Annotation inferences using phylogenetic trees
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PAINT/IBA methodology propagating experimental annotations within the PANTHER phylogenetic tree. Source of the SAN1 IBA annotations (ubiquitin protein ligase activity, ubiquitin-dependent protein catabolic process, and cytoplasm), consistent with experimentally established San1 function as a nuclear E3 ligase for misfolded substrates.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
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UniProt keyword-to-GO mapping methodology. Source of the IEA annotations on SAN1 derived from Swiss-Prot keywords (Zinc / Metal- binding / Zinc-finger), mapping to zinc ion binding (KW-0863) and metal ion binding (KW-0479) — consistent with the experimentally established RING-type zinc finger of San1.
Sir Antagonist 1 (San1) is a ubiquitin ligase.
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San1 contains a RING domain and possesses ubiquitin-protein isopeptide ligase activity in vitro. Mutant sir4 and spt16 proteins are unstable in SAN1 cells but stabilized in san1-delta cells.
"We demonstrate that San1 possesses ubiquitin-protein isopeptide ligase activity in vitro, and the ubiquitin-protein isopeptide ligase activity of San1 is required for its function in vivo"
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San1 targets a specific class of unstable nuclear proteins for degradation. Wild-type Spt16, Sir3, Sir2, and Ste6-166 are not affected by san1-delta.
"san1Delta did not affect the stability of wild-type Spt16, Sir3, Sir2, or the Spt16-associated proteins Pob3 and Nhp6. Loss of SAN1 also did not affect the stability of Ste6-166, a highly unstable protein in yeast"
Degradation-mediated protein quality control in the nucleus.
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San1 defines a nuclear protein quality control degradation system. It targets four distinct mutant nuclear proteins for ubiquitination and proteasomal destruction, working with E2 enzymes Cdc34 and Ubc1.
"San1p, a ubiquitin-protein ligase that, in conjunction with the ubiquitin-conjugating enzymes Cdc34p and Ubc1p, targets four distinct mutant nuclear proteins for ubiquitination and destruction by the proteasome"
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San1 is nuclear localized and requires nuclear localization for function. It has exquisite specificity for aberrant proteins and does not target wild-type versions.
"San1p has exquisite specificity for aberrant proteins and does not target the wild-type versions of its mutant substrates. San1p is nuclear localized and requires nuclear localization for function"
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Loss of SAN1 results in a chronic stress response, indicating its essential role in nuclear protein quality control.
"Loss of SAN1 results in a chronic stress response, underscoring its role of protein quality control in the cell"
Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1.
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San1 also participates in cytoplasmic PQC alongside Ubr1. Two strategies are employed: chaperone-assisted ubiquitination by Ubr1 and chaperone-dependent delivery to nuclear San1.
"Ubr1 and San1 mediate chaperone-dependent ubiquitination of numerous misfolded cytoplasmic proteins"
Disorder targets misorder in nuclear quality control degradation: a disordered ubiquitin ligase directly recognizes its misfolded substrates.
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San1 directly recognizes misfolded substrates via intrinsically disordered N- and C-terminal domains, which contain conserved substrate-recognition sites interspersed among flexible disordered regions.
"the yeast nuclear PQC ubiquitin ligase San1 directly recognizes its misfolded substrates via intrinsically disordered N- and C-terminal domains. These disordered domains are punctuated with small segments of order and high sequence conservation that serve as substrate-recognition sites"
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The intrinsic plasticity of San1 disordered domains allows it to bind many differently shaped misfolded substrates, explaining its broad substrate specificity.
"these substrate-recognition sites, interspersed among flexible, disordered regions, provide San1 an inherent plasticity which allows it to bind its many, differently shaped misfolded substrates"
The cellular economy of the Saccharomyces cerevisiae zinc proteome.
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San1 was identified as a zinc-binding protein in the yeast zinc proteome analysis, consistent with its RING-type zinc finger domain.
"The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis"
Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulating Lysine Biosynthesis.
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High-throughput screen for peroxisomal proteins using overexpression under strong TEF2 promoter. San1 is not discussed by name in the paper; the HDA annotation for peroxisomal localization may be an artifact of overexpression.
"we utilized a collection of strains containing a peroxisomal marker in which each protein is expressed from the constitutive and strong TEF2 promoter"