DEPTOR
entrez
64798
canonical
uniprot
Q8TB45
canonical
ensembl
ENSG00000155792
resolver
ensp
ENSP00000286234
resolver
ensp
ENSP00000430457
resolver
genesymbol
DEPTOR
resolver
genesymbol_syn
DEPDC6
resolver
hgnc
HGNC:22953
resolver
uniprot
B2RCL9
resolver
uniprot
B4DN97
resolver
uniprot
E7EV87
resolver
uniprot
Q96EQ1
resolver
uniprot
Q9H0R7
resolver
uniprot
Q9H894
resolver
uniprot
Q9HA07
resolver
uniprot_entry
DPTOR_HUMAN
resolver
uniprot_sec
B2RCL9
resolver
uniprot_sec
B4DN97
resolver
uniprot_sec
E7EV87
resolver
uniprot_sec
Q96EQ1
resolver
uniprot_sec
Q9H0R7
resolver
uniprot_sec
Q9H894
resolver
uniprot_sec
Q9HA07
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited upon phosphatidic acid-binding: phosphatidic acid produced upon mitogenic stimulation promotes DEPTOR dissociatiom from the mTORC1 and mTORC2 complexes, leading to their activation (PubMed:25936805, PubMed:33865870). Specifically binds unsaturated phosphatidic acid, such as 16:0-18:1, 18:0-18:1 and di-18:1 (PubMed:25936805). Inhibited when nutrients are present via a feedback loop: phosphorylation by MTOR promotes DEPTOR ubiquitination and degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877). {ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:33865870}.
uniprot
proteins
amino_acid_sequence
MEEGGSTGSAGSDSSTSGSGGAQQRELERMAEVLVTGEQLRLRLHEEKVIKDRRHHLKTYPNCFVAKELIDWLIEHKEASDRETAIKLMQKLADRGIIHHVCDEHKEFKDVKLFYRFRKDDGTFPLDNEVKAFMRGQRLYEKLMSPENTLLQPREEEGVKYERTFMASEFLDWLVQEGEATTRKEAEQLCHRLMEHGIIQHVSNKHPFVDSNLLYQFRMNFRRRRRLMELLNEKSPSSQETHDSPFCLRKQSHDNRKSTSFMSVSPSKEIKIVSAVRRSSMSSCGSSGYFSSSPTLSSSPPVLCNPKSVLKRPVTSEELLTPGAPYARKTFTIVGDAVGWGFVVRGSKPCHIQAVDPSGPAAAAGMKVCQFVVSVNGLNVLHVDYRTVSNLILTGPRTIVMEVMEELEC
uniprot
proteins
function
FUNCTION: Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519268, PubMed:34519269). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519268, PubMed:34519269). {ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:34519268, ECO:0000269|PubMed:34519269}.
uniprot
proteins
mass_dalton
46294
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="R->A: Decreased phosphatidic acid-binding."; /evidence="ECO:0000269|PubMed:33865870"; MUTAGEN 54; /note="R->A: Decreased phosphatidic acid-binding."; /evidence="ECO:0000269|PubMed:33865870"; MUTAGEN 58; /note="K->A: Decreased phosphatidic acid-binding."; /evidence="ECO:0000269|PubMed:33865870"; MUTAGEN 225; /note="R->A: Decreased phosphatidic acid-binding."; /evidence="ECO:0000269|PubMed:33865870"; MUTAGEN 231; /note="L->D: Decreased phosphatidic acid-binding."; /evidence="ECO:0000269|PubMed:33865870"; MUTAGEN 235; /note="S->A: Decreased phosphorylation, leading to impaired deubiquitination by USP7."; /evidence="ECO:0000269|PubMed:35216969"; MUTAGEN 235; /note="S->D: Mimics phosphorylation, leading to slightly increased stability."; /evidence="ECO:0000269|PubMed:35216969"; MUTAGEN 241; /note="T->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 244; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 258; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 259; /note="T->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-263, A-265, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 263; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-265, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 265; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-282, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 282; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-283, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 283; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-287, A-293, A-297, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 286..291; /note="SSGYFS->DDGYFD: Mimics phosphorylation; promoting association with the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:22017877"; MUTAGEN 286; /note="S->A: Reduced ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877"; MUTAGEN 287; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-293, A-297, A-298 and A-299. Reduced ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:25936805"; MUTAGEN 289; /note="Y->E: Mimics phosphorylation, leading to slightly decreased interaction with MTOR."; /evidence="ECO:0000269|PubMed:34634301"; MUTAGEN 289; /note="Y->F: Decreased phosphorylation, leading to increased interaction with MTOR."; /evidence="ECO:0000269|PubMed:34634301"; MUTAGEN 291; /note="S->A: Reduced ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877"; MUTAGEN 293; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-297, A-298 and A-299. Reduced ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:25936805"; MUTAGEN 295..299; /note="TLSSS->ALSSA: Reduced ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:22017875"; MUTAGEN 297; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-298 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 298; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-297 and A-299."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 299; /note="S->A: In mutant 13A; abolished phosphorylation, leading to promote interaction with MTOR without affecting ability to bind phosphatidic acid; when associated with A-241, A-244, A-258, A-259, A-263, A-265, A-282, A-283, A-287, A-293, A-297 and A-298."; /evidence="ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:25936805"; MUTAGEN 326; /note="Y->F: Does not affect phosphorylation."; /evidence="ECO:0000269|PubMed:34634301
uniprot
proteins
post_translational_modification
PTM: Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2 (PubMed:19446321). Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1 (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability (PubMed:35216969). Phosphorylation at Tyr-289 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling (PubMed:34634301). {ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:35216969}.; PTM: Ubiquitinated; leading to proteasomal degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:30080879, PubMed:33110214). Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:33110214). Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability (PubMed:29382726). Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability (PubMed:35216969). {ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:30080879, ECO:0000269|PubMed:33110214, ECO:0000269|PubMed:35216969}.
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19446321
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22017875
uniprot
proteins
pubmed
22017876
uniprot
proteins
pubmed
22017877
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25936805
uniprot
proteins
pubmed
29382726
uniprot
proteins
pubmed
30080879
uniprot
proteins
pubmed
30232230
uniprot
proteins
pubmed
33110214
uniprot
proteins
pubmed
33865870
uniprot
proteins
pubmed
34519268
uniprot
proteins
pubmed
34519269
uniprot
proteins
pubmed
34634301
uniprot
proteins
pubmed
35216969
uniprot
proteins
sequence_length
409
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000305|PubMed:25936805}. Note=Localizes to the lysosomal membrane when associated with the mTORC1 and mTORC2 complexes. {ECO:0000305|PubMed:25936805}.
uniprot
proteins