SIP2/YGL208W Summary Help

Standard Name SIP2 1
Systematic Name YGL208W
Alias SPM2
Feature Type ORF, Verified
Description One of three beta subunits of the Snf1 kinase complex; involved in the response to glucose starvation; null mutants exhibit accelerated aging; N-myristoylprotein localized to the cytoplasm and the plasma membrane; SIP2 has a paralog, GAL83, that arose from the whole genome duplication (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description SNF1-Interacting Protein 7
Chromosomal Location
ChrVII:97338 to 98585 | ORF Map | GBrowse
Gene Ontology Annotations All SIP2 GO evidence and references
  View Computational GO annotations for SIP2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
Large-scale survey
88 total interaction(s) for 41 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 21
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 4
  • Biochemical Activity: 5
  • Co-crystal Structure: 1
  • Protein-peptide: 6
  • Reconstituted Complex: 2
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 11
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 1
  • Positive Genetic: 1
  • Synthetic Growth Defect: 12
  • Synthetic Lethality: 1
  • Synthetic Rescue: 4

Expression Summary
Length (a.a.) 415
Molecular Weight (Da) 46,404
Isoelectric Point (pI) 5.43
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVII:97338 to 98585 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 2011-02-03
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1248 97338..98585 2011-02-03 2011-02-03
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003176

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 (8, 9, 10, 11, 12, 13, 14). 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 (15, 16, 17, 18, 19, 20, 21, 22, 23). 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 (24, 25, 26, 27, 28, 29, 30, 31, 13, 32, 7, 33, 34, 35, 36, 1, 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, 1).

The three beta subunits of the Snf1p kinase complex (Gal83p, Sip1p, and Sip2p) define a family of homologous proteins that tightly associate with alternative forms of the Snf1p kinase complex (30, 1, 38). Each of the beta subunits is able to bind independently to both Snf1p and Snf4p through a conserved KIS domain that binds to the Snf1p regulatory domain and a conserved C-terminal ASC domain that binds to Snf4p. At least one functional beta subunit is required to mediate the protein-protein interaction between Snf1p and Snf4p. gal83, sip1 or sip2 null mutants are viable on all carbon sources, but gal83 sip1 sip2 triple null mutants display phenotypes similar to snf1 null mutants, and cannot grow on non-fermentable carbon sources (7, 1, 33, 3). The beta subunits also confer functional specificity to the Snf1p kinase (3, 4) and each of the beta subunits is phosphorylated by Snf1p in vitro (1, 35). The Snf1p-Gal83p kinase is responsible for approximately 75% of all Snf1p kinase activity shortly after a switch from growth in high-glucose to low-glucose media, and the Snf1p-Sip2p kinase is responsible for the major fraction of Snf1p kinase activity during growth on glycerol-ethanol medium (45, 46).

In either glucose- or glycerol-grown cells Sip2p is excluded from the nucleus (4). As cells age, Sip2p disassociates from the plasma membrane and becomes localized in the cytoplasm (5). Sip2p is N-terminally myristolated by Kre2p (47, 3) and mutations that block the N-myristoylation of Sip2p also block its localization to the plasma membrane, and result in a shift of Snf4p to the nucleus. sip2 null mutants age rapidly, suggesting that Sip2p acts as a negative regulator of nuclear Snf1p activity in young cells by sequestering Snf4p at the plasma membrane, and that loss of Sip2p from the plasma membrane to the cytoplasm in aging cells facilitates Snf4p entry into the nucleus so that Snf1p can modify chromatin structure (2, 5). Sip2p also positively regulates glycogen accumulation in vivo (48). Either Gal83p-Snf1p or Sip2p-Snf1p is sufficient for filamentation, and Sip2p-Snf1p can effect adherent growth (49).

Last updated: 2006-03-24 Contact SGD

References cited on this page View Complete Literature Guide for SIP2
1) 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
2) Ashrafi K, et al.  (2000) Sip2p and its partner snf1p kinase affect aging in S. cerevisiae. Genes Dev 14(15):1872-85
3) Schmidt MC and McCartney RR  (2000) beta-subunits of Snf1 kinase are required for kinase function and substrate definition. EMBO J 19(18):4936-43
4) Vincent O, et al.  (2001) Subcellular localization of the Snf1 kinase is regulated by specific beta subunits and a novel glucose signaling mechanism. Genes Dev 15(9):1104-14
5) 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
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) Yang X, et al.  (1992) A protein kinase substrate identified by the two-hybrid system. Science 257(5070):680-2
8) 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
9) 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
10) 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
11) Vallier LG and Carlson M  (1994) Synergistic release from glucose repression by mig1 and ssn mutations in Saccharomyces cerevisiae. Genetics 137(1):49-54
12) 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
13) 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
14) 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
15) 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
16) 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
17) 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
18) 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
19) Ashe MP, et al.  (2000) Glucose depletion rapidly inhibits translation initiation in yeast. Mol Biol Cell 11(3):833-48
20) 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
21) 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
22) Bertram PG, et al.  (2002) Convergence of TOR-nitrogen and Snf1-glucose signaling pathways onto Gln3. Mol Cell Biol 22(4):1246-52
23) 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
24) 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
25) 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
26) Carlson M, et al.  (1981) Mutants of yeast defective in sucrose utilization. Genetics 98(1):25-40
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) 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
32) Kunau WH and Hartig A  (1992) Peroxisome biogenesis in Saccharomyces cerevisiae. Antonie Van Leeuwenhoek 62(1-2):63-78
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) 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
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) 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
46) 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
47) Ashrafi K, et al.  (1998) A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J Biol Chem 273(40):25864-74
48) Wiatrowski HA, et al.  (2004) Mutations in the gal83 glycogen-binding domain activate the snf1/gal83 kinase pathway by a glycogen-independent mechanism. Mol Cell Biol 24(1):352-61
49) Vyas VK, et al.  (2003) Snf1 kinases with different beta-subunit isoforms play distinct roles in regulating haploid invasive growth. Mol Cell Biol 23(4):1341-8