SNF4/YGL115W Summary Help

Standard Name SNF4 1, 2
Systematic Name YGL115W
Alias CAT3 3 , SCI1 4
Feature Type ORF, Verified
Description Activating gamma subunit of the AMP-activated Snf1p kinase complex; additional subunits of the complex are Snf1p and a Sip1p/Sip2p/Gal83p family member; activates glucose-repressed genes, represses glucose-induced genes; role in sporulation, and peroxisome biogenesis; protein abundance increases in response to DNA replication stress (2, 5, 6, 7 and see Summary Paragraph)
Name Description Sucrose NonFermenting 8
Chromosomal Location
ChrVII:292033 to 293001 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All SNF4 GO evidence and references
  View Computational GO annotations for SNF4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All SNF4 Phenotype evidence and references
Classical genetics
null
reduction of function
Large-scale survey
null
Resources
interactions All SNF4 Interaction evidence and references
415 total interaction(s) for 271 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 57
  • Affinity Capture-Western: 6
  • Co-crystal Structure: 3
  • Co-purification: 1
  • Reconstituted Complex: 3
  • Two-hybrid: 53
Genetic Interactions
  • Dosage Rescue: 8
  • Negative Genetic: 195
  • Phenotypic Enhancement: 5
  • Phenotypic Suppression: 1
  • Positive Genetic: 55
  • Synthetic Growth Defect: 10
  • Synthetic Lethality: 4
  • Synthetic Rescue: 14
Resources
Expression Summary
histogram
Resources
Protein Information All SNF4 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:292033 to 293001 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..969 292033..293001 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003083
SUMMARY PARAGRAPH for SNF4

Transcriptional regulation is an important mechanism for controlling carbon metabolism in Saccharomyces cerevisiae. The Snf1p kinase complex, which phosphorylates serine and threonine residues, is essential for regulating the transcriptional changes associated with glucose derepression through its activation of the transcriptional activators Cat8p and Sip4p, and its deactivation of the transcriptional repressor Mig1p (9, 10, 11, 12, 13, 14, 15). The complex has also been shown to be involved in multiple processes, including phosphorylation of histone H3; direct regulation of RNA polymerase II holoenzyme; regulation of translation, glycogen biosynthesis, and lipid biosynthesis; and regulation of general stress responses, response to salt stress and response to heat stress (16, 17, 18, 19, 20, 21, 22, 23, 24). The active Snf1p kinase complex is a heterotrimeric complex composed of Snf1p, the catalytic (alpha) subunit; Snf4p, a regulatory (gamma) subunit; and one of three possible beta subunits (Gal83p, Sip1p, or Sip2p) which appear to tether Snf1p and Snf4p together and also may determine substrate specificity of the Snf1p kinase complex (25, 26, 8, 27, 28, 29, 30, 2, 14, 31, 32, 33, 34, 35, 6, 36, 37).

The Snf1p kinase complex belongs to a highly conserved family of serine/threonine protein kinases, and homologs to each of the subunits (Snf1p, Snf4p, Sip1p, Sip2p, and Gal83p) have been found in all eukaryotes, including plants and mammals (38, 30, 39, 40, 41, 42, 43, 33, 44, 36).

Snf4p appears to activate Snf1p by inhibiting the autoinhibitory interaction of the C-terminus (regulatory domain) of Snf1p with the catalytic N-terminus of Snf1p, but Snf4p does not influence the phosphorylation state of Snf1p (6, 37, 45, 2). Snf4p is associated with Snf1p in cells grown in both high and low levels of glucose (33). SNF4 is not regulated by glucose repression (2), but binding of Snf4p to Elc1p inhibits the degradation of Snf4p (46).

snf4 null mutants are viable, but are unable to grow on maltose or on non-fermentable carbon sources (1, 3, 47). As compared to wild type, snf4 null mutants display increased temperature sensitivity, an extended generational life span, a shortened G1 phase and longer S and G2 phases, and decreased production of Cdc28p during growth in glucose-limited cultures, and they also lack peroxisomes (5, 2, 48, 49).

Snf4p has similarity to human PRKAG2, mutations in which are associated with hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome (50). Snf4p also contains a region with homology to the known mammalian Elongin C binding proteins, and this region is necessary for the interaction between Snf4p and Elc1p (51). The growth defects of snf4 null mutants are complemented by Arabidopsis thaliana SNF4 and Candida albicans SNF4 (52, 53).

Last updated: 2006-03-24

References cited on this page View Complete Literature Guide for SNF4
1) Neigeborn L and Carlson M  (1984) Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics 108(4):845-58
2) Celenza JL, et al.  (1989) Molecular analysis of the SNF4 gene of Saccharomyces cerevisiae: evidence for physical association of the SNF4 protein with the SNF1 protein kinase. Mol Cell Biol 9(11):5045-54
3) Schuller HJ and Entian KD  (1988) Molecular characterization of yeast regulatory gene CAT3 necessary for glucose derepression and nuclear localization of its product. Gene 67(2):247-57
4) Blazquez MA and Gancedo C  (1994) Identification of extragenic suppressors of the cif1 mutation in Saccharomyces cerevisiae. Curr Genet 25(2):89-94
5) Simon M, et al.  (1992) Control of peroxisome proliferation in Saccharomyces cerevisiae by ADR1, SNF1 (CAT1, CCR1) and SNF4 (CAT3). Yeast 8(4):303-9
6) Celenza JL and Carlson M  (1989) Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein. Mol Cell Biol 9(11):5034-44
7) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
8) Carlson M, et al.  (1981) Mutants of yeast defective in sucrose utilization. Genetics 98(1):25-40
9) Randez-Gil F, et al.  (1997) Glucose derepression of gluconeogenic enzymes in Saccharomyces cerevisiae correlates with phosphorylation of the gene activator Cat8p. Mol Cell Biol 17(5):2502-10
10) Vincent O and Carlson M  (1998) Sip4, a Snf1 kinase-dependent transcriptional activator, binds to the carbon source-responsive element of gluconeogenic genes. EMBO J 17(23):7002-8
11) Schuller HJ and Entian KD  (1991) Extragenic suppressors of yeast glucose derepression mutants leading to constitutive synthesis of several glucose-repressible enzymes. J Bacteriol 173(6):2045-52
12) Vallier LG and Carlson M  (1994) Synergistic release from glucose repression by mig1 and ssn mutations in Saccharomyces cerevisiae. Genetics 137(1):49-54
13) Hedges D, et al.  (1995) CAT8, a new zinc cluster-encoding gene necessary for derepression of gluconeogenic enzymes in the yeast Saccharomyces cerevisiae. Mol Cell Biol 15(4):1915-22
14) Lesage P, et al.  (1996) Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster transcriptional activator: a new role for SNF1 in the glucose response. Mol Cell Biol 16(5):1921-8
15) Rahner A, et al.  (1996) Dual influence of the yeast Cat1p (Snf1p) protein kinase on carbon source-dependent transcriptional activation of gluconeogenic genes by the regulatory gene CAT8. Nucleic Acids Res 24(12):2331-7
16) Kuchin S, et al.  (2000) A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A 97(14):7916-20
17) Lo WS, et al.  (2001) Snf1--a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Science 293(5532):1142-6
18) Hardy TA, et al.  (1994) Interactions between cAMP-dependent and SNF1 protein kinases in the control of glycogen accumulation in Saccharomyces cerevisiae. J Biol Chem 269(45):27907-13
19) Woods A, et al.  (1994) Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem 269(30):19509-15
20) Ashe MP, et al.  (2000) Glucose depletion rapidly inhibits translation initiation in yeast. Mol Biol Cell 11(3):833-48
21) Thompson-Jaeger S, et al.  (1991) Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. Genetics 129(3):697-706
22) Mayordomo I, et al.  (2002) Convergence of the target of rapamycin and the Snf1 protein kinase pathways in the regulation of the subcellular localization of Msn2, a transcriptional activator of STRE (Stress Response Element)-regulated genes. J Biol Chem 277(38):35650-6
23) Bertram PG, et al.  (2002) Convergence of TOR-nitrogen and Snf1-glucose signaling pathways onto Gln3. Mol Cell Biol 22(4):1246-52
24) Alepuz PM, et al.  (1997) Glucose repression affects ion homeostasis in yeast through the regulation of the stress-activated ENA1 gene. Mol Microbiol 26(1):91-8
25) Zimmermann FK, et al.  (1977) Genetics of carbon catabolite repression in Saccharomycess cerevisiae: genes involved in the derepression process. Mol Gen Genet 151(1):95-103
26) Ciriacy M  (1977) Isolation and characterization of yeast mutants defective in intermediary carbon metabolism and in carbon catabolite derepression. Mol Gen Genet 154(2):213-20
27) Scholer A and Schuller HJ  (1994) A carbon source-responsive promoter element necessary for activation of the isocitrate lyase gene ICL1 is common to genes of the gluconeogenic pathway in the yeast Saccharomyces cerevisiae. Mol Cell Biol 14(6):3613-22
28) Celenza JL and Carlson M  (1984) Cloning and genetic mapping of SNF1, a gene required for expression of glucose-repressible genes in Saccharomyces cerevisiae. Mol Cell Biol 4(1):49-53
29) Celenza JL and Carlson M  (1984) Structure and expression of the SNF1 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(1):54-60
30) Erickson JR and Johnston M  (1993) Genetic and molecular characterization of GAL83: its interaction and similarities with other genes involved in glucose repression in Saccharomyces cerevisiae. Genetics 135(3):655-64
31) Kunau WH and Hartig A  (1992) Peroxisome biogenesis in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek 62(1-2):63-78
32) Yang X, et al.  (1992) A protein kinase substrate identified by the two-hybrid system. Science 257(5070):680-2
33) Jiang R and Carlson M  (1997) The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex. Mol Cell Biol 17(4):2099-106
34) Fernandez E, et al.  (1993) Transcriptional regulation of the isocitrate lyase encoding gene in Saccharomyces cerevisiae. FEBS Lett 333(3):238-42
35) Mylin LM, et al.  (1994) SIP1 is a catabolite repression-specific negative regulator of GAL gene expression. Genetics 137(3):689-700
36) Yang X, et al.  (1994) A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex. EMBO J 13(24):5878-86
37) McCartney RR and Schmidt MC  (2001) Regulation of Snf1 kinase. Activation requires phosphorylation of threonine 210 by an upstream kinase as well as a distinct step mediated by the Snf4 subunit. J Biol Chem 276(39):36460-6
38) Stapleton D, et al.  (1994) Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase. J Biol Chem 269(47):29343-6
39) Mitchelhill KI, et al.  (1994) Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J Biol Chem 269(4):2361-4
40) Woods A, et al.  (1996) Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro. J Biol Chem 271(17):10282-90
41) Muranaka T, et al.  (1994) Characterization of tobacco protein kinase NPK5, a homolog of Saccharomyces cerevisiae SNF1 that constitutively activates expression of the glucose-repressible SUC2 gene for a secreted invertase of S. cerevisiae. Mol Cell Biol 14(5):2958-65
42) Bouly JP, et al.  (1999) Arabidopsis thaliana proteins related to the yeast SIP and SNF4 interact with AKINalpha1, an SNF1-like protein kinase. Plant J 18(5):541-50
43) Goffrini P, et al.  (1996) FOG1 and FOG2 genes, required for the transcriptional activation of glucose-repressible genes of Kluyveromyces lactis, are homologous to GAL83 and SNF1 of saccharomyces cerevisiae. Curr Genet 29(4):316-26
44) Gao G, et al.  (1996) Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated protein kinase. J Biol Chem 271(15):8675-81
45) Jiang R and Carlson M  (1996) Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes Dev 10(24):3105-15
46) Hyman LE, et al.  (2002) Binding to Elongin C inhibits degradation of interacting proteins in yeast. J Biol Chem 277(18):15586-91
47) Entian KD and Zimmermann FK  (1982) New genes involved in carbon catabolite repression and derepression in the yeast Saccharomyces cerevisiae. J Bacteriol 151(3):1123-8
48) Lin SS, et al.  (2001) Enhanced gluconeogenesis and increased energy storage as hallmarks of aging in Saccharomyces cerevisiae. J Biol Chem 276(38):36000-7
49) Aon MA and Cortassa S  (1998) Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose-limited chemostat cultures. Biotechnol Bioeng 59(2):203-13
50) Arad M, et al.  (2002) Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 109(3):357-62
51) Jackson T, et al.  (2000) Novel roles for elongin C in yeast. Biochim Biophys Acta 1491(1-3):161-76
52) Kleinow T, et al.  (2000) Functional identification of an Arabidopsis snf4 ortholog by screening for heterologous multicopy suppressors of snf4 deficiency in yeast. Plant J 23(1):115-22
53) Corvey C, et al.  (2005) Carbon Source-dependent assembly of the Snf1p kinase complex in Candida albicans. J Biol Chem 280(27):25323-30