Full text data of MLST8
MLST8
(GBL, LST8)
[Confidence: low (only semi-automatic identification from reviews)]
Target of rapamycin complex subunit LST8; TORC subunit LST8 (G protein beta subunit-like; Gable; Protein GbetaL; Mammalian lethal with SEC13 protein 8; mLST8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Target of rapamycin complex subunit LST8; TORC subunit LST8 (G protein beta subunit-like; Gable; Protein GbetaL; Mammalian lethal with SEC13 protein 8; mLST8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9BVC4
ID LST8_HUMAN Reviewed; 326 AA.
AC Q9BVC4; B3KMM4; B4DY00; D3DU88; Q5M800; Q86Y18; Q8WUI5; Q9HA66;
read moreAC Q9UJV6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 102.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT leukemia (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,
RP AND 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
RT distinct 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 MASS 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
RT required for the nutrient-sensitive interaction between raptor and
RT 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-
RT insensitive and raptor-independent pathway that regulates the
RT 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.,
RA Hall M.N.;
RT "Mammalian TOR complex 2 controls the actin cytoskeleton and is
RT rapamycin 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.,
RA Deak M., 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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-7 (ISOFORM 3), AND MASS SPECTROMETRY.
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 MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH MTOR,
RP WD-REPEATS, AND SUBUNIT.
RX PubMed=23636326; DOI=10.1038/nature12122;
RA Yang H., Rudge D.G., Koos J.D., Vaidialingam B., Yang H.J.,
RA 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-
CC mediated phosphorylation of TSC1-TSC2, which leads to the
CC activation of the RHEB GTPase that potently activates the protein
CC kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires
CC its relocalization to the lysosomes mediated by the Ragulator
CC complex and the Rag GTPases. Activated mTORC1 up-regulates protein
CC synthesis by phosphorylating key regulators of mRNA translation
CC and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and
CC releases it from inhibiting the elongation initiation factor 4E
CC (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389',
CC which then promotes protein synthesis by phosphorylating PDCD4 and
CC targeting it for degradation. Within mTORC1, LST8 interacts
CC directly with MTOR and enhances its kinase activity. In nutrient-
CC poor conditions, stabilizes the MTOR-RPTOR interaction and favors
CC RPTOR-mediated inhibition of MTOR activity. mTORC2 is also
CC activated by growth factors, but seems to be nutrient-insensitive.
CC mTORC2 seems to function upstream of Rho GTPases to regulate the
CC actin cytoskeleton, probably by activating one or more Rho-type
CC guanine nucleotide exchange factors. mTORC2 promotes the serum-
CC induced formation of stress-fibers or F-actin. mTORC2 plays a
CC critical role in AKT1 'Ser-473' phosphorylation, which may
CC facilitate the phosphorylation of the activation loop of AKT1 on
CC 'Thr-308' by PDK1 which is a prerequisite for full activation.
CC mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2
CC also modulates the phosphorylation of PRKCA on 'Ser-657'.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1
CC (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and
CC DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part
CC of the mammalian target of rapamycin complex 2 (mTORC2) which
CC contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. 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
CC RHEB.
CC -!- INTERACTION:
CC P42345:MTOR; NbExp=4; IntAct=EBI-1387471, EBI-359260;
CC Q8N122:RPTOR; NbExp=3; IntAct=EBI-1387471, EBI-1567928;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
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 Note=Contains a N-acetylmethionine at position 1. Contains a
CC phosphoserine at position 7;
CC Name=4;
CC IsoId=Q9BVC4-5; Sequence=VSP_047368;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in
CC skeletal muscle, heart and kidney.
CC -!- SIMILARITY: Belongs to the WD repeat LST8 family.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW85539.1; Type=Erroneous gene model prediction;
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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 RefSeq; NP_001186102.1; NM_001199173.1.
DR RefSeq; NP_001186103.1; NM_001199174.1.
DR RefSeq; NP_001186104.1; NM_001199175.1.
DR RefSeq; NP_071767.3; NM_022372.4.
DR RefSeq; XP_005255537.1; XM_005255480.1.
DR RefSeq; XP_005255538.1; XM_005255481.1.
DR RefSeq; XP_005255539.1; XM_005255482.1.
DR RefSeq; XP_005255540.1; XM_005255483.1.
DR UniGene; Hs.29203; -.
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=1-326.
DR PDB; 4JT6; X-ray; 3.60 A; C/D=1-326.
DR PDBsum; 4JSN; -.
DR PDBsum; 4JSP; -.
DR PDBsum; 4JSV; -.
DR PDBsum; 4JSX; -.
DR PDBsum; 4JT5; -.
DR PDBsum; 4JT6; -.
DR ProteinModelPortal; Q9BVC4; -.
DR SMR; Q9BVC4; 8-324.
DR DIP; DIP-39481N; -.
DR IntAct; Q9BVC4; 14.
DR MINT; MINT-3046622; -.
DR STRING; 9606.ENSP00000371888; -.
DR PhosphoSite; Q9BVC4; -.
DR DMDM; 74761285; -.
DR PaxDb; Q9BVC4; -.
DR PRIDE; Q9BVC4; -.
DR DNASU; 64223; -.
DR Ensembl; ENST00000301724; ENSP00000301724; ENSG00000167965.
DR Ensembl; ENST00000301725; ENSP00000301725; ENSG00000167965.
DR Ensembl; ENST00000382450; ENSP00000371888; ENSG00000167965.
DR Ensembl; ENST00000397124; ENSP00000380313; ENSG00000167965.
DR Ensembl; ENST00000564088; ENSP00000457870; ENSG00000167965.
DR Ensembl; ENST00000565250; ENSP00000455046; ENSG00000167965.
DR Ensembl; ENST00000569417; ENSP00000456405; ENSG00000167965.
DR GeneID; 64223; -.
DR KEGG; hsa:64223; -.
DR UCSC; uc002coy.3; human.
DR CTD; 64223; -.
DR GeneCards; GC16P002254; -.
DR H-InvDB; HIX0012725; -.
DR HGNC; HGNC:24825; MLST8.
DR HPA; CAB019935; -.
DR MIM; 612190; gene.
DR neXtProt; NX_Q9BVC4; -.
DR PharmGKB; PA165450213; -.
DR eggNOG; COG2319; -.
DR HOVERGEN; HBG054763; -.
DR KO; K08266; -.
DR OMA; AGHHTVK; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q9BVC4; -.
DR GeneWiki; MLST8; -.
DR GenomeRNAi; 64223; -.
DR NextBio; 66155; -.
DR PRO; PR:Q9BVC4; -.
DR ArrayExpress; Q9BVC4; -.
DR Bgee; Q9BVC4; -.
DR Genevestigator; Q9BVC4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; 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 cascade; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0032314; P:regulation of Rac GTPase activity; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR011047; Quinonprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
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; Complete proteome;
KW Cytoplasm; Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1 326 Target of rapamycin complex subunit LST8.
FT /FTId=PRO_0000326499.
FT REPEAT 1 37 WD 1.
FT REPEAT 40 80 WD 2.
FT REPEAT 83 122 WD 3.
FT REPEAT 126 165 WD 4.
FT REPEAT 168 207 WD 5.
FT REPEAT 218 257 WD 6.
FT REPEAT 268 309 WD 7.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 66 Missing (in isoform 2).
FT /FTId=VSP_032665.
FT VAR_SEQ 1 1 M -> MEHAPWSPGASSRARAGHTM (in isoform 3).
FT /FTId=VSP_032666.
FT VAR_SEQ 44 44 Missing (in isoform 4).
FT /FTId=VSP_047368.
FT VAR_SEQ 192 198 GNCYVWN -> APRHLLG (in isoform 3).
FT /FTId=VSP_032667.
FT VAR_SEQ 199 326 Missing (in isoform 3).
FT /FTId=VSP_032668.
FT MUTAGEN 72 72 S->D: Impairs interaction with MTOR.
FT MUTAGEN 192 192 G->D: Abolishes interaction with MTOR.
FT MUTAGEN 320 320 F->S: Impairs interaction with MTOR.
FT CONFLICT 56 56 M -> V (in Ref. 2; BAB13990).
FT CONFLICT 153 153 H -> Y (in Ref. 5; AAH88354).
FT CONFLICT 248 248 R -> G (in Ref. 1; AAO73410).
FT STRAND 10 19
FT STRAND 22 27
FT TURN 29 31
FT STRAND 34 39
FT STRAND 47 50
FT STRAND 54 60
FT STRAND 65 72
FT STRAND 78 81
FT STRAND 86 93
FT STRAND 97 104
FT STRAND 107 113
FT STRAND 122 126
FT STRAND 131 136
FT STRAND 140 147
FT STRAND 152 156
FT TURN 157 159
FT STRAND 162 165
FT STRAND 173 178
FT STRAND 182 189
FT STRAND 194 199
FT HELIX 203 205
FT STRAND 210 216
FT STRAND 223 228
FT STRAND 232 239
FT STRAND 242 248
FT TURN 249 251
FT STRAND 254 259
FT STRAND 263 265
FT STRAND 273 278
FT STRAND 282 289
FT STRAND 292 298
FT TURN 299 301
FT STRAND 304 309
FT STRAND 315 322
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
//
ID LST8_HUMAN Reviewed; 326 AA.
AC Q9BVC4; B3KMM4; B4DY00; D3DU88; Q5M800; Q86Y18; Q8WUI5; Q9HA66;
read moreAC Q9UJV6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 102.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT leukemia (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,
RP AND 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
RT distinct 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 MASS 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
RT required for the nutrient-sensitive interaction between raptor and
RT 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-
RT insensitive and raptor-independent pathway that regulates the
RT 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.,
RA Hall M.N.;
RT "Mammalian TOR complex 2 controls the actin cytoskeleton and is
RT rapamycin 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.,
RA Deak M., 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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-7 (ISOFORM 3), AND MASS SPECTROMETRY.
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 MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH MTOR,
RP WD-REPEATS, AND SUBUNIT.
RX PubMed=23636326; DOI=10.1038/nature12122;
RA Yang H., Rudge D.G., Koos J.D., Vaidialingam B., Yang H.J.,
RA 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-
CC mediated phosphorylation of TSC1-TSC2, which leads to the
CC activation of the RHEB GTPase that potently activates the protein
CC kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires
CC its relocalization to the lysosomes mediated by the Ragulator
CC complex and the Rag GTPases. Activated mTORC1 up-regulates protein
CC synthesis by phosphorylating key regulators of mRNA translation
CC and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and
CC releases it from inhibiting the elongation initiation factor 4E
CC (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389',
CC which then promotes protein synthesis by phosphorylating PDCD4 and
CC targeting it for degradation. Within mTORC1, LST8 interacts
CC directly with MTOR and enhances its kinase activity. In nutrient-
CC poor conditions, stabilizes the MTOR-RPTOR interaction and favors
CC RPTOR-mediated inhibition of MTOR activity. mTORC2 is also
CC activated by growth factors, but seems to be nutrient-insensitive.
CC mTORC2 seems to function upstream of Rho GTPases to regulate the
CC actin cytoskeleton, probably by activating one or more Rho-type
CC guanine nucleotide exchange factors. mTORC2 promotes the serum-
CC induced formation of stress-fibers or F-actin. mTORC2 plays a
CC critical role in AKT1 'Ser-473' phosphorylation, which may
CC facilitate the phosphorylation of the activation loop of AKT1 on
CC 'Thr-308' by PDK1 which is a prerequisite for full activation.
CC mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2
CC also modulates the phosphorylation of PRKCA on 'Ser-657'.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1
CC (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and
CC DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part
CC of the mammalian target of rapamycin complex 2 (mTORC2) which
CC contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. 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
CC RHEB.
CC -!- INTERACTION:
CC P42345:MTOR; NbExp=4; IntAct=EBI-1387471, EBI-359260;
CC Q8N122:RPTOR; NbExp=3; IntAct=EBI-1387471, EBI-1567928;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
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 Note=Contains a N-acetylmethionine at position 1. Contains a
CC phosphoserine at position 7;
CC Name=4;
CC IsoId=Q9BVC4-5; Sequence=VSP_047368;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in
CC skeletal muscle, heart and kidney.
CC -!- SIMILARITY: Belongs to the WD repeat LST8 family.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW85539.1; Type=Erroneous gene model prediction;
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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 RefSeq; NP_001186102.1; NM_001199173.1.
DR RefSeq; NP_001186103.1; NM_001199174.1.
DR RefSeq; NP_001186104.1; NM_001199175.1.
DR RefSeq; NP_071767.3; NM_022372.4.
DR RefSeq; XP_005255537.1; XM_005255480.1.
DR RefSeq; XP_005255538.1; XM_005255481.1.
DR RefSeq; XP_005255539.1; XM_005255482.1.
DR RefSeq; XP_005255540.1; XM_005255483.1.
DR UniGene; Hs.29203; -.
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=1-326.
DR PDB; 4JT6; X-ray; 3.60 A; C/D=1-326.
DR PDBsum; 4JSN; -.
DR PDBsum; 4JSP; -.
DR PDBsum; 4JSV; -.
DR PDBsum; 4JSX; -.
DR PDBsum; 4JT5; -.
DR PDBsum; 4JT6; -.
DR ProteinModelPortal; Q9BVC4; -.
DR SMR; Q9BVC4; 8-324.
DR DIP; DIP-39481N; -.
DR IntAct; Q9BVC4; 14.
DR MINT; MINT-3046622; -.
DR STRING; 9606.ENSP00000371888; -.
DR PhosphoSite; Q9BVC4; -.
DR DMDM; 74761285; -.
DR PaxDb; Q9BVC4; -.
DR PRIDE; Q9BVC4; -.
DR DNASU; 64223; -.
DR Ensembl; ENST00000301724; ENSP00000301724; ENSG00000167965.
DR Ensembl; ENST00000301725; ENSP00000301725; ENSG00000167965.
DR Ensembl; ENST00000382450; ENSP00000371888; ENSG00000167965.
DR Ensembl; ENST00000397124; ENSP00000380313; ENSG00000167965.
DR Ensembl; ENST00000564088; ENSP00000457870; ENSG00000167965.
DR Ensembl; ENST00000565250; ENSP00000455046; ENSG00000167965.
DR Ensembl; ENST00000569417; ENSP00000456405; ENSG00000167965.
DR GeneID; 64223; -.
DR KEGG; hsa:64223; -.
DR UCSC; uc002coy.3; human.
DR CTD; 64223; -.
DR GeneCards; GC16P002254; -.
DR H-InvDB; HIX0012725; -.
DR HGNC; HGNC:24825; MLST8.
DR HPA; CAB019935; -.
DR MIM; 612190; gene.
DR neXtProt; NX_Q9BVC4; -.
DR PharmGKB; PA165450213; -.
DR eggNOG; COG2319; -.
DR HOVERGEN; HBG054763; -.
DR KO; K08266; -.
DR OMA; AGHHTVK; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q9BVC4; -.
DR GeneWiki; MLST8; -.
DR GenomeRNAi; 64223; -.
DR NextBio; 66155; -.
DR PRO; PR:Q9BVC4; -.
DR ArrayExpress; Q9BVC4; -.
DR Bgee; Q9BVC4; -.
DR Genevestigator; Q9BVC4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; 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 cascade; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0032314; P:regulation of Rac GTPase activity; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR011047; Quinonprotein_ADH-like_supfam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
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; Complete proteome;
KW Cytoplasm; Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1 326 Target of rapamycin complex subunit LST8.
FT /FTId=PRO_0000326499.
FT REPEAT 1 37 WD 1.
FT REPEAT 40 80 WD 2.
FT REPEAT 83 122 WD 3.
FT REPEAT 126 165 WD 4.
FT REPEAT 168 207 WD 5.
FT REPEAT 218 257 WD 6.
FT REPEAT 268 309 WD 7.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 66 Missing (in isoform 2).
FT /FTId=VSP_032665.
FT VAR_SEQ 1 1 M -> MEHAPWSPGASSRARAGHTM (in isoform 3).
FT /FTId=VSP_032666.
FT VAR_SEQ 44 44 Missing (in isoform 4).
FT /FTId=VSP_047368.
FT VAR_SEQ 192 198 GNCYVWN -> APRHLLG (in isoform 3).
FT /FTId=VSP_032667.
FT VAR_SEQ 199 326 Missing (in isoform 3).
FT /FTId=VSP_032668.
FT MUTAGEN 72 72 S->D: Impairs interaction with MTOR.
FT MUTAGEN 192 192 G->D: Abolishes interaction with MTOR.
FT MUTAGEN 320 320 F->S: Impairs interaction with MTOR.
FT CONFLICT 56 56 M -> V (in Ref. 2; BAB13990).
FT CONFLICT 153 153 H -> Y (in Ref. 5; AAH88354).
FT CONFLICT 248 248 R -> G (in Ref. 1; AAO73410).
FT STRAND 10 19
FT STRAND 22 27
FT TURN 29 31
FT STRAND 34 39
FT STRAND 47 50
FT STRAND 54 60
FT STRAND 65 72
FT STRAND 78 81
FT STRAND 86 93
FT STRAND 97 104
FT STRAND 107 113
FT STRAND 122 126
FT STRAND 131 136
FT STRAND 140 147
FT STRAND 152 156
FT TURN 157 159
FT STRAND 162 165
FT STRAND 173 178
FT STRAND 182 189
FT STRAND 194 199
FT HELIX 203 205
FT STRAND 210 216
FT STRAND 223 228
FT STRAND 232 239
FT STRAND 242 248
FT TURN 249 251
FT STRAND 254 259
FT STRAND 263 265
FT STRAND 273 278
FT STRAND 282 289
FT STRAND 292 298
FT TURN 299 301
FT STRAND 304 309
FT STRAND 315 322
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
//
MIM
612190
*RECORD*
*FIELD* NO
612190
*FIELD* TI
*612190 MTOR-ASSOCIATED PROTEIN LST8; MLST8
;;G-BETA-LIKE PROTEIN; GBL;;
G PROTEIN BETA SUBUNIT-LIKE PROTEIN;;
read moreLST8, S. CEREVISIAE, HOMOLOG OF; LST8;;
WAT1, S. POMBE, HOMOLOG OF; WAT1;;
POP3, S. POMBE, HOMOLOG OF; POP3
*FIELD* TX
CLONING
Rodgers et al. (2001) cloned rat Gbl and identified its human homolog by
database analysis. The predicted human GBL protein shares 96.6% amino
acid identity with rat Gbl, which contains 7 WD40 repeats similar to
those of G protein beta subunits (see 139380). Northern blot analysis
detected ubiquitous expression of Gbl in rat tissues.
Immunoprecipitation of membrane and cytosolic fractions of transfected
human embryonic kidney cells showed that rat Gbl was predominantly
cytosolic.
MAPPING
Rodgers et al. (2001) stated that the GBL gene maps to chromosome
16p13.3.
BIOCHEMICAL FEATURES
- Crystal Structure
Yang et al. (2013) reported cocrystal structures of a complex of
truncated mTOR (601231) and mammalian lethal with SEC13 protein-8
(mLST8) with an ATP transition state mimic and with ATP-site inhibitors.
The structures revealed an intrinsically active kinase conformation,
with catalytic residues and a catalytic mechanism remarkably similar to
canonical protein kinases. The active site is highly recessed owing to
the FKBP12 (186945)-rapamycin-binding (FRB) domain and an inhibitory
helix protruding from the catalytic cleft. mTOR-activating mutations map
to the structural framework that holds these elements in place,
indicating that the kinase is controlled by restricted access. In vitro
biochemistry showed that the FRB domain acts as a gatekeeper, with its
rapamycin-binding site interacting with substrates to grant them access
to the restricted active site. Rapamycin-FKBP12 inhibits the kinase by
directly blocking substrate recruitment and by further restricting
active-site access. Yang et al. (2013) concluded that the structures
also revealed active-site residues and conformational changes that
underlie inhibitor potency and specificity.
GENE FUNCTION
Using Western blot and RT-PCR analyses, Rodgers et al. (2001) found that
insulin upregulated Gbl protein and mRNA levels in fully differentiated
mouse adipocytes in a concentration-dependent manner.
MTOR (FRAP1) and raptor (607130) are components of a signaling pathway
that regulates cell growth in response to nutrients and growth factors.
By immunoprecipitation analysis, Kim et al. (2003) identified GBL as an
additional subunit of the MTOR signaling complex in human embryonic
kidney cells. GBL bound the kinase domain of MTOR and stabilized the
interaction of raptor with MTOR. Loss-of-function experiments using
small interfering RNA showed that, like MTOR and raptor, GBL
participated in nutrient- and growth factor-mediated signaling to S6K1
(RPS6KB1; 608938), a downstream effector of MTOR, and in control of cell
size. Binding of GBL to MTOR strongly stimulated MTOR kinase activity
toward S6K1 and 4EBP1 (EIF4EPB1; 602223), and this effect was reversed
by stable interaction of raptor with MTOR. Nutrients and rapamycin
regulated the association of MTOR with raptor only in complexes that
also contained GBL. Kim et al. (2003) proposed that GBL and raptor
function together to modulate MTOR kinase activity.
*FIELD* RF
1. Kim, D.-H.; Sarbassov, D. D.; Ali, S. M.; Latek, R. R.; Guntur,
K. V. P.; Erdjument-Bromage, H.; Tempst, P.; Sabatani, D. M.: G-beta-L,
a positive regulator of the rapamycin-sensitive pathway required for
the nutrient-sensitive interaction between raptor and mTOR. Molec.
Cell 11: 895-904, 2003.
2. Rodgers, B. D.; Levine, M. A.; Bernier, M.; Montrose-Rafizadeh,
C.: Insulin regulation of a novel WD-40 repeat protein in adipocytes. J.
Endocr. 168: 325-332, 2001.
3. Yang, H.; Rudge, D. G.; Koos, J. D.; Vaidialingam, B.; Yang, H.
J.; Pavletich, N. P.: mTOR kinase structure, mechanism and regulation. Nature 497:
217-223, 2013.
*FIELD* CN
Ada Hamosh - updated: 05/22/2013
*FIELD* CD
Matthew B. Gross: 7/22/2008
*FIELD* ED
alopez: 05/22/2013
alopez: 3/31/2011
wwang: 7/22/2008
mgross: 7/22/2008
*RECORD*
*FIELD* NO
612190
*FIELD* TI
*612190 MTOR-ASSOCIATED PROTEIN LST8; MLST8
;;G-BETA-LIKE PROTEIN; GBL;;
G PROTEIN BETA SUBUNIT-LIKE PROTEIN;;
read moreLST8, S. CEREVISIAE, HOMOLOG OF; LST8;;
WAT1, S. POMBE, HOMOLOG OF; WAT1;;
POP3, S. POMBE, HOMOLOG OF; POP3
*FIELD* TX
CLONING
Rodgers et al. (2001) cloned rat Gbl and identified its human homolog by
database analysis. The predicted human GBL protein shares 96.6% amino
acid identity with rat Gbl, which contains 7 WD40 repeats similar to
those of G protein beta subunits (see 139380). Northern blot analysis
detected ubiquitous expression of Gbl in rat tissues.
Immunoprecipitation of membrane and cytosolic fractions of transfected
human embryonic kidney cells showed that rat Gbl was predominantly
cytosolic.
MAPPING
Rodgers et al. (2001) stated that the GBL gene maps to chromosome
16p13.3.
BIOCHEMICAL FEATURES
- Crystal Structure
Yang et al. (2013) reported cocrystal structures of a complex of
truncated mTOR (601231) and mammalian lethal with SEC13 protein-8
(mLST8) with an ATP transition state mimic and with ATP-site inhibitors.
The structures revealed an intrinsically active kinase conformation,
with catalytic residues and a catalytic mechanism remarkably similar to
canonical protein kinases. The active site is highly recessed owing to
the FKBP12 (186945)-rapamycin-binding (FRB) domain and an inhibitory
helix protruding from the catalytic cleft. mTOR-activating mutations map
to the structural framework that holds these elements in place,
indicating that the kinase is controlled by restricted access. In vitro
biochemistry showed that the FRB domain acts as a gatekeeper, with its
rapamycin-binding site interacting with substrates to grant them access
to the restricted active site. Rapamycin-FKBP12 inhibits the kinase by
directly blocking substrate recruitment and by further restricting
active-site access. Yang et al. (2013) concluded that the structures
also revealed active-site residues and conformational changes that
underlie inhibitor potency and specificity.
GENE FUNCTION
Using Western blot and RT-PCR analyses, Rodgers et al. (2001) found that
insulin upregulated Gbl protein and mRNA levels in fully differentiated
mouse adipocytes in a concentration-dependent manner.
MTOR (FRAP1) and raptor (607130) are components of a signaling pathway
that regulates cell growth in response to nutrients and growth factors.
By immunoprecipitation analysis, Kim et al. (2003) identified GBL as an
additional subunit of the MTOR signaling complex in human embryonic
kidney cells. GBL bound the kinase domain of MTOR and stabilized the
interaction of raptor with MTOR. Loss-of-function experiments using
small interfering RNA showed that, like MTOR and raptor, GBL
participated in nutrient- and growth factor-mediated signaling to S6K1
(RPS6KB1; 608938), a downstream effector of MTOR, and in control of cell
size. Binding of GBL to MTOR strongly stimulated MTOR kinase activity
toward S6K1 and 4EBP1 (EIF4EPB1; 602223), and this effect was reversed
by stable interaction of raptor with MTOR. Nutrients and rapamycin
regulated the association of MTOR with raptor only in complexes that
also contained GBL. Kim et al. (2003) proposed that GBL and raptor
function together to modulate MTOR kinase activity.
*FIELD* RF
1. Kim, D.-H.; Sarbassov, D. D.; Ali, S. M.; Latek, R. R.; Guntur,
K. V. P.; Erdjument-Bromage, H.; Tempst, P.; Sabatani, D. M.: G-beta-L,
a positive regulator of the rapamycin-sensitive pathway required for
the nutrient-sensitive interaction between raptor and mTOR. Molec.
Cell 11: 895-904, 2003.
2. Rodgers, B. D.; Levine, M. A.; Bernier, M.; Montrose-Rafizadeh,
C.: Insulin regulation of a novel WD-40 repeat protein in adipocytes. J.
Endocr. 168: 325-332, 2001.
3. Yang, H.; Rudge, D. G.; Koos, J. D.; Vaidialingam, B.; Yang, H.
J.; Pavletich, N. P.: mTOR kinase structure, mechanism and regulation. Nature 497:
217-223, 2013.
*FIELD* CN
Ada Hamosh - updated: 05/22/2013
*FIELD* CD
Matthew B. Gross: 7/22/2008
*FIELD* ED
alopez: 05/22/2013
alopez: 3/31/2011
wwang: 7/22/2008
mgross: 7/22/2008