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NPRL2 (GATOR1 complex protein NPRL2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma.
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 signalling. In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2.
IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Pancreas.
In plain words · NPRL2 (GATOR1 complex protein NPRL2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma.
NPRL2 (GATOR1 complex protein NPRL2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Pancreatic ductal adenocarcinoma.
Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway.
No product in this corpus aims at NPRL2 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1998. Earliest sequence paper UniProt cites for the protein: Kondo et al, 1998, "Gene 21, a new candidate human tumor suppressor gene located in the 3p21.3 small cell lung cancer homozygous deletion region homologous to the yeast nitrogen permease regulator NPR2". Source.
Sources: HGNC HGNC:24969 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8WTW4 (protein name, function text, keywords and locations (REST API)); IntOGen NPRL2 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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 signalling. In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2. 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. Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signalling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. Location: Lysosome membrane (UniProt). Locus 3p21.31 (HGNC).
Query for this target: (TITLE:"NPRL2" OR ABSTRACT:"NPRL2" OR TITLE:"NPR2 like, GATOR1 complex subunit" OR ABSTRACT:"NPR2 like, GATOR1 complex subunit" OR TITLE:"GATOR1 complex protein NPRL2" OR ABSTRACT:"GATOR1 complex protein NPRL2" OR TITLE:"NPR2L" OR ABSTRACT:"NPR2L" OR TITLE:"NPR2" OR ABSTRACT:"NPR2" OR TITLE:"TUSC4" OR ABSTRACT:"TUSC4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NPRL2, not a curated reading list.