View source for 9qwx


==Cryo-EM structure of the human UBR4/KCMF1/CALM1 complex (N-term focused refinement)==
<StructureSection load='9qwx' size='340' side='right'caption='[[9qwx]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qwx]] 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=9QWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QWX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</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=9qwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qwx OCA], [https://pdbe.org/9qwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qwx RCSB], [https://www.ebi.ac.uk/pdbsum/9qwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qwx ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UBR4_HUMAN UBR4_HUMAN] The gene represented in this entry may be involved in disease pathogenesis.
== Function ==
[https://www.uniprot.org/uniprot/UBR4_HUMAN UBR4_HUMAN] E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886).<ref>PMID:16214886</ref> <ref>PMID:23932781</ref> <ref>PMID:25582440</ref> <ref>PMID:29033132</ref> <ref>PMID:34893540</ref> <ref>PMID:37891180</ref> <ref>PMID:38030679</ref> <ref>PMID:38182926</ref> <ref>PMID:38297121</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Clausen T]]
[[Category: Grabarczyk DB]]