O43781 · DYRK3_HUMAN
- ProteinDual specificity tyrosine-phosphorylation-regulated kinase 3
- GeneDYRK3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids588 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Inhibited by harmine, an ATP competitive inhibitor (PubMed:29634919).
Inhibited by small-compound GSK-626616 (PubMed:29973724).
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDual specificity tyrosine-phosphorylation-regulated kinase 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO43781
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 238 | 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. | ||||
Sequence: K → M | ||||||
Natural variant | VAR_040464 | 239 | ||||
Sequence: M → L | ||||||
Mutagenesis | 350 | Decreased stability of the protein. | ||||
Sequence: S → A | ||||||
Mutagenesis | 350 | Phosphomimetic mutant; increased stability of the protein. | ||||
Sequence: S → E or D | ||||||
Mutagenesis | 470-474 | Abolishes localization to the nucleus, leading to impaired dissolution of nuclear speckles during mitosis. | ||||
Sequence: RRGKK → AAGAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 690 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000085938 | 1-588 | UniProt | Dual specificity tyrosine-phosphorylation-regulated kinase 3 | |||
Sequence: MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLACMMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKRVVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS | |||||||
Modified residue (large scale data) | 106 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 350 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 368 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 369 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 369 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Isoform 1: Predominant form in fetal liver and bone marrow (PubMed:10779429).
Isoform 1: Present at low levels in heart, pancreas, lymph node and thymus (PubMed:10779429).
Isoform 2: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow (PubMed:10779429).
Isoform 2: Predominant form in testis. Isoform 2: Present at low levels in heart, pancreas, lymph node and thymus (PubMed:10779429).
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O43781-2 | GORASP2 Q9H8Y8 | 5 | EBI-13332019, EBI-739467 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-188 | Disordered | ||||
Sequence: MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNG | ||||||
Domain | 209-522 | Protein kinase | ||||
Sequence: YEVLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLACMMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWI | ||||||
Motif | 468-481 | Nuclear localization signal | ||||
Sequence: RSRRGKKRGPPGSK |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O43781-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsLong
- Length588
- Mass (Da)65,714
- Last updated2007-06-26 v3
- Checksum9950F51C39AFED82
O43781-2
- Name2
- SynonymsShort
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q5SY34 | Q5SY34_HUMAN | DYRK3 | 243 | ||
A0A3B3ISB2 | A0A3B3ISB2_HUMAN | DYRK3 | 71 |
Features
Showing features for alternative sequence, sequence conflict.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y12735 EMBL· GenBank· DDBJ | CAA73266.2 EMBL· GenBank· DDBJ | mRNA | ||
AF186773 EMBL· GenBank· DDBJ | AAG17028.1 EMBL· GenBank· DDBJ | mRNA | ||
AF186774 EMBL· GenBank· DDBJ | AAG17029.1 EMBL· GenBank· DDBJ | mRNA | ||
AF327561 EMBL· GenBank· DDBJ | AAK16443.1 EMBL· GenBank· DDBJ | mRNA | ||
AY590695 EMBL· GenBank· DDBJ | AAT06103.1 EMBL· GenBank· DDBJ | mRNA | ||
AL591846 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471100 EMBL· GenBank· DDBJ | EAW93533.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471100 EMBL· GenBank· DDBJ | EAW93534.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC015501 EMBL· GenBank· DDBJ | AAH15501.1 EMBL· GenBank· DDBJ | mRNA |