Any feedback?
Literature summary for 2.7.11.24 extracted from
- Two hydrophobic residues can determine the specificity of mitogen-activated protein kinase docking interactions (2015), J. Biol. Chem., 290, 26661-26674.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | the ERK2 MAPK is activated by phosphorylation through MEK1 and MEK2 | Mus musculus | |
| additional information | the JNK1 MAPK is activated by phosphorylation through MKK4 and MKK7 | Homo sapiens | |
| additional information | the JNK2 MAPK is activated by phosphorylation through MKK4 and MKK7 | Homo sapiens | |
| additional information | the p38 MAPK is activated by phosphorylation through MKK3, MKK6, and MKK4 | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of GST-tagged enzyme | Mus musculus |
| recombinant expression of GST-tagged enzyme | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| MKK4 | wild-type and L44I mutant MKK4, the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2; wild-type MKK4, the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2 | Homo sapiens | |
| MKK4 mutant F48K | the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2, but to a lesser degree compared to the wild-type MKK4; the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2, but to a lesser degree compared to the wild-type MKK4 | Homo sapiens | |
| MKK4 mutant L44I | the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2; wild-type and L44I mutant MKK4, the D-site from enzyme MKK4 competitively inhibits JNK-mediated phosphorylation of c-Jun and ATF2 | Homo sapiens | |
| additional information | no inhibition by MKK4 mutant L44I/F48K. Creation of MEK1-like, MEK2-like, MKK3-like, and MKK6-like alleles of MKK4 by changing 2 residues, L44 and F48, in the MKK4 D-site; no inhibition by MKK4 mutant L44I/F48K. Creation of MEK1-like, MEK2-like, MKK3-like, and MKK6-like alleles of MKK4 by changing 2 residues, L44 and F48, in the MKK4 D-site | Homo sapiens |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mus musculus |  |
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + ATF2 | Homo sapiens | - |
ADP + phosphorylated ATF2 | - |
? | |
| ATP + c-Jun | Homo sapiens | - |
ADP + phosphorylated c-Jun | - |
? | |
| ATP + Elk-1 | Mus musculus | an ETS family transcription factor | ADP + phosphorylated Elk-1 | - |
? | |
| ATP + Elk-1 | Homo sapiens | an ETS family transcription factor | ADP + phosphorylated Elk-1 | - |
? | |
| ATP + Net | Mus musculus | an ETS family transcription factor | ADP + phosphorylated Net | - |
? | |
| ATP + Net | Homo sapiens | an ETS family transcription factor | ADP + phosphorylated Net | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P45983 | - |
- |
| Homo sapiens | P45984 | - |
- |
| Homo sapiens | Q15759 | - |
- |
| Mus musculus | P63085 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | MKKs efficiently phosphorylate their cognate, within-pathway MAPKs and do not appreciably phosphorylate MAPKs in other pathways. The ERK MAPK is activated by phosphorylation through MEK1 and MEK2 | Mus musculus |
| phosphoprotein | MKKs efficiently phosphorylate their cognate, within-pathway MAPKs and do not appreciably phosphorylate MAPKs in other pathways. The JNK1 MAPK is activated by phosphorylation through MKK4 and MKK7. MKK7 binds to JNK1 preferentially over JNK2 and does not bind to p38. MKK4 exhibits the highest affinity binding for JNK2, followed by JNK1 and then p38 | Homo sapiens |
| phosphoprotein | MKKs efficiently phosphorylate their cognate, within-pathway MAPKs and do not appreciably phosphorylate MAPKs in other pathways. The JNK2 MAPK is activated by phosphorylation through MKK4 and MKK7. MKK7 binds to JNK1 preferentially over JNK2 and does not bind to p38. MKK4 exhibits the highest affinity binding for JNK2, followed by JNK1 and then p38 | Homo sapiens |
| phosphoprotein | MKKs efficiently phosphorylate their cognate, within-pathway MAPKs and do not appreciably phosphorylate MAPKs in other pathways. The p38 MAPK is activated by phosphorylation through MKK3, MKK6, and MKK4. MKK7 binds to JNK1 preferentially over JNK2 and does not bind to p38. MKK4 exhibits the highest affinity binding for JNK2, followed by JNK1 and then p38 | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| commercial preparation | activated ERK2 | Mus musculus | - |
| commercial preparation | activated ERK2 | Homo sapiens | - |
| commercial preparation | activated JNK1alpha1 | Homo sapiens | - |
| commercial preparation | activated JNK2alpha2 | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + ATF2 | - |
Homo sapiens | ADP + phosphorylated ATF2 | - |
? | |
| ATP + c-Jun | - |
Homo sapiens | ADP + phosphorylated c-Jun | - |
? | |
| ATP + Elk-1 | an ETS family transcription factor | Mus musculus | ADP + phosphorylated Elk-1 | - |
? | |
| ATP + Elk-1 | an ETS family transcription factor | Homo sapiens | ADP + phosphorylated Elk-1 | - |
? | |
| ATP + Elk-1 | an ETS family transcription factor with modified D-site by swapping two hydrophobic residues | Homo sapiens | ADP + phosphorylated Elk-1 | - |
? | |
| ATP + Net | an ETS family transcription factor | Mus musculus | ADP + phosphorylated Net | - |
? | |
| ATP + Net | an ETS family transcription factor | Homo sapiens | ADP + phosphorylated Net | - |
? | |
| ATP + Net | an ETS family transcription factor with modified D-site by swapping two hydrophobic residues | Homo sapiens | ADP + phosphorylated Net | - |
? | |
| additional information | MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK. Comparison of the hydrophobic submotif in strong versus weak JNK-binding D-sites, overview. The D-sites of the JNK pathway activator MKK4 contains LXL, as do all three of the D-sites in activator MKK7 in the first 3 residues of the hydrophobic submotif. MKK D-sites that bind JNK weakly lack an extended hydrophobic motif | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ERK2 | - |
Mus musculus |
| JNK1alpha1 | - |
Homo sapiens |
| JNK2alpha2 | - |
Homo sapiens |
| MAPK | - |
Mus musculus |
| MAPK | - |
Homo sapiens |
| MAPK1 | - |
Mus musculus |
| MAPK11 | - |
Homo sapiens |
| MAPK8 | - |
Homo sapiens |
| MAPK9 | - |
Homo sapiens |
| p38beta | - |
Homo sapiens |
| Prkm1 | - |
Mus musculus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Mus musculus |
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Mus musculus |
| 7.5 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mus musculus | |
| ATP | - |
Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.002 | - |
pH 7.5, 30°C, wild-type MKK4, JNK1, substrate ATF2 | Homo sapiens | MKK4 | |
| 0.003 | - |
pH 7.5, 30°C, JNK1, wild-type MKK4, substrate ATF2 | Homo sapiens | MKK4 mutant L44I | |
| 0.006 | - |
pH 7.5, 30°C, wild-type MKK4, JNK2, substrate c-Jun | Homo sapiens | MKK4 | |
| 0.045 | - |
pH 7.5, 30°C, JNK2, wild-type MKK4, substrate c-Jun | Homo sapiens | MKK4 mutant L44I | |
| 0.3 | - |
pH 7.5, 30°C, JNK1, wild-type MKK4, substrate ATF2 | Homo sapiens | MKK4 mutant F48K | |
| 0.4 | - |
pH 7.5, 30°C, JNK2, wild-type MKK4, substrate c-Jun | Homo sapiens | MKK4 mutant F48K |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | MAPK cascade proteins bind to each other selectively via docking interactions | Mus musculus |
| metabolism | MAPK cascade proteins bind to each other selectively via docking interactions | Homo sapiens |
| metabolism | MAPK cascade proteins bind to each other selectively via docking interactions. The high selectivity of JNK family MAPKs for cognate binding partners is controlled by two key hydrophobic residues in the docking site | Homo sapiens |
| additional information | MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The D-sites of the ERK pathway activators MEK1 and MEK2 contain IXL and LXI, respectively, in the first 3 residues of the hydrophobic submotif | Mus musculus |
| additional information | MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The D-sites of the p38 activators MKK3 and MKK6 both contain LXI in the first 3 residues of the hydrophobic submotif | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
