LST8_MOUSE
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 03-AUG-2022, entry version 167.
DE RecName: Full=Target of rapamycin complex subunit LST8;
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; 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 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:Q9BVC4, ECO:0000269|PubMed:17141160}.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1)
CC which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR (By
CC similarity). mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part
CC of the mammalian target of rapamycin complex 2 (mTORC2) which contains
CC MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (By similarity). Contrary
CC to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-
CC rapamycin. Interacts directly with MTOR and RPTOR. Interacts with RHEB
CC (By similarity). Interacts with MTOR. Interacts with MEAK7 (By
CC similarity). Interacts with SIK3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9BVC4, ECO:0000269|PubMed:12718876,
CC ECO:0000269|PubMed:20801936}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Z2K5}.
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.ENSMUSP00000136287; -.
DR iPTMnet; Q9DCJ1; -.
DR PhosphoSitePlus; Q9DCJ1; -.
DR SwissPalm; Q9DCJ1; -.
DR EPD; Q9DCJ1; -.
DR MaxQB; Q9DCJ1; -.
DR PaxDb; Q9DCJ1; -.
DR PeptideAtlas; Q9DCJ1; -.
DR PRIDE; Q9DCJ1; -.
DR ProteomicsDB; 293409; -.
DR Antibodypedia; 23622; 483 antibodies from 39 providers.
DR DNASU; 56716; -.
DR Ensembl; ENSMUST00000070888; ENSMUSP00000065004; ENSMUSG00000024142.
DR Ensembl; ENSMUST00000179163; ENSMUSP00000136287; ENSMUSG00000024142.
DR Ensembl; ENSMUST00000234335; ENSMUSP00000157301; ENSMUSG00000024142.
DR Ensembl; ENSMUST00000234686; ENSMUSP00000157137; ENSMUSG00000024142.
DR GeneID; 56716; -.
DR KEGG; mmu:56716; -.
DR UCSC; uc008awg.3; mouse.
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 73 CRISPR screens.
DR PRO; PR:Q9DCJ1; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9DCJ1; protein.
DR Bgee; ENSMUSG00000024142; Expressed in granulocyte and 243 other tissues.
DR ExpressionAtlas; Q9DCJ1; baseline and differential.
DR Genevisible; Q9DCJ1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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: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; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:MGI.
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; 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:0043087; P:regulation of GTPase activity; IMP:MGI.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR GO; GO:0038202; P:TORC1 signaling; ISO:MGI.
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 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 Acetylation; Cytoplasm; Reference proteome; Repeat; 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 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
