GenomeNet

Database: UniProt
Entry: Q9BVC4
LinkDB: Q9BVC4
Original site: Q9BVC4 
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   11-DEC-2019, entry version 162.
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       P42345:MTOR; NbExp=7; IntAct=EBI-16056342, EBI-359260;
CC       Q8N122:RPTOR; NbExp=3; IntAct=EBI-1387471, EBI-1567928;
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};
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   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   SMR; Q9BVC4; -.
DR   BioGrid; 122113; 62.
DR   ComplexPortal; CPX-4402; mTORC2 complex.
DR   ComplexPortal; CPX-503; mTORC1 complex.
DR   CORUM; Q9BVC4; -.
DR   DIP; DIP-39481N; -.
DR   IntAct; Q9BVC4; 37.
DR   MINT; Q9BVC4; -.
DR   STRING; 9606.ENSP00000456405; -.
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   DNASU; 64223; -.
DR   Ensembl; ENST00000382450; ENSP00000371888; ENSG00000167965. [Q9BVC4-5]
DR   Ensembl; ENST00000397124; ENSP00000380313; ENSG00000167965. [Q9BVC4-1]
DR   Ensembl; ENST00000564088; ENSP00000457870; ENSG00000167965. [Q9BVC4-1]
DR   Ensembl; ENST00000565250; ENSP00000455046; ENSG00000167965. [Q9BVC4-1]
DR   Ensembl; ENST00000569417; ENSP00000456405; ENSG00000167965. [Q9BVC4-1]
DR   GeneID; 64223; -.
DR   KEGG; hsa:64223; -.
DR   UCSC; uc002coz.4; human. [Q9BVC4-1]
DR   CTD; 64223; -.
DR   DisGeNET; 64223; -.
DR   EuPathDB; HostDB:ENSG00000167965.17; -.
DR   GeneCards; MLST8; -.
DR   HGNC; HGNC:24825; MLST8.
DR   HPA; CAB019935; -.
DR   HPA; HPA041841; -.
DR   MIM; 612190; gene.
DR   neXtProt; NX_Q9BVC4; -.
DR   OpenTargets; ENSG00000167965; -.
DR   PharmGKB; PA165450213; -.
DR   eggNOG; KOG0315; Eukaryota.
DR   eggNOG; ENOG410XPVD; LUCA.
DR   GeneTree; ENSGT00390000014795; -.
DR   InParanoid; Q9BVC4; -.
DR   KO; K08266; -.
DR   OMA; LISCDQA; -.
DR   OrthoDB; 779909at2759; -.
DR   PhylomeDB; Q9BVC4; -.
DR   TreeFam; TF318577; -.
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   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 203 organ(s), highest expression level in right hemisphere of cerebellum.
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:0032148; P:activation of protein kinase B activity; TAS:Reactome.
DR   GO; GO:0007050; P:cell cycle arrest; TAS:Reactome.
DR   GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
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:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR   GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR   GO; GO:0016241; P:regulation of macroautophagy; TAS:Reactome.
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   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   InterPro; IPR017986; WD40_repeat_dom.
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:0000244|PubMed:19369195,
FT                   ECO:0000244|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..19
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          22..27
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            29..31
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          34..39
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          47..50
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          54..60
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          65..72
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          77..80
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          86..93
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          97..104
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          107..113
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          122..126
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          131..136
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          140..147
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          152..156
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            157..159
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          162..168
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          173..178
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          182..189
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          194..199
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            203..206
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          210..216
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          223..228
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          232..239
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            240..242
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          243..248
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            249..251
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          254..259
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          263..265
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          273..278
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          282..289
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          292..298
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   TURN            299..301
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          304..309
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   STRAND          315..322
FT                   /evidence="ECO:0000244|PDB:5WBY"
FT   MOD_RES         Q9BVC4-4:1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000244|PubMed:19369195"
FT   MOD_RES         Q9BVC4-4:7
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|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
//
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