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| | <StructureSection load='2j6k' size='340' side='right'caption='[[2j6k]], [[Resolution|resolution]] 2.77Å' scene=''> | | <StructureSection load='2j6k' size='340' side='right'caption='[[2j6k]], [[Resolution|resolution]] 2.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2j6k]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J6K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2j6k]] is a 12 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=2J6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J6K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.77Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2j6f|2j6f]], [[2j6o|2j6o]], [[2j7i|2j7i]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=2j6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6k OCA], [https://pdbe.org/2j6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j6k RCSB], [https://www.ebi.ac.uk/pdbsum/2j6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6k 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=2j6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6k OCA], [https://pdbe.org/2j6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j6k RCSB], [https://www.ebi.ac.uk/pdbsum/2j6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN]] Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:[https://omim.org/entry/607832 607832]]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.<ref>PMID:12764198</ref>
| + | [https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN] Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:[https://omim.org/entry/607832 607832]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.<ref>PMID:12764198</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN]] Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.<ref>PMID:15800069</ref>
| + | [https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN] Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.<ref>PMID:15800069</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: Bravo, J]] | + | [[Category: Bravo J]] |
| - | [[Category: Cardenes, N]] | + | [[Category: Cardenes N]] |
| - | [[Category: Deribe, Y L]] | + | [[Category: Deribe YL]] |
| - | [[Category: Dikic, I]] | + | [[Category: Dikic I]] |
| - | [[Category: Moncalian, G]] | + | [[Category: Moncalian G]] |
| - | [[Category: Spinola-Amilibia, M]] | + | [[Category: Spinola-Amilibia M]] |
| - | [[Category: Adaptor protein]]
| + | |
| - | [[Category: Cd2 associated protein]]
| + | |
| - | [[Category: Cytoskeletal rearrangement]]
| + | |
| - | [[Category: Egfr downregulation]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Sh3]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Sh3-binding]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Surface active protein]]
| + | |
| Structural highlights
Disease
CD2AP_HUMAN Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:607832. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.[1]
Function
CD2AP_HUMAN Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.[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
The CIN85/CMS (human homologs of mouse SH3KBP1/CD2AP) family of endocytic adaptor proteins has the ability to engage multiple effectors and couple cargo trafficking with the cytoskeleton. CIN85 and CMS (Cas ligand with multiple Src homology 3 (SH3) domains) facilitate the formation of large multiprotein complexes required for an efficient internalization of cell surface receptors. It has recently been shown that c-Cbl/Cbl-b could mediate the formation of a ternary complex between one c-Cbl/Cbl-b molecule and two SH3 domains of CIN85, important for the ability of Cbl to promote epidermal growth factor receptor down-regulation. To further investigate whether multimerization is conserved within the family of adaptor proteins, we have solved the crystal structures of the CMS N-terminal SH3 domain-forming complexes with Cbl-b- and CD2-derived peptides. Together with biochemical evidence, the structures support the notion that, despite clear differences in the interaction surface, both Cbl-b and CD2 can mediate multimerization of N-terminal CMS SH3 domains. Detailed analyses on the interacting surfaces also provide the basis for a differential Cbl-b molecular recognition of CMS and CIN85.
Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain.,Moncalian G, Cardenes N, Deribe YL, Spinola-Amilibia M, Dikic I, Bravo J J Biol Chem. 2006 Dec 15;281(50):38845-53. Epub 2006 Oct 3. PMID:17020880[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003 May 23;300(5623):1298-300. PMID:12764198 doi:10.1126/science.1081068
- ↑ Monzo P, Gauthier NC, Keslair F, Loubat A, Field CM, Le Marchand-Brustel Y, Cormont M. Clues to CD2-associated protein involvement in cytokinesis. Mol Biol Cell. 2005 Jun;16(6):2891-902. Epub 2005 Mar 30. PMID:15800069 doi:E04-09-0773
- ↑ Moncalian G, Cardenes N, Deribe YL, Spinola-Amilibia M, Dikic I, Bravo J. Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain. J Biol Chem. 2006 Dec 15;281(50):38845-53. Epub 2006 Oct 3. PMID:17020880 doi:10.1074/jbc.M606411200
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