GLC7/YER133W Summary Help

Standard Name GLC7 1
Systematic Name YER133W
Alias CID1 2 , DIS2 3
Feature Type ORF, Verified
Description Type 1 serine/threonine protein phosphatase catalytic subunit; cleavage and polyadenylation factor (CPF) component; involved in various processes including glycogen metabolism, sporulation, mitosis; accumulates at mating projections by interaction with Afr1p; interacts with many regulatory subunits; involved in regulation of the nucleocytoplasmic shuttling of Hxk2p; import into nucleus is inhibited during spindle assembly checkpoint arrest (4, 5, 6, 7, 8, 9, 10 and see Summary Paragraph)
Also known as: PP1 11 , DIS2S1 12 , 5
Name Description GLyCogen 1
Chromosomal Location
ChrV:432495 to 433958 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All GLC7 GO evidence and references
  View Computational GO annotations for GLC7
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Resources
Classical genetics
conditional
null
overexpression
reduction of function
unspecified
Large-scale survey
conditional
null
overexpression
reduction of function
Resources
869 total interaction(s) for 544 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 269
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 47
  • Biochemical Activity: 13
  • Co-fractionation: 1
  • FRET: 1
  • PCA: 3
  • Reconstituted Complex: 5
  • Two-hybrid: 71

Genetic Interactions
  • Dosage Growth Defect: 6
  • Dosage Lethality: 5
  • Dosage Rescue: 20
  • Negative Genetic: 127
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 3
  • Positive Genetic: 35
  • Synthetic Growth Defect: 116
  • Synthetic Lethality: 125
  • Synthetic Rescue: 18

Resources
Expression Summary
histogram
Resources
Length (a.a.) 312
Molecular Weight (Da) 35,907
Isoelectric Point (pI) 5.21
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrV:432495 to 433958 | 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..177 432495..432671 2011-02-03 1996-07-31
Intron 178..702 432672..433196 2011-02-03 1996-07-31
CDS 703..1464 433197..433958 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 SGDIDS000000935
SUMMARY PARAGRAPH for GLC7

Glc7p is the catalytic subunit of type 1 protein phosphatase (PP1) (5), which is a member of the highly conserved PPP family of protein serine-threonine phosphatases (12). Like mammalian PP1 catalytic subunits, Glc7p regulates many physiological processes, including glycogen metabolism, glucose repression, transcription, membrane fusion, sporulation, mitosis, ion homeostasis, and cell wall organization (13, 14, 15). Glc7p functions in opposition to the Ipl1p Aurora kinase to ensure proper levels of histone H3 phosphorylation and the fidelity of chromosome segregation during mitosis (16). Glc7p also appears to function in opposition to the Gcn2p kinase in modulating phosphorylation levels of the Sui2p alpha-subunit of translation initiation factor eIF2, which effects translation of some mRNAs (17). Glc7p dephosphorylates proteins involved in a variety of processes including Cbf2p (an essential kinetochore protein) (18), Fin1p (mitosis) (19), and Red1p (meiotic chromosome segregation) (20). Scd5p, which is involved in cortical actin organization and endocytosis, and Npl3p, which is involved in mRNA export, are both activated by Glc7p-dependent dephosphorylation (21, 22, 23).

Glc7p itself has little substrate specificity (24). Instead, specificity is dictated by regulatory subunits that target Glc7p to various substrates for different functions under different growth conditions (25), or alter its activity (6). Glc7p is targeted to the bud neck before bud emergence by Bni4p, which is required for the assembly of the chitin ring, and is also involved in septum formation and the maintenance of bud neck integrity (26, 27). Glc7p is targeted to the bud cortex and shmoo tip by Bud14p, and Bud14p-Glc7p interactions are important for bud-site selection, filamentous growth, polarized growth, and transcription of some STRE-dependent genes (28, 29). Gac1p targets Glc7p to the glycogen synthase Gsy2p, is required for glycogen accumulation, and is involved in the transcription of some heat-shock responsive genes (15, 30). Reg1p is required for the involvement of Glc7p in various processes including glucose repression, cell growth, and glycogen accumulation (25), and Sip5p may increase Glc7p-Reg1p complex binding to Snf1p (31). Reg2p appears to target Glc7p to substrates that are phosphorylated by Snf1p during glucose repression (32). Ref2p targets Glc7p to the cleavage and polyadenylation factor-containing complex (holo-CPF), that associates with the 3' ends of mRNA-encoding genes and also with snoRNA genes, and is involved in pre-mRNA polyadenylation and snoRNA 3'-end maturation (33).

Although GLC7 is induced during stationary phase, the level of GLC7 mRNA is constant during exponential growth (5). Glc7p displays a constant level of activity throughout the cell cycle, and is quite stable, with a half-life of several generations (180 minutes) (6). Glc7p activation by the regulatory subunit Glc8p is important for stationary phase and chromosome segregation, and to a lesser degree for glycogen accumulation (6, 34, 35). Glc7p is also activated by the PP1 regulator Shp1p, either directly or indirectly, which effects sporulation and normal growth (36, 25), and is inhibited by the PP1 inhibitor Ypi1p (37).

Glc7p is found in a variety of cellular locations, as dictated by its various functions and targeting partners, including spindle pole bodies from start of anaphase until cytokinesis, the bud neck ring after anaphase, the base of mating projections in alpha-factor treated cells, and in the nucleus with high concentrations in the nucleolus throughout the mitotic cell cycle (38). Glc7p requires Sds22p for its for normal nuclear localization during mitosis (39, 14), and requires Gip1p for its meiotic nuclear localization and involvement in the regulation of septin organization and spore wall formation (40).

While glc7 null mutants are inviable, reduction-of-function mutations result in a wide range of phenotypes. glc7-1 mutants display a severe defect in glycogen accumulation but normal glucose repression, whereas glc7-T152K mutations do not prevent glycogen accumulation, but do relieve glucose repression (41). At restrictive temperatures, glc7-10 mutants display a high frequency of chromosome loss, hyperphosphorylation of Cbf2p (18), a high proportion of budded cells with an unmigrated nucleus, duplicated spindle pole bodies, a short spindle, delocalized cortical actin and 2C DNA content (42). glc7-109 mutants display a dominant hyperglycogen defect and recessive ion and drug sensitivity (15). glc7-129, glc7-131, and glc7-127 mutants display elevated levels of mitotic histone H3 phosphorylation (43), and glc7-129 cells also display a G2/M cell cycle arrest (44). glc7Y-170 mutants display a defect in the G2/M phase of the cell cycle (45). GLC7 mutations have also been associated with defects in premeiotic DNA synthesis and sporulation (35) and depletion of Glc7p is associated with G1 arrest (35). Overexpression of GLC7 results in chromosome missegregation (16, 36), growth defects, aberrant bud morphology (46), and mitotic delay with increased numbers of large budded cells which are blocked in mitosis (46).

Amino acid sequences of catalytic subunits of type 1 protein phosphatase are highly conserved across many species (35), such that GLC7 displays similarity to many PP1 eukaryotic counterparts, including Schizosaccharomyces pombe dis2, Drosophila melanogaster and rabbit protein phosphatase 1 catalytic subunits (5), and human PPP1CA and PPP1CB, PPP1CC (11, 13).

Last updated: 2005-11-01 Contact SGD

References cited on this page View Complete Literature Guide for GLC7
1) Peng ZY, et al.  (1990) Purification and characterization of glycogen synthase from a glycogen-deficient strain of Saccharomyces cerevisiae. J Biol Chem 265(23):13871-7
2) Neigeborn L and Carlson M  (1987) Mutations causing constitutive invertase synthesis in yeast: genetic interactions with snf mutations. Genetics 115(2):247-53
3) Ohkura H, et al.  (1989) The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell 57(6):997-1007
4) Stark MJ  (1996) Yeast protein serine/threonine phosphatases: multiple roles and diverse regulation. Yeast 12(16):1647-75
5) Feng ZH, et al.  (1991) The yeast GLC7 gene required for glycogen accumulation encodes a type 1 protein phosphatase. J Biol Chem 266(35):23796-801
6) Nigavekar SS, et al.  (2002) Glc8 is a glucose-repressible activator of Glc7 protein phosphatase-1. Arch Biochem Biophys 404(1):71-9
7) Nedea E, et al.  (2008) The Glc7 phosphatase subunit of the cleavage and polyadenylation factor is essential for transcription termination on snoRNA genes. Mol Cell 29(5):577-87
8) Bharucha JP, et al.  (2008) Saccharomyces cerevisiae Afr1 protein is a protein phosphatase 1/Glc7-targeting subunit that regulates the septin cytoskeleton during mating. Eukaryot Cell 7(8):1246-55
9) Fernandez-Garcia P, et al.  (2012) Phosphorylation of yeast hexokinase 2 regulates its nucleocytoplasmic shuttling. J Biol Chem 287(50):42151-64
10) Cairo LV, et al.  (2013) Mitosis-specific regulation of nuclear transport by the spindle assembly checkpoint protein Mad1p. Mol Cell 49(1):109-20
11) Chen MX, et al.  (1992) Polymerase chain reactions using Saccharomyces, Drosophila and human DNA predict a large family of protein serine/threonine phosphatases. FEBS Lett 306(1):54-8
12) Clotet J, et al.  (1991) The gene DIS2S1 is essential in Saccharomyces cerevisiae and is involved in glycogen phosphorylase activation. Curr Genet 19(5):339-42
13) Tan YS, et al.  (2003) Pho85 phosphorylates the Glc7 protein phosphatase regulator Glc8 in vivo. J Biol Chem 278(1):147-53
14) Peggie MW, et al.  (2002) Essential functions of Sds22p in chromosome stability and nuclear localization of PP1. J Cell Sci 115(Pt 1):195-206
15) Williams-Hart T, et al.  (2002) Protein phosphatase type 1 regulates ion homeostasis in Saccharomyces cerevisiae. Genetics 160(4):1423-37
16) Francisco L, et al.  (1994) Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol Cell Biol 14(7):4731-40
17) Wek RC, et al.  (1992) Truncated protein phosphatase GLC7 restores translational activation of GCN4 expression in yeast mutants defective for the eIF-2 alpha kinase GCN2. Mol Cell Biol 12(12):5700-10
18) Sassoon I, et al.  (1999) Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p. Genes Dev 13(5):545-55
19) Mayordomo I and Sanz P  (2002) The Saccharomyces cerevisiae 14-3-3 protein Bmh2 is required for regulation of the phosphorylation status of Fin1, a novel intermediate filament protein. Biochem J 365(Pt 1):51-6
20) Bailis JM and Roeder GS  (2000) Pachytene exit controlled by reversal of Mek1-dependent phosphorylation. Cell 101(2):211-21
21) Chang JS, et al.  (2002) Protein phosphatase-1 binding to scd5p is important for regulation of actin organization and endocytosis in yeast. J Biol Chem 277(50):48002-8
22) Huang B, et al.  (2003) Identification of novel recognition motifs and regulatory targets for the yeast actin-regulating kinase Prk1p. Mol Biol Cell 14(12):4871-84
23) Gilbert W and Guthrie C  (2004) The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA. Mol Cell 13(2):201-12
24) Lenssen E, et al.  (2005) The Ccr4-Not complex independently controls both Msn2-dependent transcriptional activation--via a newly identified Glc7/Bud14 type I protein phosphatase module--and TFIID promoter distribution. Mol Cell Biol 25(1):488-98
25) Cui DY, et al.  (2004) The type 1 phosphatase Reg1p-Glc7p is required for the glucose-induced degradation of fructose-1,6-bisphosphatase in the vacuole. J Biol Chem 279(11):9713-24
26) Kozubowski L, et al.  (2003) A Bni4-Glc7 phosphatase complex that recruits chitin synthase to the site of bud emergence. Mol Biol Cell 14(1):26-39
27) Sanz M, et al.  (2004) Saccharomyces cerevisiae Bni4p directs the formation of the chitin ring and also participates in the correct assembly of the septum structure. Microbiology 150(Pt 10):3229-41
28) Ni L and Snyder M  (2001) A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell 12(7):2147-70
29) Knaus M, et al.  (2005) The Bud14p-Glc7p complex functions as a cortical regulator of dynein in budding yeast. EMBO J 24(17):3000-11
30) Lin JT and Lis JT  (1999) Glycogen synthase phosphatase interacts with heat shock factor to activate CUP1 gene transcription in Saccharomyces cerevisiae. Mol Cell Biol 19(5):3237-45
31) Sanz P, et al.  (2000) Sip5 interacts with both the Reg1/Glc7 protein phosphatase and the Snf1 protein kinase of Saccharomyces cerevisiae. Genetics 154(1):99-107
32) Frederick DL and Tatchell K  (1996) The REG2 gene of Saccharomyces cerevisiae encodes a type 1 protein phosphatase-binding protein that functions with Reg1p and the Snf1 protein kinase to regulate growth. Mol Cell Biol 16(6):2922-31
33) Nedea E, et al.  (2003) Organization and function of APT, a subcomplex of the yeast cleavage and polyadenylation factor involved in the formation of mRNA and small nucleolar RNA 3'-ends. J Biol Chem 278(35):33000-10
34) Tung HY, et al.  (1995) Regulation of chromosome segregation by Glc8p, a structural homolog of mammalian inhibitor 2 that functions as both an activator and an inhibitor of yeast protein phosphatase 1. Mol Cell Biol 15(11):6064-74
35) Ramaswamy NT, et al.  (1998) Regulation of yeast glycogen metabolism and sporulation by Glc7p protein phosphatase. Genetics 149(1):57-72
36) Zhang S, et al.  (1995) The Saccharomyces SHP1 gene, which encodes a regulator of phosphoprotein phosphatase 1 with differential effects on glycogen metabolism, meiotic differentiation, and mitotic cell cycle progression. Mol Cell Biol 15(4):2037-50
37) Garcia-Gimeno MA, et al.  (2003) Molecular characterization of Ypi1, a novel Saccharomyces cerevisiae type 1 protein phosphatase inhibitor. J Biol Chem 278(48):47744-52
38) Bloecher A and Tatchell K  (2000) Dynamic localization of protein phosphatase type 1 in the mitotic cell cycle of Saccharomyces cerevisiae. J Cell Biol 149(1):125-40
39) Hisamoto N, et al.  (1995) The EGP1 gene may be a positive regulator of protein phosphatase type 1 in the growth control of Saccharomyces cerevisiae. Mol Cell Biol 15(7):3767-76
40) Tachikawa H, et al.  (2001) A Gip1p-Glc7p phosphatase complex regulates septin organization and spore wall formation. J Cell Biol 155(5):797-808
41) Tu J and Carlson M  (1994) The GLC7 type 1 protein phosphatase is required for glucose repression in Saccharomyces cerevisiae. Mol Cell Biol 14(10):6789-96
42) Andrews PD and Stark MJ  (2000) Type 1 protein phosphatase is required for maintenance of cell wall integrity, morphogenesis and cell cycle progression in Saccharomyces cerevisiae. J Cell Sci 113 ( Pt 3)():507-20
43) Hsu JY, et al.  (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102(3):279-91
44) Bloecher A and Tatchell K  (1999) Defects in Saccharomyces cerevisiae protein phosphatase type I activate the spindle/kinetochore checkpoint. Genes Dev 13(5):517-22
45) Hisamoto N, et al.  (1994) The Glc7 type 1 protein phosphatase of Saccharomyces cerevisiae is required for cell cycle progression in G2/M. Mol Cell Biol 14(5):3158-65
46) Black S, et al.  (1995) A regulated MET3-GLC7 gene fusion provides evidence of a mitotic role for Saccharomyces cerevisiae protein phosphatase 1. Yeast 11(8):747-59