EC Number | Activating Compound | Comment | Organism | Structure |
---|---|---|---|---|
2.7.11.11 | cAMP | binds to the 2 catalytic subunits and activates via dissociation of the regulatory dimer | 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 2-3fold activation | eukaryota | |
2.7.11.22 | cyclin A | cdk2 is dependent on, required as activating subunit, complexes with cdk2 | eukaryota | |
2.7.11.24 | additional information | activation mechanism, phosphorylation/activation of ERK1 and ERK2 by the MAPK kinase-1 | eukaryota |
EC Number | Crystallization (Comment) | Organism |
---|---|---|
2.7.10.2 | - |
eukaryota |
2.7.11.11 | X-ray diffraction structure analysis of the catalytic subunits and the regulatory R2 dimer, enzyme cocrystallized with ATP and a peptide inhibitor | eukaryota |
2.7.11.22 | cdk2, X-ray diffraction structure analysis | eukaryota |
2.7.11.24 | ERK2, X-ray diffraction structure analysis | eukaryota |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
2.7.11.11 | ADP | noncompetitive inhibition with respect to ATP | eukaryota | |
2.7.11.11 | guanethidine | noncompetitive inhibiting serine peptide analogue with respect to ATP | eukaryota | |
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 | |
2.7.11.11 | peptide inhibitor PKI | - |
eukaryota |
EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|---|
2.7.10.2 | additional information | - |
additional information | c-Src, Csk: random kinetic mechanism, reaction kinetic can be influenced by the sort of substrate, high affinity for ADP | eukaryota | |
2.7.11.11 | additional information | - |
additional information | kinetics, random kinetic mechanism with kemptide as substrate, reaction kinetic can be influenced by the sort of substrate, pre-steady-state kinetics, slow structural changes during reaction | eukaryota | |
2.7.11.19 | additional information | - |
additional information | random kinetic mechanism, reaction order can be influenced by the sort of substrate | eukaryota | |
2.7.11.24 | additional information | - |
additional information | p38alpha: kinetic mechanism, reaction kinetics can be influenced by the sort of substrate | eukaryota |
EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|---|
2.7.10.2 | soluble | - |
eukaryota | - |
- |
EC Number | Metals/Ions | Comment | Organism | Structure |
---|---|---|---|---|
2.7.10.2 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.10.2 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.10.2 | 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 | |
2.7.10.2 | Mn2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.11 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.11 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.11 | Mg2+ | dependent on, chelates the beta- and gamma-phosphate of ATP, 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 | |
2.7.11.11 | Mn2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.19 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.19 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.19 | 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 | |
2.7.11.19 | Mn2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.22 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.22 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.22 | 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 | |
2.7.11.22 | Mn2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.24 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.24 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.11.24 | 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 | |
2.7.11.24 | Mn2+ | can partially substitue Mg2+ | eukaryota | |
2.7.12.2 | Cd2+ | can partially substitue Mg2+ | eukaryota | |
2.7.12.2 | Co2+ | can partially substitue Mg2+ | eukaryota | |
2.7.12.2 | 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 | |
2.7.12.2 | Mn2+ | can partially substitue Mg2+ | eukaryota |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
2.7.10.2 | ATP + a protein | eukaryota | - |
ADP + a phosphoprotein | - |
? | |
2.7.11.11 | ATP + a protein | eukaryota | regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms | ADP + a phosphoprotein | - |
? | |
2.7.11.19 | ATP + phosphorylase b | eukaryota | - |
ADP + phosphorylase a | - |
? | |
2.7.11.22 | ATP + a protein | eukaryota | - |
ADP + a phosphoprotein | - |
? | |
2.7.11.24 | ATP + a protein | eukaryota | - |
ADP + a phosphoprotein | - |
? | |
2.7.12.2 | ATP + a protein | eukaryota | - |
ADP + a phosphoprotein | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
2.7.10.2 | eukaryota | - |
- |
- |
2.7.11.11 | eukaryota | - |
- |
- |
2.7.11.19 | eukaryota | - |
- |
- |
2.7.11.22 | eukaryota | - |
- |
- |
2.7.11.24 | eukaryota | - |
- |
- |
2.7.12.2 | eukaryota | - |
- |
- |
EC Number | Posttranslational Modification | Comment | Organism |
---|---|---|---|
2.7.10.2 | phosphoprotein | regulation by phosphorylation of the activation loop, decreases ATP binding and substrate binding, enhances the phosphotransfer rate | eukaryota |
2.7.11.11 | phosphoprotein | regulation by phosphorylation at Thr197 of the activation loop, enhances ATP binding and phosphotransfer, but only slightly the substrate binding | eukaryota |
2.7.11.22 | phosphoprotein | regulation by phosphorylation of the activation loop, does not affect ATP binding, but enhances the phosphotransfer rate and the substrate binding | eukaryota |
2.7.11.24 | phosphoprotein | regulation by phosphorylation of the activation loop, increases substrate and ATP binding as well as the phosphotransfer rate, phosphorylation/activation of ERK1 and ERK2 by the MAPK kinase-1 | eukaryota |
EC Number | Reaction | Comment | Organism | Reaction ID |
---|---|---|---|---|
2.7.10.2 | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate | reaction mechanism | eukaryota | |
2.7.11.11 | ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | random kinetic mechanism, active site structure with key residues E91, K72, N171, K168, the general base catalyst D166, and essential catalytic D184, overview, reaction mechanism | eukaryota | |
2.7.11.22 | ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | reaction mechanism | eukaryota | |
2.7.11.24 | ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate | reaction mechanism | eukaryota |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
2.7.10.2 | ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.10.2 | ATP + a protein | PhK phosphorylates e.g. the protein substrate GPb, v-Fps phosphorylates e.g. the peptide substrate EAEIYEAEI, Csk phosphorylates e.g. the substrate poly-Glu4-Tyr | eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.10.2 | additional information | poor activity on free amino acids, consensus sequence of c-Src is E-EIYE/G-XF, that of v-Fps is E-IYE-XI/V, and that of Csk is IYM-F-F-F, specificity overview | eukaryota | ? | - |
? | |
2.7.11.11 | ATP + a protein | regulation of the enzyme involves reversible phosphorylation at the activation loop, and associative or dissociative mechanisms | eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.11 | ATP + a protein | the enzyme phosphorylates the peptide substrate LRRASLG | eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.11 | ATP + kemptide | - |
eukaryota | ADP + phospho-kemptide | - |
? | |
2.7.11.11 | additional information | poor activity on free amino acids, consensus sequence of PKA is R-RXS/T hyd | eukaryota | ? | - |
? | |
2.7.11.19 | ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.19 | ATP + phosphorylase b | - |
eukaryota | ADP + phosphorylase a | - |
? | |
2.7.11.19 | additional information | poor activity on free amino acids, consensus sequence of PhK is R-XXS/TF-F | eukaryota | ? | - |
? | |
2.7.11.22 | ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.22 | ATP + a protein | cdk2-cyclin A phosphorylates e.g. protein substrate p107 and peptide substrate PKTPKKAKKL, requiring a small hydrophobic patch RXL, known as a recruitment peptide | eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.22 | additional information | poor activity on free amino acids, consensus sequence of cdk2 is S/TP-XR/K | eukaryota | ? | - |
? | |
2.7.11.24 | ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.24 | ATP + a protein | ERK2 phosphorylates MBP, p38 phosphorylates the protein substrate MAPKAP2 and the peptide substrate KRELVEPLTPSGEAPNQALLR, other substrates of MAPK are transcription factors, such as c-Jun, ATF-2, and MEF2A | eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.11.24 | additional information | poor activity on free amino acids, consensus sequence of ERK2 is P-XS/TP, substrate specificity and recognition elements, e.g. PXTP, the activity on the protein substrate is much higher compared to a 14-residue peptide containing the phosphorylation site | eukaryota | ? | - |
? | |
2.7.12.2 | ATP + a protein | - |
eukaryota | ADP + a phosphoprotein | - |
? | |
2.7.12.2 | ATP + a protein | MKK1 phosphorylates and activates the MAP kinases ERK1 and ERK2 | eukaryota | ADP + a phosphoprotein | - |
? |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
2.7.10.2 | More | the enzyme consists of a kinase core and 2 noncatalytic portions SH2 and SH3 | eukaryota |
2.7.11.11 | More | structure modeling, structural elements, overview | eukaryota |
2.7.11.11 | tetramer | a heterotetramer composed of a regulatory dimer and 2 catalytic subunits, the tetramer is inactive, dissociation of the tetramer occurs during activation and cAMP binding | eukaryota |
2.7.11.19 | More | phosphorylase kinase is a multisubunit protein kinase with molecular weight above 1000000 Da | eukaryota |
2.7.11.22 | More | the enzyme requires a cyclin as activating subunit | eukaryota |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
2.7.10.2 | C-SRC | - |
eukaryota |
2.7.10.2 | C-terminal Src kinase | - |
eukaryota |
2.7.10.2 | cellular form of the transforming agent of Rous sarcoma virus | - |
eukaryota |
2.7.10.2 | Csk | - |
eukaryota |
2.7.10.2 | transforming agent of Fujinami sarcoma virus | - |
eukaryota |
2.7.10.2 | v-Fps | - |
eukaryota |
2.7.11.11 | PKA | - |
eukaryota |
2.7.11.19 | PhK | - |
eukaryota |
2.7.11.22 | CDK2 | - |
eukaryota |
2.7.11.22 | cyclin-dependent kinase-2 | - |
eukaryota |
2.7.11.24 | ERK1 | - |
eukaryota |
2.7.11.24 | ERK2 | - |
eukaryota |
2.7.11.24 | extracellular-regulated kinase-1 | - |
eukaryota |
2.7.11.24 | extracellular-regulated kinase-2 | - |
eukaryota |
2.7.11.24 | MAP kinase | - |
eukaryota |
2.7.11.24 | MAPK | - |
eukaryota |
2.7.11.24 | p38 | - |
eukaryota |
2.7.12.2 | MAPK kinase-1 | - |
eukaryota |
EC Number | Cofactor | Comment | Organism | Structure |
---|---|---|---|---|
2.7.10.2 | ATP | dependent on | eukaryota | |
2.7.11.11 | ATP | dependent on, 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 | |
2.7.11.19 | ATP | dependent on | eukaryota | |
2.7.11.22 | ATP | dependent on | eukaryota | |
2.7.11.24 | ATP | dependent on | eukaryota | |
2.7.12.2 | ATP | dependent on | eukaryota |