GATOR1 complex subunit that inhibits TORC1 signaling and supports starvation responses in the germline and soma.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0034198 cellular response to amino acid starvation | IBA GO_REF:0000033 | ACCEPT | Summary: Nprl3 participates in the response to amino-acid starvation. Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation. Supporting Evidence: PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:1904262 negative regulation of TORC1 signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. |
| GO:0010508 positive regulation of autophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nprl3 promotes autophagy during nutrient stress via TORC1 inhibition. Reason: Mutants fail to activate autophagy under amino-acid starvation, indicating positive regulation of autophagy by GATOR1. Supporting Evidence: PMID:27672113 nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation |
| GO:1990130 GATOR1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Nprl3 is a core subunit of the GATOR1 complex. Reason: UniProt annotates Nprl3 as a probable GATOR1 subcomplex component, supporting this complex membership. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3 file:genes/DROME/Nprl3/Nprl3-deep-research-falcon.md GATOR1 is a conserved heterotrimer composed of DEPDC5, NPRL2, and NPRL3. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nprl3 localizes to the cytoplasm. Reason: UniProt reports cytoplasmic localization. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005764 lysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nprl3 localizes to lysosomes under nutrient stress. Reason: Lysosomal targeting is reported for Nprl2/Nprl3. Supporting Evidence: PMID:24786828 Nprl2 and Nprl3 physically interact and are targeted to lysosomes and autolysosomes |
| GO:0032007 negative regulation of TOR signaling | IEA GO_REF:0000002 | MODIFY | Summary: This term is too general for the specific TORC1 inhibition shown for Nprl3. Reason: Evidence supports inhibition of TORC1 specifically; replace with the TORC1-specific term. Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway |
| GO:0051301 cell division | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: General cell division is too broad relative to the specific mitotic-to-meiotic transition role. Reason: Evidence indicates a specific mitotic/meiotic transition control rather than broad cell division. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition |
| GO:0051321 meiotic cell cycle | IEA GO_REF:0000043 | MODIFY | Summary: Meiotic cell cycle is captured more precisely by germline mitotic-to-meiotic switching. Reason: Use the more specific germline cell cycle switching term supported by ovarian cyst data. Proposed replacements: germline cell cycle switching, mitotic to meiotic cell cycle Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition |
| GO:0005515 protein binding | IPI PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | KEEP AS NON CORE | Summary: Nprl3 physically interacts with Nprl2; high-throughput interaction datasets also report binding. Reason: Interaction evidence supports protein binding, but the term is generic and not core. Supporting Evidence: PMID:24786828 Nprl2 and Nprl3 physically interact PMID:38944040 We describe a next-generation Drosophila protein interaction map PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:0005515 protein binding | IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f... | KEEP AS NON CORE | Summary: Nprl3 physically interacts with Nprl2; high-throughput interaction datasets also report binding. Reason: Interaction evidence supports protein binding, but the term is generic and not core. Supporting Evidence: PMID:24786828 Nprl2 and Nprl3 physically interact PMID:38944040 We describe a next-generation Drosophila protein interaction map |
| GO:0034198 cellular response to amino acid starvation | NAS PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | ACCEPT | Summary: Nprl3 participates in the response to amino-acid starvation. Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation. Supporting Evidence: PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:1904262 negative regulation of TORC1 signaling | NAS PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. |
| GO:1904262 negative regulation of TORC1 signaling | IMP PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. |
| GO:0009267 cellular response to starvation | IMP PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the R... | KEEP AS NON CORE | Summary: Starvation response is supported but primarily in the amino-acid limitation context. Reason: Evidence supports amino-acid starvation response; the broader starvation term is acceptable but not core. Supporting Evidence: PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster. |
| GO:0010898 positive regulation of triglyceride catabolic process | IMP PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the R... | MARK AS OVER ANNOTATED | Summary: Nprl3 affects TAG storage, but direct positive regulation of triglyceride catabolism is not shown. Reason: Reported phenotype is reduced TAG storage in mutants, which does not directly demonstrate increased triglyceride catabolism. Supporting Evidence: PMID:27672113 nprl2 and nprl3 mutant adults contain reduced amounts of stored TAG relative to wild-type animals |
| GO:1904262 negative regulation of TORC1 signaling | IGI PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the R... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster. |
| GO:0005764 lysosome | IDA PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... | KEEP AS NON CORE | Summary: Nprl3 localizes to lysosomes under nutrient stress. Reason: Lysosomal targeting is reported for Nprl2/Nprl3. Supporting Evidence: PMID:24786828 Nprl2 and Nprl3 physically interact and are targeted to lysosomes and autolysosomes PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila. |
| GO:1904262 negative regulation of TORC1 signaling | IMP PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the R... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. PMID:27672113 The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster. |
| GO:0016239 positive regulation of macroautophagy | IGI PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | KEEP AS NON CORE | Summary: Nprl3 supports macroautophagy during amino-acid starvation. Reason: GATOR1 mutants fail to activate autophagy during amino-acid starvation. Supporting Evidence: PMID:27672113 nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:0035859 Seh1-associated complex | IDA PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | MODIFY | Summary: The SEA/GATOR complex term is broader than the specific GATOR1 complex membership. Reason: Evidence supports GATOR1 subcomplex membership; use the specific GATOR1 complex term. Proposed replacements: GATOR1 complex Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt Component of the GATOR complex consisting of mio, Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13 PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:1904262 negative regulation of TORC1 signaling | IGI PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:1990130 GATOR1 complex | TAS PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | ACCEPT | Summary: Nprl3 is a core subunit of the GATOR1 complex. Reason: UniProt annotates Nprl3 as a probable GATOR1 subcomplex component, supporting this complex membership. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3 PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:0061700 GATOR2 complex | IDA PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | MODIFY | Summary: Nprl3 is a GATOR1 subunit, not a GATOR2 complex component. Reason: UniProt places Nprl3 in the GATOR1 subcomplex; annotate to GATOR1 rather than GATOR2. Proposed replacements: GATOR1 complex Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3 PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:1904262 negative regulation of TORC1 signaling | IMP PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lyso... | ACCEPT | Summary: Nprl3 inhibits TORC1 signaling, especially under amino-acid starvation. Reason: Both UniProt and starvation studies describe Nprl3-mediated inhibition of TORC1 in response to amino-acid limitation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:24786828 Nprl2 and Nprl3 inhibit TORC1 signaling in the female germline in response to amino-acid starvation. PMID:27166823 The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. |
| GO:0032007 negative regulation of TOR signaling | IMP PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... | MODIFY | Summary: This term is too general for the specific TORC1 inhibition shown for Nprl3. Reason: Evidence supports inhibition of TORC1 specifically; replace with the TORC1-specific term. Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. |
| GO:0034198 cellular response to amino acid starvation | IMP PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... | ACCEPT | Summary: Nprl3 participates in the response to amino-acid starvation. Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation. Supporting Evidence: PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. |
| GO:0007293 germarium-derived egg chamber formation | IGI PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entr... | MODIFY | Summary: Evidence points to oogenesis/meiotic entry roles rather than the specific egg chamber formation term. Reason: Use the broader oogenesis term supported by meiotic entry/oocyte development data. Proposed replacements: oogenesis Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt control meiotic entry and promote oocyte growth and development PMID:25512509 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila. |
| GO:0005515 protein binding | IPI PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | KEEP AS NON CORE | Summary: Nprl3 physically interacts with Nprl2; high-throughput interaction datasets also report binding. Reason: Interaction evidence supports protein binding, but the term is generic and not core. Supporting Evidence: PMID:24786828 Nprl2 and Nprl3 physically interact PMID:38944040 We describe a next-generation Drosophila protein interaction map |
| GO:0005634 nucleus | IDA PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | UNDECIDED | Summary: Nuclear localization is not supported by the accessible sources used for this review. Reason: Available curated localization statements emphasize cytoplasm/lysosome/autolysosome without nuclear evidence. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24786828}. Lysosome PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0005737 cytoplasm | IDA PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | KEEP AS NON CORE | Summary: Nprl3 localizes to the cytoplasm. Reason: UniProt reports cytoplasmic localization. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0034198 cellular response to amino acid starvation | IMP PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | ACCEPT | Summary: Nprl3 participates in the response to amino-acid starvation. Reason: The Nprl2/Nprl3 complex mediates an adaptive response to amino-acid starvation. Supporting Evidence: PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0044754 autolysosome | IDA PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | KEEP AS NON CORE | Summary: Nprl3 localizes to autolysosomes during amino-acid starvation. Reason: UniProt notes primary localization to autolysosomes under amino-acid starvation. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt Localizes primarily to the autolysosomes during amino-acid starvation PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0045792 negative regulation of cell size | IMP PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | KEEP AS NON CORE | Summary: Nprl3 restrains TORC1-dependent cell growth, consistent with negative regulation of cell size. Reason: GATOR1 inhibition of TORC1-dependent growth supports reduced cell size/growth phenotypes. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt inhibiting TORC1-dependent cell growth PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0048477 oogenesis | IMP PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive res... | KEEP AS NON CORE | Summary: Nprl3 participates in oogenesis through GATOR1 control of meiotic entry and oocyte development. Reason: UniProt describes GATOR1 roles in meiotic entry and oocyte growth. Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt control meiotic entry and promote oocyte growth and development PMID:24786828 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. |
| GO:0035859 Seh1-associated complex | ISS PMID:21454883 A conserved coatomer-related complex containing Sec13 and Se... | MODIFY | Summary: The SEA/GATOR complex term is broader than the specific GATOR1 complex membership. Reason: Evidence supports GATOR1 subcomplex membership; use the specific GATOR1 complex term. Proposed replacements: GATOR1 complex Supporting Evidence: file:genes/DROME/Nprl3/Nprl3-uniprot.txt Component of the GATOR complex consisting of mio, Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13 PMID:21454883 A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae. |
| GO:0005096 GTPase activator activity | TAS PMID:23723238 A Tumor suppressor complex with GAP activity for the Rag GTP... | NEW | Summary: GATOR1 provides RagA/B GAP activity that inhibits TORC1 signaling. Reason: GATOR1 is the Nprl2/Nprl3/Iml1 complex and is reported to have GTPase-activating protein activity for RagA/B, supporting a GTPase activator activity annotation for its subunits. Supporting Evidence: PMID:23723238 GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer |
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