PHO4/YFR034C Summary Help

Standard Name PHO4
Systematic Name YFR034C
Feature Type ORF, Verified
Description Basic helix-loop-helix (bHLH) transcription factor of the myc-family; activates transcription cooperatively with Pho2p in response to phosphate limitation; binding to 'CACGTG' motif is regulated by chromatin restriction, competitive binding of Cbf1p to the same DNA binding motif and cooperation with Pho2p,; function is regulated by phosphorylation at multiple sites and by phosphate availability (1, 2, 3, 4 and see Summary Paragraph)
Also known as: phoD 5
Name Description PHOsphate metabolism
Chromosomal Location
ChrVI:225958 to 225020 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 47 cM
Gene Ontology Annotations All PHO4 GO evidence and references
  View Computational GO annotations for PHO4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 46 genes
Regulators 9 genes
Classical genetics
reduction of function
Large-scale survey
260 total interaction(s) for 191 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 126
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 13
  • Biochemical Activity: 23
  • Co-crystal Structure: 2
  • Co-localization: 1
  • PCA: 2
  • Protein-peptide: 1
  • Protein-RNA: 1
  • Reconstituted Complex: 20
  • Two-hybrid: 11

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 2
  • Negative Genetic: 16
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 13
  • Positive Genetic: 8
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 1
  • Synthetic Rescue: 5

Expression Summary
Length (a.a.) 312
Molecular Weight (Da) 34,089
Isoelectric Point (pI) 7.91
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVI:225958 to 225020 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 47 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..939 225958..225020 2011-02-03 1996-07-31
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 SGDIDS000001930

PHO4 was the first S. cerevisiae gene shown to encode a basic helix-loop-helix (bHLH) protein transcription factor (2). Pho4p binds to DNA sequences containing the core bHLH binding site, 5'-CACGTG-3'as a homodimer (6). This sequence is found in the promoters of a variety of genes positively regulated in response to phosphate availability like the PHO5 gene (3). Multiple phosphorylation sites on Pho4p play distinct roles in regulating its subcellular localization and its DNA binding function (1). The Pho80p-Pho85p kinase complex phosphorylates Pho4p on five Ser-Pro (SP) dipeptides referred to as SP1, SP2, SP3, SP4 and SP6 (1). Sites SP2 and SP3 regulate the nuclear export of Pho4p, site SP4 regulates the import of Pho4p and site SP6 regulates its interaction with Pho2p, which is required for expression of the acid phosphatase PHO5. The exact role of SP1 is still unknown (1). When phosphate is abundant, Pho4p is phosphorylated by the Pho80p-Pho85p complex and exported to the cytoplasm by the receptor Msn5p (7) where it is unable to activate transcription of phosphate-responsive genes such PHO5 (1). When phosphate is limiting, the cyclin-dependent kinase (CDK) inhibitor Pho81p inactivates the Pho80p-Pho85p complex, leading to accumulation of unphosphorylated Pho4p in the nucleus and subsequent activation of phosphate-responsive genes (8).

Last updated: 2003-03-14 Contact SGD

References cited on this page View Complete Literature Guide for PHO4
1) Komeili A and O'Shea EK  (1999) Roles of phosphorylation sites in regulating activity of the transcription factor Pho4. Science 284(5416):977-80
2) Berben G, et al.  (1990) The yeast regulatory gene PHO4 encodes a helix-loop-helix motif. Yeast 6(5):451-4
3) Ogawa N and Oshima Y  (1990) Functional domains of a positive regulatory protein, PHO4, for transcriptional control of the phosphatase regulon in Saccharomyces cerevisiae. Mol Cell Biol 10(5):2224-36
4) Zhou X and O'Shea EK  (2011) Integrated Approaches Reveal Determinants of Genome-wide Binding and Function of the Transcription Factor Pho4. Mol Cell 42(6):826-36
5) To-E A, et al.  (1973) Isolation and characterization of acid phosphatase mutants in Saccharomyces cerevisiae. J Bacteriol 113(2):727-38
6) Shao D, et al.  (1998) A cysteine residue in helixII of the bHLH domain is essential for homodimerization of the yeast transcription factor Pho4p. Nucleic Acids Res 26(3):710-4
7) Kaffman A, et al.  (1998) The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus. Nature 396(6710):482-6
8) Kaffman A, et al.  (1994) Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85. Science 263(5150):1153-6
9) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
10) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87
11) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66
12) Matys V, et al.  (2003) TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31(1):374-8