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| | ==Crystal structure of human APPL2BARPH domain== | | ==Crystal structure of human APPL2BARPH domain== |
| - | <StructureSection load='4h8s' size='340' side='right' caption='[[4h8s]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='4h8s' size='340' side='right'caption='[[4h8s]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4h8s]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4h8s]] 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=4H8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H8S FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2z0o|2z0o]], [[2elb|2elb]], [[2q13|2q13]], [[2z0n|2z0n]], [[2q12|2q12]]</td></tr> | + | </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=4h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8s OCA], [https://pdbe.org/4h8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h8s RCSB], [https://www.ebi.ac.uk/pdbsum/4h8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8s ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APPL2, DIP13B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h8s OCA], [http://pdbe.org/4h8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h8s RCSB], [http://www.ebi.ac.uk/pdbsum/4h8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h8s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DP13B_HUMAN DP13B_HUMAN]] A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2. | + | [https://www.uniprot.org/uniprot/DP13B_HUMAN DP13B_HUMAN] A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DP13B_HUMAN DP13B_HUMAN]] Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.<ref>PMID:15016378</ref> | + | [https://www.uniprot.org/uniprot/DP13B_HUMAN DP13B_HUMAN] Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.<ref>PMID:15016378</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: King, G J]] | + | [[Category: Large Structures]] |
| - | [[Category: Martin, J L]] | + | [[Category: King GJ]] |
| - | [[Category: Adaptor protein]] | + | [[Category: Martin JL]] |
| - | [[Category: Bar domain]]
| + | |
| - | [[Category: Pleckstrin homology domain]]
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| - | [[Category: Rab binding]]
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| - | [[Category: Signaling protein]]
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| Structural highlights
Disease
DP13B_HUMAN A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2.
Function
DP13B_HUMAN Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.[1]
Publication Abstract from PubMed
The APPL1 and APPL2 proteins (APPL=adaptor protein, phosphotyrosine interaction, pleckstrin homology (PH) domain and leucine zipper containing protein) are localised to their own endosomal sub-compartment and interact with a wide range of proteins and small molecules at the cell surface and in the nucleus. They play important roles in signal transduction, through their ability to act as Rab effectors (Rabs are a family of Ras GTP-ases involved in membrane trafficking). Both APPL1 and APPL2 comprise an N-terminal membrane-curving BAR (Bin-amphiphysin-Rvs) domain linked to a PH domain and a C-terminal phosphotyrosine-binding domain. The structure and interactions of APPL1 are well characterised, but little is known about APPL2. Here we report the crystal structure and low resolution solution structure of the BARPH domains of APPL2. We identify a previously undetected hinge site for rotation between the two domains, and speculate that this motion may regulate APPL2 functions. We also identified Rab binding partners of APPL2 and show that these differ from those of APPL1, suggesting that APPL:Rab interaction partners have co-evolved over time. Isothermal titration calorimetry data reveal the interaction between APPL2 and Rab31 has a Kd of 140 nM. Together with other biophysical data we conclude the stoichiometry of the complex is 2:2.
Membrane-curvature protein exhibits interdomain flexibility and binds a small GTPase.,King GJ, Stoeckli J, Hu SH, Winnen B, Duprez WG, Meoli CC, Junutula JR, Jarrott RJ, James DE, Whitten AE, Martin JL J Biol Chem. 2012 Oct 10. PMID:23055524[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miaczynska M, Christoforidis S, Giner A, Shevchenko A, Uttenweiler-Joseph S, Habermann B, Wilm M, Parton RG, Zerial M. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell. 2004 Feb 6;116(3):445-56. PMID:15016378
- ↑ King GJ, Stoeckli J, Hu SH, Winnen B, Duprez WG, Meoli CC, Junutula JR, Jarrott RJ, James DE, Whitten AE, Martin JL. Membrane-curvature protein exhibits interdomain flexibility and binds a small GTPase. J Biol Chem. 2012 Oct 10. PMID:23055524 doi:http://dx.doi.org/10.1074/jbc.M112.349803
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