NPRL3_DROME
ID NPRL3_DROME Reviewed; 610 AA.
AC Q9VUB4; A4V1X9; Q95RI3;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=GATOR complex protein NPRL3 {ECO:0000305};
DE AltName: Full=Nitrogen permease regulator 3-like protein;
GN Name=Nprl3 {ECO:0000312|FlyBase:FBgn0036397};
GN ORFNames=CG8783 {ECO:0000312|FlyBase:FBgn0036397};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [5]
RP FUNCTION.
RX PubMed=23723238; DOI=10.1126/science.1232044;
RA Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A.,
RA Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M.;
RT "A Tumor suppressor complex with GAP activity for the Rag GTPases that
RT signal amino acid sufficiency to mTORC1.";
RL Science 340:1100-1106(2013).
RN [6]
RP FUNCTION, INTERACTION WITH NPRL2, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24786828; DOI=10.1038/cdd.2014.63;
RA Wei Y., Lilly M.A.;
RT "The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to
RT amino-acid starvation in Drosophila.";
RL Cell Death Differ. 21:1460-1468(2014).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25512509; DOI=10.1073/pnas.1419156112;
RA Wei Y., Reveal B., Reich J., Laursen W.J., Senger S., Akbar T.,
RA Iida-Jones T., Cai W., Jarnik M., Lilly M.A.;
RT "TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte
RT development in Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5670-E5677(2014).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27672113; DOI=10.1534/g3.116.035337;
RA Wei Y., Reveal B., Cai W., Lilly M.A.;
RT "The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to
RT Nutrient Stress in Drosophila melanogaster.";
RL G3 (Bethesda) 6:3859-3867(2016).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE GATOR COMPLEX, INTERACTION WITH WDR24, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=27166823; DOI=10.1371/journal.pgen.1006036;
RA Cai W., Wei Y., Jarnik M., Reich J., Lilly M.A.;
RT "The GATOR2 component Wdr24 regulates TORC1 activity and lysosome
RT function.";
RL PLoS Genet. 12:E1006036-E1006036(2016).
CC -!- FUNCTION: An essential component of the GATOR subcomplex GATOR1 which
CC functions as an inhibitor of the amino acid-sensing branch of the TORC1
CC signaling pathway (PubMed:23723238, PubMed:27166823, PubMed:25512509).
CC The two GATOR subcomplexes, GATOR1 and GATOR2, regulate the TORC1
CC pathway in order to mediate metabolic homeostasis, female gametogenesis
CC and the response to amino acid limitation and complete starvation
CC (PubMed:23723238, PubMed:27166823, PubMed:25512509). The function of
CC GATOR1 in negatively regulating the TORC1 pathway is essential for
CC maintaining baseline levels of TORC1 activity under nutrient rich
CC conditions, and for promoting survival during amino acid or complete
CC starvation by inhibiting TORC1-dependent cell growth and promoting
CC catabolic metabolism and autophagy (PubMed:23723238, PubMed:27166823).
CC In addition, this inhibition of TORC1 is necessary to maintain female
CC fertility under normal conditions and during periods of nutrient stress
CC (PubMed:24786828, PubMed:27672113, PubMed:25512509). GATOR1 and GATOR2
CC act at different stages of oogenesis to regulate TORC1 in order to
CC control meiotic entry and promote oocyte growth and development
CC (PubMed:25512509). After exactly four mitotic cyst divisions, the
CC GATOR1 complex members (Iml1, Nprl2 and Nprl3) down-regulate TORC1 to
CC slow cellular metabolism and promote the mitotic/meiotic transition
CC (PubMed:25512509). At later stages of oogenesis, the mio and Nup44A
CC components of the GATOR2 complex inhibit GATOR1 and thus activate TORC1
CC to promote meiotic progression, and drive oocyte growth and development
CC (PubMed:25512509). {ECO:0000269|PubMed:23723238,
CC ECO:0000269|PubMed:24786828, ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27166823, ECO:0000269|PubMed:27672113}.
CC -!- SUBUNIT: Component of the GATOR complex consisting of mio, Nup44A/Seh1,
CC Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13 (PubMed:27166823). Within
CC the GATOR complex, probable component of the GATOR1 subcomplex which is
CC likely composed of Iml1, Nplr2 and Nplr3 (PubMed:27166823). Interacts
CC with Nprl2 (PubMed:24786828). {ECO:0000269|PubMed:24786828,
CC ECO:0000269|PubMed:27166823}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24786828}. Lysosome
CC {ECO:0000269|PubMed:24786828, ECO:0000269|PubMed:25512509}.
CC Note=Localizes primarily to the autolysosomes during amino-acid
CC starvation (PubMed:24786828). {ECO:0000269|PubMed:24786828}.
CC -!- DISRUPTION PHENOTYPE: A high percentage of mutants die as pupae or
CC pharate adults (PubMed:27166823, PubMed:27672113). Under nutrient-
CC replete conditions, larvae display a significant increase in TORC1
CC activity (PubMed:27672113, PubMed:27166823). Adult escapers display a
CC small but significant increase in body weight and a reduction in
CC climbing (PubMed:27672113). Newly hatched males have a decreased
CC tolerance to both complete starvation and amino acid starvation, likely
CC due to decreased triacylglyceride (TAG) storage and the inability to
CC down-regulate TORC1 activity and activate catabolic metabolism and
CC autophagy (PubMed:27672113). Conditional RNAi-mediated knockdown in the
CC female germline results in a small decrease in the rate of egg
CC production when females are provided with a protein source of wet yeast
CC (PubMed:24786828). Females starved of amino acids for a brief period
CC have increased numbers of degenerating young eggs and show permanent
CC loss of fertility (PubMed:24786828). Mid-stage egg chambers are
CC unaffected (PubMed:24786828). {ECO:0000269|PubMed:24786828,
CC ECO:0000269|PubMed:27166823, ECO:0000269|PubMed:27672113}.
CC -!- SIMILARITY: Belongs to the NPR3 family. {ECO:0000305}.
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DR EMBL; AE014296; AAF49774.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11821.1; -; Genomic_DNA.
DR EMBL; AY061356; AAL28904.1; -; mRNA.
DR RefSeq; NP_001261818.1; NM_001274889.1.
DR RefSeq; NP_648680.2; NM_140423.3.
DR RefSeq; NP_729945.1; NM_168570.1.
DR AlphaFoldDB; Q9VUB4; -.
DR BioGRID; 64889; 8.
DR DIP; DIP-23525N; -.
DR IntAct; Q9VUB4; 1.
DR STRING; 7227.FBpp0075527; -.
DR iPTMnet; Q9VUB4; -.
DR PaxDb; Q9VUB4; -.
DR DNASU; 39550; -.
DR EnsemblMetazoa; FBtr0075785; FBpp0075527; FBgn0036397.
DR EnsemblMetazoa; FBtr0075786; FBpp0075528; FBgn0036397.
DR EnsemblMetazoa; FBtr0333025; FBpp0305239; FBgn0036397.
DR GeneID; 39550; -.
DR KEGG; dme:Dmel_CG8783; -.
DR UCSC; CG8783-RA; d. melanogaster.
DR CTD; 8131; -.
DR FlyBase; FBgn0036397; Nprl3.
DR VEuPathDB; VectorBase:FBgn0036397; -.
DR eggNOG; KOG3830; Eukaryota.
DR GeneTree; ENSGT00390000015916; -.
DR HOGENOM; CLU_014030_1_0_1; -.
DR InParanoid; Q9VUB4; -.
DR OMA; CLPQKVH; -.
DR OrthoDB; 628619at2759; -.
DR PhylomeDB; Q9VUB4; -.
DR BioGRID-ORCS; 39550; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 39550; -.
DR PRO; PR:Q9VUB4; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036397; Expressed in cleaving embryo and 21 other tissues.
DR ExpressionAtlas; Q9VUB4; baseline and differential.
DR Genevisible; Q9VUB4; DM.
DR GO; GO:0044754; C:autolysosome; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:1990130; C:GATOR1 complex; IBA:GO_Central.
DR GO; GO:0061700; C:GATOR2 complex; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0007293; P:germarium-derived egg chamber formation; IGI:FlyBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:FlyBase.
DR GO; GO:1904766; P:negative regulation of macroautophagy by TORC1 signaling; IMP:FlyBase.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IGI:FlyBase.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IMP:FlyBase.
DR GO; GO:0038202; P:TORC1 signaling; IMP:FlyBase.
DR InterPro; IPR005365; Npr3.
DR PANTHER; PTHR13153; PTHR13153; 1.
DR Pfam; PF03666; NPR3; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Lysosome; Meiosis; Mitosis;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..610
FT /note="GATOR complex protein NPRL3"
FT /id="PRO_0000220639"
FT REGION 474..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 590
FT /note="R -> S (in Ref. 3; AAL28904)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 610 AA; 68787 MW; E84D87FF2B831898 CRC64;
METNVNPLAV ILVYFDSKGD RLLYRYPYQT LGQTEVANDE QRKSRKRNPY AVANTDDLLQ
TPTHLGAAKS QGQLQGFADE VLSALFAVKP QLCNQKFELK LNDVRFVSHP TLIPQKEQRS
GPMAKQQMLI NIVFALHAQA SYSIVKCYHE LSKRLGLALK FEEQRSGYLT EQTAQMARTH
DEQQQQPLER TLELIAERCS LAQALRSIFH DLCTTGLLST SLNHNLTLCF CLPAKAHQLH
KKGSMVDPET IDRCLRALKP YHGMLLLVDF AELLDCVPPT GARMLWQLVD VYDPLISLQS
MSSNADLSIE HVYKLVSHLV YWAKATIIYP LCETNVYVIA PDAPLHTKSH LVEKFSARFA
GMSLFEVISD FSLPTSIGHL TTPLQQPARQ GILAQMVIWM LQHHLLMQLH TYVQFMPSED
EFGDSASCSN HLRDAISDEE GDQEPDADEL HGSMLSMSSH PLPVPAVLVG GHRREASEDH
SSLASDNIAV QPSSSHKSNF SITASMSTDN CDSLDSMEDE QKLKELLQVF SDADRAAIRR
IPASANVDDL SLLVKLYQMG YFKSEHHLEE IMYFENLRRS QLLQLLDKFR DVLIIYETED
PAIASMYNTK
