Protein: GATOR1 complex protein NPRL2 (Q9WUE4)
Organism: Mus musculus (Mouse)
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. 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
Subcellular location: Lysosome membrane. Note=Localization to lysosomes is mediated by the KICSTOR complex and is amino acid-independent
InterPro domains:
- IPR009348: Nitrogen permease regulator 2-like (family) [4-370]
Sequence:
MGSSCRIECIFFSEFHPTLGPKITYQVPEDFISRELFDTVQVYIITKPELQNKLITVTAMEKKLIGCPVCIEHKKYSRNALLFNLGFVCDAQAKTCALEPIVKKLAGYLTTLELESSFVSNEESKQKLVPIMTILLEELNASGRCTLPIDESNTIHLKVIEQRPDPPVAQEYDVPVFTKDKEDFFSSQWDLTTQQILPYIDGFRHVQKISAEADVELNLVRIAIQNLLYYGVVTLVSILQYSNVYCPTPKVQDLVDDKSLQEACLSYVTKQGHKRASLRDVFQLYCSLSPGTTVRDLIGRHPQQLQHVDERKLIQFGLMKNLIRRLQKYPVRVSREERSHPARLYTGCHSYDEICCKTGMSYHELDERLENDPNIIICWK
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0023057 (negative regulation of signaling), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0009892 (negative regulation of metabolic process), GO:0009991 (response to extracellular stimulus), GO:0050790 (regulation of catalytic activity), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:0042594 (response to starvation), GO:0010646 (regulation of cell communication), GO:0033554 (cellular response to stress), GO:0044092 (negative regulation of molecular function), GO:0009966 (regulation of signal transduction), GO:0031323 (regulation of cellular metabolic process), GO:0031668 (cellular response to extracellular stimulus), GO:0031324 (negative regulation of cellular metabolic process), GO:0071496 (cellular response to external stimulus), GO:0043086 (negative regulation of catalytic activity), GO:0009267 (cellular response to starvation), GO:0031667 (response to nutrient levels), GO:0010563 (negative regulation of phosphorus metabolic process), GO:1990928 (response to amino acid starvation), GO:1902532 (negative regulation of intracellular signal transduction), GO:0051338 (regulation of transferase activity), GO:0031669 (cellular response to nutrient levels), GO:0051174 (regulation of phosphorus metabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0034198 (cellular response to amino acid starvation), GO:0032006 (regulation of TOR signaling), GO:0043549 (regulation of kinase activity), GO:0051348 (negative regulation of transferase activity), GO:0032007 (negative regulation of TOR signaling), GO:0045936 (negative regulation of phosphate metabolic process), GO:0019220 (regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0033673 (negative regulation of kinase activity), GO:0042326 (negative regulation of phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0042995 (cell projection), GO:0005737 (cytoplasm), GO:0005773 (vacuole), GO:0120025 (plasma membrane bounded cell projection), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043005 (neuron projection), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0005764 (lysosome), GO:0030424 (axon)