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| - | [[Image:1pht.jpg|left|200px]] | |
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| - | <!--
| + | ==PHOSPHATIDYLINOSITOL 3-KINASE P85-ALPHA SUBUNIT SH3 DOMAIN, RESIDUES 1-85== |
| - | The line below this paragraph, containing "STRUCTURE_1pht", creates the "Structure Box" on the page.
| + | <StructureSection load='1pht' size='340' side='right'caption='[[1pht]], [[Resolution|resolution]] 2.00Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1pht]] is a 1 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=1PHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PHT FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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=1pht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pht OCA], [https://pdbe.org/1pht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pht RCSB], [https://www.ebi.ac.uk/pdbsum/1pht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pht ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1pht| PDB=1pht | SCENE= }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/P85A_HUMAN P85A_HUMAN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.<ref>PMID:7518429</ref> <ref>PMID:17626883</ref> <ref>PMID:19805105</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ph/1pht_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pht ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''PHOSPHATIDYLINOSITOL 3-KINASE P85-ALPHA SUBUNIT SH3 DOMAIN, RESIDUES 1-85'''
| + | ==See Also== |
| - | | + | *[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]] |
| - | | + | == References == |
| - | ==Overview== | + | <references/> |
| - | The P13K SH3 domain, residues 1 to 85 of the P1-3 kinase p85 subunit, has been characterized by X-ray diffraction. Crystals belonging to space group P4(3)2(1)2 diffract to 2.0 angstroms resolution and the structure was phased by single isomorphous replacement and anomalous scattering (SIRAS). As expected, the domain is a compact beta barrel with an over-all confirmation very similar to the independently determined NMR structures. The X-ray structure illuminates a discrepancy between the two NMR structures on the conformation of the loop region unique to P13K SH3. Furthermore, the ligand binding pockets of P13K SH3 domain are occupied by amino acid residues from symmetry-related P13K SH3 molecules: the C-terminal residues I(82) SPP of one and R18 of another. The interaction modes clearly resemble those observed for the P13K SH3 domain complexed with the synthetic peptide RLP1, a class 1 ligand, although there are significant differences. The solid-state interactions suggest a model of protein-protein aggregation that could be mediated by SH3 domains.
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | |
| - | 1PHT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PHT OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Crystal structure of P13K SH3 domain at 20 angstroms resolution., Liang J, Chen JK, Schreiber ST, Clardy J, J Mol Biol. 1996 Apr 5;257(3):632-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8648629 8648629]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, J K.]] | + | [[Category: Chen JK]] |
| - | [[Category: Clardy, J.]] | + | [[Category: Clardy J]] |
| - | [[Category: Liang, J.]] | + | [[Category: Liang J]] |
| - | [[Category: Schreiber, S L.]] | + | [[Category: Schreiber SL]] |
| - | [[Category: P85-alpha subunit]]
| + | |
| - | [[Category: Phosphatidylinositol 3-kinase]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:06:06 2008''
| + | |
| Structural highlights
Function
P85A_HUMAN Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.[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.
See Also
References
- ↑ Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG, Alitalo K. Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1. J Biol Chem. 1994 Jul 15;269(28):18320-6. PMID:7518429
- ↑ Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007 Jul 13;317(5835):239-42. PMID:17626883 doi:317/5835/239
- ↑ Mandelker D, Gabelli SB, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. Epub 2009 Sep 23. PMID:19805105
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