LTOR2_MOUSE
ID LTOR2_MOUSE Reviewed; 125 AA.
AC Q9JHS3;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Ragulator complex protein LAMTOR2;
DE AltName: Full=Endosomal adaptor protein p14;
DE AltName: Full=Late endosomal/lysosomal Mp1-interacting protein;
DE AltName: Full=Late endosomal/lysosomal adaptor and MAPK and MTOR activator 2;
DE AltName: Full=Mitogen-activated protein-binding protein-interacting protein;
DE AltName: Full=Roadblock domain-containing protein 3;
GN Name=Lamtor2; Synonyms=Mapbpip, Robld3;
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], PARTIAL PROTEIN SEQUENCE, INTERACTION WITH
RP LAMTOR3; MAPK1 AND MAP2K1, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary 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 [4]
RP PROTEIN SEQUENCE OF 97-105, 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 [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-124 IN COMPLEX WITH LAMTOR3.
RX PubMed=15016825; DOI=10.1074/jbc.m401648200;
RA Lunin V.V., Munger C., Wagner J., Ye Z., Cygler M., Sacher M.;
RT "The structure of the MAPK scaffold, MP1, bound to its partner, p14. A
RT complex with a critical role in endosomal MAP kinase signaling.";
RL J. Biol. Chem. 279:23422-23430(2004).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH LAMTOR3, 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).
RN [8]
RP STRUCTURE BY NMR, AND INTERACTION WITH LAMTOR3.
RX PubMed=15740743; DOI=10.1016/j.jmb.2005.01.031;
RA Qian C., Zhang Q., Wang X., Zeng L., Farooq A., Zhou M.-M.;
RT "Structure of the adaptor protein p14 reveals a profilin-like fold with
RT distinct function.";
RL J. Mol. Biol. 347:309-321(2005).
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}.
CC -!- SUBUNIT: Part of the Ragulator complex composed of LAMTOR1, LAMTOR2,
CC LAMTOR3, LAMTOR4 and LAMTOR5 (PubMed:15016825, PubMed:15263099,
CC PubMed:15740743, PubMed:19177150). LAMTOR4 and LAMTOR5 form a
CC heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3
CC heterodimer (PubMed:15016825, PubMed:15263099, PubMed:15740743,
CC PubMed:19177150). The Ragulator complex interacts with both the mTORC1
CC complex and heterodimers constituted of the Rag GTPases RRAGA, RRAGB,
CC RRAGC and RRAGD; regulated by amino acid availability (PubMed:15016825,
CC PubMed:15263099, PubMed:15740743, PubMed:19177150). The Ragulator
CC complex interacts with SLC38A9; the probable amino acid sensor (By
CC similarity). Interacts with LAMTOR1 and LAMTOR3; the interaction is
CC direct. Interacts with MAPK1 and MAP2K1 (PubMed:11266467). 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).
CC {ECO:0000250|UniProtKB:Q9Y2Q5, ECO:0000269|PubMed:11266467,
CC ECO:0000269|PubMed:15016825, ECO:0000269|PubMed:15263099,
CC ECO:0000269|PubMed:15740743, ECO:0000269|PubMed:19177150}.
CC -!- INTERACTION:
CC Q9JHS3; O88653: Lamtor3; NbExp=2; IntAct=EBI-1038198, EBI-1039530;
CC Q9JHS3; Q6P791: Lamtor1; Xeno; NbExp=4; IntAct=EBI-1038198, EBI-919067;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane
CC protein; Cytoplasmic side.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11266467}.
CC -!- SIMILARITY: Belongs to the GAMAD 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; AJ277386; CAB97177.1; -; mRNA.
DR EMBL; AK019006; BAB31506.1; -; mRNA.
DR EMBL; BC031816; AAH31816.1; -; mRNA.
DR CCDS; CCDS17478.1; -.
DR RefSeq; NP_112538.1; NM_031248.3.
DR PDB; 1SKO; X-ray; 2.00 A; B=2-124.
DR PDB; 1SZV; NMR; -; A=1-125.
DR PDB; 1VET; X-ray; 1.90 A; B=1-125.
DR PDB; 1VEU; X-ray; 2.15 A; B=1-125.
DR PDB; 2ZL1; X-ray; 2.00 A; B=2-125.
DR PDB; 3CPT; X-ray; 1.90 A; B=2-125.
DR PDBsum; 1SKO; -.
DR PDBsum; 1SZV; -.
DR PDBsum; 1VET; -.
DR PDBsum; 1VEU; -.
DR PDBsum; 2ZL1; -.
DR PDBsum; 3CPT; -.
DR AlphaFoldDB; Q9JHS3; -.
DR BMRB; Q9JHS3; -.
DR SMR; Q9JHS3; -.
DR BioGRID; 219917; 7.
DR ComplexPortal; CPX-4761; Ragulator complex.
DR CORUM; Q9JHS3; -.
DR IntAct; Q9JHS3; 5.
DR MINT; Q9JHS3; -.
DR STRING; 10090.ENSMUSP00000029698; -.
DR iPTMnet; Q9JHS3; -.
DR PhosphoSitePlus; Q9JHS3; -.
DR EPD; Q9JHS3; -.
DR jPOST; Q9JHS3; -.
DR MaxQB; Q9JHS3; -.
DR PaxDb; Q9JHS3; -.
DR PeptideAtlas; Q9JHS3; -.
DR PRIDE; Q9JHS3; -.
DR ProteomicsDB; 292049; -.
DR Antibodypedia; 1218; 101 antibodies from 25 providers.
DR DNASU; 83409; -.
DR Ensembl; ENSMUST00000029698; ENSMUSP00000029698; ENSMUSG00000028062.
DR GeneID; 83409; -.
DR KEGG; mmu:83409; -.
DR UCSC; uc008pvo.1; mouse.
DR CTD; 28956; -.
DR MGI; MGI:1932697; Lamtor2.
DR VEuPathDB; HostDB:ENSMUSG00000028062; -.
DR eggNOG; KOG4107; Eukaryota.
DR GeneTree; ENSGT00390000006100; -.
DR HOGENOM; CLU_141118_0_0_1; -.
DR InParanoid; Q9JHS3; -.
DR OMA; WAAYEKN; -.
DR OrthoDB; 1515483at2759; -.
DR PhylomeDB; Q9JHS3; -.
DR TreeFam; TF313929; -.
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; 83409; 28 hits in 74 CRISPR screens.
DR ChiTaRS; Lamtor2; mouse.
DR EvolutionaryTrace; Q9JHS3; -.
DR PRO; PR:Q9JHS3; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9JHS3; protein.
DR Bgee; ENSMUSG00000028062; Expressed in right kidney and 260 other tissues.
DR ExpressionAtlas; Q9JHS3; baseline and differential.
DR Genevisible; Q9JHS3; 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:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IDA:MGI.
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:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0150116; P:regulation of cell-substrate junction organization; IDA:MGI.
DR GO; GO:0038202; P:TORC1 signaling; IC:ComplexPortal.
DR InterPro; IPR037587; LAMTOR2-like.
DR InterPro; IPR004942; Roadblock/LAMTOR2_dom.
DR PANTHER; PTHR13323; PTHR13323; 1.
DR Pfam; PF03259; Robl_LC7; 1.
DR SMART; SM00960; Robl_LC7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endosome; Lysosome; Membrane;
KW Reference proteome.
FT CHAIN 1..125
FT /note="Ragulator complex protein LAMTOR2"
FT /id="PRO_0000220961"
FT REGION 57..70
FT /note="Required for location at endosomes"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:1SZV"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:1VET"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:1SZV"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:1VEU"
FT HELIX 42..60
FT /evidence="ECO:0007829|PDB:1VET"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 79..86
FT /evidence="ECO:0007829|PDB:1VET"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 101..116
FT /evidence="ECO:0007829|PDB:1VET"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:1VEU"
SQ SEQUENCE 125 AA; 13480 MW; 69448F11DFD6C03D CRC64;
MLRPKALTQV LSQANTGGVQ STLLLNNEGS LLAYSGYGDT DARVTAAIAS NIWAAYDRNG
NQAFNEDSLK FILMDCMEGR VAITRVANLL LCMYAKETVG FGMLKAKAQA LVQYLEEPLT
QVAAS
