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Literature summary for 2.7.12.1 extracted from

  • Papadopoulos, C.; Arato, K.; Lilienthal, E.; Zerweck, J.; Schutkowski, M.; Chatain, N.; Mueller-Newen, G.; Becker, W.; de la Luna, S
    Splice variants of the dual specificity tyrosine phosphorylation-regulated kinase 4 (DYRK4) differ in their subcellular localization and catalytic activity (2011), J. Biol. Chem., 286, 5494-5505.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity Homo sapiens
additional information autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
gene DYRK4, DNA and amino acid sequence determination and analysis, splicing variants analysis and comparison to the human splicing variants, expression analysis, overview. Recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS and of the GFP-tagged DYRK4 N-terminus in HEK-293T cells Mus musculus
gene DYRK4, DNA and amino acid sequence determination and analysis, splicing variants analysis and comparison to the murine splicing variants, expression analysis, overview. Recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS and in insect cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
Y246F site-directed mutagenesis, mutation of the autophosphorylation site. The DYRK4 mutant is neither autophosphorylated nor does it display kinase activity on a synthetic substrate, the exogenous peptide substrate DYRKtide Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm most of the DYRK4 isoforms show a preferential cytoplasmic localization Homo sapiens 5737
-
cytoplasm most of the DYRK4 isoforms show a preferential cytoplasmic localization Mus musculus 5737
-
nucleoplasm one of several splice variants of DYRK4 contains a nuclear localization signal in its extended N-terminus that mediates its interaction with importin alpha3 and alpha5 and that is capable of targeting a heterologous protein to the nucleus. The nucleocytoplasmic mobility of this variant differs from that of a shorter isoform. The long isoform (mDYRK4642) does not exit the nucleus Mus musculus 5654
-
nucleoplasm one of several splice variants of DYRK4, the long isoform, contains a nuclear localization signal in its extended N-terminus that mediates its interaction with importin alpha3 and alpha5 and that is capable of targeting a heterologous protein to the nucleus. The nucleocytoplasmic mobility of this variant differs from that of a shorter isoform Homo sapiens 5654
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + a protein Homo sapiens
-
ADP + a phosphoprotein
-
?
ATP + a protein Mus musculus
-
ADP + a phosphoprotein
-
?
additional information Mus musculus autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity ?
-
?
additional information Homo sapiens autophosphorylation of the tyrosine 246 residue within the activation loop is necessary for full DYRK4 kinase activity, no differences in tyrosine phosphorylation are evident for the long and the short human DYRK4 isoforms ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NR20
-
-
Mus musculus Q8BI55
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity Homo sapiens
phosphoprotein autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
additional information several splice variants of DYRK4 are expressed in tissue-specific patterns, Dyrk4 shows a wide tissue distribution in humans Homo sapiens
-
additional information several splice variants of DYRK4 are expressed in tissue-specific patterns, Dyrk4 shows a wide tissue distribution in humans Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + a protein
-
Homo sapiens ADP + a phosphoprotein
-
?
ATP + a protein
-
Mus musculus ADP + a phosphoprotein
-
?
ATP + biotin-Ttds-TPGSRSRTPSLPT i.e. peptide PEP3 Homo sapiens ADP + phosphorylated biotin-Ttds-TPGSRSRTPSLPT
-
?
ATP + biotin-Ttds-TPGSRSRTPSLPT i.e. peptide PEP3 Mus musculus ADP + phosphorylated biotin-Ttds-TPGSRSRTPSLPT
-
?
ATP + biotin-Ttds-VGLLKLASPELER i.e. peptide PEP285 Homo sapiens ADP + phosphorylated biotin-Ttds-VGLLKLASPELER
-
?
ATP + biotin-Ttds-VGLLKLASPELER i.e. peptide PEP285 Mus musculus ADP + phosphorylated biotin-Ttds-VGLLKLASPELER
-
?
ATP + RRARKLTATPTPLGG i.e. peptide SAPtide Homo sapiens ADP + RRARKLTApTPTPLGG
-
?
ATP + RRARKLTATPTPLGG i.e. peptide SAPtide Mus musculus ADP + RRARKLTApTPTPLGG
-
?
ATP + RRRFRPASPLRGPPK i.e. peptide DYRKtide, designed on the basis of the phosphorylation consensus sequence for DYRK1A Homo sapiens ADP + RRRFRPApSPLRGPPK
-
?
ATP + RRRFRPASPLRGPPK i.e. peptide DYRKtide, designed on the basis of the phosphorylation consensus sequence for DYRK1A Mus musculus ADP + RRRFRPApSPLRGPPK
-
?
additional information autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity Mus musculus ?
-
?
additional information autophosphorylation of the tyrosine 246 residue within the activation loop is necessary for full DYRK4 kinase activity, no differences in tyrosine phosphorylation are evident for the long and the short human DYRK4 isoforms Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
dual specificity tyrosine phosphorylation-regulated kinase 4
-
Homo sapiens
dual specificity tyrosine phosphorylation-regulated kinase 4
-
Mus musculus
DYRK4
-
Homo sapiens
DYRK4
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at, recombinant enzyme Homo sapiens
30
-
assay at, recombinant enzyme Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at, recombinant enzyme Homo sapiens
7.4
-
assay at, recombinant enzyme Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
ATP
-
Mus musculus

General Information

General Information Comment Organism
evolution enzyme DYRK4 belongs to the dual specificity tyrosine phosphorylation-regulated kinases, DYRKs, a family of conserved protein kinases that play key roles in the regulation of cell differentiation, proliferation, and survival. DYRKs contain a conserved Tyr-Xaa-Tyr motif in the activation loop. Autophosphorylation of a second tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity and is a defining feature of the DYRK family. Family members DYRK1A, DYRK2, and DYRK4 differ in their target recognition sequence, and preference for an arginine residue at position P -3 is a feature of DYRK1A but not of DYRK2 and DYRK4 Homo sapiens
evolution enzyme DYRK4 belongs to the dual specificity tyrosine phosphorylation-regulated kinases, DYRKs, a family of conserved protein kinases that play key roles in the regulation of cell differentiation, proliferation, and survival. DYRKs contain a conserved Tyr-Xaa-Tyr motif in the activation loop. Autophosphorylation of a second tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity and is a defining feature of the DYRK family. Family members DYRK1A, DYRK2, and DYRK4 differ in their target recognition sequence, and preference for an arginine residue at position P -3 is a feature of DYRK1A but not of DYRK2 and DYRK4 Mus musculus
malfunction some splicing events affect the catalytic domain, including a three-amino acid deletion within subdomain XI that markedly reduces the enzymatic activity of DYRK4 Homo sapiens
malfunction some splicing events affect the catalytic domain, including a three-amino acid deletion within subdomain XI that markedly reduces the enzymatic activity of DYRK4 Mus musculus
additional information both human and murine DYRK4 genes express several transcripts as a result of alternative splicing, with the two main protein products differing in their N-terminal domain Homo sapiens
additional information both human and murine DYRK4 genes express several transcripts as a result of alternative splicing, with the two main protein products differing in their N-terminal domain Mus musculus
physiological function several splice variants of DYRK4 have distinct functional capacities Homo sapiens
physiological function several splice variants of DYRK4 have distinct functional capacities Mus musculus