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)
1_MLGTG 6_ PAAAT 11_ TAATT 16_ SSNVS 21_ VLQQF 26_ ASGLK 31_ SRNEE 36_ TRAKA 41_ AKELQ 46_ HYVTM 51_ ELREM 56_ SQEES 61_ TRFYD 66_ QLNHH 71_ IFELV 76_ SSSDA 81_ NERKG 86_ GILAI 91_ ASLIG 96_ VEGGN 101_ ATRIG 106_ RFANY 111_ LRNLL 116_ PSNDP 121_ VVMEM 126_ ASKAI 131_ GRLAM 136_ AGDTF 141_ TAEYV 146_ EFEVK 151_ RALEW 156_ LGADR 161_ NEGRR 166_ HAAVL 171_ VLREL 176_ AISVP 181_ TFFFQ 186_ QVQPF 191_ FDNIF 196_ VAVWD 201_ PKQAI 206_ REGAV 211_ AALRA 216_ CLILT 221_ TQREP 226_ KEMQK 231_ PQWYR 236_ HTFEE 241_ AEKGF 246_ DETLA 251_ KEKGM 256_ NRDDR 261_ IHGAL 266_ LILNE 271_ LVRIS 276_ SMEGE 281_ RLREE 286_ MEEIT 291_ QQQLV 296_ HDKYC 301_ KDLMG 306_ FGTKP 311_ RHITP 316_ FTSFQ 321_ AVQPQ 326_ QSNAL 331_ VGLLG 336_ YSSHQ 341_ GLMGF 346_ GTSPS 351_ PAKST 356_ LVESR 361_ CCRDL 366_ MEEKF 371_ DQVCQ 376_ WVLKC 381_ RNSKN 386_ SLIQM 391_ TILNL 396_ LPRLA 401_ AFRPS 406_ AFTDT 411_ QYLQD 416_ TMNHV 421_ LSCVK 426_ KEKER 431_ TAAFQ 436_ ALGLL 441_ SVAVR 446_ SEFKV 451_ YLPRV 456_ LDIIR 461_ AALPP 466_ KDFAH 471_ KRQKA 476_ MQVDA 481_ TVFTC 486_ ISMLA 491_ RAMGP 496_ GIQQD 501_ IKELL 506_ EPMLA 511_ VGLSP 516_ ALTAV 521_ LYDLS 526_ RQIPQ 531_ LKKDI 536_ QDGLL 541_ KMLSL 546_ VLMHK 551_ PLRHP 556_ GMPKG 561_ LAHQL 566_ ASPGL 571_ TTLPE 576_ ASDVG 581_ SITLA 586_ LRTLG 591_ SFEFE 596_ GHSLT 601_ QFVRH 606_ CADHF 611_ LNSEH 616_ KEIRM 621_ EAART 626_ CSRLL 631_ TPSIH 636_ LISGH 641_ AHVVS 646_ QTAVQ 651_ VVADV 656_ LSKLL 661_ VVGIT 666_ DPDPD 671_ IRYCV 676_ LASLD 681_ ERFDA 686_ HLAQA 691_ ENLQA 696_ LFVAL 701_ NDQVF 706_ EIREL 711_ AICTV 716_ GRLSS 721_ MNPAF 726_ VMPFL 731_ RKMLI 736_ QILTE 741_ LEHSG 746_ IGRIK 751_ EQSAR 756_ MLGHL 761_ VSNAP 766_ RLIRP 771_ YMEPI 776_ LKALI 781_ LKLKD 786_ PDPDP 791_ NPGVI 796_ NNVLA 801_ TIGEL 806_ AQVSG 811_ LEMRK 816_ WVDEL 821_ FIIIM 826_ DMLQD 831_ SSLLA 836_ KRQVA 841_ LWTLG 846_ QLVAS 851_ TGYVV 856_ EPYRK 861_ YPTLL 866_ EVLLN 871_ FLKTE 876_ QNQGT 881_ RREAI 886_ RVLGL 891_ LGALD 896_ PYKHK 901_ VNIGM 906_ IDQSR 911_ DASAV 916_ SLSES 921_ KSSQD 926_ SSDYS 931_ TSEML 936_ VNMGN 941_ LPLDE 946_ FYPAV 951_ SMVAL 956_ MRIFR 961_ DQSLS 966_ HHHTM 971_ VVQAI 976_ TFIFK 981_ SLGLK 986_ CVQFL 991_ PQVMP 996_ TFLNV 1001_ IRVCD 1006_ GAIRE 1011_ FLFQQ 1016_ LGMLV 1021_ SFVKS 1026_ HIRPY 1031_ MDEIV 1036_ TLMRE 1041_ FWVMN 1046_ TSIQS 1051_ TIILL 1056_ IEQIV 1061_ VALGG 1066_ EFKLY 1071_ LPQLI 1076_ PHMLR 1081_ VFMHD 1086_ NSPGR 1091_ IVSIK 1096_ LLAAI 1101_ QLFGA 1106_ NLDDY 1111_ LHLLL 1116_ PPIVK 1121_ LFDAP 1126_ EAPLP 1131_ SRKAA 1136_ LETVD 1141_ RLTES 1146_ LDFTD 1151_ YASRI 1156_ IHPIV 1161_ RTLDQ 1166_ SPELR 1171_ STAMD 1176_ TLSSL 1181_ VFQLG 1186_ KKYQI 1191_ FIPMV 1196_ NKVLV 1201_ RHRIN 1206_ HQRYD 1211_ VLICR 1216_ IVKGY 1221_ TLADE 1226_ EEDPL 1231_ IYQHR 1236_ MLRSG 1241_ QGDAL 1246_ ASGPV 1251_ ETGPM 1256_ KKLHV 1261_ STINL 1266_ QKAWG 1271_ AARRV 1276_ SKDDW 1281_ LEWLR 1286_ RLSLE 1291_ LLKDS 1296_ SSPSL 1301_ RSCWA 1306_ LAQAY 1311_ NPMAR 1316_ DLFNA 1321_ AFVSC 1326_ WSELN 1331_ EDQQD 1336_ ELIRS 1341_ IELAL 1346_ TSQDI 1351_ AEVTQ 1356_ TLLNL 1361_ AEFME 1366_ HSDKG 1371_ PLPLR 1376_ DDNGI 1381_ VLLGE 1386_ RAAKC 1391_ RAYAK 1396_ ALHYK 1401_ ELEFQ 1406_ KGPTP 1411_ AILES 1416_ LISIN 1421_ NKLQQ 1426_ PEAAA 1431_ GVLEY 1436_ AMKHF 1441_ GELEI 1446_ QATWY 1451_ EKLHE 1456_ WEDAL 1461_ VAYDK 1466_ KMDTN 1471_ KDDPE 1476_ LMLGR 1481_ MRCLE 1486_ ALGEW 1491_ GQLHQ 1496_ QCCEK 1501_ WTLVN 1506_ DETQA 1511_ KMARM 1516_ AAAAA 1521_ WGLGQ 1526_ WDSME 1531_ EYTCM 1536_ IPRDT 1541_ HDGAF 1546_ YRAVL 1551_ ALHQD 1556_ LFSLA 1561_ QQCID 1566_ KARDL 1571_ LDAEL 1576_ TAMAG 1581_ ESYSR 1586_ AYGAM 1591_ VSCHM 1596_ LSELE 1601_ EVIQY 1606_ KLVPE 1611_ RREII 1616_ RQIWW 1621_ ERLQG 1626_ CQRIV 1631_ EDWQK 1636_ ILMVR 1641_ SLVVS 1646_ PHEDM 1651_ RTWLK 1656_ YASLC 1661_ GKSGR 1666_ LALAH 1671_ KTLVL 1676_ LLGVD 1681_ PSRQL 1686_ DHPLP 1691_ TVHPQ 1696_ VTYAY 1701_ MKNMW 1706_ KSARK 1711_ IDAFQ 1716_ HMQHF 1721_ VQTMQ 1726_ QQAQH 1731_ AIATE 1736_ DQQHK 1741_ QELHK 1746_ LMARC 1751_ FLKLG 1756_ EWQLN 1761_ LQGIN 1766_ ESTIP 1771_ KVLQY 1776_ YSAAT 1781_ EHDRS 1786_ WYKAW 1791_ HAWAV 1796_ MNFEA 1801_ VLHYK 1806_ HQNQA 1811_ RDEKK 1816_ KLRHA 1821_ SGANI 1826_ TNATT 1831_ AATTA 1836_ ATATT 1841_ TASTE 1846_ GSNSE 1851_ SEAES 1856_ TENSP 1861_ TPSPL 1866_ QKKVT 1871_ EDLSK 1876_ TLLMY 1881_ TVPAV 1886_ QGFFR 1891_ SISLS 1896_ RGNNL 1901_ QDTLR 1906_ VLTLW 1911_ FDYGH 1916_ WPDVN 1921_ EALVE 1926_ GVKAI 1931_ QIDTW 1936_ LQVIP 1941_ QLIAR 1946_ IDTPR 1951_ PLVGR 1956_ LIHQL 1961_ LTDIG 1966_ RYHPQ 1971_ ALIYP 1976_ LTVAS 1981_ KSTTT 1986_ ARHNA 1991_ ANKIL 1996_ KNMCE 2001_ HSNTL 2006_ VQQAM 2011_ MVSEE 2016_ LIRVA 2021_ ILWHE 2026_ MWHEG 2031_ LEEAS 2036_ RLYFG 2041_ ERNVK 2046_ GMFEV 2051_ LEPLH 2056_ AMMER 2061_ GPQTL 2066_ KETSF 2071_ NQAYG 2076_ RDLME 2081_ AQEWC 2086_ RKYMK 2091_ SGNVK 2096_ DLTQA 2101_ WDLYY 2106_ HVFRR 2111_ ISKQL 2116_ PQLTS 2121_ LELQY 2126_ VSPKL 2131_ LMCRD 2136_ LELAV 2141_ PGTYD 2146_ PNQPI 2151_ IRIQS 2156_ IAPSL 2161_ QVITS 2166_ KQRPR 2171_ KLTLM 2176_ GSNGH 2181_ EFVFL 2186_ LKGHE 2191_ DLRQD 2196_ ERVMQ 2201_ LFGLV 2206_ NTLLA 2211_ NDPTS 2216_ LRKNL 2221_ SIQRY 2226_ AVIPL 2231_ STNSG 2236_ LIGWV 2241_ PHCDT 2246_ LHALI 2251_ RDYRE 2256_ KKKIL 2261_ LNIEH 2266_ RIMLR 2271_ MAPDY 2276_ DHLTL 2281_ MQKVE 2286_ VFEHA 2291_ VNNTA 2296_ GDDLA 2301_ KLLWL 2306_ KSPSS 2311_ EVWFD 2316_ RRTNY 2321_ TRSLA 2326_ VMSMV 2331_ GYILG 2336_ LGDRH 2341_ PSNLM 2346_ LDRLS 2351_ GKILH 2356_ IDFGD 2361_ CFEVA 2366_ MTREK 2371_ FPEKI 2376_ PFRLT 2381_ RMLTN 2386_ AMEVT 2391_ GLDGN 2396_ YRITC 2401_ HTVME 2406_ VLREH 2411_ KDSVM 2416_ AVLEA 2421_ FVYDP 2426_ LLNWR 2431_ LMDTN 2436_ TKGNK 2441_ RSRTR 2446_ TDSYS 2451_ AGQSV 2456_ EILDG 2461_ VELGE 2466_ PAHKK 2471_ TGTTV 2476_ PESIH 2481_ SFIGD 2486_ GLVKP 2491_ EALNK 2496_ KAIQI 2501_ INRVR 2506_ DKLTG 2511_ RDFSH 2516_ DDTLD 2521_ VPTQV 2526_ ELLIK 2531_ QATSH 2536_ ENLCQ 2541_CYIGW
1: 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)