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| | <StructureSection load='5af6' size='340' side='right'caption='[[5af6]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='5af6' size='340' side='right'caption='[[5af6]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5af6]] is a 10 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=5AF6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AF6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5af6]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AF6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5af4|5af4]], [[5af5|5af5]]</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=5af6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5af6 OCA], [https://pdbe.org/5af6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5af6 RCSB], [https://www.ebi.ac.uk/pdbsum/5af6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5af6 ProSAT]</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=5af6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5af6 OCA], [http://pdbe.org/5af6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5af6 RCSB], [http://www.ebi.ac.uk/pdbsum/5af6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5af6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZRAN1_HUMAN ZRAN1_HUMAN]] Specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin. Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones. Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration. May also modulate TNF-alpha signaling.<ref>PMID:18281465</ref> <ref>PMID:21834987</ref> <ref>PMID:23827681</ref> <ref>PMID:22157957</ref> | + | [https://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin|Ubiquitin]] | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Elliott, P R]] | + | [[Category: Elliott PR]] |
| - | [[Category: Freund, S M.V]] | + | [[Category: Freund SMV]] |
| - | [[Category: Komander, D]] | + | [[Category: Komander D]] |
| - | [[Category: Michel, M A]] | + | [[Category: Michel MA]] |
| - | [[Category: Pruneda, J N]] | + | [[Category: Pruneda JN]] |
| - | [[Category: Simicek, M]] | + | [[Category: Simicek M]] |
| - | [[Category: Swatek, K N]] | + | [[Category: Swatek KN]] |
| - | [[Category: Wagstaff, J L]] | + | [[Category: Wagstaff JL]] |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| - | [[Category: Ubiquitin trabid]]
| + | |
| Structural highlights
Function
UBC_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[1] [2]
Publication Abstract from PubMed
Protein ubiquitination regulates many cellular processes via attachment of structurally and functionally distinct ubiquitin (Ub) chains. Several atypical chain types have remained poorly characterized because the enzymes mediating their assembly and receptors with specific binding properties have been elusive. We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and K11/K33-linked Ub chains, respectively, and can be used in combination with DUBs to generate K29- and K33-linked chains for biochemical and structural analyses. Solution studies indicate that both chains adopt open and dynamic conformations. We further show that the N-terminal Npl4-like zinc finger (NZF1) domain of the K29/K33-specific deubiquitinase TRABID specifically binds K29/K33-linked diUb, and a crystal structure of this complex explains TRABID specificity and suggests a model for chain binding by TRABID. Our work uncovers linkage-specific components in the Ub system for atypical K29- and K33-linked Ub chains, providing tools to further understand these unstudied posttranslational modifications.
Assembly and Specific Recognition of K29- and K33-Linked Polyubiquitin.,Michel MA, Elliott PR, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SM, Komander D Mol Cell. 2015 Mar 4. pii: S1097-2765(15)00091-X. doi:, 10.1016/j.molcel.2015.01.042. PMID:25752577[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
- ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
- ↑ Michel MA, Elliott PR, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SM, Komander D. Assembly and Specific Recognition of K29- and K33-Linked Polyubiquitin. Mol Cell. 2015 Mar 4. pii: S1097-2765(15)00091-X. doi:, 10.1016/j.molcel.2015.01.042. PMID:25752577 doi:http://dx.doi.org/10.1016/j.molcel.2015.01.042
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