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| | ==Solution structure of phosphoprotein enriched in astrocytes 15 kDa (PEA-15)== | | ==Solution structure of phosphoprotein enriched in astrocytes 15 kDa (PEA-15)== |
| - | <StructureSection load='1n3k' size='340' side='right' caption='[[1n3k]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1n3k' size='340' side='right'caption='[[1n3k]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n3k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cho_cell_lines Cho cell lines]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N3K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n3k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N3K FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PEA15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10029 CHO cell lines])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1n3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3k OCA], [http://pdbe.org/1n3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n3k RCSB], [http://www.ebi.ac.uk/pdbsum/1n3k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n3k 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=1n3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n3k OCA], [https://pdbe.org/1n3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n3k RCSB], [https://www.ebi.ac.uk/pdbsum/1n3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n3k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PEA15_CRIGR PEA15_CRIGR]] Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity). Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm.<ref>PMID:9852038</ref> <ref>PMID:10982386</ref> <ref>PMID:14506247</ref> | + | [https://www.uniprot.org/uniprot/PEA15_CRIGR PEA15_CRIGR] Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity). Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm.<ref>PMID:9852038</ref> <ref>PMID:10982386</ref> <ref>PMID:14506247</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cho cell lines]] | + | [[Category: Cricetulus griseus]] |
| - | [[Category: Ginsberg, M H]] | + | [[Category: Large Structures]] |
| - | [[Category: Hill, J M]] | + | [[Category: Ginsberg MH]] |
| - | [[Category: Ramos, J W]] | + | [[Category: Hill JM]] |
| - | [[Category: Vaidyanathan, H]] | + | [[Category: Ramos JW]] |
| - | [[Category: Werner, M H]] | + | [[Category: Vaidyanathan H]] |
| - | [[Category: Apoptosis]] | + | [[Category: Werner MH]] |
| - | [[Category: Death effector domain]]
| + | |
| - | [[Category: Six helix bundle]]
| + | |
| Structural highlights
Function
PEA15_CRIGR Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity). Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
PEA-15 is a multifunctional protein that modulates signaling pathways which control cell proliferation and cell death. In particular, PEA-15 regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. The three-dimensional structure of PEA-15 has been determined using NMR spectroscopy and its interaction with ERK defined by characterization of mutants that modulate ERK function. PEA-15 is composed of an N-terminal death effector domain (DED) and a C-terminal tail of irregular structure. NMR 'footprinting' and mutagenesis identified elements of both the DED and tail that are required for ERK binding. Comparison of the DED-binding surface for ERK2 with the death domain (DD)-binding surface of Drosophila Tube revealed an unexpected similarity between the interaction modes of the DD and DED motifs in these proteins. Despite a lack of functional or sequence similarity between PEA-15 and Tube, these proteins utilize a common surface of the structurally similar DD and DED to recognize functionally diverse targets.
Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain.,Hill JM, Vaidyanathan H, Ramos JW, Ginsberg MH, Werner MH EMBO J. 2002 Dec 2;21(23):6494-504. PMID:12456656[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ramos JW, Kojima TK, Hughes PE, Fenczik CA, Ginsberg MH. The death effector domain of PEA-15 is involved in its regulation of integrin activation. J Biol Chem. 1998 Dec 18;273(51):33897-900. PMID:9852038
- ↑ Ramos JW, Hughes PE, Renshaw MW, Schwartz MA, Formstecher E, Chneiweiss H, Ginsberg MH. Death effector domain protein PEA-15 potentiates Ras activation of extracellular signal receptor-activated kinase by an adhesion-independent mechanism. Mol Biol Cell. 2000 Sep;11(9):2863-72. PMID:10982386
- ↑ Chou FL, Hill JM, Hsieh JC, Pouyssegur J, Brunet A, Glading A, Uberall F, Ramos JW, Werner MH, Ginsberg MH. PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation. J Biol Chem. 2003 Dec 26;278(52):52587-97. Epub 2003 Sep 23. PMID:14506247 doi:10.1074/jbc.M309322200
- ↑ Hill JM, Vaidyanathan H, Ramos JW, Ginsberg MH, Werner MH. Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain. EMBO J. 2002 Dec 2;21(23):6494-504. PMID:12456656
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