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| - | [[Image:3dxc.png|left|200px]] | |
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| - | <!--
| + | ==Crystal structure of the intracellular domain of human APP in complex with Fe65-PTB2== |
| - | The line below this paragraph, containing "STRUCTURE_3dxc", creates the "Structure Box" on the page.
| + | <StructureSection load='3dxc' size='340' side='right'caption='[[3dxc]], [[Resolution|resolution]] 2.10Å' 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'>[[3dxc]] is a 4 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=3DXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DXC 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]] 2.1Å</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=3dxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dxc OCA], [https://pdbe.org/3dxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dxc RCSB], [https://www.ebi.ac.uk/pdbsum/3dxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dxc ProSAT]</span></td></tr> |
| - | {{STRUCTURE_3dxc| PDB=3dxc | SCENE= }}
| + | </table> |
| - | | + | == Function == |
| - | ===Crystal structure of the intracellular domain of human APP in complex with Fe65-PTB2===
| + | [https://www.uniprot.org/uniprot/APBB1_HUMAN APBB1_HUMAN] Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s).<ref>PMID:15031292</ref> <ref>PMID:18468999</ref> <ref>PMID:18922798</ref> <ref>PMID:19234442</ref> <ref>PMID:19343227</ref> |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | <!-- | + | Check<jmol> |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_18833287}}, adds the Publication Abstract to the page
| + | <jmolCheckbox> |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 18833287 is the PubMed ID number.
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dx/3dxc_consurf.spt"</scriptWhenChecked> |
| - | -->
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | {{ABSTRACT_PUBMED_18833287}}
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==About this Structure== | + | </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=3dxc ConSurf]. |
| - | [[3dxc]] is a 4 chain structure with 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=3DXC OCA]. | + | <div style="clear:both"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Human APP Intracellular Domain Complex with Fe65-PTB2]] | + | *[[Amyloid precursor protein 3D structures|Amyloid precursor protein 3D structures]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:18833287</ref><ref group="xtra">PMID:18453713</ref><references group="xtra"/> | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Radzimanowski, J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Sinning, I.]] | + | [[Category: Radzimanowski J]] |
| - | [[Category: Wild, K.]] | + | [[Category: Sinning I]] |
| - | [[Category: Aicd]] | + | [[Category: Wild K]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Alzheimer disease]]
| + | |
| - | [[Category: Alzheimer's disease]]
| + | |
| - | [[Category: Amyloid]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: App]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Coated pit]]
| + | |
| - | [[Category: Copper]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Fe65]]
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| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Heparin-binding]]
| + | |
| - | [[Category: Iron]]
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| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Notch signaling pathway]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protease inhibitor]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Proteoglycan]]
| + | |
| - | [[Category: Ptb domain]]
| + | |
| - | [[Category: Serine protease inhibitor]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Zinc]]
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| Structural highlights
Function
APBB1_HUMAN Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s).[1] [2] [3] [4] [5]
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
- ↑ Perkinton MS, Standen CL, Lau KF, Kesavapany S, Byers HL, Ward M, McLoughlin DM, Miller CC. The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling. J Biol Chem. 2004 May 21;279(21):22084-91. Epub 2004 Mar 18. PMID:15031292 doi:10.1074/jbc.M311479200
- ↑ Nakaya T, Kawai T, Suzuki T. Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. J Biol Chem. 2008 Jul 4;283(27):19119-31. Epub 2008 May 9. PMID:18468999 doi:M801827200
- ↑ Lau KF, Chan WM, Perkinton MS, Tudor EL, Chang RC, Chan HY, McLoughlin DM, Miller CC. Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. J Biol Chem. 2008 Dec 12;283(50):34728-37. Epub 2008 Oct 15. PMID:18922798 doi:M801874200
- ↑ Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009 Apr 2;458(7238):591-6. doi: 10.1038/nature07849. Epub 2009 Feb 22. PMID:19234442 doi:10.1038/nature07849
- ↑ Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, Haines JL, Pericak-Vance MA, Buxbaum JD. FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PLoS One. 2009;4(4):e5071. doi: 10.1371/journal.pone.0005071. Epub 2009 Apr 3. PMID:19343227 doi:10.1371/journal.pone.0005071
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