TOS3/YGL179C Summary Help

Standard Name TOS3
Systematic Name YGL179C
Feature Type ORF, Verified
Description Protein kinase; related to and functionally redundant with Elm1p and Sak1p for the phosphorylation and activation of Snf1p; functionally orthologous to LKB1, a mammalian kinase associated with Peutz-Jeghers cancer-susceptibility syndrome; TOS3 has a paralog, SAK1, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description Target Of Sbf
Chromosomal Location
ChrVII:165091 to 163409 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All TOS3 GO evidence and references
  View Computational GO annotations for TOS3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 9 genes
Classical genetics
Large-scale survey
128 total interaction(s) for 115 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 3
  • Affinity Capture-RNA: 2
  • Biochemical Activity: 79
  • Reconstituted Complex: 3

Genetic Interactions
  • Dosage Growth Defect: 4
  • Negative Genetic: 11
  • Phenotypic Suppression: 1
  • Positive Genetic: 16
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 1

Expression Summary
Length (a.a.) 560
Molecular Weight (Da) 62,090
Isoelectric Point (pI) 7.41
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVII:165091 to 163409 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1683 165091..163409 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 SGDIDS000003147

TOS3 encodes a protein kinase that phosphorylates and activates the Snf1p kinase, which is a member of the family of eukaryotic AMP-activated protein kinases (AMPK) that play key roles in cellular response to nutrient stress (3). Snf1p activation is required for utilization of nonfermentable and non-preferred carbon sources, such as raffinose and glycerol-ethanol (reviewed in 7).

Three kinases function as upstream activators of Snf1p: Tos3p, Sak1p (formerly called Pak1p), and Elm1p. These kinases exhibit sequence similarity in the 300-residue kinase domain, while the N- and C-terminal regions are divergent. Each kinase activates Snf1p through phosphorylation of threonine 210, a conserved residue in the activation loop of the Snf1p kinase domain (3). Tos3p, Sak1p, and Elm1p exhibit a considerable degree of functional redundancy, as only the triple null mutant confers a snf1- phenotype (3, 2). Studies attempting to elucidate distinct roles for the three kinases have shown that, while each kinase does not specifically activate one of the three known isoforms of Snf1p, these isoforms do exhibit preferences for a particular kinase, depending in part on the nature of the available carbon source (8, 4).

TOS3 (target of SBF) was first identified by a genomic screen for promoters that are bound by the SBF (Swi4p-Swi6p) complex, which regulates transcription during the cell cycle (9). TOS3 RNA does not appear to be cell-cycle regulated (10) nor is it regulated in response to carbon source (7). Tos3p localizes to the cytoplasm regardless of the carbon source present during cell growth (7). It appears that Tos3p function is most important during growth on nonfermentable carbon sources. When tos3 null mutants are grown on glycerol-ethanol, they exhibit slow growth, reduced Snf1p catalytic activity, and reduced activation of the Snf1p-dependent CSREs (carbon source responsive elements) of gluconeogenic genes, relative to wild type cells (7).

The catalytic domain of Tos3p is similar to mammalian LKB1 tumor suppressor kinase, which is essential for mammalian embryonic development and is mutated in Peutz-Jeghers syndrome (11, 12, 13). Both LKB1 and Tos3p phosphorylate mammalian AMPK in vitro, providing evidence for their similar function as upstream kinases for the AMPK protein family members (3).

Last updated: 2006-10-24 Contact SGD

References cited on this page View Complete Literature Guide for TOS3
1) Nath N, et al.  (2003) Yeast Pak1 kinase associates with and activates Snf1. Mol Cell Biol 23(11):3909-17
2) Sutherland CM, et al.  (2003) Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol 13(15):1299-305
3) Hong SP, et al.  (2003) Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci U S A 100(15):8839-43
4) Hedbacker K, et al.  (2004) Pak1 protein kinase regulates activation and nuclear localization of Snf1-Gal83 protein kinase. Mol Cell Biol 24(18):8255-63
5) Elbing K, et al.  (2006) Purification and characterization of the three Snf1-activating kinases of Saccharomyces cerevisiae. Biochem J 393(Pt 3):797-805
6) 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
7) Kim MD, et al.  (2005) Role of Tos3, a Snf1 protein kinase kinase, during growth of Saccharomyces cerevisiae on nonfermentable carbon sources. Eukaryot Cell 4(5):861-6
8) McCartney RR, et al.  (2005) Snf1 kinase complexes with different beta subunits display stress-dependent preferences for the three Snf1-activating kinases. Curr Genet 47(6):335-44
9) Iyer VR, et al.  (2001) Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409(6819):533-8
10) Cho RJ, et al.  (1998) A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell 2(1):65-73
11) Jenne DE, et al.  (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18(1):38-43
12) Hemminki A, et al.  (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391(6663):184-7
13) Ylikorkala A, et al.  (2001) Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 293(5533):1323-6