SHR3 encodes an endoplasmic-reticulum membrane packaging chaperone required for folding, quality control, and ER exit of yeast amino acid permeases. Shr3 is a multi-pass ER membrane protein that assists substrate-specific folding of polytopic amino acid transporters, prevents their aggregation and premature ER-associated degradation, and promotes COPII-dependent packaging for trafficking from the ER toward the Golgi and plasma membrane. Shr3 is not itself an amino acid transporter; its core role is client-specific membrane protein chaperoning in the early secretory pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PANTHER IBA to endoplasmic reticulum membrane is consistent with the specific Shr3 family, UniProt localization, and direct experimental evidence. Reason: Shr3 is an integral ER membrane protein and functions at the ER membrane during amino acid permease biogenesis. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002000498 · PANTHER:PTN002000498 SOURCE STALE OR MISSING GOA identifies this ancestral SHR3-family node, but no current PTHR28228 PAINT table or PTN record is cached locally; direct yeast IDA rows and the family-specific UniProt/PANTHER classification corroborate endoplasmic reticulum membrane as the correct core compartment for S. cerevisiae Shr3. Supporting Evidence: file:yeast/SHR3/SHR3-deep-research-falcon.md Shr3 localizes to the endoplasmic reticulum membrane |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: Family-transfer annotation to ER-to-Golgi vesicle transport is appropriate for Shr3 because it promotes ER exit of amino acid permease cargo. Reason: Shr3 is required for efficient packaging of permeases into ER-derived COPII vesicles and therefore supports ER-to-Golgi transport of those clients. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002000498 · PANTHER:PTN002000498 SOURCE STALE OR MISSING GOA traces this IBA to the SHR3-family PTN node, but the local repository has no current PTHR28228 PAINT export to inspect. The transfer remains biologically sound because yeast genetic and biochemical evidence directly places Shr3 in COPII-dependent ER export of amino acid permeases. Supporting Evidence: file:yeast/SHR3/SHR3-deep-research-falcon.md promoting COPII-dependent packaging of amino acid permeases |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: Shr3 is a substrate-specific chaperone for polytopic permeases, but "unfolded protein binding" is a vague binding term. Reason: The evidence supports protein folding chaperone activity for amino acid permease clients rather than a generic unfolded-protein binding annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002000498 · PANTHER:PTN002000498 SOURCE STALE OR MISSING The GOA row still reports a 2017 GO:0051082 IBA from this SHR3-family node, but no current PTHR28228 PAINT table is cached locally. Independent Shr3 experiments establish protein folding chaperone activity, so GO:0044183 is the informative replacement for the generic unfolded-protein-binding term. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15623581 Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER. PMID:37477900 Shr3 exerts its essential chaperone functions in a co-translational and transient manner |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to ER membrane is consistent with direct Shr3 localization. Reason: Shr3 is a multi-pass ER membrane protein, and this localization is central to its permease-chaperone function. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: The keyword-derived protein transport annotation is broad but reflects Shr3's role in ER export of amino acid permeases. Reason: More specific experimental terms capture COPII budding and ER-to-Golgi transport, but the broad transport term remains accurate. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | REMOVE | Summary: This high-throughput interaction supports physical association with the amino acid permease Gnp1 but the term protein binding is uninformative. Reason: The Gnp1 interaction is compatible with Shr3's client-specific chaperone activity, but GO:0005515 only restates physical association and does not add a specific molecular function. |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | REMOVE | Summary: These interaction data are consistent with Shr3 contacts with membrane cargo or related proteins, but protein binding does not convey the specific function. Reason: These generic interaction rows do not add a molecular function beyond the specific permease folding and packaging chaperone activity captured by GO:0044183 and the ER-export process terms. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: Large-scale interaction evidence does not provide a specific molecular function beyond physical association. Reason: GO:0005515 is too generic to retain as a Shr3 molecular-function annotation; the reported physical associations should not displace the better-supported permease-chaperone and ER-export functions. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | REMOVE | Summary: The inter-species interaction screen reports a physical interaction but does not establish a yeast Shr3 molecular activity. Reason: The xeno interaction is much less informative than direct yeast Shr3 chaperone evidence and supports no specific molecular-function term more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Modern high-throughput interactome data reinforce Shr3 physical associations but still use a generic binding term. Reason: Protein binding is not an informative endpoint for Shr3; specific client-chaperone and ER-export annotations should carry the curation. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:1423607 SHR3: a novel component of the secretory pathway specificall... | ACCEPT | Summary: Direct experimental evidence from the original SHR3 study identified Shr3 as an ER integral membrane component. Reason: This localization is the correct compartment for Shr3's role in amino acid permease processing and ER exit. Supporting Evidence: PMID:1423607 SHR3 is a novel integral membrane protein component of the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | ACCEPT | Summary: Direct experimental evidence supports Shr3 as an integral ER membrane chaperone for amino acid permeases. Reason: The ER membrane location is required for Shr3 to act on nascent or newly inserted polytopic permease clients. Supporting Evidence: PMID:15623581 The integral endoplasmic reticulum (ER) membrane protein Shr3p |
| GO:0090114 COPII-coated vesicle budding | IGI PMID:10564255 Shr3p mediates specific COPII coatomer-cargo interactions re... | ACCEPT | Summary: Genetic-interaction evidence supports Shr3 participation in COPII-coated vesicle budding for amino acid permease cargo. Reason: Shr3 mediates specific COPII coatomer-cargo interactions needed for packaging permeases into ER-derived transport vesicles. Supporting Evidence: PMID:10564255 Shr3p mediates specific COPII coatomer-cargo interactions |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: High-throughput SWAp-Tag localization supports ER localization, consistent with direct ER membrane evidence. Reason: The high-throughput annotation is congruent with multiple direct studies placing Shr3 in the ER membrane. Supporting Evidence: PMID:26928762 streamlining the creation of yeast libraries via a SWAp-Tag strategy |
| GO:0043332 mating projection tip | HDA PMID:19053807 Systematic definition of protein constituents along the majo... | KEEP AS NON CORE | Summary: High-throughput pheromone-treatment localization suggests a condition-specific signal at the mating projection tip. Reason: This may reflect condition-specific relocalization of ER/cortical membrane-associated Shr3, but it is not the core compartment for the permease-chaperone mechanism. |
| GO:0006457 protein folding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | ACCEPT | Summary: Mutant phenotype evidence supports Shr3's role in folding of polytopic amino acid permease clients and preventing their aggregation in the ER. Reason: Protein folding is a core biological process for Shr3 because failure of Shr3 causes permease misfolding/aggregation and ER retention. Supporting Evidence: PMID:15623581 prevent aggregation of polytopic proteins in the ER |
| GO:0051082 unfolded protein binding | IMP PMID:10564255 Shr3p mediates specific COPII coatomer-cargo interactions re... | MODIFY | Summary: Shr3's activity involves chaperoning amino acid permease cargo, but unfolded protein binding is less precise than a chaperone activity term. Reason: The evidence supports specific protein folding/packaging chaperone activity in the ER membrane rather than a generic binding term. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:10564255 Shr3p acts as a packaging chaperone |
| GO:0051082 unfolded protein binding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | MODIFY | Summary: The evidence shows Shr3 prevents aggregation of polytopic permeases during folding, which is better represented as protein folding chaperone activity. Reason: The more informative curation is GO:0044183 protein folding chaperone coupled to ER membrane permease biogenesis. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15623581 Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER. |
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Download this section (compressed HTML)Q: For Shr3 and related ER-resident packaging factors, should GO curation distinguish folding chaperone activity from cargo-receptor or COPII-adaptor activity with a more specific child term?
Experiment: Reconstitute Shr3 with defined amino acid permease transmembrane segments and COPII components to separate its folding/stabilization activity from any direct COPII recruitment activity.
Hypothesis: Shr3 first stabilizes early permease transmembrane segments and then promotes COPII packaging indirectly by producing export-competent cargo.
Type: biochemical reconstitution
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Download this section (compressed HTML)Endoplasmic reticulum packaging chaperone; required for incorporation of amino acid permeases into COPII coated vesicles for transport to the cell surface
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