Protein: GATOR2 complex protein MIOS (Q802U2)
Organism: {ECO:0000305};
Function: As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1. 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. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex. Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex
Subcellular location: Lysosome membrane
Sequence: MSSGYKPDILWSPHHADRYVICDTELSLYRIGPSGSSETKAGALQLSEETAATLLAINSDTPFMKCVAWYPKHEPECLLAVGHTNGRVVLTSLGQSHNSKSKDLAGKEFVPKHARQCNTLAWNPVDSNWLAAGLDKHRADFSVLIWDISSKFSPEAVPAEKVRLSGDADSGLLVTKPLYELGQNDACLSLCWLPRDHQKLLLAGMHRNLAIFDLRNTSQKTFVNTKAIQGVTVDPHFQDRVASYFEGQVAIWDLRKFEKPVFTLNEQPKPLTKVAWCPTRMGLLATLTRDSNIIRLYDMQHTPMPFGDEVEPTIMERGVQPCSESIISSFAWHPSAQNRMVVVSPSRVMNDFTLFERISLAWSSTTSLMWACGRHLYECAEDSGQAAEAEKDIATKMRERAQSRYGHDTVQVWRNHVLAGGDDPQLRSLWYTLHFMKQYTENVEQKQQSNKQSLIYSGIKNIVKSSSGTTETRRCWSGSDRQTDVPRFHSEERSLALQLCGWISQGPDTDVEPFLKSLEQEGEWERAAAVALFNLDIRRAIQILNKGASSEKGDLNLNVVAMALSGYTDEKNSLWREMCSSLRLQLKKPYLCIMFAFLTSEPGAYDGVLYESRVAVRDRVAFACMFLNDAQLPRYIDKLTNEMKEAGNLEGILLTGLTKDGVDLMESYVDRTGDVQTASFCMLKGSPGEVLKDPRVQCWIENYRNLLDAWRFWHKRAEFDIHRSKLDPSSKPLAQVFVSCNFCGKSISYSCSAMPHQGRGFSQYGVSGSPTKSKVTSCPGCRKPLPRCALCLMNMGTPVSSCPGTGKADEKADLTRDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHSECPVSACTCKCMQLDTTGNLVPSDSV
InterPro domains: - IPR037593: MIOS/Sea4 (family) [488-870]
- IPR031488: GATOR2 complex protein MIO, zinc-ribbon like domain (domain) [740-862]
- IPR049092: MIOS-like, alpha-solenoid domain (domain) [397-626]
- IPR036322: WD40-repeat-containing domain superfamily (homologous_superfamily) [66-368]
- IPR015943: WD40/YVTN repeat-like-containing domain superfamily (homologous_superfamily) [64-355]
- IPR001680: WD40 repeat (repeat) [50-356]
Interaction partners: - Nucleoporin SEH1
- GATOR2 complex protein WDR59 isoform X1
- GATOR2 complex protein WDR24
- GATOR complex protein NPRL2
- Protein SEC13 homolog
- Sestrin-2
- KICSTOR complex protein kaptin
- Sestrin-1
- Zinc finger C2HC domain-containing protein 1A
- Cytosolic arginine sensor for mTORC1 subunit 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0009605 (response to external stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0023056 (positive regulation of signaling), GO:0006950 (response to stress), GO:0048584 (positive regulation of response to stimulus), GO:0007154 (cell communication), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0009991 (response to extracellular stimulus), GO:0009967 (positive regulation of signal transduction), GO:0010647 (positive regulation of cell communication), GO:0031668 (cellular response to extracellular stimulus), GO:0009966 (regulation of signal transduction), GO:0042594 (response to starvation), GO:0010646 (regulation of cell communication), GO:0071496 (cellular response to external stimulus), GO:0033554 (cellular response to stress), GO:1902533 (positive regulation of intracellular signal transduction), GO:1990928 (response to amino acid starvation), GO:0031669 (cellular response to nutrient levels), GO:0009267 (cellular response to starvation), GO:0031667 (response to nutrient levels), GO:1902531 (regulation of intracellular signal transduction), GO:0034198 (cellular response to amino acid starvation), GO:0032006 (regulation of TOR signaling), GO:0032008 (positive regulation of TOR signaling)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0035859 (Seh1-associated complex), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0030054 (cell junction), GO:0005654 (nucleoplasm), GO:0061700 (GATOR2 complex), GO:0005773 (vacuole), GO:0031090 (organelle membrane), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0005774 (vacuolar membrane), GO:0098588 (bounding membrane of organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005764 (lysosome), GO:0098852 (lytic vacuole membrane), GO:0005634 (nucleus), GO:0005765 (lysosomal membrane)