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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 [https://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 [https://proteopedia.org/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 ([https://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'>[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>
<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 ==
[[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>
[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: Large Structures]]
[[Category: Large Structures]]
[[Category: Ginsberg, M H]]
[[Category: Ginsberg MH]]
[[Category: Hill, J M]]
[[Category: Hill JM]]
[[Category: Ramos, J W]]
[[Category: Ramos JW]]
[[Category: Vaidyanathan, H]]
[[Category: Vaidyanathan H]]
[[Category: Werner, M H]]
[[Category: Werner MH]]
[[Category: Apoptosis]]
[[Category: Death effector domain]]
[[Category: Six helix bundle]]

Latest revision as of 11:52, 22 May 2024

Solution structure of phosphoprotein enriched in astrocytes 15 kDa (PEA-15)Solution structure of phosphoprotein enriched in astrocytes 15 kDa (PEA-15)

Structural highlights

1n3k is a 1 chain structure with sequence from Cricetulus griseus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. 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
  2. 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
  3. 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
  4. 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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