MTOR (mechanistic target of rapamycin kinase)

Gene

• Entrez ID: 2475
• Gene name: Mechanistic target of rapamycin kinase
• Gene symbol: MTOR
• Synonyms: FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS
• Chromosome: 1
• Chromosome location: 1p36.22
• Summary: The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs55881943	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs147774167	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant
rs587777893	G>A,T	Not-provided, pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant
rs587777894	G>A,T	Pathogenic, likely-pathogenic, not-provided	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant
rs587777900	C>T	Likely-pathogenic, not-provided	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant
rs774204282	G>A,C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, synonymous variant, missense variant, genic downstream transcript variant
rs778855567	C>A,T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs786205165	C>A,T	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs863225264	C>T	Pathogenic, uncertain-significance	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs869312666	A>C	Pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs878855328	C>T	Pathogenic	Missense variant, coding sequence variant, intron variant, genic downstream transcript variant
rs1057519777	C>G,T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519778	G>T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519779	A>G	Likely-pathogenic, pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519780	C>T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519913	G>C	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519914	A>G	Likely-pathogenic, pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519915	A>C	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519916	T>A	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057519917	A>G,T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057524044	A>G	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1057524049	C>T	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1085307113	A>G,T	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1085307114	A>C	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs1557739557	C>A,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	21878637
MIRT006146	hsa-miR-99a-5p	FACS, Luciferase reporter assay, qRT-PCR, Western blot	22299047
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23292834
MIRT006146	hsa-miR-99a-5p	Reporter assay;Western blot	21383697
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	22751686
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, Western blot	23762265
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23173671
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24668416
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24637915
MIRT006146	hsa-miR-99a-5p	ChIP-seq, Flow, Immunohistochemistry, Immunoprecipitaion, qRT-PCR, Western blot	24810364
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24312487
MIRT006146	hsa-miR-99a-5p	Immunoblot, Luciferase reporter assay, qRT-PCR	25348507
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23893385
MIRT006146	hsa-miR-99a-5p	FACS, Luciferase reporter assay, qRT-PCR, Western blot	24030073
MIRT006146	hsa-miR-99a-5p	Luciferase reporter assay	27158364
MIRT006146	hsa-miR-99a-5p	Flow, Immunohistochemistry, qRT-PCR, Western blot	28387375
MIRT006155	hsa-miR-520c-3p	Luciferase reporter assay, qRT-PCR, Western blot	21898400
MIRT006157	hsa-miR-373-3p	Luciferase reporter assay, qRT-PCR, Western blot	21898400
MIRT006564	hsa-miR-99b-5p	FACS, Luciferase reporter assay, qRT-PCR, Western blot	22299047
MIRT006564	hsa-miR-99b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24668416
MIRT006564	hsa-miR-99b-5p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	26259252
MIRT006872	hsa-miR-144-3p	Luciferase reporter assay	22983984
MIRT006872	hsa-miR-144-3p	Immunofluorescence, Western blot	26687302
MIRT006872	hsa-miR-144-3p	Luciferase reporter assay, qRT-PCR, Western blot	27072960
MIRT007365	hsa-miR-100-5p	Luciferase reporter assay, qRT-PCR, Western blot	23292834
MIRT007365	hsa-miR-100-5p	qRT-PCR, Western blot	23778488
MIRT007365	hsa-miR-100-5p	Luciferase reporter assay	23270926
MIRT007365	hsa-miR-100-5p	FACS, Luciferase reporter assay, qRT-PCR, Western blot	24030073
MIRT007365	hsa-miR-100-5p	Western blot	26744318
MIRT026023	hsa-miR-199a-3p	Immunofluorescence, Microarray, QRTPCR, Western blot	24810336
MIRT026023	hsa-miR-199a-3p	Luciferase reporter assay, Wetsern blot, qRT-PCR	24378853
MIRT026023	hsa-miR-199a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26051997
MIRT026023	hsa-miR-199a-3p	Immunofluorescence, qRT-PCR, Western blot, Immunohistochemistry analysis	25854175
MIRT031485	hsa-miR-16-5p	Proteomics	18668040
MIRT031485	hsa-miR-16-5p	Luciferase reporter assay	25311506
MIRT037492	hsa-miR-744-5p	CLASH	23622248
MIRT047241	hsa-miR-181b-5p	CLASH	23622248
MIRT054040	hsa-miR-101-3p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	22989749
MIRT054040	hsa-miR-101-3p	qRT-PCR, Western blot	26458815
MIRT437347	hsa-let-7c-5p	Luciferase reporter assay	25311506
MIRT440200	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT732906	hsa-miR-496	Luciferase reporter assay	27097372
MIRT733142	hsa-miR-196b-5p	Flow, qRT-PCR, Western blot	26998071
MIRT733173	hsa-miR-224-5p	ChIP-seq, Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	27315344
MIRT733518	hsa-miR-128-3p	Chromatin immunoprecipitation, Immunoblot, Luciferase reporter assay, Microarray, qRT-PCR	27893811
MIRT734058	hsa-miR-193a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24469061
MIRT734303	hsa-miR-125a-5p	qRT-PCR, Western blot	26622553
MIRT734576	hsa-miR-497-5p	Luciferase reporter assay, qRT-PCR, Western blot	26238185
MIRT734711	hsa-miR-3188	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	27095304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0001002	Function	RNA polymerase III type 1 promoter sequence-specific DNA binding	IDA	20233713
GO:0001003	Function	RNA polymerase III type 2 promoter sequence-specific DNA binding	IDA	20233713
GO:0001006	Function	RNA polymerase III type 3 promoter sequence-specific DNA binding	IDA	20233713
GO:0001156	Function	TFIIIC-class transcription factor complex binding	IDA	20543138
GO:0001558	Process	Regulation of cell growth	IDA	18762023
GO:0001933	Process	Negative regulation of protein phosphorylation	IEA
GO:0001938	Process	Positive regulation of endothelial cell proliferation	IEA
GO:0002296	Process	T-helper 1 cell lineage commitment	IEA
GO:0003007	Process	Heart morphogenesis	IEA
GO:0003179	Process	Heart valve morphogenesis	IEA
GO:0004672	Function	Protein kinase activity	IDA	12150926
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	22768106
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	12718876, 15467718, 22343943, 22576015, 22692423, 30704899
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	10089303, 11438723, 12150925, 12150926, 12408816, 15467718, 16915281, 17148612, 17461779, 17565979, 18339839, 18550814, 18566587, 18955708, 19446321, 19619545, 19875983, 20080789, 20543138, 20562859, 20864032, 21045808, 21376236, 21471201, 21614075, 22307628, 22343943, 22424946, 225
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005635	Component	Nuclear envelope	IDA	25294810
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	11853878, 20381137
GO:0005741	Component	Mitochondrial outer membrane	IEA
GO:0005764	Component	Lysosome	IDA	20381137, 25936802, 29750193
GO:0005764	Component	Lysosome	IMP	22424946
GO:0005765	Component	Lysosomal membrane	HDA	17897319
GO:0005765	Component	Lysosomal membrane	IDA	30956113
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005979	Process	Regulation of glycogen biosynthetic process	IEA
GO:0006112	Process	Energy reserve metabolic process	IEA
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IEA
GO:0006468	Process	Protein phosphorylation	IDA	12150926, 15467718, 18925875
GO:0006468	Process	Protein phosphorylation	IMP	17028174
GO:0007040	Process	Lysosome organization	IDA	22692423
GO:0007050	Process	Cell cycle arrest	TAS
GO:0007281	Process	Germ cell development	IEA
GO:0007420	Process	Brain development	IEA
GO:0007569	Process	Cell aging	IEA
GO:0007584	Process	Response to nutrient	IMP	17028174
GO:0007616	Process	Long-term memory	IEA
GO:0008361	Process	Regulation of cell size	IMP	22424946
GO:0008542	Process	Visual learning	IEA
GO:0009267	Process	Cellular response to starvation	IDA	22343943, 22576015, 22692423, 28223137
GO:0009791	Process	Post-embryonic development	IEA
GO:0010507	Process	Negative regulation of autophagy	IDA	22576015, 30704899
GO:0010507	Process	Negative regulation of autophagy	IMP	22424946
GO:0010507	Process	Negative regulation of autophagy	ISS
GO:0010592	Process	Positive regulation of lamellipodium assembly	IEA
GO:0010628	Process	Positive regulation of gene expression	IMP	17028174
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IMP	27919618
GO:0010831	Process	Positive regulation of myotube differentiation	IEA
GO:0010976	Process	Positive regulation of neuron projection development	IEA
GO:0012505	Component	Endomembrane system	IDA	18497260, 22424946
GO:0014042	Process	Positive regulation of neuron maturation	IEA
GO:0014736	Process	Negative regulation of muscle atrophy	IEA
GO:0014823	Process	Response to activity	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IDA	11853878
GO:0016241	Process	Regulation of macroautophagy	TAS
GO:0016242	Process	Negative regulation of macroautophagy	IBA	21873635
GO:0016242	Process	Negative regulation of macroautophagy	IDA	25327288
GO:0016301	Function	Kinase activity	IDA	15467718, 25327288
GO:0016301	Function	Kinase activity	TAS	11853878
GO:0016310	Process	Phosphorylation	IDA	11853878, 25327288
GO:0016605	Component	PML body	ISS
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	22343943, 22576015, 22692423
GO:0018105	Process	Peptidyl-serine phosphorylation	IMP	20537536, 23728790
GO:0018105	Process	Peptidyl-serine phosphorylation	ISS
GO:0018107	Process	Peptidyl-threonine phosphorylation	IEA
GO:0019901	Function	Protein kinase binding	IEA
GO:0019904	Function	Protein domain specific binding	IEA
GO:0021510	Process	Spinal cord development	IEA
GO:0030163	Process	Protein catabolic process	TAS	11853878
GO:0030425	Component	Dendrite	IEA
GO:0030838	Process	Positive regulation of actin filament polymerization	IEA
GO:0031397	Process	Negative regulation of protein ubiquitination	IEA
GO:0031529	Process	Ruffle organization	IEA
GO:0031641	Process	Regulation of myelination	IEA
GO:0031667	Process	Response to nutrient levels	IDA	29750193
GO:0031669	Process	Cellular response to nutrient levels	ISS
GO:0031929	Process	TOR signaling	IMP	15467718, 17028174, 18762023, 26018084, 29750193
GO:0031929	Process	TOR signaling	NAS	23778976
GO:0031931	Component	TORC1 complex	IBA	21873635
GO:0031931	Component	TORC1 complex	IDA	12150926, 12718876, 15467718, 18925875
GO:0031931	Component	TORC1 complex	IMP	20537536
GO:0031932	Component	TORC2 complex	IBA	21873635
GO:0031932	Component	TORC2 complex	IDA	15467718, 18925875
GO:0031998	Process	Regulation of fatty acid beta-oxidation	IEA
GO:0032095	Process	Regulation of response to food	IEA
GO:0032148	Process	Activation of protein kinase B activity	TAS
GO:0032516	Process	Positive regulation of phosphoprotein phosphatase activity	TAS	28386764
GO:0032868	Process	Response to insulin	IEA
GO:0032956	Process	Regulation of actin cytoskeleton organization	IMP	15467718
GO:0034198	Process	Cellular response to amino acid starvation	IDA	22343943, 22424946, 22576015, 22692423
GO:0035176	Process	Social behavior	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0038202	Process	TORC1 signaling	IBA	21873635
GO:0038202	Process	TORC1 signaling	IDA	28223137
GO:0038202	Process	TORC1 signaling	IMP	12718876, 22424946
GO:0042060	Process	Wound healing	IEA
GO:0042220	Process	Response to cocaine	IEA
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0042802	Function	Identical protein binding	IPI	11438723, 24670654
GO:0043022	Function	Ribosome binding	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0043087	Process	Regulation of GTPase activity	IEA
GO:0043200	Process	Response to amino acid	IDA	18497260
GO:0043276	Process	Anoikis	NAS	23778976
GO:0043278	Process	Response to morphine	IEA
GO:0043610	Process	Regulation of carbohydrate utilization	IEA
GO:0045182	Function	Translation regulator activity	IEA
GO:0045335	Component	Phagocytic vesicle	IDA	27623384
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IEA
GO:0045670	Process	Regulation of osteoclast differentiation	ISS
GO:0045727	Process	Positive regulation of translation	IDA	18762023
GO:0045792	Process	Negative regulation of cell size	IEA
GO:0045945	Process	Positive regulation of transcription by RNA polymerase III	IMP	20233713
GO:0046777	Process	Protein autophosphorylation	IDA	15467718
GO:0046889	Process	Positive regulation of lipid biosynthetic process	IMP	18762023
GO:0048255	Process	MRNA stabilization	IEA
GO:0048511	Process	Rhythmic process	IEA
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0048714	Process	Positive regulation of oligodendrocyte differentiation	IEA
GO:0050731	Process	Positive regulation of peptidyl-tyrosine phosphorylation	IEA
GO:0050882	Process	Voluntary musculoskeletal movement	IEA
GO:0051219	Function	Phosphoprotein binding	IPI	11853878
GO:0051496	Process	Positive regulation of stress fiber assembly	IEA
GO:0051549	Process	Positive regulation of keratinocyte migration	IMP	27919618
GO:0051647	Process	Nucleus localization	IDA	22343943, 22576015, 22692423
GO:0051897	Process	Positive regulation of protein kinase B signaling	IEA
GO:0055013	Process	Cardiac muscle cell development	IEA
GO:0060048	Process	Cardiac muscle contraction	IEA
GO:0060135	Process	Maternal process involved in female pregnancy	IEA
GO:0060252	Process	Positive regulation of glial cell proliferation	IEA
GO:0060999	Process	Positive regulation of dendritic spine development	IEA
GO:0061051	Process	Positive regulation of cell growth involved in cardiac muscle cell development	IEA
GO:0070885	Process	Negative regulation of calcineurin-NFAT signaling cascade	IEA
GO:0071230	Process	Cellular response to amino acid stimulus	IDA	22424946
GO:0071233	Process	Cellular response to leucine	IDA	22424946
GO:0071456	Process	Cellular response to hypoxia	ISS
GO:0090335	Process	Regulation of brown fat cell differentiation	IEA
GO:0090559	Process	Regulation of membrane permeability	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099524	Component	Postsynaptic cytosol	IEA
GO:0099547	Process	Regulation of translation at synapse, modulating synaptic transmission	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1901216	Process	Positive regulation of neuron death	IEA
GO:1901838	Process	Positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	IMP	24036451
GO:1903691	Process	Positive regulation of wound healing, spreading of epidermal cells	IMP	27919618
GO:1904000	Process	Positive regulation of eating behavior	IEA
GO:1904056	Process	Positive regulation of cholangiocyte proliferation	IEA
GO:1904058	Process	Positive regulation of sensory perception of pain	IEA
GO:1904059	Process	Regulation of locomotor rhythm	ISS
GO:1904193	Process	Negative regulation of cholangiocyte apoptotic process	IEA
GO:1904197	Process	Positive regulation of granulosa cell proliferation	IEA
GO:1904206	Process	Positive regulation of skeletal muscle hypertrophy	IEA
GO:1904213	Process	Negative regulation of iodide transmembrane transport	IEA
GO:1904690	Process	Positive regulation of cytoplasmic translational initiation	TAS	28386764
GO:1990253	Process	Cellular response to leucine starvation	IDA	22424946

Other IDs

• MIM: 601231
• HGNC: 3942
• e!Ensembl: ENSG00000198793

Protein

• UniProt ID: P42345
• Protein name: 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)
• Protein 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). 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) (PubMed:15268862, PubMed:15467718, PubMed:18925875, PubMed:18497260, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704). Activated mTORC1 up-regulates protein 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). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (By similarity). 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:12150925, PubMed:12087098, PubMed:18925875). This also includes mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3: in the presence of nutrients, mediates phosphorylation of TFEB and TFE3, promoting their cytosolic retention and inactivation (PubMed:22576015, PubMed:22343943, PubMed:22692423). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423). 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:23429704, PubMed:23429703). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (By similarity). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). mTORC1 also negatively regulates autophagy through phosphorylation of ULK1 (By similarity). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (By similarity). 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). 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). As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton (PubMed:15268862, PubMed:15467718). 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 (PubMed:15718470). 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). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). 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). Phosphorylates SQSTM1, promoting interaction between SQSTM1 and KEAP1 and subsequent inactivation of the BCR(KEAP1) complex (By similarity).
• PDB: 1AUE, 1FAP, 1NSG, 2FAP, 2GAQ, 2NPU, 2RSE, 3FAP, 3JBZ, 4DRH, 4DRI, 4DRJ, 4FAP, 4JSN, 4JSP, 4JSV, 4JSX, 4JT5, 4JT6, 5FLC, 5GPG, 5H64, 5WBH, 5WBU, 5WBY, 5ZCS, 6BCU, 6BCX, 6M4U, 6M4W, 6SB0, 6SB2, 6ZWM, 6ZWO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11865	DUF3385	854 → 1024	Domain of unknown function (DUF3385)	Family
  PF02259	FAT	1513 → 1908	FAT domain	Family
  PF08771	FRB_dom	2015 → 2113	FKBP12-rapamycin binding domain	Domain
  PF00454	PI3_PI4_kinase	2181 → 2431	Phosphatidylinositol 3- and 4-kinase	Family
  PF02260	FATC	2518 → 2549	FATC domain	Family

• Sequence:

  MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEES
  TRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDP
  VVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVP
  TFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEE
  AEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYC
  KDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESR
  CCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHV
  LSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDA
  TVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLL
  KMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLT
  QFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLL
  VVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSS
  MNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALI
  LKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVA
  LWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHK
  VNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFR
  DQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLV
  SFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLR
  VFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVD
  RLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLV
  RHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHV
  STINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNA
  AFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGI
  VLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHF
  GELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEK
  WTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLA
  QQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWW
  ERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVD
  PSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHK
  QELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEA
  VLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSP
  TPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVN
  EALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVAS
  KSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFG
  ERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQA
  WDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSL
  QVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNL
  SIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTL
  MQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRH
  PSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITC
  HTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDG
  VELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLD
  VPTQVELLIKQATSHENLCQCYIGWCPFW

• Sequence length: 2549