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2lb1

From Proteopedia

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Current revision

Structure of the second domain of human Smurf1 in complex with a human Smad1 derived peptide

Structural highlights

2lb1 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SMUF1_HUMAN E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA.^[1] ^[2] ^[3]

Publication Abstract from PubMed

When directed to the nucleus by TGF-beta or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events-Smad activation first and destruction later-and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains. Similarly, in the TGF-beta pathway, Smad3 phosphorylation by CDK8/9 creates binding sites for Pin1 and GSK3, then adds sites to enhance Nedd4L binding. Thus, a Smad phosphoserine code and a set of WW domain code readers provide an efficient solution to the problem of coupling TGF-beta signal delivery to turnover of the Smad signal transducers.

A Smad action turnover switch operated by WW domain readers of a phosphoserine code.,Aragon E, Goerner N, Zaromytidou AI, Xi Q, Escobedo A, Massague J, Macias MJ Genes Dev. 2011 Jun 15;25(12):1275-88. PMID:21685363^[4]

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

References

↑ Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature. 1999 Aug 12;400(6745):687-93. PMID:10458166 doi:10.1038/23293
↑ Li S, Lu K, Wang J, An L, Yang G, Chen H, Cui Y, Yin X, Xie P, Xing G, He F, Zhang L. Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Mol Cell Biochem. 2010 May;338(1-2):11-7. doi: 10.1007/s11010-009-0315-y. Epub, 2009 Nov 24. PMID:19937093 doi:10.1007/s11010-009-0315-y
↑ Lu K, Li P, Zhang M, Xing G, Li X, Zhou W, Bartlam M, Zhang L, Rao Z, He F. Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection. J Biol Chem. 2011 May 13;286(19):16861-70. Epub 2011 Mar 14. PMID:21402695 doi:10.1074/jbc.M110.211979
↑ Aragon E, Goerner N, Zaromytidou AI, Xi Q, Escobedo A, Massague J, Macias MJ. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 2011 Jun 15;25(12):1275-88. PMID:21685363 doi:10.1101/gad.2060811

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lb1"

@@ Line 1: / Line 1: @@
 ==Structure of the second domain of human Smurf1 in complex with a human Smad1 derived peptide==
-<StructureSection load='2lb1' size='340' side='right' caption='[[2lb1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2lb1' size='340' side='right'caption='[[2lb1]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2lb1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LB1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2lb1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LB1 FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2law|2law]], [[2lax|2lax]], [[2lay|2lay]], [[2laz|2laz]], [[2lb0|2lb0]], [[2lb2|2lb2]], [[2lb3|2lb3]]</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=2lb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lb1 OCA], [https://pdbe.org/2lb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lb1 RCSB], [https://www.ebi.ac.uk/pdbsum/2lb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lb1 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMURF1, KIAA1625 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2lb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lb1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lb1 RCSB], [http://www.ebi.ac.uk/pdbsum/2lb1 PDBsum]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/SMAD1_HUMAN SMAD1_HUMAN]] Defects in SMAD1 may be a cause of primary pulmonary hypertension (PPH1) [MIM:[http://omim.org/entry/178600 178600]]. A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.<ref>PMID:21898662</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/SMUF1_HUMAN SMUF1_HUMAN]] E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA.<ref>PMID:10458166</ref> <ref>PMID:19937093</ref> <ref>PMID:21402695</ref>  [[http://www.uniprot.org/uniprot/SMAD1_HUMAN SMAD1_HUMAN]] Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.<ref>PMID:12097147</ref>
+[https://www.uniprot.org/uniprot/SMUF1_HUMAN SMUF1_HUMAN] E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA.<ref>PMID:10458166</ref> <ref>PMID:19937093</ref> <ref>PMID:21402695</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2lb1" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
+*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 26: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Aragon, E]]
+[[Category: Large Structures]]
-[[Category: Escobedo, A]]
+[[Category: Aragon E]]
-[[Category: Goerner, N]]
+[[Category: Escobedo A]]
-[[Category: Macias, M J]]
+[[Category: Goerner N]]
-[[Category: Massague, J]]
+[[Category: Macias MJ]]
-[[Category: Xi, Q]]
+[[Category: Massague J]]
-[[Category: Zaromytidou, A]]
+[[Category: Xi Q]]
-[[Category: Cdk]]
+[[Category: Zaromytidou A]]
-[[Category: Signal transduction]]
-[[Category: Signaling protein-transcription complex]]
-[[Category: Smad]]
-[[Category: Smurf]]

2lb1

From Proteopedia

Current revision

Structure of the second domain of human Smurf1 in complex with a human Smad1 derived peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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