LTOR1_MOUSE
ID LTOR1_MOUSE Reviewed; 161 AA.
AC Q9CQ22; Q9CYS0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Ragulator complex protein LAMTOR1;
DE AltName: Full=Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1;
DE AltName: Full=Lipid raft adaptor protein p18;
GN Name=Lamtor1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Head, Ovary, Tongue, and Uterus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Lung, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH LAMTOR2 AND LAMTOR3, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=19177150; DOI=10.1038/emboj.2008.308;
RA Nada S., Hondo A., Kasai A., Koike M., Saito K., Uchiyama Y., Okada M.;
RT "The novel lipid raft adaptor p18 controls endosome dynamics by anchoring
RT the MEK-ERK pathway to late endosomes.";
RL EMBO J. 28:477-489(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH PIP4P1.
RX PubMed=29644770; DOI=10.1111/gtc.12583;
RA Hashimoto Y., Shirane M., Nakayama K.I.;
RT "TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1
RT activation.";
RL Genes Cells 23:418-434(2018).
RN [9]
RP FUNCTION.
RX PubMed=30595499; DOI=10.1016/j.stem.2018.11.021;
RA Villegas F., Lehalle D., Mayer D., Rittirsch M., Stadler M.B., Zinner M.,
RA Olivieri D., Vabres P., Duplomb-Jego L., De Bont E.S.J.M., Duffourd Y.,
RA Duijkers F., Avila M., Genevieve D., Houcinat N., Jouan T., Kuentz P.,
RA Lichtenbelt K.D., Thauvin-Robinet C., St-Onge J., Thevenon J.,
RA van Gassen K.L.I., van Haelst M., van Koningsbruggen S., Hess D.,
RA Smallwood S.A., Riviere J.B., Faivre L., Betschinger J.;
RT "Lysosomal signaling licenses embryonic stem cell differentiation via
RT inactivation of Tfe3.";
RL Cell Stem Cell 24:257-270(2019).
CC -!- FUNCTION: As part of the Ragulator complex it is involved in amino acid
CC sensing and activation of mTORC1, a signaling complex promoting cell
CC growth in response to growth factors, energy levels, and amino acids.
CC Activated by amino acids through a mechanism involving the lysosomal V-
CC ATPase, the Ragulator functions as a guanine nucleotide exchange factor
CC activating the small GTPases Rag. Activated Ragulator and Rag GTPases
CC function as a scaffold recruiting mTORC1 to lysosomes where it is in
CC turn activated. LAMTOR1 is directly responsible for anchoring the
CC Ragulator complex to membranes. Also required for late
CC endosomes/lysosomes biogenesis it may regulate both the recycling of
CC receptors through endosomes and the MAPK signaling pathway through
CC recruitment of some of its components to late endosomes. May be
CC involved in cholesterol homeostasis regulating LDL uptake and
CC cholesterol release from late endosomes/lysosomes. May also play a role
CC in RHOA activation. Involved in the control of embryonic stem cells
CC differentiation; together with FLCN it is necessary to recruit and
CC activate RRAGC/RagC and RRAGD/RagD at the lysosomes, and to induce exit
CC of embryonic stem cells from pluripotency via non-canonical, mTOR-
CC independent TFE3 inactivation (PubMed:30595499).
CC {ECO:0000269|PubMed:19177150, ECO:0000269|PubMed:30595499}.
CC -!- SUBUNIT: Part of the Ragulator complex composed of LAMTOR1, LAMTOR2,
CC LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer
CC that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer.
CC The Ragulator complex interacts with both the mTORC1 complex and
CC heterodimers constituted of the Rag GTPases RRAGA, RRAGB, RRAGC and
CC RRAGD; regulated by amino acid availability. The Ragulator complex
CC interacts with SLC38A9; the probable amino acid sensor. Component of
CC the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or
CC FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD
CC GTP-bound, and Ragulator (By similarity). Interacts with LAMTOR2 and
CC LAMTOR3; the interaction is direct (PubMed:19177150). Interacts with
CC RRAGB and RRAGD; the interaction is direct indicating that it probably
CC constitutes the main RAG-interacting subunit of the Ragulator complex.
CC Interacts with MMP14. Interacts with CDKN1B; prevents the interaction
CC of CDKN1B with RHOA leaving RHOA in a form accessible to activation by
CC ARHGEF2 (By similarity). Interacts with PIP4P1 (PubMed:29644770).
CC {ECO:0000250|UniProtKB:Q6IAA8, ECO:0000269|PubMed:19177150,
CC ECO:0000269|PubMed:29644770}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000250}; Lipid-
CC anchor {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Lysosome membrane
CC {ECO:0000250}; Lipid-anchor {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Cell membrane {ECO:0000250|UniProtKB:Q6IAA8}; Lipid-
CC anchor {ECO:0000250|UniProtKB:Q6IAA8}.
CC -!- DEVELOPMENTAL STAGE: At 6.5 dpc expressed throughout the embryo with
CC relative abundance in the visceral endoderm.
CC {ECO:0000269|PubMed:19177150}.
CC -!- DISRUPTION PHENOTYPE: Embryos die at egg cylinder stage due to growth
CC retardation, associated with altered endosomes and lysosomes
CC organizations and impaired membrane protein transport in the visceral
CC endoderm. {ECO:0000269|PubMed:19177150}.
CC -!- SIMILARITY: Belongs to the LAMTOR1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK009320; BAB26214.1; -; mRNA.
DR EMBL; AK013389; BAB28825.1; -; mRNA.
DR EMBL; AK019947; BAB31928.1; -; mRNA.
DR EMBL; AK144476; BAE25909.1; -; mRNA.
DR EMBL; BC020142; AAH20142.1; -; mRNA.
DR EMBL; BC092062; AAH92062.1; -; mRNA.
DR EMBL; BC096412; AAH96412.1; -; mRNA.
DR EMBL; BC115458; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC115459; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC126973; AAI26974.1; -; mRNA.
DR CCDS; CCDS21519.1; -.
DR RefSeq; NP_079881.2; NM_025605.3.
DR AlphaFoldDB; Q9CQ22; -.
DR SMR; Q9CQ22; -.
DR BioGRID; 211525; 17.
DR ComplexPortal; CPX-4761; Ragulator complex.
DR CORUM; Q9CQ22; -.
DR IntAct; Q9CQ22; 5.
DR MINT; Q9CQ22; -.
DR STRING; 10090.ENSMUSP00000033131; -.
DR iPTMnet; Q9CQ22; -.
DR PhosphoSitePlus; Q9CQ22; -.
DR SwissPalm; Q9CQ22; -.
DR EPD; Q9CQ22; -.
DR jPOST; Q9CQ22; -.
DR MaxQB; Q9CQ22; -.
DR PaxDb; Q9CQ22; -.
DR PeptideAtlas; Q9CQ22; -.
DR PRIDE; Q9CQ22; -.
DR ProteomicsDB; 290191; -.
DR Antibodypedia; 721; 88 antibodies from 24 providers.
DR DNASU; 66508; -.
DR Ensembl; ENSMUST00000033131; ENSMUSP00000033131; ENSMUSG00000030842.
DR GeneID; 66508; -.
DR KEGG; mmu:66508; -.
DR UCSC; uc009ipw.2; mouse.
DR CTD; 55004; -.
DR MGI; MGI:1913758; Lamtor1.
DR VEuPathDB; HostDB:ENSMUSG00000030842; -.
DR eggNOG; ENOG502RYX2; Eukaryota.
DR GeneTree; ENSGT00390000016789; -.
DR HOGENOM; CLU_136283_1_0_1; -.
DR InParanoid; Q9CQ22; -.
DR OMA; LHETAAN; -.
DR OrthoDB; 1420294at2759; -.
DR PhylomeDB; Q9CQ22; -.
DR TreeFam; TF323788; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 66508; 27 hits in 76 CRISPR screens.
DR ChiTaRS; Lamtor1; mouse.
DR PRO; PR:Q9CQ22; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9CQ22; protein.
DR Bgee; ENSMUSG00000030842; Expressed in white adipose tissue and 61 other tissues.
DR ExpressionAtlas; Q9CQ22; baseline and differential.
DR Genevisible; Q9CQ22; MM.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IC:ComplexPortal.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071986; C:Ragulator complex; ISS:UniProtKB.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0010874; P:regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0010872; P:regulation of cholesterol esterification; ISS:UniProtKB.
DR GO; GO:0060620; P:regulation of cholesterol import; ISS:UniProtKB.
DR GO; GO:0001919; P:regulation of receptor recycling; IMP:UniProtKB.
DR GO; GO:0038202; P:TORC1 signaling; IC:ComplexPortal.
DR InterPro; IPR028209; LAMTOR1/MEH1.
DR Pfam; PF15454; LAMTOR; 1.
DR SMART; SM01262; LAMTOR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endosome; Lipoprotein; Lysosome; Membrane; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT CHAIN 2..161
FT /note="Ragulator complex protein LAMTOR1"
FT /id="PRO_0000274293"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 121..161
FT /note="Interaction with LAMTOR2 and LAMTOR3"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT MOD_RES 28
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q6IAA8"
FT CONFLICT 82
FT /note="M -> I (in Ref. 1; BAB28825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 161 AA; 17749 MW; D50CC6C05C36B457 CRC64;
MGCCYSSENE DSDQDREERK LLLDPSSTPT KALNGAEPNY HSLPSARTDE QALLSSILAK
TASNIIDVSA ADSQGMEQHE YMDRARQYST RLAVLSSSLT HWKKLPPLPS LTSQPHQVLA
SEPIPFSDLQ QVSRIAAYAY SALSQIRVDA KEELVVQFGI P
