small GTPase / mTORC1 activation / amino acid signaling / lysosome / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
asparagine transport / L-asparagine transmembrane transporter activity / sterol sensor activity / L-arginine transmembrane transporter activity / L-arginine transmembrane transport / regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux ...asparagine transport / L-asparagine transmembrane transporter activity / sterol sensor activity / L-arginine transmembrane transporter activity / L-arginine transmembrane transport / regulation of cholesterol import / positive regulation of protein localization to lysosome / regulation of cell-substrate junction organization / Gtr1-Gtr2 GTPase complex / regulation of cholesterol efflux / L-glutamine transmembrane transporter activity / glutamine transport / FNIP-folliculin RagC/D GAP / Ragulator complex / protein localization to cell junction / L-leucine transmembrane transporter activity / amino acid transmembrane transport / L-amino acid transmembrane transporter activity / regulation of TORC1 signaling / protein localization to lysosome / regulation of TOR signaling / MTOR signalling / fibroblast migration / Amino acids regulate mTORC1 / lysosome localization / Energy dependent regulation of mTOR by LKB1-AMPK / endosome organization / TORC1 signaling / amino acid transmembrane transporter activity / kinase activator activity / protein localization to membrane / arginine binding / endosomal transport / azurophil granule membrane / lysosome organization / cholesterol binding / small GTPase-mediated signal transduction / Macroautophagy / regulation of cell size / RHOJ GTPase cycle / RHOQ GTPase cycle / mTORC1-mediated signalling / CDC42 GTPase cycle / tertiary granule membrane / RHOH GTPase cycle / ficolin-1-rich granule membrane / RHOG GTPase cycle / regulation of receptor recycling / RAC2 GTPase cycle / positive regulation of TOR signaling / RAC3 GTPase cycle / enzyme-substrate adaptor activity / response to amino acid / cellular response to nutrient levels / specific granule membrane / protein-membrane adaptor activity / RAC1 GTPase cycle / positive regulation of TORC1 signaling / negative regulation of autophagy / cellular response to amino acid starvation / RNA splicing / guanyl-nucleotide exchange factor activity / viral genome replication / cholesterol homeostasis / cellular response to starvation / Regulation of PTEN gene transcription / tumor necrosis factor-mediated signaling pathway / positive regulation of interleukin-8 production / TP53 Regulates Metabolic Genes / cellular response to amino acid stimulus / phosphoprotein binding / regulation of cell growth / MAP2K and MAPK activation / positive regulation of protein localization to nucleus / response to virus / GDP binding / late endosome membrane / intracellular protein localization / late endosome / glucose homeostasis / E3 ubiquitin ligases ubiquitinate target proteins / GTPase binding / molecular adaptor activity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / lysosome / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / endosome membrane / intracellular signal transduction / membrane raft / protein heterodimerization activity / lysosomal membrane / focal adhesion / intracellular membrane-bounded organelle / GTPase activity / apoptotic process / DNA-templated transcription / ubiquitin protein ligase binding / Neutrophil degranulation / positive regulation of gene expression 類似検索 - 分子機能
Amino acid transporter, transmembrane domain / Transmembrane amino acid transporter protein / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / Mitogen-activated protein kinase kinase 1 interacting ...Amino acid transporter, transmembrane domain / Transmembrane amino acid transporter protein / LAMTOR1/MEH1 / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Late endosomal/lysosomal adaptor and MAPK and MTOR activator / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR5 / RagA/B / Mitogen-activated protein kinase kinase 1 interacting / Ragulator complex protein LAMTOR5 / Mitogen-activated protein kinase kinase 1 interacting / RagC/D / Gtr1/RagA G protein / Gtr1/RagA G protein conserved region / Ragulator complex protein LAMTOR2-like / Roadblock/LAMTOR2 domain / Roadblock/LC7 domain / Roadblock/LC7 domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Ragulator complex protein LAMTOR5 / Ragulator complex protein LAMTOR4 / Ragulator complex protein LAMTOR1 / Ras-related GTP-binding protein A / Neutral amino acid transporter 9 / Ras-related GTP-binding protein C / Ragulator complex protein LAMTOR3 / Ragulator complex protein LAMTOR2 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM111730
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2020 タイトル: Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9. 著者: Simon A Fromm / Rosalie E Lawrence / James H Hurley / 要旨: The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin ...The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) consists of the inactive Rag dimer, the pentameric scaffold Ragulator, and the FLCN:FNIP2 (FLCN-interacting protein 2) GTPase activating protein (GAP) complex, and prevents Rag dimer activation during amino acid starvation. How the LFC is disassembled upon amino acid refeeding is an outstanding question. Here we show that the cytoplasmic tail of the human lysosomal solute carrier family 38 member 9 (SLC38A9) destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RagC. We present the cryo-EM structures of Rags in complex with their lysosomal anchor complex Ragulator and the cytoplasmic tail of SLC38A9 in the pre- and post-GTP hydrolysis state of RagC, which explain how SLC38A9 destabilizes the LFC and so promotes Rag dimer activation.