Q9BVC4 · LST8_HUMAN
- ProteinTarget of rapamycin complex subunit LST8
- GeneMLST8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids326 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals (PubMed:12718876, PubMed:15268862, PubMed:15467718, PubMed:24403073).
mTORC1 is activated in response to growth factors or amino acids (PubMed:12718876, PubMed:15268862, PubMed:15467718, PubMed:24403073).
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) (PubMed:12718876, PubMed:15268862, PubMed:15467718, PubMed:24403073).
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 (PubMed:24403073).
The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:24403073).
Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity (PubMed:12718876).
In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity (PubMed:12718876).
mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (PubMed:15467718).
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 (PubMed:15467718).
mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718).
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 (PubMed:15467718).
mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:15467718).
mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' (PubMed:15467718).
mTORC1 is activated in response to growth factors or amino acids (PubMed:12718876, PubMed:15268862, PubMed:15467718, PubMed:24403073).
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) (PubMed:12718876, PubMed:15268862, PubMed:15467718, PubMed:24403073).
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 (PubMed:24403073).
The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:24403073).
Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity (PubMed:12718876).
In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity (PubMed:12718876).
mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (PubMed:15467718).
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 (PubMed:15467718).
mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718).
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 (PubMed:15467718).
mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:15467718).
mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' (PubMed:15467718).
GO annotations
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTarget of rapamycin complex subunit LST8
- Short namesTORC subunit LST8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9BVC4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 51 | Reduced ubiquitination by the SCF(FBXW7) complex. | ||||
Sequence: T → A | ||||||
Mutagenesis | 55 | Does not affect ubiquitination by the SCF(FBXW7) complex. | ||||
Sequence: S → A | ||||||
Mutagenesis | 72 | Impairs interaction with MTOR. | ||||
Sequence: S → D | ||||||
Mutagenesis | 192 | Abolishes interaction with MTOR. | ||||
Sequence: G → D | ||||||
Mutagenesis | 320 | Impairs interaction with MTOR. | ||||
Sequence: F → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 399 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | In isoform Q9BVC4-4; N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000326499 | 1-326 | UniProt | Target of rapamycin complex subunit LST8 | |||
Sequence: MNTSPGTVGSDPVILATAGYDHTVRFWQAHSGICTRTVQHQDSQVNALEVTPDRSMIAAAGYQHIRMYDLNSNNPNPIISYDGVNKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQCQRIFQVNAPINCVCLHPNQAELIVGDQSGAIHIWDLKTDHNEQLIPEPEVSITSAHIDPDASYMAAVNSTGNCYVWNLTGGIGDEVTQLIPKTKIPAHTRYALQCRFSPDSTLLATCSADQTCKIWRTSNFSLMTELSIKSGNPGESSRGWMWGCAFSGDSQYIVTASSDNLARLWCVETGEIKREYGGHQKAVVCLAFNDSVLG | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 7 | UniProt | In isoform Q9BVC4-4; Phosphoserine | ||||
Sequence: T | |||||||
Modified residue | 51 | UniProt | Phosphothreonine; by CDK1 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 80 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 81 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylation at Thr-51 by CDK1 promotes ubiquitination by the SCF(FBXW7) complex, followed by degradation.
Ubiquitination by the SCF(FBXW7) and SCF(FBXW11) complexes following phosphorylation at Thr-51 by CDK1, leads to its degradation by the proteasome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Broadly expressed, with highest levels in skeletal muscle, heart and kidney.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:12408816, PubMed:12718876, PubMed:15268862, PubMed:17510057, PubMed:23636326, PubMed:24403073, PubMed:26678875, PubMed:27909983, PubMed:29236692, PubMed:31601764, PubMed:34519268, PubMed:34519269, PubMed:36697823).
mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity (PubMed:31601764).
mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:12408816).
Within mTORC1, interacts directly with MTOR and RPTOR (PubMed:12718876).
Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15268862, PubMed:15467718, PubMed:17461779, PubMed:17510057, PubMed:23636326, PubMed:26678875, PubMed:34519268).
Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin (PubMed:12408816).
mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity (PubMed:34519268, PubMed:34519269).
Interacts with RHEB (PubMed:15854902).
Interacts with MEAK7 (PubMed:29750193).
Interacts with SIK3 (PubMed:30232230).
Interacts with SLC38A7; this interaction promotes the recruitment of mTORC1 to the lysosome and its subsequent activation (PubMed:35561222).
mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity (PubMed:31601764).
mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:12408816).
Within mTORC1, interacts directly with MTOR and RPTOR (PubMed:12718876).
Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15268862, PubMed:15467718, PubMed:17461779, PubMed:17510057, PubMed:23636326, PubMed:26678875, PubMed:34519268).
Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin (PubMed:12408816).
mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity (PubMed:34519268, PubMed:34519269).
Interacts with RHEB (PubMed:15854902).
Interacts with MEAK7 (PubMed:29750193).
Interacts with SIK3 (PubMed:30232230).
Interacts with SLC38A7; this interaction promotes the recruitment of mTORC1 to the lysosome and its subsequent activation (PubMed:35561222).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9BVC4 | MTOR P42345 | 6 | EBI-1387471, EBI-359260 | |
BINARY | Q9BVC4 | RPTOR Q8N122 | 3 | EBI-1387471, EBI-1567928 | |
BINARY | Q9BVC4-1 | MTOR P42345 | 7 | EBI-16056342, EBI-359260 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 1-37 | WD 1 | ||||
Sequence: MNTSPGTVGSDPVILATAGYDHTVRFWQAHSGICTRT | ||||||
Repeat | 40-80 | WD 2 | ||||
Sequence: HQDSQVNALEVTPDRSMIAAAGYQHIRMYDLNSNNPNPIIS | ||||||
Repeat | 83-122 | WD 3 | ||||
Sequence: GVNKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQCQ | ||||||
Repeat | 126-165 | WD 4 | ||||
Sequence: QVNAPINCVCLHPNQAELIVGDQSGAIHIWDLKTDHNEQL | ||||||
Repeat | 168-207 | WD 5 | ||||
Sequence: EPEVSITSAHIDPDASYMAAVNSTGNCYVWNLTGGIGDEV | ||||||
Repeat | 218-257 | WD 6 | ||||
Sequence: AHTRYALQCRFSPDSTLLATCSADQTCKIWRTSNFSLMTE | ||||||
Repeat | 268-309 | WD 7 | ||||
Sequence: SSRGWMWGCAFSGDSQYIVTASSDNLARLWCVETGEIKREYG |
Sequence similarities
Belongs to the WD repeat LST8 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q9BVC4-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length326
- Mass (Da)35,876
- Last updated2001-06-01 v1
- Checksum43A600D4EF2B6543
Q9BVC4-3
- Name2
- Differences from canonical
- 1-66: Missing
Q9BVC4-4
- Name3
Q9BVC4-5
- Name4
- Differences from canonical
- 44-44: Missing
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_032666 | 1 | in isoform 3 | |||
Sequence: M → MEHAPWSPGASSRARAGHTM | ||||||
Alternative sequence | VSP_032665 | 1-66 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_047368 | 44 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 56 | in Ref. 2; BAB13990 | ||||
Sequence: M → V | ||||||
Sequence conflict | 153 | in Ref. 5; AAH88354 | ||||
Sequence: H → Y | ||||||
Alternative sequence | VSP_032667 | 192-198 | in isoform 3 | |||
Sequence: GNCYVWN → APRHLLG | ||||||
Alternative sequence | VSP_032668 | 199-326 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 248 | in Ref. 1; AAO73410 | ||||
Sequence: R → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY223837 EMBL· GenBank· DDBJ | AAO73410.1 EMBL· GenBank· DDBJ | mRNA | ||
AK021536 EMBL· GenBank· DDBJ | BAG51036.1 EMBL· GenBank· DDBJ | mRNA | ||
AK022227 EMBL· GenBank· DDBJ | BAB13990.1 EMBL· GenBank· DDBJ | mRNA | ||
AK302201 EMBL· GenBank· DDBJ | BAG63562.1 EMBL· GenBank· DDBJ | mRNA | ||
AC009065 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471112 EMBL· GenBank· DDBJ | EAW85538.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471112 EMBL· GenBank· DDBJ | EAW85539.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
CH471112 EMBL· GenBank· DDBJ | EAW85541.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471112 EMBL· GenBank· DDBJ | EAW85542.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001313 EMBL· GenBank· DDBJ | AAH01313.1 EMBL· GenBank· DDBJ | mRNA | ||
BC017119 EMBL· GenBank· DDBJ | AAH17119.1 EMBL· GenBank· DDBJ | mRNA | ||
BC052292 EMBL· GenBank· DDBJ | AAH52292.1 EMBL· GenBank· DDBJ | mRNA | ||
BC088354 EMBL· GenBank· DDBJ | AAH88354.1 EMBL· GenBank· DDBJ | mRNA | ||
AF195883 EMBL· GenBank· DDBJ | AAF04308.1 EMBL· GenBank· DDBJ | mRNA |