Q9NXC5 · MIOS_HUMAN
- ProteinGATOR2 complex protein MIOS
- GeneMIOS
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids875 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027).
The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027).
GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027).
In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027).
In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25263562, PubMed:25457612, PubMed:26586190, PubMed:27487210).
Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex (PubMed:35831510).
The GATOR2 complex is required for brain myelination (By similarity).
The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027).
GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027).
In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027).
In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25263562, PubMed:25457612, PubMed:26586190, PubMed:27487210).
Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex (PubMed:35831510).
The GATOR2 complex is required for brain myelination (By similarity).
Activity regulation
The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids (PubMed:25263562, PubMed:26586190, PubMed:26972053, PubMed:27487210, PubMed:35831510).
In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated (PubMed:25263562, PubMed:26586190, PubMed:26972053, PubMed:27487210, PubMed:35831510).
In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated (PubMed:25263562, PubMed:26586190, PubMed:26972053, PubMed:27487210, PubMed:35831510).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 737 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 740 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 775 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 778 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 788 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 827 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 830 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 830 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 832 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 835 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 838 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 849 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 854 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 858 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell junction | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | GATOR2 complex | |
Cellular Component | lysosomal membrane | |
Cellular Component | nucleoplasm | |
Molecular Function | metal ion binding | |
Biological Process | cellular response to amino acid starvation | |
Biological Process | cellular response to nutrient levels | |
Biological Process | central nervous system myelin formation | |
Biological Process | negative regulation of TORC1 signaling | |
Biological Process | oligodendrocyte differentiation | |
Biological Process | oligodendrocyte progenitor proliferation | |
Biological Process | positive regulation of TORC1 signaling | |
Biological Process | protein-containing complex localization |
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGATOR2 complex protein MIOS
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NXC5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 560 | Impaired assembly of the GATOR2 complex. | ||||
Sequence: A → E | ||||||
Mutagenesis | 785-788 | Impaired amino-acid-mediated mTORC1 activation. | ||||
Sequence: CALC → AALA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 995 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000329404 | 1-875 | UniProt | GATOR2 complex protein MIOS | |||
Sequence: MSGTKPDILWAPHHVDRFVVCDSELSLYHVESTVNSELKAGSLRLSEDSAATLLSINSDTPYMKCVAWYLNYDPECLLAVGQANGRVVLTSLGQDHNSKFKDLIGKEFVPKHARQCNTLAWNPLDSNWLAAGLDKHRADFSVLIWDICSKYTPDIVPMEKVKLSAGETETTLLVTKPLYELGQNDACLSLCWLPRDQKLLLAGMHRNLAIFDLRNTSQKMFVNTKAVQGVTVDPYFHDRVASFYEGQVAIWDLRKFEKPVLTLTEQPKPLTKVAWCPTRTGLLATLTRDSNIIRLYDMQHTPTPIGDETEPTIIERSVQPCDNYIASFAWHPTSQNRMIVVTPNRTMSDFTVFERISLAWSPITSLMWACGRHLYECTEEENDNSLEKDIATKMRLRALSRYGLDTEQVWRNHILAGNEDPQLKSLWYTLHFMKQYTEDMDQKSPGNKGSLVYAGIKSIVKSSLGMVESSRHNWSGLDKQSDIQNLNEERILALQLCGWIKKGTDVDVGPFLNSLVQEGEWERAAAVALFNLDIRRAIQILNEGASSEKGDLNLNVVAMALSGYTDEKNSLWREMCSTLRLQLNNPYLCVMFAFLTSETGSYDGVLYENKVAVRDRVAFACKFLSDTQLNRYIEKLTNEMKEAGNLEGILLTGLTKDGVDLMESYVDRTGDVQTASYCMLQGSPLDVLKDERVQYWIENYRNLLDAWRFWHKRAEFDIHRSKLDPSSKPLAQVFVSCNFCGKSISYSCSAVPHQGRGFSQYGVSGSPTKSKVTSCPGCRKPLPRCALCLINMGTPVSSCPGGTKSDEKVDLSKDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHAECPVSACTCKCMQLDTTGNLVPAETVQP | |||||||
Modified residue | 759 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 764 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 766 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 766 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 768 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59 (PubMed:23723238, PubMed:35831510, PubMed:36528027).
The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine (PubMed:26972053).
CASTOR1 and CASTOR2 convey leucine availability via direct interaction with MIOS (PubMed:35831510).
The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids (PubMed:25263562, PubMed:25457612, PubMed:26586190).
Interacts with SAR1A and SAR1B; the interaction is direct, disrupted by leucine and mediates the interaction of SAR1A or SAR1B with the GATOR2 complex to negatively regulate the TORC1 signaling upon leucine deprivation (PubMed:34290409).
The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine (PubMed:26972053).
CASTOR1 and CASTOR2 convey leucine availability via direct interaction with MIOS (PubMed:35831510).
The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids (PubMed:25263562, PubMed:25457612, PubMed:26586190).
Interacts with SAR1A and SAR1B; the interaction is direct, disrupted by leucine and mediates the interaction of SAR1A or SAR1B with the GATOR2 complex to negatively regulate the TORC1 signaling upon leucine deprivation (PubMed:34290409).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NXC5 | CASTOR1 Q8WTX7 | 7 | EBI-2515122, EBI-10276168 | |
BINARY | Q9NXC5 | CASTOR2 A6NHX0 | 2 | EBI-2515122, EBI-11102839 | |
BINARY | Q9NXC5 | SESN2 P58004 | 5 | EBI-2515122, EBI-3939642 | |
BINARY | Q9NXC5 | WDR24 Q96S15 | 18 | EBI-2515122, EBI-746424 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 58-100 | WD 1 | ||||
Sequence: SDTPYMKCVAWYLNYDPECLLAVGQANGRVVLTSLGQDHNSKF | ||||||
Repeat | 111-155 | WD 2 | ||||
Sequence: KHARQCNTLAWNPLDSNWLAAGLDKHRADFSVLIWDICSKYTPDI | ||||||
Repeat | 182-221 | WD 3 | ||||
Sequence: GQNDACLSLCWLPRDQKLLLAGMHRNLAIFDLRNTSQKMF | ||||||
Repeat | 223-261 | WD 4 | ||||
Sequence: NTKAVQGVTVDPYFHDRVASFYEGQVAIWDLRKFEKPVL | ||||||
Repeat | 265-306 | WD 5 | ||||
Sequence: EQPKPLTKVAWCPTRTGLLATLTRDSNIIRLYDMQHTPTPIG | ||||||
Repeat | 395-437 | WD 6 | ||||
Sequence: RLRALSRYGLDTEQVWRNHILAGNEDPQLKSLWYTLHFMKQYT | ||||||
Zinc finger | 735-781 | C4-type | ||||
Sequence: VSCNFCGKSISYSCSAVPHQGRGFSQYGVSGSPTKSKVTSCPGCRKP | ||||||
Zinc finger | 782-863 | RING-type; atypical | ||||
Sequence: LPRCALCLINMGTPVSSCPGGTKSDEKVDLSKDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHAECPVSACTCKCMQLDT |
Sequence similarities
Belongs to the WD repeat mio family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9NXC5-1
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
- Length875
- Mass (Da)98,584
- Last updated2008-04-08 v2
- Checksum481D3AA0C9A3A1CB
Q9NXC5-2
- Name2
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK000330 EMBL· GenBank· DDBJ | BAA91090.1 EMBL· GenBank· DDBJ | mRNA | ||
AC004982 EMBL· GenBank· DDBJ | AAC31788.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
CH471073 EMBL· GenBank· DDBJ | EAW93598.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471073 EMBL· GenBank· DDBJ | EAW93601.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005883 EMBL· GenBank· DDBJ | AAH05883.2 EMBL· GenBank· DDBJ | mRNA | ||
BC140833 EMBL· GenBank· DDBJ | AAI40834.1 EMBL· GenBank· DDBJ | mRNA | ||
BC140834 EMBL· GenBank· DDBJ | AAI40835.1 EMBL· GenBank· DDBJ | mRNA | ||
AL136892 EMBL· GenBank· DDBJ | CAB66826.2 EMBL· GenBank· DDBJ | mRNA |