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Literature summary extracted from

  • Alexeeva, M.; Aberg, E.; Engh, R.A.; Rothweiler, U.
    The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine (2015), Acta Crystallogr. Sect. D, 71, 1207-1215.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.7.12.1 diagnostics DYRK1A is a risk factor for Alzheimer's disease, enabling detection of the disease prior to the development of behavioural symptoms by analyzing human plasma Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.12.1 recombinant expression of His6-tagged Dyrk1b kinase domain, residues 78-451 Homo sapiens
2.7.12.1 the dyrk1a gene is located in the Down syndrome critical region (DSCR) on chromosome 21 and full or partial trisomy of DSCR in Down syndrome (DS) leads to overexpression of DYRK1A, recombinant expression of His6-tagged Dyrk1a kinase domain, residues 126-490 Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.12.1 purified enzyme DYRK1A bound to inhibitor midostaurin, sitting drop vapour diffusion method, mixing of 200 nl of 7-10 mg/ml protein in 50 mM MOPS, pH 6.8, 50 mM KCl, 2 mM 2-mercaptoethanol, with 200 nl of precipitant solution containing 10-16% PEG 3350, 0.1 M potassium thiocyanate, 0.1 M KCl (or 0.1 M NaCl or 0.1 M LiCl), for co-crystallization with the inhibitor midostaurin, protein is mixed in a 1:1 ratio with the inhibitor in crystallization solution, containing 100 mM potassium thiocyanate, 50-100 mM LiCl (or NaCl or KCl), and 10-16% PEG 3350, to give a final drop size of 0.004 ml, by hanging drop vapour diffusion method, 5-7 days at room temperature, X-ray diffraction structure determination and analysis at 2.6 A resolution Homo sapiens
2.7.12.1 purified enzyme DYRK1B bound to inhibitor midostaurin, X-ray diffraction structure determination and analysis Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.12.1 harmine
-
 Homo sapiens
2.7.12.1 midostaurin i.e. PKC412, a derivative of the broad-spectrum kinase inhibitor staurosporine, an alkaloid isolated from Streptomyces staurosoreus; i.e. PKC412, a derivative of the broad-spectrum kinase inhibitor staurosporine, an alkaloid isolated from Streptomyces staurosoreus. Enzyme binding structure analysis, overview Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.12.1 additional information
-
 additional information Michaelis-Menten kinetics Homo sapiens
2.7.12.1 0.0807
-
 ATP pH 6.8, 22°C Homo sapiens
2.7.12.1 0.1185
-
 ATP pH 6.8, 22°C Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.12.1 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.12.1 ATP + a protein Homo sapiens
-
 ADP + a phosphoprotein
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.12.1 Homo sapiens Q13627
-
-
2.7.12.1 Homo sapiens Q9Y463
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.12.1 ATP + a protein
-
 Homo sapiens ADP + a phosphoprotein
-
 ?
2.7.12.1 ATP + RRRFRPASPLRGPPK i.e. DYRKtide Homo sapiens ADP + RRRFRPApSPLRGPPK
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.12.1 dual-specificity tyrosine phosphorylation-regulated kinase 1A
-
 Homo sapiens
2.7.12.1 dual-specificity tyrosine phosphorylation-regulated kinase 1B
-
 Homo sapiens
2.7.12.1 DYRK1A
-
 Homo sapiens
2.7.12.1 DYRK1B
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.12.1 22
-
 assay at room temperature Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.7.12.1 additional information
-
 inhibitors PKC412 and harmine elevate the melting point in buffer of the enzyme from 51°C to 53°C and 57°C, respectively Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.12.1 6.8
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.12.1 ATP
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.7.12.1 0.0000254
-
 midostaurin pH 6.8, 22°C Homo sapiens
2.7.12.1 0.0000284
-
 midostaurin pH 6.8, 22°C Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.12.1 0.000059
-
 pH 6.8, 22°C Homo sapiens midostaurin
2.7.12.1 0.000066
-
 pH 6.8, 22°C Homo sapiens midostaurin

General Information

EC Number General Information Comment Organism
2.7.12.1 malfunction the dyrk1a gene is located in the Down syndrome critical region (DSCR) on chromosome 21 and full or partial trisomy of DSCR in Down syndrome (DS) leads to overexpression of DYRK1A Homo sapiens
2.7.12.1 physiological function dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein kinase associated with neuronal development and brain physiology. Activity of DYRK1A to prime the tau protein for further phosphorylation by GSK-3beta. This leads to the hyperphosphorylation of tau, followed by selfaggregation into neurofibrillary tangles, which are the primary biomarker of Alzheimer's disease Homo sapiens