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Literature summary extracted from

  • Wippich, F.; Bodenmiller, B.; Trajkovska, M.G.; Wanka, S.; Aebersold, R.; Pelkmans, L.
    Dual specificity kinase DYRK3 couples stress granule condensation/dissolution to mTORC1 signaling (2013), Cell, 152, 791-805.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.12.1 gene DYRK3, recombinant expression of GST-tagged wild-type and mutant enzymes Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.12.1 K218M site-directed mutagenesis, a kinase-deficient mutant Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.12.1 (5Z)-2-(2,6-dichloroanilino)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazol-4-one i.e. GSK-626616, the DYRK kinase inhibitor GSK-626616 affects, among others, the phosphorylation of mRNA-associated proteins and proteins downstream of mTORC1 signaling Homo sapiens
2.7.12.1 2-methyl-5-[(4-methylphenyl)amino]benzothiazole-4,7-dione i.e. CDK4 inhibitor III Homo sapiens
2.7.12.1 3-(N-benzyl-N-isopropyl)amino-1-(naphthalen-2-yl)propan-1-one hydrochloride i.e. Jak3 inhibitor IV Homo sapiens
2.7.12.1 4-(2-phenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3-(2H,6H)-dione i.e. Wee1/Chk1 inhibitor Homo sapiens
2.7.12.1 4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide i.e. CDK2 inhibitor IV Homo sapiens
2.7.12.1 5-chloro-3-(3,5-dichloro-4-hydroxybenzylidene)-1,3-dihydro-indol-2-one i.e. HMS3229I17, a CDK2 inhibitor IV Homo sapiens
2.7.12.1 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole i.e. harmine Homo sapiens
2.7.12.1 DMSO
-
 Homo sapiens
2.7.12.1 RAD-001 a rapamycin derivative Homo sapiens
2.7.12.1 sorbitol
-
 Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.12.1 cytosol
-
 Homo sapiens 5829
-
2.7.12.1 additional information DYRK3 regulates its own partitioning between stress granules and the cytosol in a cyclic manner through Its kinase activity Homo sapiens
-
-
2.7.12.1 stress granule
-
 Homo sapiens
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.12.1 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.12.1 ATP + PRAS40 Homo sapiens phosphorylation at Thr246 ADP + phospho-PRAS40
-
 ?
2.7.12.1 ATP + S6K1 Homo sapiens phosphorylation at Thr389 ADP + phospho-S6K1
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.12.1 Homo sapiens O43781
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.12.1 HeLa cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.12.1 ATP + PRAS40 phosphorylation at Thr246 Homo sapiens ADP + phospho-PRAS40
-
 ?
2.7.12.1 ATP + S6K1 phosphorylation at Thr389 Homo sapiens ADP + phospho-S6K1
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.12.1 dual specificity kinase
-
 Homo sapiens
2.7.12.1 dual specificity tyrosine-phosphorylation-regulated kinase 3
-
 Homo sapiens
2.7.12.1 DYRK3
-
 Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.12.1 7.2
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.12.1 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.12.1 malfunction kinase-inactive DYRK3 inhibits mTORC1 by preventing dissociation from stress granules Homo sapiens
2.7.12.1 physiological function during cellular stress the dual specificity kinase DYRK3 regulates the stability of P-granule-like structures and mTORC1 signaling. DYRK3 displays a cyclic partitioning mechanism between stress granules and the cytosol via a low-complexity domain in its N-terminus and its kinase activity. When DYRK3 is inactive, it prevents stress granule dissolution and the release of sequestered mTORC1. When DYRK3 is active, it allows stress granule dissolution, releasing mTORC1 for signaling and promoting its activity by directly phosphorylating the mTORC1 inhibitor PRAS40. This mechanism links cytoplasmic compartmentalization via liquid phase transitions with cellular signaling. DYRK3 has the potential to condense granules in the cytosol of human cells to which the mRNA-binding protein GW182 can be recruited, and DYRK3 localizes to stress granules during oxidative and osmotic stress. Activity-dependent dynamic cycling of DYRK3 on stress granules and mechanism of mTORC1 reactivation by DYRK3, overview Homo sapiens