LTOR3_MOUSE
ID LTOR3_MOUSE Reviewed; 124 AA.
AC O88653;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ragulator complex protein LAMTOR3;
DE AltName: Full=Late endosomal/lysosomal adaptor and MAPK and MTOR activator 3;
DE AltName: Full=MEK-binding partner 1;
DE Short=Mp1;
DE AltName: Full=Mitogen-activated protein kinase kinase 1-interacting protein 1;
DE AltName: Full=Mitogen-activated protein kinase scaffold protein 1;
GN Name=Lamtor3; Synonyms=Map2k1ip1, Mapbp, Mapksp1;
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 [MRNA], FUNCTION, AND INTERACTION WITH MAP2K1/MEK1.
RX PubMed=9733512; DOI=10.1126/science.281.5383.1668;
RA Schaeffer H.J., Catling A.D., Eblen S.T., Collier L.S., Krauss A.,
RA Weber M.J.;
RT "MP1: a MEK binding partner that enhances enzymatic activation of the MAP
RT kinase cascade.";
RL Science 281:1668-1671(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary gland;
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 PROTEIN SEQUENCE OF 109-119, INTERACTION WITH LAMTOR1, AND SUBCELLULAR
RP LOCATION.
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 [4]
RP INTERACTION WITH LAMTOR2.
RX PubMed=11266467; DOI=10.1083/jcb.152.4.765;
RA Wunderlich W., Fialka I., Teis D., Alpi A., Pfeifer A., Parton R.G.,
RA Lottspeich F., Huber L.A.;
RT "A novel 14-kilodalton protein interacts with the mitogen-activated protein
RT kinase scaffold mp1 on a late endosomal/lysosomal compartment.";
RL J. Cell Biol. 152:765-776(2001).
RN [5]
RP INTERACTION WITH MORG1.
RX PubMed=15118098; DOI=10.1073/pnas.0305894101;
RA Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E.,
RA Bissonette E.A., Weber M.J.;
RT "Modular construction of a signaling scaffold: MORG1 interacts with
RT components of the ERK cascade and links ERK signaling to specific
RT agonists.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2004).
RN [6]
RP IDENTIFICATION BY 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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH LAMTOR2, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=15263099; DOI=10.1073/pnas.0403435101;
RA Kurzbauer R., Teis D., de Araujo M.E.G., Maurer-Stroh S., Eisenhaber F.,
RA Bourenkov G.P., Bartunik H.D., Hekman M., Rapp U.R., Huber L.A.,
RA Clausen T.;
RT "Crystal structure of the p14/MP1 scaffolding complex: how a twin couple
RT attaches mitogen-activated protein kinase signaling to late endosomes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10984-10989(2004).
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. Adapter protein that enhances the efficiency of the MAP
CC kinase cascade facilitating the activation of MAPK2.
CC {ECO:0000269|PubMed:15263099, ECO:0000269|PubMed:9733512}.
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 (By similarity).
CC Interacts with LAMTOR1 and LAMTOR2; the interaction is direct
CC (PubMed:11266467, PubMed:15263099, PubMed:19177150). Component of the
CC lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2),
CC RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound,
CC and Ragulator (By similarity). Interacts with MAP2K1/MEK1 and MAPK2
CC (PubMed:9733512). Interacts with MORG1 (PubMed:15118098).
CC {ECO:0000250|UniProtKB:Q9UHA4, ECO:0000269|PubMed:11266467,
CC ECO:0000269|PubMed:15118098, ECO:0000269|PubMed:15263099,
CC ECO:0000269|PubMed:19177150, ECO:0000269|PubMed:9733512}.
CC -!- INTERACTION:
CC O88653; Q9JHS3: Lamtor2; NbExp=2; IntAct=EBI-1039530, EBI-1038198;
CC O88653; Q6P791: Lamtor1; Xeno; NbExp=5; IntAct=EBI-1039530, EBI-919067;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:15263099, ECO:0000269|PubMed:19177150}; Peripheral
CC membrane protein {ECO:0000269|PubMed:15263099,
CC ECO:0000269|PubMed:19177150}; Cytoplasmic side
CC {ECO:0000269|PubMed:15263099, ECO:0000269|PubMed:19177150}.
CC -!- SIMILARITY: Belongs to the LAMTOR3 family. {ECO:0000305}.
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DR EMBL; AF082526; AAC34591.1; -; mRNA.
DR EMBL; BC016417; AAH16417.1; -; mRNA.
DR EMBL; BC083155; AAH83155.1; -; mRNA.
DR CCDS; CCDS51078.1; -.
DR RefSeq; NP_064304.1; NM_019920.2.
DR PDB; 1VET; X-ray; 1.90 A; A=1-124.
DR PDB; 1VEU; X-ray; 2.15 A; A=1-124.
DR PDBsum; 1VET; -.
DR PDBsum; 1VEU; -.
DR AlphaFoldDB; O88653; -.
DR SMR; O88653; -.
DR BioGRID; 208123; 13.
DR ComplexPortal; CPX-4761; Ragulator complex.
DR CORUM; O88653; -.
DR IntAct; O88653; 7.
DR MINT; O88653; -.
DR STRING; 10090.ENSMUSP00000130811; -.
DR iPTMnet; O88653; -.
DR PhosphoSitePlus; O88653; -.
DR EPD; O88653; -.
DR jPOST; O88653; -.
DR PaxDb; O88653; -.
DR PeptideAtlas; O88653; -.
DR PRIDE; O88653; -.
DR ProteomicsDB; 292050; -.
DR TopDownProteomics; O88653; -.
DR Antibodypedia; 3792; 234 antibodies from 33 providers.
DR DNASU; 56692; -.
DR Ensembl; ENSMUST00000168345; ENSMUSP00000130811; ENSMUSG00000091512.
DR Ensembl; ENSMUST00000197064; ENSMUSP00000142512; ENSMUSG00000091512.
DR GeneID; 56692; -.
DR KEGG; mmu:56692; -.
DR UCSC; uc008rms.1; mouse.
DR CTD; 8649; -.
DR MGI; MGI:1929467; Lamtor3.
DR VEuPathDB; HostDB:ENSMUSG00000091512; -.
DR eggNOG; ENOG502RYGZ; Eukaryota.
DR GeneTree; ENSGT00390000013159; -.
DR HOGENOM; CLU_134641_0_0_1; -.
DR InParanoid; O88653; -.
DR OMA; FLYKQMQ; -.
DR OrthoDB; 1525606at2759; -.
DR PhylomeDB; O88653; -.
DR TreeFam; TF324889; -.
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-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 56692; 16 hits in 74 CRISPR screens.
DR ChiTaRS; Lamtor3; mouse.
DR EvolutionaryTrace; O88653; -.
DR PRO; PR:O88653; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O88653; protein.
DR Bgee; ENSMUSG00000091512; Expressed in bone fossa and 249 other tissues.
DR ExpressionAtlas; O88653; baseline and differential.
DR Genevisible; O88653; MM.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IC:ComplexPortal.
DR GO; GO:0005765; C:lysosomal membrane; IC:ComplexPortal.
DR GO; GO:0071986; C:Ragulator complex; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0019209; F:kinase activator activity; IDA: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:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:1902414; P:protein localization to cell junction; IMP:MGI.
DR GO; GO:0038202; P:TORC1 signaling; IC:ComplexPortal.
DR InterPro; IPR015019; LAMTOR3.
DR PANTHER; PTHR13378; PTHR13378; 1.
DR Pfam; PF08923; MAPKK1_Int; 1.
DR SMART; SM01278; MAPKK1_Int; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endosome; Membrane;
KW Reference proteome.
FT CHAIN 1..124
FT /note="Ragulator complex protein LAMTOR3"
FT /id="PRO_0000221006"
FT REGION 57..70
FT /note="Required for interaction with LAMTOR2"
FT /evidence="ECO:0000269|PubMed:11266467"
FT HELIX 5..12
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 19..26
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 76..85
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 100..117
FT /evidence="ECO:0007829|PDB:1VET"
FT TURN 118..121
FT /evidence="ECO:0007829|PDB:1VET"
SQ SEQUENCE 124 AA; 13553 MW; 3B9C8A0241D806A9 CRC64;
MADDLKRFLY KKLPSVEGLH AIVVSDRDGV PVIKVANDSA PEHALRPGFL STFALATDQG
SKLGLSKNKS IICYYNTYQV VQFNRLPLVV SFIASSSANT GLIVSLEKEL APLFEELIKV
VEVS
