LST8_HUMAN
ID LST8_HUMAN Reviewed; 326 AA.
AC Q9BVC4; B3KMM4; B4DY00; D3DU88; Q5M800; Q86Y18; Q8WUI5; Q9HA66; Q9UJV6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Target of rapamycin complex subunit LST8;
DE Short=TORC subunit LST8;
DE AltName: Full=G protein beta subunit-like;
DE Short=Gable;
DE Short=Protein GbetaL;
DE AltName: Full=Mammalian lethal with SEC13 protein 8;
DE Short=mLST8;
GN Name=MLST8; Synonyms=GBL, LST8;
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 [MRNA] (ISOFORM 2).
RA Mao Y., Li Y., Xie Y., Huo K., Hu Q.;
RT "Cloning and characterization of human LST8 gene.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Embryo, Mammary gland, and Testis;
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=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph, Placenta, Skin, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 97-326 (ISOFORMS 1/2).
RC TISSUE=Promyelocytic leukemia;
RA Ramachandiran S., Lau S.S., Monks T.J.;
RT "A novel G protein beta subunit (G beta 6) in human promyelocytic leukemia
RT (HL-60) cells.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INTERACTION WITH MTOR AND RPTOR, IDENTIFICATION IN THE TORC1 COMPLEX, AND
RP TISSUE SPECIFICITY.
RX PubMed=12408816; DOI=10.1016/s1097-2765(02)00636-6;
RA Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L.,
RA Bonenfant D., Oppliger W., Jenoe P., Hall M.N.;
RT "Two TOR complexes, only one of which is rapamycin sensitive, have distinct
RT roles in cell growth control.";
RL Mol. Cell 10:457-468(2002).
RN [8]
RP FUNCTION, INTERACTION WITH MTOR, IDENTIFICATION IN THE TORC1 COMPLEX,
RP MUTAGENESIS OF SER-72; GLY-192 AND PHE-320, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12718876; DOI=10.1016/s1097-2765(03)00114-x;
RA Kim D.-H., Sarbassov D.D., Ali S.M., Latek R.R., Guntur K.V.P.,
RA Erdjument-Bromage H., Tempst P., Sabatini D.M.;
RT "GbetaL, a positive regulator of the rapamycin-sensitive pathway required
RT for the nutrient-sensitive interaction between raptor and mTOR.";
RL Mol. Cell 11:895-904(2003).
RN [9]
RP IDENTIFICATION IN THE TORC1 AND TORC2 COMPLEXES.
RX PubMed=15268862; DOI=10.1016/j.cub.2004.06.054;
RA Sarbassov D.D., Ali S.M., Kim D.-H., Guertin D.A., Latek R.R.,
RA Erdjument-Bromage H., Tempst P., Sabatini D.M.;
RT "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive
RT and raptor-independent pathway that regulates the cytoskeleton.";
RL Curr. Biol. 14:1296-1302(2004).
RN [10]
RP IDENTIFICATION IN THE TORC2 COMPLEX, AND FUNCTION.
RX PubMed=15467718; DOI=10.1038/ncb1183;
RA Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., Hall M.N.;
RT "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin
RT insensitive.";
RL Nat. Cell Biol. 6:1122-1128(2004).
RN [11]
RP INTERACTION WITH RHEB.
RX PubMed=15854902; DOI=10.1016/j.cub.2005.02.053;
RA Long X., Lin Y., Ortiz-Vega S., Yonezawa K., Avruch J.;
RT "Rheb binds and regulates the mTOR kinase.";
RL Curr. Biol. 15:702-713(2005).
RN [12]
RP IDENTIFICATION IN THE TORC2 COMPLEX.
RX PubMed=17461779; DOI=10.1042/bj20070540;
RA Pearce L.R., Huang X., Boudeau J., Pawlowski R., Wullschleger S., Deak M.,
RA Ibrahim A.F.M., Gourlay R., Magnuson M.A., Alessi D.R.;
RT "Identification of Protor as a novel Rictor-binding component of mTOR
RT complex-2.";
RL Biochem. J. 405:513-522(2007).
RN [13]
RP IDENTIFICATION IN THE TORC1 AND TORC2 COMPLEXES.
RX PubMed=17510057; DOI=10.1074/jbc.m702376200;
RA Wang L., Harris T.E., Roth R.A., Lawrence J.C. Jr.;
RT "PRAS40 regulates mTORC1 kinase activity by functioning as a direct
RT inhibitor of substrate binding.";
RL J. Biol. Chem. 282:20036-20044(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, ACETYLATION [LARGE SCALE
RP ANALYSIS] AT MET-1 (ISOFORM 3), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-7 (ISOFORM 3), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP INTERACTION WITH MEAK7.
RX PubMed=29750193; DOI=10.1126/sciadv.aao5838;
RA Nguyen J.T., Ray C., Fox A.L., Mendonca D.B., Kim J.K., Krebsbach P.H.;
RT "Mammalian EAK-7 activates alternative mTOR signaling to regulate cell
RT proliferation and migration.";
RL Sci. Adv. 4:EAAO5838-EAAO5838(2018).
RN [19]
RP INTERACTION WITH SIK3.
RX PubMed=30232230; DOI=10.1126/scitranslmed.aat9356;
RA Csukasi F., Duran I., Barad M., Barta T., Gudernova I., Trantirek L.,
RA Martin J.H., Kuo C.Y., Woods J., Lee H., Cohn D.H., Krejci P., Krakow D.;
RT "The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR
RT signaling.";
RL Sci. Transl. Med. 10:0-0(2018).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH MTOR, WD REPEATS, AND
RP SUBUNIT.
RX PubMed=23636326; DOI=10.1038/nature12122;
RA Yang H., Rudge D.G., Koos J.D., Vaidialingam B., Yang H.J., Pavletich N.P.;
RT "mTOR kinase structure, mechanism and regulation.";
RL Nature 497:217-223(2013).
CC -!- FUNCTION: Subunit of both mTORC1 and mTORC2, which regulates cell
CC growth and survival in response to nutrient and hormonal signals.
CC mTORC1 is activated in response to growth factors or amino acids.
CC Growth factor-stimulated mTORC1 activation involves a AKT1-mediated
CC phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB
CC GTPase that potently activates the protein kinase activity of mTORC1.
CC Amino acid-signaling to mTORC1 requires its relocalization to the
CC lysosomes mediated by the Ragulator complex and the Rag GTPases.
CC Activated mTORC1 up-regulates protein synthesis by phosphorylating key
CC regulators of mRNA translation and ribosome synthesis. mTORC1
CC phosphorylates EIF4EBP1 and releases it from inhibiting the elongation
CC initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1
CC at 'Thr-389', which then promotes protein synthesis by phosphorylating
CC PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts
CC directly with MTOR and enhances its kinase activity. In nutrient-poor
CC conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-
CC mediated inhibition of MTOR activity. mTORC2 is also activated by
CC growth factors, but seems to be nutrient-insensitive. mTORC2 seems to
CC function upstream of Rho GTPases to regulate the actin cytoskeleton,
CC probably by activating one or more Rho-type guanine nucleotide exchange
CC factors. mTORC2 promotes the serum-induced formation of stress-fibers
CC or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473'
CC phosphorylation, which may facilitate the phosphorylation of the
CC activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite
CC for full activation. mTORC2 regulates the phosphorylation of SGK1 at
CC 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-
CC 657'. {ECO:0000250|UniProtKB:Q9DCJ1, ECO:0000269|PubMed:12718876,
CC ECO:0000269|PubMed:15467718}.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1)
CC which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1
CC binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian
CC target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8,
CC PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not
CC bind to and is not sensitive to FKBP12-rapamycin. Interacts directly
CC with MTOR and RPTOR. Interacts with RHEB. Interacts with MEAK7
CC (PubMed:29750193). Interacts with SIK3 (PubMed:30232230).
CC {ECO:0000269|PubMed:12408816, ECO:0000269|PubMed:12718876,
CC ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718,
CC ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:17461779,
CC ECO:0000269|PubMed:17510057, ECO:0000269|PubMed:23636326,
CC ECO:0000269|PubMed:29750193, ECO:0000269|PubMed:30232230}.
CC -!- INTERACTION:
CC Q9BVC4; P42345: MTOR; NbExp=5; IntAct=EBI-1387471, EBI-359260;
CC Q9BVC4; Q8N122: RPTOR; NbExp=3; IntAct=EBI-1387471, EBI-1567928;
CC Q9BVC4-1; P42345: MTOR; NbExp=7; IntAct=EBI-16056342, EBI-359260;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Z2K5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BVC4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BVC4-3; Sequence=VSP_032665;
CC Name=3;
CC IsoId=Q9BVC4-4; Sequence=VSP_032666, VSP_032667, VSP_032668;
CC Name=4;
CC IsoId=Q9BVC4-5; Sequence=VSP_047368;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in skeletal
CC muscle, heart and kidney. {ECO:0000269|PubMed:12408816}.
CC -!- SIMILARITY: Belongs to the WD repeat LST8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW85539.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY223837; AAO73410.1; -; mRNA.
DR EMBL; AK021536; BAG51036.1; -; mRNA.
DR EMBL; AK022227; BAB13990.1; -; mRNA.
DR EMBL; AK302201; BAG63562.1; -; mRNA.
DR EMBL; AC009065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85538.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85539.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471112; EAW85541.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85542.1; -; Genomic_DNA.
DR EMBL; BC001313; AAH01313.1; -; mRNA.
DR EMBL; BC017119; AAH17119.1; -; mRNA.
DR EMBL; BC052292; AAH52292.1; -; mRNA.
DR EMBL; BC088354; AAH88354.1; -; mRNA.
DR EMBL; AF195883; AAF04308.1; -; mRNA.
DR CCDS; CCDS10462.2; -. [Q9BVC4-1]
DR CCDS; CCDS58409.1; -. [Q9BVC4-5]
DR RefSeq; NP_001186102.1; NM_001199173.1. [Q9BVC4-1]
DR RefSeq; NP_001186103.1; NM_001199174.1. [Q9BVC4-1]
DR RefSeq; NP_001186104.1; NM_001199175.1. [Q9BVC4-5]
DR RefSeq; NP_071767.3; NM_022372.4. [Q9BVC4-1]
DR RefSeq; XP_016879037.1; XM_017023548.1. [Q9BVC4-3]
DR RefSeq; XP_016879038.1; XM_017023549.1. [Q9BVC4-3]
DR PDB; 4JSN; X-ray; 3.20 A; C/D=1-326.
DR PDB; 4JSP; X-ray; 3.30 A; C/D=1-326.
DR PDB; 4JSV; X-ray; 3.50 A; C/D=1-326.
DR PDB; 4JSX; X-ray; 3.50 A; C/D=1-326.
DR PDB; 4JT5; X-ray; 3.45 A; C/D=1-323.
DR PDB; 4JT6; X-ray; 3.60 A; C/D=1-326.
DR PDB; 5FLC; EM; 5.90 A; D/H=1-326.
DR PDB; 5H64; EM; 4.40 A; C/c=1-326.
DR PDB; 5WBU; X-ray; 3.42 A; C/D=1-326.
DR PDB; 5WBY; X-ray; 3.10 A; C/D=1-326.
DR PDB; 5ZCS; EM; 4.90 A; C/D=1-326.
DR PDB; 6BCU; EM; 3.43 A; D/E=1-326.
DR PDB; 6BCX; EM; 3.00 A; D/E=1-326.
DR PDB; 6SB0; EM; 5.50 A; E/H=1-326.
DR PDB; 6SB2; EM; 6.20 A; E/H=1-326.
DR PDB; 6ZWM; EM; 3.20 A; C/D=1-326.
DR PDB; 6ZWO; EM; 3.00 A; D=1-326.
DR PDB; 7OWG; EM; 4.70 A; E=1-326.
DR PDB; 7PE7; EM; 3.41 A; C/D=1-326.
DR PDB; 7PE8; EM; 3.20 A; C=1-326.
DR PDB; 7PE9; EM; 3.70 A; C=1-326.
DR PDB; 7PEA; EM; 4.07 A; C/D=1-326.
DR PDB; 7PEB; EM; 3.67 A; C=1-326.
DR PDB; 7PEC; EM; 4.24 A; C=1-326.
DR PDBsum; 4JSN; -.
DR PDBsum; 4JSP; -.
DR PDBsum; 4JSV; -.
DR PDBsum; 4JSX; -.
DR PDBsum; 4JT5; -.
DR PDBsum; 4JT6; -.
DR PDBsum; 5FLC; -.
DR PDBsum; 5H64; -.
DR PDBsum; 5WBU; -.
DR PDBsum; 5WBY; -.
DR PDBsum; 5ZCS; -.
DR PDBsum; 6BCU; -.
DR PDBsum; 6BCX; -.
DR PDBsum; 6SB0; -.
DR PDBsum; 6SB2; -.
DR PDBsum; 6ZWM; -.
DR PDBsum; 6ZWO; -.
DR PDBsum; 7OWG; -.
DR PDBsum; 7PE7; -.
DR PDBsum; 7PE8; -.
DR PDBsum; 7PE9; -.
DR PDBsum; 7PEA; -.
DR PDBsum; 7PEB; -.
DR PDBsum; 7PEC; -.
DR AlphaFoldDB; Q9BVC4; -.
DR SMR; Q9BVC4; -.
DR BioGRID; 122113; 132.
DR ComplexPortal; CPX-4402; mTORC2 complex.
DR ComplexPortal; CPX-503; mTORC1 complex.
DR CORUM; Q9BVC4; -.
DR DIP; DIP-39481N; -.
DR IntAct; Q9BVC4; 38.
DR MINT; Q9BVC4; -.
DR STRING; 9606.ENSP00000456405; -.
DR BindingDB; Q9BVC4; -.
DR ChEMBL; CHEMBL4296661; -.
DR ChEMBL; CHEMBL4523999; -.
DR iPTMnet; Q9BVC4; -.
DR PhosphoSitePlus; Q9BVC4; -.
DR BioMuta; MLST8; -.
DR DMDM; 74761285; -.
DR EPD; Q9BVC4; -.
DR jPOST; Q9BVC4; -.
DR MassIVE; Q9BVC4; -.
DR MaxQB; Q9BVC4; -.
DR PaxDb; Q9BVC4; -.
DR PeptideAtlas; Q9BVC4; -.
DR PRIDE; Q9BVC4; -.
DR ProteomicsDB; 79194; -. [Q9BVC4-1]
DR ProteomicsDB; 79195; -. [Q9BVC4-3]
DR ProteomicsDB; 79196; -. [Q9BVC4-4]
DR Antibodypedia; 23622; 483 antibodies from 39 providers.
DR DNASU; 64223; -.
DR Ensembl; ENST00000382450.8; ENSP00000371888.4; ENSG00000167965.18. [Q9BVC4-5]
DR Ensembl; ENST00000397124.5; ENSP00000380313.1; ENSG00000167965.18. [Q9BVC4-1]
DR Ensembl; ENST00000564088.5; ENSP00000457870.1; ENSG00000167965.18. [Q9BVC4-1]
DR Ensembl; ENST00000565250.1; ENSP00000455046.1; ENSG00000167965.18. [Q9BVC4-1]
DR Ensembl; ENST00000569417.6; ENSP00000456405.1; ENSG00000167965.18. [Q9BVC4-1]
DR GeneID; 64223; -.
DR KEGG; hsa:64223; -.
DR MANE-Select; ENST00000569417.6; ENSP00000456405.1; NM_022372.6; NP_071767.3.
DR UCSC; uc002coz.4; human. [Q9BVC4-1]
DR CTD; 64223; -.
DR DisGeNET; 64223; -.
DR GeneCards; MLST8; -.
DR HGNC; HGNC:24825; MLST8.
DR HPA; ENSG00000167965; Low tissue specificity.
DR MIM; 612190; gene.
DR neXtProt; NX_Q9BVC4; -.
DR OpenTargets; ENSG00000167965; -.
DR PharmGKB; PA165450213; -.
DR VEuPathDB; HostDB:ENSG00000167965; -.
DR eggNOG; KOG0315; Eukaryota.
DR GeneTree; ENSGT00390000014795; -.
DR InParanoid; Q9BVC4; -.
DR OMA; VQRNYKH; -.
DR OrthoDB; 779909at2759; -.
DR PhylomeDB; Q9BVC4; -.
DR TreeFam; TF318577; -.
DR PathwayCommons; Q9BVC4; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
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-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q9BVC4; -.
DR SIGNOR; Q9BVC4; -.
DR BioGRID-ORCS; 64223; 487 hits in 1092 CRISPR screens.
DR ChiTaRS; MLST8; human.
DR GeneWiki; MLST8; -.
DR GenomeRNAi; 64223; -.
DR Pharos; Q9BVC4; Tbio.
DR PRO; PR:Q9BVC4; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9BVC4; protein.
DR Bgee; ENSG00000167965; Expressed in right hemisphere of cerebellum and 181 other tissues.
DR ExpressionAtlas; Q9BVC4; baseline and differential.
DR Genevisible; Q9BVC4; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031931; C:TORC1 complex; IDA:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:WormBase.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
DR GO; GO:0071456; P:cellular response to hypoxia; IC:ComplexPortal.
DR GO; GO:0031669; P:cellular response to nutrient levels; IC:ComplexPortal.
DR GO; GO:0071470; P:cellular response to osmotic stress; IC:ComplexPortal.
DR GO; GO:0007010; P:cytoskeleton organization; IC:ComplexPortal.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0010507; P:negative regulation of autophagy; IC:ComplexPortal.
DR GO; GO:0016310; P:phosphorylation; IDA:ComplexPortal.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IC:ComplexPortal.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IC:ComplexPortal.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IC:ComplexPortal.
DR GO; GO:1905857; P:positive regulation of pentose-phosphate shunt; IC:ComplexPortal.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR GO; GO:0038202; P:TORC1 signaling; IMP:WormBase.
DR Gene3D; 2.130.10.10; -; 1.
DR IDEAL; IID00599; -.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR037588; MLST8.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR PANTHER; PTHR19842; PTHR19842; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50998; SSF50998; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..326
FT /note="Target of rapamycin complex subunit LST8"
FT /id="PRO_0000326499"
FT REPEAT 1..37
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 40..80
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 83..122
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 126..165
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 168..207
FT /note="WD 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 218..257
FT /note="WD 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT REPEAT 268..309
FT /note="WD 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23636326"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..66
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.1"
FT /id="VSP_032665"
FT VAR_SEQ 1
FT /note="M -> MEHAPWSPGASSRARAGHTM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032666"
FT VAR_SEQ 44
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047368"
FT VAR_SEQ 192..198
FT /note="GNCYVWN -> APRHLLG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032667"
FT VAR_SEQ 199..326
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032668"
FT MUTAGEN 72
FT /note="S->D: Impairs interaction with MTOR."
FT /evidence="ECO:0000269|PubMed:12718876"
FT MUTAGEN 192
FT /note="G->D: Abolishes interaction with MTOR."
FT /evidence="ECO:0000269|PubMed:12718876"
FT MUTAGEN 320
FT /note="F->S: Impairs interaction with MTOR."
FT /evidence="ECO:0000269|PubMed:12718876"
FT CONFLICT 56
FT /note="M -> V (in Ref. 2; BAB13990)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="H -> Y (in Ref. 5; AAH88354)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="R -> G (in Ref. 1; AAO73410)"
FT /evidence="ECO:0000305"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:5WBU"
FT STRAND 14..27
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 97..113
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 152..160
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:6ZWM"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 203..206
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 232..239
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:5WBY"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 282..298
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 315..321
FT /evidence="ECO:0007829|PDB:6ZWO"
FT MOD_RES Q9BVC4-4:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES Q9BVC4-4:7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
SQ SEQUENCE 326 AA; 35876 MW; 43A600D4EF2B6543 CRC64;
MNTSPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEV TPDRSMIAAA
GYQHIRMYDL NSNNPNPIIS YDGVNKNIAS VGFHEDGRWM YTGGEDCTAR IWDLRSRNLQ
CQRIFQVNAP INCVCLHPNQ AELIVGDQSG AIHIWDLKTD HNEQLIPEPE VSITSAHIDP
DASYMAAVNS TGNCYVWNLT GGIGDEVTQL IPKTKIPAHT RYALQCRFSP DSTLLATCSA
DQTCKIWRTS NFSLMTELSI KSGNPGESSR GWMWGCAFSG DSQYIVTASS DNLARLWCVE
TGEIKREYGG HQKAVVCLAF NDSVLG
