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 |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Nitrogen permease regulator-like 3 (Nprl3) encodes a component of the highly conserved GAP activity towards rags 1 (GATOR1) complex, which inhibits the product of mTor activity in response to amino acid starvation. The product of Nprl3, as well as the other GATOR1 components encoded by Nprl2 and Iml1, regulates early meiotic progression.
Loading supporting content…
Download this section (compressed HTML)