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| | ==Crystal structures of non-phosphorylated MAP2K4== | | ==Crystal structures of non-phosphorylated MAP2K4== |
| - | <StructureSection load='3vut' size='340' side='right' caption='[[3vut]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='3vut' size='340' side='right'caption='[[3vut]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vut]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VUT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vut]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VUT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP2K4, JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP2K4, JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vut OCA], [http://pdbe.org/3vut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vut RCSB], [http://www.ebi.ac.uk/pdbsum/3vut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vut ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vut OCA], [https://pdbe.org/3vut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vut RCSB], [https://www.ebi.ac.uk/pdbsum/3vut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vut ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MP2K4_HUMAN MP2K4_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.<ref>PMID:7716521</ref> | + | [[https://www.uniprot.org/uniprot/MP2K4_HUMAN MP2K4_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.<ref>PMID:7716521</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3vut" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3vut" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mitogen-activated protein kinase kinase]] | | [[Category: Mitogen-activated protein kinase kinase]] |
| | [[Category: Kinoshita, T]] | | [[Category: Kinoshita, T]] |
| Structural highlights
3vut is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | MAP2K4, JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1 (HUMAN) |
| Activity: | Mitogen-activated protein kinase kinase, with EC number 2.7.12.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MP2K4_HUMAN] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.[1]
Publication Abstract from PubMed
Mitogen-activated protein kinase kinase 4 (MAP2K4) plays a crucial role in the stress-activated signal cascade and is enzymatically regulated by ligand or substrate binding, and/or post-translational modification. Crystal structures combined with small-angle X-ray scattering experiments revealed that the apo form of non-phosphorylated MAP2K4 (npMAP2K4) exists in a transient state which has a longer conformation compared with the typical kinase folding. Upon ATP-binding, the transient conformation adopted the configuration of typical kinase folding. In the absence of ATP-binding, the transient state of apo npMAP2K4 may shift to a state of aggregation via non-particular hydrophobic interactions as a result of the exposed hydrophobic residues.
Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4.,Matsumoto T, Kinoshita T, Kirii Y, Tada T, Yamano A Biochem Biophys Res Commun. 2012 Aug 24;425(2):195-200. Epub 2012 Jul 22. PMID:22828509[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286-90. PMID:7716521
- ↑ Matsumoto T, Kinoshita T, Kirii Y, Tada T, Yamano A. Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4. Biochem Biophys Res Commun. 2012 Aug 24;425(2):195-200. Epub 2012 Jul 22. PMID:22828509 doi:http://dx.doi.org/10.1016/j.bbrc.2012.07.066
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