TOR_DICDI
ID TOR_DICDI Reviewed; 2380 AA.
AC Q86C65; Q54TG2;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Serine/threonine-protein kinase tor;
DE EC=2.7.11.1;
DE AltName: Full=Target of rapamycin;
GN Name=tor; ORFNames=DDB_G0281569;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12626495; DOI=10.1074/jbc.m212467200;
RA Otto G.P., Wu M.Y., Kazgan N., Anderson O.R., Kessin R.H.;
RT "Macroautophagy is required for multicellular development of the social
RT amoeba Dictyostelium discoideum.";
RL J. Biol. Chem. 278:17636-17645(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP FUNCTION, IDENTIFICATION IN A TORC1 AND TORC2 COMPLEX, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=16079174; DOI=10.1091/mbc.e05-04-0342;
RA Lee S., Comer F.I., Sasaki A., McLeod I.X., Duong Y., Okumura K.,
RA Yates J.R. III, Parent C.A., Firtel R.A.;
RT "TOR complex 2 integrates cell movement during chemotaxis and signal relay
RT in Dictyostelium.";
RL Mol. Biol. Cell 16:4572-4583(2005).
RN [4]
RP FUNCTION.
RA Rosel D., Majithia A., Khurana T., Kimmel A.R.;
RT "TOR, the central controller of cell growth negatively regulates
RT phagocytosis.";
RL (In) Abstracts of Annual International Dictyostelium Conference, pp.18-18,
RL Autrans (2005).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=18657484; DOI=10.1016/j.arr.2008.04.003;
RA McMains V.C., Liao X.-H., Kimmel A.R.;
RT "Oscillatory signaling and network responses during the development of
RT Dictyostelium discoideum.";
RL Ageing Res. Rev. 7:234-248(2008).
RN [6]
RP FUNCTION.
RX PubMed=18812082; DOI=10.1016/j.cub.2008.07.051;
RA King J.S., Insall R.H.;
RT "Chemotaxis: TorC before you Akt.";
RL Curr. Biol. 18:R864-R866(2008).
RN [7]
RP FUNCTION.
RX PubMed=18635356; DOI=10.1016/j.cub.2008.06.068;
RA Kamimura Y., Xiong Y., Iglesias P.A., Hoeller O., Bolourani P.,
RA Devreotes P.N.;
RT "PIP3-independent activation of TorC2 and PKB at the cell's leading edge
RT mediates chemotaxis.";
RL Curr. Biol. 18:1034-1043(2008).
CC -!- FUNCTION: Regulates cell growth, chemotaxis, signal relay and the actin
CC cytoskeleton. Functions as a part of 2 distinct protein complexes TORC1
CC and TORC2. TORC1 is a rapamycin-sensitive complex that controls cell
CC growth in response to nutrients and growth factors. The second TOR
CC complex, TORC2, is presumed to be indirectly negatively modulated by
CC rapamycin and regulates actin polarization. TORC2 but not TORC1
CC negatively regulates phagocytosis. TORC2-dependent regulation of the
CC cytoskeleton may follow differential phosphorylation of pkbA. May have
CC some protein kinase activity, as it appears to phosphorylate pkgB.
CC {ECO:0000269|PubMed:16079174, ECO:0000269|PubMed:18635356,
CC ECO:0000269|PubMed:18812082, ECO:0000269|Ref.4}.
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: Part of a complex, TORC1, consisting of tor, raptor and lst8.
CC Part of a complex, TORC2, consisting of tor, lst8, piaA and ripA.
CC Additional proteins, such as 14-3-3 and heat-shock proteins, may also
CC belong to the TORC2 complex. {ECO:0000269|PubMed:16079174}.
CC -!- DISRUPTION PHENOTYPE: Null cells are lethal due to a growth defect
CC involving TOR protein complex 1, TORC1. {ECO:0000269|PubMed:18657484}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; AY204354; AAO43977.1; -; Genomic_DNA.
DR EMBL; AAFI02000042; EAL66546.1; -; Genomic_DNA.
DR RefSeq; XP_640629.1; XM_635537.1.
DR AlphaFoldDB; Q86C65; -.
DR SMR; Q86C65; -.
DR STRING; 44689.DDB0214908; -.
DR PaxDb; Q86C65; -.
DR PRIDE; Q86C65; -.
DR EnsemblProtists; EAL66546; EAL66546; DDB_G0281569.
DR GeneID; 8623240; -.
DR KEGG; ddi:DDB_G0281569; -.
DR dictyBase; DDB_G0281569; tor.
DR eggNOG; KOG0891; Eukaryota.
DR HOGENOM; CLU_000178_7_1_1; -.
DR InParanoid; Q86C65; -.
DR OMA; DPYKHQQ; -.
DR PhylomeDB; Q86C65; -.
DR Reactome; R-DDI-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DDI-1632852; Macroautophagy.
DR Reactome; R-DDI-165159; MTOR signalling.
DR Reactome; R-DDI-166208; mTORC1-mediated signalling.
DR Reactome; R-DDI-3371571; HSF1-dependent transactivation.
DR Reactome; R-DDI-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-DDI-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DDI-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-DDI-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DDI-6804757; Regulation of TP53 Degradation.
DR Reactome; R-DDI-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-DDI-9639288; Amino acids regulate mTORC1.
DR PRO; PR:Q86C65; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005634; C:nucleus; IDA:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:0031931; C:TORC1 complex; IBA:GO_Central.
DR GO; GO:0031932; C:TORC2 complex; IPI:dictyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:1903664; P:regulation of asexual reproduction; IMP:dictyBase.
DR GO; GO:0031156; P:regulation of sorocarp development; IMP:dictyBase.
DR GO; GO:0031000; P:response to caffeine; IDA:dictyBase.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.20.120.150; -; 1.
DR Gene3D; 1.25.10.10; -; 5.
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; IPR021133; HEAT_type_2.
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; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 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 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Chemotaxis; Coiled coil; Kinase;
KW Nucleotide-binding; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; TPR repeat; Transferase.
FT CHAIN 1..2380
FT /note="Serine/threonine-protein kinase tor"
FT /id="PRO_0000376000"
FT REPEAT 266..303
FT /note="HEAT 1"
FT REPEAT 493..530
FT /note="HEAT 2"
FT REPEAT 540..578
FT /note="HEAT 3"
FT REPEAT 580..614
FT /note="HEAT 4"
FT REPEAT 660..697
FT /note="HEAT 5"
FT REPEAT 701..739
FT /note="HEAT 6"
FT REPEAT 745..783
FT /note="HEAT 7"
FT REPEAT 863..900
FT /note="HEAT 8"
FT REPEAT 982..1021
FT /note="HEAT 9"
FT REPEAT 1023..1060
FT /note="HEAT 10"
FT REPEAT 1210..1249
FT /note="HEAT 11"
FT REPEAT 1255..1288
FT /note="TPR 1"
FT DOMAIN 1260..1790
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT REPEAT 1316..1349
FT /note="TPR 2"
FT REPEAT 1611..1644
FT /note="TPR 3"
FT REPEAT 1672..1706
FT /note="TPR 4"
FT REPEAT 1942..1974
FT /note="TPR 5"
FT DOMAIN 1964..2279
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2348..2380
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1970..1976
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2143..2151
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2163..2188
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT COILED 11..38
FT /evidence="ECO:0000255"
SQ SEQUENCE 2380 AA; 268750 MW; 5E2998128B92711E CRC64;
MSQHEQPSIW ADALTKLLND LKSKKEEDRV KASKNLKSYV ISQSREMTNE NFTKFMNELN
NNLIFELVNS SVIPEKIGGI MAIDELIDVD YDENATKITR LANYLRIGLG FNDFTVMLMA
SKALGRLARS SGTLTAEFVE FEVTRALEWL SGDRIEARRH AAVLVLKELA QNAPTLFYVH
ASSFVDLIWV ALKDPKVAIR EGAVEALRAC LELISERESR LRLQWYQKIY DEAQKSFKQN
GSPESIHGSL ITVSELLRNT GDFMLSKFKD ICETVLKYKD HRDKLVKKTV LALFPRLAVF
CSRDFVLNYF NACMNHLLAA LRNQNERPTA FIALGEIAMA VGGSIKPYLD SIVVMIKQGL
MTKGKQFCPE VLTCISMLAS AVGQSMYPHM QVILPQMIVS SGLTVVLTDA LRDLTINLPT
LIPNIQYKLL NLISQVLANK PFSEPGAPSP YRKSATPFQG GSIPQLGQNS DVDPQMIALA
LKTLGSFDFS KHNLLEFVRE CVVNYLDDDN IEIRREAAIT CAQLMVGTEE PTPTRGHSAV
IVGEVLEKLL VVGIADPDPS IRKTVLSSLE ARFDHYLAQA ENLRSLFIAL NDELFEIREL
AITVIGRLTI RNPAYVMPSL RKTLIQLLTE LEFSGDGRNK EESARLLGHL ISASEKLIKP
YVEPILKALL PKLRDSNPRV ASCVLAALGE LSVVGGEEMV QHIDSLLPLI IDTLQDQSST
SKREVALKTL AQLASSTGYV IKPFSKYPML LDTLLNAIKT ERIGSIRREV IKVLGILGSL
DPYKHKMNEL GKRREDPKAN DDKNNNMTNE VITISPSNED YYPTVALTAL MKILRDPSLS
SHHTSVIQAV MYIFKSLSLK SIPFLPQIMP PFLHAMNTGE PLFREFLFQQ LGSLVSIVKQ
HIRDYLVNVF ALIEKYWNSN LLIPIIKLVE EISSALNDEF KVYLPNLIPQ MLNVLHTDRS
PKRSPTTKVL RALEVFGTNL DDYLHLVIPA IVKLFEQVDV TTQVRTLAIQ TIGRLCKKLN
FSDYASRIIH PLARVLDSTE SELREETLNT LCALVYQLGS DYAIFIPMVG KVLARREIQS
TNYELLISKL LKNQQLMLTP GSGDDGGMGA NRFGGDHNGH HLGEDHNNTS TPLDIGVKKL
KANEQHLKNA WETSQRSTKE DWGEWIRRFS VELLRESPSP ALRSCLSLAQ DYHPLVKELF
NAGFVSCWTE LHEQFQEELV RSLETALLSP NIPPEILQTL LNLAEFMELH EKPLPIDIRT
LGALAEKCHA YAKALHYKES EFSQSPSSTI EALISINNQL QQPEAAIGIL IYAQKNHSVE
LKEGWYEKLR RWEDALAAYE KKQKDDPNGG TIENTMGILR CLHALGEWER LSALSSETWK
SDINDHTRAT IAPLAAAAAW NLVNWDKMDE YVCAMNKDTV EGSFYRAILE VHHDNFTLAH
GFIDHARTLV DTELTALLGE SYNRAYKVVV RLQQLSELEE IIEYKKCVDS PERRNMIKNT
WKTRLRGCQH NVDIWQSILA VHSLVISPHE ELDMWLKFVG LCRKGSRLGL AQKTLTMLMG
KDPSTTSQFG SVLPNTHPRI TFAYIKQLWS AGAKQPAFEK LRTFVQALRD TDDLPLQGRA
YLKLGEWQLA LGDTLSEASI PHIISSFKAA TECDPNWYKA WHSWALINFE VVSHYEQNGG
TPEQIGAHLL PAVHSFFKSI SLGPDRSLQD TLRLLTLWFK HGAQKEVEAA LMQGFNTISI
DTWLHVIPQI IARIHAPVLP VRRLLHELID TIGKEHPQAL VYPLTVATKS HSPARLAAAK
SLMDKMRKHS ATLVDQALPV SQELVRTAIL WLEMWYEGLE EASRQYFGDH NPEAMLATLA
PLHQILEKGP ETTSETSFLQ AFGRDLQEAL EWSKKYEKTR KEGDLNQAWD LYYQVFRRIY
KQLPQMSSLE LQYVSPKLLN SNNMELAVPG TYKASENVIR IQSFSQALSV IPSKQRPRKL
TIIGSDGLEY TFLLKGHEDL RQDERVMQLF SLVNNLLSAN HETAKSHLSI RRFSVIPLSP
NSGLIGWVPH SDTLHTLIKD FRDSNKILLS IEHRLMLQMC SDYDNLTLLQ KVEVFQYALE
NSNGLDLHKV LWLKSRNSEV WLDRRTNYTR SLAVMSMVGY ILGLGDRHPS NLMLDRHTGH
ILHIDFGDCF EVAMHRDKYP EKIPFRLTRM LINAMEVSGI EGNFRLTCEA VMNVLRNNKE
SLMAVLEAFV HDPLINWRLL TPNENNTKHK ATNIASNNST SNSTTKIEGD LNTIDNPINK
ESPDHEAVAG SLKSSPVHGR QIARNQRVGV DAEQVEAEIV PEALNERALS VINRVNKKLT
GRDFSSNETL DVPEQVQKLI DQATSHENLC LSYVGWCPFW
