TOR_CAEEL
ID TOR_CAEEL Reviewed; 2697 AA.
AC Q95Q95; O01438;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Target of rapamycin homolog;
DE EC=2.7.11.1;
DE AltName: Full=CeTOR;
DE AltName: Full=Lethal protein 363;
GN Name=let-363 {ECO:0000312|WormBase:B0261.2a};
GN Synonyms=CeTor {ECO:0000312|WormBase:B0261.2a};
GN ORFNames=B0261.2 {ECO:0000312|WormBase:B0261.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Bristol N2;
RX PubMed=12225660; DOI=10.1016/s0960-9822(02)01091-6;
RA Long X., Spycher C., Han Z.S., Rose A.M., Mueller F., Avruch J.;
RT "TOR deficiency in C. elegans causes developmental arrest and intestinal
RT atrophy by inhibition of mRNA translation.";
RL Curr. Biol. 12:1448-1461(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14668850; DOI=10.1038/426620a;
RA Vellai T., Takacs-Vellai K., Zhang Y., Kovacs A.L., Orosz L., Mueller F.;
RT "Genetics: influence of TOR kinase on lifespan in C. elegans.";
RL Nature 426:620-620(2003).
RN [4]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17327275; DOI=10.1242/jcs.03401;
RA Toth M.L., Simon P., Kovacs A.L., Vellai T.;
RT "Influence of autophagy genes on ion-channel-dependent neuronal
RT degeneration in Caenorhabditis elegans.";
RL J. Cell Sci. 120:1134-1141(2007).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19377305; DOI=10.4161/auto.5.5.8624;
RA Tian E., Wang F., Han J., Zhang H.;
RT "epg-1 functions in autophagy-regulated processes and may encode a highly
RT divergent Atg13 homolog in C. elegans.";
RL Autophagy 5:608-615(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22278922; DOI=10.1242/dev.074047;
RA Korta D.Z., Tuck S., Hubbard E.J.;
RT "S6K links cell fate, cell cycle and nutrient response in C. elegans
RT germline stem/progenitor cells.";
RL Development 139:859-870(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28853436; DOI=10.1038/ncomms16083;
RA Tiku V., Jain C., Raz Y., Nakamura S., Heestand B., Liu W., Spaeth M.,
RA Suchiman H.E.D., Mueller R.U., Slagboom P.E., Partridge L., Antebi A.;
RT "Small nucleoli are a cellular hallmark of longevity.";
RL Nat. Commun. 8:16083-16083(2016).
CC -!- FUNCTION: Serine/threonine-protein kinase that regulates the mRNA
CC translation machinery, probably by modulating the activity of
CC translation factors such as eIF-4G and eIF-2 (PubMed:12225660). It may
CC have some protein kinase activity instead of lipid kinase activity
CC (PubMed:12225660). May play a role in P-granule degradation by
CC autophagy in somatic cells during embryogenesis (PubMed:19377305).
CC Required, during larval development, for the establishment of the
CC proper number of germline progenitors, probably upstream of rsks-1 and
CC ife-1 (PubMed:22278922). Required for larval development
CC (PubMed:22278922). May act as a mediator of lifespan regulation by
CC insulin signaling and nutrient sensing (PubMed:14668850,
CC PubMed:28853436). {ECO:0000269|PubMed:12225660,
CC ECO:0000269|PubMed:14668850, ECO:0000269|PubMed:19377305,
CC ECO:0000269|PubMed:22278922, ECO:0000269|PubMed:28853436}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12225660}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:B0261.2a};
CC IsoId=Q95Q95-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:B0261.2b};
CC IsoId=Q95Q95-2; Sequence=VSP_009223;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in all major tissues and
CC organs, including the intestine, gonads and hypodermal cells
CC (PubMed:12225660). Expressed in neurons (PubMed:17327275).
CC {ECO:0000269|PubMed:12225660, ECO:0000269|PubMed:17327275}.
CC -!- DISRUPTION PHENOTYPE: Defects strongly increase lifespan, the mean
CC lifetime being of 25 days instead of 10 days, suggesting that it may be
CC involved in aging process (PubMed:14668850). RNAi-mediated knockdown
CC results in increased longevity and a reduced nucleoli size
CC (PubMed:28853436). RNAi-mediated knockdown in a ncl-1 mutant background
CC (e1942) reduces the increased longevity and suppresses the reduced
CC nucleoli size of the let-363 single mutant, and reduces the increased
CC ribosomal protein synthesis in the ncl-1 single mutant (e1942)
CC (PubMed:28853436). RNAi-mediated knockdown in the germline causes
CC sterility, a severe reduction in the number of germline progenitors and
CC a delay in G2 phase of the cell cycle (PubMed:22278922). RNAi-mediated
CC knockdown results in no sepa-1 containing aggregates at the comma stage
CC of embryonic development indicative of no germ cell specific P-granules
CC at this stage (PubMed:19377305). RNAi-mediated knockdown enhances the
CC loss of touch receptor neurons in a mec-4 u231 mutant
CC (PubMed:17327275). {ECO:0000269|PubMed:14668850,
CC ECO:0000269|PubMed:17327275, ECO:0000269|PubMed:19377305,
CC ECO:0000269|PubMed:22278922, ECO:0000269|PubMed:28853436}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; BX284601; CCD61569.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD61570.1; -; Genomic_DNA.
DR RefSeq; NP_491549.2; NM_059148.4.
DR RefSeq; NP_491552.2; NM_059151.5.
DR AlphaFoldDB; Q95Q95; -.
DR SMR; Q95Q95; -.
DR BioGRID; 37625; 18.
DR STRING; 6239.B0261.2a; -.
DR iPTMnet; Q95Q95; -.
DR EPD; Q95Q95; -.
DR PaxDb; Q95Q95; -.
DR PeptideAtlas; Q95Q95; -.
DR EnsemblMetazoa; B0261.2a.1; B0261.2a.1; WBGene00002583.
DR EnsemblMetazoa; B0261.2b.1; B0261.2b.1; WBGene00002583.
DR GeneID; 172167; -.
DR KEGG; cel:CELE_B0261.2; -.
DR UCSC; B0261.2b; c. elegans. [Q95Q95-1]
DR CTD; 172167; -.
DR WormBase; B0261.2a; CE32559; WBGene00002583; let-363. [Q95Q95-1]
DR WormBase; B0261.2b; CE32560; WBGene00002583; let-363. [Q95Q95-2]
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00940000174195; -.
DR InParanoid; Q95Q95; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; Q95Q95; -.
DR Reactome; R-CEL-1257604; PIP3 activates AKT signaling.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR Reactome; R-CEL-165159; MTOR signalling.
DR Reactome; R-CEL-166208; mTORC1-mediated signalling.
DR Reactome; R-CEL-3371571; HSF1-dependent transactivation.
DR Reactome; R-CEL-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-CEL-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-CEL-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-CEL-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-CEL-6804757; Regulation of TP53 Degradation.
DR Reactome; R-CEL-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-CEL-9639288; Amino acids regulate mTORC1.
DR PRO; PR:Q95Q95; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00002583; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0031931; C:TORC1 complex; IDA:WormBase.
DR GO; GO:0031932; C:TORC2 complex; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISS:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:InterPro.
DR GO; GO:0000492; P:box C/D snoRNP assembly; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0048382; P:mesendoderm development; IGI:WormBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IBA:GO_Central.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; ISS:WormBase.
DR GO; GO:0006417; P:regulation of translation; IMP:WormBase.
DR GO; GO:1903935; P:response to sodium arsenite; IGI:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:WormBase.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.20.120.150; -; 1.
DR Gene3D; 1.25.10.10; -; 3.
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 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; 1.
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.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding; Nucleus;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Translation regulation.
FT CHAIN 1..2697
FT /note="Target of rapamycin homolog"
FT /id="PRO_0000088811"
FT REPEAT 235..272
FT /note="HEAT 1"
FT REPEAT 649..687
FT /note="HEAT 2"
FT REPEAT 689..726
FT /note="HEAT 3"
FT REPEAT 731..768
FT /note="HEAT 4"
FT REPEAT 815..853
FT /note="HEAT 5"
FT REPEAT 863..900
FT /note="HEAT 6"
FT REPEAT 1073..1110
FT /note="HEAT 7"
FT DOMAIN 1438..2153
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2332..2647
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2665..2697
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1945..1981
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2017..2039
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2338..2344
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2512..2520
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2532..2557
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2615..2635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1965..1979
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 2212..2215
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_009223"
FT CONFLICT 1295
FT /note="K -> ISE (in Ref. 2; CCD61569/CCD61570)"
FT /evidence="ECO:0000305"
FT CONFLICT 1992..1994
FT /note="Missing (in Ref. 2; CCD61570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2697 AA; 306529 MW; CBC59D6CE02BFEC0 CRC64;
MLQQHGISFQ MNADRQNKAA TTSNRIVSAP ATNEFDERHR KQGIDAARAL ASQYRSRITE
NRDANQRQAA RELSRYVRSE LKDEPNTFSD AFLNAIDGRT DIASQSAIYN CMKSNSNIDQ
KRAGIYLIVC LAETHSGNVI RYANYLLKML NNGNGLDEDT VKMASKALAF LIATCKSYAA
ELVDRCLDHC HEWLGQNVPH SQQPKNQQEI DQIRRLAASH LSRELALATP TAFFLRVNLF
FKYIFNAVRD KNPAVRIAGI DALHVVLTIV SQREAKNKTE WFKKCFDEAL EGQPNPSQKD
DLDRWHAVAL ILNELLRISD QRFELIRCES SQFIKQKFLK EDEEEGVEWL VLTKQQTIVE
SVTARKLVLE RFPKILDCVR QIIPLANKTS STKQQSSIYL NTVLMQLLPR ICAFPQCDRT
FQTISFDTSF TILQRNAVAA PAIGMMMLSN PDVHATHIEK TISFISAAIK KTTNSDVLDN
YFTFLFLFVD AYHEQVTTQI KAIIPQLMDI TLSRSLANVL KMIMMRIPKL RLNVQDGVMA
SVYQTLTGSL IPPKSEPIGR PASPKAILQK AETDPKELQR IVLAVDVLGE FYFSRGALQR
IMQYVADYYL TADNVEIRLA AVSSCCEMVV PFVGVYKKVT SDKRNSLLQT IYGVLRAVCS
VIVNDQDVRV RMQVISCFGQ MPRPFLAHLA QPEMLEVQFM ALHDEKLEMQ QACVTLLGRL
AELNPALVLP RLRLMLLETL SQMQQSGQAR LEQHSAKMIA QLAKQSPKFM RPYVGSLMIA
MIPKLRNDQK YAEVTAQVLN AVSEIAVIGG AEIVKNLKPL FEKLTHMIND SSSLHKREAA
LRAIGGICRS TAYVVDPYRD YPSLLDDLLR ILKTVMSNTM RREAIKTLGI LGAIDPYTHK
VFTGSVQSST AISTALSLPI SETDSKDPRQ DIIHWFNYEK CTLEEFYPAI TIANLMLMMQ
DEDSQSYAEI AQAIVTIFRS LGDMAPLYTE QVIPRLIEVC RRATESSNRA NLREFFLQQL
ANFVAIIRKH AAPYMPAIFT IIADAWKEDI SVKMVVIEVL TDMGTAIGND FSKYTGELIP
YLLTVLQTDK TKERVLTVKV MESIQKLTHC IVQHLHLVLP PLLIILDDFS LKLSIRNTAL
STVLHMTQQV DVSAYAPRMM QSWHHNISTA EMRDKLLLLL IEIIKQLGKF FDIFKRGVDQ
KLRDYNLDKS VHYEQYRKLA QRAQMSRDVL TSSVFAGSNG NIQYSSTQAG MRGQANNVYA
NNDLHERLMN GSIDSGASRQ DNRDDYYRYG VEEKKEVPKV APTTARPTSE LVTVQITKQR
LNKDALMPQW KNENLTSKDE WLQWLMKIRI GFLTYGSSPS LRAASSLGDQ HPHLARDLFP
AAFMSVWTEL DSDVQNDLTS CLLRAISTGI PELIQTILNL AEFMDHSEKG PLPISHDVLG
RWAEQTKAFA KACRYKEMSV LKKSGSMQTT FTRKVKLEPN DCQSLITYAN KLNVQEEAAG
VVRYAERNEM NFQMRGRWYE KLNEWEKALG AYELEEKKKS SCPNLQVYDE KDHLMTPEEA
ATAEEARMHE MRCLEALGRW DELNSKSVVW ADQRGNRNDS VRDEINKKQL DHKMAVIAAR
GAWAVDNWER MADYVSVISE NTQDGAMLRA VVAVHNDENT KAMGLIEKVR EMIDSELTAM
ANESYERAYI PMVSVQQMAE LEEAIEYKTR PERRPRIALL WSRRLQGCRR NVEQWQRLIM
LRGLVLSPQE MHPLRVKFSS MCRKQGKNSM SRAVLRELLS LPANSDLVRA KAPFDKPLLV
LALAKQLYQD DHKDEAIRAL EDLANHWNKR INPIPKATGR ELIPPSTKEP ARICAKVLLK
LGEWTELKSK TSNNMQVGEL SFVRQQVSPQ YRTKESRTPE TIAFENTINY YQQATQYDPG
WHKVWHKLAS THFYAVCRER PHPTTVISPP QQPQQPKKMH IPPVTRATSP PPPAQKSPQP
APFHSITEPL SVIIDYPVPP PLGSLVGLPP MPAYLSSNSS LPPQHHHVSP LSNDSPSNSA
ENKLYLKHAA HAVRCFAKAL MCSPGSRLED TLRLMQLWFD HGDDKDQDVY FALTETIFDL
PVTTWLEAIP QLMARLDCPD DQKSVQLVLR VLCEIARHRP QAVIYALTVA SRSKDVHRSK
NAGTVLEKMM EYHSKLVREA SLVTEELVRC AILWHEQWHD ALDDASRVYF HRRLQDNNVQ
AMFDALRNMN DLMQKGAPTT MKEHSFQQTY SSDLKEAGRY VQAFESSGNV KDLNQAWEIY
CSVFKKLRDQ LATLNSLDLV YVSPNLVSAK DLELVVPGTY DPSAPIVSIQ SFSSKMNVIT
SKQRPRKMVI RGSNGLDYQF LLKGHEDPRQ DERVMQLFGL VNTLLANNSE TCRRNLTIQR
YSIVALSKDS GLIGWVPNCD TLHTLVKEYR EKKAKIPLSI EHKTLQKLSL ETEHLTLMQK
LQLFESALSV TQGEDLRHVL WLKSPSSEVW FDRRTNYTRS VACMSMVGYI LGLGDRHPSN
LMLDRLTGKV VHIDFGDCFE VAMLREKFPE RVPFRLTRML INAMEVTGLD GVYNYTAERV
LKMLRTNQES LLAVLEAFVY DPVINWRLVE GMKKDPKTRK DTGGRQNMAG AVLPSSSTTD
SIMETIKRKL DGTEFVHTDG STPPEPLQVT EQLAMLTEQA TSPLNLCQSY IGWCPFW
