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| | <StructureSection load='4x86' size='340' side='right'caption='[[4x86]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='4x86' size='340' side='right'caption='[[4x86]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x86]] is a 2 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=4X86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X86 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x86]] is a 2 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=4X86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X86 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBL4A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BAG6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4x86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x86 OCA], [https://pdbe.org/4x86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x86 RCSB], [https://www.ebi.ac.uk/pdbsum/4x86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x86 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=4x86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x86 OCA], [http://pdbe.org/4x86 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x86 RCSB], [http://www.ebi.ac.uk/pdbsum/4x86 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x86 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBL4A_HUMAN UBL4A_HUMAN]] Component of the BAT3 complex, a multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. The complex acts by facilitating TA proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins, and transfers them to ASNA1/TRC40 for targeting.<ref>PMID:20676083</ref> [[http://www.uniprot.org/uniprot/BAG6_HUMAN BAG6_HUMAN]] Chaperone that plays a key role in various processes such as apoptosis, insertion of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane and regulation of chromatin. Acts in part by regulating stability of proteins and their degradation by the proteasome. Participates in endoplasmic reticulum stress-induced apoptosis via its interaction with AIFM1/AIF by regulating AIFM1/AIF stability and preventing its degradation. Also required during spermatogenesis for synaptonemal complex assembly via its interaction with HSPA2, by inhibiting polyubiquitination and subsequent proteasomal degradation of HSPA2. Required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, may play a role in immuno-proteasomes to generate antigenic peptides via targeted degradation, thereby playing a role in antigen presentation in immune response. Key component of the BAG6/BAT3 complex, a cytosolic multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. BAG6/BAT3 acts by facilitating TA membrane proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins and transfers them to ASNA1/TRC40 for targeting to the endoplasmic reticulum membrane.<ref>PMID:14960581</ref> <ref>PMID:17403783</ref> <ref>PMID:18055229</ref> <ref>PMID:18765639</ref> <ref>PMID:18852879</ref> <ref>PMID:20516149</ref> <ref>PMID:20676083</ref> Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity. When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2).<ref>PMID:14960581</ref> <ref>PMID:17403783</ref> <ref>PMID:18055229</ref> <ref>PMID:18765639</ref> <ref>PMID:18852879</ref> <ref>PMID:20516149</ref> <ref>PMID:20676083</ref> Can be released from tumor and dendritic cells in membrane vesicles or exosomes, and engage NCR3 thereby promoting natural killer cell (NK) activation and cytotoxicity.<ref>PMID:14960581</ref> <ref>PMID:17403783</ref> <ref>PMID:18055229</ref> <ref>PMID:18765639</ref> <ref>PMID:18852879</ref> <ref>PMID:20516149</ref> <ref>PMID:20676083</ref> | + | [https://www.uniprot.org/uniprot/UBL4A_HUMAN UBL4A_HUMAN] Component of the BAT3 complex, a multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. The complex acts by facilitating TA proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins, and transfers them to ASNA1/TRC40 for targeting.<ref>PMID:20676083</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kato, R]] | + | [[Category: Kato R]] |
| - | [[Category: Kuwabara, N]] | + | [[Category: Kuwabara N]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Quality control of protein]]
| + | |
| - | [[Category: Tail-anchored transmembrane protein biogenesis]]
| + | |
| Structural highlights
Function
UBL4A_HUMAN Component of the BAT3 complex, a multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. The complex acts by facilitating TA proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins, and transfers them to ASNA1/TRC40 for targeting.[1]
Publication Abstract from PubMed
BAG6 is an essential protein that functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored (TA) transmembrane protein biogenesis in mammals, although its structural and functional properties remain unknown. We solved a crystal structure of the C-terminal heterodimerization domains of BAG6 and Ubl4a, and characterized their interaction biochemically. Unexpectedly, the specificity and structure of the C-terminus of BAG6, which was previously classified as a BAG domain, were completely distinct from those of the canonical BAG domain. Furthermore, the tight association of BAG6 and Ubl4a resulted in modulation of Ubl4a protein stability in cells. Therefore, we propose to designate the Ubl4a-binding region of BAG6 as the novel BAGS (BAG-similar) domain. The structure of Ubl4a, which interacts with BAG6, is similar to the yeast homologue Get5, which forms a homodimer. These observations indicate that the BAGS domain of BAG6 promotes the TA protein biogenesis pathway in mammals by the interaction with Ubl4a.
Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (Ubiquitin-like protein 4a) Complex Reveals a Novel Binding Interface that Functions in Tail-Anchored Protein Biogenesis.,Kuwabara N, Minami R, Yokota N, Matsumoto H, Senda T, Kawahara H, Kato R J Biol Chem. 2015 Feb 20. pii: jbc.M114.631804. PMID:25713138[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mariappan M, Li X, Stefanovic S, Sharma A, Mateja A, Keenan RJ, Hegde RS. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature. 2010 Aug 26;466(7310):1120-4. doi: 10.1038/nature09296. Epub 2010 Aug 1. PMID:20676083 doi:http://dx.doi.org/10.1038/nature09296
- ↑ Kuwabara N, Minami R, Yokota N, Matsumoto H, Senda T, Kawahara H, Kato R. Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (Ubiquitin-like protein 4a) Complex Reveals a Novel Binding Interface that Functions in Tail-Anchored Protein Biogenesis. J Biol Chem. 2015 Feb 20. pii: jbc.M114.631804. PMID:25713138 doi:http://dx.doi.org/10.1074/jbc.M114.631804
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