CPR6

Summary: CPR6 is a cyclophilin with well-established PPIase activity. IBA annotation is correct.

Reason: PPIase activity is the core molecular function of CPR6. UniProt describes it as catalyzing cis-trans isomerization of proline imidic peptide bonds (EC 5.2.1.8). IDA evidence from PMID:10942767 and PMID:9191025 confirms this activity.

Summary: CPR6 is a cytoplasmic protein. IBA annotation is correct.

Reason: Consistent with IDA evidence (PMID:9191025) and HDA evidence (PMID:11914276, PMID:14562095) for cytoplasmic localization.

Summary: CPR6 contributes to protein folding through its PPIase activity and co-chaperone function with Hsp90.

Reason: CPR6 participates in protein folding through two mechanisms: its PPIase catalytic activity (proline isomerization facilitates protein folding) and its role as an Hsp90 co-chaperone via its TPR domain. IDA and IPI evidence from PMID:9927435 supports this annotation.

Summary: CPR6 is a cyclophilin that binds cyclosporin A. IBA annotation is correct.

Reason: Cyclosporin A binding is a defining characteristic of cyclophilins. The name CPR6 (Cyclosporin-sensitive Proline Rotamase 6) reflects this property. The IBA inference is well-supported phylogenetically.

Summary: IEA annotation for PPIase activity. Redundant with IBA and IDA but correct.

Reason: Consistent with IBA and IDA annotations for PPIase activity.

Summary: IEA annotation for cytoplasm from UniProt subcellular location mapping. Correct.

Reason: Consistent with IDA and HDA evidence for cytoplasmic localization.

Summary: IEA annotation for protein folding from InterPro. Correct.

Reason: Consistent with IBA and experimental annotations for protein folding involvement.

Summary: IEA annotation from UniProt keyword mapping. Broader than PPIase activity but not incorrect.

Reason: Isomerase activity is a parent term of peptidyl-prolyl cis-trans isomerase activity. While more specific annotations exist, this broader IEA annotation is not incorrect.

Summary: ARBA prediction for protein refolding. Supported by IDA evidence.

Reason: Supported by IDA evidence from PMID:10942767 which showed CPR6 has protein refolding activity.

Summary: ARBA prediction for unfolded protein binding. GO:0051082 is formally obsolete (QuickGO: "obsolete unfolded protein binding") and its own obsoletion comment directs replacement by GO:0044183 (protein folding chaperone) or GO:0140309 (unfolded protein holdase activity); the direct yeast evidence supports GO:0044183 as the replacement.

Reason: GO:0051082 is obsolete, so it cannot be retained as-is. GO:0044183 (protein folding chaperone) is defined simply as "Binding to a protein or a protein-containing complex to assist the protein folding process" with no ATP-dependence requirement, so it is not restricted to ATP-dependent chaperones (the ATP-dependent foldase term is the separate GO:0140662). Direct yeast evidence supports a folding-chaperone term rather than discarding the annotation: the abstract of PMID:10942767 reports that CPR6 possesses chaperone activity, and SGD independently made a GO:0042026 (protein refolding) IDA on that same paper, which this review ACCEPTs elsewhere in this file. The closest precedent is the direct paralog CPR7, whose IEA and IDA GO:0051082 rows — from the same paper — are both already MODIFY to GO:0044183 (genes/yeast/CPR7/CPR7-ai-review.yaml). Caveat: PMID:10942767 is cached abstract-only (full_text_available: false), so the abstract cannot by itself discriminate foldase activity (GO:0044183) from in-situ aggregation prevention (GO:0140309, unfolded protein holdase activity); GO:0044183 is chosen for consistency with the CPR7 decision and with the curator-asserted GO:0042026 refolding annotation, and that discrimination is deferred pending full text.

Proposed replacements: protein folding chaperone

Summary: IPI from mass spectrometry study. Uninformative "protein binding" annotation.

Reason: "Protein binding" is uninformative. CPR6 interacts with Hsp90 via its TPR domain; the more informative annotation would be GO:0051087 (protein-folding chaperone binding).

Summary: IPI from chaperone network study.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from large-scale protein complex study.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from atlas of chaperone-protein interactions.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from mixed Hsp90-cochaperone complex study.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from Aha1 integration into Hsp90 co-chaperone cycle study.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from yeast protein interactome architecture study.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: IPI from original identification of CPR6 as CyP-40-like cyclophilin.

Reason: Uninformative "protein binding" for an Hsp90 co-chaperone.

Summary: High-throughput data for cytoplasmic localization.

Reason: Consistent with IDA evidence. Core localization.

Summary: High-throughput GFP localization data confirming cytoplasm.

Reason: Global protein localization study. Consistent with IDA evidence.

Summary: IPI evidence for protein folding involvement through interaction with Hsp90.

Reason: CPR6 participates in protein folding as an Hsp90 co-chaperone. The IPI evidence documents the functional interaction in the context of protein folding.

Summary: IDA evidence for ribosome binding. CPR6 associates with ribosomes.

Reason: CPR6 has been shown to bind ribosomes by direct assay. This may be related to co-translational protein folding but is not the core PPIase/co-chaperone function.

Summary: IDA evidence for PPIase activity from comparative study of CPR6 and CPR7.

Reason: Direct assay demonstrates PPIase activity. Study compared CPR6 and CPR7, showing both have PPIase activity but differ in other functional properties.

Summary: IDA evidence for PPIase activity from functional analysis of yeast 40 kDa cyclophilin.

Reason: Direct assay demonstrates PPIase activity. Core molecular function of CPR6.

Summary: IDA evidence for cytoplasmic localization.

Reason: Core localization of CPR6.

Summary: IDA evidence for protein folding involvement.

Reason: Direct assay demonstrates CPR6 role in protein folding, consistent with its PPIase and co-chaperone functions.

Summary: IDA evidence for protein refolding activity from comparative study of CPR6 and CPR7.

Reason: PMID:10942767 demonstrated that CPR6 has protein refolding activity in vitro. This is consistent with its PPIase and co-chaperone functions.

Summary: Direct IDA evidence for chaperone activity. GO:0051082 is formally obsolete; its own obsoletion comment directs replacement by GO:0044183 (protein folding chaperone) or GO:0140309 (unfolded protein holdase activity), and the direct evidence here supports GO:0044183.

Reason: GO:0051082 is obsolete, so it cannot be retained as-is. The abstract of PMID:10942767 reports that CPR6 possesses chaperone activity, though "the chaperone activity of Cpr6 is much lower than that of Cpr7" (its paralog). The refolding claim for CPR6 rests not on this abstract, which never uses the word, but on SGD's separate GO:0042026 (protein refolding) IDA made by a curator with the full text on this same paper — a row this review ACCEPTs elsewhere in this file. GO:0044183 (protein folding chaperone) is defined as "Binding to a protein or a protein-containing complex to assist the protein folding process," with no ATP-dependence requirement (that is the separate GO:0140662), so it captures this weaker-but-real chaperone activity as the specific, non-obsolete replacement term. The closest precedent is the direct paralog CPR7, whose IEA and IDA GO:0051082 rows — from the same paper — are both already MODIFY to GO:0044183 (genes/yeast/CPR7/CPR7-ai-review.yaml). Caveat: PMID:10942767 is cached abstract-only (full_text_available: false), so the abstract cannot by itself discriminate foldase activity (GO:0044183) from in-situ aggregation prevention (GO:0140309); GO:0044183 is chosen for consistency with the CPR7 decision and with the curator-asserted GO:0042026 refolding annotation, and that discrimination is deferred pending full text.

Proposed replacements: protein folding chaperone