TOR_DROME
ID TOR_DROME Reviewed; 2470 AA.
AC Q9VK45;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Serine/threonine-protein kinase Tor;
DE EC=2.7.11.1;
DE AltName: Full=Target of rapamycin;
GN Name=Tor; ORFNames=CG5092;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-1956.
RX PubMed=11069885; DOI=10.1101/gad.845700;
RA Oldham S., Montagne J., Radimerski T., Thomas G., Hafen E.;
RT "Genetic and biochemical characterization of dTOR, the Drosophila homolog
RT of the target of rapamycin.";
RL Genes Dev. 14:2689-2694(2000).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11069888; DOI=10.1101/gad.835000;
RA Zhang H., Stallock J.P., Ng J.C., Reinhard C., Neufeld T.P.;
RT "Regulation of cellular growth by the Drosophila target of rapamycin
RT dTOR.";
RL Genes Dev. 14:2712-2724(2000).
RN [5]
RP FUNCTION.
RX PubMed=14505573; DOI=10.1016/s0092-8674(03)00713-x;
RA Colombani J., Raisin S., Pantalacci S., Radimerski T., Montagne J.,
RA Leopold P.;
RT "A nutrient sensor mechanism controls Drosophila growth.";
RL Cell 114:739-749(2003).
RN [6]
RP REVIEW.
RX PubMed=12559758; DOI=10.1016/s0962-8924(02)00042-9;
RA Oldham S., Hafen E.;
RT "Insulin/IGF and target of rapamycin signaling: a TOR de force in growth
RT control.";
RL Trends Cell Biol. 13:79-85(2003).
RN [7]
RP FUNCTION.
RX PubMed=15454083; DOI=10.1016/j.cell.2004.08.028;
RA Bateman J.M., McNeill H.;
RT "Temporal control of differentiation by the insulin receptor/tor pathway in
RT Drosophila.";
RL Cell 119:87-96(2004).
RN [8]
RP REVIEW.
RX PubMed=16469695; DOI=10.1016/j.cell.2006.01.016;
RA Wullschleger S., Loewith R., Hall M.N.;
RT "TOR signaling in growth and metabolism.";
RL Cell 124:471-484(2006).
RN [9]
RP SUBUNIT.
RX PubMed=16219781; DOI=10.1534/genetics.105.051979;
RA Zhang Y., Billington C.J. Jr., Pan D., Neufeld T.P.;
RT "Drosophila target of rapamycin kinase functions as a multimer.";
RL Genetics 172:355-362(2006).
RN [10]
RP FUNCTION.
RX PubMed=18604198; DOI=10.1038/ncb1753;
RA Kim E., Goraksha-Hicks P., Li L., Neufeld T.P., Guan K.L.;
RT "Regulation of TORC1 by Rag GTPases in nutrient response.";
RL Nat. Cell Biol. 10:935-945(2008).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=19211682; DOI=10.1242/dev.027466;
RA Demontis F., Perrimon N.;
RT "Integration of Insulin receptor/Foxo signaling and dMyc activity during
RT muscle growth regulates body size in Drosophila.";
RL Development 136:983-993(2009).
RN [12]
RP REVIEW.
RX PubMed=18992839; DOI=10.1016/j.biocel.2008.10.010;
RA Grewal S.S.;
RT "Insulin/TOR signaling in growth and homeostasis: a view from the fly
RT world.";
RL Int. J. Biochem. Cell Biol. 41:1006-1010(2009).
RN [13]
RP FUNCTION.
RX PubMed=19225150; DOI=10.1091/mbc.e08-12-1250;
RA Chang Y.Y., Neufeld T.P.;
RT "An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy
RT regulation.";
RL Mol. Biol. Cell 20:2004-2014(2009).
RN [14]
RP FUNCTION.
RX PubMed=25920570; DOI=10.1016/j.devcel.2015.03.013;
RA Tiebe M., Lutz M., De La Garza A., Buechling T., Boutros M., Teleman A.A.;
RT "REPTOR and REPTOR-BP regulate organismal metabolism and transcription
RT downstream of TORC1.";
RL Dev. Cell 33:272-284(2015).
CC -!- FUNCTION: Promotes cell and tissue growth, maintains tissue homeostatis
CC and controls responses to environmental stress and aging
CC (PubMed:11069885, PubMed:11069888, PubMed:19211682, PubMed:19225150).
CC Regulates growth during animal development by coupling growth factor
CC signaling to nutrient availability (PubMed:11069888). Central
CC regulators of autophagy (PubMed:18604198, PubMed:19225150). May be
CC involved in atg1 phosphorylation (PubMed:19225150). May also be
CC involved, directly or indirectly, in the control of neuronal function
CC (PubMed:15454083). Phosphorylates S6K/p70S6K, in vitro
CC (PubMed:11069888). May regulate the activity of S6K (PubMed:11069885).
CC Overexpression inhibits growth and reduces cell size (PubMed:14505573).
CC Affects the timing of neuronal cell differentiation (PubMed:15454083).
CC Hyperactivation of the signaling leads to accelerated differentiation,
CC whereas inhibition of the signaling retards differentiation
CC (PubMed:15454083). Thus, in addition to controlling growth of the cell
CC in which it resides, it can also influence growth of distant cells and
CC organs during development via a humoral mechanism (PubMed:14505573). As
CC part of the TORC1 complex regulates energy homeostasis and promotes
CC certain aspects of larval growth by negatively regulating REPTOR
CC (PubMed:25920570). REPTOR functions downstream of TORC1 to regulate the
CC expression of stress response genes in response to TORC1 inhibition
CC resulting from nutrient deprivation (PubMed:25920570). When TORC1
CC activity is high it phosphorylates REPTOR which inhibits its
CC recruitment into the nucleus and antagonizes their function
CC (PubMed:25920570). This function is essential under normal feeding
CC conditions to promote TORC1-dependent growth during larval development
CC and, in adults and larvae to prevent the REPTOR-dependent expression of
CC nutrient stress response genes (PubMed:25920570). In short, during
CC development, it primarily controls growth, whereas in the adult, where
CC there is relatively little growth, it controls aging and other aspects
CC of nutrient-related physiology (PubMed:11069885, PubMed:11069888,
CC PubMed:19211682, PubMed:19225150). Rag GTPases act as activators of
CC TORC1 in response to amino acid signals (PubMed:18604198).
CC {ECO:0000269|PubMed:11069885, ECO:0000269|PubMed:11069888,
CC ECO:0000269|PubMed:14505573, ECO:0000269|PubMed:15454083,
CC ECO:0000269|PubMed:18604198, ECO:0000269|PubMed:19211682,
CC ECO:0000269|PubMed:19225150, ECO:0000269|PubMed:25920570}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: May be part of a minimal complex, TORC1, consisting of tor,
CC raptor and lst8. May be part of a minimal complex, TORC2, consisting of
CC tor, rictor and lst8 (By similarity). Self-associates; assembles into
CC homomultimeric complexes. Component of a multiprotein complex.
CC {ECO:0000250, ECO:0000269|PubMed:16219781}.
CC -!- INDUCTION: By PI3K/Akt signaling, or by nutrients such as amino acids,
CC and by high cellular energy levels. {ECO:0000269|PubMed:19211682}.
CC -!- DISRUPTION PHENOTYPE: Not lethal. Displays phenotypes characteristic of
CC amino acid deprivation, including reduced nucleolar size, lipid vesicle
CC aggregation in the larval fat body, and a cell type-specific pattern of
CC cell cycle arrest that can be bypassed by overexpression of the S-phase
CC regulator cyclin E. Reach only the size of second instar larvae, at
CC which point they undergo cell cycle arrest.
CC {ECO:0000269|PubMed:11069885, ECO:0000269|PubMed:11069888}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; AE014134; AAF53237.1; -; Genomic_DNA.
DR RefSeq; NP_524891.1; NM_080152.3.
DR AlphaFoldDB; Q9VK45; -.
DR SMR; Q9VK45; -.
DR BioGRID; 70789; 52.
DR IntAct; Q9VK45; 16.
DR STRING; 7227.FBpp0080003; -.
DR PaxDb; Q9VK45; -.
DR PRIDE; Q9VK45; -.
DR EnsemblMetazoa; FBtr0080422; FBpp0080003; FBgn0021796.
DR GeneID; 47396; -.
DR KEGG; dme:Dmel_CG5092; -.
DR UCSC; CG5092-RA; d. melanogaster.
DR FlyBase; FBgn0021796; Tor.
DR VEuPathDB; VectorBase:FBgn0021796; -.
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00930000151037; -.
DR HOGENOM; CLU_000178_7_1_1; -.
DR InParanoid; Q9VK45; -.
DR OMA; DPYKHQQ; -.
DR PhylomeDB; Q9VK45; -.
DR Reactome; R-DME-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DME-1632852; Macroautophagy.
DR Reactome; R-DME-165159; MTOR signalling.
DR Reactome; R-DME-166208; mTORC1-mediated signalling.
DR Reactome; R-DME-3371571; HSF1-dependent transactivation.
DR Reactome; R-DME-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-DME-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DME-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-DME-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DME-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-DME-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q9VK45; -.
DR BioGRID-ORCS; 47396; 2 hits in 3 CRISPR screens.
DR ChiTaRS; Egfr; fly.
DR GenomeRNAi; 47396; -.
DR PRO; PR:Q9VK45; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0021796; Expressed in eye disc (Drosophila) and 25 other tissues.
DR ExpressionAtlas; Q9VK45; baseline and differential.
DR Genevisible; Q9VK45; DM.
DR GO; GO:0005737; C:cytoplasm; HDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0031931; C:TORC1 complex; IMP:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:FlyBase.
DR GO; GO:0004672; F:protein kinase activity; IDA:FlyBase.
DR GO; GO:0043621; F:protein self-association; IDA:FlyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:FlyBase.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:InterPro.
DR GO; GO:0045176; P:apical protein localization; IMP:FlyBase.
DR GO; GO:0006914; P:autophagy; IMP:FlyBase.
DR GO; GO:0031670; P:cellular response to nutrient; IDA:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0032456; P:endocytic recycling; IDA:FlyBase.
DR GO; GO:0048142; P:germarium-derived cystoblast division; IMP:FlyBase.
DR GO; GO:0051729; P:germline cell cycle switching, mitotic to meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:0008406; P:gonad development; IMP:FlyBase.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:FlyBase.
DR GO; GO:0035171; P:lamellocyte differentiation; IDA:FlyBase.
DR GO; GO:0035096; P:larval midgut cell programmed cell death; IMP:FlyBase.
DR GO; GO:0035264; P:multicellular organism growth; IMP:FlyBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:FlyBase.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; IDA:FlyBase.
DR GO; GO:1902669; P:positive regulation of axon guidance; IGI:FlyBase.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:FlyBase.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:FlyBase.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:FlyBase.
DR GO; GO:0090070; P:positive regulation of ribosome biogenesis; IMP:FlyBase.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IGI:FlyBase.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IMP:FlyBase.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; ISS:FlyBase.
DR GO; GO:0001558; P:regulation of cell growth; IDA:FlyBase.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IGI:FlyBase.
DR GO; GO:2001023; P:regulation of response to drug; IMP:FlyBase.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:FlyBase.
DR GO; GO:0007430; P:terminal branching, open tracheal system; IMP:FlyBase.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR GO; GO:0038202; P:TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:FlyBase.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.20.120.150; -; 1.
DR Gene3D; 1.25.10.10; -; 4.
DR Gene3D; 1.25.40.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024585; DUF3385_TOR.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR009076; FRB_dom.
DR InterPro; IPR036738; FRB_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR026683; TOR.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR11139:SF9; PTHR11139:SF9; 1.
DR Pfam; PF11865; DUF3385; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF08771; FRB_dom; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR SMART; SM01346; DUF3385; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF47212; SSF47212; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS50005; TPR; 2.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Kinase; Nucleotide-binding; Reference proteome;
KW Repeat; TPR repeat; Transferase.
FT CHAIN 1..2470
FT /note="Serine/threonine-protein kinase Tor"
FT /id="PRO_0000377458"
FT REPEAT 172..209
FT /note="HEAT 1"
FT /evidence="ECO:0000255"
FT REPEAT 746..785
FT /note="HEAT 2"
FT /evidence="ECO:0000255"
FT REPEAT 791..829
FT /note="HEAT 3"
FT /evidence="ECO:0000255"
FT REPEAT 835..873
FT /note="HEAT 4"
FT /evidence="ECO:0000255"
FT REPEAT 962..999
FT /note="HEAT 5"
FT /evidence="ECO:0000255"
FT REPEAT 1043..1080
FT /note="HEAT 6"
FT /evidence="ECO:0000255"
FT REPEAT 1083..1122
FT /note="HEAT 7"
FT /evidence="ECO:0000255"
FT REPEAT 1124..1160
FT /note="HEAT 8"
FT /evidence="ECO:0000255"
FT DOMAIN 1349..1903
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT REPEAT 1407..1440
FT /note="TPR 1"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00339"
FT REPEAT 1718..1751
FT /note="TPR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT REPEAT 1854..1891
FT /note="HEAT 9"
FT /evidence="ECO:0000255"
FT DOMAIN 2077..2389
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2438..2470
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 2083..2089
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2256..2264
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2276..2301
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2364..2389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 1956
FT /note="S->T: Rapamycin resistance and loss of activity."
FT /evidence="ECO:0000269|PubMed:11069885"
SQ SEQUENCE 2470 AA; 281033 MW; 5D78D2ECC07C7FF9 CRC64;
MSTTSVVQQF VNGLKSRNRN VQNKATQDLL FYVKTELREM SQEELAQFFD EFDHHIFTMV
NATDINEKKG GALAMKCLIN CEGSLTARKG ISPYLNRLRD LLLINDVSVM EIAARSLVKL
ANMPTSKGAD SFDFDIKKAF EVLRGERQEY RRHSAVFILR ELAIALPTYF YQHILTFFEV
IFNAIFDPKP AIRESAGEAL RAALIVTAQR ESTKQSSEPQ WYRICYDEAN GSFNADLGSS
KDQKGVTRDD RIHGGLVVFN ELFRCANATW ERRYTSLKTL FPKTQHNKFL EASSSSSMGS
QLNTLVPRLK VPFIDKLGST QTHLGEGEHH KGVAKFASHN VLESAYAQEI LQEHYTSICD
NVLEQRTSKS PYVQQALLQI LPRLAAFNRA VFVEKYLQTC VSHLMQILRG KEKDRTVAYI
TIGYMAVAVQ SAIEVHLSSI MTSVKVALPS KDLTSKRKVP VDPAVFACIT LLAHAVKSEI
ADDVKDILEQ MFYTGLSPAL TVCLRELSEN VPQLKSAITE GLIGILSQVL MNKAAILPYT
ALPTIAIDGS LMQNGDGATT VLALKTLGTF NFEEQNMLDF VQRCADYFIV HEQQEIRLEA
VQTCTRLLKL AVQSSESMEN SKTLSDTVSH VIERLLMVAI TDMDCNVRIR ILRSLDETFD
GKLAQPESLN SLFITLHDEI FEIRELAMVT IGRLSSINPA YVMPKLRTTM IELITDLKYS
GMSRNKEQSA KMLDHLVIST PRLISSYMNP ILKALVPKLH EPESNPGVIL NVLRTIGDLA
EVNGGSDEME LWADDLLSIL LEMLGDAGSP DKRGVALWTL GQLISATGRV VTPYHKYPVL
IDILINFLKT EQRRSIRRET IRVLGLLGAM DPYKHKMNKG LIDSQKDNVL IAYSDGKVDE
SQDISTAELL VNMGNALDEY YPAVAIAALM RILRDPTLST RHTSVVQAVT FIFQSLGIKC
VPYLAQVLPN LLDNVRTADN NLREFLFQQL AILVAFVKLH IISYMGDIFK LIKEFWTINT
PLQNTLINLI EQIAVALGCE FRDYLAELIP QILRVLQHDN SKDRMVTRRL LQALQKFGST
LGYYLPLILP PIVKLFDSPY VPQQVSMVAL ETINNLACQL DFTDFSSRII HPLVRVLDAE
PELRDQAMTT LRSLAKQLGK KYLVFVPMVQ RTLNKHRIVD PEYEELLSKI KSCSTLADSY
GAGESELRPS RFKNNEPFVT DRNSNNKNLQ VTTNELRTAW QVTRRVSKDD WVEWLKRLSI
GLLKESPSHA LRACRSLAQE YDTLLRDLFN AAFISCWTEL SPDLKNELTQ SLIQALQVTD
MPEITQTILN LAEFMEHCDR DPIPIETKLL GTRAMACRAY AKALRYKEEE FLLREDSQVF
ESLILINNKL QQREAAEGLL TRYRNAANEL NVQGRWYEKL HNWDEALEHY ERNLKTDSSD
LEARLGHMRC LEALGDWSEL SNVTKHEWEN FGTEAKSRAG PLAAVAAWGL QDWEAMREYV
RCIPEDTQDG SYYRAVLAVH HDDFETAQRL IDETRDLLDT ELTSMAGESY ERAYGAMVCV
QMLAELEEVI QYKLIPERRE PLKTMWWKRL QGGQRLVEDW RRIIQVHSLV VKPHEDIHTW
LKYASLCRKS GSLHLSHKTL VMLLGTDPKL NPNQPLPCNQ PQVTYAYTKY MAANNQLQEA
YEQLTHFVST YSQELSCLPP EALKQQDQRL MARCYLRMAT WQNKLQDSIR PDAIQGALEC
FEKATSYDPN WYKAWHLWAY MNFKVVQAQK SALDKQQPPG ASMGMTMGSG LDSDLMIIQR
YAVPAVQGFF RSISLIKGNS LQDTLRLLTL WFDYGNHAEV YEALLSGMKL IEINTWLQVI
PQLIARIDTH RQLVGQLIHQ LLMDIGKNHP QALVYPLTVA SKSASLARRN AAFKILDSMR
KHSPTLVEQA VMCSEELIRV AILWHEQWHE GLEEASRLYF GDRNVKGMFE ILEPLHAMLE
RGPQTLKETS FSQAYGRELT EAYEWSQRYK TSAVVMDLDR AWDIYYHVFQ KISRQLPQLT
SLELPYVSPK LMTCKDLELA VPGSYNPGQE LIRISIIKTN LQVITSKQRP RKLCIRGSNG
KDYMYLLKGH EDLRQDERVM QLFSLVNTLL LDDPDTFRRN LAIQRYAVIP LSTNSGLIGW
VPHCDTLHTL IRDYRDKKKV PLNQEHRTML NFAPDYDHLT LMQKVEVFEH ALGQTQGDDL
AKLLWLKSPS SELWFERRNN YTRSLAVMSM VGYILGLGDR HPSNLMLDRM SGKILHIDFG
DCFEVAMTRE KFPEKIPFRL TRMLIKAMEV TGIEGTYRRT CESVMLVLRR NKDSLMAVLE
AFVYDPLLNW RLLDVDKKGN DAVAGAGAPG GRGGSGMQDS LSNSVEDSLP MAKSKPYDPT
LQQGGLHNNV ADETNSKASQ VIKRVKCKLT GTDFQTEKSV NEQSQVELLI QQATNNENLC
QCYIGWCPFW
