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. 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. 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. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15623581 Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER. |
| 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 ... | MARK AS OVER ANNOTATED | Summary: This high-throughput interaction supports physical association with the amino acid permease Gnp1 but the term protein binding is uninformative. Reason: The curated molecular function should describe Shr3's client-specific chaperone activity rather than retain generic protein binding. |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | MARK AS OVER ANNOTATED | 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: A generic protein-binding annotation should not be treated as a core molecular function when the biological role is permease folding and packaging chaperone activity. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | MARK AS OVER ANNOTATED | Summary: Large-scale interaction evidence does not provide a specific molecular function beyond physical association. Reason: This annotation is too generic for curation; the better-supported role is Shr3 chaperoning and ER export of amino acid permeases. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: The inter-species interaction screen reports a physical interaction but does not establish a yeast Shr3 molecular activity. Reason: The xeno interaction is not suitable as a core function annotation and is much less informative than the experimentally supported Shr3 chaperone mechanism. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | 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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