ID   LST8_MOUSE              Reviewed;         326 AA.
AC   Q9DCJ1; Q8BNG8; Q8C882; Q9JKK6;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 175.
DE   RecName: Full=Target of rapamycin complex subunit LST8 {ECO:0000305};
DE            Short=TORC subunit LST8;
DE   AltName: Full=G protein beta subunit-like;
DE            Short=Protein GbetaL;
DE   AltName: Full=Mammalian lethal with SEC13 protein 8;
DE            Short=mLST8;
GN   Name=Mlst8 {ECO:0000312|MGI:MGI:1929514}; Synonyms=Gbl, Lst8;
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].
RX   PubMed=11182770; DOI=10.1677/joe.0.1680325;
RA   Rodgers B.D., Levine M.A., Bernier M., Montrose-Rafizadeh C.;
RT   "Insulin regulation of a novel WD-40 repeat protein in adipocytes.";
RL   J. Endocrinol. 168:325-332(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, Hypothalamus, Kidney, and Thymus;
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=Kidney;
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   INTERACTION WITH MTOR.
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   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17141160; DOI=10.1016/j.devcel.2006.10.007;
RA   Guertin D.A., Stevens D.M., Thoreen C.C., Burds A.A., Kalaany N.Y.,
RA   Moffat J., Brown M., Fitzgerald K.J., Sabatini D.M.;
RT   "Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals
RT   that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not
RT   S6K1.";
RL   Dev. Cell 11:859-871(2006).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   INTERACTION WITH MTOR.
RX   PubMed=20801936; DOI=10.1101/gad.1956410;
RA   Takai H., Xie Y., de Lange T., Pavletich N.P.;
RT   "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and
RT   ATR complexes.";
RL   Genes Dev. 24:2019-2030(2010).
CC   -!- FUNCTION: Subunit of both mTORC1 and mTORC2, which regulates cell
CC       growth and survival in response to nutrient and hormonal signals
CC       (PubMed:17141160). mTORC1 is activated in response to growth factors or
CC       amino acids (By similarity). In response to nutrients, mTORC1 is
CC       recruited to the lysosome membrane and promotes protein, lipid and
CC       nucleotide synthesis by phosphorylating several substrates, such as
CC       ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1)
CC       (By similarity). In the same time, it inhibits catabolic pathways by
CC       phosphorylating the autophagy initiation components ULK1 and ATG13, as
CC       well as transcription factor TFEB, a master regulators of lysosomal
CC       biogenesis and autophagy (By similarity). The mTORC1 complex is
CC       inhibited in response to starvation and amino acid depletion (By
CC       similarity). Within mTORC1, LST8 interacts directly with MTOR and
CC       enhances its kinase activity (By similarity). In nutrient-poor
CC       conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-
CC       mediated inhibition of MTOR activity (By similarity). mTORC2 is also
CC       activated by growth factors, but seems to be nutrient-insensitive (By
CC       similarity). mTORC2 seems to function upstream of Rho GTPases to
CC       regulate the actin cytoskeleton, probably by activating one or more
CC       Rho-type guanine nucleotide exchange factors (By similarity). mTORC2
CC       promotes the serum-induced formation of stress-fibers or F-actin (By
CC       similarity). 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 (By similarity). mTORC2 regulates the
CC       phosphorylation of SGK1 at 'Ser-422' (By similarity). mTORC2 also
CC       modulates the phosphorylation of PRKCA on 'Ser-657' (By similarity).
CC       {ECO:0000250|UniProtKB:Q9BVC4, ECO:0000269|PubMed:17141160}.
CC   -!- SUBUNIT: Part of the mechanistic target of rapamycin complex 1 (mTORC1)
CC       which contains MTOR, MLST8 and RPTOR. mTORC1 associates with
CC       AKT1S1/PRAS40, which inhibits its activity. mTORC1 binds to and is
CC       inhibited by FKBP12-rapamycin. Within mTORC1, interacts directly with
CC       MTOR and RPTOR. Part of the mechanistic target of rapamycin complex 2
CC       (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR.
CC       Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to
CC       FKBP12-rapamycin. mTORC1 and mTORC2 associate with DEPTOR, which
CC       regulates its activity. Interacts with RHEB. Interacts with MEAK7.
CC       Interacts with SIK3. Interacts with SLC38A7; this interaction promotes
CC       the recruitment of mTORC1 to the lysosome and its subsequent
CC       activation. {ECO:0000250|UniProtKB:Q9BVC4}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9BVC4}.
CC       Cytoplasm {ECO:0000250|UniProtKB:Q9Z2K5}. Note=Targeting to lysosomal
CC       membrane depends on amino acid availability: mTORC1 is recruited to
CC       lysosome membranes via interaction with GTP-bound form of RagA/RRAGA
CC       (or RagB/RRAGB) in complex with the GDP-bound form of RagC/RRAGC (or
CC       RagD/RRAGD), promoting its mTORC1 recruitment to the lysosomes.
CC       {ECO:0000250|UniProtKB:Q9BVC4}.
CC   -!- PTM: Phosphorylation at Thr-51 by CDK1 promotes ubiquitination by the
CC       SCF(FBXW7) complex, followed by degradation.
CC       {ECO:0000250|UniProtKB:Q9BVC4}.
CC   -!- PTM: Ubiquitination by the SCF(FBXW7) and SCF(FBXW11) complexes
CC       following phosphorylation at Thr-51 by CDK1, leads to its degradation
CC       by the proteasome. {ECO:0000250|UniProtKB:Q9BVC4}.
CC   -!- DISRUPTION PHENOTYPE: Death around 10.5 dpc due to multiple defects in
CC       vascular system development. In addition, they exhibit a delayed
CC       development of their cephalic region. {ECO:0000269|PubMed:17141160}.
CC   -!- SIMILARITY: Belongs to the WD repeat LST8 family. {ECO:0000305}.
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DR   EMBL; AF237676; AAF37719.1; -; mRNA.
DR   EMBL; AK002751; BAB22328.1; -; mRNA.
DR   EMBL; AK038515; BAC30024.1; -; mRNA.
DR   EMBL; AK040100; BAC30510.1; -; mRNA.
DR   EMBL; AK048102; BAC33243.1; -; mRNA.
DR   EMBL; AK077680; BAC36952.1; -; mRNA.
DR   EMBL; AK083731; BAC39006.1; -; mRNA.
DR   EMBL; BC015279; AAH15279.1; -; mRNA.
DR   CCDS; CCDS28484.1; -.
DR   RefSeq; NP_001239392.1; NM_001252463.1.
DR   RefSeq; NP_001239393.1; NM_001252464.1.
DR   RefSeq; NP_001239394.1; NM_001252465.1.
DR   RefSeq; NP_064372.2; NM_019988.5.
DR   AlphaFoldDB; Q9DCJ1; -.
DR   SMR; Q9DCJ1; -.
DR   BioGRID; 208141; 8.
DR   ComplexPortal; CPX-4472; mTORC2 complex.
DR   ComplexPortal; CPX-4473; mTORC1 complex.
DR   DIP; DIP-46976N; -.
DR   IntAct; Q9DCJ1; 4.
DR   STRING; 10090.ENSMUSP00000157137; -.
DR   iPTMnet; Q9DCJ1; -.
DR   PhosphoSitePlus; Q9DCJ1; -.
DR   SwissPalm; Q9DCJ1; -.
DR   EPD; Q9DCJ1; -.
DR   MaxQB; Q9DCJ1; -.
DR   PaxDb; 10090-ENSMUSP00000136287; -.
DR   PeptideAtlas; Q9DCJ1; -.
DR   ProteomicsDB; 293409; -.
DR   Pumba; Q9DCJ1; -.
DR   Antibodypedia; 23622; 529 antibodies from 39 providers.
DR   DNASU; 56716; -.
DR   Ensembl; ENSMUST00000070888.14; ENSMUSP00000065004.7; ENSMUSG00000024142.16.
DR   Ensembl; ENSMUST00000179163.3; ENSMUSP00000136287.2; ENSMUSG00000024142.16.
DR   Ensembl; ENSMUST00000234335.2; ENSMUSP00000157301.2; ENSMUSG00000024142.16.
DR   Ensembl; ENSMUST00000234686.2; ENSMUSP00000157137.2; ENSMUSG00000024142.16.
DR   GeneID; 56716; -.
DR   KEGG; mmu:56716; -.
DR   UCSC; uc008awg.3; mouse.
DR   AGR; MGI:1929514; -.
DR   CTD; 64223; -.
DR   MGI; MGI:1929514; Mlst8.
DR   VEuPathDB; HostDB:ENSMUSG00000024142; -.
DR   eggNOG; KOG0315; Eukaryota.
DR   GeneTree; ENSGT00390000014795; -.
DR   HOGENOM; CLU_000288_57_5_1; -.
DR   InParanoid; Q9DCJ1; -.
DR   OMA; VQRNYKH; -.
DR   PhylomeDB; Q9DCJ1; -.
DR   TreeFam; TF318577; -.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
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-3371571; HSF1-dependent transactivation.
DR   Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR   Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR   Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR   Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR   Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR   Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR   BioGRID-ORCS; 56716; 17 hits in 78 CRISPR screens.
DR   PRO; PR:Q9DCJ1; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; Q9DCJ1; Protein.
DR   Bgee; ENSMUSG00000024142; Expressed in granulocyte and 246 other cell types or tissues.
DR   ExpressionAtlas; Q9DCJ1; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031931; C:TORC1 complex; IDA:WormBase.
DR   GO; GO:0031932; C:TORC2 complex; ISO:MGI.
DR   GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:MGI.
DR   GO; GO:0071456; P:cellular response to hypoxia; NAS:ComplexPortal.
DR   GO; GO:0031669; P:cellular response to nutrient levels; NAS:ComplexPortal.
DR   GO; GO:0071470; P:cellular response to osmotic stress; NAS:ComplexPortal.
DR   GO; GO:0007010; P:cytoskeleton organization; NAS:ComplexPortal.
DR   GO; GO:0006974; P:DNA damage response; NAS:ComplexPortal.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; NAS:ComplexPortal.
DR   GO; GO:0010507; P:negative regulation of autophagy; NAS:ComplexPortal.
DR   GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:MGI.
DR   GO; GO:0030307; P:positive regulation of cell growth; NAS:ComplexPortal.
DR   GO; GO:0045821; P:positive regulation of glycolytic process; NAS:ComplexPortal.
DR   GO; GO:0046889; P:positive regulation of lipid biosynthetic process; NAS:ComplexPortal.
DR   GO; GO:1905857; P:positive regulation of pentose-phosphate shunt; NAS:ComplexPortal.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR   GO; GO:0032008; P:positive regulation of TOR signaling; ISO:MGI.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR   GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR   GO; GO:0038202; P:TORC1 signaling; ISO:MGI.
DR   CDD; cd00200; WD40; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 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; IPR019775; WD40_repeat_CS.
DR   InterPro; IPR001680; WD40_rpt.
DR   PANTHER; PTHR19842; G BETA-LIKE PROTEIN GBL; 1.
DR   PANTHER; PTHR19842:SF0; TARGET OF RAPAMYCIN COMPLEX SUBUNIT LST8; 1.
DR   Pfam; PF00400; WD40; 5.
DR   PRINTS; PR00320; GPROTEINBRPT.
DR   SMART; SM00320; WD40; 6.
DR   SUPFAM; SSF50998; Quinoprotein alcohol dehydrogenase-like; 1.
DR   PROSITE; PS00678; WD_REPEATS_1; 1.
DR   PROSITE; PS50082; WD_REPEATS_2; 3.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
DR   Genevisible; Q9DCJ1; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Lysosome; Membrane; Phosphoprotein;
KW   Reference proteome; Repeat; Ubl conjugation; WD repeat.
FT   CHAIN           1..326
FT                   /note="Target of rapamycin complex subunit LST8"
FT                   /id="PRO_0000326500"
FT   REPEAT          1..37
FT                   /note="WD 1"
FT   REPEAT          40..80
FT                   /note="WD 2"
FT   REPEAT          83..122
FT                   /note="WD 3"
FT   REPEAT          126..165
FT                   /note="WD 4"
FT   REPEAT          168..207
FT                   /note="WD 5"
FT   REPEAT          218..257
FT                   /note="WD 6"
FT   REPEAT          268..309
FT                   /note="WD 7"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BVC4"
FT   MOD_RES         51
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BVC4"
FT   CONFLICT        24
FT                   /note="V -> G (in Ref. 2; BAC39006)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        127
FT                   /note="V -> G (in Ref. 2; BAC39006)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        171
FT                   /note="S -> F (in Ref. 1; AAF37719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        195
FT                   /note="Y -> F (in Ref. 1; AAF37719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        206
FT                   /note="D -> E (in Ref. 1; AAF37719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        229
FT                   /note="S -> G (in Ref. 2; BAC33243)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   326 AA;  35851 MW;  2F6E75383905667A CRC64;
     MNTTPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEI TPDRSMIAAA
     GYQHIRMYDL NSNNPNPIIS YDGVSKNIAS VGFHEDGRWM YTGGEDCTAR IWDLRSRNLQ
     CQRIFQVNAP INCVCLHPNQ AELIVGDQSG AIHIWDLKTD HNEQLIPEPE SSITSAHIDP
     DASYMAAVNS AGNCYVWNLT GGIGDDVTQL IPKTKIPAHT RYALQCRFSP DSTLLATCSA
     DQTCKIWRTS NFSLMTELSI KSSNPGESSR GWMWGCAFSG DSQYIVTASS DNLARLWCVE
     TGEIKREYGG HQKAVVCLAF NDSVLG
//