ID   NPRL2_BOVIN             Reviewed;         380 AA.
AC   Q5E9U9; Q3MHG8;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=GATOR complex protein NPRL2 {ECO:0000305};
DE   AltName: Full=Nitrogen permease regulator 2-like protein {ECO:0000250|UniProtKB:Q8WTW4};
DE            Short=NPR2-like protein {ECO:0000250|UniProtKB:Q8WTW4};
GN   Name=NPRL2 {ECO:0000250|UniProtKB:Q8WTW4};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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; BT020810; AAX08827.1; -; mRNA.
DR   EMBL; BT020821; AAX08838.1; -; mRNA.
DR   EMBL; BC105243; AAI05244.1; -; mRNA.
DR   AlphaFoldDB; Q5E9U9; -.
DR   SMR; Q5E9U9; -.
DR   STRING; 9913.ENSBTAP00000025503; -.
DR   PaxDb; Q5E9U9; -.
DR   PRIDE; Q5E9U9; -.
DR   eggNOG; KOG3789; Eukaryota.
DR   HOGENOM; CLU_014995_0_0_1; -.
DR   InParanoid; Q5E9U9; -.
DR   TreeFam; TF106159; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:1990130; C:GATOR1 complex; IBA:GO_Central.
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; IEA:UniProtKB-KW.
DR   GO; GO:0034198; P:cellular response to amino acid starvation; IBA:GO_Central.
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_0000245018"
FT   REGION          1..133
FT                   /note="Interaction with PDPK1"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        226
FT                   /note="N -> D (in Ref. 2; AAI05244)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   380 AA;  43636 MW;  851DC2D6DD7294DD CRC64;
     MGSSCRIECI FFSEFHPTLG PKITYQVPED FISRELFDTV QVYIITKPEL QNKLITVTAM
     EKKLIGCPVC IEHKKYSRNA LLFNLGFVCD AQAKTCALEP IVKKLAGYLT TLELESSFVS
     TEESKQKLVP IMTILLEELN ASGRCTLPID ESNTIHLKVI EQRPDPPVAQ EYDVPVFTKD
     KEDFFNSQWD LTTQQILPYI DGFRHVQKIS AEADVELNLV RIAIQNLLYY GVVTLVSILQ
     YSNVYCPTPK VQDLVDDKSL QEACLSYVTK EGHKRASLRD VFQLYCSLSP GTTVRDLIGR
     HPQQLQHVDE RKLIQFGLMK NLIRRLQKYP VRVSRDERSH PARLYTGCHS YDEICCKTGM
     SYQELDERLE NDPNIIICWK