statA

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	REMOVE	Summary: Defense response is a metazoan STAT function (immune/cytokine signaling) propagated by phylogenetic inference. There is no evidence that Dd-STATa participates in a defense response; its documented roles are in cAMP-triggered developmental gene regulation. Reason: This IBA term is an over-propagation from animal STATs. Dictyostelium Dd-STATa is activated by developmental cAMP signaling, not by an immune pathway, and no defense-response phenotype has been reported for it. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000927860 · PANTHER node for the metazoan STAT transcription-factor family SUPPORTS SOURCE BUT NOT TARGET Defense response is a metazoan immune and cytokine STAT function that does not occur in the amoeba UniProtKB:P42224 · human STAT1 SUPPORTS SOURCE BUT NOT TARGET STAT1 defense and immune role is metazoan-specific and does not transfer to Dictyostelium
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	REMOVE	Summary: Regulation of cell proliferation is a metazoan STAT function (e.g. cytokine-driven proliferation) transferred by phylogenetic inference. Dd-STATa acts in a developmental, largely post-mitotic differentiation program, and no proliferation role has been demonstrated. Reason: This IBA term is an over-propagation from animal STATs and is not supported by any experimental evidence for Dd-STATa, whose characterized roles concern developmental cell-type differentiation rather than proliferation. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000927860 · PANTHER node for the metazoan STAT transcription-factor family SUPPORTS SOURCE BUT NOT TARGET Regulation of cell-population proliferation is a metazoan STAT function absent from Dictyostelium biology UniProtKB:P42224 · human STAT1 SUPPORTS SOURCE BUT NOT TARGET Metazoan STAT proliferation control does not transfer to the amoeba
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 · PANTHER node for the metazoan STAT transcription-factor family SUPPORTS SOURCE BUT NOT TARGET The JAK-STAT term presupposes a JAK kinase; Dictyostelium has no JAK, so STATa signaling should be described without the JAK-dependent qualifier UniProtKB:P42224 · human STAT1 SUPPORTS SOURCE BUT NOT TARGET Metazoan STAT1 is activated by JAK kinases; Dictyostelium lacks JAKs so the JAK-STAT scoping is inappropriate Proposed replacements: cell surface receptor signaling pathway via STAT 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.	KEEP AS NON CORE	Summary: This IPI reflects the physical interaction between Dd-STATa and the receptor-like kinase DrkA, which phosphorylates STATa on Tyr702 in an SH2-dependent manner. The bare protein binding term is uninformative; the biologically meaningful relationship is kinase-substrate. Reason: Per curation guidelines, generic protein binding is not treated as a core function. The interaction is real (with the activating kinase DrkA) but is better represented as being a substrate of that kinase. 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

📄 View Raw YAML

id: O00910
gene_symbol: statA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
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:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: Phylogenetic inference of nuclear activity is strongly corroborated by
      direct experimental evidence for this gene product.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: translocates into the nuclei of all cells
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Dd-STATa is cytoplasmic in growing cells and prior to activation, only
      translocating to the nucleus after tyrosine phosphorylation. Cytoplasmic
      localization is correct.
    action: ACCEPT
    reason: The cytoplasmic pool is where the latent, unphosphorylated STAT resides
      before signal-induced nuclear import, consistent with direct evidence.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated
        and is not selectively localized in the nucleus.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: The transcription-factor role is central to Dd-STATa function and is
      supported by extensive experimental evidence.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dd-STATa is a STAT protein which transcriptionally regulates
        cellular
- term:
    id: GO:0006952
    label: defense response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Defense response is a metazoan STAT function (immune/cytokine
      signaling) propagated by phylogenetic inference. There is no evidence that
      Dd-STATa participates in a defense response; its documented roles are in
      cAMP-triggered developmental gene regulation.
    action: REMOVE
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - LINEAGE_OR_TAXON_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000927860
        source_label: "PANTHER node for the metazoan STAT transcription-factor family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Defense response is a metazoan immune and cytokine STAT function that does not occur in the amoeba"
      - source_id: UniProtKB:P42224
        source_label: "human STAT1"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "STAT1 defense and immune role is metazoan-specific and does not transfer to Dictyostelium"
    reason: This IBA term is an over-propagation from animal STATs. Dictyostelium
      Dd-STATa is activated by developmental cAMP signaling, not by an immune
      pathway, and no defense-response phenotype has been reported for it.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Direct experimental evidence shows sequence-specific promoter-element
      binding, so this IBA annotation is well supported.
    supported_by:
    - reference_id: PMID:10393118
      supporting_text: Dd-STATa binds these repressor elements
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Regulation of cell proliferation is a metazoan STAT function (e.g.
      cytokine-driven proliferation) transferred by phylogenetic inference.
      Dd-STATa acts in a developmental, largely post-mitotic differentiation
      program, and no proliferation role has been demonstrated.
    action: REMOVE
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - LINEAGE_OR_TAXON_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000927860
        source_label: "PANTHER node for the metazoan STAT transcription-factor family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Regulation of cell-population proliferation is a metazoan STAT function absent from Dictyostelium biology"
      - source_id: UniProtKB:P42224
        source_label: "human STAT1"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Metazoan STAT proliferation control does not transfer to the amoeba"
    reason: This IBA term is an over-propagation from animal STATs and is not
      supported by any experimental evidence for Dd-STATa, whose characterized
      roles concern developmental cell-type differentiation rather than
      proliferation.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: MODIFY
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - LINEAGE_OR_TAXON_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000927860
        source_label: "PANTHER node for the metazoan STAT transcription-factor family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "The JAK-STAT term presupposes a JAK kinase; Dictyostelium has no JAK, so STATa signaling should be described without the JAK-dependent qualifier"
      - source_id: UniProtKB:P42224
        source_label: "human STAT1"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Metazoan STAT1 is activated by JAK kinases; Dictyostelium lacks JAKs so the JAK-STAT scoping is inappropriate"
    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.
    proposed_replacement_terms:
    - id: GO:0097696
      label: cell surface receptor signaling pathway via STAT
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
        are induced very rapidly by extracellular cAMP through the serpentine cAMP
        receptor cAR1
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Both structural and functional evidence establish Dd-STATa as a
      DNA-binding transcription factor acting on Pol II genes.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dd-STATa is a STAT protein which transcriptionally regulates
        cellular
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: InterPro2GO inference of DNA binding is supported by direct evidence,
      though this is a general parent of the more specific annotations.
    supported_by:
    - reference_id: PMID:9200609
      supporting_text: it will bind specifically to a mammalian
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Dd-STATa is a DNA-binding transcription factor; the InterPro2GO
      inference is correct and captures a core molecular function.
    action: ACCEPT
    reason: Well supported by structural and functional data establishing STAT
      transcription-factor activity.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dd-STATa is a STAT protein which transcriptionally regulates
        cellular
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Nuclear localization is a core property of Dd-STATa, confirmed by
      direct experimental evidence.
    action: ACCEPT
    reason: The automated nuclear localization annotation agrees with direct
      immunolocalization of the activated protein.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: translocates into the nuclei of all cells
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Dd-STATa is cytoplasmic in growing/unactivated cells; the UniProt
      subcellular-location-based annotation is correct.
    action: ACCEPT
    reason: Consistent with direct evidence that the latent protein resides in the
      cytoplasm before signal-induced nuclear import.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated
        and is not selectively localized in the nucleus.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Dd-STATa regulates transcription of target genes; this general term is
      correct.
    action: ACCEPT
    reason: Supported by extensive evidence for transcriptional regulation of
      prestalk genes.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dd-STATa is a STAT protein which transcriptionally regulates
        cellular
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Correct but a high-level parent; the more specific STAT signaling term
      (GO:0097696) better captures the core role.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
        are induced very rapidly by extracellular cAMP through the serpentine cAMP
        receptor cAR1
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Activated Dd-STATa forms homodimers via reciprocal SH2-phosphotyrosine
      interactions, so identical protein (homodimer) binding is correct.
    action: ACCEPT
    reason: Homodimerization is directly demonstrated by the crystal structure of
      the tyrosine-phosphorylated Dd-STATa homodimer.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dimerization is mediated by SH2 domain:phosphopeptide
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: The repressor role is directly demonstrated by ectopic ecmB expression
      in null cells, agreeing with this ARBA-derived annotation.
    supported_by:
    - reference_id: PMID:10393118
      supporting_text: Dd-STATa is the repressor protein that regulates commitment
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:9670017
  qualifier: is_active_in
  review:
    summary: Direct immunolocalization shows activated Dd-STATa in the nucleus,
      where it acts as a transcription factor. Core localization.
    action: ACCEPT
    reason: Directly demonstrated nuclear translocation upon cAMP-induced tyrosine
      phosphorylation.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: translocates into the nuclei of all cells
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15053873
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Direct structural and mutagenesis evidence for sequence-specific DNA
      binding by the activated dimer.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: implying a large conformational change
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9200609
  qualifier: enables
  review:
    summary: The TTGA-binding factor identified as Dd-STATa binds DNA
      sequence-specifically, including a mammalian interferon-stimulated response
      element. Core molecular function.
    action: ACCEPT
    reason: Direct DNA-binding evidence (TTGA element and mammalian ISRE) from the
      founding characterization of the protein.
    supported_by:
    - reference_id: PMID:9200609
      supporting_text: it will bind specifically to a mammalian
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31002205
  qualifier: enables
  review:
    summary: This IPI reflects the physical interaction between Dd-STATa and the
      receptor-like kinase DrkA, which phosphorylates STATa on Tyr702 in an
      SH2-dependent manner. The bare protein binding term is uninformative; the
      biologically meaningful relationship is kinase-substrate.
    action: KEEP_AS_NON_CORE
    reason: Per curation guidelines, generic protein binding is not treated as a
      core function. The interaction is real (with the activating kinase DrkA) but
      is better represented as being a substrate of that kinase.
    supported_by:
    - reference_id: PMID:31002205
      supporting_text: phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine
        binding)
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11032815
  qualifier: is_active_in
  review:
    summary: Anti-Dd-STATa antibody staining shows the protein in nuclei of growing
      and developing cells, with regulated nuclear enrichment. Core localization.
    action: ACCEPT
    reason: Direct evidence localizes Dd-STATa to the nucleus; this study also
      dissects the regulation of its nuclear import/export.
    supported_by:
    - reference_id: PMID:11032815
      supporting_text: All growing and developing Dictyostelium cells appear to contain
        a small amount of Dd-STATa in their nuclei
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12506009
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: translocates into the nuclei of all cells
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:9670017
  qualifier: part_of
  review:
    summary: Before activation, Dd-STATa is present in the cytosol/cytoplasm and is
      not selectively nuclear, consistent with the latent cytosolic STAT pool.
    action: ACCEPT
    reason: Directly supported by the observation that the unphosphorylated protein
      is not selectively localized to the nucleus.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated
        and is not selectively localized in the nucleus.
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: HMP
  original_reference_id: PMID:17659086
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:17659086
      supporting_text: 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
- term:
    id: GO:0031149
    label: sorocarp stalk cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:10393118
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Strong mutant-phenotype evidence that Dd-STATa regulates commitment to
      and completion of stalk-cell differentiation.
    supported_by:
    - reference_id: PMID:10393118
      supporting_text: show little or no terminal stalk cell differentiation within
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:15053873
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Directly demonstrated homodimer interface; homodimerization is the
      activating mechanism of the STAT.
    supported_by:
    - reference_id: PMID:15053873
      supporting_text: Dimerization is mediated by SH2 domain:phosphopeptide
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:10393118
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Mutant-phenotype evidence directly establishes Dd-STATa as a
      transcriptional repressor of stalk-cell genes.
    supported_by:
    - reference_id: PMID:10393118
      supporting_text: is greatly overinduced by DIF in Dd-STATa null cells.
- term:
    id: GO:0097696
    label: cell surface receptor signaling pathway via STAT
  evidence_type: IDA
  original_reference_id: PMID:9670017
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Directly demonstrated STAT activation downstream of the cAR1 serpentine
      receptor; this is the accurate (non-JAK) STAT signaling term.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
        are induced very rapidly by extracellular cAMP through the serpentine cAMP
        receptor cAR1
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:27125566
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27125566
      supporting_text: whose expression is positively regulated by STATa.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:15733068
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Direct in situ/reporter evidence that Dd-STATa controls target-gene
      expression during prestalk differentiation.
    supported_by:
    - reference_id: PMID:15733068
      supporting_text: the aslA::lacZ fusion gene is not expressed in Dd-STATa-null
        slugs.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:15470642
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: A real activating role for specific prestalk targets, secondary to the
      predominant repressor function of Dd-STATa.
    supported_by:
    - reference_id: PMID:15470642
      supporting_text: 13 genes which are candidates for direct induction by Dd-STATa.
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:15053873
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:15733068
      supporting_text: is necessary in the slug for correct
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:10393118
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: ACCEPT
    reason: Direct null-mutant phenotype evidence that Dd-STATa is required for
      culmination into a normal fruiting body.
    supported_by:
    - reference_id: PMID:10393118
      supporting_text: Dd-STATa null slugs remain developmentally arrested for several
        days
core_functions:
- description: 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.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0045892
    label: negative regulation of DNA-templated transcription
  - id: GO:0031149
    label: sorocarp stalk cell differentiation
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:10393118
    supporting_text: Dd-STATa is the repressor protein that regulates commitment
  - reference_id: PMID:10393118
    supporting_text: Dd-STATa binds these repressor elements
- description: 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.
  molecular_function:
    id: GO:0042802
    label: identical protein binding
  directly_involved_in:
  - id: GO:0097696
    label: cell surface receptor signaling pathway via STAT
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:15053873
    supporting_text: Dimerization is mediated by SH2 domain:phosphopeptide
  - reference_id: PMID:9670017
    supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
      are induced very rapidly by extracellular cAMP through the serpentine cAMP
      receptor cAR1
- description: 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).
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0031154
    label: culmination involved in sorocarp development
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:10393118
    supporting_text: Dd-STATa null slugs remain developmentally arrested for several
      days
  - reference_id: PMID:27125566
    supporting_text: important for the organizer function in the tip region of the
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10393118
  title: Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates
    commitment to stalk cell differentiation and is also required for efficient chemotaxis.
  findings:
  - statement: Dd-STATa is the transcriptional repressor that binds stalk-cell gene
      repressor elements and regulates commitment to stalk-cell differentiation.
    supporting_text: Dd-STATa is the repressor protein that regulates commitment
  - statement: Loss of Dd-STATa leads to over-induction of the stalk-cell gene ecmB
      by DIF, confirming its repressor role.
    supporting_text: is greatly overinduced by DIF in Dd-STATa null cells.
  - statement: Dd-STATa null slugs arrest and fail to culminate normally.
    supporting_text: Dd-STATa null slugs remain developmentally arrested for several
      days
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; primary genetic evidence for the repressor role,
      stalk-cell differentiation, chemotaxis, and culmination phenotypes.
- id: PMID:11032815
  title: Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT
    protein.
  findings:
  - statement: Dd-STATa is present in the nuclei of growing and developing cells,
      with regulated nuclear enrichment.
    supporting_text: All growing and developing Dictyostelium cells appear to contain
      a small amount of Dd-STATa in their nuclei
  - statement: GskA (GSK-3) phosphorylation enhances nuclear export of Dd-STATa,
      providing biphasic control of its nuclear residence.
    supporting_text: Phosphorylation by GskA enhances nuclear export of
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; full text available. Supports nuclear localization
      and the GskA-dependent nuclear export mechanism.
- id: PMID:12506009
  title: The Dictyostelium prestalk cell inducer DIF regulates nuclear accumulation
    of a STAT protein by controlling its rate of export from the nucleus.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified. The abstract characterizes the paralog Dd-STATc
      (DIF-controlled CRM1-dependent nuclear export); used by dictyBase to support
      nuclear activity. Nuclear localization of Dd-STATa itself is independently
      established (PMID:9670017, PMID:11032815).
- id: PMID:15053873
  title: Structure of an activated Dictyostelium STAT in its DNA-unbound form.
  findings:
  - statement: The tyrosine-phosphorylated Dd-STATa homodimer has a four-domain STAT
      architecture similar to mammalian STAT1/STAT3.
    supporting_text: Dd-STATa is a STAT protein which transcriptionally regulates cellular
  - statement: Dd-STATa homodimerizes through SH2 domain:phosphopeptide and direct
      SH2-SH2 interactions.
    supporting_text: Dimerization is mediated by SH2 domain:phosphopeptide
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; crystal structure (PDB 1UUR/1UUS) of the activated
      homodimer, establishing dimerization mechanism and DNA-binding domain.
- id: PMID:15470642
  title: Identification of new modes of Dd-STATa regulation of gene expression in
    Dictyostelium by in situ hybridisation.
  findings:
  - statement: In situ hybridization identified candidate directly induced Dd-STATa
      target genes downregulated in null cells.
    supporting_text: 13 genes which are candidates for direct induction by Dd-STATa.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; supports positive (activating) regulation of a
      subset of prestalk target genes.
- id: PMID:15733068
  title: Evidence that the Dictyostelium STAT protein Dd-STATa plays a role in the
    differentiation of inner basal disc cells and identification of a promoter element
    essential for expression in these cells.
  findings:
  - statement: Dd-STATa is required in the slug for correct entry into culmination
      and for differentiation of pstAB core cells.
    supporting_text: is necessary in the slug for correct
  - statement: The aslA::lacZ reporter, a Dd-STATa target, is not expressed in null
      slugs.
    supporting_text: the aslA::lacZ fusion gene is not expressed in Dd-STATa-null
      slugs.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; supports regulation of gene expression and
      culmination/inner basal disc differentiation.
- id: PMID:17659086
  title: High-throughput analysis of spatio-temporal dynamics in Dictyostelium.
  findings:
  - statement: A dstA (STATa) insertion mutant is developmentally defective from the
      slug stage onward in a high-throughput phenotype screen.
    supporting_text: 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
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; full text available. Genome-scale mutant screen
      corroborating a developmental (post-slug) phenotype for dstA/STATa.
- id: PMID:27125566
  title: Regulation of ecmF gene expression and genetic hierarchy among STATa, CudA,
    and MybC on several prestalk A-specific gene expressions in Dictyostelium.
  findings:
  - statement: STATa is important for tip organizer function in the migrating slug.
    supporting_text: important for the organizer function in the tip region of the
  - statement: STATa positively regulates mybC and indirectly upregulates ecmF in a
      CudA-independent manner.
    supporting_text: whose expression is positively regulated by STATa.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; establishes STATa-CudA-MybC genetic hierarchy and
      organizer/positive-regulation roles.
- id: PMID:31002205
  title: Analysis of DrkA kinase's role in STATa activation.
  findings:
  - statement: STATa is activated by tyrosine phosphorylation on Tyr702 in response
      to extracellular cAMP.
    supporting_text: STATa is activated by phosphorylation on Tyr702 when cells are
      exposed to
  - statement: The receptor-like kinase DrkA phosphorylates STATa on Tyr702 in an
      SH2-dependent manner.
    supporting_text: phosphorylate STATa on Tyr702 in a STATa-SH2 (phosphotyrosine
      binding)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; identifies DrkA as a candidate direct activating
      kinase and provides the physical/kinase-substrate interaction basis for the
      protein binding IPI.
- id: PMID:9200609
  title: 'SH2 signaling in a lower eukaryote: a STAT protein that regulates stalk
    cell differentiation in dictyostelium.'
  findings:
  - statement: The DIF-activated TTGA-binding factor that regulates stalk-cell
      differentiation is a STAT protein.
    supporting_text: The TTGA-binding factor is a transcriptional regulator activated
      by DIF
  - statement: Dd-STATa binds specifically to a mammalian interferon-stimulated
      response element, demonstrating sequence-specific DNA binding.
    supporting_text: it will bind specifically to a mammalian
  - statement: Dd-STATa functions via reciprocal phosphotyrosine-SH2 interactions
      like metazoan STATs.
    supporting_text: a phosphotyrosine residue on one molecule with an SH2 domain on
      a dimerizing
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; founding paper identifying Dd-STATa as a STAT and
      SH2-signaling transcription factor.
- id: PMID:9670017
  title: Developmentally and spatially regulated activation of a Dictyostelium STAT
    protein by a serpentine receptor.
  findings:
  - statement: Dd-STATa tyrosine phosphorylation and nuclear translocation are
      induced by extracellular cAMP through the serpentine receptor cAR1.
    supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
      are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor
      cAR1
  - statement: Activated Dd-STAT translocates into nuclei; nuclear enrichment is
      maintained in tip-forming prestalk cells.
    supporting_text: translocates into the nuclei of all cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; full text available. Establishes cAR1-dependent
      activation and the spatial pattern of nuclear Dd-STATa in the tip organizer.

Gene Description

Existing Annotations Review

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.

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.

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).

References

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