Uniprot ID: P42345	Protein name : Serine/threonine-protein kinase mTOR	Gene : MTOR FRAP FRAP1 FRAP2 RAFT1 RAPT1
Protein Families : PI3/PI4-kinase family	Squence Length : 2549

Sequence	>P42345 2550 MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW
Repeat regions	REPEAT 16 53 HEAT 1 REPEAT 55 99 HEAT 2 REPEAT 100 137 HEAT 3 REPEAT 138 179 HEAT 4 REPEAT 180 220 HEAT 5 REPEAT 222 276 HEAT 6 REPEAT 277 313 HEAT 7 REPEAT 314 364 HEAT 8 REPEAT 365 409 HEAT 9 REPEAT 410 445 HEAT 10 REPEAT 446 494 HEAT 11 REPEAT 495 529 HEAT 12 REPEAT 530 563 HEAT 13 REPEAT 564 596 HEAT 14 REPEAT 597 636 HEAT 15 REPEAT 637 683 HEAT 16 REPEAT 686 724 HEAT 17 REPEAT 727 766 HEAT 18 REPEAT 769 811 HEAT 19 REPEAT 814 853 HEAT 20 REPEAT 857 893 HEAT 21 REPEAT 894 942 HEAT 22 REPEAT 943 988 HEAT 23 REPEAT 989 1027 HEAT 24 REPEAT 1029 1068 HEAT 25 REPEAT 1069 1105 HEAT 26 REPEAT 1106 1144 HEAT 27 REPEAT 1145 1188 HEAT 28 REPEAT 1189 1225 HEAT 29 REPEAT 1226 1273 HEAT 30 REPEAT 1274 1311 HEAT 31 REPEAT 1312 1345 HEAT 32 REPEAT 1346 1382 TPR 1 REPEAT 1383 1408 TPR 2 REPEAT 1409 1442 TPR 3 REPEAT 1443 1473 TPR 4 REPEAT 1474 1507 TPR 5 REPEAT 1508 1541 TPR 6 REPEAT 1542 1574 TPR 7 REPEAT 1575 1614 TPR 8 REPEAT 1615 1649 TPR 9 REPEAT 1650 1693 TPR 10 REPEAT 1694 1731 TPR 11 REPEAT 1732 1786 TPR 12 REPEAT 1787 1846 TPR 13 REPEAT 1898 1930 TPR 14 REPEAT 1931 1970 TPR 15 REPEAT 1971 2005 TPR 16
Sequence region of repeats	16- 53 NVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREM 55- 99 QEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNA 100- 137 TRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDT 138- 179 FTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPT 180- 220 FFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQ 222- 276 EPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSME 277- 313 GERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITP 314- 364 FTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLM 365- 409 EEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQ 410- 445 YLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSE 446- 494 FKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPG 495- 529 IQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQL 530- 563 KKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQL 564- 596 ASPGLTTLPEASDVGSITLALRTLGSFEFEGHS 597- 636 LTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLIS 637- 683 GHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDA 686- 724 AQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFV 727- 766 FLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLI 769- 811 YMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEM 814- 853 WVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVV 857- 893 RKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALD 894- 942 PYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLD 943- 988 EFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFL 989- 1027 PQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRP 1029- 1068 MDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLY 1069- 1105 LPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGANL 1106- 1144 DDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTESL 1145- 1188 DFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQI 1189- 1225 FIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEE 1226- 1273 DPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAARRV 1274- 1311 SKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPM 1312- 1345 ARDLFNAAFVSCWSELNEDQQDELIRSIELALTS
Domains	DOMAIN 1382 1982 FAT. DOMAIN 2182 2516 PI3K/PI4K. DOMAIN 2517 2549 FATC
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' (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). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity)"
Mutation	2159 2159 S->A: Reduces mTORC1-associated S-2481 autophosphorylation when associated with A-2164 2159 2159 S->D: Stronger phosphorylation of RPS6KB1 when associated with E-2164 2164 2164 T->A: Reduces mTORC1-associated S-2481 autophosphorylation when associated with A-2159 2164 2164 T->E: Stronger phosphorylation of RPS6KB1 when associated with D-2159 2173 2173 T->A: Increased mTOR kinase activity 2340 2340 H->A: Barely detectable kinase activity
Disease	"DISEASE: Smith-Kingsmore syndrome (SKS) [MIM:616638]: An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells Note=The disease is caused by mutations affecting the gene represented in this entry"

P42345 Proteins with HEAT Repeats