: 24900749]
pIC50 7.15

Structure of compound 3b [PMID: 23454515]

compound 3b [PMID: 23454515]
pIC50 6.74

Structure of kinase inhibitor 2 [PMID: 30199702]

kinase inhibitor 2 [PMID: 30199702]
pIC50 6.42

Gene RIF (6)

AA Sequence 

MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFT      1 - 70
GDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVP     71 - 140
LTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNGGYDDADGAYIHVPRDHLAYRYE    141 - 210
VLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTF    211 - 280
RNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSS    281 - 350
TKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLAC    351 - 420
MMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGC    421 - 490
DDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKRVVNPASAFQGLGSKLPPVVG    491 - 560
IANKLKANLMSETNGSIPLCSVLPKLIS                                              561 - 588
//

Text Mined References (16)

PMID Year Title