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Protein

Target of rapamycin complex subunit LST8

Gene

Mlst8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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'.1 Publication

GO - Molecular functioni

GO - Biological processi

  • positive regulation of actin filament polymerization Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of TOR signaling Source: MGI
  • regulation of actin cytoskeleton organization Source: MGI
  • regulation of GTPase activity Source: MGI
  • TORC1 signaling Source: MGI
  • TOR signaling Source: GO_Central

Enzyme and pathway databases

ReactomeiR-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1632852 Macroautophagy
R-MMU-165159 mTOR signalling
R-MMU-166208 mTORC1-mediated signalling
R-MMU-3371571 HSF1-dependent transactivation
R-MMU-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-MMU-389357 CD28 dependent PI3K/Akt signaling
R-MMU-5218920 VEGFR2 mediated vascular permeability
R-MMU-5628897 TP53 Regulates Metabolic Genes
R-MMU-6804757 Regulation of TP53 Degradation
R-MMU-8943724 Regulation of PTEN gene transcription

Names & Taxonomyi

Protein namesi
Recommended name:
Target of rapamycin complex subunit LST8
Short name:
TORC subunit LST8
Alternative name(s):
G protein beta subunit-like
Short name:
Protein GbetaL
Mammalian lethal with SEC13 protein 8
Short name:
mLST8
Gene namesi
Name:Mlst8
Synonyms:Gbl, Lst8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1929514 Mlst8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Death around E10.5 due to multiple defects in vascular system development. In addition, they exhibit a delayed development of their cephalic region.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003265001 – 326Target of rapamycin complex subunit LST8Add BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9DCJ1
MaxQBiQ9DCJ1
PaxDbiQ9DCJ1
PeptideAtlasiQ9DCJ1
PRIDEiQ9DCJ1

PTM databases

iPTMnetiQ9DCJ1
PhosphoSitePlusiQ9DCJ1

Expressioni

Gene expression databases

BgeeiENSMUSG00000024142
GenevisibleiQ9DCJ1 MM

Interactioni

Subunit structurei

Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR (By similarity). mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (By similarity). Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Interacts directly with MTOR and RPTOR. Interacts with RHEB (By similarity). Interacts with MTOR.By similarity2 Publications

Protein-protein interaction databases

BioGridi208141, 3 interactors
DIPiDIP-46976N
IntActiQ9DCJ1, 4 interactors
STRINGi10090.ENSMUSP00000065004

Structurei

3D structure databases

ProteinModelPortaliQ9DCJ1
SMRiQ9DCJ1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati1 – 37WD 1Add BLAST37
Repeati40 – 80WD 2Add BLAST41
Repeati83 – 122WD 3Add BLAST40
Repeati126 – 165WD 4Add BLAST40
Repeati168 – 207WD 5Add BLAST40
Repeati218 – 257WD 6Add BLAST40
Repeati268 – 309WD 7Add BLAST42

Sequence similaritiesi

Belongs to the WD repeat LST8 family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0315 Eukaryota
ENOG410XPVD LUCA
GeneTreeiENSGT00390000014795
HOGENOMiHOG000208395
HOVERGENiHBG054763
InParanoidiQ9DCJ1
KOiK08266
OMAiLISCDQA
OrthoDBiEOG091G0ADW
PhylomeDBiQ9DCJ1
TreeFamiTF318577

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR037588 MLST8
IPR011047 Quinoprotein_ADH-like_supfam
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
PANTHERiPTHR19842 PTHR19842, 1 hit
PfamiView protein in Pfam
PF00400 WD40, 5 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00320 WD40, 6 hits
SUPFAMiSSF50998 SSF50998, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

Q9DCJ1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNTTPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEI
60 70 80 90 100
TPDRSMIAAA GYQHIRMYDL NSNNPNPIIS YDGVSKNIAS VGFHEDGRWM
110 120 130 140 150
YTGGEDCTAR IWDLRSRNLQ CQRIFQVNAP INCVCLHPNQ AELIVGDQSG
160 170 180 190 200
AIHIWDLKTD HNEQLIPEPE SSITSAHIDP DASYMAAVNS AGNCYVWNLT
210 220 230 240 250
GGIGDDVTQL IPKTKIPAHT RYALQCRFSP DSTLLATCSA DQTCKIWRTS
260 270 280 290 300
NFSLMTELSI KSSNPGESSR GWMWGCAFSG DSQYIVTASS DNLARLWCVE
310 320
TGEIKREYGG HQKAVVCLAF NDSVLG
Length:326
Mass (Da):35,851
Last modified:June 1, 2001 - v1
Checksum:i2F6E75383905667A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24V → G in BAC39006 (PubMed:16141072).Curated1
Sequence conflicti127V → G in BAC39006 (PubMed:16141072).Curated1
Sequence conflicti171S → F in AAF37719 (PubMed:11182770).Curated1
Sequence conflicti195Y → F in AAF37719 (PubMed:11182770).Curated1
Sequence conflicti206D → E in AAF37719 (PubMed:11182770).Curated1
Sequence conflicti229S → G in BAC33243 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF237676 mRNA Translation: AAF37719.1
AK002751 mRNA Translation: BAB22328.1
AK038515 mRNA Translation: BAC30024.1
AK040100 mRNA Translation: BAC30510.1
AK048102 mRNA Translation: BAC33243.1
AK077680 mRNA Translation: BAC36952.1
AK083731 mRNA Translation: BAC39006.1
BC015279 mRNA Translation: AAH15279.1
CCDSiCCDS28484.1
RefSeqiNP_001239392.1, NM_001252463.1
NP_001239393.1, NM_001252464.1
NP_001239394.1, NM_001252465.1
NP_064372.2, NM_019988.5
UniGeneiMm.289516

Genome annotation databases

EnsembliENSMUST00000070888; ENSMUSP00000065004; ENSMUSG00000024142
ENSMUST00000179163; ENSMUSP00000136287; ENSMUSG00000024142
GeneIDi56716
KEGGimmu:56716
UCSCiuc008awg.3 mouse

Similar proteinsi

Entry informationi

Entry nameiLST8_MOUSE
AccessioniPrimary (citable) accession number: Q9DCJ1
Secondary accession number(s): Q8BNG8, Q8C882, Q9JKK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: June 1, 2001
Last modified: June 20, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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