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As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.; 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.
Gene References into Functions
NPRL2 overexpression enhances sensitivity to CPT-11 treatment in colon cancer cells. PMID: 29519997
This study demonstrated that NPRL2 mutation in familial focal epilepsies and focal cortical dysplasia. PMID: 27173016
Data confirmed NPRL2 was downregulated in gliomas. More importantly, NPRL2 was able to inhibit cell proliferation in vitro and repress tumorigenicity in vivo, suggesting its role as a tumor suppressor. PMID: 26455908
The positive regulation of mTORC1 activity by NPRL2 is mediated through NPRL2 interaction with Raptor. PMID: 26582740
NPRL2 mutations are significant cause of focal epilepsy. PMID: 26505888
NPRL2 acts as a functional tumor suppressor in colorectal cancer cell lines. PMID: 26044952
NPRL2 enhances sensitivity to oxaliplatin in colon cancer cells. PMID: 25777765
Decreased expression of NPRL2 is associated with renal cancer. PMID: 24789683
NPRL2 mRNA blood levels could be a potentially useful marker for the detection of early stage adenomas and colorectal cancers. PMID: 24521741
Results provide a set of genetic and biologic proofs that TUSC4 functions as a bona fide tumor suppressor by regulating the protein stability and function of BRCA1 in breast cancer. PMID: 25480944
NPRL2 expression is negatively related with the survival of osteosarcoma patients, indicating its value as a prognosis factor of osteosarcoma. PMID: 23321467
Lower NPRL2 expression was observed significantly more frequently in poorly differentiated tumor samples than in highly or moderately differentiated colon tumors. PMID: 23079973
Data indicate that Npr2, a homolog of human NPRL2, is a phosphorylation-dependent target of the SCF(Grr1) E3 ubiquitin ligase that plays a role in cell growth on some nitrogen sources. PMID: 20154027
NPRL2 is a multiple tumor suppressor gene. PMID: 15374952
Expression of NPRL2 was significantly and reciprocally correlated to cisplatin sensitivity. PMID: 17018626
TUSC4/NPRL2, a novel PDK1-interacting protein, plays a role in regulating the Src/PDK1 signaling pathway and cell sensitivity to multiple cancer chemotherapeutic drugs. PMID: 18616680
Our results suggest that NPRL2 mRNA expression has prognostic significance for the survival of patients with HCC. PMID: 19274676
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Involvement in disease
Epilepsy, familial focal, with variable foci 2 (FFEVF2)
Subcellular Location
Lysosome membrane.
Protein Families
NPR2 family
Tissue Specificity
Most abundant in skeletal muscle, followed by brain, liver and pancreas, with lower amounts in lung, kidney, placenta and heart. Expressed in the frontal lobe cortex as well as in the temporal, parietal, and occipital lobes. Expressed in most lung cancer