MTOR protein expression summary - The Human Protein Atlas

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MTOR

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MTOR

MTOR INFORMATION
Proteinⁱ Full gene name according to HGNC.	Mechanistic target of rapamycin kinase
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	MTOR (FLJ44809, FRAP, FRAP1, FRAP2, RAFT1, RAPT1)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s). Read more	Cancer-related genes Disease related genes Enzymes Essential proteins FDA approved drug targets Human disease related genes Plasma proteins
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	3
Protein interactions	Interacting with 21 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Cytoplasmic expression in most tissues.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Golgi apparatus, Cytosol
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Intracellular

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Low tissue specificity
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Sub-cortical - Mixed function (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Low cell type specificity
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Testis - Early spermatids, Testis - Spermatocytes)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Low immune cell specificity
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Unknown function (mainly)

CANCER & CELL LINES
Prognostic summary	MTOR is not prognostic
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Low cancer specificity
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - mRNA processing (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Low cancer specificity

PROTEINS IN BLOOD
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics dataset obtained from the PeptideAtlas. Read more	No
Proximity extension assayⁱ Indicates whether the protein has been measured (Data available) or not (Not available) using the Olink Explore HT proximity extension assay platform. Read more	Not available
SomaScanⁱ Indicates whether the protein has been measured (Data available) or not (Not available) using the SomaScan 11K platform. Read more	Data available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	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 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51. 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 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) 76, 77. 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 78, 79, 80, 81, 82. 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 83, 84. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor 85. Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation 86. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 87. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 88. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 89. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP 90. Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions 91. Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA 92, 93. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor 94. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules 95. The mTORC1 complex is inhibited in response to starvation and amino acid depletion 96, 97, 98, 99. The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation 100, 101, 102, 103, 104, 105, 106. Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity 107, 108, 109, 110, 111, 112. The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization 113. MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output 114, 115, 116, 117, 118, 119. In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 120, 121, 122, 123, 124, 125, 126. In contrast to mTORC1, mTORC2 is nutrient-insensitive 127. mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation 128, 129, 130, 131, 132. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' 133. 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 134. The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo 135. 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).... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Kinase, Serine/threonine-protein kinase, Transferase
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	ATP-binding, Nucleotide-binding
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	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]... show less

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