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| | <StructureSection load='2cm0' size='340' side='right'caption='[[2cm0]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2cm0' size='340' side='right'caption='[[2cm0]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CM0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cm0]] is a 1 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=2CM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CM0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ccq|2ccq]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=2cm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm0 OCA], [https://pdbe.org/2cm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2cm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cm0 ProSAT]</span></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=2cm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm0 OCA], [https://pdbe.org/2cm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cm0 RCSB], [https://www.ebi.ac.uk/pdbsum/2cm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cm0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/NGLY1_HUMAN NGLY1_HUMAN]] Alacrimia-choreoathetosis-liver dysfunction syndrome. The disease is caused by mutations affecting the gene represented in this entry.
| + | [https://www.uniprot.org/uniprot/NGLY1_HUMAN NGLY1_HUMAN] Alacrimia-choreoathetosis-liver dysfunction syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NGLY1_HUMAN NGLY1_HUMAN]] Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.<ref>PMID:14749736</ref> <ref>PMID:15358861</ref>
| + | [https://www.uniprot.org/uniprot/NGLY1_HUMAN NGLY1_HUMAN] Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.<ref>PMID:14749736</ref> <ref>PMID:15358861</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allen, M D]] | + | [[Category: Allen MD]] |
| - | [[Category: Buchberger, A]] | + | [[Category: Buchberger A]] |
| - | [[Category: Bycroft, M]] | + | [[Category: Bycroft M]] |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Pug domain]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
NGLY1_HUMAN Alacrimia-choreoathetosis-liver dysfunction syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
NGLY1_HUMAN Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.[1] [2]
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 AAA ATPase p97 is a ubiquitin-selective molecular machine involved in multiple cellular processes, including protein degradation through the ubiquitin-proteasome system and homotypic membrane fusion. Specific p97 functions are mediated by a variety of cofactors, among them peptide N-glycanase, an enzyme that removes glycans from misfolded glycoproteins. Here we report the three-dimensional structure of the aminoterminal PUB domain of human peptide N-glycanase. We demonstrate that the PUB domain is a novel p97 binding module interacting with the D1 and/or D2 ATPase domains of p97 and identify an evolutionary conserved surface patch required for p97 binding. Furthermore, we show that the PUB and UBX domains do not bind to p97 in a mutually exclusive manner. Our results suggest that PUB domain-containing proteins constitute a widespread family of diverse p97 cofactors.
The PUB domain functions as a p97 binding module in human peptide N-glycanase.,Allen MD, Buchberger A, Bycroft M J Biol Chem. 2006 Sep 1;281(35):25502-8. Epub 2006 Jun 28. PMID:16807242[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blom D, Hirsch C, Stern P, Tortorella D, Ploegh HL. A glycosylated type I membrane protein becomes cytosolic when peptide: N-glycanase is compromised. EMBO J. 2004 Feb 11;23(3):650-8. Epub 2004 Jan 29. PMID:14749736 doi:http://dx.doi.org/10.1038/sj.emboj.7600090
- ↑ Katiyar S, Li G, Lennarz WJ. A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13774-9. Epub 2004 Sep 9. PMID:15358861 doi:http://dx.doi.org/10.1073/pnas.0405663101
- ↑ Allen MD, Buchberger A, Bycroft M. The PUB domain functions as a p97 binding module in human peptide N-glycanase. J Biol Chem. 2006 Sep 1;281(35):25502-8. Epub 2006 Jun 28. PMID:16807242 doi:10.1074/jbc.M601173200
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