O43781 · DYRK3_HUMAN

  • Protein
    Dual specificity tyrosine-phosphorylation-regulated kinase 3
  • Gene
    DYRK3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

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).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site215-223ATP (UniProtKB | ChEBI)
Binding site238ATP (UniProtKB | ChEBI)
Binding site288-291ATP (UniProtKB | ChEBI)
Active site335Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytoplasmic stress granule
Cellular Componentcytoskeleton
Cellular Componentcytosol
Cellular Componentintracellular membrane-bounded organelle
Cellular Componentnuclear speck
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentpericentriolar material
Molecular FunctionATP binding
Molecular Functionmagnesium ion binding
Molecular Functionprotein kinase activity
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Molecular Functionprotein serine/threonine/tyrosine kinase activity
Molecular Functionprotein tyrosine kinase activity
Biological Processcell division
Biological Processerythrocyte differentiation
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of DNA damage response, signal transduction by p53 class mediator
Biological Processnuclear speck organization
Biological Processorganelle disassembly
Biological Processpositive regulation of cell cycle G2/M phase transition
Biological Processprotein phosphorylation
Biological Processregulation of cellular response to stress
Biological Processregulation of TORC1 signaling
Biological Processstress granule disassembly

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Dual specificity tyrosine-phosphorylation-regulated kinase 3
  • EC number
  • Alternative names
    • Regulatory erythroid kinase
      (REDK
      )

Gene names

    • Name
      DYRK3

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O43781
  • Secondary accessions
    • D3DT79
    • Q7Z752
    • Q9HBY6
    • Q9HBY7

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
Nucleus speckle
Cytoplasmic granule
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).

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis238Kinase 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.
Natural variantVAR_040464239
Mutagenesis350Decreased stability of the protein.
Mutagenesis350Phosphomimetic mutant; increased stability of the protein.
Mutagenesis470-474Abolishes localization to the nucleus, leading to impaired dissolution of nuclear speckles during mitosis.

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00000859381-588UniProtDual specificity tyrosine-phosphorylation-regulated kinase 3
Modified residue (large scale data)106PRIDEPhosphoserine
Modified residue350UniProtPhosphoserine
Modified residue (large scale data)368PRIDEPhosphothreonine
Modified residue369UniProtPhosphotyrosine
Modified residue (large scale data)369PRIDEPhosphotyrosine

Post-translational modification

Ubiquitinated at anaphase by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome.
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).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Isoform 1: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow (PubMed:10779429).
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

By EPO/erythropoietin.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with SIRT1.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY O43781-2GORASP2 Q9H8Y85EBI-13332019, EBI-739467

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, domain, motif.

TypeIDPosition(s)Description
Region1-188Disordered
Domain209-522Protein kinase
Motif468-481Nuclear localization signal

Domain

The N-terminal domain, which is intrinsically disordered, is required for stress granule localization.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Name
    1
  • Synonyms
    Long
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    588
  • Mass (Da)
    65,714
  • Last updated
    2007-06-26 v3
  • Checksum
    9950F51C39AFED82
MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLACMMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKRVVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS

O43781-2

  • Name
    2
  • Synonyms
    Short
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-20: Missing
    • 21-26: PPQQRR → MKWKEK

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q5SY34Q5SY34_HUMANDYRK3243
A0A3B3ISB2A0A3B3ISB2_HUMANDYRK371

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0261781-20in isoform 2
Alternative sequenceVSP_02617921-26in isoform 2
Sequence conflict313in Ref. 9; AAH15501
Sequence conflict396in Ref. 1; CAA73266

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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