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Details on Person UniProt:Q6IAA8 LAMTOR1
| Class:Id | ReferenceGeneProduct:223974 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-161 added on Sat February 7 2015;initiator methionine:1 for 223974 removed on Fri Nov 03 2023;initiator methionine: for 223974 added on Fri Nov 03 2023;initiator methionine: for 223974 removed on Fri Aug 15 2025;initiator methionine:1 for 223974 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q6IAA8 LAMTOR1 |
| _timestamp | 2025-08-15 21:01:01 |
| chain | initiator methionine:1 chain:2-161 |
| checksum | 610CC6C548356051 |
| comment | 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: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).SUBUNIT Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 (PubMed:20381137, PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:29285400, PubMed:31601708, PubMed:32868926, PubMed:35338845, PubMed:36103527, PubMed:36697823). LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer (PubMed:20381137, PubMed:22980980). Interacts with LAMTOR2 and LAMTOR3; the interaction is direct (PubMed:20381137, PubMed:22980980). The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability (PubMed:20381137, PubMed:22980980, PubMed:32868926). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (PubMed:22980980, PubMed:25561175, PubMed:25567906). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (PubMed:31672913, PubMed:31704029). Associates with the lysosomal V-ATPase complex; interaction promotes the guanine nucleotide exchange factor (GEF) of the Ragulator complex (PubMed:36476874). Interacts with MMP14 (PubMed:19654316). Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2 (PubMed:19654316). Interacts with PIP4P1 (PubMed:29644770).INTERACTION Recruited to lysosome and endosome membranes through N-terminal myristoylation and palmitoylation.INDUCTION Down-regulated by cholesterol (at protein level).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).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).SIMILARITY Belongs to the LAMTOR1 family. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: fullName evidence="36"Ragulator complex protein LAMTOR1 alternativeName: Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1 alternativeName: fullName evidence="34"Lipid raft adaptor protein p18 alternativeName: fullName evidence="33"Protein associated with DRMs and endosomes alternativeName: fullName evidence="32"p27Kip1-releasing factor from RhoA shortName evidence="32"p27RF-Rho |
| geneName | LAMTOR1 C11orf59 PDRO PP7157 |
| identifier | Q6IAA8 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Direct protein sequencing Endosome Isopeptide bond Lipoprotein Lysosome Membrane Myristate Palmitate Phosphoprotein Proteomics identification Reference proteome Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | LAMTOR1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8997257] ENSEMBL:ENSG00000149357 LAMTOR1 [Homo sapiens] |
| secondaryIdentifier | LTOR1_HUMAN Q8WZ09 Q9NWT0 |
| sequenceLength | 161 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:5653582] LAMTOR1 [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:6799631] LAMTOR1 [specific granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:6799633] LAMTOR1 [azurophil granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:6799673] LAMTOR1 [extracellular exosome] [Homo sapiens] [EntityWithAccessionedSequence:6801003] LAMTOR1 [ficolin-1-rich granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:6806270] LAMTOR1 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q6IAA8 LAMTOR1 (223974)
