NPRL2_MOUSE
ID NPRL2_MOUSE Reviewed; 380 AA.
AC Q9WUE4;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=GATOR complex protein NPRL2 {ECO:0000305};
DE AltName: Full=Gene 21 protein {ECO:0000312|EMBL:AAD33474.1};
DE Short=G21 protein {ECO:0000312|EMBL:AAD33474.1};
DE AltName: Full=Nitrogen permease regulator 2-like protein {ECO:0000312|MGI:MGI:1914482};
DE Short=NPR2-like protein {ECO:0000312|MGI:MGI:1914482};
GN Name=Nprl2 {ECO:0000312|MGI:MGI:1914482};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Duh F.-M., Minna J.D., Lerman M.I.;
RT "Mouse ortholog of human G21 gene.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Embryonic stem cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: As a component of the GATOR1 complex functions as an
CC inhibitor of the amino acid-sensing branch of the TORC1 pathway. The
CC GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB
CC within RRAGC-containing heterodimers, thereby deactivating RRAGs,
CC releasing mTORC1 from lysosomal surface and inhibiting mTORC1
CC signaling. The GATOR1 complex is negatively regulated by GATOR2 the
CC other GATOR subcomplex in this amino acid-sensing branch of the TORC1
CC pathway. {ECO:0000250|UniProtKB:Q8WTW4}.
CC -!- FUNCTION: Suppresses Src-dependent tyrosine phosphorylation and
CC activation of PDPK1 and its downstream signaling. Down-regulates PDPK1
CC kinase activity by interfering with tyrosine phosphorylation at 'Tyr-
CC 9', 'Tyr-373' and 'Tyr-376' residues. May act as a tumor suppressor.
CC Suppresses cell growth and enhances sensitivity to various anticancer
CC drugs. {ECO:0000250|UniProtKB:Q8WTW4}.
CC -!- SUBUNIT: Forms a heterodimer with NPRL3. Interacts with PDPK1 (By
CC similarity). Within the GATOR complex, component of the GATOR1
CC subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong
CC interaction of the GATOR complex with RRAGA/RRAGC and RRAGB/RRAGC
CC heterodimers (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8WTW4}.
CC Note=Localization to lysosomes is amino acid-independent.
CC {ECO:0000250|UniProtKB:Q8WTW4}.
CC -!- SIMILARITY: Belongs to the NPR2 family. {ECO:0000305}.
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DR EMBL; AF131207; AAD33474.1; -; mRNA.
DR EMBL; AK013299; BAB28777.1; -; mRNA.
DR EMBL; AK010331; BAB26858.1; -; mRNA.
DR EMBL; BC026548; AAH26548.1; -; mRNA.
DR CCDS; CCDS23492.1; -.
DR RefSeq; NP_061367.1; NM_018879.2.
DR AlphaFoldDB; Q9WUE4; -.
DR SMR; Q9WUE4; -.
DR STRING; 10090.ENSMUSP00000010201; -.
DR iPTMnet; Q9WUE4; -.
DR PhosphoSitePlus; Q9WUE4; -.
DR EPD; Q9WUE4; -.
DR MaxQB; Q9WUE4; -.
DR PaxDb; Q9WUE4; -.
DR PRIDE; Q9WUE4; -.
DR ProteomicsDB; 293714; -.
DR Antibodypedia; 30939; 296 antibodies from 34 providers.
DR DNASU; 56032; -.
DR Ensembl; ENSMUST00000010201; ENSMUSP00000010201; ENSMUSG00000010057.
DR GeneID; 56032; -.
DR KEGG; mmu:56032; -.
DR UCSC; uc009rln.2; mouse.
DR CTD; 10641; -.
DR MGI; MGI:1914482; Nprl2.
DR VEuPathDB; HostDB:ENSMUSG00000010057; -.
DR eggNOG; KOG3789; Eukaryota.
DR GeneTree; ENSGT00390000001414; -.
DR HOGENOM; CLU_014995_0_0_1; -.
DR InParanoid; Q9WUE4; -.
DR OMA; YASMTHG; -.
DR OrthoDB; 500740at2759; -.
DR PhylomeDB; Q9WUE4; -.
DR TreeFam; TF106159; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 56032; 9 hits in 75 CRISPR screens.
DR ChiTaRS; Nprl2; mouse.
DR PRO; PR:Q9WUE4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9WUE4; protein.
DR Bgee; ENSMUSG00000010057; Expressed in interventricular septum and 245 other tissues.
DR ExpressionAtlas; Q9WUE4; baseline and differential.
DR Genevisible; Q9WUE4; MM.
DR GO; GO:1990130; C:GATOR1 complex; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI.
DR GO; GO:0033673; P:negative regulation of kinase activity; ISO:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:MGI.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IBA:GO_Central.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR InterPro; IPR009348; NPR2.
DR PANTHER; PTHR12991; PTHR12991; 2.
DR Pfam; PF06218; NPR2; 1.
PE 2: Evidence at transcript level;
KW GTPase activation; Lysosome; Membrane; Reference proteome;
KW Tumor suppressor.
FT CHAIN 1..380
FT /note="GATOR complex protein NPRL2"
FT /id="PRO_0000213320"
FT REGION 1..133
FT /note="Interaction with PDPK1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 380 AA; 43644 MW; 72AE3A46AB50B21D CRC64;
MGSSCRIECI FFSEFHPTLG PKITYQVPED FISRELFDTV QVYIITKPEL QNKLITVTAM
EKKLIGCPVC IEHKKYSRNA LLFNLGFVCD AQAKTCALEP IVKKLAGYLT TLELESSFVS
NEESKQKLVP IMTILLEELN ASGRCTLPID ESNTIHLKVI EQRPDPPVAQ EYDVPVFTKD
KEDFFSSQWD LTTQQILPYI DGFRHVQKIS AEADVELNLV RIAIQNLLYY GVVTLVSILQ
YSNVYCPTPK VQDLVDDKSL QEACLSYVTK QGHKRASLRD VFQLYCSLSP GTTVRDLIGR
HPQQLQHVDE RKLIQFGLMK NLIRRLQKYP VRVSREERSH PARLYTGCHS YDEICCKTGM
SYHELDERLE NDPNIIICWK
