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| | <StructureSection load='1oqn' size='340' side='right'caption='[[1oqn]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1oqn' size='340' side='right'caption='[[1oqn]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1oqn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OQN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1oqn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OQN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene></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=1oqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oqn OCA], [https://pdbe.org/1oqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oqn RCSB], [https://www.ebi.ac.uk/pdbsum/1oqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oqn 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=1oqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oqn OCA], [https://pdbe.org/1oqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oqn RCSB], [https://www.ebi.ac.uk/pdbsum/1oqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oqn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DAB1_MOUSE DAB1_MOUSE]] Adapter molecule functioning in neural development. May regulate SIAH1 activity.<ref>PMID:9009273</ref> [[https://www.uniprot.org/uniprot/A4_RAT A4_RAT]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1 (By similarity). Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts (By similarity). Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis (By similarity). N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (By similarity).
| + | [https://www.uniprot.org/uniprot/DAB1_MOUSE DAB1_MOUSE] Adapter molecule functioning in neural development. May regulate SIAH1 activity.<ref>PMID:9009273</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Curran, T]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Dickerson, J B]] | + | [[Category: Curran T]] |
| - | [[Category: Keshvara, L]] | + | [[Category: Dickerson JB]] |
| - | [[Category: Park, C G]] | + | [[Category: Keshvara L]] |
| - | [[Category: Park, H W]] | + | [[Category: Park C-G]] |
| - | [[Category: Rock, C O]] | + | [[Category: Park H-W]] |
| - | [[Category: Yun, M]] | + | [[Category: Rock CO]] |
| - | [[Category: Zhang, Y M]] | + | [[Category: Yun M]] |
| - | [[Category: Zheng, J]] | + | [[Category: Zhang Y-M]] |
| - | [[Category: App]]
| + | [[Category: Zheng J]] |
| - | [[Category: Inositol]]
| + | |
| - | [[Category: Ptb]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
DAB1_MOUSE Adapter molecule functioning in neural development. May regulate SIAH1 activity.[1]
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
Disabled (Dab) 1 and 2 are mammalian homologues of Drosophila DAB. Dab1 is a key cytoplasmic mediator in Reelin signaling that controls cell positioning in the developing central nervous system, whereas Dab2 is an adapter protein that plays a role in endocytosis. DAB family proteins possess an amino-terminal DAB homology (DH) domain that is similar to the phosphotyrosine binding/phosphotyrosine interaction (PTB/PI) domain. We have solved the structures of the DH domains of Dab2 (Dab2-DH) and Dab1 (Dab1-DH) in three different ligand forms, ligand-free Dab2-DH, the binary complex of Dab2-DH with the Asn-Pro-X-Tyr (NPXY) peptide of amyloid precursor protein (APP), and the ternary complex of Dab1-DH with the APP peptide and inositol 1,4,5-trisphosphate (Ins-1,4,5-P3, the head group of phosphatidylinositol-4,5-diphosphate (PtdIns-4,5-P2)). The similarity of these structures suggests that the rigid Dab DH domain maintains two independent pockets for binding of the APP/lipoprotein receptors and phosphoinositides. Mutagenesis confirmed the structural determinants specific for the NPXY sequence and PtdIns-4,5-P2 binding. NMR spectroscopy confirmed that the DH domain binds to Ins-1,4,5-P3 independent of the NPXY peptides. These findings suggest that simultaneous interaction of the rigid DH domain with the NPXY sequence and PtdIns-4,5-P2 plays a role in the attachment of Dab proteins to the APP/lipoprotein receptors and phosphoinositide-rich membranes.
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.,Yun M, Keshvara L, Park CG, Zhang YM, Dickerson JB, Zheng J, Rock CO, Curran T, Park HW J Biol Chem. 2003 Sep 19;278(38):36572-81. Epub 2003 Jun 24. PMID:12826668[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Howell BW, Gertler FB, Cooper JA. Mouse disabled (mDab1): a Src binding protein implicated in neuronal development. EMBO J. 1997 Jan 2;16(1):121-32. PMID:9009273 doi:http://dx.doi.org/10.1093/emboj/16.1.121
- ↑ Yun M, Keshvara L, Park CG, Zhang YM, Dickerson JB, Zheng J, Rock CO, Curran T, Park HW. Crystal structures of the Dab homology domains of mouse disabled 1 and 2. J Biol Chem. 2003 Sep 19;278(38):36572-81. Epub 2003 Jun 24. PMID:12826668 doi:10.1074/jbc.M304384200
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