Nprl2
entrez
56032
canonical
uniprot
Q9WUE4
canonical
ensembl
ENSMUSG00000010057
resolver
ensp
ENSMUSP00000010201
resolver
ensp
ENSMUSP00000263216
resolver
ensp
ENSMUSP00000263222
resolver
enst
ENSMUST00000010201
resolver
genesymbol
Nprl2
resolver
uniprot_entry
NPRL2_MOUSE
resolver
amino_acid_sequence
MGSSCRIECIFFSEFHPTLGPKITYQVPEDFISRELFDTVQVYIITKPELQNKLITVTAMEKKLIGCPVCIEHKKYSRNALLFNLGFVCDAQAKTCALEPIVKKLAGYLTTLELESSFVSNEESKQKLVPIMTILLEELNASGRCTLPIDESNTIHLKVIEQRPDPPVAQEYDVPVFTKDKEDFFSSQWDLTTQQILPYIDGFRHVQKISAEADVELNLVRIAIQNLLYYGVVTLVSILQYSNVYCPTPKVQDLVDDKSLQEACLSYVTKQGHKRASLRDVFQLYCSLSPGTTVRDLIGRHPQQLQHVDERKLIQFGLMKNLIRRLQKYPVRVSREERSHPARLYTGCHSYDEICCKTGMSYHELDERLENDPNIIICWK
uniprot
proteins
function
FUNCTION: Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:26166573, PubMed:29768191, PubMed:38006878). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (By similarity). In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2 (By similarity). Within the GATOR1 complex, NPRL2 constitutes the catalytic subunit that mediates the GTPase activator activity and under methionine-sufficient conditions, the GTPase activator activity is inhibited by PRMT1 through methylation and consequently inducing timely mTORC1 activation (PubMed:38006878). {ECO:0000250|UniProtKB:Q8WTW4, ECO:0000269|PubMed:26166573, ECO:0000269|PubMed:29768191, ECO:0000269|PubMed:38006878}.; FUNCTION: Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs. {ECO:0000250|UniProtKB:Q8WTW4}.
uniprot
proteins
mass_dalton
43644
uniprot
proteins
post_translational_modification
PTM: In the presence of abundant amino acids, ubiquitinated at Lys-158 and Lys-357 via 'Lys-6'-linked ubiquitination by the WDR24 component of the GATOR2 complex, thereby inhibiting the GATOR1 complex and promoting mTORC1 activation. {ECO:0000250|UniProtKB:Q8WTW4}.; PTM: Asymmetric dimethylation at Arg-78 by PRMT1 inhibits the GTPase activator activity of the GATOR1 complex and consequently inducing timely mTORC1 activation under methionine-sufficient conditions. {ECO:0000269|PubMed:38006878}.
uniprot
proteins
protein_family
NPR2 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
26166573
uniprot
proteins
pubmed
29768191
uniprot
proteins
pubmed
38006878
uniprot
proteins
sequence_length
380
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q8WTW4}. Note=Localization to lysosomes is mediated by the KICSTOR complex and is amino acid-independent. {ECO:0000250|UniProtKB:Q8WTW4}.
uniprot
proteins