statA

UniProt ID: O00910
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene Description

Dd-STATa (STATa/dstA) is the founding STAT-family signal-dependent transcription factor of Dictyostelium discoideum, and the clearest example of metazoan-like SH2-domain signaling in a non-metazoan. It has the canonical STAT domain architecture (a four-domain fold resembling mammalian STAT1/STAT3, an N-terminal coiled-coil, a DNA-binding domain, and a C-terminal SH2 domain) and is activated by tyrosine phosphorylation on Tyr702 in response to extracellular cAMP acting through the serpentine receptor cAR1; the receptor-like tyrosine kinase DrkA is implicated as a direct activating kinase. Upon phosphorylation it forms homodimers via reciprocal SH2-phosphotyrosine interactions and translocates from the cytoplasm into the nucleus, where it binds TTGA-containing sequence elements in target-gene promoters. Nuclear residence is dynamically controlled, since DIF (the prestalk inducer) promotes nuclear accumulation by inhibiting CRM1-dependent export, while GSK-3 (GskA) phosphorylation enhances nuclear export. Functionally, Dd-STATa acts chiefly as a transcriptional repressor of stalk-cell genes (notably ecmB) but also positively regulates a set of prestalk genes (e.g. cudA, mybC, aslA, ecmF), either directly or through downstream factors. Nuclear-enriched Dd-STATa marks the prestalk cells that form the slug tip organizer, and the protein is required for regulated commitment to stalk-cell differentiation, tip organizer function, and culmination into a mature fruiting body (sorocarp).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nuclear localization is a core, well-established property of Dd-STATa, which translocates into the nucleus upon cAMP-induced tyrosine phosphorylation and acts there as a transcription factor.
Reason: Phylogenetic inference of nuclear activity is strongly corroborated by direct experimental evidence for this gene product.
Supporting Evidence:
PMID:9670017
translocates into the nuclei of all cells
GO:0005737 cytoplasm
IBA
GO_REF:0000033
ACCEPT
Summary: Dd-STATa is cytoplasmic in growing cells and prior to activation, only translocating to the nucleus after tyrosine phosphorylation. Cytoplasmic localization is correct.
Reason: The cytoplasmic pool is where the latent, unphosphorylated STAT resides before signal-induced nuclear import, consistent with direct evidence.
Supporting Evidence:
PMID:9670017
Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated and is not selectively localized in the nucleus.
GO:0006357 regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033
ACCEPT
Summary: Dd-STATa is a sequence-specific transcription factor that regulates protein-coding (RNA polymerase II) gene expression, acting mainly as a repressor but also as an activator of specific prestalk genes.
Reason: The transcription-factor role is central to Dd-STATa function and is supported by extensive experimental evidence.
Supporting Evidence:
PMID:15053873
Dd-STATa is a STAT protein which transcriptionally regulates cellular
GO:0006952 defense response
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Retain defense response as a non-core ancestral STAT inference after the focused report found no target-specific loss.
Reason: PTHR11801 places GO:0006952 at PTN000927860. The report confirms the ancestral placement but objects that its experimental descendants are metazoan and that Dictyostelium STATa lacks a direct assay. Neither establishes loss along the STATa branch. GO:0006952 is not restricted to animal immunity; the separate TirA/sentinel-cell mechanism is not evidence that STATa cannot contribute to defense. Conversely, STATa differentiation and STATc osmotic stress are not positive defense evidence. Retain the IBA as a non-core inference, without claiming a tested STATa antibacterial or injury response.
Supporting Evidence:
file:interpro/panther/PTHR11801/PTHR11801-paint.tsv
PTHR11801 PTN000927860 GO:0006952 P IBD false FB:FBgn0016917|MGI:MGI:103038|MGI:MGI:103039|MGI:MGI:103063|RGD:3772|RGD:3774|UniProtKB:P42224|UniProtKB:P52630|WB:WBGene00010251|ZFIN:ZDB-GENE-030131-9359 taxon: 20260828
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IBA
GO_REF:0000033
ACCEPT
Summary: Dd-STATa binds sequence-specific TTGA cis-regulatory elements in the promoters of target genes (e.g. the ecmB repressor elements), consistent with sequence-specific binding to Pol II cis-regulatory regions.
Reason: Direct experimental evidence shows sequence-specific promoter-element binding, so this IBA annotation is well supported.
Supporting Evidence:
PMID:10393118
Dd-STATa binds these repressor elements
GO:0042127 regulation of cell population proliferation
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Retain regulation of cell population proliferation as a non-core inherited function, without conflating it with differentiation.
Reason: PTN000927860 has the proliferation-regulation IBD with experimentally characterized Dictyostelium STATb among its descendants. The focused report identifies STATb rather than STATa as the source of the measured growth phenotype, which is useful provenance but not evidence of STATa-specific loss. It explicitly acknowledges that STATa-null vegetative growth was not directly quantified in the retrieved literature. Developmental specialization does not exclude a second inherited role, and proliferation is not inferred from terminal differentiation. Retain the ancestral assertion as non-core pending any future target-specific assay.
Supporting Evidence:
file:DICDI/statA/statA-hypotheses/proliferation-and-defense-response/openscientist.md
**Vegetative growth rate of statA-null** β€” Not directly quantified in the retrieved literature.
PMID:14701681
Dd-STATb-null cells are gradually lost from the population when they are co-cultured with parental cells
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IBA
GO_REF:0000033
MODIFY
Summary: Dd-STATa functions in STAT-type signaling downstream of the serpentine cAMP receptor cAR1, but Dictyostelium has no JAK; the activating kinase is a receptor-like TKL (DrkA), not a Janus kinase. The more accurate, already-annotated term is cell surface receptor signaling pathway via STAT.
Reason: The JAK-STAT term is incorrect for this organism because no JAK exists in Dictyostelium. The pathway is a STAT signaling cascade triggered by a serpentine receptor, better captured by GO:0097696.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: LINEAGE OR TAXON MISMATCH
Sources checked:
PANTHER:PTN000927860 Β· PTN000927860 SUPPORTS SOURCE BUT NOT TARGET
The cached PTHR11801 PAINT table places the JAK-dependent pathway at this ancestor. The GO definition explicitly requires receptor-associated JAK activation, whereas Dictyostelium STAT activation uses non-JAK kinases. The mechanistic mismatch concerns this pathway term, not a general exclusion of amoebal STAT signaling.
Supporting Evidence:
PMID:9670017
The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IBA
GO_REF:0000033
ACCEPT
Summary: Dd-STATa is a bona fide sequence-specific DNA-binding transcription factor, structurally and functionally homologous to mammalian STAT1/STAT3. This is a core molecular function.
Reason: Both structural and functional evidence establish Dd-STATa as a DNA-binding transcription factor acting on Pol II genes.
Supporting Evidence:
PMID:15053873
Dd-STATa is a STAT protein which transcriptionally regulates cellular
GO:0003677 DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: Dd-STATa contains a STAT DNA-binding domain and binds DNA sequence-specifically. The general DNA binding term is correct but less informative than the sequence-specific/transcription-factor terms.
Reason: InterPro2GO inference of DNA binding is supported by direct evidence, though this is a general parent of the more specific annotations.
Supporting Evidence:
PMID:9200609
it will bind specifically to a mammalian
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000002
ACCEPT
Summary: Dd-STATa is a DNA-binding transcription factor; the InterPro2GO inference is correct and captures a core molecular function.
Reason: Well supported by structural and functional data establishing STAT transcription-factor activity.
Supporting Evidence:
PMID:15053873
Dd-STATa is a STAT protein which transcriptionally regulates cellular
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Nuclear localization is a core property of Dd-STATa, confirmed by direct experimental evidence.
Reason: The automated nuclear localization annotation agrees with direct immunolocalization of the activated protein.
Supporting Evidence:
PMID:9670017
translocates into the nuclei of all cells
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: Dd-STATa is cytoplasmic in growing/unactivated cells; the UniProt subcellular-location-based annotation is correct.
Reason: Consistent with direct evidence that the latent protein resides in the cytoplasm before signal-induced nuclear import.
Supporting Evidence:
PMID:9670017
Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated and is not selectively localized in the nucleus.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: Dd-STATa regulates transcription of target genes; this general term is correct.
Reason: Supported by extensive evidence for transcriptional regulation of prestalk genes.
Supporting Evidence:
PMID:15053873
Dd-STATa is a STAT protein which transcriptionally regulates cellular
GO:0007165 signal transduction
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: As a STAT, Dd-STATa transduces extracellular cAMP signals via tyrosine phosphorylation into a transcriptional response. The general signal transduction term is correct but less specific than the STAT signaling term.
Reason: Correct but a high-level parent; the more specific STAT signaling term (GO:0097696) better captures the core role.
Supporting Evidence:
PMID:9670017
The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1
GO:0042802 identical protein binding
IEA
GO_REF:0000117
ACCEPT
Summary: Activated Dd-STATa forms homodimers via reciprocal SH2-phosphotyrosine interactions, so identical protein (homodimer) binding is correct.
Reason: Homodimerization is directly demonstrated by the crystal structure of the tyrosine-phosphorylated Dd-STATa homodimer.
Supporting Evidence:
PMID:15053873
Dimerization is mediated by SH2 domain:phosphopeptide
GO:0045892 negative regulation of DNA-templated transcription
IEA
GO_REF:0000117
ACCEPT
Summary: Dd-STATa acts principally as a transcriptional repressor (e.g. of the stalk-cell gene ecmB), so negative regulation of transcription is a core function.
Reason: The repressor role is directly demonstrated by ectopic ecmB expression in null cells, agreeing with this ARBA-derived annotation.
Supporting Evidence:
PMID:10393118
Dd-STATa is the repressor protein that regulates commitment
GO:0005634 nucleus
IDA
PMID:9670017
Developmentally and spatially regulated activation of a Dict...
ACCEPT
Summary: Direct immunolocalization shows activated Dd-STATa in the nucleus, where it acts as a transcription factor. Core localization.
Reason: Directly demonstrated nuclear translocation upon cAMP-induced tyrosine phosphorylation.
Supporting Evidence:
PMID:9670017
translocates into the nuclei of all cells
GO:0003677 DNA binding
IDA
PMID:15053873
Structure of an activated Dictyostelium STAT in its DNA-unbo...
ACCEPT
Summary: The crystallographic and mutagenesis study of activated Dd-STATa establishes DNA binding via its STAT DNA-binding domain (key residues K443, R449/K450, N484 required for binding). Core molecular function.
Reason: Direct structural and mutagenesis evidence for sequence-specific DNA binding by the activated dimer.
Supporting Evidence:
PMID:15053873
implying a large conformational change
GO:0003677 DNA binding
IDA
PMID:9200609
SH2 signaling in a lower eukaryote: a STAT protein that regu...
ACCEPT
Summary: The TTGA-binding factor identified as Dd-STATa binds DNA sequence-specifically, including a mammalian interferon-stimulated response element. Core molecular function.
Reason: Direct DNA-binding evidence (TTGA element and mammalian ISRE) from the founding characterization of the protein.
Supporting Evidence:
PMID:9200609
it will bind specifically to a mammalian
GO:0005515 protein binding
IPI
PMID:31002205
Analysis of DrkA kinase's role in STATa activation.
MODIFY
Summary: STATa physically interacts with its activating tyrosine kinase DrkA through an SH2-dependent mechanism.
Reason: The curated IPI interaction and identification of DrkA as a STATa Tyr702 kinase support the informative protein tyrosine kinase binding term. This replacement describes the interacting enzyme class without converting kinase-substrate recognition into catalytic activity of STATa.
Proposed replacements: protein tyrosine kinase binding
Supporting Evidence:
PMID:31002205
phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine binding)
GO:0005634 nucleus
IDA
PMID:11032815
Glycogen synthase kinase-3 enhances nuclear export of a Dict...
ACCEPT
Summary: Anti-Dd-STATa antibody staining shows the protein in nuclei of growing and developing cells, with regulated nuclear enrichment. Core localization.
Reason: Direct evidence localizes Dd-STATa to the nucleus; this study also dissects the regulation of its nuclear import/export.
Supporting Evidence:
PMID:11032815
All growing and developing Dictyostelium cells appear to contain a small amount of Dd-STATa in their nuclei
GO:0005634 nucleus
IDA
PMID:12506009
The Dictyostelium prestalk cell inducer DIF regulates nuclea...
ACCEPT
Summary: This dictyBase IDA supports nuclear activity of the STAT protein. Note the cached abstract focuses on the paralog Dd-STATc and its DIF-controlled nuclear export; nuclear localization is nevertheless firmly established for Dd-STATa by independent studies.
Reason: Nuclear localization is a core, robustly supported property of Dd-STATa. The curator (dictyBase) made this IDA from full text; per policy an experimental annotation is retained rather than removed on the basis of an abstract that foregrounds a paralog.
Supporting Evidence:
PMID:9670017
translocates into the nuclei of all cells
GO:0005829 cytosol
IDA
PMID:9670017
Developmentally and spatially regulated activation of a Dict...
ACCEPT
Summary: Before activation, Dd-STATa is present in the cytosol/cytoplasm and is not selectively nuclear, consistent with the latent cytosolic STAT pool.
Reason: Directly supported by the observation that the unphosphorylated protein is not selectively localized to the nucleus.
Supporting Evidence:
PMID:9670017
Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated and is not selectively localized in the nucleus.
GO:0030587 sorocarp development
HMP
PMID:17659086
High-throughput analysis of spatio-temporal dynamics in Dict...
KEEP AS NON CORE
Summary: A high-throughput mutant-phenotype screen found that a dstA (STATa) insertion mutant is developmentally defective from the slug stage onward, consistent with a role in fruiting-body (sorocarp) development.
Reason: Supported by mutant phenotype, but this is a broad developmental-outcome term. The core, specific roles are in stalk-cell differentiation and culmination; sorocarp development is retained as a valid higher-level process.
Supporting Evidence:
PMID:17659086
carrying an insertion in dstA, a gene encoding the STATa transcription factor, which under our assay conditions was defective only from the slug stage on
GO:0031149 sorocarp stalk cell differentiation
IMP
PMID:10393118
Evidence that the Dictyostelium Dd-STATa protein is a repres...
ACCEPT
Summary: Dd-STATa null cells show aberrant stalk-cell gene expression and fail to complete terminal stalk-cell differentiation, establishing a direct role in regulating stalk-cell differentiation. Core biological process.
Reason: Strong mutant-phenotype evidence that Dd-STATa regulates commitment to and completion of stalk-cell differentiation.
Supporting Evidence:
PMID:10393118
show little or no terminal stalk cell differentiation within
GO:0042802 identical protein binding
IPI
PMID:15053873
Structure of an activated Dictyostelium STAT in its DNA-unbo...
ACCEPT
Summary: The crystal structure of the tyrosine-phosphorylated Dd-STATa homodimer directly demonstrates homodimerization through reciprocal SH2-phosphopeptide and SH2-SH2 interactions. This dimerization is central to STAT activation.
Reason: Directly demonstrated homodimer interface; homodimerization is the activating mechanism of the STAT.
Supporting Evidence:
PMID:15053873
Dimerization is mediated by SH2 domain:phosphopeptide
GO:0045892 negative regulation of DNA-templated transcription
IMP
PMID:10393118
Evidence that the Dictyostelium Dd-STATa protein is a repres...
ACCEPT
Summary: In Dd-STATa null cells the stalk-cell gene ecmB is ectopically and prematurely expressed and is over-induced by DIF, demonstrating that Dd-STATa normally represses transcription of stalk-cell genes. Core function.
Reason: Mutant-phenotype evidence directly establishes Dd-STATa as a transcriptional repressor of stalk-cell genes.
Supporting Evidence:
PMID:10393118
is greatly overinduced by DIF in Dd-STATa null cells.
GO:0097696 cell surface receptor signaling pathway via STAT
IDA
PMID:9670017
Developmentally and spatially regulated activation of a Dict...
ACCEPT
Summary: Dd-STATa is tyrosine-phosphorylated and nuclear-translocated in response to extracellular cAMP acting through the serpentine receptor cAR1, a STAT signaling pathway downstream of a cell-surface receptor. Core process.
Reason: Directly demonstrated STAT activation downstream of the cAR1 serpentine receptor; this is the accurate (non-JAK) STAT signaling term.
Supporting Evidence:
PMID:9670017
The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1
GO:0010628 positive regulation of gene expression
IMP
PMID:27125566
Regulation of ecmF gene expression and genetic hierarchy amo...
KEEP AS NON CORE
Summary: Besides its repressor role, Dd-STATa positively regulates several prestalk-A genes, including mybC (whose expression is positively regulated by STATa) and, indirectly, ecmF. Represents a genuine activating role.
Reason: Supported by mutant-phenotype/expression evidence. Positive regulation of specific target genes is a real but secondary aspect relative to the predominant repressor function.
Supporting Evidence:
PMID:27125566
whose expression is positively regulated by STATa.
GO:0010468 regulation of gene expression
IDA
PMID:15733068
Evidence that the Dictyostelium STAT protein Dd-STATa plays ...
ACCEPT
Summary: Dd-STATa is required for activation of the aslA gene in pstAB core cells; the aslA::lacZ reporter is not expressed in null slugs, demonstrating regulation of gene expression. General but correct.
Reason: Direct in situ/reporter evidence that Dd-STATa controls target-gene expression during prestalk differentiation.
Supporting Evidence:
PMID:15733068
the aslA::lacZ fusion gene is not expressed in Dd-STATa-null slugs.
GO:0010628 positive regulation of gene expression
IDA
PMID:15470642
Identification of new modes of Dd-STATa regulation of gene e...
KEEP AS NON CORE
Summary: In situ hybridization identified genes that are candidates for direct induction by Dd-STATa and that show little or no expression in null cells, supporting a positive (activating) role for a subset of target genes.
Reason: A real activating role for specific prestalk targets, secondary to the predominant repressor function of Dd-STATa.
Supporting Evidence:
PMID:15470642
13 genes which are candidates for direct induction by Dd-STATa.
GO:0031154 culmination involved in sorocarp development
IMP
PMID:15053873
Structure of an activated Dictyostelium STAT in its DNA-unbo...
ACCEPT
Summary: Dd-STATa is required for correct entry into culmination; null mutants fail to culminate. The role in culmination is well established, though this particular reference (a structure paper) is an unusual source for a culmination phenotype annotation.
Reason: The culmination requirement is firmly supported by null-mutant phenotypes across studies; per policy the experimental annotation is retained and the process is corroborated below.
Supporting Evidence:
PMID:15733068
is necessary in the slug for correct
GO:0031154 culmination involved in sorocarp development
IMP
PMID:10393118
Evidence that the Dictyostelium Dd-STATa protein is a repres...
ACCEPT
Summary: Dd-STATa null slugs remain developmentally arrested and only later form very small spore masses supported by undifferentiated cells, demonstrating a requirement for Dd-STATa in culmination. Core developmental role.
Reason: Direct null-mutant phenotype evidence that Dd-STATa is required for culmination into a normal fruiting body.
Supporting Evidence:
PMID:10393118
Dd-STATa null slugs remain developmentally arrested for several days

Core Functions

Dd-STATa is a sequence-specific DNA-binding transcription factor that binds TTGA cis-regulatory elements in target-gene promoters and acts chiefly as a repressor of stalk-cell genes (e.g. ecmB), thereby regulating commitment to stalk-cell differentiation.

Supporting Evidence:

Dd-STATa is a STAT-type signal transducer that is activated by cAMP/cAR1-triggered tyrosine phosphorylation on Tyr702 and homodimerizes via reciprocal SH2-phosphotyrosine interactions, transducing an extracellular signal into nuclear translocation and a transcriptional response.

Supporting Evidence:
  • PMID:15053873
    Dimerization is mediated by SH2 domain:phosphopeptide
  • PMID:9670017
    The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1

Through regulated transcription of prestalk/stalk target genes, Dd-STATa marks and maintains the slug tip organizer and is required for culmination into a mature fruiting body (sorocarp).

Supporting Evidence:
  • PMID:10393118
    Dd-STATa null slugs remain developmentally arrested for several days
  • PMID:27125566
    important for the organizer function in the tip region of the

References

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Deep Research

OpenScientist

(statA-hypotheses/proliferation-and-defense-response/openscientist.md)

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πŸ“š Additional Documentation

Notes

(statA-notes.md)

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