Information on EC 2.7.12.1 - dual-specificity kinase and Organism(s) Mus musculus and UniProt Accession P22518

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This record set is specific for:
Mus musculus
UNIPROT: P22518


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea


The taxonomic range for the selected organisms is: Mus musculus

EC NUMBER
COMMENTARY hide
2.7.12.1
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RECOMMENDED NAME
GeneOntology No.
dual-specificity kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (Ser/Thr- and Tyr-phosphorylating)
This family of enzymes can phosphorylate both Ser/Thr and Tyr residues.
CAS REGISTRY NUMBER
COMMENTARY hide
134549-83-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
malfunction
physiological function
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + Ser/Arg-rich splicing factors
ADP + phosphorylated Ser/Arg-rich splicing factor
show the reaction diagram
-
-
-
?
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + amphiphysin I
ADP + phosphorylated amphiphysin I
show the reaction diagram
-
-
-
-
?
ATP + biotin-Ttds-TPGSRSRTPSLPT
ADP + phosphorylated biotin-Ttds-TPGSRSRTPSLPT
show the reaction diagram
i.e. peptide PEP3
-
-
?
ATP + biotin-Ttds-VGLLKLASPELER
ADP + phosphorylated biotin-Ttds-VGLLKLASPELER
show the reaction diagram
i.e. peptide PEP285
-
-
?
ATP + caspase-9
ADP + phosphorylated caspase-9
show the reaction diagram
-
-
-
-
?
ATP + CREB
ADP + phosphorylated CREB
show the reaction diagram
-
-
-
-
?
ATP + cyclin L2
ADP + phosphorylated cyclin L2
show the reaction diagram
-
-
-
-
?
ATP + dynamin I
ADP + phosphorylated dynamin I
show the reaction diagram
-
-
-
-
?
ATP + eIF2Bepsilon
ADP + phosphorylated eIF2Bepsilon
show the reaction diagram
-
-
-
-
?
ATP + extracellular MAP kinase kinase
ADP + phospho-[MAP kinase kinase]
show the reaction diagram
-
-
-
-
?
ATP + extracellular signal-regulated kinase
ADP + phospho-[extracellular signal-regulated kinase]
show the reaction diagram
-
-
-
-
?
ATP + Gli1 protein
ADP + phosphorylated Gli1 protein
show the reaction diagram
-
-
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
show the reaction diagram
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
phosphorylation on serine, threonine, and tyrosine residues
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-
?
ATP + neurodegeneration-related septin 4
ADP + phosphorylated neurodegeneration-related septin 4
show the reaction diagram
-
SEPT4, also known as Pnutl2/CDCrel-2
-
-
?
ATP + NFAT
ADP + phosphorylated NFAT
show the reaction diagram
-
-
-
-
?
ATP + Notch protein
ADP + phosphorylated Notch protein
show the reaction diagram
-
-
-
-
?
ATP + peptide DYRKtide
ADP + phosphorylated peptide DYRKtide
show the reaction diagram
synthetic peptide substrate
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-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + RRARKLTATPTPLGG
ADP + RRARKLTApTPTPLGG
show the reaction diagram
i.e. peptide SAPtide
-
-
?
ATP + RRRFRPASPLRGPPK
ADP + RRRFRPApSPLRGPPK
show the reaction diagram
i.e. peptide DYRKtide, designed on the basis of the phosphorylation consensus sequence for DYRK1A
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-
?
ATP + splicing factor 2
ADP + phosphorylated splicing factor 2
show the reaction diagram
-
-
-
-
?
ATP + splicing factor 3
ADP + phosphorylated splicing factor 3
show the reaction diagram
-
-
-
-
?
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + SR protein
ADP + hyperphosphorylated SR protein
show the reaction diagram
i.e. serine-rich and arginine-rich proteins
-
?
ATP + STAT3
ADP + phosphorylated STAT3
show the reaction diagram
-
-
-
-
?
ATP + synaptojanin I
ADP + phosphorylated synaptojanin I
show the reaction diagram
-
-
-
-
?
ATP + transcription factor FKHR
ADP + phosphorylated transcription factor FKHR
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + amphiphysin I
ADP + phosphorylated amphiphysin I
show the reaction diagram
-
-
-
-
?
ATP + caspase-9
ADP + phosphorylated caspase-9
show the reaction diagram
-
-
-
-
?
ATP + CREB
ADP + phosphorylated CREB
show the reaction diagram
-
-
-
-
?
ATP + cyclin L2
ADP + phosphorylated cyclin L2
show the reaction diagram
-
-
-
-
?
ATP + dynamin I
ADP + phosphorylated dynamin I
show the reaction diagram
-
-
-
-
?
ATP + eIF2Bepsilon
ADP + phosphorylated eIF2Bepsilon
show the reaction diagram
-
-
-
-
?
ATP + extracellular MAP kinase kinase
ADP + phospho-[MAP kinase kinase]
show the reaction diagram
-
-
-
-
?
ATP + extracellular signal-regulated kinase
ADP + phospho-[extracellular signal-regulated kinase]
show the reaction diagram
-
-
-
-
?
ATP + Gli1 protein
ADP + phosphorylated Gli1 protein
show the reaction diagram
-
-
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
show the reaction diagram
-
-
-
-
?
ATP + neurodegeneration-related septin 4
ADP + phosphorylated neurodegeneration-related septin 4
show the reaction diagram
-
SEPT4, also known as Pnutl2/CDCrel-2
-
-
?
ATP + NFAT
ADP + phosphorylated NFAT
show the reaction diagram
-
-
-
-
?
ATP + Notch protein
ADP + phosphorylated Notch protein
show the reaction diagram
-
-
-
-
?
ATP + splicing factor 2
ADP + phosphorylated splicing factor 2
show the reaction diagram
-
-
-
-
?
ATP + splicing factor 3
ADP + phosphorylated splicing factor 3
show the reaction diagram
-
-
-
-
?
ATP + SR protein
ADP + ?
show the reaction diagram
ATP + STAT3
ADP + phosphorylated STAT3
show the reaction diagram
-
-
-
-
?
ATP + synaptojanin I
ADP + phosphorylated synaptojanin I
show the reaction diagram
-
-
-
-
?
ATP + transcription factor FKHR
ADP + phosphorylated transcription factor FKHR
show the reaction diagram
-
-
-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
harmine
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
embryonal carcinoma cell line
Manually annotated by BRENDA team
DYRK3 expression in, ex vivo analysis of erythroid progenitor cells of DYRK3-knockout mice
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
most of the DYRK4 isoforms show a preferential cytoplasmic localization
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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enzyme contains a nuclear targeting signal sequence
Manually annotated by BRENDA team
additional information
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STY protein contains a putative nuclear localization signal
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65000
x * 65000, splicing variant 1, SDS-PAGE, x * 70000, splicing variant 2, SDS-PAGE, x * 75000, splicing variant 3 from skeletal muscle, SDS-PAGE
70000
x * 65000, splicing variant 1, SDS-PAGE, x * 70000, splicing variant 2, SDS-PAGE, x * 75000, splicing variant 3 from skeletal muscle, SDS-PAGE
75000
x * 65000, splicing variant 1, SDS-PAGE, x * 70000, splicing variant 2, SDS-PAGE, x * 75000, splicing variant 3 from skeletal muscle, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 65000, splicing variant 1, SDS-PAGE, x * 70000, splicing variant 2, SDS-PAGE, x * 75000, splicing variant 3 from skeletal muscle, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, the enzyme occurs in several splicing variants, analysis overview, expression in murine hypothalamic GT1-7 cell line, expression of splicing variants in COS_7 cells and in Escherichia coli
EGFP-tagged DYRK1A is expressed in HEK-293 cell
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gene DYRK1A, quantitative expression analysis
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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
genomic clones of DYRK3 isolated from a 129svJ Lambda phage library, transgenic mice generated, DYRK3 gene deletion in E14 ES cells using a floxed PGKneo targeting vector, targeted cells injected into C57BL/6J blastocysts, transgenic pA2gata1-DYRK3 mice prepared using an Myc epitope-tagged mDYRK3 cDNA within a pA2gata1 vector
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Dyrk1A expression can be enhanced by treatment with beta-amyloid or overexpression of the transcription factor E2F1, Dyrk1A activity can be increased by binding of 14-3-3 protein
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Dyrk1A expression can be reressed by the AP4- geminin complex
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
role of DYRK3 as an erythropoietic suppressor selectively during stress erythropoiesis, possible candidate for targeting by small molecule inhibitors as potentially important anti-anemia agents