Abstract
Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL-ubiquitin-associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites / genetics
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Phenotype
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Proteasome Endopeptidase Complex / chemistry*
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Protein Subunits / chemistry
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Ubiquitin / metabolism*
Substances
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ADRM1 protein, human
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Adrm1 protein, mouse
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Cell Adhesion Molecules
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Protein Subunits
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RPN13 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Ubiquitin
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Proteasome Endopeptidase Complex