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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000603741 · SURF1-family ancestral node SUPPORTS TRANSFER PTN000603741 is the SURF1-family ancestral node carrying the mitochondrial complex-IV-assembly IBD; the extant fly, mouse, yeast, and human seeds support the transfer to S. cerevisiae SHY1. SGD:S000003344 · S. cerevisiae SHY1 SUPPORTS TRANSFER SHY1 itself is an IBD seed for this PAINT node, reflecting direct S. cerevisiae experimental evidence for complex IV assembly. UniProtKB:Q15526 · human SURF1 SUPPORTS TRANSFER Human SURF1 is a characterized orthologous complex IV assembly factor in the same PTHR23427:SF2 subfamily. FB:FBgn0029117 · Drosophila Surf1 SUPPORTS TRANSFER FlyBase Surf1 contributes an independent metazoan source for the conserved SURF1-family complex IV assembly inference. 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. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000603741 · SURF1-family ancestral node SUPPORTS TRANSFER PTN000603741 is the SURF1-family ancestral node carrying the mitochondrion IBD; the extant mouse, fission-yeast, and budding-yeast sources support the transfer to S. cerevisiae SHY1. SGD:S000003344 · S. cerevisiae SHY1 SUPPORTS TRANSFER SHY1 itself is an IBD seed for this PAINT node, matching direct yeast evidence that Shy1 acts at the mitochondrial inner membrane. PomBase:SPBC1215.01 · S. pombe shy1 SUPPORTS TRANSFER Recent fission-yeast work independently localized the PomBase Shy1 homolog to mitochondria/inner mitochondrial membrane and showed that it participates in complex IV assembly. 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... | REMOVE | Summary: The IntAct IPI row traces a Shy1-Coa1 interaction observed during complex IV assembly, 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: Coa1 and Shy1 act in the Cox1 maturation branch of the complex IV assembly pathway, but GO:0005515 does not add a specific molecular function beyond Shy1's established role in complex IV assembly. Supporting Evidence: PMID:17882259 Coa1 (YIL157c), a novel assembly factor that cooperates with Shy1. |
| GO:0005515 protein binding | IPI PMID:17882260 Coa1 links the Mss51 post-translational function to Cox1 cof... | REMOVE | Summary: The Coa1/Shy1 interaction supports the assembly pathway model but does not justify retaining a generic protein binding MF annotation. Reason: The Coa1 interaction is better represented as evidence for complex IV assembly; generic protein binding is not informative enough to retain. 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... | MODIFY | 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, and is better captured by protein-containing complex stabilizing activity. Reason: The annotation over-interprets an assembly-factor phenotype as broad unfolded-substrate binding. Shy1 acts with Cox1-containing complex IV assembly intermediates and its loss destabilizes assembled cytochrome c oxidase, which is better represented as protein-containing complex stabilizing activity than as generic unfolded protein binding. Proposed replacements: protein-containing complex stabilizing activity 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. |
| 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. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000603741 · SURF1-family ancestral node SUPPORTS TRANSFER PTN000603741 carries the PTHR23427 SURF1-family IBD for mitochondrial localization; the mouse, S. pombe, and S. cerevisiae seeds support transfer to S. cerevisiae Shy1, whose more specific site of action is the 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: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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000603741 · SURF1-family ancestral node SUPPORTS TRANSFER PTN000603741 carries the PTHR23427 SURF1-family IBD for mitochondrial respiratory chain complex IV assembly; its fly, mouse, S. cerevisiae, and human seeds support inheritance of this core assembly-factor function by S. cerevisiae 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. |
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Download this section (compressed HTML)Q: Is protein-containing complex stabilizing activity the best molecular-function term for Shy1's Cox1 assembly-intermediate role, or would the evidence support a more specific Cox1 cofactor-insertion activity if such a GO term existed?
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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Download this section (compressed HTML)Mitochondrial inner membrane protein required for complex IV assembly; associates with complex IV assembly intermediates and complex III/complex IV supercomplexes; similar to human SURF1 involved in Leigh Syndrome; complex IV is also known as cytochrome c oxidase; also localizes to the peroxisome
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