General Information of the Protein
Protein ID
PT02733
Protein Name
Serine/threonine-protein kinase mTOR
Secondarily
Protein Name
FK506-binding protein 12-rapamycin complex-associated protein 1
FKBP12-rapamycin complex-associated protein
Mammalian target of rapamycin
Mechanistic target of rapamycin
Rapamycin target protein 1
Gene Name
MTOR
Secondarily
Gene Name
Frap
Frap1
Sequence
MLGTGPAVATASAATSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNSTRIGRFANYLRNLLPSSDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQPNALVGLLGYSSPQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRSSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKTVQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVASITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSQGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEVPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSSQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAASGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKEDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTAHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAASAAAATSTEGSNSESEAESNENSPTPSPLQKKVTEDLSKTLLLYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRTTCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKAGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW
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Organism
Mus musculus, Mouse
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
Atypical protein kinase group
>
Atypical protein kinase PIKK family
>
Atypical protein kinase FRAP subfamily
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:15467718, PubMed:15545625, PubMed:15485918, PubMed:16221682, PubMed:16915281, PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15467718, PubMed:15545625, PubMed:16221682, PubMed:16915281, PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15467718, PubMed:16962653, PubMed:21659604). 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:15485918). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:15485918). 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:15485918). 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 (By similarity). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (By similarity). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (By similarity). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:11792863). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (PubMed:18046414). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:21258367). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:21258367). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (By similarity). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (By similarity). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (By similarity). 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 (By similarity). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (By similarity). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:27913603). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (PubMed:19346248). As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. mTORC2 plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. 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. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (By similarity). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (PubMed:19440205). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (PubMed:29750810). Phosphorylates SQSTM1, promoting interaction between SQSTM1 and KEAP1 and subsequent inactivation of the BCR(KEAP1) complex (PubMed:24011591).
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Uniprot ID
Primary ID:
Q9JLN9

Secondarily ID:
Q2KHT0
Q811J5
Q9CST1
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Ensembl ID
ENSG00000198793
Subcellular Location
Lysosome membrane
Endoplasmic reticulum membrane
Golgi apparatus membrane
Mitochondrion outer membrane
Cytoplasm
Nucleus
Nucleus
PML body
Microsome membrane
Cytoplasmic vesicle
Phagosome
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL001056 , MEF-1 [Mouse fibroblast]
Compound ID Compound Name Compound Formula
CP0243589
4-[2-methyl-4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C41H35N5O2
 1
1
EC50 = 1 nM
   TI
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CP0023857
N-(1-methylpiperidin-4-yl)-4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzamide
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C41H32F3N5O2
 1
1
EC50 = 5 nM
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CP0503237
4-[4-[9-(2-aminopyrimidin-5-yl)-2-oxobenzo[h][1,6]naphthyridin-1-yl]-2-(trifluoromethyl)phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C36H30F3N7O2
 1
1
EC50 = 10 nM
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CP0512569
N-(1-methylpiperidin-4-yl)-4-[4-[2-oxo-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-1-yl]-2-(trifluoromethyl)phenyl]benzamide
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C35H29F3N6O2
 1
1
EC50 = 10 nM
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CP0503175
N-methyl-4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzamide
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C36H23F3N4O2
 1
1
EC50 = 15 nM
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CP0436112
4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzoic acid
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C35H20F3N3O3
 1
1
EC50 = 20 nM
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CP0452004
1-[4-[4-(oxan-2-yloxymethyl)phenyl]-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one
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C40H30F3N3O3
 1
1
EC50 = 25 nM
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CP0465089
4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzamide
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C35H21F3N4O2
 1
1
EC50 = 25 nM
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CP0483779
4-[2-methyl-4-[2-oxo-9-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzo[h][1,6]naphthyridin-1-yl]phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C39H34N6O2
 1
1
EC50 = 25 nM
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CP0465088
1-[4-[4-(hydroxymethyl)phenyl]-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one
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C35H22F3N3O2
 1
1
EC50 = 30 nM
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CP0499736
4-[4-[9-(6-aminopyridin-3-yl)-2-oxobenzo[h][1,6]naphthyridin-1-yl]-2-methylphenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C37H34N6O2
 1
1
EC50 = 50 nM
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CP0441402
4-[2-methyl-4-[9-(1-methylpyrazol-4-yl)-2-oxobenzo[h][1,6]naphthyridin-1-yl]phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C36H34N6O2
 1
1
EC50 = 150 nM
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CP0499167
4-[2-methyl-4-[2-oxo-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-1-yl]phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C35H32N6O2
 1
1
EC50 = 150 nM
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CP0521650
methyl 4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzoate
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C36H22F3N3O3
 1
1
EC50 = 200 nM
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CP0501237
4-[2-methyl-4-(2-oxobenzo[h][1,6]naphthyridin-1-yl)phenyl]-N-(1-methylpiperidin-4-yl)benzamide
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C32H30N4O2
 1
1
EC50 > 1000 nM
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CP0543985
4-[7-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-5-yl]-1,4-oxazepane
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C18H23N7O2S
 1
1
IC50 = 2.7 nM
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CP0354280
(3R)-3-methyl-4-[5-propan-2-yl-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C16H20N6OS
 1
1
IC50 = 3.7 nM
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CP0347328
(3R)-3-methyl-4-[5-morpholin-4-yl-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C17H21N7O2S
 1
1
IC50 = 5.3 nM
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CP0198509
(3R)-3-methyl-4-[5-[(3S)-3-methylmorpholin-4-yl]-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C18H23N7O2S
 1
1
IC50 = 5.6 nM
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CP0567500
(3R)-3-methyl-4-[5-(oxan-4-yl)-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C18H22N6O2S
 1
1
IC50 = 6.3 nM
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CP0355964
(3R)-3-methyl-4-[5-[(3S)-3-methylmorpholin-4-yl]-2-(2H-triazol-4-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C17H22N8O2S
 1
1
IC50 = 6.9 nM
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CP0534120
(3R)-4-[2-(1H-imidazol-5-yl)-5-[(3S)-3-methylmorpholin-4-yl]-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]-3-methylmorpholine
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C18H23N7O2S
 1
1
IC50 = 7.8 nM
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CP0228417
(3R)-3-methyl-4-[5-[(3S)-3-methylmorpholin-4-yl]-2-(1H-pyrazol-4-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C18H23N7O2S
 1
1
IC50 = 56 nM
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CP0529546
(3R)-3-methyl-4-[5-(morpholin-4-ylmethyl)-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C18H23N7O2S
 1
1
IC50 = 92 nM
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CP0354279
(3R)-3-methyl-4-[5-(4-methylpiperazin-1-yl)-2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C18H24N8OS
 1
1
IC50 = 134 nM
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CP0355965
3-[7-[(3R)-3-methylmorpholin-4-yl]-5-[(3S)-3-methylmorpholin-4-yl]-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]phenol
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C21H25N5O3S
 1
1
IC50 = 278 nM
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CP0355945
(3R)-4-[2-(1H-indol-4-yl)-5-[(3S)-3-methylmorpholin-4-yl]-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]-3-methylmorpholine
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C23H26N6O2S
 1
1
IC50 = 305 nM
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CP0198510
(3R)-3-methyl-4-[2-(1H-pyrazol-5-yl)-[1,3]thiazolo[5,4-d]pyrimidin-7-yl]morpholine
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C13H14N6OS
 1
1
IC50 = 603 nM
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Similar Protein(s) and Bioactivity Statistics
90% Identity
Protein ID Protein Name Protein Organism
PT01065 Serine/threonine-protein kinase mTOR Homo sapiens, Human