IZH4/YOL101C Summary Help

Standard Name IZH4 1
Systematic Name YOL101C
Feature Type ORF, Verified
Description Membrane protein involved in zinc ion homeostasis; member of the four-protein IZH family; expression induced by fatty acids and altered zinc levels; deletion reduces sensitivity to excess zinc; possible role in sterol metabolism; protein increases in abundance and relocalizes from nucleus to ER upon DNA replication stress; IZH4 has a paralog, IZH1, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description Implicated in Zinc Homeostasis 1
Chromosomal Location
ChrXV:127920 to 126982 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All IZH4 GO evidence and references
  View Computational GO annotations for IZH4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Regulators 13 genes
Classical genetics
Large-scale survey
29 total interaction(s) for 17 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 2
  • Two-hybrid: 2

Genetic Interactions
  • Negative Genetic: 20
  • Positive Genetic: 3

Expression Summary
Length (a.a.) 312
Molecular Weight (Da) 36,607
Isoelectric Point (pI) 8.09
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXV:127920 to 126982 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2006-01-05 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..939 127920..126982 2006-01-05 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 SGDIDS000005461

IZH1, IZH2, IZH3, and IZH4 encode a family of paralogous membrane proteins thought to affect zinc homeostasis either by altering membrane sterol content or by directly altering cellular zinc levels. The Izh proteins belong to a large and nearly ubiquitous family of proteins found in both prokaryotes and eukaryotes. This family is characterized by the presence of at least seven transmembrane domains and four highly conserved motifs rich in metal-binding amino acids. All of the conserved motifs are predicted to cluster on the cytoplasmic face of the membrane (1). Izh2p is located in the plasma membrane (4).

All four IZH genes exhibit elevated expression in zinc-deficient cells. IZH1 and IZH2 are direct targets of the Zap1p transcription factor that senses zinc deficiency, whereas IZH4 is induced by excess zinc. IZH1 and IZH2 possess putative zinc responsive elements (ZREs) in their promoter regions, located at -416 (ACCTTTAGGGT) and -225 (TCCTCTAGGGT), respectively (1). IZH1, IZH2, and IZH4 are also induced by fatty acids via the Oaf1p/Pip2p complex that binds to oleate response elements (OREs). Putative OREs are present in the IZH1 (-302 to -328 bp), IZH2 (-159 to -167 bp), and IZH4 (-240 to -263 bp) promoters (5). The induction of IZH1 and IZH2 by Zap1p under zinc deficiency, as well as the specific decrease in Zap1p activity in cells overexpressing Izh proteins, suggests a connection between these genes, sterols, and zinc metabolism (1).

No single IZH gene or combination of genes is essential for viability. Deletion of either IZH1 or IZH2 results in increased sensitivity to elevated zinc, whereas deletion of IZH3 or IZH4 results in reduced sensitivity. The izh2 mutation increases the length of the cell cycle in zinc-treated cells, whereas izh3 mutation decreases the lag phase under the same conditions. Overexpression of any of these four genes results in decreased activity of the Zap1p transcription factor when cells are grown in zinc-limiting medium (1).

Three possible functions have been proposed for the Izh proteins. First, these proteins may function solely in sterol metabolism by influencing the permeability of the plasma membrane and, consequently, the homeostasis of cations such as zinc. It is also possible that the Izh proteins function as transporters for zinc used in a signaling capacity, a possibility that may explain their regulation by Zap1p and their effect on Zap1p activity. A third possibility is that the Izh proteins are involved in a signal transduction cascade that is independent of zinc, and that Zap1p is a downstream target of this pathway (1).

Last updated: 2007-01-04 Contact SGD

References cited on this page View Complete Literature Guide for IZH4
1) Lyons TJ, et al.  (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11
2) 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
3) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
4) Narasimhan ML, et al.  (2005) Osmotin is a homolog of mammalian adiponectin and controls apoptosis in yeast through a homolog of mammalian adiponectin receptor. Mol Cell 17(2):171-80
5) Karpichev IV, et al.  (2002) Multiple regulatory roles of a novel Saccharomyces cerevisiae protein, encoded by YOL002c, in lipid and phosphate metabolism. J Biol Chem 277(22):19609-17