GSF2, also known as ECM6, encodes an endoplasmic-reticulum membrane accessory factor required for efficient ER exit of selected polytopic hexose transporters. The best-supported clients are Hxt1 and Gal2: in gsf2 mutants, Hxt1 accumulates in the ER and Gal2 is mislocalized, whereas Hxt2 is much less affected. Mechanistic work places Gsf2 with cargo-specific membrane-localized chaperones such as Shr3, Pho86, and Chs7 that prevent aggregation or incorrect transmembrane-segment interactions in specific membrane-protein clients during ER biogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to ER membrane is consistent with direct experimental evidence that Gsf2 is an integral ER membrane protein. Reason: The ER membrane is the correct compartment for Gsf2's cargo-specific chaperone/accessory function in hexose-transporter biogenesis. Supporting Evidence: PMID:10377429 We show that gsf2 mutants accumulate Hxt1p in the endoplasmic reticulum (ER) and that Gsf2p is a 46-kDa integral membrane protein localized to the ER. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:10377429 Efficient export of the glucose transporter Hxt1p from the e... | ACCEPT | Summary: Sherwood and Carlson experimentally localized Gsf2 as an integral ER membrane protein while showing that loss of GSF2 causes ER retention of Hxt1. Reason: This is direct localization evidence for the core compartment where Gsf2 acts. Supporting Evidence: PMID:10377429 We show that gsf2 mutants accumulate Hxt1p in the endoplasmic reticulum (ER) and that Gsf2p is a 46-kDa integral membrane protein localized to the ER. |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: The high-throughput ER localization is consistent with the better-supported ER membrane localization and the core ER function of Gsf2. Reason: Although broader than ER membrane, this annotation remains correct and agrees with focused localization evidence. Supporting Evidence: PMID:10377429 Gsf2p is a 46-kDa integral membrane protein localized to the ER. |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome | MARK AS OVER ANNOTATED | Summary: A broad cytoplasm annotation from a high-throughput localization study is not the best representation of Gsf2 biology. Focused studies and UniProt place Gsf2 in the ER membrane. Reason: Gsf2 is an ER membrane protein with a cargo-specific function in ER export and folding of membrane transporters. The cytoplasm annotation is too broad and should not be treated as a core localization. Supporting Evidence: PMID:10377429 Gsf2p is a 46-kDa integral membrane protein localized to the ER. |
| GO:0005741 mitochondrial outer membrane | HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane... | REMOVE | Summary: The mitochondrial outer membrane assignment is from a large-scale proteomic study and conflicts with focused experimental evidence for ER membrane localization and ER export function. Reason: No gene-specific evidence supports mitochondrial outer membrane localization for Gsf2. The experimentally supported localization is the ER membrane. Supporting Evidence: PMID:10377429 These findings suggest that Gsf2p functions in the ER to promote the secretion of certain hexose transporters. |
| GO:0006457 protein folding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | ACCEPT | Summary: Gsf2 acts as a cargo-specific membrane-localized chaperone that prevents aggregation of its cognate polytopic hexose-transporter substrates during ER membrane folding/biogenesis. Reason: PMID:15623581 directly supports a protein folding/homeostasis role for Gsf2 in the ER membrane, although the process should be interpreted as specific client maturation rather than general folding of all proteins. Supporting Evidence: PMID:15623581 Also, we show that the integral ER proteins, Gsf2p, Pho86p, and Chs7p, function similarly to Shr3p. In cells individually lacking one of these components only their cognate substrates, hexose transporters, phosphate transporters, and chitin synthase-III, respectively, aggregate and consequently fail to exit the ER membrane. |
| GO:0034394 protein localization to cell surface | IMP PMID:10377429 Efficient export of the glucose transporter Hxt1p from the e... | ACCEPT | Summary: Gsf2 is required for efficient ER export and plasma-membrane delivery of selected hexose transporters, especially Hxt1 and Gal2. Reason: Loss of GSF2 causes Hxt1 retention in the ER and abnormal Gal2 localization, supporting this biological-process annotation. Supporting Evidence: PMID:10377429 gsf2 mutants accumulate Hxt1p in the endoplasmic reticulum (ER) ... gsf2 mutants also display a galactose growth defect and abnormal localization of the galactose transporter Gal2p. |
| GO:0034394 protein localization to cell surface | IGI PMID:10377429 Efficient export of the glucose transporter Hxt1p from the e... | ACCEPT | Summary: The genetic interaction evidence with HXT1 is consistent with Gsf2's requirement for cell-surface delivery of selected hexose transporters. Reason: HXT1 was isolated as a multicopy suppressor of a gsf2 mutation, and direct localization experiments showed Hxt1 ER accumulation in gsf2 mutants. Supporting Evidence: PMID:10377429 We have isolated the HXT1 gene, which encodes a low-affinity, high-capacity glucose transporter, as a multicopy suppressor of a gsf2 mutation. |
| GO:0051082 unfolded protein binding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | MODIFY | Summary: The evidence supports a specialized membrane-protein chaperone role rather than generic unfolded protein binding. Reason: Gsf2 prevents aggregation and inappropriate interactions of cognate polytopic hexose-transporter substrates in the ER membrane. GO:0044183 protein folding chaperone captures the demonstrated client-specific chaperone function better than the broad GO:0051082 term. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15623581 These findings indicate that polytopic membrane proteins depend on specialized membrane-localized chaperones to prevent inappropriate interactions between membrane-spanning segments as they insert and fold in the lipid bilayer of the ER membrane. file:yeast/GSF2/GSF2-deep-research-falcon.md **GSF2 (ECM6; YML048W)** encodes an **ER-localized integral membrane accessory/chaperone-like factor** that promotes proper folding/assembly and **efficient ER exit** of a **select subset of polytopic hexose transporters**, with strongest evidence for **Hxt1p** and effects on **Gal2p** |
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Download this section (compressed HTML)Q: Which sequence or structural features of Hxt1 and Gal2 define dependence on Gsf2, and why is Hxt2 largely Gsf2-independent?
Q: Does Gsf2 directly bind its hexose-transporter clients during insertion, or does it act indirectly by recruiting ER export or quality-control machinery?
Q: How do the newer hydroxyurea and metabolic-engineering phenotypes connect to Gsf2's core ER membrane-protein biogenesis role?
Experiment: Map Gsf2-client specificity using tagged Hxt1, Gal2, Hxt2, and transporter chimeras, measuring ER retention, aggregation, and plasma-membrane delivery in wild-type and gsf2 deletion cells.
Type: cell biology
Experiment: Perform crosslinking or proximity-labeling proteomics from functional tagged Gsf2 to identify direct transporter clients and ER export/quality-control partners.
Type: proteomics
Experiment: Test whether Gsf2-dependent transporter folding defects explain hydroxyurea recovery and organic-acid production phenotypes by separating transporter localization effects from downstream glucose-signaling changes.
Type: genetics
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