{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9VUB4","secondaryAccessions":["A4V1X9","Q95RI3"],"uniProtkbId":"NPRL3_DROME","entryAudit":{"firstPublicDate":"2001-09-26","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-05-01","entryVersion":140,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Drosophila melanogaster","commonName":"Fruit fly","taxonId":7227,"lineage":["Eukaryota","Metazoa","Ecdysozoa","Arthropoda","Altocrustacea","Allotriocarida","Hexapoda","Insecta","Pterygota","Neoptera","Eumetabola","Endopterygota","Aparaglossata","Panorpida","Diptera","Brachycera","Muscomorpha","Ephydroidea","Drosophilidae","Drosophila","Sophophora"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"GATOR complex protein NPRL3"}},"alternativeNames":[{"fullName":{"value":"Nitrogen permease regulator 3-like protein"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"FlyBase","id":"FBgn0036397"}],"value":"Nprl3"},"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"FlyBase","id":"FBgn0036397"}],"value":"CG8783"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23723238"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25512509"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27166823"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27672113"}],"value":"An essential component of the GATOR subcomplex GATOR1 which functions as an inhibitor of the amino acid-sensing branch of the TORC1 signaling pathway (PubMed:23723238, PubMed:25512509, PubMed:27166823). The two GATOR subcomplexes, GATOR1 and GATOR2, regulate the TORC1 pathway in order to mediate metabolic homeostasis, female gametogenesis and the response to amino acid limitation and complete starvation (PubMed:23723238, PubMed:25512509, PubMed:27166823). The function of GATOR1 in negatively regulating the TORC1 pathway is essential for maintaining baseline levels of TORC1 activity under nutrient rich conditions, and for promoting survival during amino acid or complete starvation by inhibiting TORC1-dependent cell growth and promoting catabolic metabolism and autophagy (PubMed:23723238, PubMed:27166823). In addition, this inhibition of TORC1 is necessary to maintain female fertility under normal conditions and during periods of nutrient stress (PubMed:24786828, PubMed:25512509, PubMed:27672113). GATOR1 and GATOR2 act at different stages of oogenesis to regulate TORC1 in order to control meiotic entry and promote oocyte growth and development (PubMed:25512509). After exactly four mitotic cyst divisions, the GATOR1 complex members (Iml1, Nprl2 and Nprl3) down-regulate TORC1 to slow cellular metabolism and promote the mitotic/meiotic transition (PubMed:25512509). At later stages of oogenesis, the mio and Nup44A components of the GATOR2 complex inhibit GATOR1 and thus activate TORC1 to promote meiotic progression, and drive oocyte growth and development (PubMed:25512509)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27166823"}],"value":"Component of the GATOR complex consisting of mio, Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13 (PubMed:27166823). Within the GATOR complex, probable component of the GATOR1 subcomplex which is likely composed of Iml1, Nplr2 and Nplr3 (PubMed:27166823). Interacts with Nprl2 (PubMed:24786828)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9VUB4","intActId":"EBI-113252"},"interactantTwo":{"uniProtKBAccession":"Q9XZ25","geneName":"Wdr24","intActId":"EBI-3407214"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"}],"value":"Localizes primarily to the autolysosomes during amino-acid starvation (PubMed:24786828)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25512509"}],"value":"Lysosome","id":"SL-0158"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24786828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27166823"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27672113"}],"value":"A high percentage of mutants die as pupae or pharate adults (PubMed:27166823, PubMed:27672113). Under nutrient-replete conditions, larvae display a significant increase in TORC1 activity (PubMed:27166823, PubMed:27672113). Adult escapers display a small but significant increase in body weight and a reduction in climbing (PubMed:27672113). Newly hatched males have a decreased tolerance to both complete starvation and amino acid starvation, likely due to decreased triacylglyceride (TAG) storage and the inability to down-regulate TORC1 activity and activate catabolic metabolism and autophagy (PubMed:27672113). Conditional RNAi-mediated knockdown in the female germline results in a small decrease in the rate of egg production when females are provided with a protein source of wet yeast (PubMed:24786828). Females starved of amino acids for a brief period have increased numbers of degenerating young eggs and show permanent loss of fertility (PubMed:24786828). Mid-stage egg chambers are unaffected (PubMed:24786828)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the NPR3 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":610,"modifier":"EXACT"}},"description":"GATOR complex protein NPRL3","featureId":"PRO_0000220639"},{"type":"Region","location":{"start":{"value":474,"modifier":"EXACT"},"end":{"value":501,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":482,"modifier":"EXACT"},"end":{"value":501,"modifier":"EXACT"}},"description":"Polar residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified 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