tigA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006457 protein folding	IEA GO_REF:0000118	ACCEPT	Summary: TreeGrafter IEA annotation for protein folding. TigA is a PDI family member with demonstrated chaperone activity assisting protein folding (PMID:16234854). Consistent with IDA evidence for the same term. Reason: TigA has experimentally demonstrated protein folding chaperone activity (refolding of denatured prochymosin; PMID:16234854) and PDI isomerase activity that assists protein folding. This IEA is consistent with experimental evidence. Supporting Evidence: PMID:16234854 TIGA also exhibited chaperone activity in the refolding of denatured prochymosin
GO:0003756 protein disulfide isomerase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for PDI activity based on InterPro and EC number mapping. UniProt names this protein "Protein disulfide-isomerase tigA" with EC 5.3.4.1. Experimentally, TigA catalyzes refolding of denatured and reduced RNase A via disulfide isomerase activity (PMID:16234854). Reason: This is a core molecular function of TigA. The protein belongs to the PDI family, has two thioredoxin domains with CXXC active sites, and experimentally demonstrates isomerase activity catalyzing RNase A refolding (PMID:16234854). Supporting Evidence: PMID:16234854 TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. file:ASPNG/tigA/tigA-deep-research-falcon.md Protein disulfide-isomerase / thiol-disulfide oxidoreductase that catalyzes disulfide exchange reactions during oxidative folding of ER client proteins; demonstrated by RNase A refolding assay and dependence on CGHC motifs.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for ER localization based on InterPro (ERp29 domain) and PANTHER. TigA has a signal peptide and a C-terminal KDEL ER retention signal (positions 356-359), consistent with ER lumen residence. Reason: TigA contains a signal peptide (residues 1-19) and C-terminal ER retention motif (KDEL). UniProt annotates subcellular location as ER lumen. This is consistent with its function as a PDI in the ER. The more specific term GO:0005788 (ER lumen) is also annotated.
GO:0005788 endoplasmic reticulum lumen	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for ER lumen based on UniProt subcellular location mapping. TigA has a signal peptide and C-terminal KDEL ER retention signal, placing it in the ER lumen. Reason: Correct and more specific than GO:0005783. TigA is a soluble ER lumen protein with signal peptide and KDEL retention motif. Supporting Evidence: file:ASPNG/tigA/tigA-deep-research-falcon.md ER lumen, supported by N-terminal signal peptide and C-terminal KDEL retention signal.
GO:0016853 isomerase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation for isomerase activity from UniProt keyword mapping. This is a broad parent of the more specific GO:0003756 (protein disulfide isomerase activity). Reason: Correct but very broad. The more specific term GO:0003756 is also annotated. Acceptable as a broad IEA.
GO:0006457 protein folding	IDA PMID:16234854 Functional analysis of tunicamycin-inducible gene A polypept...	ACCEPT	Summary: IDA annotation for protein folding from Liang et al. (2005). The study demonstrated that TigA assists protein folding through two mechanisms: PDI isomerase activity (refolding denatured/reduced RNase A) and chaperone activity (refolding denatured prochymosin). The chaperone activity showed substrate specificity, working on prochymosin but not on GAPDH (PMID:16234854). Reason: Direct experimental evidence for protein folding activity through both isomerase and chaperone mechanisms. This is a core biological process for TigA. Supporting Evidence: PMID:16234854 TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. TIGA also exhibited chaperone activity in the refolding of denatured prochymosin
GO:0051082 unfolded protein binding	IDA PMID:16234854 Functional analysis of tunicamycin-inducible gene A polypept...	MODIFY	Summary: IDA annotation for unfolded protein binding. TigA is a PDI family member with demonstrated chaperone activity -- it binds unfolded/denatured prochymosin and assists its refolding (PMID:16234854). This binding is part of its genuine chaperone function, not merely incidental interaction. GO:0051082 is now formally obsolete. The appropriate replacement is GO:0044183 (protein folding chaperone), which captures the functional role of TigA's binding to unfolded substrates. Reason: GO:0051082 is now formally obsolete. TigA genuinely binds unfolded proteins as part of its chaperone function (PMID:16234854), assisting their refolding. This is a true protein folding chaperone activity. The appropriate replacement term is GO:0044183 (protein folding chaperone), which accurately describes the functional context of TigA's interaction with unfolded substrates. TigA is not ATP-dependent, so the non-ATP-dependent parent term is appropriate. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:16234854 TIGA also exhibited chaperone activity in the refolding of denatured prochymosin but not in the refolding of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), indicating that it had substrate specificity with respect to chaperone activity. file:ASPNG/tigA/tigA-deep-research-falcon.md Chaperone assistance demonstrated for disulfide-containing prochymosin, but not for non-disulfide GAPDH, implying selective substrate interaction and a narrower chaperone profile than canonical PDI.
GO:0034975 protein folding in endoplasmic reticulum	NAS PMID:16234854 Functional analysis of tunicamycin-inducible gene A polypept...	NEW	Summary: New biological-process annotation to capture the ER-specific context of TigA-mediated oxidative protein folding. Existing GO annotations already capture protein folding, PDI activity, and ER lumen localization separately; the current literature synthesis supports the more specific ER protein folding process. Reason: TigA is a PDI-family foldase/chaperone with experimentally demonstrated disulfide isomerase and substrate-selective chaperone activities, and its signal peptide plus C-terminal KDEL motif place it in the ER lumen. The field-level interpretation is therefore not just generic protein folding but folding of secretory-pathway client proteins in the ER, particularly oxidative folding of disulfide-containing substrates. Supporting Evidence: PMID:16234854 TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. TIGA also exhibited chaperone activity in the refolding of denatured prochymosin PMID:9256071 Current strategies to improve the secretion of heterologous proteins in Aspergillus niger include the manipulation of chaperones and foldases specific to the endoplasmic reticulum (ER). file:ASPNG/tigA/tigA-deep-research-falcon.md Protein disulfide-isomerase / thiol-disulfide oxidoreductase that catalyzes disulfide exchange reactions during oxidative folding of ER client proteins.