Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.52 (PNGase F)
 1,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide N-glycanase (PNGase) is involved in the cleavage of oligosaccharide chains from misfolded glycoproteins that are destined for degradation by the proteasome. Earlier, a number of potential binding partners of mouse PNGase (mPNGase) were detected by using the yeast two-hybrid system. In the current study, an in vitro system was set up to investigate direct interactions between mPNGase and these candidate proteins. Although the yeast two-hybrid system suggested an interaction of six different proteins with mPNGase, only mHR23B and the proteasome subunit mS4 were found to interact with mPNGase. In fact, mS4 competes with mHR23B for binding to mPNGase. These results suggested two possible pathways for the interaction between mPNGase and the proteasome. In one pathway, mHR23B mediates the interaction between mPNGase and the proteasome. In an alternative pathway, mPNGase directly binds to the proteasome subunit, mS4. In either case, it is clear that PNGase is located in close proximity to the proteasome and is available for deglycosylation of glycoproteins destined for degradation. Surprisingly, mPNGase also was found to mediate binding of the cytoplasmic protein, p97, to the proteasome through the formation of a ternary complex made up of mHR23B, mPNGase, and p97. Because p97 is known to bind to the endoplasmic reticulum membrane protein AMFR (gp78), an E3 ligase, we propose a model in which p97, mPNGase, and mHR23B mediate interaction of the endoplasmic reticulum with the proteasome.
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PMID:Multiple modes of interaction of the deglycosylation enzyme, mouse peptide N-glycanase, with the proteasome. 1624 33

Mouse peptide N-glycanase (mPNGase) cleaves the N-glycan chain from misfolded glycoproteins and glycopeptides. Previously, several proteins were found to directly interact with mPNGase; among them, both mHR23B and mS4 were found to link mPNGase to the proteasome. In this study, we found that the cytoplasmic protein mp97 participates in the formation of a ternary complex containing mouse autocrine motility factor receptor (mAMFR), mp97, and mPNGase. This assemblage recruits the cytosolic mPNGase close to the endoplasmic reticulum (ER) membrane, where the retrotranslocation of misfolded glycoproteins is thought to occur. In addition to the ER membrane-associated E3 ligase mAMFR, a cytosolic protein mY33K, containing both UBA and UBX domains, was found to also directly interact with mp97. Thus, a complex containing five proteins, mAMFR, mY33K, mp97, mPNGase, and mHR23B, is formed in close proximity to the ER membrane and serves to couple the activities of retrotranslocation, ubiquitination, and deglycosylation and, thereby, route misfolded glycoproteins to the proteasome.
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PMID:The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor. 1670 68