Search Results

Overview

Uniprot IDP42345
Protein NameSerine/threonine-protein kinase mTOR
Gene NameMTOR
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1868 TPSPLQKKVTEDLSK
2066 ERGPQTLKETSFNQA
30 QQFASGLKSRNEETR

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, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed: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, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). 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:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). 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:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). 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 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). 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). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). 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). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). 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 (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). 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 (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). 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 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). 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 (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). 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). 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 (PubMed:26584640). 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)

Protein Sequence

10 MLGTGPAAAT 20 TAATTSSNVS 30 VLQQFASGLK 40 SRNEETRAKA 50 AKELQHYVTM 60 ELREMSQEES 70 TRFYDQLNHH 80 IFELVSSSDA 90 NERKGGILAI 100 ASLIGVEGGN 110 ATRIGRFANY 120 LRNLLPSNDP 130 VVMEMASKAI 140 GRLAMAGDTF 150 TAEYVEFEVK 160 RALEWLGADR 170 NEGRRHAAVL 180 VLRELAISVP 190 TFFFQQVQPF 200 FDNIFVAVWD 210 PKQAIREGAV 220 AALRACLILT 230 TQREPKEMQK 240 PQWYRHTFEE 250 AEKGFDETLA 260 KEKGMNRDDR 270 IHGALLILNE 280 LVRISSMEGE 290 RLREEMEEIT 300 QQQLVHDKYC 310 KDLMGFGTKP 320 RHITPFTSFQ 330 AVQPQQSNAL 340 VGLLGYSSHQ 350 GLMGFGTSPS 360 PAKSTLVESR 370 CCRDLMEEKF 380 DQVCQWVLKC 390 RNSKNSLIQM 400 TILNLLPRLA 410 AFRPSAFTDT 420 QYLQDTMNHV 430 LSCVKKEKER 440 TAAFQALGLL 450 SVAVRSEFKV 460 YLPRVLDIIR 470 AALPPKDFAH 480 KRQKAMQVDA 490 TVFTCISMLA 500 RAMGPGIQQD 510 IKELLEPMLA 520 VGLSPALTAV 530 LYDLSRQIPQ 540 LKKDIQDGLL 550 KMLSLVLMHK 560 PLRHPGMPKG 570 LAHQLASPGL 580 TTLPEASDVG 590 SITLALRTLG 600 SFEFEGHSLT 610 QFVRHCADHF 620 LNSEHKEIRM 630 EAARTCSRLL 640 TPSIHLISGH 650 AHVVSQTAVQ 660 VVADVLSKLL 670 VVGITDPDPD 680 IRYCVLASLD 690 ERFDAHLAQA 700 ENLQALFVAL 710 NDQVFEIREL 720 AICTVGRLSS 730 MNPAFVMPFL 740 RKMLIQILTE 750 LEHSGIGRIK 760 EQSARMLGHL 770 VSNAPRLIRP 780 YMEPILKALI 790 LKLKDPDPDP 800 NPGVINNVLA 810 TIGELAQVSG 820 LEMRKWVDEL 830 FIIIMDMLQD 840 SSLLAKRQVA 850 LWTLGQLVAS 860 TGYVVEPYRK 870 YPTLLEVLLN 880 FLKTEQNQGT 890 RREAIRVLGL 900 LGALDPYKHK 910 VNIGMIDQSR 920 DASAVSLSES 930 KSSQDSSDYS 940 TSEMLVNMGN 950 LPLDEFYPAV 960 SMVALMRIFR 970 DQSLSHHHTM 980 VVQAITFIFK 990 SLGLKCVQFL 1000 PQVMPTFLNV 1010 IRVCDGAIRE 1020 FLFQQLGMLV 1030 SFVKSHIRPY 1040 MDEIVTLMRE 1050 FWVMNTSIQS 1060 TIILLIEQIV 1070 VALGGEFKLY 1080 LPQLIPHMLR 1090 VFMHDNSPGR 1100 IVSIKLLAAI 1110 QLFGANLDDY 1120 LHLLLPPIVK 1130 LFDAPEAPLP 1140 SRKAALETVD 1150 RLTESLDFTD 1160 YASRIIHPIV 1170 RTLDQSPELR 1180 STAMDTLSSL 1190 VFQLGKKYQI 1200 FIPMVNKVLV 1210 RHRINHQRYD 1220 VLICRIVKGY 1230 TLADEEEDPL 1240 IYQHRMLRSG 1250 QGDALASGPV 1260 ETGPMKKLHV 1270 STINLQKAWG 1280 AARRVSKDDW 1290 LEWLRRLSLE 1300 LLKDSSSPSL 1310 RSCWALAQAY 1320 NPMARDLFNA 1330 AFVSCWSELN 1340 EDQQDELIRS 1350 IELALTSQDI 1360 AEVTQTLLNL 1370 AEFMEHSDKG 1380 PLPLRDDNGI 1390 VLLGERAAKC 1400 RAYAKALHYK 1410 ELEFQKGPTP 1420 AILESLISIN 1430 NKLQQPEAAA 1440 GVLEYAMKHF 1450 GELEIQATWY 1460 EKLHEWEDAL 1470 VAYDKKMDTN 1480 KDDPELMLGR 1490 MRCLEALGEW 1500 GQLHQQCCEK 1510 WTLVNDETQA 1520 KMARMAAAAA 1530 WGLGQWDSME 1540 EYTCMIPRDT 1550 HDGAFYRAVL 1560 ALHQDLFSLA 1570 QQCIDKARDL 1580 LDAELTAMAG 1590 ESYSRAYGAM 1600 VSCHMLSELE 1610 EVIQYKLVPE 1620 RREIIRQIWW 1630 ERLQGCQRIV 1640 EDWQKILMVR 1650 SLVVSPHEDM 1660 RTWLKYASLC 1670 GKSGRLALAH 1680 KTLVLLLGVD 1690 PSRQLDHPLP 1700 TVHPQVTYAY 1710 MKNMWKSARK 1720 IDAFQHMQHF 1730 VQTMQQQAQH 1740 AIATEDQQHK 1750 QELHKLMARC 1760 FLKLGEWQLN 1770 LQGINESTIP 1780 KVLQYYSAAT 1790 EHDRSWYKAW 1800 HAWAVMNFEA 1810 VLHYKHQNQA 1820 RDEKKKLRHA 1830 SGANITNATT 1840 AATTAATATT 1850 TASTEGSNSE 1860 SEAESTENSP 1870 TPSPLQKKVT 1880 EDLSKTLLMY 1890 TVPAVQGFFR 1900 SISLSRGNNL 1910 QDTLRVLTLW 1920 FDYGHWPDVN 1930 EALVEGVKAI 1940 QIDTWLQVIP 1950 QLIARIDTPR 1960 PLVGRLIHQL 1970 LTDIGRYHPQ 1980 ALIYPLTVAS 1990 KSTTTARHNA 2000 ANKILKNMCE 2010 HSNTLVQQAM 2020 MVSEELIRVA 2030 ILWHEMWHEG 2040 LEEASRLYFG 2050 ERNVKGMFEV 2060 LEPLHAMMER 2070 GPQTLKETSF 2080 NQAYGRDLME 2090 AQEWCRKYMK 2100 SGNVKDLTQA 2110 WDLYYHVFRR 2120 ISKQLPQLTS 2130 LELQYVSPKL 2140 LMCRDLELAV 2150 PGTYDPNQPI 2160 IRIQSIAPSL 2170 QVITSKQRPR 2180 KLTLMGSNGH 2190 EFVFLLKGHE 2200 DLRQDERVMQ 2210 LFGLVNTLLA 2220 NDPTSLRKNL 2230 SIQRYAVIPL 2240 STNSGLIGWV 2250 PHCDTLHALI 2260 RDYREKKKIL 2270 LNIEHRIMLR 2280 MAPDYDHLTL 2290 MQKVEVFEHA 2300 VNNTAGDDLA 2310 KLLWLKSPSS 2320 EVWFDRRTNY 2330 TRSLAVMSMV 2340 GYILGLGDRH 2350 PSNLMLDRLS 2360 GKILHIDFGD 2370 CFEVAMTREK 2380 FPEKIPFRLT 2390 RMLTNAMEVT 2400 GLDGNYRITC 2410 HTVMEVLREH 2420 KDSVMAVLEA 2430 FVYDPLLNWR 2440 LMDTNTKGNK 2450 RSRTRTDSYS 2460 AGQSVEILDG 2470 VELGEPAHKK 2480 TGTTVPESIH 2490 SFIGDGLVKP 2500 EALNKKAIQI 2510 INRVRDKLTG 2520 RDFSHDDTLD 2530 VPTQVELLIK 2540 QATSHENLCQ CYIGWCPFW

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0000822 inositol hexakisphosphate binding
Molecular Function GO:0004715 non-membrane spanning protein tyrosine kinase activity
Molecular Function GO:0051219 phosphoprotein binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0004713 protein tyrosine kinase activity
Molecular Function GO:0043022 ribosome binding
Molecular Function GO:0001002 RNA polymerase III type 1 promoter sequence-specific DNA binding
Molecular Function GO:0001003 RNA polymerase III type 2 promoter sequence-specific DNA binding
Molecular Function GO:0001006 RNA polymerase III type 3 promoter sequence-specific DNA binding
Molecular Function GO:0001156 TFIIIC-class transcription factor complex binding
Molecular Function GO:0044325 transmembrane transporter binding
Biological Process GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
Biological Process GO:0043276 anoikis
Biological Process GO:0048266 behavioral response to pain
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030425 dendrite
Biological Process GO:0055006 cardiac cell development
Biological Process GO:0034198 cellular response to amino acid starvation
Biological Process GO:0071230 cellular response to amino acid stimulus
Biological Process GO:0071456 cellular response to hypoxia
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:0071233 cellular response to L-leucine
Biological Process GO:1990253 cellular response to leucine starvation
Biological Process GO:0061431 cellular response to methionine
Biological Process GO:0031670 cellular response to nutrient
Biological Process GO:0031669 cellular response to nutrient levels
Biological Process GO:0071470 cellular response to osmotic stress
Biological Process GO:0009267 cellular response to starvation
Biological Process GO:0007010 cytoskeleton organization
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006954 inflammatory response
Cellular Component GO:0012505 endomembrane system
Cellular Component GO:0005783 endoplasmic reticulum
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:0010507 negative regulation of autophagy
Biological Process GO:0046627 negative regulation of insulin receptor signaling pathway
Biological Process GO:1905672 negative regulation of lysosome organization
Biological Process GO:0016242 negative regulation of macroautophagy
Biological Process GO:1900181 negative regulation of protein localization to nucleus
Biological Process GO:0019228 neuronal action potential
Biological Process GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:0030307 positive regulation of cell growth
Biological Process GO:1904690 positive regulation of cytoplasmic translational initiation
Biological Process GO:0010718 positive regulation of epithelial to mesenchymal transition
Biological Process GO:0045821 positive regulation of glycolytic process
Biological Process GO:0051549 positive regulation of keratinocyte migration
Biological Process GO:0046889 positive regulation of lipid biosynthetic process
Biological Process GO:1905857 positive regulation of pentose-phosphate shunt
Biological Process GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Process GO:0045860 positive regulation of protein kinase activity
Biological Process GO:0062027 positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process
Biological Process GO:0045945 positive regulation of transcription by RNA polymerase III
Biological Process GO:1901838 positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
Biological Process GO:0045727 positive regulation of translation
Biological Process GO:0045948 positive regulation of translational initiation
Biological Process GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process
Biological Process GO:1903691 positive regulation of wound healing, spreading of epidermal cells
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0050821 protein stabilization
Biological Process GO:0032956 regulation of actin cytoskeleton organization
Biological Process GO:2000785 regulation of autophagosome assembly
Biological Process GO:0001558 regulation of cell growth
Biological Process GO:0008361 regulation of cell size
Biological Process GO:1900034 regulation of cellular response to heat
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:1904059 regulation of locomotor rhythm
Biological Process GO:1905671 regulation of lysosome organization
Biological Process GO:0016241 regulation of macroautophagy
Biological Process GO:0045670 regulation of osteoclast differentiation
Biological Process GO:1901796 regulation of signal transduction by p53 class mediator
Biological Process GO:0043200 response to amino acid
Biological Process GO:0009408 response to heat
Biological Process GO:0031667 response to nutrient levels
Biological Process GO:0031295 T cell costimulation
Biological Process GO:0002296 T-helper 1 cell lineage commitment
Biological Process GO:0031929 TOR signaling
Biological Process GO:0038202 TORC1 signaling
Biological Process GO:0038203 TORC2 signaling
Biological Process GO:0097700 vascular endothelial cell response to laminar fluid shear stress
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0005794 Golgi apparatus
Cellular Component GO:0000139 Golgi membrane
Cellular Component GO:0005765 lysosomal membrane
Cellular Component GO:0005764 lysosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005741 mitochondrial outer membrane
Cellular Component GO:0005635 nuclear envelope
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0045335 phagocytic vesicle
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0016605 PML body
Cellular Component GO:0031931 TORC1 complex
Cellular Component GO:0031932 TORC2 complex
Molecular Function GO:0005524 ATP binding

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.