Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy.
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Founding paper identifying SDHAF1 as the first bona fide SDH (Complex II) assembly factor; biallelic mutations cause SDH-defective infantile leukoencephalopathy, and wild-type re-expression restores SDH activity and amount.
"SDH activity and amount were restored in mutant fibroblasts proportionally with re-expression of the wild-type gene."
Cochaperone binding to LYR motifs confers specificity of iron sulfur cluster delivery.
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SDHAF1 (LYRM8) is an HSC20 binding partner; LYR-motif proteins engage the ISCU-HSC20-HSPA9 Fe-S transfer complex, and SDHAF1 associates with SDHB via a non-LYR site while positioning the Fe-S transfer complex through its own LYR motif.
"members of the LYR motif family which assist assembly of complexes II or III, SDHAF1 and LYRM7, respectively, are HSC20 binding partners."
Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB.
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SDHAF1 contributes to Fe-S cluster incorporation into SDHB by binding SDHB (C-terminal arginine-rich region) and engaging the HSC20-HSPA9 co-chaperone/chaperone pair with the ISCU scaffold via its N-terminal LYR motif; disease mutations abrogate SDHB binding, leading to LONP1-mediated SDHB degradation, and riboflavin ameliorates the phenotype.
"SDHAF1 transiently binds to aromatic peptides of SDHB through an arginine-rich region in its C terminus and specifically engages a Fe-S donor complex, consisting of the scaffold, holo-ISCU, and the co-chaperone-chaperone pair, HSC20-HSPA9, through an LYR motif near its N-terminal domain."
A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III.
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The HSC20-HSPA9-ISCU Fe-S transfer complex delivers clusters to LYR-motif-associated respiratory chain assembly intermediates (complexes I-III), the general framework in which SDHAF1 acts for Complex II.
"Binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates Fe-S cluster transfer to UQCRFS1."
A reference map of the human binary protein interactome.
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Large-scale binary (Y2H) interactome (HuRI); source of high-throughput SDHAF1 interactions with KRT27 and CIDEB that are not physiologically meaningful for a matrix assembly factor.
"With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 AP-MS interactome; recovers the SDHAF1-SDHB interaction consistent with SDHAF1's role as an SDHB-binding assembly factor.
"Comparison across cell lines validates thousands of interactions and reveals extensive customization."
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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High-confidence quantitative human mitochondrial proteome; supports SDHAF1 mitochondrial localization (source of the HTP localization annotation).
"Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context."
Transfer of Fe-S clusters to SDHB
SDHA:SDHB binds to SDHC:SDHD