Lamtor1
entrez
66508
canonical
uniprot
Q9CQ22
canonical
ensembl
ENSMUSG00000030842
resolver
ensp
ENSMUSP00000033131
resolver
enst
ENSMUST00000033131
resolver
genesymbol
Lamtor1
resolver
uniprot
Q9CYS0
resolver
uniprot_entry
LTOR1_MOUSE
resolver
uniprot_sec
Q9CYS0
resolver
amino_acid_sequence
MGCCYSSENEDSDQDREERKLLLDPSSTPTKALNGAEPNYHSLPSARTDEQALLSSILAKTASNIIDVSAADSQGMEQHEYMDRARQYSTRLAVLSSSLTHWKKLPPLPSLTSQPHQVLASEPIPFSDLQQVSRIAAYAYSALSQIRVDAKEELVVQFGIP
uniprot
proteins
function
FUNCTION: Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:19177150, PubMed:29158492, PubMed:30020076). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:19177150, PubMed:29158492, PubMed:30020076). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:19177150). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:19177150). LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (By similarity). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (PubMed:30595499). Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (By similarity). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (By similarity). May also play a role in RHOA activation (By similarity). {ECO:0000250|UniProtKB:Q6IAA8, ECO:0000269|PubMed:19177150, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:30020076, ECO:0000269|PubMed:30595499}.
uniprot
proteins
mass_dalton
17749
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="G->A: Abolished N-myristoylation and subsequent localization to lysosomes."; /evidence="ECO:0000269|PubMed:30020076"; MUTAGEN 60; /note="K->R: Reduces ubiquitination by UBE3A."; /evidence="ECO:0000269|PubMed:30020076"; MUTAGEN 103..104; /note="KK->RR: Reduces ubiquitination by UBE3A."; /evidence="ECO:0000269|PubMed:30020076
uniprot
proteins
post_translational_modification
PTM: N-terminal myristoylation and palmitoylation mediates its recruitment to lysosome membranes, thereby promoting localization of the Ragulator complex to lysosomes. N-myristoylation by NMT1 is required for palmitoylation at Cys-3 and Cys-4. {ECO:0000250|UniProtKB:Q6IAA8}.; PTM: Ubiquitinated at Lys-60, Lys-103 and Lys-104 by UBE3A in neurons, promoting its degradation by the proteasome, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (PubMed:30020076). Ubiquitination at Lys-20 impairs the association with the lysosomal V-ATPase complex. Deubiquitination at Lys-20 by USP32 promotes the association with the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (By similarity). {ECO:0000250|UniProtKB:Q6IAA8, ECO:0000269|PubMed:30020076}.
uniprot
proteins
protein_family
LAMTOR1 family
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19177150
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
29158492
uniprot
proteins
pubmed
29644770
uniprot
proteins
pubmed
30020076
uniprot
proteins
pubmed
30595499
uniprot
proteins
sequence_length
161
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:30020076}; Lipid-anchor {ECO:0000269|PubMed:30020076}; Cytoplasmic side {ECO:0000269|PubMed:30020076}. Late endosome membrane {ECO:0000269|PubMed:19177150}; Lipid-anchor {ECO:0000250|UniProtKB:Q6IAA8}; Cytoplasmic side {ECO:0000250|UniProtKB:Q6IAA8}. Note=Recruited to lysosome and endosome membranes through N-terminal myristoylation and palmitoylation. {ECO:0000269|PubMed:30020076}.
uniprot
proteins