2ak5

From Proteopedia

(Difference between revisions)

Revision as of 14:42, 17 November 2021

beta PIX-SH3 complexed with a Cbl-b peptide

Structural highlights

2ak5 is a 3 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ARHG7_RAT] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions. May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons (By similarity). [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.^[1] ^[2] ^[3] ^[4]

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 ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.

Cbl promotes clustering of endocytic adaptor proteins.,Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J Nat Struct Mol Biol. 2005 Nov;12(11):972-9. PMID:16228008^[5]

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

References

↑ 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
↑ Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J. Cbl promotes clustering of endocytic adaptor proteins. Nat Struct Mol Biol. 2005 Nov;12(11):972-9. PMID:16228008 doi:http://dx.doi.org/10.1038/nsmb1000

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ak5"

@@ Line 3: / Line 3: @@
 <StructureSection load='2ak5' size='340' side='right'caption='[[2ak5]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ak5]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AK5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AK5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ak5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AK5 FirstGlance]. <br>
-</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=2ak5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ak5 OCA], [http://pdbe.org/2ak5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ak5 RCSB], [http://www.ebi.ac.uk/pdbsum/2ak5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ak5 ProSAT]</span></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=2ak5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ak5 OCA], [https://pdbe.org/2ak5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ak5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ak5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ak5 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ARHG7_RAT ARHG7_RAT]] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions. May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons (By similarity). [[http://www.uniprot.org/uniprot/CBLB_HUMAN 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.<ref>PMID:10022120</ref> <ref>PMID:10086340</ref> <ref>PMID:11087752</ref> <ref>PMID:11526404</ref>
+[[https://www.uniprot.org/uniprot/ARHG7_RAT ARHG7_RAT]] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions. May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons (By similarity). [[https://www.uniprot.org/uniprot/CBLB_HUMAN 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.<ref>PMID:10022120</ref> <ref>PMID:10086340</ref> <ref>PMID:11087752</ref> <ref>PMID:11526404</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2ak5

From Proteopedia

Revision as of 14:42, 17 November 2021

beta PIX-SH3 complexed with a Cbl-b peptide

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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