Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Functional differences in yeast protein disulfide isomerases.
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PDI1 is the essential PDI gene in budding yeast, but four nonessential
homologues (MPD1, MPD2, EUG1, EPS1) provide partial, non-interchangeable
redundancy; Mpd1p alone can carry out all essential Pdi1p functions, and an
endogenous CXXC-motif homologue is required for EUG1 (CXXS) suppression,
underlining the essentiality of PDI-catalyzed oxidation.
"The Saccharomyces cerevisiae genome, however, contains four other nonessential
genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1....This shows that the
homologues are not functionally interchangeable. In fact, Mpd1p was the only
homologue capable of carrying out all the essential functions of Pdi1p."
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PDI-family deletion strains show defects in carboxypeptidase Y (CPY) folding
and glycan modification, but no significant effect on ER-associated protein
degradation, indicating PDI1's primary role is in oxidative folding of
secretory clients such as CPY.
"Most mutant combinations show defects in carboxypeptidase Y folding as well as
in glycan modification."
Interactions among yeast protein-disulfide isomerase proteins and endoplasmic reticulum chaperone proteins influence their activities.
Domain architecture of protein-disulfide isomerase facilitates its dual role as an oxidase and an isomerase in Ero1p-mediated disulfide formation.
The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites.
Proteome survey reveals modularity of the yeast cell machinery.
Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
The Saccharomyces cerevisiae TRG1 gene is essential for growth and encodes a lumenal endoplasmic reticulum glycoprotein involved in the maturation of vacuolar carboxypeptidase.
Htm1 protein generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum.
A complex of Pdi1p and the mannosidase Htm1p initiates clearance of unfolded glycoproteins from the endoplasmic reticulum.
One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.
A Complex of Htm1 and the Oxidoreductase Pdi1 Accelerates Degradation of Misfolded Glycoproteins.
An inter-species protein-protein interaction network across vast evolutionary distance.
The social and structural architecture of the yeast protein interactome.
The contributions of protein disulfide isomerase and its homologues to oxidative protein folding in the yeast endoplasmic reticulum.
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Yeast Pdi1p both introduces disulfides into nascent proteins (oxidase activity)
and provides quality control by catalyzing rearrangement of incorrect disulfides
(isomerase activity); these are the two core catalytic activities of the enzyme.
"In vitro, protein disulfide isomerase (Pdi1p) introduces disulfides into
proteins (oxidase activity) and provides quality control by catalyzing the
rearrangement of incorrect disulfides (isomerase activity)."
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Consistent with an in vivo disulfide-isomerase role, the active sites of Pdi1p
are partially reduced (~32 +/- 8%) in vivo, indicating a mixed steady-state
redox state that supports both oxidation and isomerization/proofreading.
"Consistent with its function as a disulfide isomerase in vivo, the active sites
of Pdi1p are partially reduced (32 +/- 8%) in vivo."
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Oxidative folding of complex substrates such as carboxypeptidase Y (CPY) is
greatly compromised in isomerase-defective Pdi1p mutants, even though oxidase
activity alone supports wild-type growth, showing isomerization becomes
rate-limiting for multi-disulfide clients.
"pulse-chase experiments monitoring the maturation of carboxypeptidase Y reveal
that oxidative folding is greatly compromised in mutants that are defective in
isomerase activity."
Oxidative activity of yeast Ero1p on protein disulfide isomerase and related oxidoreductases of the endoplasmic reticulum.
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The sulfhydryl oxidase Ero1p oxidizes Pdi1p, which in turn catalyzes disulfide
formation in folding ER proteins, defining the Ero1p->Pdi1p->substrate oxidative
folding relay.
"The sulfhydryl oxidase Ero1 oxidizes protein disulfide isomerase (PDI), which in
turn catalyzes disulfide formation in proteins folding in the endoplasmic
reticulum (ER)."
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The amino-terminal (a) domain of Pdi1p is oxidized most rapidly by Ero1p and is
on a preferred pathway for oxidizing the ER thiol pool, with synthetic lethality
observed between a temperature-sensitive Ero1p variant and Pdi1p lacking the
N-terminal active-site disulfide.
"the Pdi1p amino-terminal domain was oxidized most rapidly compared with the
other oxidoreductase active sites tested...we observed synthetic lethality
between a temperature-sensitive Ero1p variant and mutant Pdi1p lacking the
amino-terminal active-site disulfide."
Analysis of ER resident proteins in Saccharomyces cerevisiae: implementation of H/KDEL retrieval sequences.
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Pdi1p is a soluble ER luminal resident protein; like most soluble ER residents
it cycles to the Golgi and is returned by retrograde transport via a C-terminal
HDEL retrieval motif, consistent with its ER lumen localization.
"Most, if not all, soluble ER resident proteins are transported continuously to
the Golgi where they are then returned to the ER by retrograde transport
machinery...an HDEL retrieval motif was both necessary and sufficient to retain
proteins within the early secretory pathway."
Falcon (Edison Scientific) deep research report: Saccharomyces cerevisiae PDI1 (UniProt P17967) functional annotation.
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Pdi1p is a multidomain thioredoxin-fold enzyme with canonical a-b-b'-a'
organization and two catalytic thioredoxin-like (CGHC/CXXC) active sites,
underlying both its enzymatic and chaperone/holdase properties.
"Yeast Pdi1p is a multidomain thioredoxin-fold enzyme with canonical
**a–b–b′–a′** organization"
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Pdi1p acts as oxidase, reductase, or isomerase depending on active-site redox
state: oxidized active sites oxidize client proteins; reduced active sites
reduce or isomerize incorrect disulfides.
"active-site cysteines are oxidized (forming a disulfide), it can oxidize client
proteins; when reduced (dithiol), it can reduce or isomerize incorrect disulfides"
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Pdi1p is an ER luminal resident; a systematic yeast ER-resident survey reports
its C-terminal ER retrieval motif as AIHDEL, consistent with HDEL-mediated
ER-Golgi retrieval cycling.
"Pdi1p is an **ER luminal resident** protein. A systematic yeast ER-resident
analysis reports its C-terminal ER retrieval motif as **AIHDEL**"
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In an ERAD context, association of Pdi1 with the mannosidase Htm1/Mnl1 can block
its canonical oxidative function and enable it to act as a disulfide reductase on
misfolded glycoproteins destined for retrotranslocation.
"the **Htm1/Mnl1–Pdi1** complex proposes that association with the mannosidase can
**block canonical oxidative function** of Pdi1 and enable it to operate as a
**disulfide reductase** for misfolded glycoproteins"
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PDI1 and its homologues are regulated by the unfolded protein response (UPR),
linking PDI capacity to ER stress sensing.
"PDI1 and its homologues are reported to be regulated by the unfolded protein
response (UPR)"