InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NPRL2

Summary

InnateDB Protein

IDBP-36918.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NPRL2

Protein Name

nitrogen permease regulator-like 2 (S. cerevisiae)

Synonyms

NPR2; NPR2L; TUSC4;

Species

Homo sapiens

Ensembl Protein

ENSP00000232501

InnateDB Gene

IDBG-36916 (NPRL2)

Protein Structure

UniProt Annotation

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. As a component of the GATOR1 complex, 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. {ECO:0000269PubMed:18616680, ECO:0000269PubMed:23723238}.

Subcellular Localization

Disease Associations

Note=Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including NPRL2, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238). {ECO:0000269PubMed:23723238}.

Tissue Specificity

Most abundant in skeletal muscle, followed by brain, liver and pancreas, with lower amounts in lung, kidney, placenta and heart. Expressed in most lung cancer cell lines tested.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.