Annotation inferences using phylogenetic trees
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NSG2 IBA annotations are family-transfer annotations from the INSIG/PANTHER context and should be interpreted as conserved regulatory/chaperone functions, not sterol-enzyme activity.
"GOA WITH/FROM includes PANTHER:PTN000393022 for ER and sterol biosynthetic process annotations."
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
UniProtKB entry for NSG2_YEAST
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Nsg2 is an ER membrane INSIG-family protein.
"FUNCTION: Stabilizes the HMG-CoA reductase HMG2 by preventing its HRD1-dependent degradation. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the INSIG family."
Global analysis of protein localization in budding yeast
INSIG: a broadly conserved transmembrane chaperone for sterol-sensing domain proteins
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Nsg1 and Nsg2 are yeast INSIG homologs that regulate Hmg2 stability through direct interaction with its SSD-containing transmembrane region.
"We now show that the yeast INSIG homologs NSG1 and NSG2 function to control the stability of yeast Hmg2p, the HMGR isozyme that undergoes regulated ubiquitination."
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The NSG proteins are best interpreted as dedicated chaperones for SSD-containing client proteins.
"One way to unify the known, disparate actions of INSIGs is to view them as known adaptations of a chaperone dedicated to SSD-containing client proteins."
One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy
Role of Pex31 in metabolic adaptation of the nucleus-vacuole junction
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Nsg2 is a conditional nucleus-vacuole junction resident during low-glucose conditions.
"Here, we used systematic microscopy-based approaches to compare the NVJ at glucose-replete and -restricted conditions and identified five additional NVJ proteins: the permanent NVJ resident Shr5 and the conditional residents Nsg1, Nsg2, Tcb1 and Pex31."
Glucose starvation signaling via nucleus-vacuole junction remodeling controls ergosterol synthesis.
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Glucose starvation recruits Nsg2 to the NVJ with Nsg1 and the Hmg1/Hmg2 HMG-CoA reductases, and the remodelled NVJ stabilizes Nsg2 to suppress Hmg1-dependent sterol synthesis.
"Ypf1 promotes the recruitment of Nsg1, Nsg2, and the HMG-CoA reductases Hmg1 and Hmg2 to the NVJ, likely in association with changes in nuclear membrane lipid composition caused by suppression of fatty acid elongases. This remodeling destabilizes Nsg1, thereby activating Hmg1, while stabilizing Nsg2, which suppresses Hmg1 to fine-tune sterol synthesis."
Falcon deep research report for NSG2
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Falcon supports the interpretation of NSG2 as an INSIG-family ER membrane chaperone/regulator of Hmg2 stability with conditional NVJ localization.
"NSG2/YNL156C is best annotated as an ER and starvation-induced NVJ multi-pass INSIG-family membrane protein that participates in sterol homeostasis primarily by modulating the stability and/or activity of HMG-CoA reductase isozymes."
Automatic assignment of GO terms using logical inference, based on on inter-ontology links