MET4 / YNL103W Overview


Standard Name
MET4 1
Systematic Name
YNL103W
SGD ID
SGD:S000005047
Feature Type
ORF , Verified
Description
Leucine-zipper transcriptional activator; regulates the sulfur amino acid pathway; requires different combinations of auxiliary factors Cbf1p, Met28p, Met31p and Met32p; specific involvement in sulfur starvation-induced autophagy with Gcn4p; feedforward loop exists in the regulation of genes controlled by Met4p and Met32p; ubiquitinated by SCF-Met30p, leading to either degradation or maintenance in an inactive state; regulates degradation of its DNA-binding cofactors by SCF-Met30p targeting 2 3 4
Name Description
METhionine requiring 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Length (a.a.)
672
Mol. Weight (Da)
74275.2
Isoelectric Point
5.54
Median Abundance (molecules/cell)
1907 +/- 1021
Half-life (hr)
3.0

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all MET4 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Transcription coactivator and subunit of the Cbf1-Met4-Met28 complex, which activates the transcription of genes involved in sulfur amino acid metabolism; involved in the response to arsenic and cadmium

View computational annotations

Molecular Function

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


133 total interactions for 81 unique genes

Physical Interactions

  • Affinity Capture-MS: 41
  • Affinity Capture-RNA: 7
  • Affinity Capture-Western: 9
  • Biochemical Activity: 1
  • Co-localization: 2
  • FRET: 3
  • PCA: 1
  • Protein-peptide: 1
  • Reconstituted Complex: 6
  • Two-hybrid: 21

Genetic Interactions

  • Dosage Growth Defect: 3
  • Dosage Lethality: 7
  • Dosage Rescue: 2
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 4
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 5
  • Synthetic Rescue: 13
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Summary
MET4 encodes a zipper-type transcriptional coactivator of the Leucine Zipper family, but does not itself have DNA-binding activity. The expression of the majority of genes encoding enzymes involved in sulfur metabolism requires Met4p. Because Met4p lacks DNA-binding activity, it instead relies on either of two dedicated DNA-binding adaptors, Met31p and Met32p, for recruitment to promoters. Met4p can also function with DNA-binding factor Cbf1p, which also recruits Met4p, to promote transcription. Met28p, which also lack DNA-binding activity, stabilizes DNA-bound Cbf1p-Met4p complexes. A subset of the Met4 regulon is strictly dependent on Cbf1p and Met28p in low-sulfur conditions. Cbf1p binds as a homodimer to an E-box site, and recruitment of Met4p also requires a Met4 recruitment motif (RYAAT) upstream and separated from the E-box sequence by a 2-bp spacer. Binding to the composite DNA binding site occurs only with the full trimeric Met4p-Met28p-Cbf1p complex. The activity of Met4p is controlled based on sulfur status of the cell. Limiting intracellular methionine levels or heavy metal stress trigger Met4 activation and subsequent MET gene expression. The intracellular level of cysteine provides the major regulatory signals for MET gene expression. Under repressing conditions when cysteine is abundant, the activation potential of Met4p is negatively regulated by SCF-Met30 ubiquitin ligase, though ubiquitylation of Met4p by SCF-Met30 does not induce its immediate degradation. Met4 appears to control its own levels and activity through a feedback-like mechanism that regulates the amount of assembled SCF-Met30. Met4p also functions as a substrate recruitment factor for SCF-Met30.
Regulators
12
Targets
333
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2011-02-07

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
62
Additional
102
Reviews
21

Resources