LST8_YEAST
ID LST8_YEAST Reviewed; 303 AA.
AC P41318; D6W1H1;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Target of rapamycin complex subunit LST8;
DE Short=TORC subunit LST8;
DE AltName: Full=Lethal with SEC13 protein 8;
GN Name=LST8 {ECO:0000312|SGD:S000004951}; OrderedLocusNames=YNL006W;
GN ORFNames=N2005;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=7985421; DOI=10.1002/yea.320100709;
RA Verhasselt P., Aert R., Voet M., Volckaert G.;
RT "Nucleotide sequence analysis of an 8887 bp region of the left arm of yeast
RT chromosome XIV, encompassing the centromere sequence.";
RL Yeast 10:945-951(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF LEU-300.
RX PubMed=9409822; DOI=10.1093/genetics/147.4.1569;
RA Roberg K.J., Bickel S., Rowley N., Kaiser C.A.;
RT "Control of amino acid permease sorting in the late secretory pathway of
RT Saccharomyces cerevisiae by SEC13, LST4, LST7 and LST8.";
RL Genetics 147:1569-1584(1997).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLY-138; GLY-146; GLY-171 AND GLY-181.
RX PubMed=11742997; DOI=10.1093/emboj/20.24.7209;
RA Liu Z., Sekito T., Epstein C.B., Butow R.A.;
RT "RTG-dependent mitochondria to nucleus signaling is negatively regulated by
RT the seven WD-repeat protein Lst8p.";
RL EMBO J. 20:7209-7219(2001).
RN [6]
RP IDENTIFICATION IN TORC1 AND TORC2, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TOR1 AND TOR2.
RX PubMed=12719473; DOI=10.1083/jcb.200210141;
RA Chen E.J., Kaiser C.A.;
RT "LST8 negatively regulates amino acid biosynthesis as a component of the
RT TOR pathway.";
RL J. Cell Biol. 161:333-347(2003).
RN [8]
RP SUBCELLULAR LOCATION, IDENTIFICATION IN TORC2, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND INTERACTION WITH TOR1 AND TOR2.
RX PubMed=12631735; DOI=10.1091/mbc.e02-09-0609;
RA Wedaman K.P., Reinke A., Anderson S., Yates J.R. III, McCaffery J.M.,
RA Powers T.;
RT "Tor kinases are in distinct membrane-associated protein complexes in
RT Saccharomyces cerevisiae.";
RL Mol. Biol. Cell 14:1204-1220(2003).
RN [9]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [10]
RP SUBUNIT, AND INTERACTION WITH TOR2.
RX PubMed=16002396; DOI=10.1074/jbc.m505553200;
RA Wullschleger S., Loewith R., Oppliger W., Hall M.N.;
RT "Molecular organization of target of rapamycin complex 2.";
RL J. Biol. Chem. 280:30697-30704(2005).
RN [11]
RP INTERACTION WITH PIB2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29698392; DOI=10.1371/journal.pgen.1007334;
RA Ukai H., Araki Y., Kira S., Oikawa Y., May A.I., Noda T.;
RT "Gtr/Ego-independent TORC1 activation is achieved through a glutamine-
RT sensitive interaction with Pib2 on the vacuolar membrane.";
RL PLoS Genet. 14:e1007334-e1007334(2018).
CC -!- FUNCTION: Essential component of both TORC1 and TORC2. TORC1 regulates
CC multiple cellular processes to control cell growth in response to
CC environmental signals. Nutrient limitation and environmental stress
CC signals cause inactivation of TORC1. Active TORC1 positively controls
CC ribosome biogenesis via control of rRNA, ribosomal protein and tRNA
CC gene expression, and rRNA processing. TORC1 positively controls protein
CC biosynthesis by regulation of mRNA stability, translation initiation
CC factor activity, and high-affinity amino acid permeases that serve to
CC provide amino acids for use by the translation machinery. TORC1 also
CC promotes growth by sequestering a number of nutrient and general
CC stress-responsive transcription factors in the cytoplasm. TORC1
CC negatively controls macroautophagy, a process to recycle surplus
CC cytoplasmic mass under nutrient starvation conditions. LST8 is involved
CC in the negative regulation of transcription factors GLN3 and RTG1-RTG3,
CC limiting the synthesis of alpha-ketoglutarate, glutamate and glutamine.
CC LST8 is required for targeting of amino acid permeases (AAPs) to the
CC plasma membrane. TORC2 regulates cell cycle-dependent polarization of
CC the actin-cytoskeleton, cell wall integrity, and receptor endocytosis.
CC TORC2 controls polarity of the actin cytoskeleton, which is required
CC for orienting the secretory pathway toward discrete growth sites, via
CC the RHO1/PKC1/MAPK cell integrity pathway. LST8 is involved in
CC maintenance of cell wall integrity. LST8 modulates TOR2 kinase
CC activity. {ECO:0000269|PubMed:11742997, ECO:0000269|PubMed:12719473,
CC ECO:0000269|PubMed:9409822}.
CC -!- SUBUNIT: The target of rapamycin complex 1 (TORC1) is composed of at
CC least KOG1, LST8, TCO89 and either TOR1 (TORC1-A) or TOR2 (TORC1-B)
CC (PubMed:12408816, PubMed:12631735, PubMed:12719473). TORC1 binds to and
CC is inhibited by FKBP-rapamycin (PubMed:12408816). Interacts with PIB2;
CC following activation of PIB2 by glutamine or cysteine and as part of
CC the TORC1 complex (PubMed:29698392). The target of rapamycin complex 2
CC (TORC2) is composed of at least AVO1, AVO2, BIT61, LST8, TOR2 and TSC11
CC (PubMed:12408816, PubMed:12631735, PubMed:12719473). TORC2 likely forms
CC a homodimer (PubMed:16002396). Contrary to TORC1, TORC2 does not bind
CC to and is not sensitive to FKBP-rapamycin (PubMed:12408816). LST8 binds
CC to the C-terminal kinase domain in TOR2 (PubMed:16002396).
CC {ECO:0000269|PubMed:12408816, ECO:0000269|PubMed:12631735,
CC ECO:0000269|PubMed:12719473, ECO:0000269|PubMed:16002396,
CC ECO:0000269|PubMed:29698392}.
CC -!- INTERACTION:
CC P41318; Q08236: AVO1; NbExp=2; IntAct=EBI-28598, EBI-29284;
CC P41318; Q04749: AVO2; NbExp=2; IntAct=EBI-28598, EBI-28131;
CC P41318; P38873: KOG1; NbExp=3; IntAct=EBI-28598, EBI-24864;
CC P41318; P35169: TOR1; NbExp=5; IntAct=EBI-28598, EBI-19374;
CC P41318; P32600: TOR2; NbExp=7; IntAct=EBI-28598, EBI-19385;
CC P41318; P40061: TSC11; NbExp=2; IntAct=EBI-28598, EBI-22621;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Vacuole membrane; Peripheral membrane protein;
CC Cytoplasmic side. Note=Also localizes to membranous structures both
CC proximal to, yet distinct from, the plasma membrane as well as within
CC the cell interior, probably endosomal or Golgi membranes.
CC -!- MISCELLANEOUS: Present with 589 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the WD repeat LST8 family. {ECO:0000305}.
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DR EMBL; X77114; CAA54380.1; -; Genomic_DNA.
DR EMBL; Z71282; CAA95865.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10537.1; -; Genomic_DNA.
DR PIR; S45461; S45461.
DR RefSeq; NP_014392.3; NM_001182845.3.
DR PDB; 6EMK; EM; 8.00 A; B/D=1-303.
DR PDBsum; 6EMK; -.
DR AlphaFoldDB; P41318; -.
DR SMR; P41318; -.
DR BioGRID; 35819; 733.
DR ComplexPortal; CPX-1715; TORC1 serine/threonine-protein kinase complex, TOR1 variant.
DR ComplexPortal; CPX-1716; TORC1 serine/threonine-protein kinase complex, TOR2 variant.
DR ComplexPortal; CPX-1717; TORC2 complex.
DR DIP; DIP-5318N; -.
DR IntAct; P41318; 39.
DR MINT; P41318; -.
DR STRING; 4932.YNL006W; -.
DR MaxQB; P41318; -.
DR PaxDb; P41318; -.
DR PRIDE; P41318; -.
DR EnsemblFungi; YNL006W_mRNA; YNL006W; YNL006W.
DR GeneID; 855726; -.
DR KEGG; sce:YNL006W; -.
DR SGD; S000004951; LST8.
DR VEuPathDB; FungiDB:YNL006W; -.
DR eggNOG; KOG0315; Eukaryota.
DR GeneTree; ENSGT00390000014795; -.
DR HOGENOM; CLU_000288_57_5_1; -.
DR InParanoid; P41318; -.
DR OMA; VQRNYKH; -.
DR BioCyc; YEAST:G3O-33048-MON; -.
DR Reactome; R-SCE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-SCE-3371571; HSF1-dependent transactivation.
DR Reactome; R-SCE-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-SCE-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-SCE-6804757; Regulation of TP53 Degradation.
DR Reactome; R-SCE-9639288; Amino acids regulate mTORC1.
DR PRO; PR:P41318; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P41318; protein.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0010008; C:endosome membrane; IDA:SGD.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IDA:SGD.
DR GO; GO:0034399; C:nuclear periphery; IDA:SGD.
DR GO; GO:0031931; C:TORC1 complex; IPI:SGD.
DR GO; GO:0031932; C:TORC2 complex; IPI:SGD.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:SGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IMP:SGD.
DR GO; GO:0031930; P:mitochondria-nucleus signaling pathway; IMP:SGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; IC:ComplexPortal.
DR GO; GO:0001558; P:regulation of cell growth; IPI:SGD.
DR GO; GO:0007584; P:response to nutrient; IC:ComplexPortal.
DR GO; GO:0007165; P:signal transduction; IMP:SGD.
DR GO; GO:0031929; P:TOR signaling; IMP:SGD.
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; 4.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Membrane; Reference proteome; Repeat; Vacuole;
KW WD repeat.
FT CHAIN 1..303
FT /note="Target of rapamycin complex subunit LST8"
FT /id="PRO_0000051483"
FT REPEAT 1..27
FT /note="WD 1"
FT REPEAT 30..68
FT /note="WD 2"
FT REPEAT 73..112
FT /note="WD 3"
FT REPEAT 114..153
FT /note="WD 4"
FT REPEAT 157..196
FT /note="WD 5"
FT REPEAT 205..244
FT /note="WD 6"
FT REPEAT 248..287
FT /note="WD 7"
FT MUTAGEN 138
FT /note="G->D: In LST8-3; abolishes repression of RTG1-RTG3-
FT dependent gene expression."
FT /evidence="ECO:0000269|PubMed:11742997"
FT MUTAGEN 146
FT /note="G->E: In LST8-2; abolishes repression of RTG1-RTG3-
FT dependent gene expression."
FT /evidence="ECO:0000269|PubMed:11742997"
FT MUTAGEN 171
FT /note="G->E: In LST8-5; abolishes repression of RTG1-RTG3-
FT dependent gene expression."
FT /evidence="ECO:0000269|PubMed:11742997"
FT MUTAGEN 181
FT /note="G->E: In LST8-4; abolishes repression of RTG1-RTG3-
FT dependent gene expression."
FT /evidence="ECO:0000269|PubMed:11742997"
FT MUTAGEN 300
FT /note="L->S: In LST8-1; abolishes repression of RTG2- and
FT RTG1-RTG3-dependent gene expression."
FT /evidence="ECO:0000269|PubMed:9409822"
SQ SEQUENCE 303 AA; 34034 MW; 536AA1DB8E8151F0 CRC64;
MSVILVSAGY DHTIRFWEAL TGVCSRTIQH SDSQVNRLEI TNDKKLLATA GHQNVRLYDI
RTTNPNPVAS FEGHRGNVTS VSFQQDNRWM VTSSEDGTIK VWDVRSPSIP RNYKHNAPVN
EVVIHPNQGE LISCDRDGNI RIWDLGENQC THQLTPEDDT SLQSLSMASD GSMLAAANTK
GNCYVWEMPN HTDASHLKPV TKFRAHSTYI TRILLSSDVK HLATCSADHT ARVWSIDDDF
KLETTLDGHQ RWVWDCAFSA DSAYLVTASS DHYVRLWDLS TREIVRQYGG HHKGAVCVAL
NDV
