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IZH2/YOL002C Single Page Format

This page provides an alternative format to the SGD Locus Summary Page. Note that additional information may be available on or linked from the standard format SGD Locus Summary page.

Contents

Names and Identifiers GO Annotations Pathways Summary Paragraph Mutant Phenotypes Interactions Homologs Protein Info (physical properties, transcript info) PDB Homologs (protein structure info) Motifs Genome-wide Expression (and other large-scale analyses) Locus History (misc. notes) Sequence Retrieval and Analysis Map and Displays Localization Community Annotation Literature Guide

Sequence Coordinates   ChrXV: 324365 to 323412 CDS: 324365 - 323412 Click on map for expanded view SGD ORF map GBrowse

SGD Locus Page

Names and Identifiers [TOP] [NEXT]
Standard Name	Systematic Name	Alias	Feature Type	SGDID
IZH2	YOL002C	PHO36	ORF, Verified	S000005362
Description
Plasma membrane protein involved in zinc homeostasis and osmotin-induced apoptosis; transcription regulated by Zap1p, zinc and fatty acid levels; similar to mammalian adiponectins; deletion increases sensitivity to elevated zinc

GO Annotations [TOP] [NEXT]
Molecular Function Annotation(s) Reference(s) Evidence Assigned By metal ion binding Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11        ISS : Inferred from Sequence or structural Similarity Assigned on 2004-05-27 SGD protein binding 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          IPI : Inferred from Physical Interaction with GenBank/EMBL/DDBJ:CAA46622 Assigned on 2007-01-04 SGD receptor activity GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.      IEA : Inferred from Electronic Annotation with EBI:KW-0675 Assigned on 2007-05-23 UniProtKB
Biological Process Annotation(s) Reference(s) Evidence Assigned By cellular lipid metabolic process Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11        TAS : Traceable Author Statement Assigned on 2004-05-27 SGD cellular zinc ion homeostasis Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11        ISS : Inferred from Sequence or structural Similarity IMP : Inferred from Mutant Phenotype Assigned on 2004-05-27 SGD fatty acid metabolic process GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.      IEA : Inferred from Electronic Annotation with EBI:KW-0276 Assigned on 2007-05-23 UniProtKB lipid metabolic process GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.      IEA : Inferred from Electronic Annotation with EBI:KW-0443 Assigned on 2009-10-01 UniProtKB response to toxin 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          IMP : Inferred from Mutant Phenotype Assigned on 2007-01-04 SGD response to zinc ion Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11        ISS : Inferred from Sequence or structural Similarity Assigned on 2004-05-27 SGD translational elongation Huttenhower C and Troyanskaya OG (2009) Prediction of Gene Ontology annotations by integrating high-throughput datasets    RCA : Reviewed Computational Analysis Assigned on 2009-08-06 bioPIXIE_MEFIT
Cellular Component Annotation(s) Reference(s) Evidence Assigned By integral to membrane Karpichev IV and Small GM (1998) Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Mol Cell Biol 18(11):6560-70        ISS : Inferred from Sequence or structural Similarity Assigned on 2004-01-22 SGD DDB, et al. (2001) Gene Ontology annotation through association of InterPro records with GO terms.      IEA : Inferred from Electronic Annotation with EBI:IPR004254 Assigned on 2007-05-23 UniProtKB GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.      IEA : Inferred from Electronic Annotation with EBI:KW-0812 Assigned on 2007-05-23 UniProtKB GOA curators and UniProt curators (2007) Gene Ontology annotation based on Swiss-Prot Subcellular Location vocabulary mapping.      IEA : Inferred from Electronic Annotation with EBI:SL-9909 Assigned on 2009-10-01 UniProtKB membrane Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11        ISS : Inferred from Sequence or structural Similarity Assigned on 2004-05-27 SGD GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.      IEA : Inferred from Electronic Annotation with EBI:KW-0472 Assigned on 2009-06-29 UniProtKB plasma membrane 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          IDA : Inferred from Direct Assay Assigned on 2007-01-04 SGD

Pathways [TOP] [NEXT]
No pathways available

Summary Paragraph [TOP] [NEXT]

SUMMARY PARAGRAPH for IZH2/YOL002C for IZH2 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 (2). Izh2p mediates the effects of the tobacco antifungal protein osmotin, which induces yeast to undergo apoptosis. Izh2p binds osmotin at the plasma membrane, and overexpression or deletion of IZH2 causes increased or decreased osmotin sensitivity, respectively (2). Genetic interactions with RAS2 suggest that IZH2 and RAS2 act in the same pathway for osmotin-induced apoptosis (2). 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 (3). 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

Basic References [TOP]

BASIC INFORMATION REFERENCES forIZH2/YOL002C for IZH2 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) 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          3) 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

Mutant Phenotypes [TOP] [NEXT]
Phenotype page for IZH2/YOL002C

Interactions: genetic, physical, and other gene-gene links. [TOP] [NEXT]
Interaction page for IZH2/YOL002C

Homologs [TOP] [NEXT]
Comparison Resources PSI-BLAST Results Ashbya Homologs (AGD) BLASTN vs. fungi BLASTP at NCBI BLASTP vs. fungi Candida Homologs (CGD) Candida Homologs (CandidaDB) Fungal Alignment Fungal Orthogroups Repository Ortholog Search (P-POD) PhylomeDB Synteny Viewer Yeast Gene Order Browser (YGOB) eukarYotic OrtholoGY (YOGY)

Physical Properties and Transcript Information: predicted from sequence [TOP] [NEXT]
Protein Sequence Calculations from Predicted Full length Translation N-term MSTLLER C-term MENGIVS Length(aa) 317 MW(Da) 36,278 pI 9.07 Amino Acid Composition (full length) GCG tools: PepPlot, Helical Wheel, PepStruct Transcript Translation Calculations Codon Bias 0.022   Codon Adaptation Index 0.125   Frequency of Optimal Codons 0.416   Hydropathicity of Protein 0.435   Aromaticity Score 0.148	10 20 30 40 50 | | | | | MSTLLERTKSVQELKKRAAGKTSANPAEVAKAKKVLRRLYSWDEIPEWQR DNDFILHGYVKETSSFIETFKSLFYLHNESVNIYSHLIPALGFFTVLLLD KSTIKVFATTTWLDHMVIDLFYSGAFACLILSSSFHCLKSHSLRIATLGN KLDYLGICILIVTSMVSILYYGYFEKFSLFCLFALITVSFGIACSIVSLK DKFRKREWRPYRAGLFVCFGLSSIIPIFSGLYCYSFSEIWTQIQLFWVLL GGVLYIIGAVLYGMRFPEKICPGKFDIWGHSHQLFHFLVVIAALCHLRGL LNSYELVHIKMENGIVS*

Protein Structures from PDB: proteins of known structure with sequence similarity to IZH2/YOL002C, based on Smith-Waterman analysis. [TOP] [NEXT]
No protein structure information available.

Genome-wide Expression and Other Large-Scale Analyses [TOP] [NEXT]
Functional Analysis Expression Connection Summary Cell cycle and metabolic oscillation Cell cycle transcript profile Cyclebase Genevestigator GermOnline SPELL Microarray Search YGAC Triples Yeast Microarray Global Viewer YeastFunc	You can also search multiple datasets simultaneously using Expression Connection for expression studies or Function Junction for other large scale analyses.

Locus History (misc. notes) [TOP] [NEXT]

Nomenclature History

Standard Name	Reference
IZH2	Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11

Nomenclature History Notes

Date	Note
2004-01-22	January 22, 2004 PHO36 gene name was reserved for YOL002C for a brief period, but never published. This name was moved to be an alias name following the author's request.

Sequence Annotation Notes

Date	Note
2008-11-04	Data from Nagalakshmi et al. 2008 suggest that there is an in-frame AUG 10 codons upstream of the currently annotated AUG for either all or some of the transcripts of IZH2/YOL002C. The upstream AUG represents the previously annotated start for this ORF; the annotation of which was changed based on experimental work done by Karpichev I.V. et al. (2003). 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        Nagalakshmi U, et al. (2008) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320(5881):1344-9
2003-01-09	The start site of YOL002C has been moved 30 nt downstream from 324394 to 324364. Chromosomal coordinates change from old:324394-323441 to new:324364-323411. Relative coordinates go from old:1-984 to new:1-954. Thanks to Gillian Small for reporting this sequence annotation change to SGD. 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

Sequence Retrieval [TOP] [NEXT]
Sequence Type	Output Format
Genomic DNA	GCG | FASTA | NoHeader
Genomic DNA with 1 kb up and downstream	GCG | FASTA | NoHeader
DNA coding sequence (without introns, without flanking regions)	GCG | FASTA | NoHeader
Protein Translation of ORF	GCG | FASTA | NoHeader
6-Frame Translation(with Restriction Map)	GCG
Restriction Fragment Sizes	GCG
Sequence Analysis Tools BLASTP BLASTN Design Primers FASTA aa FASTA nt Restriction Fragment Map Restriction Fragment Sizes Six-Frame Translation

Sequence from other databases
Sequence ID	Source
YOL002C	SGD Systematic Sequence
854160	NCBI: Gene ID
NP_014641.2	NCBI: RefSeq protein version ID
NP_014641.2	NCBI: RefSeq protein version ID
27808716	NCBI: NCBI protein GI

Map and Displays [TOP] [NEXT]
Physical, Genetic Maps:	Chromosomal Feature Map	GBrowse	Combined Physical and Genetic Map	Genetic Distance vs. Physical Distance Ratios
Similarity Viewers:	Synteny Viewer	Genomic Stripe View	SAGE Results Map

Localization [TOP] [NEXT]
Localization Resources YGAC Triples YeastGFP DB (UCSF) at SGD

Community Annotation [TOP] [NEXT]
No community annotation available.

Literature Guide: papers categorized by topic. [TOP]
Topics	Reference	Other Genes Addressed
18 curated references; 0 references not yet curated
Mutants/Phenotypes Protein Sequence Features Regulatory Role Strains/Constructs Substrates/Ligands/Cofactors	Villa NY, et al. (2009) Sphingolipids function as downstream effectors of a fungal PAQR. Mol Pharmacol 75(4):866-75	|FET3 |NRG1 |NRG2 |PKH1 |PKH2 |TPK2 |YDC1 |YPC1
Regulation of Transcription	Cheraiti N, et al. (2008) Acetaldehyde addition throughout the growth phase alleviates the phenotypic effect of zinc deficiency in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 77(5):1093-1109	|AAD14 |AAD15 |AAD16 |AAD3 |AAD4 |AAH1 |ACH1 |ADH1 |ADH4 |ALD3 |ALO1 |ARG3 |ARO1 |ASC1 |MORE
DNA/RNA Sequence Features Regulation of Transcription	Karpichev IV, et al. (2008) Binding characteristics and regulatory mechanisms of the transcription factors controlling oleate-responsive genes in Saccharomyces cerevisiae. J Biol Chem 283(16):10264-75	|ADR1 |CRC1 |CTA1 |DUS3 |ECI1 |IZH1 |IZH4 |OAF1 |PEX11 |PEX5 |PIP2 |POT1 |POX1 |QDR1 |MORE
Function/Process Infection and Antifungals Mutants/Phenotypes Regulatory Role Strains/Constructs	Kupchak BR, et al. (2008) Dissecting the regulation of yeast genes by the osmotin receptor. Biochem Biophys Res Commun 374(2):210-3	|FET3 |FET4 |MSN2 |MSN4 |MUC1 |NRG1 |NRG2 |OLE1 |ZPS1 |ZRC1 |ZRT1
DNA/RNA Sequence Features Regulation of Transcription	Wu CY, et al. (2008) Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae. BMC Genomics 9:370	|ADE17 |ADH4 |ALD2 |ALD3 |ATG19 |BAG7 |COS1 |COS6 |CTT1 |DPP1 |ENO1 |ENO2 |FET4 |FMP43 |MORE
Genetic Interactions Mutants/Phenotypes Strains/Constructs	Alvaro D, et al. (2007) Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination. PLoS Genet 3(12):e228	|AHC1 |ATR1 |BCK1 |BDF1 |BDF2 |BUB2 |BUD27 |CBT1 |COX16 |CTF19 |CTF4 |DAK2 |DDC1 |DDR2 |MORE
Regulation of Transcription	De Nicola R, et al. (2007) Physiological and Transcriptional Responses of Saccharomyces cerevisiae to Zinc Limitation in Chemostat Cultures. Appl Environ Microbiol 73(23):7680-92	|ADE17 |ADH4 |ATP14 |ATP15 |ATP18 |ATP20 |ATP3 |ATP4 |COM2 |COX14 |COX23 |DPP1 |FET4 |GAC1 |MORE
Function/Process Mutants/Phenotypes Regulatory Role Strains/Constructs	Kupchak BR, et al. (2007) Probing the mechanism of FET3 repression by Izh2p overexpression. Biochim Biophys Acta 1773(7):1124-32	|FET3 |GAL83 |MSN2 |MSN4 |NRG1 |NRG2 |RAS2 |SAK1 |SIP1 |SIP3 |SNF1 |SNF4 |TPK1 |TPK2 |MORE
Mutants/Phenotypes Strains/Constructs	Morton CO, et al. (2007) An amphibian-derived, cationic, alpha-helical antimicrobial peptide kills yeast by caspase-independent but AIF-dependent programmed cell death. Mol Microbiol 65(2):494-507	|AIF1 |AMD1 |ATS1 |CSI1 |FMS1 |GAL2 |HST3 |IZH3 |MCA1 |MPA43 |PIP2 |PTP3 |SPO13 |SRC1 |MORE
RNA Levels and Processing Regulation of	Tanaka F, et al. (2006) Functional genomic analysis of commercial baker's yeast during initial stages of model dough-fermentation. Food Microbiol 23(8):717-28	|ACE2 |ACO1 |ACS1 |ACS2 |ACT1 |ADH1 |ADH2 |ADH5 |ADK1 |AIM38 |ALD2 |ALG8 |ARG1 |ARG3 |MORE
Cellular Location Function/Process Fungal Related Genes/Proteins Genetic Interactions Mutants/Phenotypes Non-Fungal Related Genes/Proteins Protein-protein Interactions Strains/Constructs	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	|IZH1 |RAS2 |STE12 |STE18 |STE20 |STE7
Cellular Location DNA/RNA Sequence Features Function/Process Fungal Related Genes/Proteins Mutants/Phenotypes Non-Fungal Related Genes/Proteins Regulation of Strains/Constructs Transcription	Lyons TJ, et al. (2004) Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 101(15):5506-11	|AFT1 |IZH1 |IZH3 |IZH4 |MGA2 |ZAP1
Reviews	Rutherford JC and Bird AJ (2004) Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot Cell 3(1):1-13	|ADE17 |ADH4 |AFT1 |AFT2 |AKR1 |ARN1 |ARN2 |ATX1 |BAG7 |BNA2 |CCC2 |COS1 |COS2 |COS3 |MORE
Non-Fungal Related Genes/Proteins	Yamauchi T, et al. (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423(6941):762-9
Function/Process Mutants/Phenotypes Non-Fungal Related Genes/Proteins RNA Levels and Processing Strains/Constructs	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
DNA/RNA Sequence Features RNA Levels and Processing Regulation of Strains/Constructs Transcription	Lyons TJ, et al. (2000) Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci U S A 97(14):7957-62	|ADE17 |ADH4 |BAG7 |COS1 |COS2 |COS3 |COS4 |COS6 |COS8 |DPP1 |FET4 |GPG1 |GRE2 |ICY2 |MORE
DNA/RNA Sequence Features RNA Levels and Processing	Karpichev IV and Small GM (1998) Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Mol Cell Biol 18(11):6560-70	|ATF1 |CAT2 |CIN1 |CIT1 |CIT2 |CRC1 |CTA1 |CUP2 |DCI1 |DUS3 |ECI1 |EEB1 |FAA2 |FOX2 |MORE
Alias DNA/RNA Sequence Features	Sterky F, et al. (1996) The sequence of a 30 kb fragment on the left arm of chromosome XV from Saccharomyces cerevisiae reveals 15 open reading frames, five of which correspond to previously identified genes. Yeast 12(10B Suppl):1091-5	|ALG6 |PFA4 |PHO80 |RRP6 |SGT2 |SLG1 |TIR2 |TIR4 |TSR3 |UTP23 |YSP3

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