SHY1 encodes the yeast SURF1-family cytochrome c oxidase assembly factor. Shy1 is an intrinsic mitochondrial inner membrane protein required for efficient complex IV biogenesis, acting during early Cox1 maturation and coupling Cox1 translational regulation by the Mss51/Cox14 module to downstream complex IV assembly. Shy1 is not a mature cytochrome c oxidase subunit and is not a general unfolded-protein chaperone; its core role is assembly of mitochondrial respiratory chain complex IV.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IBA GO_REF:0000033 | ACCEPT | Summary: The PANTHER/IBA annotation is consistent with direct yeast evidence and conserved SURF1-family biology. Shy1 is repeatedly shown to be required for efficient cytochrome c oxidase assembly and Cox1 maturation. Reason: Core biological process for SHY1. Supporting Evidence: PMID:17882259 Shy1 is an assembly factor for complex IV in Saccharomyces cerevisiae file:yeast/SHY1/SHY1-deep-research-falcon.md Falcon deep research identifies SHY1 as a SURF1-family mitochondrial inner membrane complex IV assembly factor. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial localization is correct for Shy1. The more specific mitochondrial inner membrane term is also present, but the broader mitochondrion annotation is supported by direct studies and family transfer. Reason: Shy1 performs its assembly-factor function in mitochondria. Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to mitochondrial inner membrane is accurate and agrees with direct localization experiments. Reason: Core localization for Shy1. Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro transfer to the generic membrane term is directionally correct for a SURF1-family membrane protein but too broad for this curated review. Shy1 is specifically an inner mitochondrial membrane protein. Reason: Replace generic membrane with the experimentally supported mitochondrial inner membrane location. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
| GO:0005515 protein binding | IPI PMID:17882259 Shy1 couples Cox1 translational regulation to cytochrome c o... | MARK AS OVER ANNOTATED | Summary: Shy1 interactions with Cox14, Mss51, Coa1 and complex IV assembly intermediates are central to its biology, but the generic protein binding term is not informative. The functional consequence is complex IV assembly rather than protein binding as a standalone molecular function. Reason: Use complex IV assembly and mitochondrial inner membrane annotations instead of generic protein binding. Supporting Evidence: PMID:17882259 Shy1 interacts with Mss51 and Cox14, translational regulators of Cox1. |
| GO:0005515 protein binding | IPI PMID:17882260 Coa1 links the Mss51 post-translational function to Cox1 cof... | MARK AS OVER ANNOTATED | Summary: The Coa1/Shy1 interaction supports the assembly pathway model but does not justify retaining a generic protein binding MF annotation. Reason: The interaction is better represented as part of complex IV assembly. Supporting Evidence: PMID:17882260 The interaction between Coa1 and Cox1, and the physical and genetic interactions between Coa1 and Mss51, Shy1 and Cox14 suggest that Coa1 coordinates the transition |
| GO:0016020 membrane | IDA PMID:15306853 Mss51p and Cox14p jointly regulate mitochondrial Cox1p expre... | MODIFY | Summary: The direct membrane annotation is valid but less specific than the mitochondrial inner membrane annotations supported by SHY1 localization and function. Reason: Use the specific inner mitochondrial membrane component term. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
| GO:0005777 peroxisome | HDA PMID:35563734 Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulati... | KEEP AS NON CORE | Summary: Retain as non-core only. The canonical and mechanistic Shy1 localization is the mitochondrial inner membrane. The peroxisome annotation comes from a high-throughput peroxisomal screen and has no demonstrated role in Shy1's complex IV assembly function. Reason: Possible context-specific or high-throughput localization, not the core functional location. Supporting Evidence: PMID:35563734 we used a high-throughput screen to discover peroxisomal proteins in yeast. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: High-throughput mitochondrial proteomics detection is consistent with Shy1's established mitochondrial role. Reason: Correct broad mitochondrial localization. Supporting Evidence: PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome detection is consistent with Shy1's canonical localization and function. Reason: Correct broad mitochondrial localization. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE |
| GO:0005743 mitochondrial inner membrane | IDA PMID:15306853 Mss51p and Cox14p jointly regulate mitochondrial Cox1p expre... | ACCEPT | Summary: Inner mitochondrial membrane localization is appropriate for Shy1's role in Cox1 maturation and complex IV assembly. Reason: Core cellular component for Shy1 function. Supporting Evidence: PMID:15306853 The release of Mss51p from the complex occurs at a downstream step in the assembly pathway, probably catalyzed by Shy1p. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:9162072 SHY1, the yeast homolog of the mammalian SURF-1 gene, encode... | ACCEPT | Summary: The original SHY1 characterization directly localized Shy1 to the inner mitochondrial membrane. Reason: Direct localization evidence for the core site of action. Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:17882259 Shy1 couples Cox1 translational regulation to cytochrome c o... | ACCEPT | Summary: Strong mutant and biochemical evidence supports Shy1 as a complex IV assembly factor that links Cox1 translational control with assembly intermediate progression. Reason: Core biological process supported by direct experimental evidence. Supporting Evidence: PMID:17882259 We suggest that Shy1 links Cox1 translational regulation to complex IV assembly and supercomplex formation. |
| GO:0051082 unfolded protein binding | IMP PMID:11389896 Shy1p occurs in a high molecular weight complex and is requi... | MARK AS OVER ANNOTATED | Summary: The evidence shows that Shy1 occurs in an assembly-associated complex and is required for efficient cytochrome c oxidase assembly. It does not show general unfolded-protein binding or a broad chaperone substrate range. Reason: The annotation over-interprets an assembly-factor phenotype. Shy1 should be curated to complex IV assembly rather than generic unfolded protein binding. Supporting Evidence: PMID:11389896 Shy1p may either facilitate assembly of the enzyme, or increase its stability. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:9162072 SHY1, the yeast homolog of the mammalian SURF-1 gene, encode... | ACCEPT | Summary: Duplicate direct UniProt annotation for Shy1 inner mitochondrial membrane localization; retain because it accurately reflects the original experimental localization. Reason: Direct localization evidence for the core site of action. Supporting Evidence: PMID:9162072 An antibody against the carboxyl-terminal half of Shy1p has been used to localize the protein in the inner mitochondrial membrane. |
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Download this section (compressed HTML)Q: Is there enough direct evidence to annotate a specific Shy1 molecular function for Cox1 cofactor insertion or assembly-intermediate stabilization, rather than leaving SHY1 represented only by the biological-process term for complex IV assembly?
Suggested experts: Mick DU, Rehling P, Winge DR
Experiment: Reconstitute Shy1-containing Cox1 assembly intermediates with Cox14, Mss51, Coa1 and cofactor-insertion factors, then test Shy1 mutants for Cox1 cofactor incorporation, assembly-intermediate stability, and release of Mss51.
Hypothesis: Shy1 promotes Cox1 heme a3:CuB maturation or maintains Cox1 in an assembly-competent state rather than binding unfolded proteins generally.
Type: mitochondrial complex IV assembly intermediate assay
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