PHO85/YPL031C Summary Help

Standard Name PHO85
Systematic Name YPL031C
Alias LDB15 1
Feature Type ORF, Verified
Description Cyclin-dependent kinase; has ten cyclin partners; involved in regulating the cellular response to nutrient levels and environmental conditions and progression through the cell cycle (2 and see Summary Paragraph)
Also known as: phoU 3
Name Description PHOsphate metabolism
Chromosomal Location
ChrXVI:493037 to 492018 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -34 cM
Gene Ontology Annotations All PHO85 GO evidence and references
  View Computational GO annotations for PHO85
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
Regulators 3 genes
Resources
Classical genetics
conditional
null
reduction of function
Large-scale survey
null
Resources
854 total interaction(s) for 590 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 45
  • Affinity Capture-Western: 11
  • Biochemical Activity: 453
  • Co-crystal Structure: 1
  • PCA: 2
  • Reconstituted Complex: 20
  • Two-hybrid: 46

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 64
  • Dosage Rescue: 3
  • Negative Genetic: 4
  • Phenotypic Enhancement: 10
  • Phenotypic Suppression: 8
  • Positive Genetic: 1
  • Synthetic Growth Defect: 34
  • Synthetic Lethality: 143
  • Synthetic Rescue: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 305
Molecular Weight (Da) 34,906
Isoelectric Point (pI) 8.37
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXVI:493037 to 492018 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: -34 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..17 493037..493021 2011-02-03 1996-07-31
Intron 18..119 493020..492919 2011-02-03 1996-07-31
CDS 120..1020 492918..492018 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 SGDIDS000005952
SUMMARY PARAGRAPH for PHO85

Pho85p is a cyclin-dependent kinase (CDK) with diverse roles in the regulation of cellular responses to nutrient levels and progression through the cell cycle, which are reflected by its interactions with ten different cyclins subunits (2). The cyclins that interact with Pho85p can be divided into two families based on sequence similarity (4). The Pho80p subfamily, comprised of Pho80p, Pcl6p, Pcl7p, Pcl8p, and Pcl10p, primarily regulate the response to nutrient levels and environmental conditions (4, 2). The Pcl1,2 subfamily, comprised of Pcl1p, Pcl2p, Pcl9p, Clg1p, and Pcl5p, is involved in regulating transcription during the cell cycle and progression through the cell cycle, with the exception of Pcl5p, which regulates the response to amino acid starvation (4, 5, 2).

Pho85p phosphorylates numerous proteins resulting in diverse regulatory consequences, including changes in the localization, stability, and/or enzymatic activity of its targets (6, 7). For example, under high phosphate conditions, phosphorylation of the transcription factor Pho4p by the Pho80p-Pho85p complex results in the nuclear export of Pho4p, thereby preventing the transcription of genes involved in the response to phosphate starvation (8). The phosphorylation of the cell cycle inhibitor Sic1p by Pcl1p-Pho85p contributes to its degradation, allowing exit from G1 (9, 10). Pcl10p-Pho85p phosphorylates the glycogen synthase Gsy2p to inhibit glycogen biosynthesis (11). In general, the substrate specificity of Pho85p can be determined by its cyclin partner; with Pcl10p and Pho80p, for example, targeting the phosphorylation of Gsy2p and Pho4p, respectively (12, 13).

Many substrates of Pho85p are also substrates of the CDK Cdc28p, which has more than 50% sequence identity with Pho85p (14, 15, 2, and references therein). Like CLN1 and CLN2, the cyclins associated with Cdc28p, the transcription of PCL1, PCL2, and PCL9 are cell cycle regulated with peak expression in the G1 phase (4). In addition, the synthetic lethality of a pcl1 pcl2 cln1 cln2 quadruple mutant suggests at least one overlapping essential function for these G1 cyclins, via their associated CDKs (16). The functional overlap between Pho85p and Cdc28p has led to the suggestions Pho85p may regulate the resumption of growth after cell cycle arrest (10, 2).

Pho85p is regulated under conditions of low phosphate where the small molecule inositol heptakisphosphate (IP7) and the CDK inhibitor Pho81p contribute to the inhibition of the Pho85p-Pho80p CDK-cyclin complex (17, 18). Pho85p is related to the mammalian cyclin-dependent kinase, CDK5, which is involved in development of the central nervous system and neurite outgrowth (19, 20). Overexpression of this mammalian CDK can complement yeast cells containing a pho85 null mutation (19, 20).

Last updated: 2008-02-29 Contact SGD

References cited on this page View Complete Literature Guide for PHO85
1) Corbacho I, et al.  (2004) Identification of low-dye-binding (ldb) mutants of Saccharomyces cerevisiae. FEMS Yeast Res 4(4-5):437-44
2) Huang D, et al.  (2007) Pho85, a multifunctional cyclin-dependent protein kinase in budding yeast. Mol Microbiol 66(2):303-14
3) Ueda Y, et al.  (1975) Isolation and characterization of recessive, constitutive mutations for repressible acid phosphatase synthesis in Saccharomyces cerevisiae. J Bacteriol 122(3):911-22
4) Measday V, et al.  (1997) A family of cyclin-like proteins that interact with the Pho85 cyclin-dependent kinase. Mol Cell Biol 17(3):1212-23
5) Shemer R, et al.  (2002) Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5. Mol Cell Biol 22(15):5395-404
6) Carroll AS and O'Shea EK  (2002) Pho85 and signaling environmental conditions. Trends Biochem Sci 27(2):87-93
7) Irniger S and Braus GH  (2003) Controlling transcription by destruction: the regulation of yeast Gcn4p stability. Curr Genet 44(1):8-18
8) O'Neill EM, et al.  (1996) Regulation of PHO4 nuclear localization by the PHO80-PHO85 cyclin-CDK complex. Science 271(5246):209-12
9) Nishizawa M, et al.  (1998) Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation. Mol Biol Cell 9(9):2393-405
10) Wysocki R, et al.  (2006) CDK Pho85 targets CDK inhibitor Sic1 to relieve yeast G1 checkpoint arrest after DNA damage. Nat Struct Mol Biol 13(10):908-14
11) Wilson WA, et al.  (1999) Substrate targeting of the yeast cyclin-dependent kinase Pho85p by the cyclin Pcl10p. Mol Cell Biol 19(10):7020-30
12) Dephoure N, et al.  (2005) Combining chemical genetics and proteomics to identify protein kinase substrates. Proc Natl Acad Sci U S A 102(50):17940-5
13) Huang D, et al.  (1998) Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10. Mol Cell Biol 18(6):3289-99
14) Toh-e A, et al.  (1988) PHO85, a negative regulator of the PHO system, is a homolog of the protein kinase gene, CDC28, of Saccharomyces cerevisiae. Mol Gen Genet 214(1):162-4
15) Kung C, et al.  (2005) Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor. Proc Natl Acad Sci U S A 102(10):3587-92
16) Moffat J and Andrews B  (2004) Late-G1 cyclin-CDK activity is essential for control of cell morphogenesis in budding yeast. Nat Cell Biol 6(1):59-66
17) Lee YS, et al.  (2007) Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science 316(5821):109-12
18) Lee YS, et al.  (2008) Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate. Nat Chem Biol 4(1):25-32
19) Nishizawa M, et al.  (1999) Mouse cyclin-dependent kinase (Cdk) 5 is a functional homologue of a yeast Cdk, pho85 kinase. J Biol Chem 274(48):33859-62
20) Huang D, et al.  (1999) Mammalian Cdk5 is a functional homologue of the budding yeast Pho85 cyclin-dependent protein kinase. Proc Natl Acad Sci U S A 96(25):14445-50