TOR1/YJR066W Summary Help

Standard Name TOR1 1
Systematic Name YJR066W
Alias DRR1 2
Feature Type ORF, Verified
Description PIK-related protein kinase and rapamycin target; subunit of TORC1, a complex that controls growth in response to nutrients by regulating translation, transcription, ribosome biogenesis, nutrient transport and autophagy; involved in meiosis; TOR1 has a paralog, TOR2, that arose from the whole genome duplication (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and see Summary Paragraph)
Name Description Target Of Rapamycin 14, 15
Chromosomal Location
ChrX:559416 to 566828 | ORF Map | GBrowse
Genetic position: 44.84 cM
Gene Ontology Annotations All TOR1 GO evidence and references
  View Computational GO annotations for TOR1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Classical genetics
Large-scale survey
566 total interaction(s) for 369 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 38
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 38
  • Biochemical Activity: 8
  • Co-fractionation: 50
  • Co-localization: 2
  • Co-purification: 6
  • PCA: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 12

Genetic Interactions
  • Dosage Growth Defect: 10
  • Dosage Rescue: 7
  • Negative Genetic: 157
  • Phenotypic Enhancement: 14
  • Phenotypic Suppression: 18
  • Positive Genetic: 33
  • Synthetic Growth Defect: 107
  • Synthetic Lethality: 14
  • Synthetic Rescue: 46

Expression Summary
Length (a.a.) 2,470
Molecular Weight (Da) 281,137
Isoelectric Point (pI) 7.2
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:559416 to 566828 | ORF Map | GBrowse
Genetic position: 44.84 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..7413 559416..566828 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003827

TOR1 and TOR2 encode two closely related factors that regulate cell growth in response to nutrient availability and cellular stresses (8, 9, 16). TOR1 and TOR2 are involved in the regulation of many cellular processes including: protein synthesis, ribosome biogenesis, autophagy, transcriptional activation, meiosis, cell cycling, nutrient permease sorting and turnover, and actin organization (6, 7, 4, 8, 3, 15, 17, 18). These processes are carried out by two functionally distinct TOR complexes (9). The TOR complex 1 (TORC1) is responsible for most of the aforementioned processes and modulates translation initiation, inhibits protein turnover, contributes to tetrad formation, and represses the transcription of specific genes that are induced by nutrient starvation (reviewed in 19, 20). TORC1 consists of either Tor1p or Tor2p, together with Kog1p, Lst8p, and Tco89p (9, 21). TORC1 is sensitive to the drug rapamycin, which forms a complex with Fpr1p that binds to the Tor protein and inhibits complex activity (22, 9). TOR complex 2 (TORC2) is involved in regulating actin cytoskeleton polarization during cell cycle progression, cell wall integrity, and receptor endocytosis (18, 23). TORC2 does not include Tor1p and contains only Tor2p along with Avo1p, Avo2p, Tsc11p, Lst8p, Bit61p, Slm1p, and Slm2p (9, 21, 24). TORC2 is rapamycin insensitive because the rapamycin-Fpr1p complex does not bind to Tor2p when it is present in TORC2 (25, 9).

Tor1p and Tor2p are peripheral membrane proteins (26, 27) comprised of 2470 (281.2 kDa) and 2474 (282 kDa) amino acid residues, respectively, and the two proteins have 80% overall amino acid similarity (28). The Tor proteins consist of several functional domains (reviewed in 29). The amino-terminal 1200 residues consist of stretches of HEAT (Huntingtin, Elongation factor 3, regulatory subunit A of PP2A, TOR1) repeats, which typically mediate protein-protein interactions (30, 26). Following the HEAT repeats is a 550-amino acid-long FAT (FRAP, ATM, TTRAP) domain that has also been suggested to facilitate protein binding (31). The FAT domain is adjacent to the amino side of the FKBP12-rapamycin binding site that is flanked on its C-terminal side by the catalytic serine/threonine kinase domain (25, 32). This kinase domain contains a conserved lipid kinase motif, making Tor1p and Tor2p members of the phosphatidylinositol-kinase-related kinase family (33). Finally, the carboxyl-terminal 33 residues of Tor1/2p comprise a FATC (FAT C-terminus) domain that is postulated to contribute to redox-dependent Tor protein degradation (31).

Under nutrient-rich conditions, TORC1 inhibits the function of transcriptional activators that are involved in nitrogen catabolite-repression (e.g., Gat1p, Gln3p; 34, 5), retrograde response (e.g., Rtg1p, Rtg3p; 35, 36), and stress-response (e.g., Msn2p, Msn4p; 37), while activating those involved in ribosome biosynthesis (e.g., Fhl1p, Spf1p; 38, 12) usually by affecting the cellular translocation of these transcription factors. One common mechanism by which this occurs is through a TORC1-influenced change to the phosphorylation state of these factors leading them to bind a cytoplasmic anchor protein, thus preventing nuclear localization (5, 12). These phosphorylation/dephosphorylation events are not directly mediated by the TORC1 complex but instead are carried out by an upstream regulator on which TORC1 acts, such as the phosphatase Sit4p or the RAS/cAMP signaling-related kinase Yak1p (39, 5, 40). Loss of Tor protein also results in a rapid and strong inhibition of translation initiation. Biochemical analysis indicates that TORC1 is involved in translation by stabilizing eIF4G, encoded by TIF4631 and TIF4632, an essential initiation factor required for mRNA translation via the 5' cap structure (41). TORC2-mediated regulation of signal transduction cascades required for actin organization, cell integrity, and endocytosis involves direct phosphorylation of the effector protein Ypk2p (32).

Although S. cerevisiae has two TOR genes, all other eukaryotes appear to have only one. However, higher eukaryotes do have both TORC1 and TORC2 complexes and studies demonstrate that the complexes are both structurally and functionally conserved (9). In higher eukaryotes, TOR activity has also been shown to participate in apoptosis, hypoxia, and aging (reviewed in 42, 19). The upstream regulators of TOR have been more extensively studied in Drosophila and mammalian systems and appear to be more differentially regulated than yeast Tor1/2p as they involve factors and TOR domains not conserved in S. cerevisiae (reviewed in 42, 19). Because both the upstream and downstream signaling pathways of mammalian TOR are deregulated in tuberous sclerosis complex (OMIM), Peutz-Jeghers syndrome (OMIM) and many malignant human cancers, TOR-targeting drugs are being clinically developed as anti-tumor therapies (reviewed in 42).

Last updated: 2005-10-31 Contact SGD

References cited on this page View Complete Literature Guide for TOR1
1) Hall, M.  (1993) Personal Communication, Mortimer Map Edition 12
2) Cafferkey R, et al.  (1993) Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol 13(10):6012-23
3) Zheng XF and Schreiber SL  (1997) Target of rapamycin proteins and their kinase activities are required for meiosis. Proc Natl Acad Sci U S A 94(7):3070-5
4) Kamada Y, et al.  (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150(6):1507-13
5) Beck T and Hall MN  (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402(6762):689-92
6) Barbet NC, et al.  (1996) TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell 7(1):25-42
7) Powers T and Walter P  (1999) Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol Biol Cell 10(4):987-1000
8) Cardenas ME, et al.  (1999) The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev 13(24):3271-9
9) Loewith R, et al.  (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10(3):457-68
10) Torres J, et al.  (2002) Regulation of the cell integrity pathway by rapamycin-sensitive TOR function in budding yeast. J Biol Chem 277(45):43495-504
11) Lorberg A and Hall MN  (2004) TOR: the first 10 years. Curr Top Microbiol Immunol 279():1-18
12) Martin DE, et al.  (2004) TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119(7):969-79
13) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
14) Kunz J, et al.  (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73(3):585-96
15) Heitman J, et al.  (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253(5022):905-9
16) Weisman R and Choder M  (2001) The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. J Biol Chem 276(10):7027-32
17) Schmidt A, et al.  (1998) The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J 17(23):6924-31
18) Schmidt A, et al.  (1996) TOR2 is required for organization of the actin cytoskeleton in yeast. Proc Natl Acad Sci U S A 93(24):13780-5
19) Martin DE and Hall MN  (2005) The expanding TOR signaling network. Curr Opin Cell Biol 17(2):158-66
20) Inoki K, et al.  (2005) Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev 69(1):79-100
21) Reinke A, et al.  (2004) TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem 279(15):14752-62
22) Stan R, et al.  (1994) Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue. J Biol Chem 269(51):32027-30
23) deHart AK, et al.  (2003) Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway. Mol Biol Cell 14(11):4676-84
24) Fadri M, et al.  (2005) The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell 16(4):1883-900
25) Zheng XF, et al.  (1995) TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin. Cell 82(1):121-30
26) Kunz J, et al.  (2000) HEAT repeats mediate plasma membrane localization of Tor2p in yeast. J Biol Chem 275(47):37011-20
27) Chen EJ and Kaiser CA  (2003) LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. J Cell Biol 161(2):333-47
28) Cafferkey R, et al.  (1994) Yeast TOR (DRR) proteins: amino-acid sequence alignment and identification of structural motifs. Gene 141(1):133-6
29) Dames SA, et al.  (2005) The solution structure of the FATC domain of the protein kinase target of rapamycin suggests a role for redox-dependent structural and cellular stability. J Biol Chem 280(21):20558-64
30) Andrade MA and Bork P  (1995) HEAT repeats in the Huntington's disease protein. Nat Genet 11(2):115-6
31) Bosotti R, et al.  (2000) FAT: a novel domain in PIK-related kinases. Trends Biochem Sci 25(5):225-7
32) Kamada Y, et al.  (2005) Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Mol Cell Biol 25(16):7239-48
33) Keith CT and Schreiber SL  (1995) PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science 270(5233):50-1
34) Shamji AF, et al.  (2000) Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins. Curr Biol 10(24):1574-81
35) Dilova I, et al.  (2004) Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes. J Biol Chem 279(45):46527-35
36) Tate JJ, et al.  (2002) Mks1p is required for negative regulation of retrograde gene expression in Saccharomyces cerevisiae but does not affect nitrogen catabolite repression-sensitive gene expression. J Biol Chem 277(23):20477-82
37) Monteiro G and Netto LE  (2004) Glucose repression of PRX1 expression is mediated by Tor1p and Ras2p through inhibition of Msn2/4p in Saccharomyces cerevisiae. FEMS Microbiol Lett 241(2):221-8
38) Marion RM, et al.  (2004) Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression. Proc Natl Acad Sci U S A 101(40):14315-22
39) Jiang Y and Broach JR  (1999) Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J 18(10):2782-92
40) Schmelzle T, et al.  (2004) Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Mol Cell Biol 24(1):338-51
41) Berset C, et al.  (1998) The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 95(8):4264-9
42) Bjornsti MA and Houghton PJ  (2004) The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4(5):335-48