LST8_DROME
ID LST8_DROME Reviewed; 313 AA.
AC Q9W328; Q95RK5;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Protein LST8 homolog;
GN Name=Lst8; ORFNames=CG3004;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, INTERACTION WITH TOR, AND DISRUPTION PHENOTYPE.
RX PubMed=22493059; DOI=10.1128/mcb.06474-11;
RA Wang T., Blumhagen R., Lao U., Kuo Y., Edgar B.A.;
RT "LST8 regulates cell growth via target-of-rapamycin complex 2 (TORC2).";
RL Mol. Cell. Biol. 32:2203-2213(2012).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25999153; DOI=10.1038/srep10339;
RA Kuo Y., Huang H., Cai T., Wang T.;
RT "Target of Rapamycin Complex 2 regulates cell growth via Myc in
RT Drosophila.";
RL Sci. Rep. 5:10339-10339(2015).
CC -!- FUNCTION: Subunit of TORC1 and TORC2, which regulate cell growth and
CC survival in response to nutrient and hormonal signals (PubMed:22493059,
CC PubMed:25999153). Essential for TORC2-mediated regulation of cell
CC growth and phosphorylation of Akt1 (PubMed:22493059, PubMed:25999153).
CC However it is not required for TORC1-mediated functions such as TORC1-
CC dependent regulation of cell growth, autophagy and phosphorylation of
CC S6K (PubMed:22493059). {ECO:0000269|PubMed:22493059,
CC ECO:0000269|PubMed:25999153}.
CC -!- SUBUNIT: Part of a minimal complex, TORC1, consisting of tor, raptor
CC and lst8. Interacts with tor but not raptor. Does not require raptor
CC for binding to tor. Part of a minimal complex, TORC2, consisting of
CC tor, rictor and lst8. {ECO:0000269|PubMed:22493059}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Reduced tissue growth (PubMed:22493059,
CC PubMed:25999153). Adults display an overall reduction in size with a
CC 25% reduction in body weight, and have smaller wings and eyes
CC (PubMed:22493059, PubMed:25999153). Reduced phosphorylation of Akt1
CC which is a direct target of the TORC2 complex but no effect on the
CC phosphorylation of SK6 which is a major target of the TORC1 complex
CC (PubMed:22493059). {ECO:0000269|PubMed:22493059,
CC ECO:0000269|PubMed:25999153}.
CC -!- SIMILARITY: Belongs to the WD repeat LST8 family. {ECO:0000305}.
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DR EMBL; AE014298; AAF46509.2; -; Genomic_DNA.
DR EMBL; AY061311; AAL28859.1; -; mRNA.
DR RefSeq; NP_572572.1; NM_132344.4.
DR AlphaFoldDB; Q9W328; -.
DR SMR; Q9W328; -.
DR BioGRID; 58343; 39.
DR IntAct; Q9W328; 13.
DR STRING; 7227.FBpp0071303; -.
DR PaxDb; Q9W328; -.
DR PRIDE; Q9W328; -.
DR DNASU; 31903; -.
DR EnsemblMetazoa; FBtr0071368; FBpp0071303; FBgn0264691.
DR GeneID; 31903; -.
DR KEGG; dme:Dmel_CG3004; -.
DR UCSC; CG3004-RA; d. melanogaster.
DR CTD; 31903; -.
DR FlyBase; FBgn0264691; Lst8.
DR VEuPathDB; VectorBase:FBgn0264691; -.
DR eggNOG; KOG0315; Eukaryota.
DR GeneTree; ENSGT00390000014795; -.
DR HOGENOM; CLU_000288_57_5_1; -.
DR InParanoid; Q9W328; -.
DR OMA; VQRNYKH; -.
DR OrthoDB; 779909at2759; -.
DR PhylomeDB; Q9W328; -.
DR Reactome; R-DME-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DME-1632852; Macroautophagy.
DR Reactome; R-DME-165159; MTOR signalling.
DR Reactome; R-DME-166208; mTORC1-mediated signalling.
DR Reactome; R-DME-3371571; HSF1-dependent transactivation.
DR Reactome; R-DME-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-DME-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DME-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-DME-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DME-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-DME-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q9W328; -.
DR BioGRID-ORCS; 31903; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 31903; -.
DR PRO; PR:Q9W328; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0264691; Expressed in wing disc and 22 other tissues.
DR ExpressionAtlas; Q9W328; baseline and differential.
DR Genevisible; Q9W328; DM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:FlyBase.
DR GO; GO:0061586; P:positive regulation of transcription by transcription factor localization; IPI:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IPI:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR GO; GO:0038203; P:TORC2 signaling; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR037588; MLST8.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR19842; PTHR19842; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..313
FT /note="Protein LST8 homolog"
FT /id="PRO_0000326505"
FT REPEAT 1..33
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 35..73
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 78..117
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 121..160
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 163..202
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 212..251
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 254..293
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REPEAT 296..313
FT /note="WD 8"
FT /evidence="ECO:0000255"
SQ SEQUENCE 313 AA; 35347 MW; C723AF39D05419AC CRC64;
MGDQQQLILA TGGYDHTIKV WQAHTGNCIK TMRFVETSQV NALDRTPDKT RLAACGYQCI
RLYDLESNCT APVINFDGVQ KNVTRLGFQE DGNWMFTAGE DHHVRIWDMI AAPPHCSRIF
DCEAPVNAAC LHPNQVEIAM GSQNGSVFLW DVKSERHERI VPEVDASIQD VAISPDGRYL
AAANNKGNCY IWSLTSQDQK MSTLRPNRKI PAHSRYILRC KFSPDSRLLL TTSGDGTVCI
WKTDDFSKWR ELCIENYWVW DAAFSADSKW LFTASSDGIA RLWKLQTKSS IRDYTGHTKA
ITALSFKDEI VGK
