GAT2 (systematic name YMR136W) is a 560-residue Saccharomyces cerevisiae protein belonging to the GATA family of Cys4 (type-IV) zinc-finger transcription factors. It has a single, canonical C-terminal GATA-type zinc finger (residues 472-497) with the hallmark C-X2-C ... C-X2-C spacing, preceded by an extensive intrinsically disordered, low-complexity region that spans most of the protein. On domain grounds the zinc finger is expected to coordinate zinc and to bind GATA-type (5'-GATA-3'/5'-GAT-3') DNA sequence motifs, consistent with a role as a sequence-specific DNA-binding transcription factor acting in the nucleus. GAT2 is one of several yeast GATA-family proteins; the best-characterized members are the nitrogen-catabolite-repression regulators Gln3, Gat1 (activators), Dal80 and Gzf3 (repressors), together with the smaller Gat3 and Gat4. GAT2 itself is poorly characterized: its direct DNA targets, the physiological condition in which it operates, and its specific biological role have not been experimentally established. GAT2 transcription is condition-responsive (repressed by leucine), and large-scale deletion studies report mild, pleiotropic phenotypes including decreased invasive growth and abnormal bud and vacuolar morphology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that GAT2, as a GATA-family zinc-finger protein, binds cis-regulatory DNA regions. GAT2 does carry a complete GATA zinc finger, so binding a GATA-type cis-regulatory sequence is domain-plausible. Reason: The GATA zinc finger is present and canonical (confirmed at 472-497), and DNA binding via this finger is a well-established property of the family. Accepting the generic cis-regulatory-region-binding term is defensible on domain grounds. Note the IBA propagates from PTHR45658 (plant/Dictyostelium GATA cluster), not from the yeast NCR factors, so it supports a generic DNA-binding capacity rather than a specific target set. This term is retained alongside GO:0043565 (sequence-specific DNA binding): the two are complementary rather than redundant — GO:0043565 asserts the finger recognizes a specific sequence, while this term places that binding at a cis-regulatory (promoter/UAS) region. Supporting Evidence: file:yeast/GAT2/GAT2-bioinformatics/RESULTS.md GAT2 carries a bona fide GATA-type Cys4 zinc finger at residues 472 to 497 matching the UniProt ZN_FING GATA-type feature. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference of nuclear localization, expected for a DNA-binding transcription factor. There is no experimental localization for GAT2 (SGD lists cellular component as unknown), but a nuclear site of action is the parsimonious expectation for a GATA zinc-finger TF. Reason: Consistent with GAT2's DNA-binding zinc finger and TF classification. Retained as a reasonable, if inferred, location. The absence of a direct localization assay is recorded as a knowledge gap rather than a reason to reject the term. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference that GAT2 participates in regulation of RNA Pol II transcription, the generic process for GATA-family TFs. Reason: The generic process term is domain-appropriate for a GATA zinc-finger TF, but no GAT2-specific target gene or regulatory event has been demonstrated (all evidence is homology/phylogeny). Keeping it as a non-core, generic capability rather than a demonstrated core function is the honest interpretation for this dark gene. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic transfer of a generic transcription-regulation process from the GATA/zinc-finger domains (IPR000679, IPR013088). Reason: Domain-based and broadly correct, but it is the DNA-templated-transcription parent of the more specific RNA-Pol-II term already present via IBA. Redundant and generic; retained as non-core. Not a GAT2-specific demonstrated function. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic transfer of zinc ion binding from the GATA zinc-finger domain (IPR013088). Reason: GAT2 has a complete Cys4 GATA zinc finger whose four cysteines coordinate a structural zinc ion; zinc binding is a robust, well-supported domain-level property. Supporting Evidence: file:yeast/GAT2/GAT2-bioinformatics/RESULTS.md The four coordinating cysteines with C-X3-C ... C-X3-C spacing are the hallmark of the DNA-binding GATA finger. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic transfer of sequence-specific DNA binding from the GATA zinc-finger domain (IPR000679). Reason: Sequence-specific (GATA-motif) DNA binding is the defining activity of the GATA zinc finger, which GAT2 carries intact. Accepted on domain grounds; the specific target sequences bound by GAT2 in vivo remain undetermined (recorded as a knowledge gap). |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | ACCEPT | Summary: Reviewed-computational-analysis (RCA) inclusion of GAT2 in the yeast zinc proteome (Wang et al. 2018), based on combined domain and motif searches for zinc-binding proteins. Reason: Independent computational support for zinc binding, consistent with the GATA zinc-finger domain. Concordant with the IEA zinc-binding annotation. Not a direct GAT2 metal-binding measurement, but a reasonable inference. Supporting Evidence: PMID:30358795 yeast zinc proteome of 582 known or potential zinc-binding proteins was |
| GO:0005575 cellular_component | ND GO_REF:0000015 | REMOVE | Summary: Root cellular_component placeholder with ND (no data) evidence, reflecting that GAT2's subcellular localization has not been experimentally determined. Reason: An IBA nucleus annotation (GO:0005634) is already present and is the more informative, domain-consistent cellular-component call. The uninformative root placeholder is superseded and can be removed. (The genuine absence of an experimental localization is captured as a knowledge gap.) |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA PMID:10392447 Genome-wide transcriptional analysis in S. cerevisiae by min... | ACCEPT | Summary: SGD ISA (inferred from sequence alignment) annotation classifying GAT2 as an RNA Pol II DNA-binding transcription factor, anchored to PMID:10392447 with with_from pointing to other GATA-factor genes. Reason: The molecular activity — a GATA-type, RNA-Pol-II DNA-binding transcription factor — is well supported by the intact GATA zinc finger and the family classification. This is the most defensible molecular-function statement for GAT2. It rests on sequence similarity (ISA), not a direct GAT2 assay; the reference is a methods paper about the GATA network rather than a GAT2-specific functional study, which is why the target genes and regulatory role remain a knowledge gap. Supporting Evidence: file:yeast/GAT2/GAT2-bioinformatics/RESULTS.md GAT2 carries a bona fide GATA-type Cys4 zinc finger at residues 472 to 497 matching the UniProt ZN_FING GATA-type feature. |
| GO:0006357 regulation of transcription by RNA polymerase II | ISA PMID:10392447 Genome-wide transcriptional analysis in S. cerevisiae by min... | KEEP AS NON CORE | Summary: SGD ISA annotation that GAT2 is involved in regulation of RNA Pol II transcription, inferred by sequence alignment to other GATA factors (with_from lists several GATA-factor SGD ids). Reason: Domain- and family-appropriate as a generic capability, but the specific genes GAT2 regulates and the condition under which it does so are unknown. As with the IBA process term, this is retained as a non-core, inferred process rather than a demonstrated GAT2 function. |
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Download this section (compressed HTML)Q: Does Gat2 bind GATA DNA sites in vivo, and which genes does it directly regulate?
Q: Under what physiological condition (nitrogen source, stress, growth phase) is Gat2 functionally active, and is it an activator or a repressor?
Q: Is Gat2 redundant with or distinct from the canonical NCR GATA factors (Gln3/Gat1/Dal80/Gzf3), and does its divergent DNA-binding domain read a different sequence?
Experiment: ChIP-seq/ChIP-exo of epitope-tagged Gat2 across nitrogen sources, stress and growth phases to identify direct binding sites and target genes.
Experiment: RNA-seq of gat2-delta and GAT2-overexpression strains, alone and in combination with gln3/gat1/dal80/gzf3 mutants, to define Gat2's regulatory role and test redundancy with the NCR factors.
Experiment: Live-cell imaging of a functional Gat2-GFP fusion under varying nitrogen and TORC1 (rapamycin) conditions to determine localization and whether nuclear entry is conditionally regulated as for Gln3/Gat1.
Experiment: In vitro DNA-binding-specificity profiling (protein-binding microarray or SELEX) of the Gat2 zinc finger to compare its recognized sequence with those of the other yeast GATA factors.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The direct DNA target genes of Gat2, the specific GATA DNA sites it occupies in vivo, and the physiological condition under which it acts are undetermined. It is also unresolved whether Gat2 functions as a transcriptional activator or repressor.
OPEN BIOLOGY BP_DARK
What is known: Gat2 is a bona fide GATA-family protein with a complete, canonical Cys4 zinc finger (472-497) that supports zinc binding and sequence-specific (GATA-motif) DNA binding on domain grounds; it is classified as an RNA Pol II DNA-binding transcription factor. Its own transcription is condition-responsive (repressed by leucine; regulated by Sut2/Rgr1/Ume6/Fkh1). All molecular- and biological-process annotations are inferred from sequence similarity (ISA), domain (IEA), phylogeny (IBA) or computation (RCA); none derives from a direct Gat2 functional assay, and SGD lists no characterized target genes.
Significance: Gat2 is one of the few S. cerevisiae GATA factors with no assigned biological role, in a family (Gln3/Gat1/Dal80/Gzf3) that is central to nitrogen-responsive gene regulation. Defining Gat2's targets and condition would establish whether the yeast GATA network has an unrecognized fifth regulatory node or whether Gat2 acts in an unrelated process.
What would resolve it: ChIP-seq / ChIP-exo of tagged Gat2 across nitrogen sources and stress conditions to map direct sites and targets; RNA-seq of gat2-delta and GAT2-overexpression strains (singly and in combination with gln3/gat1/dal80/gzf3 mutants) to test activator vs repressor role and redundancy.
Provenance (the field's own admissions):
Gap: Whether Gat2 is functionally redundant with, antagonistic to, or independent of the canonical nitrogen-catabolite-repression GATA factors (Gln3, Gat1, Dal80, Gzf3) is unknown, and its DNA-binding specificity relative to theirs has not been measured.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: The four NCR GATA factors form a tightly related group both phylogenetically (PANTHER family PTHR10071) and by DNA-binding-domain identity (58-68% among themselves). Gat2 is the most divergent yeast GATA factor at the DBD level (37-52% to any single paralog) and is assigned to a separate PANTHER family (PTHR45658); SGD nonetheless notes it is "similar to Gln3p and Dal80p." No genetic-interaction or biochemical study has directly tested Gat2's relationship to the NCR quartet.
Significance: Resolving this would show whether Gat2 has been overlooked because it is redundant with the NCR factors (buffered, hence phenotype-poor) or because it operates in a distinct regulatory context, guiding where to look for its function.
What would resolve it: In vitro DNA-binding-specificity assays (e.g. protein-binding microarray / SELEX) to compare Gat2's site preference with the NCR factors; combinatorial deletion/epistasis analysis (gat2 in gln3/gat1/dal80/gzf3 backgrounds) under nitrogen limitation and other stresses.
Provenance (the field's own admissions):
Gap: Gat2's subcellular localization and its regulation (e.g. nuclear/cytoplasmic partitioning in response to nitrogen or TORC1 signaling, as seen for Gln3 and Gat1) have not been experimentally determined.
OPEN BIOLOGYCURATION CC_DARK
What is known: Nuclear action is inferred (IBA) from GAT2's DNA-binding TF classification, but SGD records cellular component as unknown and no GFP-localization compartment call is represented in GOA. The NCR activators Gln3 and Gat1 are known to shuttle between cytoplasm and nucleus under nitrogen/TORC1 control; whether Gat2 is similarly regulated is untested.
Significance: Localization and its conditional control are the entry point to Gat2's regulation: demonstrating regulated nuclear entry would connect Gat2 to a signaling pathway and a condition, both currently unknown.
What would resolve it: GFP/mNeonGreen tagging of Gat2 with live-cell imaging across nitrogen sources and rapamycin treatment; nuclear-fractionation immunoblots to test regulated nucleocytoplasmic partitioning.
Provenance (the field's own admissions):
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