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Names & Taxonomy

Uniprot ID:: P42345
Entry Name:: MTOR_HUMAN
Status:: reviewed
Protein Names:: Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP12 target 1) (Rapamycin target protein 1)
Gene Names:: MTOR FRAP FRAP1 FRAP2 RAFT1 RAPT1
Gene Names Primary:: MTOR
Organism:: Homo sapiens (Human)

Structure

Length:: 2549
Sequence:: MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Endoplasmic reticulum membrane

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. 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'. Regulates osteoclastogensis by adjusting the expression of CEBPB isoforms (By similarity).
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: 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. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. Activation by amino acids requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175, PubMed:25567906). 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. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. 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. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. It may be regulated by RHEB but in an indirect manner through the PI3K signaling pathway.
Cross Reference Drug Bank:: DB01590 DB00337 DB00877 DB06287
Gene Ontology Go:: cytoplasm
cytosol
dendrite
endomembrane system
endoplasmic reticulum membrane
Golgi membrane
lysosomal membrane
lysosome
membrane
mitochondrial outer membrane
neuronal cell body
nucleoplasm
phosphatidylinositol 3-kinase complex
PML body
TORC1 complex
TORC2 complex
ATP binding
drug binding
kinase activity
phosphoprotein binding
protein serine/threonine kinase activity
ribosome binding
RNA polymerase III type 1 promoter DNA binding
RNA polymerase III type 2 promoter DNA binding
RNA polymerase III type 3 promoter DNA binding
TFIIIC-class transcription factor binding
'de novo' pyrimidine nucleobase biosynthetic process
brain development
cardiac muscle cell development
cardiac muscle contraction
cell aging
cell cycle arrest
cell growth
cellular response to heat
cellular response to hypoxia
cellular response to nutrient levels
DNA repair
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
gene expression
germ cell development
growth
heart morphogenesis
heart valve morphogenesis
innate immune response
insulin receptor signaling pathway
long-term memory
macroautophagy
maternal process involved in female pregnancy
mRNA stabilization
multicellular organism growth
negative regulation of autophagy
negative regulation of cell size
negative regulation of cholangiocyte apoptotic process
negative regulation of iodide transmembrane transport
negative regulation of macroautophagy
negative regulation of muscle atrophy
negative regulation of NFAT protein import into nucleus
negative regulation of protein phosphorylation
negative regulation of protein ubiquitination
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
phosphatidylinositol-mediated signaling
phosphorylation
positive regulation of actin filament polymerization
positive regulation of cell growth involved in cardiac muscle cell development
positive regulation of cholangiocyte proliferation
positive regulation of dendritic spine development
positive regulation of eating behavior
positive regulation of endothelial cell proliferation
positive regulation of gene expression
positive regulation of glial cell proliferation
positive regulation of granulosa cell proliferation
positive regulation of lamellipodium assembly
positive regulation of lipid biosynthetic process
positive regulation of myotube differentiation
positive regulation of neuron death
positive regulation of neuron maturation
positive regulation of nitric oxide biosynthetic process
positive regulation of oligodendrocyte differentiation
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of sensory perception of pain
positive regulation of skeletal muscle hypertrophy
positive regulation of smooth muscle cell proliferation
positive regulation of stress fiber assembly
positive regulation of transcription from RNA polymerase III promoter
positive regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter
positive regulation of translation
post-embryonic development
protein autophosphorylation
protein catabolic process
protein phosphorylation
regulation of actin cytoskeleton organization
regulation of brown fat cell differentiation
regulation of carbohydrate utilization
regulation of cellular response to heat
regulation of fatty acid beta-oxidation
regulation of glycogen biosynthetic process
regulation of GTPase activity
regulation of membrane permeability
regulation of myelination
regulation of osteoclast differentiation
regulation of protein kinase activity
regulation of response to food
response to amino acid
response to cocaine
response to morphine
response to nutrient
response to stress
ruffle organization
signal transduction
social behavior
spinal cord development
T cell costimulation
TOR signaling
transcription initiation from RNA polymerase II promoter
vascular endothelial growth factor receptor signaling pathway
visual learning
voluntary musculoskeletal movement
wound healing
Gene Ontology Biological Process:: 'de novo' pyrimidine nucleobase biosynthetic process
brain development
cardiac muscle cell development
cardiac muscle contraction
cell aging
cell cycle arrest
cell growth
cellular response to heat
cellular response to hypoxia
cellular response to nutrient levels
DNA repair
energy reserve metabolic process
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
gene expression
germ cell development
growth
heart morphogenesis
heart valve morphogenesis
innate immune response
insulin receptor signaling pathway
long-term memory
macroautophagy
maternal process involved in female pregnancy
mRNA stabilization
multicellular organism growth
negative regulation of autophagy
negative regulation of cell size
negative regulation of cholangiocyte apoptotic process
negative regulation of iodide transmembrane transport
negative regulation of macroautophagy
negative regulation of muscle atrophy
negative regulation of NFAT protein import into nucleus
negative regulation of protein phosphorylation
negative regulation of protein ubiquitination
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
phosphatidylinositol-mediated signaling
phosphorylation
positive regulation of actin filament polymerization
positive regulation of cell growth involved in cardiac muscle cell development
positive regulation of cholangiocyte proliferation
positive regulation of dendritic spine development
positive regulation of eating behavior
positive regulation of endothelial cell proliferation
positive regulation of gene expression
positive regulation of glial cell proliferation
positive regulation of granulosa cell proliferation
positive regulation of lamellipodium assembly
positive regulation of lipid biosynthetic process
positive regulation of myotube differentiation
positive regulation of neuron death
positive regulation of neuron maturation
positive regulation of nitric oxide biosynthetic process
positive regulation of oligodendrocyte differentiation
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
positive regulation of sensory perception of pain
positive regulation of skeletal muscle hypertrophy
positive regulation of smooth muscle cell proliferation
positive regulation of stress fiber assembly
positive regulation of transcription from RNA polymerase III promoter
positive regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter
positive regulation of translation
post-embryonic development
protein autophosphorylation
protein catabolic process
protein phosphorylation
regulation of actin cytoskeleton organization
regulation of brown fat cell differentiation
regulation of carbohydrate utilization
regulation of cellular response to heat
regulation of fatty acid beta-oxidation
regulation of glycogen biosynthetic process
regulation of GTPase activity
regulation of membrane permeability
regulation of myelination
regulation of osteoclast differentiation
regulation of protein kinase activity
regulation of response to food
response to amino acid
response to cocaine
response to morphine
response to nutrient
response to stress
ruffle organization
signal transduction
social behavior
spinal cord development
T cell costimulation
TOR signaling
transcription initiation from RNA polymerase II promoter
vascular endothelial growth factor receptor signaling pathway
visual learning
voluntary musculoskeletal movement
wound healing
Gene Ontology Molecular Function:: ATP binding
drug binding
kinase activity
phosphoprotein binding
protein serine/threonine kinase activity
ribosome binding
RNA polymerase III type 1 promoter DNA binding
RNA polymerase III type 2 promoter DNA binding
RNA polymerase III type 3 promoter DNA binding
TFIIIC-class transcription factor binding
Gene Ontology Cellular Component:: cytoplasm
cytosol
dendrite
endomembrane system
endoplasmic reticulum membrane
Golgi membrane
lysosomal membrane
lysosome
membrane
mitochondrial outer membrane
neuronal cell body
nucleoplasm
phosphatidylinositol 3-kinase complex
PML body
TORC1 complex
TORC2 complex
Keywords:: 3D-structure
ATP-binding
Acetylation
Complete proteome
Cytoplasm
Disease mutation
Endoplasmic reticulum
Epilepsy
Golgi apparatus
Kinase
Lysosome
Membrane
Mental retardation
Microsome
Mitochondrion
Mitochondrion outer membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
TPR repeat
Transferase
Interacts With:: P31749; Q8TB45; Q13541; P62942; Q9BVC4; Q13615; Q8TCU6; P62820; Q6R327; Q8N122; Q96EB6; Q8NHX9

Names & Taxonomy

Structure

Subcellular location

Function

Publication