Mlst8
entrez
56716
canonical
uniprot
Q9DCJ1
canonical
ensembl
ENSMUSG00000024142
resolver
ensp
ENSMUSP00000065004
resolver
ensp
ENSMUSP00000136287
resolver
ensp
ENSMUSP00000157137
resolver
ensp
ENSMUSP00000157225
resolver
ensp
ENSMUSP00000157301
resolver
ensp
ENSMUSP00000173451
resolver
ensp
ENSMUSP00000173452
resolver
enst
ENSMUST00000070888
resolver
enst
ENSMUST00000179163
resolver
enst
ENSMUST00000234335
resolver
enst
ENSMUST00000234543
resolver
enst
ENSMUST00000234686
resolver
genesymbol
Mlst8
resolver
genesymbol_syn
Gbl
resolver
genesymbol_syn
Lst8
resolver
uniprot
A0A3Q4EC26
resolver
uniprot
Q8BNG8
resolver
uniprot
Q8C882
resolver
uniprot
Q9JKK6
resolver
uniprot_entry
A0A3Q4EC26_MOUSE
resolver
uniprot_entry
LST8_MOUSE
resolver
uniprot_sec
Q8BNG8
resolver
uniprot_sec
Q8C882
resolver
uniprot_sec
Q9JKK6
resolver
amino_acid_sequence
MNTTPGTVGSDPVILATAGYDHTVRFWQAHSGICTRTVQHQDSQVNALEITPDRSMIAAAGYQHIRMYDLNSNNPNPIISYDGVSKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQCQRIFQVNAPINCVCLHPNQAELIVGDQSGAIHIWDLKTDHNEQLIPEPESSITSAHIDPDASYMAAVNSAGNCYVWNLTGGIGDDVTQLIPKTKIPAHTRYALQCRFSPDSTLLATCSADQTCKIWRTSNFSLMTELSIKSSNPGESSRGWMWGCAFSGDSQYIVTASSDNLARLWCVETGEIKREYGGHQKAVVCLAFNDSVLG
uniprot
proteins
function
FUNCTION: Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals (PubMed:17141160). mTORC1 is activated in response to growth factors or amino acids (By similarity). In response to nutrients, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (By similarity). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy (By similarity). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (By similarity). Within mTORC1, MLST8 interacts directly with MTOR and enhances its kinase activity (By similarity). In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity (By similarity). As part of the mTORC2 complex, transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (By similarity). mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (By similarity). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (By similarity). mTORC2 functions upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (By similarity). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (By similarity). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (By similarity). mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422' (By similarity). mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' (By similarity). Within mTORC2, MLST8 acts as a bridge between MAPKAP1/SIN1 and MTOR (By similarity). {ECO:0000250|UniProtKB:Q9BVC4, ECO:0000269|PubMed:17141160}.
uniprot
proteins
mass_dalton
35851
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-51 by CDK1 promotes ubiquitination by the SCF(FBXW7) complex, followed by degradation. {ECO:0000250|UniProtKB:Q9BVC4}.; PTM: Ubiquitination by the SCF(FBXW7) and SCF(FBXW11) complexes following phosphorylation at Thr-51 by CDK1, leads to its degradation by the proteasome (By similarity). Ubiquitination at Lys-305 and Lys-313 by TRAF2 via 'Lys-63'-linked polyubiquitin chains inhibits formation of the mTORC2 complex, while promoting formation of the mTORC1 complex: ubiquitination disrupts the interaction between MLST8 and MAPKAP1/SIN1 to favor mTORC1 assembly (PubMed:28489822). Deubiquitination at Lys-305 and Lys-313 by OTUD7B promotes MLST8 interaction with MAPKAP1/SIN1, facilitating mTORC2 assembly (PubMed:28489822). {ECO:0000250|UniProtKB:Q9BVC4, ECO:0000269|PubMed:28489822}.; PTM: Sumoylation with SUMO1, SUMO2 and SUMO3 promotes assembly of both mTORC1 and mTORC2 complexes. {ECO:0000269|PubMed:38395307}.
uniprot
proteins
protein_family
WD repeat LST8 family
uniprot
proteins
pubmed
11182770
uniprot
proteins
pubmed
12718876
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17141160
uniprot
proteins
pubmed
20801936
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
28489822
uniprot
proteins
pubmed
38395307
uniprot
proteins
sequence_length
326
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9BVC4}. Cytoplasm {ECO:0000250|UniProtKB:Q9Z2K5}. Note=Targeting to lysosomal membrane depends on amino acid availability: mTORC1 is recruited to lysosome membranes via interaction with GTP-bound form of RagA/RRAGA (or RagB/RRAGB) in complex with the GDP-bound form of RagC/RRAGC (or RagD/RRAGD), promoting its mTORC1 recruitment to the lysosomes. {ECO:0000250|UniProtKB:Q9BVC4}.
uniprot
proteins