2j6f

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Revision as of 07:18, 16 November 2017

N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG) BOUND TO CBL-B PEPTIDE

Structural highlights

2j6f is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2j6k, 2j6o, 2j7i
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [CBLB_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization.^[3] ^[4] ^[5] ^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC. Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. Oncogene. 1999 Feb 4;18(5):1147-56. PMID:10022120 doi:10.1038/sj.onc.1202411
↑ Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S. cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. PMID:10086340 doi:10.1038/sj.onc.1202499
↑ Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC. Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001 Feb 16;276(7):4872-8. Epub 2000 Nov 21. PMID:11087752 doi:10.1074/jbc.M008901200
↑ Fang D, Liu YC. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001 Sep;2(9):870-5. PMID:11526404 doi:10.1038/ni0901-870
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2j6f"

@@ Line 1: / Line 1: @@
 ==N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG) BOUND TO CBL-B PEPTIDE==
 <StructureSection load='2j6f' size='340' side='right' caption='[[2j6f]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2j6f]] is a 2 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=2J6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J6F FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2j6k|2j6k]], [[2j6o|2j6o]], [[2j7i|2j7i]]</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=2j6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6f OCA], [http://pdbe.org/2j6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j6f RCSB], [http://www.ebi.ac.uk/pdbsum/2j6f PDBsum]</span></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=2j6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6f OCA], [http://pdbe.org/2j6f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j6f RCSB], [http://www.ebi.ac.uk/pdbsum/2j6f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6f ProSAT]</span></td></tr>
 </table>
 == Disease ==

2j6f

From Proteopedia

Revision as of 07:18, 16 November 2017

N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG) BOUND TO CBL-B PEPTIDE

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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