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| | ==NMR Solution structure of ARAP3-SAM== | | ==NMR Solution structure of ARAP3-SAM== |
| - | <StructureSection load='2kg5' size='340' side='right'caption='[[2kg5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kg5' size='340' side='right'caption='[[2kg5]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kg5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KG5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kg5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KG5 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARAP3, CENTD3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kg5 OCA], [https://pdbe.org/2kg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kg5 RCSB], [https://www.ebi.ac.uk/pdbsum/2kg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kg5 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=2kg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kg5 OCA], [https://pdbe.org/2kg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kg5 RCSB], [https://www.ebi.ac.uk/pdbsum/2kg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kg5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ARAP3_HUMAN ARAP3_HUMAN]] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.<ref>PMID:11804589</ref> <ref>PMID:15569923</ref>
| + | [https://www.uniprot.org/uniprot/ARAP3_HUMAN ARAP3_HUMAN] Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.<ref>PMID:11804589</ref> <ref>PMID:15569923</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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leone, M]] | + | [[Category: Leone M]] |
| - | [[Category: Pellecchia, M]] | + | [[Category: Pellecchia M]] |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Cell projection]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Gtpase activation]]
| + | |
| - | [[Category: Helix bundle]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Sam domain]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
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| Structural highlights
Function
ARAP3_HUMAN Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.[1] [2]
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
BACKGROUND: Sterile alpha motif (Sam) domains are small protein modules that can be involved in homotypic or heterotypic associations and exhibit different functions. Previous studies have demonstrated that the Sam domain of the lipid phosphatase Ship2 can hetero-dimerize with the Sam domain of the PI3K effector protein Arap3. RESULTS: Here, we determine the NMR solution structure of Arap3-Sam and implement a multidisciplinary approach consisting of NMR spectroscopy, ITC (Isothermal Titration Calorimetry), mutagenesis and molecular modeling studies to analyze the interaction between Ship2-Sam and Arap3-Sam. This work reveals that Arap3-Sam may associate with Ship2-Sam by adopting a binding mode common to other Sam domains. This binding mode is identical to what we have very recently observed for the association between Ship2-Sam and the Sam domain from the Ephrin A2 receptor. CONCLUSION: Our studies further clarify the structural features that are relevant for Sam-Sam interactions involving Ship2 and give additional hints that could be used for the identification of new molecules able to selectively inhibit Sam-Sam associations.
The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam.,Leone M, Cellitti J, Pellecchia M BMC Struct Biol. 2009 Sep 18;9:59. PMID:19765305[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krugmann S, Anderson KE, Ridley SH, Risso N, McGregor A, Coadwell J, Davidson K, Eguinoa A, Ellson CD, Lipp P, Manifava M, Ktistakis N, Painter G, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Dove SK, Michell RH, Grewal A, Nazarian A, Erdjument-Bromage H, Tempst P, Stephens LR, Hawkins PT. Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol Cell. 2002 Jan;9(1):95-108. PMID:11804589
- ↑ Lu Q, Wei W, Kowalski PE, Chang AC, Cohen SN. EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17246-51. Epub 2004 Nov 29. PMID:15569923 doi:http://dx.doi.org/10.1073/pnas.0407794101
- ↑ Leone M, Cellitti J, Pellecchia M. The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam. BMC Struct Biol. 2009 Sep 18;9:59. PMID:19765305 doi:10.1186/1472-6807-9-59
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