UniProt:Q6IAA8 LAMTOR1

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
crossReference
databaseName UniProt
dbId 223974
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
displayName UniProt:Q6IAA8 LAMTOR1
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:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • LAMTOR1
otherIdentifier
  • 11742925_a_at
  • 11749390_x_at
  • 11756743_x_at
  • 16741643
  • 223009_PM_at
  • 223009_at
  • 3380981
  • 3380982
  • 3380986
  • 3380987
  • 3380988
  • 3380989
  • 3380990
  • 3380991
  • 3380992
  • 3380993
  • 3380994
  • 3380995
  • 55004
  • 56435_at
  • 61781_at
  • 7950119
  • A_23_P2114
  • A_24_P239266
  • GE82246
  • GO:0000045
  • GO:0001558
  • GO:0001919
  • GO:0002181
  • GO:0005085
  • GO:0005515
  • GO:0005764
  • GO:0005765
  • GO:0005768
  • GO:0005886
  • GO:0007032
  • GO:0007040
  • GO:0008104
  • GO:0010507
  • GO:0010874
  • GO:0016020
  • GO:0016192
  • GO:0016197
  • GO:0031669
  • GO:0031902
  • GO:0032008
  • GO:0032418
  • GO:0035577
  • GO:0035579
  • GO:0038202
  • GO:0042632
  • GO:0043410
  • GO:0043495
  • GO:0045121
  • GO:0045947
  • GO:0045948
  • GO:0051020
  • GO:0060090
  • GO:0060620
  • GO:0061462
  • GO:0070062
  • GO:0071230
  • GO:0071986
  • GO:0072657
  • GO:0101003
  • GO:0150032
  • GO:1904263
  • GO:1990877
  • HMNXSV003050438
  • ILMN_1815878
  • PH_hs_0025135
  • PH_hs_0035941
  • TC11002053.hg
  • g12804574_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • LTOR1_HUMAN
  • Q8WZ09
  • Q9NWT0
sequenceLength 161
species [Species:48887] Homo sapiens
stId uniprot:Q6IAA8
url http://purl.uniprot.org/uniprot/Q6IAA8

Referrals

(referenceEntity)
(interactor)
Cite Us!