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ATP + Ser/Arg-rich splicing factors
ADP + phosphorylated Ser/Arg-rich splicing factor
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
ATP + amphiphysin I
ADP + phosphorylated amphiphysin I
-
-
-
-
?
ATP + biotin-Ttds-TPGSRSRTPSLPT
ADP + phosphorylated biotin-Ttds-TPGSRSRTPSLPT
i.e. peptide PEP3
-
-
?
ATP + biotin-Ttds-VGLLKLASPELER
ADP + phosphorylated biotin-Ttds-VGLLKLASPELER
i.e. peptide PEP285
-
-
?
ATP + caspase-9
ADP + phosphorylated caspase-9
-
-
-
-
?
ATP + CREB
ADP + phosphorylated CREB
-
-
-
-
?
ATP + cyclin L2
ADP + phosphorylated cyclin L2
-
-
-
-
?
ATP + dynamin I
ADP + phosphorylated dynamin I
-
-
-
-
?
ATP + eIF2Bepsilon
ADP + phosphorylated eIF2Bepsilon
-
-
-
-
?
ATP + extracellular MAP kinase kinase
ADP + phospho-[MAP kinase kinase]
-
-
-
?
ATP + extracellular signal-regulated kinase
ADP + phospho-[extracellular signal-regulated kinase]
-
-
-
?
ATP + Gli1 protein
ADP + phosphorylated Gli1 protein
-
-
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
phosphorylation on serine, threonine, and tyrosine residues
-
-
?
ATP + neurodegeneration-related septin 4
ADP + phosphorylated neurodegeneration-related septin 4
SEPT4, also known as Pnutl2/CDCrel-2
-
-
?
ATP + NFAT
ADP + phosphorylated NFAT
-
-
-
-
?
ATP + Notch protein
ADP + phosphorylated Notch protein
-
-
-
-
?
ATP + peptide DYRKtide
ADP + phosphorylated peptide DYRKtide
synthetic peptide substrate
-
-
?
ATP + protein
ADP + phosphoprotein
ATP + RRARKLTATPTPLGG
ADP + RRARKLTApTPTPLGG
i.e. peptide SAPtide
-
-
?
ATP + RRRFRPASPLRGPPK
ADP + RRRFRPApSPLRGPPK
i.e. peptide DYRKtide, designed on the basis of the phosphorylation consensus sequence for DYRK1A
-
-
?
ATP + splicing factor 2
ADP + phosphorylated splicing factor 2
-
-
-
-
?
ATP + splicing factor 3
ADP + phosphorylated splicing factor 3
-
-
-
-
?
ATP + SR protein
ADP + hyperphosphorylated SR protein
i.e. serine-rich and arginine-rich proteins
-
?
ATP + STAT3
ADP + phosphorylated STAT3
-
-
-
-
?
ATP + synaptojanin I
ADP + phosphorylated synaptojanin I
-
-
-
-
?
ATP + transcription factor FKHR
ADP + phosphorylated transcription factor FKHR
-
-
-
-
?
additional information
?
-
ATP + SR protein
ADP + ?
enzyme may be involved in cell cycle control
-
-
?
ATP + SR protein
ADP + ?
the enzyme phosphorylates SR splicing factors and regulates their intranuclear distribution
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
ATP + protein
ADP + phosphoprotein
autophosphorylation
-
-
?
ATP + protein
ADP + phosphoprotein
autophosphorylation on serine, threonine, and tyrosine residues
-
-
?
ATP + SR protein
ADP + ?
-
-
-
?
ATP + SR protein
ADP + ?
enzyme is a good candidate to mediate some of the pleiotropic effects of Down syndrome
-
-
?
ATP + SR protein
ADP + ?
enzyme may be constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing
-
-
?
additional information
?
-
Esk kinase may play some role in the control of cell proliferation or differentiation
-
-
?
additional information
?
-
-
Esk kinase may play some role in the control of cell proliferation or differentiation
-
-
?
additional information
?
-
DYRK3 attenuates red cell production selectively during anemia
-
-
?
additional information
?
-
-
DYRK3 attenuates red cell production selectively during anemia
-
-
?
additional information
?
-
role of Dyrk1A in cognitive phenotypes of monosomy 21
-
-
?
additional information
?
-
-
Dyrk1A undergoes self-activation through autophosphorylation at Tyr 321
-
-
?
additional information
?
-
autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity
-
-
?
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ATP + a protein
ADP + a phosphoprotein
ATP + amphiphysin I
ADP + phosphorylated amphiphysin I
-
-
-
-
?
ATP + caspase-9
ADP + phosphorylated caspase-9
-
-
-
-
?
ATP + CREB
ADP + phosphorylated CREB
-
-
-
-
?
ATP + cyclin L2
ADP + phosphorylated cyclin L2
-
-
-
-
?
ATP + dynamin I
ADP + phosphorylated dynamin I
-
-
-
-
?
ATP + eIF2Bepsilon
ADP + phosphorylated eIF2Bepsilon
-
-
-
-
?
ATP + extracellular MAP kinase kinase
ADP + phospho-[MAP kinase kinase]
-
-
-
?
ATP + extracellular signal-regulated kinase
ADP + phospho-[extracellular signal-regulated kinase]
-
-
-
?
ATP + Gli1 protein
ADP + phosphorylated Gli1 protein
-
-
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
-
-
-
?
ATP + neurodegeneration-related septin 4
ADP + phosphorylated neurodegeneration-related septin 4
SEPT4, also known as Pnutl2/CDCrel-2
-
-
?
ATP + NFAT
ADP + phosphorylated NFAT
-
-
-
-
?
ATP + Notch protein
ADP + phosphorylated Notch protein
-
-
-
-
?
ATP + splicing factor 2
ADP + phosphorylated splicing factor 2
-
-
-
-
?
ATP + splicing factor 3
ADP + phosphorylated splicing factor 3
-
-
-
-
?
ATP + STAT3
ADP + phosphorylated STAT3
-
-
-
-
?
ATP + synaptojanin I
ADP + phosphorylated synaptojanin I
-
-
-
-
?
ATP + transcription factor FKHR
ADP + phosphorylated transcription factor FKHR
-
-
-
-
?
additional information
?
-
ATP + SR protein
ADP + ?
enzyme may be involved in cell cycle control
-
-
?
ATP + SR protein
ADP + ?
the enzyme phosphorylates SR splicing factors and regulates their intranuclear distribution
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
ATP + SR protein
ADP + ?
-
-
-
?
ATP + SR protein
ADP + ?
enzyme is a good candidate to mediate some of the pleiotropic effects of Down syndrome
-
-
?
ATP + SR protein
ADP + ?
enzyme may be constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing
-
-
?
additional information
?
-
Esk kinase may play some role in the control of cell proliferation or differentiation
-
-
?
additional information
?
-
-
Esk kinase may play some role in the control of cell proliferation or differentiation
-
-
?
additional information
?
-
-
Dyrk1A undergoes self-activation through autophosphorylation at Tyr 321
-
-
?
additional information
?
-
autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity
-
-
?
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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
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
malfunction
-
Dyrk1A participates in the pathogenic mechanisms underlying the mental and other physical symptoms of Down syndrome, alterations in Dyrk1A expression are frequently associated with Down syndrome phenotypes. Knock-out mice are embryonic lethal and heterozygous Dyrk1A mice exhibit decreased neonatal viability, developmental delay, and altered neocortical pyramidal cells
malfunction
-
heterozygous mice for Dyrk1A show marked alterations in traction ability, prehensile reflex and balance, but only present a slight impairment of visuo-spatial memory even though they show a robust decrease of CA1, CA2, CA3 and dentate gyrus cells
malfunction
Dyrk1A expression is increased in the brain of cystathionine-beta-synthase (CBS)-deficient mice. The murine model of hyperhomocysteinemia shows an activation of extracellular signal-regulated kinase (ERK) pathway. Significant increase of phosphorylated ERK, phosphorylated MAP kinase kinases, and phosphorylated Akt in the brain of CBS-deficient and Dyrk1A-overexpressing mice. Interaction between Dyrk1A and Grb2 is increased in the brain of Dyrk1A transgenic mice, but Dyrk1A overexpression results in decreased interaction of sprouty 2 and Grb2, and in increased receptor tyrosine kinases phosphorylation and activation, overview
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
physiological function
Dyrk1A is involved in diverse functions ranging from development and growth to apoptosis
physiological function
several splice variants of DYRK4 have distinct functional capacities
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Nayler, O.; Stamm, S.; Ullrich, A.
Characterization and comparison of four serine- and arginine-rich (SR) protein kinases
Biochem. J.
326
693-700
1997
Mus musculus (O35491), Mus musculus (O35492), Mus musculus (O35493)
brenda
Colwill, K.; Pawson, T.; Andrews, B.; Prasad, J.; Manley, J.L.; Bell, J.C.; Duncan, P.I.
The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution
EMBO J.
15
265-275
1996
Mus musculus (P22518)
brenda
Duncan, P.I.; Howell, B.W.; Marius, R.M.; Drmanic, S.; Douville, E.M.; Bell, J.C.
Alternative splicing of STY, a nuclear dual specificity kinase
J. Biol. Chem.
270
21524-21531
1995
Mus musculus (P22518), Mus musculus
brenda
Hanes, J.; von der Kammer, H.; Klaudiny, J.; Scheit, K.H.
Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases
J. Mol. Biol.
244
665-672
1994
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brenda
Howell, B.W.; Afar, D.E.; Lew, J.; Douville, E.M.; Icely, P.L.; Gray, D.A.; Bell, J.C.
STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine kinases
Mol. Cell. Biol.
11
568-572
1991
Mus musculus (P22518)
brenda
Ben-David, Y.; Letwin, K.; Tannock, L.; Bernstein, A.; Pawson, T.
A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators
EMBO J.
10
317-325
1991
Mus musculus (P22518)
brenda
Song, W.J.; Sternberg, L.R.; Kasten-Sportes, C.; et al.
Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region"
Genomics
38
331-339
1996
Homo sapiens (Q13627), Homo sapiens, Mus musculus (Q61214), Mus musculus
brenda
Song, W.J.; Chung, S.H.; Kurnit, D.M.
The murine Dyrk protein maps to chromosome 16, localizes to the nucleus, and can form multimers
Biochem. Biophys. Res. Commun.
231
640-644
1997
Mus musculus (Q61214)
brenda
Douville, E.M.; Afar, D.E.; Howell, B.W.; Letwin, K.; Tannock, L.; Ben-David, Y.; Pawson, T.; Bell, J.C.
Multiple cDNAs encoding the esk kinase predict transmembrane and intracellular enzyme isoforms
Mol. Cell. Biol.
12
2681-2689
1992
Mus musculus (P35761), Mus musculus
brenda
Leder, S.; Czajkowska, H.; Maenz, B.; De Graaf, K.; Barthel, A.; Joost, H.G.; Becker, W.
Alternative splicing variants of dual specificity tyrosine phosphorylated and regulated kinase 1B exhibit distinct patterns of expression and functional properties
Biochem. J.
372
881-888
2003
Homo sapiens, Mus musculus (Q9Z188), Mus musculus
brenda
Bogacheva, O.; Bogachev, O.; Menon, M.; Dev, A.; Houde, E.; Valoret, E.I.; Prosser, H.M.; Creasy, C.L.; Pickering, S.J.; Grau, E.; Rance, K.; Livi, G.P.; Karur, V.; Erickson-Miller, C.L.; Wojchowski, D.M.
DYRK3 dual-specificity kinase attenuates erythropoiesis during anemia
J. Biol. Chem.
283
36665-36675
2008
Mus musculus (Q922Y0), Mus musculus
brenda
Arque, G.; Fotaki, V.; Fernandez, D.; Martinez de Lagran, M.; Arbones, M.L.; Dierssen, M.
Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A)
PLoS ONE
3
e2575
2008
Mus musculus (Q61214)
brenda
Park, J.; Song, W.J.; Chung, K.C.
Function and regulation of Dyrk1A: towards understanding Down syndrome
Cell. Mol. Life Sci.
66
3235-3240
2009
Mus musculus
brenda
Arque, G.; de Lagran, M.M.; Arbones, M.L.; Dierssen, M.
Age-associated motor and visuo-spatial learning phenotype in Dyrk1A heterozygous mutant mice
Neurobiol. Dis.
36
312-319
2009
Mus musculus
brenda
Sitz, J.H.; Baumgaertel, K.; Haemmerle, B.; Papadopoulos, C.; Hekerman, P.; Tejedor, F.J.; Becker, W.; Lutz, B.
The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4
Neuroscience
157
596-605
2008
Mus musculus (Q61214), Mus musculus
brenda
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
J. Biol. Chem.
286
5494-5505
2011
Mus musculus (Q8BI55), Homo sapiens (Q9NR20)
brenda
Abekhoukh, S.; Planque, C.; Ripoll, C.; Urbaniak, P.; Paul, J.-L.; Delabar, J.-M.; Janel, N.
Dyrk1A, a serine/threonine kinase, is involved in ERK and Akt activation in the brain of hyperhomocysteinemic mice
Mol. Neurobiol.
47
105-116
2013
Mus musculus (Q61214), Mus musculus
brenda