Browse MTOR

Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Endoplasmic reticulum membrane Peripheral membrane protein Cytoplasmic side Golgi apparatus membrane Peripheral membrane protein Cytoplasmic side Mitochondrion outer membrane Peripheral membrane protein Cytoplasmic side Lysosome Cytoplasm Nucleus, PML body Microsome membrane 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).
Domain PF11865 Domain of unknown function (DUF3385)
PF02259 FAT domain
PF02260 FATC domain
PF08771 FKBP12-rapamycin binding domain
PF00454 Phosphatidylinositol 3- and 4-kinase
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. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). 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. 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. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. 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' (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). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity).

> Gene Ontology
 
Biological Process GO:0000271 polysaccharide biosynthetic process
GO:0001101 response to acid chemical
GO:0001558 regulation of cell growth
GO:0001666 response to hypoxia
GO:0001933 negative regulation of protein phosphorylation
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0003007 heart morphogenesis
GO:0003012 muscle system process
GO:0003013 circulatory system process
GO:0003015 heart process
GO:0003170 heart valve development
GO:0003179 heart valve morphogenesis
GO:0003298 physiological muscle hypertrophy
GO:0003300 cardiac muscle hypertrophy
GO:0003301 physiological cardiac muscle hypertrophy
GO:0005976 polysaccharide metabolic process
GO:0005977 glycogen metabolic process
GO:0005978 glycogen biosynthetic process
GO:0005979 regulation of glycogen biosynthetic process
GO:0005996 monosaccharide metabolic process
GO:0006006 glucose metabolic process
GO:0006073 cellular glucan metabolic process
GO:0006091 generation of precursor metabolites and energy
GO:0006109 regulation of carbohydrate metabolic process
GO:0006112 energy reserve metabolic process
GO:0006206 pyrimidine nucleobase metabolic process
GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
GO:0006356 regulation of transcription from RNA polymerase I promoter
GO:0006359 regulation of transcription from RNA polymerase III promoter
GO:0006360 transcription from RNA polymerase I promoter
GO:0006383 transcription from RNA polymerase III promoter
GO:0006417 regulation of translation
GO:0006606 protein import into nucleus
GO:0006631 fatty acid metabolic process
GO:0006635 fatty acid beta-oxidation
GO:0006809 nitric oxide biosynthetic process
GO:0006820 anion transport
GO:0006913 nucleocytoplasmic transport
GO:0006914 autophagy
GO:0006936 muscle contraction
GO:0006941 striated muscle contraction
GO:0007015 actin filament organization
GO:0007050 cell cycle arrest
GO:0007159 leukocyte cell-cell adhesion
GO:0007272 ensheathment of neurons
GO:0007281 germ cell development
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007565 female pregnancy
GO:0007568 aging
GO:0007569 cell aging
GO:0007584 response to nutrient
GO:0007611 learning or memory
GO:0007612 learning
GO:0007613 memory
GO:0007616 long-term memory
GO:0007631 feeding behavior
GO:0007632 visual behavior
GO:0008015 blood circulation
GO:0008064 regulation of actin polymerization or depolymerization
GO:0008154 actin polymerization or depolymerization
GO:0008306 associative learning
GO:0008361 regulation of cell size
GO:0008366 axon ensheathment
GO:0008542 visual learning
GO:0009062 fatty acid catabolic process
GO:0009112 nucleobase metabolic process
GO:0009250 glucan biosynthetic process
GO:0009266 response to temperature stimulus
GO:0009303 rRNA transcription
GO:0009314 response to radiation
GO:0009408 response to heat
GO:0009416 response to light stimulus
GO:0009758 carbohydrate utilization
GO:0009791 post-embryonic development
GO:0009894 regulation of catabolic process
GO:0009991 response to extracellular stimulus
GO:0010001 glial cell differentiation
GO:0010506 regulation of autophagy
GO:0010507 negative regulation of autophagy
GO:0010565 regulation of cellular ketone metabolic process
GO:0010591 regulation of lamellipodium assembly
GO:0010592 positive regulation of lamellipodium assembly
GO:0010608 posttranscriptional regulation of gene expression
GO:0010611 regulation of cardiac muscle hypertrophy
GO:0010613 positive regulation of cardiac muscle hypertrophy
GO:0010675 regulation of cellular carbohydrate metabolic process
GO:0010720 positive regulation of cell development
GO:0010830 regulation of myotube differentiation
GO:0010831 positive regulation of myotube differentiation
GO:0010906 regulation of glucose metabolic process
GO:0010962 regulation of glucan biosynthetic process
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0014009 glial cell proliferation
GO:0014013 regulation of gliogenesis
GO:0014015 positive regulation of gliogenesis
GO:0014041 regulation of neuron maturation
GO:0014042 positive regulation of neuron maturation
GO:0014072 response to isoquinoline alkaloid
GO:0014706 striated muscle tissue development
GO:0014733 regulation of skeletal muscle adaptation
GO:0014734 skeletal muscle hypertrophy
GO:0014735 regulation of muscle atrophy
GO:0014736 negative regulation of muscle atrophy
GO:0014742 positive regulation of muscle hypertrophy
GO:0014743 regulation of muscle hypertrophy
GO:0014744 positive regulation of muscle adaptation
GO:0014745 negative regulation of muscle adaptation
GO:0014888 striated muscle adaptation
GO:0014889 muscle atrophy
GO:0014896 muscle hypertrophy
GO:0014897 striated muscle hypertrophy
GO:0014902 myotube differentiation
GO:0015698 inorganic anion transport
GO:0015705 iodide transport
GO:0015980 energy derivation by oxidation of organic compounds
GO:0016042 lipid catabolic process
GO:0016049 cell growth
GO:0016051 carbohydrate biosynthetic process
GO:0016054 organic acid catabolic process
GO:0016202 regulation of striated muscle tissue development
GO:0016236 macroautophagy
GO:0016241 regulation of macroautophagy
GO:0016242 negative regulation of macroautophagy
GO:0016358 dendrite development
GO:0017038 protein import
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018210 peptidyl-threonine modification
GO:0018212 peptidyl-tyrosine modification
GO:0019216 regulation of lipid metabolic process
GO:0019217 regulation of fatty acid metabolic process
GO:0019233 sensory perception of pain
GO:0019318 hexose metabolic process
GO:0019395 fatty acid oxidation
GO:0019856 pyrimidine nucleobase biosynthetic process
GO:0021510 spinal cord development
GO:0021700 developmental maturation
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0022412 cellular process involved in reproduction in multicellular organism
GO:0030031 cell projection assembly
GO:0030032 lamellipodium assembly
GO:0030038 contractile actin filament bundle assembly
GO:0030041 actin filament polymerization
GO:0030099 myeloid cell differentiation
GO:0030258 lipid modification
GO:0030307 positive regulation of cell growth
GO:0030316 osteoclast differentiation
GO:0030832 regulation of actin filament length
GO:0030833 regulation of actin filament polymerization
GO:0030838 positive regulation of actin filament polymerization
GO:0031032 actomyosin structure organization
GO:0031294 lymphocyte costimulation
GO:0031295 T cell costimulation
GO:0031329 regulation of cellular catabolic process
GO:0031334 positive regulation of protein complex assembly
GO:0031346 positive regulation of cell projection organization
GO:0031396 regulation of protein ubiquitination
GO:0031397 negative regulation of protein ubiquitination
GO:0031529 ruffle organization
GO:0031641 regulation of myelination
GO:0031644 regulation of neurological system process
GO:0031646 positive regulation of neurological system process
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0031929 TOR signaling
GO:0031998 regulation of fatty acid beta-oxidation
GO:0032094 response to food
GO:0032095 regulation of response to food
GO:0032104 regulation of response to extracellular stimulus
GO:0032107 regulation of response to nutrient levels
GO:0032231 regulation of actin filament bundle assembly
GO:0032233 positive regulation of actin filament bundle assembly
GO:0032271 regulation of protein polymerization
GO:0032273 positive regulation of protein polymerization
GO:0032386 regulation of intracellular transport
GO:0032387 negative regulation of intracellular transport
GO:0032535 regulation of cellular component size
GO:0032868 response to insulin
GO:0032881 regulation of polysaccharide metabolic process
GO:0032885 regulation of polysaccharide biosynthetic process
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0033002 muscle cell proliferation
GO:0033157 regulation of intracellular protein transport
GO:0033692 cellular polysaccharide biosynthetic process
GO:0034248 regulation of cellular amide metabolic process
GO:0034250 positive regulation of cellular amide metabolic process
GO:0034440 lipid oxidation
GO:0034504 protein localization to nucleus
GO:0034605 cellular response to heat
GO:0034637 cellular carbohydrate biosynthetic process
GO:0034762 regulation of transmembrane transport
GO:0034763 negative regulation of transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0034766 negative regulation of ion transmembrane transport
GO:0035051 cardiocyte differentiation
GO:0035176 social behavior
GO:0035264 multicellular organism growth
GO:0035265 organ growth
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0042063 gliogenesis
GO:0042110 T cell activation
GO:0042180 cellular ketone metabolic process
GO:0042220 response to cocaine
GO:0042306 regulation of protein import into nucleus
GO:0042308 negative regulation of protein import into nucleus
GO:0042326 negative regulation of phosphorylation
GO:0042551 neuron maturation
GO:0042552 myelination
GO:0042692 muscle cell differentiation
GO:0042755 eating behavior
GO:0042790 transcription of nuclear large rRNA transcript from RNA polymerase I promoter
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0043149 stress fiber assembly
GO:0043200 response to amino acid
GO:0043254 regulation of protein complex assembly
GO:0043255 regulation of carbohydrate biosynthetic process
GO:0043271 negative regulation of ion transport
GO:0043278 response to morphine
GO:0043279 response to alkaloid
GO:0043434 response to peptide hormone
GO:0043467 regulation of generation of precursor metabolites and energy
GO:0043487 regulation of RNA stability
GO:0043488 regulation of mRNA stability
GO:0043489 RNA stabilization
GO:0043491 protein kinase B signaling
GO:0043500 muscle adaptation
GO:0043501 skeletal muscle adaptation
GO:0043502 regulation of muscle adaptation
GO:0043610 regulation of carbohydrate utilization
GO:0044042 glucan metabolic process
GO:0044057 regulation of system process
GO:0044070 regulation of anion transport
GO:0044089 positive regulation of cellular component biogenesis
GO:0044242 cellular lipid catabolic process
GO:0044262 cellular carbohydrate metabolic process
GO:0044264 cellular polysaccharide metabolic process
GO:0044282 small molecule catabolic process
GO:0044706 multi-multicellular organism process
GO:0044708 single-organism behavior
GO:0044723 single-organism carbohydrate metabolic process
GO:0044744 protein targeting to nucleus
GO:0045428 regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045444 fat cell differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045637 regulation of myeloid cell differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0045685 regulation of glial cell differentiation
GO:0045687 positive regulation of glial cell differentiation
GO:0045727 positive regulation of translation
GO:0045785 positive regulation of cell adhesion
GO:0045786 negative regulation of cell cycle
GO:0045792 negative regulation of cell size
GO:0045834 positive regulation of lipid metabolic process
GO:0045844 positive regulation of striated muscle tissue development
GO:0045927 positive regulation of growth
GO:0045943 positive regulation of transcription from RNA polymerase I promoter
GO:0045945 positive regulation of transcription from RNA polymerase III promoter
GO:0046112 nucleobase biosynthetic process
GO:0046209 nitric oxide metabolic process
GO:0046320 regulation of fatty acid oxidation
GO:0046395 carboxylic acid catabolic process
GO:0046620 regulation of organ growth
GO:0046622 positive regulation of organ growth
GO:0046777 protein autophosphorylation
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046823 negative regulation of nucleocytoplasmic transport
GO:0046889 positive regulation of lipid biosynthetic process
GO:0046890 regulation of lipid biosynthetic process
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048255 mRNA stabilization
GO:0048469 cell maturation
GO:0048520 positive regulation of behavior
GO:0048588 developmental cell growth
GO:0048634 regulation of muscle organ development
GO:0048636 positive regulation of muscle organ development
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0048709 oligodendrocyte differentiation
GO:0048713 regulation of oligodendrocyte differentiation
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0048738 cardiac muscle tissue development
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050769 positive regulation of neurogenesis
GO:0050773 regulation of dendrite development
GO:0050795 regulation of behavior
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050873 brown fat cell differentiation
GO:0050879 multicellular organismal movement
GO:0050881 musculoskeletal movement
GO:0050882 voluntary musculoskeletal movement
GO:0050890 cognition
GO:0050994 regulation of lipid catabolic process
GO:0051017 actin filament bundle assembly
GO:0051051 negative regulation of transport
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051149 positive regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051155 positive regulation of striated muscle cell differentiation
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051224 negative regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051258 protein polymerization
GO:0051492 regulation of stress fiber assembly
GO:0051493 regulation of cytoskeleton organization
GO:0051495 positive regulation of cytoskeleton organization
GO:0051496 positive regulation of stress fiber assembly
GO:0051531 NFAT protein import into nucleus
GO:0051532 regulation of NFAT protein import into nucleus
GO:0051534 negative regulation of NFAT protein import into nucleus
GO:0051703 intraspecies interaction between organisms
GO:0051705 multi-organism behavior
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0051930 regulation of sensory perception of pain
GO:0051931 regulation of sensory perception
GO:0051962 positive regulation of nervous system development
GO:0055001 muscle cell development
GO:0055002 striated muscle cell development
GO:0055006 cardiac cell development
GO:0055007 cardiac muscle cell differentiation
GO:0055013 cardiac muscle cell development
GO:0055017 cardiac muscle tissue growth
GO:0055021 regulation of cardiac muscle tissue growth
GO:0055023 positive regulation of cardiac muscle tissue growth
GO:0055024 regulation of cardiac muscle tissue development
GO:0055025 positive regulation of cardiac muscle tissue development
GO:0060047 heart contraction
GO:0060048 cardiac muscle contraction
GO:0060135 maternal process involved in female pregnancy
GO:0060251 regulation of glial cell proliferation
GO:0060252 positive regulation of glial cell proliferation
GO:0060259 regulation of feeding behavior
GO:0060419 heart growth
GO:0060420 regulation of heart growth
GO:0060421 positive regulation of heart growth
GO:0060491 regulation of cell projection assembly
GO:0060537 muscle tissue development
GO:0060996 dendritic spine development
GO:0060998 regulation of dendritic spine development
GO:0060999 positive regulation of dendritic spine development
GO:0061049 cell growth involved in cardiac muscle cell development
GO:0061050 regulation of cell growth involved in cardiac muscle cell development
GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development
GO:0061572 actin filament bundle organization
GO:0070482 response to oxygen levels
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070873 regulation of glycogen metabolic process
GO:0070997 neuron death
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071496 cellular response to external stimulus
GO:0071593 lymphocyte aggregation
GO:0072329 monocarboxylic acid catabolic process
GO:0072527 pyrimidine-containing compound metabolic process
GO:0072528 pyrimidine-containing compound biosynthetic process
GO:0072593 reactive oxygen species metabolic process
GO:0090066 regulation of anatomical structure size
GO:0090257 regulation of muscle system process
GO:0090317 negative regulation of intracellular protein transport
GO:0090335 regulation of brown fat cell differentiation
GO:0090559 regulation of membrane permeability
GO:0097581 lamellipodium organization
GO:0098656 anion transmembrane transport
GO:0098661 inorganic anion transmembrane transport
GO:0098781 ncRNA transcription
GO:1900006 positive regulation of dendrite development
GO:1900034 regulation of cellular response to heat
GO:1900180 regulation of protein localization to nucleus
GO:1900181 negative regulation of protein localization to nucleus
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901652 response to peptide
GO:1901836 regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter
GO:1901838 positive regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter
GO:1901861 regulation of muscle tissue development
GO:1901863 positive regulation of muscle tissue development
GO:1902105 regulation of leukocyte differentiation
GO:1902488 cholangiocyte apoptotic process
GO:1902593 single-organism nuclear import
GO:1902743 regulation of lamellipodium organization
GO:1902745 positive regulation of lamellipodium organization
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903321 negative regulation of protein modification by small protein conjugation or removal
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903429 regulation of cell maturation
GO:1903431 positive regulation of cell maturation
GO:1903533 regulation of protein targeting
GO:1903706 regulation of hemopoiesis
GO:1903792 negative regulation of anion transport
GO:1903795 regulation of inorganic anion transmembrane transport
GO:1903796 negative regulation of inorganic anion transmembrane transport
GO:1903828 negative regulation of cellular protein localization
GO:1903959 regulation of anion transmembrane transport
GO:1903960 negative regulation of anion transmembrane transport
GO:1903998 regulation of eating behavior
GO:1904000 positive regulation of eating behavior
GO:1904019 epithelial cell apoptotic process
GO:1904035 regulation of epithelial cell apoptotic process
GO:1904036 negative regulation of epithelial cell apoptotic process
GO:1904054 regulation of cholangiocyte proliferation
GO:1904056 positive regulation of cholangiocyte proliferation
GO:1904058 positive regulation of sensory perception of pain
GO:1904192 regulation of cholangiocyte apoptotic process
GO:1904193 negative regulation of cholangiocyte apoptotic process
GO:1904195 regulation of granulosa cell proliferation
GO:1904197 positive regulation of granulosa cell proliferation
GO:1904200 iodide transmembrane transport
GO:1904201 regulation of iodide transport
GO:1904202 negative regulation of iodide transport
GO:1904204 regulation of skeletal muscle hypertrophy
GO:1904206 positive regulation of skeletal muscle hypertrophy
GO:1904212 regulation of iodide transmembrane transport
GO:1904213 negative regulation of iodide transmembrane transport
GO:1904407 positive regulation of nitric oxide metabolic process
GO:1904589 regulation of protein import
GO:1904590 negative regulation of protein import
GO:1904950 negative regulation of establishment of protein localization
GO:1905207 regulation of cardiocyte differentiation
GO:1905209 positive regulation of cardiocyte differentiation
GO:1990705 cholangiocyte proliferation
GO:1990739 granulosa cell proliferation
GO:2000253 positive regulation of feeding behavior
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2000725 regulation of cardiac muscle cell differentiation
GO:2000727 positive regulation of cardiac muscle cell differentiation
GO:2001057 reactive nitrogen species metabolic process
Molecular Function GO:0000182 rDNA binding
GO:0001016 RNA polymerase III regulatory region DNA binding
GO:0001025 RNA polymerase III transcription factor binding
GO:0001030 RNA polymerase III type 1 promoter DNA binding
GO:0001031 RNA polymerase III type 2 promoter DNA binding
GO:0001032 RNA polymerase III type 3 promoter DNA binding
GO:0001156 TFIIIC-class transcription factor binding
GO:0004674 protein serine/threonine kinase activity
GO:0008134 transcription factor binding
GO:0043021 ribonucleoprotein complex binding
GO:0043022 ribosome binding
GO:0051219 phosphoprotein binding
GO:0080084 5S rDNA binding
Cellular Component GO:0005741 mitochondrial outer membrane
GO:0005765 lysosomal membrane
GO:0005942 phosphatidylinositol 3-kinase complex
GO:0016604 nuclear body
GO:0016605 PML body
GO:0019867 outer membrane
GO:0019898 extrinsic component of membrane
GO:0030425 dendrite
GO:0031931 TORC1 complex
GO:0031932 TORC2 complex
GO:0031968 organelle outer membrane
GO:0038201 TOR complex
GO:0043025 neuronal cell body
GO:0044297 cell body
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:0098852 lytic vacuole membrane
> KEGG and Reactome Pathway
 
KEGG hsa04012 ErbB signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04630 Jak-STAT signaling pathway
hsa04910 Insulin signaling pathway
hsa04919 Thyroid hormone signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-389356: CD28 co-stimulation
R-HSA-389357: CD28 dependent PI3K/Akt signaling
R-HSA-3371556: Cellular response to heat stress
R-HSA-2262752: Cellular responses to stress
R-HSA-5674400: Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-388841: Costimulation by the CD28 family
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-380972: Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-3371571: HSF1-dependent transactivation
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-1632852: Macroautophagy
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-109704: PI3K Cascade
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-109703: PKB-mediated events
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804757: Regulation of TP53 Degradation
R-HSA-6806003: Regulation of TP53 Expression and Degradation
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218920: VEGFR2 mediated vascular permeability
R-HSA-165159: mTOR signalling
R-HSA-166208: mTORC1-mediated signalling
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MTOR and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between MTOR and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26637667Lung CarcinomaInhibit immunity (T cell function)AKT These data suggest that oncogenic activation of the AKT-mTOR pathway promotes immune escape by driving expression of PD-L1, which was confirmed in syngeneic and genetically engineered mouse models of lung cancer where an mTOR inhibitor combined with a PD-1 antibody decreased tumor growth, increased tumor-infiltrating T cells, and decreased regulatory T cells.
27076449Oral Cavity CarcinomaInhibit immunity (T cell function); resistant to immunotherapyEnhanced Tumor Control with Combination mTOR and PD-L1 Inhibition in Syngeneic Oral Cavity Cancers.
25256739GlioblastomaInhibit immunity (T cell function)Blockade of mTOR signaling via rapamycin combined with immunotherapy augments antiglioma cytotoxic and memory T-cell functions.
18427734Pancreatic CarcinomaInhibit immunityApart from the popular monoclonal antibodies and small molecules tyrosine kinase inhibitors, other novel compounds being tested in preclinical and clinical studies target mTOR, NF-kappaB, proteasome and histone deacetylase. These new drugs along with gene therapy and immunotherapy, which are also under clinical evaluation, may alter the unfavorable natural course of this disease.
24882582melanomaInhibit immunity (T cell function); decrease the efficacy of immunotherapyActivation of mTOR pathway in myeloid-derived suppressor cells stimulates cancer cell proliferation and metastasis in lal(-/-) mice.
21540234Renal Cell CarcinomaInhibit immunity (T cell function); resistant to immunotherapymTOR kinase inhibitor AZD8055 enhances the immunotherapeutic activity of an agonist CD40 antibody in cancer treatment. On this basis, we had explored the hypothesis that mTOR inhibition can enhance cancer immunotherapy. Here, we report that a combination of αCD40 agonistic antibody and the ATP-competitive mTOR kinase inhibitory drug AZD8055 elicited synergistic antitumor responses in a model of metastatic renal cell carcinoma. Levels of Th1 cytokines, including interleukin 12, IFN-γ, TNFα, and the Th1-associated chemokines RANTES, MIG, and IP-10 were each elevated significantly in the livers of mice treated with the combinatorial therapy versus individual treatments.
28822012Head and Neck CarcinomaInhibit immunityIndeed, mTOR inhibition exerts potent anti-tumor activity in HNSCC experimental systems, and mTOR targeting clinical trials show encouraging results. In addition, although counterintuitive, emerging evidence suggests that mTOR inhibition may enhance the anti-tumor immune response.
28758198GliomaInhibit immunity (T cell function)MiR-15a/16 deficiency enhances anti-tumor immunity of glioma-infiltrating CD8+ T cells through targeting mTOR. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells. Mechanismly, mTOR was identified as a target gene of miR-15a/16 to negatively regulate the activation of CD8+ T cells.
22890326Squamous Cell CarcinomaInhibit immunityThe mTOR inhibitor rapamycin opposes carcinogenic changes to epidermal Akt1/PKBα isoform signaling. We show that rapamycin selectively upregulates epidermal Akt1, while failing to upregulate epidermal Akt2. Epidermal Akt1 is commonly downregulated in SCC while Akt2 is upregulated. We show in skin culture that rapamycin does enhance restoration of Akt1 phosphorylation in skin recovering from UV radiation, suggesting a mechanism for rapamycin's antitumor activity in epidermis in spite of its efficient immunosuppressive properties.
22826320MelanomaInhibit immunityThe improved performance of DCs in which mTOR has been inhibited is correlated with an extended life span after activation and prolonged, increased expression of costimulatory molecules. Therapeutic autologous vaccination with DCs treated with TLR agonists plus the mTOR inhibitor rapamycin results in improved generation of Ag-specific CD8+ T cells in vivo and improved antitumor immunity compared with that observed with DCs treated with TLR agonists alone.
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of MTOR in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of MTOR in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0350.853
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.3490.824
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3120.777
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1830.409
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0810.976
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3130.928
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2810.463
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2570.883
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3270.866
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2480.823
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9620.542
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0840.0638
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MTOR in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.15.55.60.384
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.16.84.30.673
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211723.8023.80.0529
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131138.5038.50.0411
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 3827011.1-11.10.067
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 2213015.4-15.40.131
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 512200200.294
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MTOR. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MTOR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MTOR.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MTOR. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MTOR expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MTOR and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMTOR
Namemechanistic target of rapamycin (serine/threonine kinase)
Aliases RAFT1; RAPT1; FLJ44809; FK506 binding protein 12-rapamycin associated protein 2; rapamycin target protein; F ......
Chromosomal Location1p36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MTOR collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MTOR.
ID Name Drug Type Targets #Targets
DB00337PimecrolimusSmall MoleculeFKBP1A, MTOR2
DB00877SirolimusSmall MoleculeFGF2, FKBP1A, MTOR3
DB01590EverolimusSmall MoleculeMTOR1
DB04974AP1903Small MoleculeMTOR1
DB05210SF1126Small MoleculeMTOR, PIK3R1, PIK3R2, PIK3R3, PRKDC5
DB05241XL765Small MoleculeMTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG5
DB06233RidaforolimusSmall MoleculeMTOR1
DB06287TemsirolimusSmall MoleculeMTOR1