CPLM-020237

Genbank Nucleotide ID

Target of rapamycin complex subunit LST8

Protein Synonyms/Alias

TORC subunit LST8; G protein beta subunit-like; Gable; Protein GbetaL; Mammalian lethal with SEC13 protein 8; mLST8

Homo sapiens (Human)

Position	Peptide	Type	References
86	ISYDGVNKNIASVGF	ubiquitination	[1, 2]
245	CSADQTCKIWRTSNF	ubiquitination	[2, 3, 4]
261	LMTELSIKSGNPGES	ubiquitination	[1, 5]
305	CVETGEIKREYGGHQ	ubiquitination	[2, 5]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[5] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]

Functional Description

Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1- mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient- poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum- induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.

REPEAT 1 37 WD 1.
REPEAT 40 80 WD 2.
REPEAT 83 122 WD 3.
REPEAT 126 165 WD 4.
REPEAT 168 207 WD 5.
REPEAT 218 257 WD 6.
REPEAT 268 309 WD 7.
MOD_RES 1 1 N-acetylmethionine.

3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Phosphoprotein; Reference proteome; Repeat; WD repeat.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO:0030838; P:positive regulation of actin filament polymerization; IEA:Compara.
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Compara.
GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
GO:0032314; P:regulation of Rac GTPase activity; IEA:Compara.
GO:0031295; P:T cell costimulation; TAS:Reactome.

IPR020472; G-protein_beta_WD-40_rep.
IPR015943; WD40/YVTN_repeat-like_dom.
IPR001680; WD40_repeat.
IPR019775; WD40_repeat_CS.
IPR017986; WD40_repeat_dom.

PS00678; WD_REPEATS_1
PS50082; WD_REPEATS_2
PS50294; WD_REPEATS_REGION

PR00320; GPROTEINBRPT.