PDI1 encodes the essential protein disulfide isomerase of the ER lumen, a multifunctional oxidoreductase required for formation and isomerization of disulfide bonds in secretory and cell-surface proteins. Pdi1p catalyzes both the oxidation of free thiols and the reduction/rearrangement of non-native disulfide bonds, ensuring correct folding of ER client proteins. It forms a complex with the exomannosidase Mnl1p to recognize misfolded glycoproteins, process Man8GlcNAc2 oligosaccharides to Man7GlcNAc2, and reduce disulfide bonds of demannosylated substrates to generate unfolded polypeptides for retrotranslocation as part of ER-associated degradation (ERAD). Pdi1p also maintains Mnl1p solubility in the ER lumen and activates the oxidase Ero1p, which regenerates oxidized Pdi1p. Orthologous to human PDIA3.
| 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.
|
|
GO:0006457
protein folding
|
IBA
GO_REF:0000033 |
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: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.
|
|
GO:0003756
protein disulfide isomerase activity
|
IBA
GO_REF:0000033 |
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
|
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: 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.
|
|
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... |
MARK AS OVER ANNOTATED |
Summary: Manual review: 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:16429126 Proteome survey reveals modularity of the yeast cell machine... |
MARK AS OVER ANNOTATED |
Summary: Manual review: 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:16554755 Global landscape of protein complexes in the yeast Saccharom... |
MARK AS OVER ANNOTATED |
Summary: Manual review: 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:19124653 Htm1 protein generates the N-glycan signal for glycoprotein ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: 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:27107014 An inter-species protein-protein interaction network across ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: 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:37968396 The social and structural architecture of the yeast protein ... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for PDI1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005788
endoplasmic reticulum lumen
|
IDA
PMID:21700223 A complex of Pdi1p and the mannosidase Htm1p initiates clear... |
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: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: Retained as supported or plausible for this gene and evidence context.
|
|
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: 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
|
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:0005515
protein binding
|
IPI
PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for PDI1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
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.
|
Exported on March 22, 2026 at 02:01 AM
Organism: Saccharomyces cerevisiae
Sequence:
MKFSAGAVLSWSSLLLASSVFAQQEAVAPEDSAVVKLATDSFNEYIQSHDLVLAEFFAPWCGHCKNMAPEYVKAAETLVEKNITLAQIDCTENQDLCMEHNIPGFPSLKIFKNSDVNNSIDYEGPRTAEAIVQFMIKQSQPAVAVVADLPAYLANETFVTPVIVQSGKIDADFNATFYSMANKHFNDYDFVSAENADDDFKLSIYLPSAMDEPVVYNGKKADIADADVFEKWLQVEALPYFGEIDGSVFAQYVESGLPLGYLFYNDEEELEEYKPLFTELAKKNRGLMNFVSIDARKFGRHAGNLNMKEQFPLFAIHDMTEDLKYGLPQLSEEAFDELSDKIVLESKAIESLVKDFLKGDASPIVKSQEIFENQDSSVFQLVGKNHDEIVNDPKKDVLVLYYAPWCGHCKRLAPTYQELADTYANATSDVLIAKLDHTENDVRGVVIEGYPTIVLYPGGKKSESVVYQGSRSLDSLFDFIKENGHFDVDGKALYEEAQEKAAEEADADAELADEEDAIHDEL
I begin by examining the InterPro architecture. The sequence is dominated by IPR013766 (Thioredoxin domain, residues 15–485) and encompassed by IPR036249 (Thioredoxin-like superfamily, residues 29–498), indicating an extended array of thioredoxin-like folds that create a redox-active scaffold. The presence of IPR017937 (Thioredoxin, conserved site, residues 53–416) points to canonical thioredoxin active-site motifs that catalyze reversible thiol–disulfide exchange. Crucially, the protein is classified within IPR005792 (Protein disulphide isomerase family, residues 33–522), which defines its catalytic repertoire as not merely generic reduction but disulfide isomerization and substrate-shuffling typical of ER folding catalysts. The ordered architecture—multiple thioredoxin-like modules arrayed across the length of the polypeptide and consolidated under the PDI family—causally equips the protein to bind nascent polypeptides and catalyze intramolecular disulfide rearrangements.
This thioredoxin/PDI architecture dictates molecular function. The repeated thioredoxin modules and the PDI family signature together enforce protein disulfide isomerase chemistry: formation, reduction, and reshuffling of disulfide bonds within client proteins. That chemistry is captured by GO:0003756 protein disulfide isomerase activity. The extended thioredoxin framework also provides hydrophobic binding surfaces that transiently engage unfolded or partially folded substrates, supporting a general GO:0051082 unfolded protein binding activity intrinsic to ER chaperoning.
From function, I infer biological process. Disulfide isomerization is a core module of ER protein biogenesis, resolving non-native disulfides and stabilizing native structures. This places the protein squarely in GO:0006457 protein folding. Because disulfide management is especially critical during maturation of secretory and membrane proteins, and because PDI-family scaffolds buffer the folding load and quality control in the secretory pathway, the activity contributes to ER proteostasis and stress adaptation.
Cellular location follows naturally from mechanism. PDI-family enzymes operate where oxidative folding occurs—inside the endoplasmic reticulum. The soluble thioredoxin fold and lack of transmembrane features argue for a luminal, soluble residency. Thus, I deduce localization to the endoplasmic reticulum, specifically the GO:0005788 endoplasmic reticulum lumen, consistent with a yeast ER folding hub.
These features together suggest a mechanism and interaction landscape. The thioredoxin array binds nascent secretory proteins and cycles between reduced and oxidized states to catalyze disulfide formation and isomerization. Electron flow likely proceeds via ER redox relays: transient complexes with ERO1 (oxidative partner) to regenerate the oxidized PDI pool, and with glutathione-dependent pathways that buffer reductive steps. Client interactions will include glycoproteins and membrane-protein precursors entering the ER via Sec61/Sec62/Sec63. Additional cooperation with the calnexin/calreticulin cycle and BiP (Kar2) is expected, collectively forming an ER folding network that channels substrates through oxidative folding to native states.
An endoplasmic reticulum luminal folding catalyst that uses multiple thioredoxin-like modules to bind nascent secretory proteins and catalyze disulfide bond formation, reduction, and isomerization. By reshuffling non-native disulfides and stabilizing native structures, it supports oxidative protein folding and ER proteostasis. Its soluble thioredoxin architecture positions it within the ER folding network, where it collaborates with luminal chaperones and redox partners to maintain efficient maturation of disulfide-rich client proteins.
Probable disulfide isomerase.
IPR013766, domain) — residues 15-485IPR036249, homologous_superfamily) — residues 29-498IPR005792, family) — residues 33-522IPR017937, conserved_site) — residues 53-416Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), isomerase activity (GO:0016853), catalytic activity, acting on a protein (GO:0140096), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors (GO:0016667), protein disulfide isomerase activity (GO:0003756), intramolecular oxidoreductase activity (GO:0016860), protein-disulfide reductase activity (GO:0015035), unfolded protein binding (GO:0051082), disulfide oxidoreductase activity (GO:0015036), intramolecular oxidoreductase activity, transposing S-S bonds (GO:0016864)
Biological Process: biological_process (GO:0008150), metabolic process (GO:0008152), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), biological regulation (GO:0065007), response to stimulus (GO:0050896), cellular process (GO:0009987), positive regulation of signaling (GO:0023056), response to chemical (GO:0042221), positive regulation of response to stimulus (GO:0048584), nitrogen compound metabolic process (GO:0006807), organic substance metabolic process (GO:0071704), catabolic process (GO:0009056), cellular metabolic process (GO:0044237), protein folding (GO:0006457), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), regulation of signaling (GO:0023051), response to stress (GO:0006950), primary metabolic process (GO:0044238), positive regulation of cellular process (GO:0048522), positive regulation of signal transduction (GO:0009967), organonitrogen compound metabolic process (GO:1901564), positive regulation of response to endoplasmic reticulum stress (GO:1905898), regulation of response to stress (GO:0080134), cellular catabolic process (GO:0044248), protein metabolic process (GO:0019538), regulation of cellular response to stress (GO:0080135), regulation of signal transduction (GO:0009966), response to oxygen-containing compound (GO:1901700), macromolecule metabolic process (GO:0043170), response to organic substance (GO:0010033), carbohydrate derivative metabolic process (GO:1901135), response to nitrogen compound (GO:1901698), regulation of cell communication (GO:0010646), cellular response to stress (GO:0033554), positive regulation of cell communication (GO:0010647), organic substance catabolic process (GO:1901575), cellular macromolecule metabolic process (GO:0044260), organonitrogen compound catabolic process (GO:1901565), proteolysis (GO:0006508), protein catabolic process (GO:0030163), regulation of response to endoplasmic reticulum stress (GO:1905897), protein modification process (GO:0036211), response to endoplasmic reticulum stress (GO:0034976), macromolecule catabolic process (GO:0009057), macromolecule modification (GO:0043412), response to organonitrogen compound (GO:0010243), glycoprotein metabolic process (GO:0009100), positive regulation of endoplasmic reticulum unfolded protein response (GO:1900103), carbohydrate derivative catabolic process (GO:1901136), cellular macromolecule catabolic process (GO:0044265), response to glycoprotein (GO:1904587), regulation of endoplasmic reticulum unfolded protein response (GO:1900101), protein deglycosylation (GO:0006517), modification-dependent macromolecule catabolic process (GO:0043632), proteolysis involved in protein catabolic process (GO:0051603), glycoprotein catabolic process (GO:0006516), ERAD pathway (GO:0036503), proteasomal protein catabolic process (GO:0010498), protein demannosylation (GO:0036507), ubiquitin-dependent ERAD pathway (GO:0030433), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), modification-dependent protein catabolic process (GO:0019941), ubiquitin-dependent protein catabolic process (GO:0006511), protein alpha-1,2-demannosylation (GO:0036508)
Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), endoplasmic reticulum protein-containing complex (GO:0140534), membrane-enclosed lumen (GO:0031974), catalytic complex (GO:1902494), cytoplasm (GO:0005737), endomembrane system (GO:0012505), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), endoplasmic reticulum lumen (GO:0005788), intracellular membrane-bounded organelle (GO:0043231), intracellular organelle lumen (GO:0070013)
Generated by BioReason
Exported on March 22, 2026 at 02:01 AM
Organism: Saccharomyces cerevisiae
Sequence:
MKFSAGAVLSWSSLLLASSVFAQQEAVAPEDSAVVKLATDSFNEYIQSHDLVLAEFFAPWCGHCKNMAPEYVKAAETLVEKNITLAQIDCTENQDLCMEHNIPGFPSLKIFKNSDVNNSIDYEGPRTAEAIVQFMIKQSQPAVAVVADLPAYLANETFVTPVIVQSGKIDADFNATFYSMANKHFNDYDFVSAENADDDFKLSIYLPSAMDEPVVYNGKKADIADADVFEKWLQVEALPYFGEIDGSVFAQYVESGLPLGYLFYNDEEELEEYKPLFTELAKKNRGLMNFVSIDARKFGRHAGNLNMKEQFPLFAIHDMTEDLKYGLPQLSEEAFDELSDKIVLESKAIESLVKDFLKGDASPIVKSQEIFENQDSSVFQLVGKNHDEIVNDPKKDVLVLYYAPWCGHCKRLAPTYQELADTYANATSDVLIAKLDHTENDVRGVVIEGYPTIVLYPGGKKSESVVYQGSRSLDSLFDFIKENGHFDVDGKALYEEAQEKAAEEADADAELADEEDAIHDEL
I begin by examining the InterPro architecture. The sequence is dominated by IPR013766 (Thioredoxin domain, residues 15–485) and encompassed by IPR036249 (Thioredoxin-like superfamily, residues 29–498), indicating an extended array of thioredoxin-like folds that create a redox-active scaffold. The presence of IPR017937 (Thioredoxin, conserved site, residues 53–416) points to canonical thioredoxin active-site motifs that catalyze reversible thiol–disulfide exchange. Crucially, the protein is classified within IPR005792 (Protein disulphide isomerase family, residues 33–522), which defines its catalytic repertoire as not merely generic reduction but disulfide isomerization and substrate-shuffling typical of ER folding catalysts. The ordered architecture—multiple thioredoxin-like modules arrayed across the length of the polypeptide and consolidated under the PDI family—causally equips the protein to bind nascent polypeptides and catalyze intramolecular disulfide rearrangements.
This thioredoxin/PDI architecture dictates molecular function. The repeated thioredoxin modules and the PDI family signature together enforce protein disulfide isomerase chemistry: formation, reduction, and reshuffling of disulfide bonds within client proteins. That chemistry is captured by GO:0003756 protein disulfide isomerase activity. The extended thioredoxin framework also provides hydrophobic binding surfaces that transiently engage unfolded or partially folded substrates, supporting a general GO:0051082 unfolded protein binding activity intrinsic to ER chaperoning.
From function, I infer biological process. Disulfide isomerization is a core module of ER protein biogenesis, resolving non-native disulfides and stabilizing native structures. This places the protein squarely in GO:0006457 protein folding. Because disulfide management is especially critical during maturation of secretory and membrane proteins, and because PDI-family scaffolds buffer the folding load and quality control in the secretory pathway, the activity contributes to ER proteostasis and stress adaptation.
Cellular location follows naturally from mechanism. PDI-family enzymes operate where oxidative folding occurs—inside the endoplasmic reticulum. The soluble thioredoxin fold and lack of transmembrane features argue for a luminal, soluble residency. Thus, I deduce localization to the endoplasmic reticulum, specifically the GO:0005788 endoplasmic reticulum lumen, consistent with a yeast ER folding hub.
These features together suggest a mechanism and interaction landscape. The thioredoxin array binds nascent secretory proteins and cycles between reduced and oxidized states to catalyze disulfide formation and isomerization. Electron flow likely proceeds via ER redox relays: transient complexes with ERO1 (oxidative partner) to regenerate the oxidized PDI pool, and with glutathione-dependent pathways that buffer reductive steps. Client interactions will include glycoproteins and membrane-protein precursors entering the ER via Sec61/Sec62/Sec63. Additional cooperation with the calnexin/calreticulin cycle and BiP (Kar2) is expected, collectively forming an ER folding network that channels substrates through oxidative folding to native states.
An endoplasmic reticulum luminal folding catalyst that uses multiple thioredoxin-like modules to bind nascent secretory proteins and catalyze disulfide bond formation, reduction, and isomerization. By reshuffling non-native disulfides and stabilizing native structures, it supports oxidative protein folding and ER proteostasis. Its soluble thioredoxin architecture positions it within the ER folding network, where it collaborates with luminal chaperones and redox partners to maintain efficient maturation of disulfide-rich client proteins.
Probable disulfide isomerase.
IPR013766, domain) — residues 15-485IPR036249, homologous_superfamily) — residues 29-498IPR005792, family) — residues 33-522IPR017937, conserved_site) — residues 53-416Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), isomerase activity (GO:0016853), catalytic activity, acting on a protein (GO:0140096), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors (GO:0016667), protein disulfide isomerase activity (GO:0003756), intramolecular oxidoreductase activity (GO:0016860), protein-disulfide reductase activity (GO:0015035), unfolded protein binding (GO:0051082), disulfide oxidoreductase activity (GO:0015036), intramolecular oxidoreductase activity, transposing S-S bonds (GO:0016864)
Biological Process: biological_process (GO:0008150), metabolic process (GO:0008152), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), biological regulation (GO:0065007), response to stimulus (GO:0050896), cellular process (GO:0009987), positive regulation of signaling (GO:0023056), response to chemical (GO:0042221), positive regulation of response to stimulus (GO:0048584), nitrogen compound metabolic process (GO:0006807), organic substance metabolic process (GO:0071704), catabolic process (GO:0009056), cellular metabolic process (GO:0044237), protein folding (GO:0006457), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), regulation of signaling (GO:0023051), response to stress (GO:0006950), primary metabolic process (GO:0044238), positive regulation of cellular process (GO:0048522), positive regulation of signal transduction (GO:0009967), organonitrogen compound metabolic process (GO:1901564), positive regulation of response to endoplasmic reticulum stress (GO:1905898), regulation of response to stress (GO:0080134), cellular catabolic process (GO:0044248), protein metabolic process (GO:0019538), regulation of cellular response to stress (GO:0080135), regulation of signal transduction (GO:0009966), response to oxygen-containing compound (GO:1901700), macromolecule metabolic process (GO:0043170), response to organic substance (GO:0010033), carbohydrate derivative metabolic process (GO:1901135), response to nitrogen compound (GO:1901698), regulation of cell communication (GO:0010646), cellular response to stress (GO:0033554), positive regulation of cell communication (GO:0010647), organic substance catabolic process (GO:1901575), cellular macromolecule metabolic process (GO:0044260), organonitrogen compound catabolic process (GO:1901565), proteolysis (GO:0006508), protein catabolic process (GO:0030163), regulation of response to endoplasmic reticulum stress (GO:1905897), protein modification process (GO:0036211), response to endoplasmic reticulum stress (GO:0034976), macromolecule catabolic process (GO:0009057), macromolecule modification (GO:0043412), response to organonitrogen compound (GO:0010243), glycoprotein metabolic process (GO:0009100), positive regulation of endoplasmic reticulum unfolded protein response (GO:1900103), carbohydrate derivative catabolic process (GO:1901136), cellular macromolecule catabolic process (GO:0044265), response to glycoprotein (GO:1904587), regulation of endoplasmic reticulum unfolded protein response (GO:1900101), protein deglycosylation (GO:0006517), modification-dependent macromolecule catabolic process (GO:0043632), proteolysis involved in protein catabolic process (GO:0051603), glycoprotein catabolic process (GO:0006516), ERAD pathway (GO:0036503), proteasomal protein catabolic process (GO:0010498), protein demannosylation (GO:0036507), ubiquitin-dependent ERAD pathway (GO:0030433), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), modification-dependent protein catabolic process (GO:0019941), ubiquitin-dependent protein catabolic process (GO:0006511), protein alpha-1,2-demannosylation (GO:0036508)
Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), endoplasmic reticulum protein-containing complex (GO:0140534), membrane-enclosed lumen (GO:0031974), catalytic complex (GO:1902494), cytoplasm (GO:0005737), endomembrane system (GO:0012505), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), endoplasmic reticulum lumen (GO:0005788), intracellular membrane-bounded organelle (GO:0043231), intracellular organelle lumen (GO:0070013)
Generated by BioReason
Source: PDI1-deep-research-bioreason-rl.md
The BioReason summary states:
An endoplasmic reticulum luminal folding catalyst that uses multiple thioredoxin-like modules to bind nascent secretory proteins and catalyze disulfide bond formation, reduction, and isomerization.
This is accurate. The curated review confirms PDI1 is the essential protein disulfide isomerase of the ER lumen with protein disulfide isomerase activity (GO:0003756) and protein-disulfide reductase activity (GO:0015035). The multiple thioredoxin-like modules are correctly identified from the InterPro architecture.
By reshuffling non-native disulfides and stabilizing native structures, it supports oxidative protein folding and ER proteostasis.
Correct. The curated review confirms protein folding (GO:0006457) and response to ER stress (GO:0034976) as documented functions.
Its soluble thioredoxin architecture positions it within the ER folding network, where it collaborates with luminal chaperones and redox partners to maintain efficient maturation of disulfide-rich client proteins.
The ER lumen localization (GO:0005788) is correct, confirmed by IEA and IDA evidence. The mention of redox partners is appropriate -- the curated review documents the Ero1p oxidase interaction for regenerating oxidized Pdi1p.
The summary captures the core oxidoreductase/isomerase function well but misses several important aspects:
- The complex with exomannosidase Mnl1p (Htm1p) for recognition of misfolded glycoproteins (GO:1904382 mannose trimming involved in glycoprotein ERAD pathway)
- The role in ERAD: reducing disulfide bonds of demannosylated substrates to generate unfolded polypeptides for retrotranslocation
- Protein alpha-1,2-demannosylation (GO:0036508)
- Positive regulation of the ER unfolded protein response (GO:1900103)
- Maintenance of Mnl1p solubility in the ER lumen
These ERAD-related functions represent a significant second role for PDI1 beyond its canonical isomerase activity.
Comparison with interpro2go:
The interpro2go pipeline (GO_REF:0000120) assigns protein disulfide isomerase activity (GO:0003756), which is the core MF. BioReason's summary essentially elaborates the interpro2go annotation with mechanistic detail about thiol-disulfide exchange chemistry and ER folding. This is a case where BioReason adds useful narrative context to the interpro2go prediction, particularly regarding the multi-module thioredoxin architecture and collaboration with ER redox partners. However, the ERAD-related functions (Mnl1p complex, mannose trimming) are entirely organism/gene-specific and beyond what either approach captures.
The trace correctly identifies the PDI family (IPR005792) and infers ER luminal localization from the domain architecture. The prediction of ERO1 as a redox partner is accurate. The trace also correctly predicts calnexin/calreticulin cycle cooperation and BiP (Kar2) interaction, both of which are documented. The reasoning is sound within the constraints of domain-based inference.
id: P17967
gene_symbol: PDI1
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:559292
label: Saccharomyces cerevisiae
description: >-
PDI1 encodes the essential protein disulfide isomerase of the ER lumen, a
multifunctional oxidoreductase required for formation and isomerization of
disulfide bonds in secretory and cell-surface proteins. Pdi1p catalyzes both
the oxidation of free thiols and the reduction/rearrangement of non-native
disulfide bonds, ensuring correct folding of ER client proteins. It forms a
complex with the exomannosidase Mnl1p to recognize misfolded glycoproteins,
process Man8GlcNAc2 oligosaccharides to Man7GlcNAc2, and reduce disulfide
bonds of demannosylated substrates to generate unfolded polypeptides for
retrotranslocation as part of ER-associated degradation (ERAD). Pdi1p also
maintains Mnl1p solubility in the ER lumen and activates the oxidase Ero1p,
which regenerates oxidized Pdi1p. Orthologous to human PDIA3.
existing_annotations:
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: endoplasmic reticulum is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0006457
label: protein folding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: protein folding is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0034976
label: response to endoplasmic reticulum stress
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: response to endoplasmic reticulum stress is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003756
label: protein disulfide isomerase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003756
label: protein disulfide isomerase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: 'Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: 'Manual review: endoplasmic reticulum lumen is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0006457
label: protein folding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: 'Manual review: protein folding is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0015035
label: protein-disulfide reductase activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: 'Manual review: protein-disulfide reductase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0016853
label: isomerase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: 'Manual review: isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: 'Manual review: unfolded protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16368681
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16429126
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16554755
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19124653
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27107014
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:37968396
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: IDA
original_reference_id: PMID:21700223
review:
summary: 'Manual review: endoplasmic reticulum lumen is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1900103
label: positive regulation of endoplasmic reticulum unfolded protein response
evidence_type: IDA
original_reference_id: PMID:21700223
review:
summary: 'Manual review: positive regulation of endoplasmic reticulum unfolded protein response is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: HDA
original_reference_id: PMID:26928762
review:
summary: 'Manual review: endoplasmic reticulum is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0036508
label: protein alpha-1,2-demannosylation
evidence_type: IDA
original_reference_id: PMID:21700223
review:
summary: 'Manual review: protein alpha-1,2-demannosylation is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1904382
label: mannose trimming involved in glycoprotein ERAD pathway
evidence_type: IDA
original_reference_id: PMID:21700223
review:
summary: 'Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1904382
label: mannose trimming involved in glycoprotein ERAD pathway
evidence_type: IMP
original_reference_id: PMID:21700223
review:
summary: 'Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1904382
label: mannose trimming involved in glycoprotein ERAD pathway
evidence_type: IGI
original_reference_id: PMID:21700223
review:
summary: 'Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1904382
label: mannose trimming involved in glycoprotein ERAD pathway
evidence_type: IDA
original_reference_id: PMID:27053108
review:
summary: 'Manual review: mannose trimming involved in glycoprotein ERAD pathway is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16002399
review:
summary: 'Manual review: protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IDA
original_reference_id: PMID:16002399
review:
summary: 'Manual review: unfolded protein binding is too generic or over-extended for PDI1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0003756
label: protein disulfide isomerase activity
evidence_type: IMP
original_reference_id: PMID:11157982
review:
summary: 'Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003756
label: protein disulfide isomerase activity
evidence_type: IDA
original_reference_id: PMID:16002399
review:
summary: 'Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003756
label: protein disulfide isomerase activity
evidence_type: IDA
original_reference_id: PMID:16413482
review:
summary: 'Manual review: protein disulfide isomerase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: IDA
original_reference_id: PMID:1761554
review:
summary: 'Manual review: endoplasmic reticulum lumen is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0006457
label: protein folding
evidence_type: IMP
original_reference_id: PMID:11157982
review:
summary: 'Manual review: protein folding is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0015035
label: protein-disulfide reductase activity
evidence_type: IDA
original_reference_id: PMID:16002399
review:
summary: 'Manual review: protein-disulfide reductase activity is consistent with known biology of PDI1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:11157982
title: Functional differences in yeast protein disulfide isomerases.
findings: []
- id: PMID:16002399
title: Interactions among yeast protein-disulfide isomerase proteins and endoplasmic reticulum chaperone proteins influence their activities.
findings: []
- id: PMID:16368681
title: Domain architecture of protein-disulfide isomerase facilitates its dual role as an oxidase and an isomerase in Ero1p-mediated disulfide formation.
findings: []
- id: PMID:16413482
title: The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites.
findings: []
- id: PMID:16429126
title: Proteome survey reveals modularity of the yeast cell machinery.
findings: []
- id: PMID:16554755
title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
findings: []
- id: PMID:1761554
title: The Saccharomyces cerevisiae TRG1 gene is essential for growth and encodes a lumenal endoplasmic reticulum glycoprotein involved in the maturation of vacuolar carboxypeptidase.
findings: []
- id: PMID:19124653
title: Htm1 protein generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum.
findings: []
- id: PMID:21700223
title: A complex of Pdi1p and the mannosidase Htm1p initiates clearance of unfolded glycoproteins from the endoplasmic reticulum.
findings: []
- id: PMID:26928762
title: 'One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.'
findings: []
- id: PMID:27053108
title: A Complex of Htm1 and the Oxidoreductase Pdi1 Accelerates Degradation of Misfolded Glycoproteins.
findings: []
- id: PMID:27107014
title: An inter-species protein-protein interaction network across vast evolutionary distance.
findings: []
- id: PMID:37968396
title: The social and structural architecture of the yeast protein interactome.
findings: []