Cloned (Comment) | Organism |
---|---|
gene DYRK3, recombinant expression of GST-tagged wild-type and mutant enzymes | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
K218M | site-directed mutagenesis, a kinase-deficient mutant | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(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-methyl-5-[(4-methylphenyl)amino]benzothiazole-4,7-dione | i.e. CDK4 inhibitor III | Homo sapiens | |
3-(N-benzyl-N-isopropyl)amino-1-(naphthalen-2-yl)propan-1-one hydrochloride | i.e. Jak3 inhibitor IV | Homo sapiens | |
4-(2-phenyl)-9-hydroxypyrrolo[3,4-c]carbazole-1,3-(2H,6H)-dione | i.e. Wee1/Chk1 inhibitor | Homo sapiens | |
4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-N,N-diethylbenzamide | i.e. CDK2 inhibitor IV | Homo sapiens | |
5-chloro-3-(3,5-dichloro-4-hydroxybenzylidene)-1,3-dihydro-indol-2-one | i.e. HMS3229I17, a CDK2 inhibitor IV | Homo sapiens | |
7-methoxy-1-methyl-9H-pyrido[3,4-b]indole | i.e. harmine | Homo sapiens | |
DMSO | - |
Homo sapiens | |
RAD-001 | a rapamycin derivative | Homo sapiens | |
sorbitol | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
additional information | DYRK3 regulates its own partitioning between stress granules and the cytosol in a cyclic manner through Its kinase activity | Homo sapiens | - |
- |
stress granule | - |
Homo sapiens | - |
- |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + PRAS40 | Homo sapiens | phosphorylation at Thr246 | ADP + phospho-PRAS40 | - |
? | |
ATP + S6K1 | Homo sapiens | phosphorylation at Thr389 | ADP + phospho-S6K1 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O43781 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HeLa cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + PRAS40 | phosphorylation at Thr246 | Homo sapiens | ADP + phospho-PRAS40 | - |
? | |
ATP + S6K1 | phosphorylation at Thr389 | Homo sapiens | ADP + phospho-S6K1 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
dual specificity kinase | - |
Homo sapiens |
dual specificity tyrosine-phosphorylation-regulated kinase 3 | - |
Homo sapiens |
DYRK3 | - |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.2 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | kinase-inactive DYRK3 inhibits mTORC1 by preventing dissociation from stress granules | Homo sapiens |
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 |