Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Adams Joseph, A.
    Activation loop phosphorylation and catalysis in protein kinases: is there functional evidence for the autoinhibitor model? (2003), Biochemistry, 42, 601-607.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.10.1 additional information activation mechanism eukaryota
2.7.11.11 cAMP
-
 eukaryota
2.7.11.11 additional information activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, dephosphorylation leads to enzyme activation by 2-3fold eukaryota
2.7.11.22 additional information phosphorylation regulates the enzyme activity, cyclin activating kinase CAK phosphorylates Thr160 of cdk2 leading to activation of cdk2 eukaryota
2.7.11.24 additional information phosphorylation activates the enzyme eukaryota

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.10.1 X-ray diffraction structure analysis of InRK and of FGFR with phosphorylated activation loop embedded in the substrate pocket eukaryota
2.7.11.11 X-ray diffraction structure analysis eukaryota

Protein Variants

EC Number Protein Variants Comment Organism
2.7.11.11 T197A site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme eukaryota
2.7.11.11 T197D site-directed mutagenesis, reduced activity compared to the wild-type enzyme eukaryota

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.11 additional information phosphorylation of the activation loop leads to enzyme inhibition, in which the phosphorylated activation loop acts as an autoinhibitory substrate blocking the nucleotide binding pocket, competition with ATP eukaryota

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.10.1 additional information
-
 additional information InRK: random kinetic mechanism, reaction kinetic can be influenced by the sort of substrate eukaryota
2.7.11.11 additional information
-
 additional information kinetics of activation and autoinhibition, modeling, pre-steady-state kinetic methods, wild-type and mutant enzymes eukaryota

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.10.1 membrane
-
 eukaryota 16020
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.10.1 Cd2+ can partially substitue Mg2+ eukaryota
2.7.10.1 Co2+ can partially substitue Mg2+ eukaryota
2.7.10.1 Mg2+
-
 eukaryota
2.7.10.1 Mg2+ dependent on, Mg2+ is the physiologic metal ion, other divalent cations are able to support nucleotide binding, but only Mn2+, Co2+, and Cd2+ can substitute Mg2+ in supporting the catalytic activity eukaryota
2.7.10.1 Mn2+ can partially substitue Mg2+ eukaryota
2.7.10.2 Mg2+
-
 eukaryota
2.7.11.11 Mg2+
-
 eukaryota
2.7.11.13 Mg2+
-
 eukaryota
2.7.11.22 Mg2+
-
 eukaryota
2.7.11.24 Mg2+
-
 eukaryota

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.10.1 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.10.1 additional information eukaryota mutations in the glycine-riche loop of MET can cause papillary renal-cell carcinomas ?
-
 ?
2.7.10.2 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + a protein eukaryota regulation by reversible phosphorylation, overview ADP + a phosphoprotein
-
 ?
2.7.11.13 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.11.22 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?
2.7.11.24 ATP + a protein eukaryota
-
 ADP + a phosphoprotein
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.10.1 eukaryota
-
-
-
2.7.10.2 eukaryota
-
-
-
2.7.11.11 eukaryota
-
-
-
2.7.11.13 eukaryota
-
-
-
2.7.11.22 eukaryota
-
-
-
2.7.11.24 eukaryota
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.10.1 phosphoprotein phosphorylation regulates the enzyme activity, but has only a small influence on substrate binding by InRK, and no influence on substrate binding of Tie-2 eukaryota
2.7.10.2 phosphoprotein phosphorylation regulates the enzyme activity, the enzyme is phosphorylated at the activation loop eukaryota
2.7.11.11 phosphoprotein the enzyme is regulated by reversible phosphorylation of the activation loop at Thr197, a polypeptide region outside the active site cleft, the enzyme is inhibited by phosphorylation, which also increases the affinity for ATP by 2fold, and activated by dephosphorylation eukaryota
2.7.11.13 phosphoprotein phosphorylation regulates the enzyme activity, the enzyme is phosphorylated by PDK-1 at the activation loop eukaryota
2.7.11.22 phosphoprotein phosphorylation regulates the enzyme activity, cyclin activating kinase CAK phosphorylates Thr160 of cdk2 leading to activation of cdk2, phosphorylation increases substrate binding of cdk2 by 2fold eukaryota
2.7.11.24 phosphoprotein the enzyme is regulated by reversible phosphorylation of the activation loop, phosphorylation enhances the substrate binding of ERK2 by 2fold eukaryota

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.10.1 ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate reaction mechanism eukaryota
a
2.7.10.1 ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate regulation of enzyme activity involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated eukaryota
a
2.7.10.2 ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate regulation of enzyme activity involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated eukaryota
a
2.7.11.11 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at Thr197, phosphorylation leads to enzyme inhibition, activation mechanism, overview eukaryota
a
2.7.11.13 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate regulation of enzyme activity involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at a Thr residue eukaryota
a
2.7.11.22 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated at a Thr residue, phosphorylation leads to enzyme inhibition eukaryota
a
2.7.11.24 ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated eukaryota
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.10.1 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.10.1 additional information mutations in the glycine-riche loop of MET can cause papillary renal-cell carcinomas eukaryota ?
-
 ?
2.7.10.1 additional information poor activity on free amino acids, consensus sequence of InRK is YM-MM, and of EGFR E-EEYF eukaryota ?
-
 ?
2.7.10.2 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.11 ATP + a protein regulation by reversible phosphorylation, overview eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.13 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.22 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?
2.7.11.22 ATP + cyclin dependent kinase 2 cyclin activating kinase CAK phosphorylates Thr160 of cdk2, a prerequisite for cell cycle control eukaryota ADP + phosphorylated cyclin dependent kinase 2
-
 ?
2.7.11.24 ATP + a protein
-
 eukaryota ADP + a phosphoprotein
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.10.1 Egfr
-
 eukaryota
2.7.10.1 epidermal growth factor receptor
-
 eukaryota
2.7.10.1 FGFR
-
 eukaryota
2.7.10.1 fibroblast growth factor receptor
-
 eukaryota
2.7.10.1 InRK
-
 eukaryota
2.7.10.1 insulin receptor kinase
-
 eukaryota
2.7.10.1 MET
-
 eukaryota
2.7.10.1 receptor PTK
-
 eukaryota
2.7.10.1 Tie-2
-
 eukaryota
2.7.10.1 tyrosine kinase domain of the insulin receptor
-
 eukaryota
2.7.10.2 nonreceptor PTK
-
 eukaryota
2.7.10.2 v-Fps
-
 eukaryota
2.7.11.11 cAMP-dependent protein kinase
-
 eukaryota
2.7.11.11 PKA
-
 eukaryota
2.7.11.13 PKC
-
 eukaryota
2.7.11.22 CAK
-
 eukaryota
2.7.11.22 CDK2
-
 eukaryota
2.7.11.22 cyclin activating kinase
-
 eukaryota
2.7.11.22 cyclin dependent kinase 2
-
 eukaryota
2.7.11.24 ERK2
-
 eukaryota
2.7.11.24 extracellular regulated kinase-2
-
 eukaryota

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.10.1 ATP dependent on eukaryota
2.7.10.1 ATP the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity of Tie-2 for ATP is not influenced by phosphorylation of the activation loop eukaryota
2.7.10.2 ATP the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity of v-Fps for ATP is not influenced by phosphorylation of the activation loop eukaryota
2.7.11.11 ATP the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity for ATP is increased 2fold by phosphorylation of the activation loop at Thr197, ATP competes with the phosphorylated activation loop, that acts as an autoinhibitory substrate eukaryota
2.7.11.13 ATP
-
 eukaryota
2.7.11.22 ATP the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity of cdk2 for ATP is not influenced by phosphorylation of the activation loop eukaryota
2.7.11.24 ATP the binding site is a deep pocket lined by hydrophobic residues, enzyme affinity for ATP is slightly increased by phosphorylation of the activation loop eukaryota