SNF1/YDR477W Summary Help

Standard Name SNF1 1
Systematic Name YDR477W
Alias CAT1 2 , CCR1 3 , GLC2 4 , HAF3 5 , PAS14 6
Feature Type ORF, Verified
Description AMP-activated serine/threonine protein kinase; found in a complex containing Snf4p and members of the Sip1p/Sip2p/Gal83p family; required for transcription of glucose-repressed genes, thermotolerance, sporulation, and peroxisome biogenesis; involved in regulation of the nucleocytoplasmic shuttling of Hxk2p; regulates filamentous growth in response to starvation; SUMOylation by Mms21p inhibits its function and targets Snf1p for destruction via the Slx5-Slx8 Ubiquitin ligase (7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Sucrose NonFermenting 12
Chromosomal Location
ChrIV:1412373 to 1414274 | ORF Map | GBrowse
Gbrowse
Genetic position: 304 cM
Gene Ontology Annotations All SNF1 GO evidence and references
  View Computational GO annotations for SNF1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
activation
conditional
gain of function
null
overexpression
reduction of function
Large-scale survey
null
overexpression
Resources
776 total interaction(s) for 428 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 78
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 51
  • Biochemical Activity: 106
  • Co-crystal Structure: 2
  • Co-fractionation: 1
  • Co-localization: 1
  • Co-purification: 2
  • PCA: 5
  • Reconstituted Complex: 36
  • Two-hybrid: 73

Genetic Interactions
  • Dosage Growth Defect: 8
  • Dosage Lethality: 1
  • Dosage Rescue: 32
  • Negative Genetic: 232
  • Phenotypic Enhancement: 9
  • Phenotypic Suppression: 13
  • Positive Genetic: 39
  • Synthetic Growth Defect: 32
  • Synthetic Lethality: 8
  • Synthetic Rescue: 46

Resources
Expression Summary
histogram
Resources
Length (a.a.) 633
Molecular Weight (Da) 72,045
Isoelectric Point (pI) 6.65
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:1412373 to 1414274 | ORF Map | GBrowse
SGD ORF map
Genetic position: 304 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1902 1412373..1414274 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002885
SUMMARY PARAGRAPH for SNF1

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 (13, 14, 15, 16, 17, 18, 19). 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 (20, 21, 22, 23, 24, 25, 26, 27, 28). 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 (2, 3, 12, 29, 1, 30, 31, 32, 18, 33, 34, 35, 36, 37, 38, 39, 40).

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 (41, 31, 42, 43, 44, 45, 46, 35, 47, 39).

Snf1p is known or predicted to phosphorylate a wide range of substrates, including histone H3 (Hht1p and Hht2p) Mig1p, Snf1p, Sip1p, Sip2p, Gal83p, Gln3p, Hsf1p, Cat8p, and Sip4p (38, 18, 13, 14, 48, 49). The kinase activity of Snf1p is under multiple types of regulation. Its N-terminal catalytic domain appears to be autoinhibited by binding to its C-terminal regulatory domain under high-glucose conditions. Under low-glucose conditions, the catalytic domain is bound by Snf4p, which alleviates the autoinhibition from the Snf1p regulatory domain (38, 50). Std1p has also been shown to enhance the kinase activity of Snf1p (51, 52). Snf1p is activated by phosphorylation on threonine 210 by either Sak1p, Tos3p, or Elm1p, and is deactivated by the dephosphorylase Glc7p/Reg1p (53, 54, 55, 56, 57). Although Snf1p is a member of the family of AMP-activated protein kinases, Snf1p is not directly regulated by an AMP signal and SNF1 transcription is not regulated by glucose repression (58, 59, 30).

snf1 null mutants are viable, but are unable to grow on sucrose, galactose, maltose, melibiose or nonfermentable carbon sources. snf1 null mutants also display sporulation defects and don't contain any detectable peroxisomes (1, 38, 60, 61). Overproduction of Snf1p causes accelerated aging (62).

Snf1p has similarity to human PRKAA2, which is implicated in pancreatic carcinoma and may be an important target for drug development against diabetes, obesity, and other diseases (35, 63). The growth defects of snf1 null mutants are complemented by tobacco NPK5 and potato StubSNF1 (44, 64).

Last updated: 2006-03-24 Contact SGD

References cited on this page View Complete Literature Guide for SNF1
1) 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
2) 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
3) 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
4) Cannon JF, et al.  (1994) Characterization of glycogen-deficient glc mutants of Saccharomyces cerevisiae. Genetics 136(2):485-503
5) Kuchin SV, et al.  (1993) Genes required for derepression of an extracellular glucoamylase gene, STA2, in the yeast Saccharomyces. Yeast 9(5):533-41
6) Van der Leij I, et al.  (1992) Isolation of peroxisome assembly mutants from Saccharomyces cerevisiae with different morphologies using a novel positive selection procedure. J Cell Biol 119(1):153-62
7) Sanz P  (2003) Snf1 protein kinase: a key player in the response to cellular stress in yeast. Biochem Soc Trans 31(Pt 1):178-81
8) Hardie DG, et al.  (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67():821-55
9) Karunanithi S and Cullen PJ  (2012) The filamentous growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 transcriptional repressors in Saccharomyces cerevisiae. Genetics 192(3):869-87
10) Fernandez-Garcia P, et al.  (2012) Phosphorylation of yeast hexokinase 2 regulates its nucleocytoplasmic shuttling. J Biol Chem 287(50):42151-64
11) Simpson-Lavy KJ and Johnston M  (2013) SUMOylation regulates the SNF1 protein kinase. Proc Natl Acad Sci U S A 110(43):17432-7
12) Carlson M, et al.  (1981) Mutants of yeast defective in sucrose utilization. Genetics 98(1):25-40
13) 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
14) 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
15) 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
16) Vallier LG and Carlson M  (1994) Synergistic release from glucose repression by mig1 and ssn mutations in Saccharomyces cerevisiae. Genetics 137(1):49-54
17) 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
18) 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
19) 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
20) 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
21) 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
22) 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
23) 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
24) Ashe MP, et al.  (2000) Glucose depletion rapidly inhibits translation initiation in yeast. Mol Biol Cell 11(3):833-48
25) 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
26) 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
27) Bertram PG, et al.  (2002) Convergence of TOR-nitrogen and Snf1-glucose signaling pathways onto Gln3. Mol Cell Biol 22(4):1246-52
28) 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
29) 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
30) Celenza JL and Carlson M  (1984) Structure and expression of the SNF1 gene of Saccharomyces cerevisiae. Mol Cell Biol 4(1):54-60
31) 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
32) 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
33) Kunau WH and Hartig A  (1992) Peroxisome biogenesis in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek 62(1-2):63-78
34) Yang X, et al.  (1992) A protein kinase substrate identified by the two-hybrid system. Science 257(5070):680-2
35) 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
36) Fernandez E, et al.  (1993) Transcriptional regulation of the isocitrate lyase encoding gene in Saccharomyces cerevisiae. FEBS Lett 333(3):238-42
37) Mylin LM, et al.  (1994) SIP1 is a catabolite repression-specific negative regulator of GAL gene expression. Genetics 137(3):689-700
38) 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
39) 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
40) 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
41) 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
42) 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
43) 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
44) 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
45) 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
46) 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
47) 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
48) Hahn JS and Thiele DJ  (2004) Activation of the Saccharomyces cerevisiae heat shock transcription factor under glucose starvation conditions by Snf1 protein kinase. J Biol Chem 279(7):5169-76
49) Nath N, et al.  (2002) Purification and characterization of Snf1 kinase complexes containing a defined Beta subunit composition. J Biol Chem 277(52):50403-8
50) Jiang R and Carlson M  (1996) Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes Dev 10(24):3105-15
51) Hubbard EJ, et al.  (1994) Dosage-dependent modulation of glucose repression by MSN3 (STD1) in Saccharomyces cerevisiae. Mol Cell Biol 14(3):1972-8
52) Kuchin S, et al.  (2003) Std1p (Msn3p) positively regulates the Snf1 kinase in Saccharomyces cerevisiae. Genetics 163(2):507-14
53) Leech A, et al.  (2003) Isolation of mutations in the catalytic domain of the snf1 kinase that render its activity independent of the snf4 subunit. Eukaryot Cell 2(2):265-73
54) 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
55) Nath N, et al.  (2003) Yeast Pak1 kinase associates with and activates Snf1. Mol Cell Biol 23(11):3909-17
56) Sutherland CM, et al.  (2003) Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol 13(15):1299-305
57) Ludin K, et al.  (1998) Glucose-regulated interaction of a regulatory subunit of protein phosphatase 1 with the Snf1 protein kinase in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 95(11):6245-50
58) Wilson WA, et al.  (1996) Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio. Curr Biol 6(11):1426-34
59) Daniel T and Carling D  (2002) Expression and regulation of the AMP-activated protein kinase-SNF1 (sucrose non-fermenting 1) kinase complexes in yeast and mammalian cells: studies using chimaeric catalytic subunits. Biochem J 365(Pt 3):629-38
60) Hubbard EJ, et al.  (1992) Relationship of the cAMP-dependent protein kinase pathway to the SNF1 protein kinase and invertase expression in Saccharomyces cerevisiae. Genetics 130(1):71-80
61) 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
62) Lin SS, et al.  (2003) Sip2, an N-myristoylated beta subunit of Snf1 kinase, regulates aging in Saccharomyces cerevisiae by affecting cellular histone kinase activity, recombination at rDNA loci, and silencing. J Biol Chem 278(15):13390-7
63) Rudolph MJ, et al.  (2005) Crystal structure of the protein kinase domain of yeast AMP-activated protein kinase Snf1. Biochem Biophys Res Commun 337(4):1224-8
64) Lovas A, et al.  (2003) Functional diversity of potato SNF1-related kinases tested in Saccharomyces cerevisiae. Gene 321:123-9