NPRL2_DROME
ID NPRL2_DROME Reviewed; 412 AA.
AC Q9VXA0;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=GATOR complex protein NPRL2 {ECO:0000305};
DE AltName: Full=Nitrogen permease regulator 2-like protein {ECO:0000312|FlyBase:FBgn0030800};
GN Name=Nprl2 {ECO:0000312|FlyBase:FBgn0030800};
GN ORFNames=CG9104 {ECO:0000312|FlyBase:FBgn0030800};
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] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAK93338.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93338.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAK93338.1};
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] {ECO:0000305}
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 [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH NPRL3, 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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [7]
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 [8]
RP FUNCTION, AND IDENTIFICATION IN THE GATOR COMPLEX.
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 Nprl3 (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}. Note=Localizes primarily to the
CC autolysosomes during amino-acid starvation.
CC {ECO:0000269|PubMed:24786828}.
CC -!- DISRUPTION PHENOTYPE: Pupal homozygous semi-lethal (PubMed:27672113).
CC Under nutrient-replete conditions, larvae display a significant
CC increase in TORC1 activity and adult escapers display a small, but
CC significant increase in body weight and a reduction in climbing
CC (PubMed:27672113). Newly hatched males display decreased tolerance to
CC both complete starvation and amino acid starvation, likely due to
CC decreased triacylglyceride (TAG) storage and the inability to down-
CC regulate TORC1 activity and activate catabolic metabolism and autophagy
CC (PubMed:27672113). Conditional RNAi-mediated knockdown in the female
CC germline results in a small decrease in the rate of egg production when
CC 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). Double RNAi-mediated knockdown with
CC another GATOR1 complex member Iml1 in the female germline, increases
CC the penetrance of ovarian cysts displaying delayed mitotic exit and
CC producing 32-cell cysts (PubMed:25512509).
CC {ECO:0000269|PubMed:24786828, ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27672113}.
CC -!- SIMILARITY: Belongs to the NPR2 family. {ECO:0000305}.
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DR EMBL; AE003503; AAF48677.1; -; Genomic_DNA.
DR EMBL; AY051914; AAK93338.1; -; mRNA.
DR RefSeq; NP_573174.1; NM_132946.3.
DR AlphaFoldDB; Q9VXA0; -.
DR SMR; Q9VXA0; -.
DR STRING; 7227.FBpp0074122; -.
DR PaxDb; Q9VXA0; -.
DR PRIDE; Q9VXA0; -.
DR DNASU; 32677; -.
DR EnsemblMetazoa; FBtr0074348; FBpp0074122; FBgn0030800.
DR GeneID; 32677; -.
DR KEGG; dme:Dmel_CG9104; -.
DR UCSC; CG9104-RA; d. melanogaster.
DR CTD; 10641; -.
DR FlyBase; FBgn0030800; Nprl2.
DR VEuPathDB; VectorBase:FBgn0030800; -.
DR eggNOG; KOG3789; Eukaryota.
DR GeneTree; ENSGT00390000001414; -.
DR HOGENOM; CLU_014995_0_0_1; -.
DR InParanoid; Q9VXA0; -.
DR OMA; YASMTHG; -.
DR OrthoDB; 500740at2759; -.
DR PhylomeDB; Q9VXA0; -.
DR BioGRID-ORCS; 32677; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32677; -.
DR PRO; PR:Q9VXA0; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030800; Expressed in oviduct (Drosophila) and 26 other tissues.
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:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
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:0051729; P:germline cell cycle switching, mitotic to meiotic cell cycle; IGI:UniProtKB.
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:FlyBase.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IMP:FlyBase.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:GOC.
DR GO; GO:0038202; P:TORC1 signaling; IMP:FlyBase.
DR InterPro; IPR009348; NPR2.
DR PANTHER; PTHR12991; PTHR12991; 1.
DR Pfam; PF06218; NPR2; 2.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Lysosome; Meiosis; Mitosis;
KW Reference proteome.
FT CHAIN 1..412
FT /note="GATOR complex protein NPRL2"
FT /id="PRO_0000435315"
SQ SEQUENCE 412 AA; 46345 MW; D11544CA83338F10 CRC64;
MHSHTNETAA TSTTAGAVTN GAGGSGAGAA GAHGSTEGKI RCIFLSEFHA TAGCKISCQV
PDNYISKDVF DAINVYIIPK QHLQRCILTV NAMDVKIVGY PVGIQDQQKY ARNAFLFNLC
FVCDSRARSV QYEPVVKKLS EYLIMMEEES CFLSREDDKR RLQNIFETVL RDLNERKVAT
IVEGDNTIYL KIVMHKPDPP PVKDHMVPLL LANLRDAPLD NWDLTTQQIL PYINGINHVA
RIAAEADVET DLVKSCIQNL VYYGVVQLLP ILKYSNVYMT QNLKHLIQSA SLSGACRKYV
ALRPDKTLPS VQRIFQFYAS MTHGVTLRAI CQRLCPQHHN IDERRMVIFG LQHRFIRCIH
KYPVFTGSVP SGRQKMYTGL ISFDEICCKT GLSPCTIERD IEKDTNVTVI WK
