PDI1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: endoplasmic reticulum is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000432607 SUPPORTS TRANSFER PAINT placed ER localization on the broad PDI family node inherited by Saccharomyces cerevisiae PDI1; this matches Pdi1p's experimentally supported ER-lumen residence.
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: Protein folding (oxidative folding of secretory clients) is a core biological process for Pdi1p. Oxidizing equivalents flow Ero1p->Pdi1p->substrate, and a principal experimental client is carboxypeptidase Y (CPY), whose maturation requires Pdi1p disulfide formation and isomerization. Reason: Retained as supported or plausible for this gene and evidence context. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000432607 SUPPORTS TRANSFER The ancestral PDI node correctly covers the conserved ER oxidative-folding role inherited by PDI1. Supporting Evidence: file:yeast/PDI1/PDI1-deep-research-falcon.md A widely supported model is that oxidizing equivalents flow from Ero1p → Pdi1p → substrates. Ero1p is essential for ER thiol oxidation
GO:0034976 response to endoplasmic reticulum stress	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: response to endoplasmic reticulum stress is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000432607 SUPPORTS TRANSFER PDI1 sits inside the PAINT clade where response to endoplasmic reticulum stress was assigned, and yeast Pdi1p capacity is tied to UPR/ER-stress physiology as a contextual consequence of its ER protein-folding role.
GO:0003756 protein disulfide isomerase activity	IBA GO_REF:0000033	ACCEPT	Summary: Protein disulfide isomerase activity is the core molecular function of Pdi1p, well supported by biochemical and genetic evidence in yeast. Pdi1p both introduces disulfides (oxidase) and rearranges incorrect disulfides (isomerase), with the active sites partially reduced (~32%) in vivo to support isomerization. Reason: Retained as supported or plausible for this gene and evidence context. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000432607 SUPPORTS TRANSFER The curated ancestral node captures the active-site CGHC thiol-disulfide exchange activity that is retained by yeast Pdi1p. Supporting Evidence: file:yeast/PDI1/PDI1-deep-research-falcon.md active-site cysteines are oxidized (forming a disulfide), it can oxidize client proteins; when reduced (dithiol), it can reduce or isomerize incorrect disulfides
GO:0003756 protein disulfide isomerase activity	IEA GO_REF:0000120	ACCEPT	Summary: Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005788 endoplasmic reticulum lumen	IEA GO_REF:0000044	ACCEPT	Summary: Manual review: endoplasmic reticulum lumen is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0006457 protein folding	IEA GO_REF:0000117	ACCEPT	Summary: Manual review: protein folding is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0015035 protein-disulfide reductase activity	IEA GO_REF:0000117	ACCEPT	Summary: Protein-disulfide reductase activity is supported by the reductive branch of Pdi1p chemistry: when its active sites are reduced, Pdi1p reduces/rearranges incorrect disulfides, and in the Htm1/Mnl1-Pdi1 ERAD complex Pdi1 can be switched toward acting as a disulfide reductase on misfolded glycoproteins. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/PDI1/PDI1-deep-research-falcon.md 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
GO:0016853 isomerase activity	IEA GO_REF:0000043	ACCEPT	Summary: Manual review: isomerase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0051082 unfolded protein binding	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Manual review: unfolded protein binding is too generic or over-extended for PDI1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:16368681 Domain architecture of protein-disulfide isomerase facilitat...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records an interaction and does not describe Pdi1p's thiol-disulfide exchange activity, its ER oxidase/isomerase relay, or its Htm1/Mnl1-associated ERAD reductase role. Removal of this generic MF annotation does not dispute the reported interaction.
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records an interaction and does not describe Pdi1p's thiol-disulfide exchange activity, its ER oxidase/isomerase relay, or its Htm1/Mnl1-associated ERAD reductase role. Removal of this generic MF annotation does not dispute the reported interaction.
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records an interaction and does not describe Pdi1p's thiol-disulfide exchange activity, its ER oxidase/isomerase relay, or its Htm1/Mnl1-associated ERAD reductase role. Removal of this generic MF annotation does not dispute the reported interaction.
GO:0005515 protein binding	IPI PMID:19124653 Htm1 protein generates the N-glycan signal for glycoprotein ...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records the Pdi1p-Htm1p/Mnl1p interaction. The specific biology is captured by Htm1-Pdi1 exomannosidase complex membership and the mannose-trimming/glycoprotein-ERAD annotations, so a generic binding MF adds no additional functional information.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records an interaction and does not describe Pdi1p's thiol-disulfide exchange activity, its ER oxidase/isomerase relay, or its Htm1/Mnl1-associated ERAD reductase role. Removal of this generic MF annotation does not dispute the reported interaction.
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records the Pdi1p-Htm1p/Mnl1p interaction. The specific biology is captured by Htm1-Pdi1 exomannosidase complex membership and the mannose-trimming/glycoprotein-ERAD annotations, so a generic binding MF adds no additional functional information.
GO:0005788 endoplasmic reticulum lumen	IDA PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Endoplasmic reticulum lumen is the established site of Pdi1p function. Pdi1p is a soluble ER luminal resident with a C-terminal AIHDEL/HDEL retrieval motif that mediates ER-Golgi retrieval cycling, keeping it in the ER lumen. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/PDI1/PDI1-deep-research-falcon.md Pdi1p is an ER luminal resident protein. A systematic yeast ER-resident analysis reports its C-terminal ER retrieval motif as AIHDEL
GO:1900103 positive regulation of endoplasmic reticulum unfolded protein response	IDA PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Manual review: positive regulation of endoplasmic reticulum unfolded protein response is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005783 endoplasmic reticulum	HDA PMID:26928762 One library to make them all: streamlining the creation of y...	ACCEPT	Summary: Manual review: endoplasmic reticulum is consistent with known biology of PDI1. Reason: The SWAT-GFP high-throughput localization row places Pdi1p in the ER, which is consistent with direct evidence that Pdi1p is an ER-lumen resident. The SWAT paper describes PCR-validated GFP clones with repeated manual localization assignments. Supporting Evidence: PMID:26928762 Only strains with a duplicate repeating localization assignment and validated by PCR were chosen to compose the SWAT-GFP and SWAP-SP-GFP collections.
GO:0036508 protein alpha-1,2-demannosylation	IDA PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Manual review: protein alpha-1,2-demannosylation is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:1904382 mannose trimming involved in glycoprotein ERAD pathway	IDA PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Pdi1p participates in glycoprotein ERAD as part of a complex with the mannosidase Htm1/Mnl1; within this complex Pdi1 can be switched from oxidative folding toward disulfide reduction of misfolded glycoproteins destined for retrotranslocation. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/PDI1/PDI1-deep-research-falcon.md 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
GO:1904382 mannose trimming involved in glycoprotein ERAD pathway	IMP PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:1904382 mannose trimming involved in glycoprotein ERAD pathway	IGI PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear...	ACCEPT	Summary: Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:1904382 mannose trimming involved in glycoprotein ERAD pathway	IDA PMID:27053108 A Complex of Htm1 and the Oxidoreductase Pdi1 Accelerates De...	ACCEPT	Summary: Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0106055 mannosyl-oligosaccharide 1,2-alpha-mannosidase complex	IDA PMID:39930008 Initiation of ERAD by the bifunctional complex of Mnl1/Htm1 ...	NEW	Summary: Pdi1p is a stable subunit of the Mnl1/Htm1 mannosyl-oligosaccharide 1,2-alpha-mannosidase complex that initiates glycoprotein ERAD. Reason: Purification and cryo-EM of the S. cerevisiae Mnl1-Pdi1 complex directly support annotating PDI1 as part_of the GO complex term for this ERAD exomannosidase complex. Supporting Evidence: PMID:39930008 The Mnl1–Pdi1 complex was purified from S. cerevisiae cells that overexpress a FLAG-tagged version of Mnl1 (Mnl1–FLAG) together with Pdi1. The complex was released from the lumen of a membrane fraction by detergent treatment, enriched with anti-FLAG antibody beads and further purified as a 1:1 complex by size-exclusion chromatography (Extended Data Fig. 1b,c).
GO:0005515 protein binding	IPI PMID:16002399 Interactions among yeast protein-disulfide isomerase protein...	REMOVE	Summary: Generic protein binding is not an informative molecular-function annotation for PDI1. Reason: GO:0005515 only records an Eps1p-Pdi1p interaction and does not state a distinct Pdi1p molecular function beyond its direct thiol-disulfide exchange activities. Removal of this generic MF annotation does not dispute the reported interaction.
GO:0051082 unfolded protein binding	IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein...	MARK AS OVER ANNOTATED	Summary: Manual review: unfolded protein binding is too generic or over-extended for PDI1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0003756 protein disulfide isomerase activity	IMP PMID:11157982 Functional differences in yeast protein disulfide isomerases...	ACCEPT	Summary: Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0003756 protein disulfide isomerase activity	IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein...	ACCEPT	Summary: Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0003756 protein disulfide isomerase activity	IDA PMID:16413482 The crystal structure of yeast protein disulfide isomerase s...	ACCEPT	Summary: Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005788 endoplasmic reticulum lumen	IDA PMID:1761554 The Saccharomyces cerevisiae TRG1 gene is essential for grow...	ACCEPT	Summary: Manual review: endoplasmic reticulum lumen is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0006457 protein folding	IMP PMID:11157982 Functional differences in yeast protein disulfide isomerases...	ACCEPT	Summary: Manual review: protein folding is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0015035 protein-disulfide reductase activity	IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein...	ACCEPT	Summary: Manual review: protein-disulfide reductase activity is consistent with known biology of PDI1. Reason: Retained as supported or plausible for this gene and evidence context.

Gene Description

Existing Annotations Review

Core Functions

Pdi1p catalyzes thiol-disulfide exchange in the ER lumen to oxidize and isomerize disulfide bonds in nascent secretory and cell-surface proteins; Ero1p preferentially reoxidizes the Pdi1p a-domain to maintain this oxidative folding relay.

In the Htm1/Mnl1-Pdi1 ERAD complex, Pdi1p is redirected from its canonical oxidative role toward reductase chemistry that reduces disulfides in demannosylated misfolded glycoproteins, generating unfolded ERAD substrates competent for retrotranslocation.

References

Deep Research

Falcon

SGD

SGD gene description for PDI1 (yeast)

📚 Additional Documentation

Notes

Bioreason Rl Predictions

Bioreason Rl Review

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