4ic8: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ic8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IC8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ic8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IC8 FirstGlance]. <br>
</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=4ic8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ic8 OCA], [https://pdbe.org/4ic8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ic8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ic8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ic8 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=4ic8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ic8 OCA], [https://pdbe.org/4ic8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ic8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ic8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ic8 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>  
[https://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mitogen-activated protein kinase (MAPK) activation depends on a linear binding motif found in all MAPK kinases (MKK). In addition, the PB1 (Phox and Bem1) domain of MKK5 is required for extracellular signal regulated kinase 5 (ERK5) activation. We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the PB1 domain and the linear binding motif. We show that ERK5 has distinct protein-protein interaction surfaces compared with ERK2, which is the closest ERK5 paralog. The two MAPKs have characteristically different physiological functions and their distinct protein-protein interaction surface topography enables them to bind different sets of activators and substrates. Structural and biochemical characterization revealed that the MKK5 PB1 domain cooperates with the MAPK binding linear motif to achieve substrate specific binding, and it also enables co-recruitment of the upstream activating enzyme and the downstream substrate into one signaling competent complex. Studies on present day MAPKs and MKKs hint on the way protein kinase networks may evolve. In particular, they suggest how paralogous enzymes with similar catalytic properties could acquire novel signaling roles by merely changing the way they make physical links to other proteins.
Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module.,Glatz G, Gogl G, Alexa A, Remenyi A J Biol Chem. 2013 Mar 22;288(12):8596-609. doi: 10.1074/jbc.M113.452235. Epub, 2013 Feb 4. PMID:23382384<ref>PMID:23382384</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ic8" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 14:53, 1 March 2024

Crystal structure of the apo ERK5 kinase domainCrystal structure of the apo ERK5 kinase domain

Structural highlights

4ic8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MK07_HUMAN Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.[1] [2] [3] [4] [5]

See Also

References

  1. ↑ Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 1997 Dec 1;16(23):7054-66. PMID:9384584 doi:10.1093/emboj/16.23.7054
  2. ↑ Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 1998 Oct 15;395(6703):713-6. PMID:9790194 doi:10.1038/27234
  3. ↑ Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD. BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase. J Biol Chem. 2001 Mar 23;276(12):8631-4. Epub 2001 Jan 31. PMID:11254654 doi:10.1074/jbc.C000838200
  4. ↑ Dong F, Gutkind JS, Larner AC. Granulocyte colony-stimulating factor induces ERK5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. J Biol Chem. 2001 Apr 6;276(14):10811-6. Epub 2001 Jan 17. PMID:11278431 doi:10.1074/jbc.M008748200
  5. ↑ Yang Q, Liao L, Deng X, Chen R, Gray NS, Yates JR 3rd, Lee JD. BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2012 Aug 6. doi: 10.1038/onc.2012.332. PMID:22869143 doi:10.1038/onc.2012.332

4ic8, resolution 2.80Å

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