LAMTOR1
entrez
55004
canonical
uniprot
Q6IAA8
canonical
ensembl
ENSG00000149357
resolver
ensp
ENSP00000278671
resolver
enst
ENST00000278671
resolver
genesymbol
LAMTOR1
resolver
genesymbol_syn
C11orf59
resolver
genesymbol_syn
PDRO
resolver
hgnc
HGNC:26068
resolver
uniprot
Q8WZ09
resolver
uniprot
Q9NWT0
resolver
uniprot_entry
LTOR1_HUMAN
resolver
uniprot_sec
Q8WZ09
resolver
uniprot_sec
Q9NWT0
resolver
amino_acid_sequence
MGCCYSSENEDSDQDREERKLLLDPSSPPTKALNGAEPNYHSLPSARTDEQALLSSILAKTASNIIDVSAADSQGMEQHEYMDRARQYSTRLAVLSSSLTHWKKLPPLPSLTSQPHQVLASEPIPFSDLQQVSRIAAYAYSALSQIRVDAKEELVVQFGIP
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:20381137, PubMed:22980980, PubMed:29158492). 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:22053050, PubMed:22980980, PubMed:28935770, PubMed:29158492, PubMed:30181260, PubMed:31001086, PubMed:32686708, PubMed:36476874). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:20381137, PubMed:22980980, PubMed:29158492). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:31001086, PubMed:32686708). 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 (PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29285400). 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 (By similarity). 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 (PubMed:20381137, PubMed:22980980). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (PubMed:20544018). May also play a role in RHOA activation (PubMed:19654316). {ECO:0000250|UniProtKB:Q9CQ22, ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22053050, ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29123114, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:29285400, ECO:0000269|PubMed:30181260, ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:32686708, ECO:0000269|PubMed:36476874}.
uniprot
proteins
mass_dalton
17745
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="G->A: Abolished N-myristoylation and subsequent palmitoylation."; /evidence="ECO:0000269|PubMed:34999170"; MUTAGEN 3..4; /note="CC->SS: Abolished palmitoylation and recruitment to lysosomes, leading to impaired activation of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:35893977"; MUTAGEN 3; /note="C->A: Decreased palmitoylation."; /evidence="ECO:0000269|PubMed:34999170"; MUTAGEN 3; /note="C->S: Does not affect interaction with ZDHHC3."; /evidence="ECO:0000269|PubMed:35893977"; MUTAGEN 4; /note="C->A: Decreased palmitoylation."; /evidence="ECO:0000269|PubMed:34999170"; MUTAGEN 4; /note="C->S: Does not affect interaction with ZDHHC3."; /evidence="ECO:0000269|PubMed:35893977"; MUTAGEN 119; /note="L->R: Impaired assembly of the Ragulator complex."; /evidence="ECO:0000269|PubMed:29123114"; MUTAGEN 132; /note="V->D: Impaired assembly of the Ragulator complex."; /evidence="ECO:0000269|PubMed:29123114"; MUTAGEN 148..149; /note="VD->AA: Impaired assembly of the Ragulator complex."; /evidence="ECO:0000269|PubMed:28935770"; MUTAGEN 151..153; /note="KEE->AAA: Impaired recruitment of Rag GTPases (RRAGA and RRAGC) to the lysosomal membrane."; /evidence="ECO:0000269|PubMed:28935770"; MUTAGEN 154..158; /note="LVVQF->DDDQD: Does not affect interaction with RRAGA and RRAGC in vitro."; /evidence="ECO:0000269|PubMed:29285400"; MUTAGEN 154..156; /note="LVV->AAA: Impaired recruitment of Rag GTPases (RRAGA and RRAGC) to the lysosomal membrane."; /evidence="ECO:0000269|PubMed:28935770
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 (PubMed:31001086). N-myristoylation by NMT1 is required for palmitoylation at Cys-3 and Cys-4 (PubMed:34999170). May be palmitoylated by ZDHHC3 (PubMed:35893977). {ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:34999170, ECO:0000269|PubMed:35893977}.; PTM: Ubiquitinated at Lys-60, Lys-103 and Lys-104 by UBE3A, promoting its degradation by the proteasome (PubMed:30020076). Ubiquitination at Lys-20 impairs the association with the lysosomal V-ATPase complex (PubMed:36476874). Deubiquitination at Lys-20 by USP32 promotes the association with the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (PubMed:36476874). {ECO:0000269|PubMed:30020076, ECO:0000269|PubMed:36476874}.
uniprot
proteins
protein_family
LAMTOR1 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19654316
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20381137
uniprot
proteins
pubmed
20544018
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22053050
uniprot
proteins
pubmed
22980980
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25255805
uniprot
proteins
pubmed
25561175
uniprot
proteins
pubmed
25567906
uniprot
proteins
pubmed
25807930
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
28935770
uniprot
proteins
pubmed
29107538
uniprot
proteins
pubmed
29123114
uniprot
proteins
pubmed
29158492
uniprot
proteins
pubmed
29285400
uniprot
proteins
pubmed
29644770
uniprot
proteins
pubmed
30020076
uniprot
proteins
pubmed
30181260
uniprot
proteins
pubmed
31001086
uniprot
proteins
pubmed
31601708
uniprot
proteins
pubmed
31672913
uniprot
proteins
pubmed
31704029
uniprot
proteins
pubmed
32686708
uniprot
proteins
pubmed
32868926
uniprot
proteins
pubmed
34999170
uniprot
proteins
pubmed
35338845
uniprot
proteins
pubmed
35893977
uniprot
proteins
pubmed
36103527
uniprot
proteins
pubmed
36476874
uniprot
proteins
pubmed
36697823
uniprot
proteins
sequence_length
161
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:32686708}; Lipid-anchor {ECO:0000269|PubMed:31001086}; Cytoplasmic side {ECO:0000269|PubMed:31001086}. Late endosome membrane {ECO:0000269|PubMed:20544018}; Lipid-anchor {ECO:0000269|PubMed:31001086}; Cytoplasmic side {ECO:0000269|PubMed:31001086}. Note=Recruited to lysosome and endosome membranes through N-terminal myristoylation and palmitoylation. {ECO:0000269|PubMed:31001086}.
uniprot
proteins