SGD gene description for SAN1 (yeast)
UniProt entry P22470 (SAN1)
Annotation inferences using phylogenetic trees
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PAINT/IBA methodology propagating experimental annotations within the PANTHER phylogenetic tree. Source of the current SAN1 IBA annotations to ubiquitin protein ligase activity, cytoplasm, ERAD quality control pathway, and response to misfolded protein, plus the retired ubiquitin-dependent protein catabolic process IBA.
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"
Role of the San1 ubiquitin ligase in the heat stress-induced degradation of nonnative Nup1 in the nuclear pore complex.
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San1 contributes to proteasome-dependent degradation of nonnative Nup1 incorporated into the nuclear pore complex under heat stress or impaired NPC biogenesis.
"These biochemical and genetic data suggest that San1 is involved in the degradation of nonnative Nups generated by genetic mutation or when NPC biogenesis is impaired."
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy, and nucleus-vacuole junctions.
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Quiescent yeast cells maintain selective degradation of model misfolded proteins through San1- and Ubr1-dependent ubiquitination, with Ubr1 dominant for the tested substrates.
"Misfolded proteins were degraded in a manner dependent on the E3 ubiquitin ligases Ubr1 and San1, with Ubr1 playing a dominant role."
TAP-MS analysis of FACT interactions and regulation by a ubiquitin ligase, San1.
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San1-dependent ubiquitylation of the FACT subunit Spt16 influences the FACT interactome, connecting San1-mediated substrate degradation to FACT-linked chromatin, transcription, and DNA repair networks.
"Further, an intrinsically disordered ubiquitin ligase, San1, that ubiquitylates the Spt16 component of FACT for proteasomal degradation to regulate chromatin, transcription and genome integrity is found to influence the interactions of FACT with a set of proteins including epigenetic, transcription and DNA repair factors."
Aberrant cohesin function in Saccharomyces cerevisiae activates Mcd1 degradation to promote cell lethality.
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Yeast cells with aberrant cohesin function can use San1 and other E3 ligases to target the cohesin subunit Mcd1 for degradation.
"Our findings further reveal that cells that exhibit aberrant cohesin function employ E3 ligases (such as San1) to target Mcd1 for degradation."
Proteasomal Degradation of Mutant Huntingtin Exon1 Regulates Autophagy.
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San1-dependent proteasomal degradation of soluble mutant huntingtin exon1 is required for efficient autophagic clearance of Htt103QP inclusion bodies in a budding-yeast model.
"Collectively, these findings demonstrate that San1, but not Ubr1, is required for both proteasomal degradation of Htt103QP and IBophagy."
Blocking protein quality control degradation leads to structural stabilization of DHFR indel variants.
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Deleting either UBR1 or SAN1 stabilizes a subset of yeast-expressed DHFR indel folding reporters, supporting the use of San1/Ubr1 knockouts to reveal PQC-sensitive hypomorphic variants.
"We show that deletion of Ubr1 or San1 leads to a greater fraction of folded DHFR indel variants, primarily positioned toward the N- and C-terminal regions in DHFR."