ID LTOR2_HUMAN Reviewed; 125 AA. AC Q9Y2Q5; Q5VY97; Q5VY98; Q5VY99; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 24-JAN-2024, entry version 186. DE RecName: Full=Ragulator complex protein LAMTOR2 {ECO:0000305}; 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 Short=MAPBP-interacting protein; DE AltName: Full=Roadblock domain-containing protein 3; GN Name=LAMTOR2 {ECO:0000312|HGNC:HGNC:29796}; Synonyms=MAPBPIP, ROBLD3; GN ORFNames=HSPC003; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [5] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., RA Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [6] RP INVOLVEMENT IN IMMUNODEFICIENCY DUE TO DEFECT IN MAPBP-INTERACTING PROTEIN. RX PubMed=17195838; DOI=10.1038/nm1528; RA Bohn G., Allroth A., Brandes G., Thiel J., Glocker E., Schaeffer A.A., RA Rathinam C., Taub N., Teis D., Zeidler C., Dewey R.A., Geffers R., Buer J., RA Huber L.A., Welte K., Grimbacher B., Klein C.; RT "A novel human primary immunodeficiency syndrome caused by deficiency of RT the endosomal adaptor protein p14."; RL Nat. Med. 13:38-45(2007). RN [7] RP FUNCTION, AND IDENTIFICATION IN RAGULATOR COMPLEX. RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024; RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.; RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is RT necessary for its activation by amino acids."; RL Cell 141:290-303(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP FUNCTION IN MTORC1 SIGNALING, IDENTIFICATION IN RAGULATOR COMPLEX, AND RP INTERACTION WITH MTORC1 COMPLEX AND RAG GTPASES. RX PubMed=22980980; DOI=10.1016/j.cell.2012.07.032; RA Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M.; RT "Ragulator is a GEF for the Rag GTPases that signal amino acid levels to RT mTORC1."; RL Cell 150:1196-1208(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP SUBUNIT. RX PubMed=25561175; DOI=10.1038/nature14107; RA Rebsamen M., Pochini L., Stasyk T., de Araujo M.E., Galluccio M., RA Kandasamy R.K., Snijder B., Fauster A., Rudashevskaya E.L., Bruckner M., RA Scorzoni S., Filipek P.A., Huber K.V., Bigenzahn J.W., Heinz L.X., RA Kraft C., Bennett K.L., Indiveri C., Huber L.A., Superti-Furga G.; RT "SLC38A9 is a component of the lysosomal amino acid sensing machinery that RT controls mTORC1."; RL Nature 519:477-481(2015). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP SUBUNIT. RX PubMed=25567906; DOI=10.1126/science.1257132; RA Wang S., Tsun Z.Y., Wolfson R.L., Shen K., Wyant G.A., Plovanich M.E., RA Yuan E.D., Jones T.D., Chantranupong L., Comb W., Wang T., Bar-Peled L., RA Zoncu R., Straub C., Kim C., Park J., Sabatini B.L., Sabatini D.M.; RT "Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine RT sufficiency to mTORC1."; RL Science 347:188-194(2015). RN [14] RP FUNCTION. RX PubMed=30181260; DOI=10.1073/pnas.1811727115; RA Shen K., Sabatini D.M.; RT "Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF RT mechanisms."; RL Proc. Natl. Acad. Sci. U.S.A. 115:9545-9550(2018). RN [15] {ECO:0007744|PDB:5YK3} RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 1-124 IN COMPLEX WITH LAMTOR1; RP LAMTOR3; LAMTOR4 AND LAMTOR5, AND IDENTIFICATION IN RAGULATOR COMPLEX. RX PubMed=29285400; DOI=10.1038/celldisc.2017.49; RA Mu Z., Wang L., Deng W., Wang J., Wu G.; RT "Structural insight into the Ragulator complex which anchors mTORC1 to the RT lysosomal membrane."; RL Cell Discov. 3:17049-17049(2017). RN [16] {ECO:0007744|PDB:5Y39, ECO:0007744|PDB:5Y3A} RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH LAMTOR1; LAMTOR3; RP LAMTOR4 AND LAMTOR5, FUNCTION, AND IDENTIFICATION IN RAGULATOR COMPLEX. RX PubMed=29123114; DOI=10.1038/s41467-017-01567-4; RA Zhang T., Wang R., Wang Z., Wang X., Wang F., Ding J.; RT "Structural basis for Ragulator functioning as a scaffold in membrane- RT anchoring of Rag GTPases and mTORC1."; RL Nat. Commun. 8:1394-1394(2017). RN [17] {ECO:0007744|PDB:5X6U, ECO:0007744|PDB:5X6V} RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) IN COMPLEX WITH RRAGA; RRAGC; RP LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, FUNCTION, AND IDENTIFICATION IN RP RAGULATOR COMPLEX. RX PubMed=29158492; DOI=10.1038/s41467-017-01762-3; RA Yonehara R., Nada S., Nakai T., Nakai M., Kitamura A., Ogawa A., RA Nakatsumi H., Nakayama K.I., Li S., Standley D.M., Yamashita E., RA Nakagawa A., Okada M.; RT "Structural basis for the assembly of the Ragulator-Rag GTPase complex."; RL Nat. Commun. 8:1625-1625(2017). RN [18] {ECO:0007744|PDB:6B9X} RP X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) IN COMPLEX WITH LAMTOR1; LAMTOR3; RP LAMTOR4 AND LAMTOR5, FUNCTION, AND IDENTIFICATION IN RAGULATOR COMPLEX. RX PubMed=29107538; DOI=10.1016/j.molcel.2017.10.016; RA Su M.Y., Morris K.L., Kim D.J., Fu Y., Lawrence R., Stjepanovic G., RA Zoncu R., Hurley J.H.; RT "Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex."; RL Mol. Cell 68:835-846(2017). RN [19] {ECO:0007744|PDB:6EHP, ECO:0007744|PDB:6EHR} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 183-313 IN COMPLEX WITH RRAGA; RP RRAGC; LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, FUNCTION, AND IDENTIFICATION RP IN RAGULATOR COMPLEX. RX PubMed=28935770; DOI=10.1126/science.aao1583; RA de Araujo M.E.G., Naschberger A., Fuernrohr B.G., Stasyk T., RA Dunzendorfer-Matt T., Lechner S., Welti S., Kremser L., Shivalingaiah G., RA Offterdinger M., Lindner H.H., Huber L.A., Scheffzek K.; RT "Crystal structure of the human lysosomal mTORC1 scaffold complex and its RT impact on signaling."; RL Science 358:377-381(2017). RN [20] {ECO:0007744|PDB:6ULG} RP STRUCTURE BY ELECTRON MICROSCOPY (3.31 ANGSTROMS) IN COMPLEX WITH FLCN; RP FNIP2; RRAGA; RRAGC; LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, AND RP IDENTIFICATION IN THE LFC COMPLEX. RX PubMed=31704029; DOI=10.1016/j.cell.2019.10.036; RA Shen K., Rogala K.B., Chou H.T., Huang R.K., Yu Z., Sabatini D.M.; RT "Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex."; RL Cell 179:1319-1329(2019). RN [21] {ECO:0007744|PDB:6U62} RP STRUCTURE BY ELECTRON MICROSCOPY (3.18 ANGSTROMS) IN COMPLEX WITH RRAGA; RP RRAGC; RPTOR; LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, IDENTIFICATION IN THE RP RAGULATOR COMPLEX, AND MUTAGENESIS OF 41-ASP--ARG-43 AND 44-VAL--ALA-47. RX PubMed=31601708; DOI=10.1126/science.aay0166; RA Rogala K.B., Gu X., Kedir J.F., Abu-Remaileh M., Bianchi L.F., RA Bottino A.M.S., Dueholm R., Niehaus A., Overwijn D., Fils A.P., Zhou S.X., RA Leary D., Laqtom N.N., Brignole E.J., Sabatini D.M.; RT "Structural basis for the docking of mTORC1 on the lysosomal surface."; RL Science 366:468-475(2019). RN [22] {ECO:0007744|PDB:6NZD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH FLCN; RP FNIP2; RRAGA; RRAGC; LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, AND RP IDENTIFICATION IN THE LFC COMPLEX. RX PubMed=31672913; DOI=10.1126/science.aax0364; RA Lawrence R.E., Fromm S.A., Fu Y., Yokom A.L., Kim D.J., Thelen A.M., RA Young L.N., Lim C.Y., Samelson A.J., Hurley J.H., Zoncu R.; RT "Structural mechanism of a Rag GTPase activation checkpoint by the RT lysosomal folliculin complex."; RL Science 366:971-977(2019). RN [23] {ECO:0007744|PDB:6WJ2, ECO:0007744|PDB:6WJ3} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SLC38A9; RP LAMTOR1; LAMTOR3; LAMTOR4; LAMTOR5 AND THE RAG GTPASES HETERODIMER (RRAGA RP AND RRAGC), AND SUBUNIT. RX PubMed=32868926; DOI=10.1038/s41594-020-0490-9; RA Fromm S.A., Lawrence R.E., Hurley J.H.; RT "Structural mechanism for amino acid-dependent Rag GTPase nucleotide state RT switching by SLC38A9."; RL Nat. Struct. Mol. Biol. 27:1017-1023(2020). RN [24] {ECO:0007744|PDB:7T3A, ECO:0007744|PDB:7T3B, ECO:0007744|PDB:7T3C} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH RRAGA; RP RRAGC; DEPDC5; NPRL2; NPRL3; LAMTOR1; LAMTOR3; LAMTOR4 AND LAMTOR5, AND RP IDENTIFICATION IN THE RAGULATOR COMPLEX. RX PubMed=35338845; DOI=10.1016/j.molcel.2022.03.002; RA Egri S.B., Ouch C., Chou H.T., Yu Z., Song K., Xu C., Shen K.; RT "Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a RT spatial-constraint regulated GAP mechanism."; RL Mol. Cell 82:1836-1849(2022). RN [25] {ECO:0007744|PDB:8DHB} RP STRUCTURE BY ELECTRON MICROSCOPY (3.53 ANGSTROMS) IN COMPLEX WITH RRAGA; RP RRAGC; LAMTOR1; LAMTOR3; LAMTOR4; LAMTOR5; FNIP2; FLCN AND SLC38A9, AND RP IDENTIFICATION IN THE RAGULATOR COMPLEX. RX PubMed=36103527; DOI=10.1126/sciadv.add2926; RA Jansen R.M., Peruzzo R., Fromm S.A., Yokom A.L., Zoncu R., Hurley J.H.; RT "Structural basis for FLCN RagC GAP activation in MiT-TFE substrate- RT selective mTORC1 regulation."; RL Sci. Adv. 8:eadd2926-eadd2926(2022). RN [26] {ECO:0007744|PDB:7UX2, ECO:0007744|PDB:7UXC, ECO:0007744|PDB:7UXH} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH RRAGA; RP RRAGC; LAMTOR1; LAMTOR3; LAMTOR4; LAMTOR5; RPTOR; MLST8; MTOR AND TFEB, AND RP IDENTIFICATION IN THE RAGULATOR COMPLEX. RX PubMed=36697823; DOI=10.1038/s41586-022-05652-7; RA Cui Z., Napolitano G., de Araujo M.E.G., Esposito A., Monfregola J., RA Huber L.A., Ballabio A., Hurley J.H.; RT "Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex."; RL Nature 614:572-579(2023). 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 (PubMed:20381137, PubMed:29123114, PubMed:29158492, PubMed:29107538, CC PubMed:28935770). Activated by amino acids through a mechanism CC involving the lysosomal V-ATPase, the Ragulator plays a dual role for CC the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or CC RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), CC activating the small GTPases Rag and (2) mediates recruitment of Rag CC GTPases to the lysosome membrane (PubMed:22980980, PubMed:30181260, CC PubMed:29123114, PubMed:29158492, PubMed:29107538, PubMed:28935770). CC Activated Ragulator and Rag GTPases function as a scaffold recruiting CC mTORC1 to lysosomes where it is in turn activated (PubMed:22980980, CC PubMed:29123114, PubMed:29158492, PubMed:29107538). Adapter protein CC that enhances the efficiency of the MAP kinase cascade facilitating the CC activation of MAPK2 (By similarity). {ECO:0000250|UniProtKB:Q9JHS3, CC ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:22980980, CC ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, CC ECO:0000269|PubMed:29123114, ECO:0000269|PubMed:29158492, CC ECO:0000269|PubMed:30181260}. CC -!- SUBUNIT: Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, CC LAMTOR3, LAMTOR4 and LAMTOR5 (PubMed:20381137, PubMed:22980980, CC PubMed:29285400, PubMed:29123114, PubMed:29158492, PubMed:29107538, CC PubMed:28935770, PubMed:31601708, PubMed:32868926, PubMed:35338845, CC PubMed:36103527, PubMed:36697823). LAMTOR4 and LAMTOR5 form a CC heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 CC heterodimer (PubMed:20381137, PubMed:22980980). Interacts with LAMTOR1 CC and LAMTOR3; the interaction is direct (PubMed:20381137, CC PubMed:22980980). The Ragulator complex interacts with both the mTORC1 CC complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, CC RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid CC availability (PubMed:20381137, PubMed:22980980, PubMed:32868926). The CC Ragulator complex interacts with SLC38A9; the probable amino acid CC sensor (PubMed:25561175, PubMed:25567906). Interacts with MAPK1 and CC MAP2K1 (By similarity). Component of the lysosomal folliculin complex CC (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB CC GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator CC (PubMed:31704029, PubMed:31672913, PubMed:32868926). CC {ECO:0000250|UniProtKB:Q9JHS3, ECO:0000269|PubMed:20381137, CC ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:25561175, CC ECO:0000269|PubMed:25567906, ECO:0000269|PubMed:28935770, CC ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29123114, CC ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:29285400, CC ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31672913, CC ECO:0000269|PubMed:31704029, ECO:0000269|PubMed:32868926, CC ECO:0000269|PubMed:35338845, ECO:0000269|PubMed:36103527, CC ECO:0000269|PubMed:36697823}. CC -!- INTERACTION: CC Q9Y2Q5; Q96GS4: BORCS6; NbExp=4; IntAct=EBI-2643704, EBI-10193358; CC Q9Y2Q5; Q6IAA8: LAMTOR1; NbExp=14; IntAct=EBI-2643704, EBI-715385; CC Q9Y2Q5; Q9UHA4: LAMTOR3; NbExp=18; IntAct=EBI-2643704, EBI-1038192; CC Q9Y2Q5; Q8NBW4: SLC38A9; NbExp=3; IntAct=EBI-2643704, EBI-9978316; CC -!- SUBCELLULAR LOCATION: Late endosome membrane CC {ECO:0000250|UniProtKB:Q9JHS3}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q9JHS3}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q9JHS3}. Lysosome membrane CC {ECO:0000269|PubMed:17897319}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q9JHS3}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q9JHS3}. Note=Recruited to lysosome and endosome CC membranes by LAMTOR1. {ECO:0000250|UniProtKB:Q9JHS3}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y2Q5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y2Q5-2; Sequence=VSP_036543; CC Name=3; CC IsoId=Q9Y2Q5-3; Sequence=VSP_040980; CC -!- DISEASE: Immunodeficiency due to defect in MAPBP-interacting protein CC (ID-MAPBPIP) [MIM:610798]: This form of primary immunodeficiency CC syndrome includes congenital neutropenia, partial albinism, short CC stature and B-cell and cytotoxic T-cell deficiency. CC {ECO:0000269|PubMed:17195838}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the GAMAD family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=MAPBPIPbase; Note=ROBLD3 mutation db; CC URL="http://structure.bmc.lu.se/idbase/MAPBPIPbase/"; 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; AF070659; AAD20965.1; -; mRNA. DR EMBL; AK307086; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL355388; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024190; AAH24190.1; -; mRNA. DR CCDS; CCDS1128.1; -. [Q9Y2Q5-1] DR CCDS; CCDS44243.1; -. [Q9Y2Q5-3] DR RefSeq; NP_001138736.1; NM_001145264.1. [Q9Y2Q5-3] DR RefSeq; NP_054736.1; NM_014017.3. [Q9Y2Q5-1] DR PDB; 5X6U; X-ray; 2.40 A; B=1-125. DR PDB; 5X6V; X-ray; 2.02 A; B=1-125. DR PDB; 5Y39; X-ray; 2.65 A; B/G=1-125. DR PDB; 5Y3A; X-ray; 2.90 A; B/G=1-125. DR PDB; 5YK3; X-ray; 3.01 A; 1/B/G=1-124. DR PDB; 6B9X; X-ray; 1.42 A; B=1-125. DR PDB; 6EHP; X-ray; 2.30 A; B=2-125. DR PDB; 6EHR; X-ray; 2.90 A; B=2-125. DR PDB; 6NZD; EM; 3.60 A; B=1-125. DR PDB; 6U62; EM; 3.18 A; E=1-125. DR PDB; 6ULG; EM; 3.31 A; B=1-125. DR PDB; 6WJ2; EM; 3.20 A; B=1-125. DR PDB; 6WJ3; EM; 3.90 A; B=1-125. DR PDB; 7T3A; EM; 4.00 A; N=1-125. DR PDB; 7T3B; EM; 3.90 A; G=1-125. DR PDB; 7T3C; EM; 4.00 A; G/N=1-125. DR PDB; 7UX2; EM; 2.90 A; E/L=1-125. DR PDB; 7UXC; EM; 3.20 A; G/N=1-125. DR PDB; 7UXH; EM; 3.20 A; I/P/Y/f=1-125. DR PDB; 8DHB; EM; 3.53 A; D=1-125. DR PDBsum; 5X6U; -. DR PDBsum; 5X6V; -. DR PDBsum; 5Y39; -. DR PDBsum; 5Y3A; -. DR PDBsum; 5YK3; -. DR PDBsum; 6B9X; -. DR PDBsum; 6EHP; -. DR PDBsum; 6EHR; -. DR PDBsum; 6NZD; -. DR PDBsum; 6U62; -. DR PDBsum; 6ULG; -. DR PDBsum; 6WJ2; -. DR PDBsum; 6WJ3; -. DR PDBsum; 7T3A; -. DR PDBsum; 7T3B; -. DR PDBsum; 7T3C; -. DR PDBsum; 7UX2; -. DR PDBsum; 7UXC; -. DR PDBsum; 7UXH; -. DR PDBsum; 8DHB; -. DR AlphaFoldDB; Q9Y2Q5; -. DR BMRB; Q9Y2Q5; -. DR EMDB; EMD-0554; -. DR EMDB; EMD-20660; -. DR EMDB; EMD-20814; -. DR EMDB; EMD-21686; -. DR EMDB; EMD-21687; -. DR EMDB; EMD-25652; -. DR EMDB; EMD-25653; -. DR EMDB; EMD-25654; -. DR EMDB; EMD-26846; -. DR EMDB; EMD-26857; -. DR EMDB; EMD-26861; -. DR EMDB; EMD-27435; -. DR SMR; Q9Y2Q5; -. DR BioGRID; 118783; 131. DR ComplexPortal; CPX-4741; Ragulator complex. DR CORUM; Q9Y2Q5; -. DR DIP; DIP-57000N; -. DR IntAct; Q9Y2Q5; 22. DR MINT; Q9Y2Q5; -. DR STRING; 9606.ENSP00000357288; -. DR iPTMnet; Q9Y2Q5; -. DR PhosphoSitePlus; Q9Y2Q5; -. DR SwissPalm; Q9Y2Q5; -. DR BioMuta; LAMTOR2; -. DR DMDM; 12585246; -. DR OGP; Q9Y2Q5; -. DR EPD; Q9Y2Q5; -. DR jPOST; Q9Y2Q5; -. DR MassIVE; Q9Y2Q5; -. DR MaxQB; Q9Y2Q5; -. DR PaxDb; 9606-ENSP00000357288; -. DR PeptideAtlas; Q9Y2Q5; -. DR ProteomicsDB; 85869; -. [Q9Y2Q5-1] DR ProteomicsDB; 85870; -. [Q9Y2Q5-2] DR ProteomicsDB; 85871; -. [Q9Y2Q5-3] DR Pumba; Q9Y2Q5; -. DR TopDownProteomics; Q9Y2Q5-1; -. [Q9Y2Q5-1] DR TopDownProteomics; Q9Y2Q5-2; -. [Q9Y2Q5-2] DR TopDownProteomics; Q9Y2Q5-3; -. [Q9Y2Q5-3] DR Antibodypedia; 1218; 117 antibodies from 25 providers. DR DNASU; 28956; -. DR Ensembl; ENST00000368302.3; ENSP00000357285.3; ENSG00000116586.12. [Q9Y2Q5-2] DR Ensembl; ENST00000368304.9; ENSP00000357287.5; ENSG00000116586.12. [Q9Y2Q5-3] DR Ensembl; ENST00000368305.9; ENSP00000357288.4; ENSG00000116586.12. [Q9Y2Q5-1] DR GeneID; 28956; -. DR KEGG; hsa:28956; -. DR MANE-Select; ENST00000368305.9; ENSP00000357288.4; NM_014017.4; NP_054736.1. DR UCSC; uc001fnb.4; human. [Q9Y2Q5-1] DR AGR; HGNC:29796; -. DR CTD; 28956; -. DR DisGeNET; 28956; -. DR GeneCards; LAMTOR2; -. DR HGNC; HGNC:29796; LAMTOR2. DR HPA; ENSG00000116586; Low tissue specificity. DR MalaCards; LAMTOR2; -. DR MIM; 610389; gene. DR MIM; 610798; phenotype. DR neXtProt; NX_Q9Y2Q5; -. DR OpenTargets; ENSG00000116586; -. DR Orphanet; 90023; Primary immunodeficiency syndrome due to LAMTOR2 deficiency. DR PharmGKB; PA164725527; -. DR VEuPathDB; HostDB:ENSG00000116586; -. DR eggNOG; KOG4107; Eukaryota. DR GeneTree; ENSGT00390000006100; -. DR HOGENOM; CLU_141118_0_0_1; -. DR InParanoid; Q9Y2Q5; -. DR OMA; FREDRLQ; -. DR OrthoDB; 5482987at2759; -. DR PhylomeDB; Q9Y2Q5; -. DR TreeFam; TF313929; -. DR PathwayCommons; Q9Y2Q5; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-165159; MTOR signalling. DR Reactome; R-HSA-166208; mTORC1-mediated signalling. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription. DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1. DR SignaLink; Q9Y2Q5; -. DR SIGNOR; Q9Y2Q5; -. DR BioGRID-ORCS; 28956; 425 hits in 1169 CRISPR screens. DR ChiTaRS; LAMTOR2; human. DR GenomeRNAi; 28956; -. DR Pharos; Q9Y2Q5; Tbio. DR PRO; PR:Q9Y2Q5; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y2Q5; Protein. DR Bgee; ENSG00000116586; Expressed in mucosa of transverse colon and 188 other cell types or tissues. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:1990877; C:FNIP-folliculin RagC/D GAP; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; ISS:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; NAS:ComplexPortal. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0071986; C:Ragulator complex; IDA:UniProtKB. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:InterPro. DR GO; GO:0060090; F:molecular adaptor activity; IEA:InterPro. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:ComplexPortal. DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB. DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB. DR GO; GO:0008104; P:protein localization; IMP:UniProtKB. DR GO; GO:1902414; P:protein localization to cell junction; IEA:Ensembl. DR GO; GO:0001558; P:regulation of cell growth; IMP:UniProtKB. DR GO; GO:0150116; P:regulation of cell-substrate junction organization; IMP:MGI. DR GO; GO:0038202; P:TORC1 signaling; NAS:ComplexPortal. DR Gene3D; 3.30.450.30; Dynein light chain 2a, cytoplasmic; 1. DR InterPro; IPR037587; LAMTOR2-like. DR InterPro; IPR004942; Roadblock/LAMTOR2_dom. DR PANTHER; PTHR13323; LATE ENDOSOMAL/LYSOSOMAL MP1 INTERACTING PROTEIN; 1. DR PANTHER; PTHR13323:SF4; RAGULATOR COMPLEX PROTEIN LAMTOR2; 1. DR Pfam; PF03259; Robl_LC7; 1. DR SMART; SM00960; Robl_LC7; 1. DR SUPFAM; SSF103196; Roadblock/LC7 domain; 1. DR Genevisible; Q9Y2Q5; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Endosome; Lysosome; Membrane; KW Reference proteome. FT CHAIN 1..125 FT /note="Ragulator complex protein LAMTOR2" FT /id="PRO_0000220960" FT REGION 57..70 FT /note="Required for location at endosomes" FT /evidence="ECO:0000250" FT VAR_SEQ 78..107 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040980" FT VAR_SEQ 109..125 FT /note="QALVQYLEEPLTQVAAS -> VCGTDLCSPSAGPGFGAVPGGAPHPSGGILT FT ALVEAGVRKEK (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_036543" FT MUTAGEN 41..43 FT /note="DAR->AAA: In M6 mutant; impaired assembly of the FT Ragulator complex." FT /evidence="ECO:0000269|PubMed:31601708" FT MUTAGEN 44..47 FT /note="VTAA->DTAD: In M7 mutant; impaired association with FT Rag GTPases." FT /evidence="ECO:0000269|PubMed:31601708" FT HELIX 4..12 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 16..18 FT /evidence="ECO:0007829|PDB:7UX2" FT STRAND 19..25 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:6ULG" FT STRAND 31..36 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:5X6U" FT HELIX 42..60 FT /evidence="ECO:0007829|PDB:6B9X" FT TURN 64..66 FT /evidence="ECO:0007829|PDB:5X6V" FT STRAND 71..76 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 79..86 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 89..95 FT /evidence="ECO:0007829|PDB:6B9X" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:7UX2" FT HELIX 101..122 FT /evidence="ECO:0007829|PDB:6B9X" SQ SEQUENCE 125 AA; 13508 MW; 69599211C2CBC03D CRC64; MLRPKALTQV LSQANTGGVQ STLLLNNEGS LLAYSGYGDT DARVTAAIAS NIWAAYDRNG NQAFNEDNLK FILMDCMEGR VAITRVANLL LCMYAKETVG FGMLKAKAQA LVQYLEEPLT QVAAS //