2laz

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{{STRUCTURE_2laz| PDB=2laz | SCENE= }}
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==Structure of the first WW domain of human Smurf1 in complex with a mono-phosphorylated human Smad1 derived peptide==
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===Structure of the first WW domain of human Smurf1 in complex with a mono-phosphorylated human Smad1 derived peptide===
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<StructureSection load='2laz' size='340' side='right' caption='[[2laz]], [[NMR_Ensembles_of_Models | 24 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_21685363}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2laz]] 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=2LAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LAZ FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2law|2law]], [[2lax|2lax]], [[2lay|2lay]], [[2lb0|2lb0]], [[2lb1|2lb1]], [[2lb2|2lb2]], [[2lb3|2lb3]]</td></tr>
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<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>
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<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=2laz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2laz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2laz RCSB], [http://www.ebi.ac.uk/pdbsum/2laz PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:21685363</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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>
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</div>
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==About this Structure==
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==See Also==
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[[2laz]] 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=2LAZ OCA].
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021685363</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Aragon, E.]]
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[[Category: Aragon, E]]
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[[Category: Escobedo, A.]]
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[[Category: Escobedo, A]]
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[[Category: Goerner, N.]]
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[[Category: Goerner, N]]
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[[Category: Macias, M J.]]
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[[Category: Macias, M J]]
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[[Category: Massague, J.]]
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[[Category: Massague, J]]
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[[Category: Xi, Q.]]
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[[Category: Xi, Q]]
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[[Category: Zaromytidou, A.]]
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[[Category: Zaromytidou, A]]
[[Category: Cdk]]
[[Category: Cdk]]
[[Category: Signal transduction]]
[[Category: Signal transduction]]

Revision as of 12:49, 18 December 2014

Structure of the first WW domain of human Smurf1 in complex with a mono-phosphorylated human Smad1 derived peptide

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