MTOR
entrez
2475
canonical
uniprot
P42345
canonical
ensembl
ENSG00000198793
resolver
ensp
ENSP00000354558
resolver
ensp
ENSP00000515198
resolver
ensp
ENSP00000515200
resolver
ensp
ENSP00000604369
resolver
ensp
ENSP00000604373
resolver
ensp
ENSP00000750833
resolver
enst
ENST00000361445
resolver
enst
ENST00000703141
resolver
enst
ENST00000703143
resolver
enst
ENST00000934310
resolver
enst
ENST00000934314
resolver
genesymbol
MTOR
resolver
genesymbol_syn
FRAP
resolver
genesymbol_syn
FRAP1
resolver
genesymbol_syn
FRAP2
resolver
genesymbol_syn
RAFT1
resolver
genesymbol_syn
RAPT1
resolver
hgnc
HGNC:3942
resolver
uniprot
A0A8V8TQ52
resolver
uniprot
Q4LE76
resolver
uniprot
Q5TER1
resolver
uniprot
Q6LE87
resolver
uniprot
Q96QG3
resolver
uniprot
Q9Y4I3
resolver
uniprot_entry
A0A8V8TQ52_HUMAN
resolver
uniprot_entry
MTOR_HUMAN
resolver
uniprot_sec
Q4LE76
resolver
uniprot_sec
Q5TER1
resolver
uniprot_sec
Q6LE87
resolver
uniprot_sec
Q96QG3
resolver
uniprot_sec
Q9Y4I3
resolver
activity_regulation
ACTIVITY REGULATION: The mTORC1 complex is activated in response to nutrients, growth factors or amino acids: activation requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175, PubMed:25567906). Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1 (PubMed:14651849, PubMed:15545625, PubMed:29236692). Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1 (PubMed:19487463). On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1 (PubMed:14651849, PubMed:15545625). The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 (PubMed:12718876). The kinase activity of MTOR is inhibited by DEPTOR and AKT1S1 (PubMed:17386266, PubMed:19446321, PubMed:29236692, PubMed:34519268, PubMed:34519269). The non-canonical mTORC1 complex is independent of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 but not other mTORC1 substrates: it is activated by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD (PubMed:32612235, PubMed:36697823). MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity (PubMed:10089303, PubMed:8662507). mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (PubMed:15467718). mTORC2 associates and is directly activated by ribosomes (PubMed:21376236). mTORC2 may also be regulated by RHEB but in an indirect manner through the PI3K signaling pathway (PubMed:15467718). {ECO:0000269|PubMed:10089303, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:17386266, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:19487463, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:25561175, ECO:0000269|PubMed:25567906, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34519268, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:8662507}.
uniprot
proteins
amino_acid_sequence
MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW
uniprot
proteins
disease_involvement
DISEASE: Smith-Kingsmore syndrome (SKS) [MIM:616638]: An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features. {ECO:0000269|PubMed:25851998, ECO:0000269|PubMed:26542245, ECO:0000269|PubMed:27830187}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells. {ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:25878179, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). 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 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). 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 (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}.
uniprot
proteins
mass_dalton
288892
uniprot
proteins
mutagenesis
MUTAGEN 2066; /note="K->R: Complete loss ubiquitination by the SCF(FBXO22) complex."; /evidence="ECO:0000269|PubMed:37979583"; MUTAGEN 2159; /note="S->A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2164. Reduced activity of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:29150432"; MUTAGEN 2159; /note="S->D: Mimics phosphorylation; leading to stronger phosphorylation of RPS6KB1; when associated with E-2164. Increased activity of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:29150432"; MUTAGEN 2164; /note="T->A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2159."; /evidence="ECO:0000269|PubMed:21576368"; MUTAGEN 2164; /note="T->E: Stronger phosphorylation of RPS6KB1; when associated with D-2159."; /evidence="ECO:0000269|PubMed:21576368"; MUTAGEN 2173; /note="T->A: Increased mTOR kinase activity."; /evidence="ECO:0000269|PubMed:24247430"; MUTAGEN 2340; /note="H->A: Barely detectable kinase activity."; /evidence="ECO:0000269|PubMed:23636326"; MUTAGEN 2357; /note="D->E: Kinase-dead mutant, loss of interaction with TM4SF5 and loss of lysosome membrane localization; when associated with I-2364."; /evidence="ECO:0000269|PubMed:30956113"; MUTAGEN 2364; /note="V->I: Kinase-dead mutant, loss of interaction with TM4SF5 and loss of lysosome membrane localization; when associated with E-2357."; /evidence="ECO:0000269|PubMed:30956113
uniprot
proteins
post_translational_modification
PTM: Autophosphorylates when part of mTORC1 or mTORC2 (PubMed:15467718, PubMed:20022946, PubMed:9434772). Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation (PubMed:19487463). Phosphorylated at Ser-2448 by RPS6KB1 (PubMed:15899889, PubMed:15905173, PubMed:19145465). Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40 and leads to increased intrinsic mTORC1 kinase activity (PubMed:15905173, PubMed:19145465, PubMed:21576368). Phosphorylation at Ser-2159 by TBK1 in response to growth factors and pathogen recognition receptors promotes mTORC1 activity (PubMed:29150432). Phosphorylation at Ser-2159 by TBK1 in response to EGF growth factor promotes mTORC2 activity, leading to AKT1 phosphorylation and activation (By similarity). Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity (PubMed:24247430). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15905173, ECO:0000269|PubMed:19145465, ECO:0000269|PubMed:19487463, ECO:0000269|PubMed:20022946, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:24247430, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:9434772}.; PTM: Ubiquitinated at Lys-2066 by the SCF(FBXO22) complex via 'Lys-27'-linked ubiquitination prevents mTORC1 substrate recruitment. {ECO:0000269|PubMed:37979583}.
uniprot
proteins
protein_family
PI3/PI4-kinase family
uniprot
proteins
pubmed
10089303
uniprot
proteins
pubmed
11426320
uniprot
proteins
pubmed
11853878
uniprot
proteins
pubmed
11930000
uniprot
proteins
pubmed
12087098
uniprot
proteins
pubmed
12150925
uniprot
proteins
pubmed
12150926
uniprot
proteins
pubmed
12231510
uniprot
proteins
pubmed
12408816
uniprot
proteins
pubmed
12718876
uniprot
proteins
pubmed
14578359
uniprot
proteins
pubmed
14651849
uniprot
proteins
pubmed
15268862
uniprot
proteins
pubmed
15467718
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15545625
uniprot
proteins
pubmed
15718470
uniprot
proteins
pubmed
15899889
uniprot
proteins
pubmed
15905173
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17386266
uniprot
proteins
pubmed
17517883
uniprot
proteins
pubmed
17599906
uniprot
proteins
pubmed
18372248
uniprot
proteins
pubmed
18497260
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18762023
uniprot
proteins
pubmed
18925875
uniprot
proteins
pubmed
19145465
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19446321
uniprot
proteins
pubmed
19487463
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20022946
uniprot
proteins
pubmed
20060908
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20381137
uniprot
proteins
pubmed
20427287
uniprot
proteins
pubmed
20516213
uniprot
proteins
pubmed
20537536
uniprot
proteins
pubmed
20542007
uniprot
proteins
pubmed
20801936
uniprot
proteins
pubmed
20810650
uniprot
proteins
pubmed
21248752
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21376236
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21576368
uniprot
proteins
pubmed
21659604
uniprot
proteins
pubmed
21867682
uniprot
proteins
pubmed
22343943
uniprot
proteins
pubmed
22576015
uniprot
proteins
pubmed
22692423
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23027611
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23394946
uniprot
proteins
pubmed
23426360
uniprot
proteins
pubmed
23429703
uniprot
proteins
pubmed
23429704
uniprot
proteins
pubmed
23524951
uniprot
proteins
pubmed
23636326
uniprot
proteins
pubmed
23762398
uniprot
proteins
pubmed
24247430
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24403073
uniprot
proteins
pubmed
24448649
uniprot
proteins
pubmed
24670654
uniprot
proteins
pubmed
25438055
uniprot
proteins
pubmed
25561175
uniprot
proteins
pubmed
25567906
uniprot
proteins
pubmed
25657994
uniprot
proteins
pubmed
25799227
uniprot
proteins
pubmed
25851998
uniprot
proteins
pubmed
25878179
uniprot
proteins
pubmed
25925585
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26018084
uniprot
proteins
pubmed
26542245
uniprot
proteins
pubmed
26584640
uniprot
proteins
pubmed
26678875
uniprot
proteins
pubmed
26812014
uniprot
proteins
pubmed
27623384
uniprot
proteins
pubmed
27830187
uniprot
proteins
pubmed
27909983
uniprot
proteins
pubmed
29150432
uniprot
proteins
pubmed
29236692
uniprot
proteins
pubmed
29424687
uniprot
proteins
pubmed
29567957
uniprot
proteins
pubmed
29750193
uniprot
proteins
pubmed
30171069
uniprot
proteins
pubmed
30704899
uniprot
proteins
pubmed
30956113
uniprot
proteins
pubmed
31036939
uniprot
proteins
pubmed
31112131
uniprot
proteins
pubmed
31601708
uniprot
proteins
pubmed
31601764
uniprot
proteins
pubmed
31695197
uniprot
proteins
pubmed
32561715
uniprot
proteins
pubmed
32612235
uniprot
proteins
pubmed
32647003
uniprot
proteins
pubmed
33158864
uniprot
proteins
pubmed
33378666
uniprot
proteins
pubmed
34289345
uniprot
proteins
pubmed
34519268
uniprot
proteins
pubmed
34519269
uniprot
proteins
pubmed
35561222
uniprot
proteins
pubmed
35904232
uniprot
proteins
pubmed
35926713
uniprot
proteins
pubmed
36608670
uniprot
proteins
pubmed
36691768
uniprot
proteins
pubmed
36697823
uniprot
proteins
pubmed
37057673
uniprot
proteins
pubmed
37751742
uniprot
proteins
pubmed
37979583
uniprot
proteins
pubmed
7809080
uniprot
proteins
pubmed
8008069
uniprot
proteins
pubmed
8662507
uniprot
proteins
pubmed
9434772
uniprot
proteins
pubmed
9653645
uniprot
proteins
sequence_length
2549
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:29750193, ECO:0000269|PubMed:30956113, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:37057673}; Peripheral membrane protein {ECO:0000269|PubMed:30956113, ECO:0000269|PubMed:31112131}; Cytoplasmic side {ECO:0000269|PubMed:30956113, ECO:0000269|PubMed:31112131}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:14578359}; Peripheral membrane protein {ECO:0000269|PubMed:14578359}; Cytoplasmic side {ECO:0000269|PubMed:14578359}. Golgi apparatus membrane {ECO:0000269|PubMed:14578359}; Peripheral membrane protein {ECO:0000269|PubMed:14578359}; Cytoplasmic side {ECO:0000269|PubMed:14578359}. Cell membrane {ECO:0000269|PubMed:21867682}; Peripheral membrane protein {ECO:0000269|PubMed:14578359}. Mitochondrion outer membrane {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}; Peripheral membrane protein {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}; Cytoplasmic side {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}. Cytoplasm {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:18497260}. Nucleus {ECO:0000250|UniProtKB:Q9JLN9}. Nucleus, PML body {ECO:0000250|UniProtKB:Q9JLN9}. Microsome membrane {ECO:0000269|PubMed:9434772}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:27623384}. Note=Shuttles between cytoplasm and nucleus. Accumulates in the nucleus in response to hypoxia (By similarity). Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB (PubMed:18497260, PubMed:20381137). Lysosome targeting also depends on interaction with MEAK7. Translocates to the lysosome membrane in the presence of TM4SF5 (PubMed:30956113). The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane and lysosomes (PubMed:21867682). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:21867682, ECO:0000269|PubMed:29750193, ECO:0000269|PubMed:30956113}.
uniprot
proteins