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| | <StructureSection load='2j7i' size='340' side='right'caption='[[2j7i]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='2j7i' size='340' side='right'caption='[[2j7i]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2j7i]] 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=2J7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J7I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2j7i]] is a 4 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=2J7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J7I FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cdb|1cdb]], [[1gya|1gya]], [[1hnf|1hnf]], [[1l2z|1l2z]], [[2bz8|2bz8]], [[2j6f|2j6f]], [[2j6k|2j6k]], [[2j6o|2j6o]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cdb|1cdb]], [[1gya|1gya]], [[1hnf|1hnf]], [[1l2z|1l2z]], [[2bz8|2bz8]], [[2j6f|2j6f]], [[2j6k|2j6k]], [[2j6o|2j6o]]</div></td></tr> |
| - | <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=2j7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j7i OCA], [http://pdbe.org/2j7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j7i RCSB], [http://www.ebi.ac.uk/pdbsum/2j7i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j7i 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=2j7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j7i OCA], [https://pdbe.org/2j7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j7i RCSB], [https://www.ebi.ac.uk/pdbsum/2j7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j7i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN]] Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:[http://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 == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/CD2_HUMAN CD2_HUMAN]] CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling 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/CD2_HUMAN CD2_HUMAN]] CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| 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] [CD2_HUMAN] CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function.
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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