DYRK3
entrez
8444
canonical
uniprot
O43781
canonical
ensembl
ENSG00000143479
resolver
ensp
ENSP00000356073
resolver
ensp
ENSP00000356075
resolver
ensp
ENSP00000356076
resolver
genesymbol
DYRK3
resolver
hgnc
HGNC:3094
resolver
uniprot
D3DT79
resolver
uniprot
Q7Z752
resolver
uniprot
Q9HBY6
resolver
uniprot
Q9HBY7
resolver
uniprot_entry
DYRK3_HUMAN
resolver
uniprot_sec
D3DT79
resolver
uniprot_sec
Q7Z752
resolver
uniprot_sec
Q9HBY6
resolver
uniprot_sec
Q9HBY7
resolver
activity_regulation
ACTIVITY REGULATION: Protein kinase activity is activated following autophosphorylation at Tyr-369 (PubMed:9748265). Inhibited by harmine, an ATP competitive inhibitor (PubMed:29634919). Inhibited by small-compound GSK-626616 (PubMed:29973724). {ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
uniprot
proteins
amino_acid_sequence
MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLACMMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKRVVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS
uniprot
proteins
ec_number
2.7.12.1
uniprot
proteins
function
FUNCTION: Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
uniprot
proteins
mass_dalton
65714
uniprot
proteins
mutagenesis
MUTAGEN 238; /note="K->M: Kinase dead; Induces formation of stress granules-like in absence of stress. Impaired dissolution of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material."; /evidence="ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724"; MUTAGEN 350; /note="S->A: Decreased stability of the protein."; /evidence="ECO:0000269|PubMed:29634919"; MUTAGEN 350; /note="S->E,D: Phosphomimetic mutant; increased stability of the protein."; /evidence="ECO:0000269|PubMed:29634919"; MUTAGEN 470..474; /note="RRGKK->AAGAA: Abolishes localization to the nucleus, leading to impaired dissolution of nuclear speckles during mitosis."; /evidence="ECO:0000269|PubMed:29973724
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated at anaphase by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. {ECO:0000269|PubMed:29973724}.; PTM: Protein kinase activity is activated following autophosphorylation at Tyr-369 (Probable). Autophosphorylation at Ser-350 stabilizes the protein and enhances the protein kinase activity (PubMed:9748265). {ECO:0000269|PubMed:9748265, ECO:0000305|PubMed:9748265}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MNB/DYRK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10779429
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
20167603
uniprot
proteins
pubmed
23415227
uniprot
proteins
pubmed
29634919
uniprot
proteins
pubmed
29973724
uniprot
proteins
pubmed
9748265
uniprot
proteins
pubmed
9845759
uniprot
proteins
sequence_length
588
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:29973724}. Cytoplasm {ECO:0000269|PubMed:29973724}. Nucleus speckle {ECO:0000269|PubMed:29973724}. Cytoplasmic granule {ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29973724}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:29973724}. Note=Associates with membraneless organelles in the cytoplasm and nucleus (PubMed:29973724). Shuttles between cytoplasm and stress granules (PubMed:20167603). Localized predominantly on distinct speckles distributed throughout the cytoplasm of the cell (PubMed:20167603). At low concentration, showns a homogeneous distribution throughout the cytoplasm and does not condense in speckles. During oxidative and osmotic stress, localizes to stress granules (PubMed:20167603). {ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:29973724}.
uniprot
proteins