CHS7 encodes an endoplasmic-reticulum membrane export chaperone for the chitin synthase Chs3, promoting Chs3 folding/proteostasis, ER-to-Golgi export, and normal chitin synthase III-dependent cell wall chitin deposition.
Definition: A protein folding chaperone activity that binds or escorts a chitin synthase client in the endoplasmic reticulum to promote its productive folding, ER quality-control evasion, and export toward the Golgi.
Justification: Chs7 is not a generic unfolded-protein binder; the yeast evidence supports a dedicated export-chaperone activity for Chs3/chitin synthase III that is more specific than existing chaperone terms. Sanchez et al. 2023 strengthens this by showing that Chs7 also functions as a degron shield, masking Chs3 cytosolic degrons to prevent ERAD-C targeting.
Parent term: protein folding chaperone
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006031 chitin biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Chitin biosynthesis is a downstream consequence of Chs7-dependent Chs3 maturation and export. Reason: Keep as a valid downstream biological-process annotation while treating Chs7-dependent ER export of the Chs3 chitin synthase as the direct core process; Chs7 does not catalyze chitin polymerization itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002175570 SUPPORTS TRANSFER Current PTHR35329 PAINT places chitin biosynthetic process at the fungal CHS7-family node inherited by budding-yeast CHS7; the SGD self-seed is expected target experimental grounding rather than circular support. Supporting Evidence: PMID:10366589 In the absence of CHS7 product, Chs3p, but not other secreted proteins, is retained in the ER, leading to a severe defect in CSIII activity and consequently, to a reduced rate of chitin synthesis. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: endoplasmic reticulum membrane reviewed for CHS7: ACCEPT. Reason: Retain as the best-supported cellular location; Chs7 is a multipass ER membrane protein acting at the Chs3 ER export step. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002175570 SUPPORTS TRANSFER Current PTHR35329 PAINT retains the endoplasmic reticulum membrane IBD on the fungal CHS7-family ancestor and CHS7 has direct SGD-curated ER membrane evidence. Supporting Evidence: PMID:10366589 Chs7p-GFP was uniformly localized in the nuclear periphery and in discrete patches associated with the cytoplasmic membrane. |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: protein folding reviewed for CHS7: ACCEPT. Reason: Retain the live PAINT-derived broad protein-folding row because current PTHR35329 places GO:0006457 at the same fungal CHS7-family node that now also has GO:0044183. Chs7's more specific export-chaperone mechanism is captured by the GO:0044183 molecular-function assertion rather than by a BP child, because GO:0061077 chaperone-mediated protein folding is obsolete. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002175570 SUPPORTS TRANSFER Current PTHR35329 PAINT places broad protein folding at the same fungal CHS7-family node as the newer protein folding chaperone IBD. Supporting Evidence: PMID:15623581 Also, we show that the integral ER proteins, Gsf2p, Pho86p, and Chs7p, function similarly to Shr3p. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: GO:0051082 is obsolete and has been replaced at the same PAINT node by GO:0044183, matching Chs7's Chs3-specific export-chaperone activity. Reason: GO:0051082 "unfolded protein binding" is obsolete. The current PTHR35329 PAINT record no longer carries that term at PTN002175570 and instead asserts GO:0044183 protein folding chaperone at the same ancestor, matching the supported Chs3-specific chaperone/escort role. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: PANTHER:PTN002175570 SOURCE STALE OR MISSING The current PAINT record retains conserved CHS7-family chaperone biology at this node and now asserts GO:0044183 there, but it no longer carries obsolete GO:0051082. Proposed replacements: protein folding chaperone Supporting Evidence: file:interpro/panther/PTHR35329/PTHR35329-paint.tsv PTHR35329 PTN002175570 GO:0044183 F IBD false SGD:S000001184 taxon:4751 20260611 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: endoplasmic reticulum membrane reviewed for CHS7: ACCEPT. Reason: Retain as the best-supported cellular location; Chs7 is a multipass ER membrane protein acting at the Chs3 ER export step. Supporting Evidence: PMID:10366589 Therefore, it can be concluded that Chs7p is an ER membrane protein. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | MODIFY | Summary: protein transport reviewed for CHS7: MODIFY. Reason: General protein transport is too broad for the curated evidence; Chs7 specifically promotes Chs3 exit from the ER toward the Golgi. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:10366589 Therefore, it can be concluded that Chs7p is required for Chs3p export from the ER and Chs7p must be the initial step in the hierarchy of proteins required for CSIII activity. |
| GO:0071555 cell wall organization | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: cell wall organization reviewed for CHS7: KEEP_AS_NON_CORE. Reason: Keep as a valid downstream phenotype of impaired Chs3-dependent chitin deposition, but not the direct molecular role of Chs7. Supporting Evidence: PMID:10366589 In the absence of CHS7 product, Chs3p, but not other secreted proteins, is retained in the ER, leading to a severe defect in CSIII activity and consequently, to a reduced rate of chitin synthesis. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: The Chs3 interaction is real but generic protein binding is less informative than Chs7's specific chaperone/export role. Reason: Remove the generic binding annotation in favor of Chs7's more informative Chs3-specific protein-folding chaperone and export role. This does not reject the Chs3 interaction from the genome-wide PCA map; GO:0005515 is simply an uninformative molecular-function term for the interaction. Supporting Evidence: file:yeast/CHS7/CHS7-deep-research-falcon.md Chs7 **physically interacts** with full-length Chs3 and certain truncated Chs3 forms |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: The proteome-scale interaction row should defer to the targeted Chs3-chaperone mechanism rather than retain generic protein binding. Reason: Remove the generic binding annotation in favor of the specific Chs3 chaperone/escort function. The proteome-scale interaction row is compatible with that physical association, but it does not add a narrower molecular function beyond the accepted chaperone and ER-export role. Supporting Evidence: file:yeast/CHS7/CHS7-deep-research-falcon.md Chs7 **physically interacts** with full-length Chs3 and certain truncated Chs3 forms |
| GO:0005783 endoplasmic reticulum | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: endoplasmic reticulum reviewed for CHS7: ACCEPT. Reason: Retain as a supported broader ER localization, consistent with the more precise ER membrane annotation. |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: endoplasmic reticulum reviewed for CHS7: ACCEPT. Reason: Retain as a supported broader ER localization, consistent with the more precise ER membrane annotation. |
| GO:0005934 cellular bud tip | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | KEEP AS NON CORE | Summary: cellular bud tip reviewed for CHS7: KEEP_AS_NON_CORE. Reason: Keep as context-dependent localization associated with Chs3/chitin deposition biology, not as the primary site of Chs7 action. |
| GO:0005935 cellular bud neck | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | KEEP AS NON CORE | Summary: cellular bud neck reviewed for CHS7: KEEP_AS_NON_CORE. Reason: Keep as context-dependent bud-neck localization associated with chitin deposition, not as the core ER export role. |
| GO:0005628 prospore membrane | HDA PMID:24390141 A visual screen of protein localization during sporulation i... | KEEP AS NON CORE | Summary: prospore membrane reviewed for CHS7: KEEP_AS_NON_CORE. Reason: Keep as a sporulation-context localization observation, peripheral to the core ER chaperone/export function. |
| GO:0005935 cellular bud neck | IDA PMID:29405545 The chaperone Chs7 forms a stable complex with Chs3 and prom... | KEEP AS NON CORE | Summary: cellular bud neck reviewed for CHS7: KEEP_AS_NON_CORE. Reason: Keep as context-dependent bud-neck localization associated with chitin deposition, not as the core ER export role. Supporting Evidence: PMID:29405545 Here, we show that Chs7 itself exits the ER and localizes with Chs3 at the bud neck and intracellular compartments. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:10366589 Chs7p, a new protein involved in the control of protein expo... | ACCEPT | Summary: endoplasmic reticulum membrane reviewed for CHS7: ACCEPT. Reason: Retain as the best-supported cellular location; Chs7 is a multipass ER membrane protein acting at the Chs3 ER export step. Supporting Evidence: PMID:10366589 Chs7p-GFP was uniformly localized in the nuclear periphery and in discrete patches associated with the cytoplasmic membrane. |
| GO:0006031 chitin biosynthetic process | IMP PMID:10366589 Chs7p, a new protein involved in the control of protein expo... | KEEP AS NON CORE | Summary: Chitin biosynthesis is a downstream consequence of Chs7-dependent Chs3 maturation and export. Reason: Keep as a valid downstream phenotype of defective Chs3 ER export while treating the export-chaperone step as Chs7's direct core process; Chs7 does not catalyze a step of chitin biosynthesis. Supporting Evidence: PMID:10366589 In the absence of CHS7 product, Chs3p, but not other secreted proteins, is retained in the ER, leading to a severe defect in CSIII activity and consequently, to a reduced rate of chitin synthesis. |
| GO:0006457 protein folding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | ACCEPT | Summary: PMID:15623581 supports Chs7's membrane-localized chaperone role during Chs3 folding and ER export. Reason: Retain the SGD-curated live GO:0006457 row. PMID:15623581 shows that Chs7 prevents aggregation/folding failure of the polytopic Chs3 cargo during ER insertion and export, and GO has obsoleted the chaperone-mediated-protein-folding BP child; mechanism-level specificity is therefore captured by the GO:0044183 protein folding chaperone molecular-function assertion rather than by a narrower biological-process replacement. Supporting Evidence: PMID:15623581 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:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IDA PMID:10366589 Chs7p, a new protein involved in the control of protein expo... | ACCEPT | Summary: endoplasmic reticulum to Golgi vesicle-mediated transport reviewed for CHS7: ACCEPT. Reason: Retain as a core process: the strongest mechanistic evidence places Chs7 at Chs3 ER exit and ER-to-Golgi trafficking. Supporting Evidence: PMID:10366589 joint overexpression of CHS3 and CHS7 increases the export of Chs3p from the ER and this is accompanied by a concomitant increase in CSIII activity |
| GO:0051082 unfolded protein binding | IMP PMID:15623581 Specialized membrane-localized chaperones prevent aggregatio... | MODIFY | Summary: GO:0051082 is obsolete; the experimental aggregation phenotype supports a Chs3-specific protein-folding chaperone activity for Chs7. Reason: GO:0051082 "unfolded protein binding" is obsolete. The genetic evidence in PMID:15623581 supports replacement with GO:0044183 protein folding chaperone because Chs7 prevents Chs3 aggregation during ER folding and export. 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. |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | NEW | Summary: Current PAINT now asserts protein folding chaperone at the conserved fungal CHS7-family node. Reason: GOA has not yet imported this 2026 PAINT IBD, but current PTHR35329 places GO:0044183 protein folding chaperone at PTN002175570. The assertion fits the Chs7 literature: Chs7 is a dedicated membrane-localized chaperone for the polytopic chitin synthase Chs3, preventing aggregation and enabling productive ER exit. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002175570 SUPPORTS TRANSFER The current fungal CHS7-family IBD transfers GO:0044183 to CHS7 and is directly grounded by the target's chaperone evidence. Supporting Evidence: file:interpro/panther/PTHR35329/PTHR35329-paint.tsv PTHR35329 PTN002175570 GO:0044183 F IBD false SGD:S000001184 taxon:4751 20260611 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. |
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Download this section (compressed HTML)Q: Does Chs7 have physiologically important clients other than Chs3, or is its conserved role essentially dedicated to chitin synthase export?
Q: Which Chs3 surfaces are shielded by Chs7 during ER quality control and ERAD avoidance?
Experiment: Map Chs3 regions that require Chs7 using endogenous tagged Chs3 truncation or degron mutants, ER export assays, co-immunoprecipitation, and ERAD/INMAD pathway perturbations.
Hypothesis: Chs7 promotes Chs3 ER export by masking Chs3 degrons while maintaining an export-competent conformation.
Type: client-mapping and trafficking assay
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Download this section (compressed HTML)Protein of unknown function; may be involved in chitin biosynthesis by regulation of Chs3p export from the ER; relocalizes from bud neck to ER upon DNA replication stress
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