statC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: STATc is a transcription factor that accumulates in the nucleus upon activation by DIF-1 or stress. Phylogenetic inference of nuclear localization is correct and independently supported by direct experimental evidence. Reason: Nuclear localization of activated STATc is directly demonstrated and is central to its transcription factor function. Supporting Evidence: PMID:12506009 Dd-STATc becomes tyrosine phosphorylated, dimerises and accumulates in the nuclei of Dictyostelium cells exposed to DIF
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: In unstimulated cells STATc is a latent cytoplasmic factor that translocates to the nucleus only upon activation. Cytoplasmic localization is correct. Reason: STATc shuttles between cytoplasm and nucleus and is predominantly cytoplasmic in the resting state, consistent with the STAT activation paradigm. Supporting Evidence: PMID:18305004 STATc becomes tyrosine phosphorylated and accumulates in the nucleus when Dictyostelium cells are exposed to the prestalk cell inducer Differentiation inducing factor 1 (DIF-1), or are subjected to hyper-osmotic stress
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: STATc is a sequence-specific transcription factor that both represses and activates specific genes; regulation of RNA polymerase II transcription is its core biological role. Reason: Directly supported by experimental evidence that STATc regulates ecmA (repression) and stress-response genes (activation). Supporting Evidence: PMID:11336701 Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations
GO:0006952 defense response	IBA GO_REF:0000033	REMOVE	Summary: This IBA term is propagated from metazoan STATs, which act in immune and defense responses. Dictyostelium STATc acts in development and in the response to abiotic stress (osmotic, heat, oxidative), not in a defense response as ontologically defined. Reason: Over-propagation of a metazoan STAT immunity function to a Dictyostelium STAT. There is no experimental evidence that STATc functions in defense response; its documented stress roles are captured by more appropriate terms such as hyperosmotic response, response to oxidative stress and response to heat. 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: STATs are sequence-specific DNA-binding transcription factors; STATc contains a STAT DNA-binding region and functions as a transcriptional regulator, so sequence-specific DNA binding is a reasonable core molecular function. Reason: Consistent with the STAT family DNA-binding domain and with STATc's documented sequence-specific transcriptional regulation of target genes. Supporting Evidence: PMID:11336701 Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations
GO:0042127 regulation of cell population proliferation	IBA GO_REF:0000033	REMOVE	Summary: This IBA term reflects metazoan STAT roles in cell proliferation. Dictyostelium STATc regulates developmental timing and the stress transcriptional program, not cell population proliferation, and statC null cells are not reported to have a proliferation phenotype. Reason: Over-propagation from metazoan STATs. No experimental support for STATc controlling cell proliferation in Dictyostelium; its characterized roles are developmental patterning and stress-response transcription. 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: STATc participates in STAT signaling, but Dictyostelium has no JAK orthologs; STATc is instead phosphorylated by tyrosine-kinase-like enzymes (Pyk2/Pyk3). The JAK-STAT-specific term is therefore inappropriate and should be generalized to STAT signaling. Reason: There are no Dictyostelium homologs of the metazoan JAK family; STATc activation is catalyzed by TKL enzymes. The parent term GO:0097696 (cell surface receptor signaling pathway via STAT), which does not require a JAK, more accurately captures STATc signaling. 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 STATc 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:22699506 There are no orthologs of the animal tyrosine kinases, but there are very many tyrosine kinase-like kinases (TKLs)
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: STATc is a bona fide DNA-binding transcription factor that regulates RNA polymerase II transcription of developmental and stress-response genes. This is a core molecular function. Reason: Well supported by experimental evidence that STATc acts as a sequence-specific transcriptional repressor and activator of target genes. Supporting Evidence: PMID:12771188 These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway
GO:0003677 DNA binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic DNA binding is correct but uninformative given the more specific transcription-factor DNA-binding annotations already present. Reason: DNA binding is subsumed by the more specific molecular functions (DNA-binding transcription factor activity, RNA polymerase II-specific); retained as a correct but general parent term.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: STATc is a DNA-binding transcription factor. This InterPro2GO annotation is correct; the RNA polymerase II-specific child term is more precise. Reason: Correct general molecular function for a STAT transcription factor, consistent with the experimental evidence for transcriptional regulation. Supporting Evidence: PMID:11336701 Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Nuclear localization is correct and directly demonstrated. Reason: Consistent with direct experimental evidence for nuclear accumulation of activated STATc. Supporting Evidence: PMID:12506009 Dd-STATc becomes tyrosine phosphorylated, dimerises and accumulates in the nuclei of Dictyostelium cells exposed to DIF
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasmic localization is correct; STATc is a latent cytoplasmic factor in the resting state. Reason: Consistent with UniProt subcellular location and with the STAT cytoplasm-to-nucleus shuttling mechanism. Supporting Evidence: PMID:18305004 STATc becomes tyrosine phosphorylated and accumulates in the nucleus when Dictyostelium cells are exposed to the prestalk cell inducer Differentiation inducing factor 1 (DIF-1), or are subjected to hyper-osmotic stress
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: Correct general biological process for a transcription factor; subsumed by the more specific regulation of transcription by RNA polymerase II. Reason: STATc regulates transcription of developmental and stress-response genes; the general term is correct. Supporting Evidence: PMID:12771188 These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway
GO:0007165 signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: STATc is an effector of DIF-1 and stress signaling. Signal transduction is correct but very general. Reason: A high-level parent process that is correct but uninformative relative to the more specific STAT signaling and stress-response annotations.
GO:0042802 identical protein binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Activated STATc homodimerizes through reciprocal SH2-phosphotyrosine interactions. Identical protein binding is correct and part of the activation mechanism, though not the core molecular function. Reason: STATc dimerizes upon tyrosine phosphorylation; homodimerization is a mechanistic feature rather than the primary evolved function. Supporting Evidence: PMID:11336701 Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000117	ACCEPT	Summary: STATc acts as a transcriptional repressor, restricting graded ecmA expression in prestalk cells. Negative regulation of transcription is well supported. Reason: Independently supported by experimental evidence that STATc represses ecmA prestalk gene expression. Supporting Evidence: PMID:11336701 Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations
GO:0006970 response to osmotic stress	IMP PMID:22944283 The calcineurin dependent transcription factor TacA is invol...	ACCEPT	Summary: STATc is a well-established mediator of the transcriptional response to hyperosmotic (osmotic) stress in Dictyostelium. Reason: STATc's role in the osmotic stress response is documented across multiple studies; the TacA study explicitly contrasts its own pathway with the well-known STATc stress response. Supporting Evidence: PMID:22944283 TacA is involved in the stress response of D. discoideum during development in a separate pathway to the well-known stress response in Dictyostelium via STATc
GO:0043157 response to cation stress	IMP PMID:22944283 The calcineurin dependent transcription factor TacA is invol...	KEEP AS NON CORE	Summary: STATc responds to several stresses; a specific role in cation stress is less clearly established and largely relates to Ca2+/calcineurin signaling studied in the TacA work. Retained as a non-core stress role. Reason: STATc is a general stress-responsive factor; the cation-stress-specific role is not a core, independently defining function and overlaps with its broader osmotic/stress response. Supporting Evidence: PMID:22944283 TacA is involved in the stress response of D. discoideum during development in a separate pathway to the well-known stress response in Dictyostelium via STATc
GO:0010628 positive regulation of gene expression	IMP PMID:24587195 Identification of the protein kinases Pyk3 and Phg2 as regul...	ACCEPT	Summary: STATc positively regulates expression of its target genes, including a positive feedback loop that upregulates STATc and STATc-dependent genes during the stress response. Reason: Directly supported by mutant analyses showing STATc-dependent upregulation of stress-response genes. Supporting Evidence: PMID:24587195 The STATc stress signalling pathway feeds back on itself by upregulating the expression of STATc and STATc-regulated genes
GO:0080135 regulation of cellular response to stress	IMP PMID:24267687 The arrestin-domain containing protein AdcA is a response el...	ACCEPT	Summary: STATc-dependent transcription contributes to the cellular stress response, including the timely dephosphorylation of the stress element AdcA. Reason: Supported by evidence that STATc-dependent transcriptional activity is required for proper timing of the AdcA stress response. Supporting Evidence: PMID:24267687 STATc-dependent transcriptional activity is involved for the timely dephosphorylation of AdcA in
GO:1990782 protein tyrosine kinase binding	IPI PMID:22699506 Identification of the kinase that activates a nonmetazoan ST...	ACCEPT	Summary: STATc binds the tyrosine-kinase-like enzyme Pyk2 through its SH2 domain; the STATc-Pyk2 complex is formed constitutively and Pyk2 phosphorylates STATc on Tyr922. This is an informative molecular function central to STATc activation. Reason: Directly demonstrated physical interaction between STATc and its activating tyrosine kinase Pyk2 in vitro and in vivo. Supporting Evidence: PMID:22699506 the STATc-Pyk2 complex is formed constitutively by an interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2 PMID:22699506 Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes with STATc both in vitro and in vivo
GO:0005634 nucleus	IDA PMID:11336701 Tyrosine phosphorylation-independent nuclear translocation o...	ACCEPT	Summary: Direct evidence that activated STATc translocates to and acts in the nucleus. Core localization. Reason: STATc translocates to the nucleus upon DIF-induced tyrosine phosphorylation and dimerization, where it exerts its transcription factor function. Supporting Evidence: PMID:11336701 Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF
GO:0005634 nucleus	IDA PMID:12506009 The Dictyostelium prestalk cell inducer DIF regulates nuclea...	ACCEPT	Summary: Direct evidence for nuclear accumulation of STATc; nuclear residence is controlled at the level of CRM1-dependent export. Reason: STATc accumulates in the nucleus of DIF-exposed cells, with DIF inhibiting its nuclear export. Supporting Evidence: PMID:12506009 Dd-STATc becomes tyrosine phosphorylated, dimerises and accumulates in the nuclei of Dictyostelium cells exposed to DIF
GO:0045892 negative regulation of DNA-templated transcription	IMP PMID:11336701 Tyrosine phosphorylation-independent nuclear translocation o...	ACCEPT	Summary: STATc functions as a repressor that restricts graded ecmA expression to specific prestalk cell populations. Core function. Reason: Mutant analysis demonstrates STATc acts as a transcriptional repressor of the ecmA prestalk marker. Supporting Evidence: PMID:11336701 Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations
GO:0005829 cytosol	IDA PMID:11336701 Tyrosine phosphorylation-independent nuclear translocation o...	ACCEPT	Summary: STATc is present in the cytosol in the resting (latent) state before activation-induced nuclear translocation. Reason: Consistent with the latent cytoplasmic nature of STATc prior to DIF/stress-induced nuclear accumulation. Supporting Evidence: PMID:11336701 Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF
GO:0005634 nucleus	IMP PMID:12771188 A STAT-regulated, stress-induced signalling pathway in Dicty...	ACCEPT	Summary: STATc localizes to the nucleus; nuclear accumulation is a hallmark of its activation by stress and DIF. Reason: Nuclear localization of activated STATc is consistent across multiple studies. Supporting Evidence: PMID:12771188 hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc
GO:0031288 sorocarp morphogenesis	IMP PMID:11336701 Tyrosine phosphorylation-independent nuclear translocation o...	KEEP AS NON CORE	Summary: STATc influences developmental timing and prestalk cell-type patterning during fruiting body (sorocarp) formation. This is a genuine but downstream developmental role rather than the core molecular function. Reason: statC null cells show altered developmental timing and prestalk patterning, and colonies form aberrant fruiting bodies; this developmental phenotype is a consequence of STATc's transcription factor activity. Supporting Evidence: PMID:11336701 which regulates the speed of early development and the timing of terminal differentiation
GO:0005515 protein binding	IPI PMID:12220630 OSBPa, a predicted oxysterol binding protein of Dictyosteliu...	KEEP AS NON CORE	Summary: Bare protein binding is uninformative. This IPI annotation derives from a study of OSBPa/culmination; the specific STATc interaction partner and its significance are not resolvable from the available record. Reason: Generic protein binding provides no functional insight and per curation guidance should not be treated as a core function; retained as a non-core curated physical interaction.
GO:0005515 protein binding	IPI PMID:18305004 Evidence that DIF-1 and hyper-osmotic stress activate a Dict...	MODIFY	Summary: This physical interaction is with the protein tyrosine phosphatase PTP3, which directly binds and dephosphorylates STATc. The bare protein binding term should be replaced by the more informative protein phosphatase binding. Reason: The interacting partner is identified as the phosphatase PTP3, so a more specific and informative molecular function is warranted instead of generic protein binding. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:18305004 the protein tyrosine phosphatase PTP3 interacts directly with STATc
GO:0005515 protein binding	IPI PMID:25143406 Two Dictyostelium tyrosine kinase-like kinases function in p...	MODIFY	Summary: This interaction is with the tyrosine-kinase-like enzymes Pyk2/Pyk3, which bind the STATc SH2 domain and phosphorylate it. The bare protein binding term should be replaced by protein tyrosine kinase binding. Reason: The interacting partners are the activating TKL kinases Pyk2/Pyk3, so the more informative protein tyrosine kinase binding term is warranted instead of generic protein binding. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:25143406 The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target of further kinase action
GO:0042802 identical protein binding	IPI PMID:11336701 Tyrosine phosphorylation-independent nuclear translocation o...	KEEP AS NON CORE	Summary: Activated STATc homodimerizes; identical protein binding is directly supported and is part of the activation mechanism. Reason: STATc dimerizes upon tyrosine phosphorylation; homodimerization is a mechanistic step rather than the core evolved function. Supporting Evidence: PMID:11336701 Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF
GO:1903013 response to differentiation-inducing factor 1	HDA PMID:25518940 The Dictyostelium prestalk inducer differentiation-inducing ...	ACCEPT	Summary: STATc is rapidly tyrosine-phosphorylated in response to DIF-1, as confirmed by global phosphoproteomics. Response to DIF-1 is a defining feature of STATc. Reason: DIF-1-triggered activation of STATc is directly observed and is central to its role in prestalk cell differentiation. Supporting Evidence: PMID:25518940 STATc is rapidly phosphorylated after exposure to DIF-1
GO:0030587 sorocarp development	IEP PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo...	KEEP AS NON CORE	Summary: STATc (dstC) is developmentally expressed with a graded trajectory during multicellular development. This expression-based annotation supports a developmental role but is non-core relative to the molecular function. Reason: An IEP (expression-pattern) inference; STATc's developmental involvement is genuine but is a downstream consequence of its transcription factor activity rather than a core function. Supporting Evidence: PMID:25887420 dstC continued on a more graded trajectory
GO:0006972 hyperosmotic response	IEP PMID:17517120 STATc is a key regulator of the transcriptional response to ...	ACCEPT	Summary: STATc is a key regulator of the transcriptional response to hyperosmotic shock, with roughly 20% of osmotically regulated genes dependent on STATc. Core stress-response role. Reason: Genome-wide analysis shows STATc controls a substantial subset of the hyperosmotic stress transcriptional program. Supporting Evidence: PMID:17517120 Approximately 20% of the differentially regulated genes were dependent on the presence of STATc
GO:0006972 hyperosmotic response	IDA PMID:12771188 A STAT-regulated, stress-induced signalling pathway in Dicty...	ACCEPT	Summary: STATc is directly activated by hyperosmotic stress and functions as a transcriptional activator in the stress-response pathway. Core role. Reason: Hyperosmotic stress directly activates STATc, which then drives stress-response gene expression (e.g. gapA, rtoA). Supporting Evidence: PMID:12771188 hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc
GO:0006979 response to oxidative stress	IDA PMID:12771188 A STAT-regulated, stress-induced signalling pathway in Dicty...	KEEP AS NON CORE	Summary: STATc is activated by oxidative stress, one of several stress stimuli that trigger its tyrosine phosphorylation and nuclear accumulation. Reason: Oxidative stress is one of multiple stress inputs that activate STATc; retained as a genuine but non-core stress response alongside the dominant osmotic response. Supporting Evidence: PMID:12771188 hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc
GO:0009408 response to heat	IDA PMID:12771188 A STAT-regulated, stress-induced signalling pathway in Dicty...	KEEP AS NON CORE	Summary: STATc is activated by heat shock, another of the stress stimuli that trigger its activation. Reason: Heat shock is one of several stresses that activate STATc; a genuine but non-core stress response relative to the dominant osmotic response. Supporting Evidence: PMID:12771188 hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc
GO:0047484 regulation of response to osmotic stress	IMP PMID:12771188 A STAT-regulated, stress-induced signalling pathway in Dicty...	ACCEPT	Summary: STATc regulates the transcriptional output of the osmotic stress response, controlling stress-induced genes such as gapA and rtoA. Reason: Mutant analysis shows osmotic-stress induction of STATc target genes is entirely dependent on STATc, placing it as a regulator of the osmotic stress response. Supporting Evidence: PMID:12771188 Osmotic stress induction of gapA and rtoA is entirely dependent on Dd-STATc

📄 View Raw YAML

id: Q54BD4
gene_symbol: statC
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: STATc (Dd-STATc) is one of four STAT-family transcription factors of
  Dictyostelium discoideum. It is a large (931-residue) SH2-domain protein that acts
  as a latent, signal-dependent transcription factor. In unstimulated cells STATc is
  predominantly cytoplasmic; upon exposure to the prestalk morphogen DIF-1 or to
  environmental stress (hyperosmotic shock, heat shock, oxidative stress) it is
  tyrosine-phosphorylated on Tyr922, dimerizes and accumulates in the nucleus, where
  it binds DNA and regulates transcription. Activation is unusual and does not use a
  metazoan JAK; instead the tyrosine-kinase-like enzymes Pyk2 and Pyk3 phosphorylate
  STATc, counterbalanced by the protein tyrosine phosphatase PTP3, whose
  stress-induced serine/threonine phosphorylation inhibits it and shifts the balance
  toward STATc phosphorylation. STATc can act both as a repressor (it restricts
  graded ecmA prestalk-gene expression to specific prestalk cell populations) and as
  a transcriptional activator (it drives a large fraction of the hyperosmotic stress
  transcriptional program, including genes such as gapA and rtoA). Through these
  activities STATc influences the speed of early development, the timing of terminal
  differentiation, prestalk cell-type patterning and the cellular response to osmotic
  and other stresses. Nuclear accumulation is controlled at the level of
  CRM1-dependent nuclear export, and STATc is enriched in pstO cells at the rear of
  the prestalk region of the slug.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: STATc is a transcription factor that accumulates in the nucleus upon
      activation by DIF-1 or stress. Phylogenetic inference of nuclear localization
      is correct and independently supported by direct experimental evidence.
    action: ACCEPT
    reason: Nuclear localization of activated STATc is directly demonstrated and is
      central to its transcription factor function.
    supported_by:
    - reference_id: PMID:12506009
      supporting_text: Dd-STATc becomes tyrosine phosphorylated, dimerises and
        accumulates in the nuclei of Dictyostelium cells exposed to DIF
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: In unstimulated cells STATc is a latent cytoplasmic factor that
      translocates to the nucleus only upon activation. Cytoplasmic localization is
      correct.
    action: ACCEPT
    reason: STATc shuttles between cytoplasm and nucleus and is predominantly
      cytoplasmic in the resting state, consistent with the STAT activation
      paradigm.
    supported_by:
    - reference_id: PMID:18305004
      supporting_text: STATc becomes tyrosine phosphorylated and accumulates in the
        nucleus when Dictyostelium cells are exposed to the prestalk cell inducer
        Differentiation inducing factor 1 (DIF-1), or are subjected to hyper-osmotic
        stress
- 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: STATc is a sequence-specific transcription factor that both represses
      and activates specific genes; regulation of RNA polymerase II transcription is
      its core biological role.
    action: ACCEPT
    reason: Directly supported by experimental evidence that STATc regulates ecmA
      (repression) and stress-response genes (activation).
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc also functions as a repressor, which directs graded
        expression of the ecmA gene in different prestalk cell populations
- term:
    id: GO:0006952
    label: defense response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This IBA term is propagated from metazoan STATs, which act in immune
      and defense responses. Dictyostelium STATc acts in development and in the
      response to abiotic stress (osmotic, heat, oxidative), not in a defense
      response as ontologically defined.
    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: Over-propagation of a metazoan STAT immunity function to a Dictyostelium
      STAT. There is no experimental evidence that STATc functions in defense
      response; its documented stress roles are captured by more appropriate terms
      such as hyperosmotic response, response to oxidative stress and response to
      heat.
- 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: STATs are sequence-specific DNA-binding transcription factors; STATc
      contains a STAT DNA-binding region and functions as a transcriptional
      regulator, so sequence-specific DNA binding is a reasonable core molecular
      function.
    action: ACCEPT
    reason: Consistent with the STAT family DNA-binding domain and with STATc's
      documented sequence-specific transcriptional regulation of target genes.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc also functions as a repressor, which directs graded
        expression of the ecmA gene in different prestalk cell populations
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This IBA term reflects metazoan STAT roles in cell proliferation.
      Dictyostelium STATc regulates developmental timing and the stress
      transcriptional program, not cell population proliferation, and statC null
      cells are not reported to have a proliferation phenotype.
    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: Over-propagation from metazoan STATs. No experimental support for STATc
      controlling cell proliferation in Dictyostelium; its characterized roles are
      developmental patterning and stress-response transcription.
- 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: STATc participates in STAT signaling, but Dictyostelium has no JAK
      orthologs; STATc is instead phosphorylated by tyrosine-kinase-like enzymes
      (Pyk2/Pyk3). The JAK-STAT-specific term is therefore inappropriate and should
      be generalized to STAT signaling.
    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 STATc 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: There are no Dictyostelium homologs of the metazoan JAK family; STATc
      activation is catalyzed by TKL enzymes. The parent term GO:0097696 (cell
      surface receptor signaling pathway via STAT), which does not require a JAK,
      more accurately captures STATc signaling.
    proposed_replacement_terms:
    - id: GO:0097696
      label: cell surface receptor signaling pathway via STAT
    supported_by:
    - reference_id: PMID:22699506
      supporting_text: There are no orthologs of the animal tyrosine kinases, but
        there are very many tyrosine kinase-like kinases (TKLs)
- 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: STATc is a bona fide DNA-binding transcription factor that regulates
      RNA polymerase II transcription of developmental and stress-response genes.
      This is a core molecular function.
    action: ACCEPT
    reason: Well supported by experimental evidence that STATc acts as a
      sequence-specific transcriptional repressor and activator of target genes.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: These data show that Dd-STATc functions as a transcriptional
        activator in a stress-response pathway
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Generic DNA binding is correct but uninformative given the more
      specific transcription-factor DNA-binding annotations already present.
    action: KEEP_AS_NON_CORE
    reason: DNA binding is subsumed by the more specific molecular functions
      (DNA-binding transcription factor activity, RNA polymerase II-specific);
      retained as a correct but general parent term.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: STATc is a DNA-binding transcription factor. This InterPro2GO
      annotation is correct; the RNA polymerase II-specific child term is more
      precise.
    action: ACCEPT
    reason: Correct general molecular function for a STAT transcription factor,
      consistent with the experimental evidence for transcriptional regulation.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc also functions as a repressor, which directs graded
        expression of the ecmA gene in different prestalk cell populations
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Nuclear localization is correct and directly demonstrated.
    action: ACCEPT
    reason: Consistent with direct experimental evidence for nuclear accumulation of
      activated STATc.
    supported_by:
    - reference_id: PMID:12506009
      supporting_text: Dd-STATc becomes tyrosine phosphorylated, dimerises and
        accumulates in the nuclei of Dictyostelium cells exposed to DIF
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is correct; STATc is a latent cytoplasmic
      factor in the resting state.
    action: ACCEPT
    reason: Consistent with UniProt subcellular location and with the STAT
      cytoplasm-to-nucleus shuttling mechanism.
    supported_by:
    - reference_id: PMID:18305004
      supporting_text: STATc becomes tyrosine phosphorylated and accumulates in the
        nucleus when Dictyostelium cells are exposed to the prestalk cell inducer
        Differentiation inducing factor 1 (DIF-1), or are subjected to hyper-osmotic
        stress
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Correct general biological process for a transcription factor; subsumed
      by the more specific regulation of transcription by RNA polymerase II.
    action: ACCEPT
    reason: STATc regulates transcription of developmental and stress-response
      genes; the general term is correct.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: These data show that Dd-STATc functions as a transcriptional
        activator in a stress-response pathway
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: STATc is an effector of DIF-1 and stress signaling. Signal transduction
      is correct but very general.
    action: KEEP_AS_NON_CORE
    reason: A high-level parent process that is correct but uninformative relative to
      the more specific STAT signaling and stress-response annotations.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Activated STATc homodimerizes through reciprocal SH2-phosphotyrosine
      interactions. Identical protein binding is correct and part of the activation
      mechanism, though not the core molecular function.
    action: KEEP_AS_NON_CORE
    reason: STATc dimerizes upon tyrosine phosphorylation; homodimerization is a
      mechanistic feature rather than the primary evolved function.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc is tyrosine phosphorylated, dimerizes, and
        translocates to the nucleus when cells are exposed to DIF
- 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: STATc acts as a transcriptional repressor, restricting graded ecmA
      expression in prestalk cells. Negative regulation of transcription is well
      supported.
    action: ACCEPT
    reason: Independently supported by experimental evidence that STATc represses
      ecmA prestalk gene expression.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc also functions as a repressor, which directs graded
        expression of the ecmA gene in different prestalk cell populations
- term:
    id: GO:0006970
    label: response to osmotic stress
  evidence_type: IMP
  original_reference_id: PMID:22944283
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc is a well-established mediator of the transcriptional response to
      hyperosmotic (osmotic) stress in Dictyostelium.
    action: ACCEPT
    reason: STATc's role in the osmotic stress response is documented across multiple
      studies; the TacA study explicitly contrasts its own pathway with the
      well-known STATc stress response.
    supported_by:
    - reference_id: PMID:22944283
      supporting_text: TacA is involved in the stress response of D. discoideum
        during development in a separate pathway to the well-known stress response
        in Dictyostelium via STATc
- term:
    id: GO:0043157
    label: response to cation stress
  evidence_type: IMP
  original_reference_id: PMID:22944283
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc responds to several stresses; a specific role in cation stress is
      less clearly established and largely relates to Ca2+/calcineurin signaling
      studied in the TacA work. Retained as a non-core stress role.
    action: KEEP_AS_NON_CORE
    reason: STATc is a general stress-responsive factor; the cation-stress-specific
      role is not a core, independently defining function and overlaps with its
      broader osmotic/stress response.
    supported_by:
    - reference_id: PMID:22944283
      supporting_text: TacA is involved in the stress response of D. discoideum
        during development in a separate pathway to the well-known stress response
        in Dictyostelium via STATc
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:24587195
  qualifier: involved_in
  review:
    summary: STATc positively regulates expression of its target genes, including a
      positive feedback loop that upregulates STATc and STATc-dependent genes during
      the stress response.
    action: ACCEPT
    reason: Directly supported by mutant analyses showing STATc-dependent
      upregulation of stress-response genes.
    supported_by:
    - reference_id: PMID:24587195
      supporting_text: The STATc stress signalling pathway feeds back on itself by
        upregulating the expression of STATc and STATc-regulated genes
- term:
    id: GO:0080135
    label: regulation of cellular response to stress
  evidence_type: IMP
  original_reference_id: PMID:24267687
  qualifier: involved_in
  review:
    summary: STATc-dependent transcription contributes to the cellular stress
      response, including the timely dephosphorylation of the stress element AdcA.
    action: ACCEPT
    reason: Supported by evidence that STATc-dependent transcriptional activity is
      required for proper timing of the AdcA stress response.
    supported_by:
    - reference_id: PMID:24267687
      supporting_text: STATc-dependent transcriptional activity is involved for the
        timely dephosphorylation of AdcA in
- term:
    id: GO:1990782
    label: protein tyrosine kinase binding
  evidence_type: IPI
  original_reference_id: PMID:22699506
  qualifier: enables
  review:
    summary: STATc binds the tyrosine-kinase-like enzyme Pyk2 through its SH2 domain;
      the STATc-Pyk2 complex is formed constitutively and Pyk2 phosphorylates STATc
      on Tyr922. This is an informative molecular function central to STATc
      activation.
    action: ACCEPT
    reason: Directly demonstrated physical interaction between STATc and its
      activating tyrosine kinase Pyk2 in vitro and in vivo.
    supported_by:
    - reference_id: PMID:22699506
      supporting_text: the STATc-Pyk2 complex is formed constitutively by an
        interaction between the STATc SH2 domain and phosphotyrosine residues on
        Pyk2
    - reference_id: PMID:22699506
      supporting_text: Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes
        with STATc both in vitro and in vivo
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11336701
  qualifier: is_active_in
  review:
    summary: Direct evidence that activated STATc translocates to and acts in the
      nucleus. Core localization.
    action: ACCEPT
    reason: STATc translocates to the nucleus upon DIF-induced tyrosine
      phosphorylation and dimerization, where it exerts its transcription factor
      function.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc is tyrosine phosphorylated, dimerizes, and
        translocates to the nucleus when cells are exposed to DIF
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12506009
  qualifier: is_active_in
  review:
    summary: Direct evidence for nuclear accumulation of STATc; nuclear residence is
      controlled at the level of CRM1-dependent export.
    action: ACCEPT
    reason: STATc accumulates in the nucleus of DIF-exposed cells, with DIF
      inhibiting its nuclear export.
    supported_by:
    - reference_id: PMID:12506009
      supporting_text: Dd-STATc becomes tyrosine phosphorylated, dimerises and
        accumulates in the nuclei of Dictyostelium cells exposed to DIF
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:11336701
  qualifier: involved_in
  review:
    summary: STATc functions as a repressor that restricts graded ecmA expression to
      specific prestalk cell populations. Core function.
    action: ACCEPT
    reason: Mutant analysis demonstrates STATc acts as a transcriptional repressor of
      the ecmA prestalk marker.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc also functions as a repressor, which directs graded
        expression of the ecmA gene in different prestalk cell populations
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:11336701
  qualifier: located_in
  review:
    summary: STATc is present in the cytosol in the resting (latent) state before
      activation-induced nuclear translocation.
    action: ACCEPT
    reason: Consistent with the latent cytoplasmic nature of STATc prior to
      DIF/stress-induced nuclear accumulation.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc is tyrosine phosphorylated, dimerizes, and
        translocates to the nucleus when cells are exposed to DIF
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:12771188
  qualifier: located_in
  review:
    summary: STATc localizes to the nucleus; nuclear accumulation is a hallmark of
      its activation by stress and DIF.
    action: ACCEPT
    reason: Nuclear localization of activated STATc is consistent across multiple
      studies.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: hyperosmotic stress, heat shock and oxidative stress also
        activate Dd-STATc
- term:
    id: GO:0031288
    label: sorocarp morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:11336701
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc influences developmental timing and prestalk cell-type patterning
      during fruiting body (sorocarp) formation. This is a genuine but downstream
      developmental role rather than the core molecular function.
    action: KEEP_AS_NON_CORE
    reason: statC null cells show altered developmental timing and prestalk
      patterning, and colonies form aberrant fruiting bodies; this developmental
      phenotype is a consequence of STATc's transcription factor activity.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: which regulates the speed of early development and the timing
        of terminal differentiation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12220630
  qualifier: enables
  review:
    summary: Bare protein binding is uninformative. This IPI annotation derives from
      a study of OSBPa/culmination; the specific STATc interaction partner and its
      significance are not resolvable from the available record.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding provides no functional insight and per curation
      guidance should not be treated as a core function; retained as a non-core
      curated physical interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18305004
  qualifier: enables
  review:
    summary: This physical interaction is with the protein tyrosine phosphatase
      PTP3, which directly binds and dephosphorylates STATc. The bare protein
      binding term should be replaced by the more informative protein phosphatase
      binding.
    action: MODIFY
    reason: The interacting partner is identified as the phosphatase PTP3, so a more
      specific and informative molecular function is warranted instead of generic
      protein binding.
    proposed_replacement_terms:
    - id: GO:0019903
      label: protein phosphatase binding
    supported_by:
    - reference_id: PMID:18305004
      supporting_text: the protein tyrosine phosphatase PTP3 interacts directly with
        STATc
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25143406
  qualifier: enables
  review:
    summary: This interaction is with the tyrosine-kinase-like enzymes Pyk2/Pyk3,
      which bind the STATc SH2 domain and phosphorylate it. The bare protein binding
      term should be replaced by protein tyrosine kinase binding.
    action: MODIFY
    reason: The interacting partners are the activating TKL kinases Pyk2/Pyk3, so the
      more informative protein tyrosine kinase binding term is warranted instead of
      generic protein binding.
    proposed_replacement_terms:
    - id: GO:1990782
      label: protein tyrosine kinase binding
    supported_by:
    - reference_id: PMID:25143406
      supporting_text: The site(s) that are generated bind the SH2 domain of STATc,
        and then STATc becomes the target of further kinase action
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:11336701
  qualifier: enables
  review:
    summary: Activated STATc homodimerizes; identical protein binding is directly
      supported and is part of the activation mechanism.
    action: KEEP_AS_NON_CORE
    reason: STATc dimerizes upon tyrosine phosphorylation; homodimerization is a
      mechanistic step rather than the core evolved function.
    supported_by:
    - reference_id: PMID:11336701
      supporting_text: Dd-STATc is tyrosine phosphorylated, dimerizes, and
        translocates to the nucleus when cells are exposed to DIF
- term:
    id: GO:1903013
    label: response to differentiation-inducing factor 1
  evidence_type: HDA
  original_reference_id: PMID:25518940
  qualifier: involved_in
  review:
    summary: STATc is rapidly tyrosine-phosphorylated in response to DIF-1, as
      confirmed by global phosphoproteomics. Response to DIF-1 is a defining feature
      of STATc.
    action: ACCEPT
    reason: DIF-1-triggered activation of STATc is directly observed and is central
      to its role in prestalk cell differentiation.
    supported_by:
    - reference_id: PMID:25518940
      supporting_text: STATc is rapidly phosphorylated after exposure to DIF-1
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc (dstC) is developmentally expressed with a graded trajectory
      during multicellular development. This expression-based annotation supports a
      developmental role but is non-core relative to the molecular function.
    action: KEEP_AS_NON_CORE
    reason: An IEP (expression-pattern) inference; STATc's developmental involvement
      is genuine but is a downstream consequence of its transcription factor
      activity rather than a core function.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: dstC continued on a more graded trajectory
- term:
    id: GO:0006972
    label: hyperosmotic response
  evidence_type: IEP
  original_reference_id: PMID:17517120
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc is a key regulator of the transcriptional response to hyperosmotic
      shock, with roughly 20% of osmotically regulated genes dependent on STATc.
      Core stress-response role.
    action: ACCEPT
    reason: Genome-wide analysis shows STATc controls a substantial subset of the
      hyperosmotic stress transcriptional program.
    supported_by:
    - reference_id: PMID:17517120
      supporting_text: Approximately 20% of the differentially regulated genes were
        dependent on the presence of STATc
- term:
    id: GO:0006972
    label: hyperosmotic response
  evidence_type: IDA
  original_reference_id: PMID:12771188
  qualifier: involved_in
  review:
    summary: STATc is directly activated by hyperosmotic stress and functions as a
      transcriptional activator in the stress-response pathway. Core role.
    action: ACCEPT
    reason: Hyperosmotic stress directly activates STATc, which then drives
      stress-response gene expression (e.g. gapA, rtoA).
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: hyperosmotic stress, heat shock and oxidative stress also
        activate Dd-STATc
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IDA
  original_reference_id: PMID:12771188
  qualifier: involved_in
  review:
    summary: STATc is activated by oxidative stress, one of several stress stimuli
      that trigger its tyrosine phosphorylation and nuclear accumulation.
    action: KEEP_AS_NON_CORE
    reason: Oxidative stress is one of multiple stress inputs that activate STATc;
      retained as a genuine but non-core stress response alongside the dominant
      osmotic response.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: hyperosmotic stress, heat shock and oxidative stress also
        activate Dd-STATc
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IDA
  original_reference_id: PMID:12771188
  qualifier: involved_in
  review:
    summary: STATc is activated by heat shock, another of the stress stimuli that
      trigger its activation.
    action: KEEP_AS_NON_CORE
    reason: Heat shock is one of several stresses that activate STATc; a genuine but
      non-core stress response relative to the dominant osmotic response.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: hyperosmotic stress, heat shock and oxidative stress also
        activate Dd-STATc
- term:
    id: GO:0047484
    label: regulation of response to osmotic stress
  evidence_type: IMP
  original_reference_id: PMID:12771188
  qualifier: acts_upstream_of_or_within
  review:
    summary: STATc regulates the transcriptional output of the osmotic stress
      response, controlling stress-induced genes such as gapA and rtoA.
    action: ACCEPT
    reason: Mutant analysis shows osmotic-stress induction of STATc target genes is
      entirely dependent on STATc, placing it as a regulator of the osmotic stress
      response.
    supported_by:
    - reference_id: PMID:12771188
      supporting_text: Osmotic stress induction of gapA and rtoA is entirely
        dependent on Dd-STATc
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:11336701
  title: Tyrosine phosphorylation-independent nuclear translocation of a dictyostelium
    STAT in response to DIF signaling.
  findings:
  - statement: STATc (Dd-STATc) regulates the speed of early development and the
      timing of terminal differentiation and acts as a repressor directing graded
      ecmA expression among prestalk cell populations.
    supporting_text: Dd-STATc also functions as a repressor, which directs graded
      expression of the ecmA gene in different prestalk cell populations
  - statement: STATc is tyrosine phosphorylated, dimerizes and translocates to the
      nucleus upon DIF exposure, but SH2-phosphotyrosine interaction is not required
      for its DIF-induced nuclear translocation.
    supporting_text: Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates
      to the nucleus when cells are exposed to DIF
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational STATc paper; establishes its transcription factor and
      repressor roles and DIF-induced nuclear translocation. Cached record is
      abstract-only.
- id: PMID:12220630
  title: OSBPa, a predicted oxysterol binding protein of Dictyostelium, is required
    for regulated entry into culmination.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Study of OSBPa/osbA and culmination; abstract does not describe a
      STATc interaction, so the source of the generic STATc protein binding IPI is
      not resolvable from the cached abstract-only record.
- 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:
  - statement: DIF controls STATc nuclear accumulation by inhibiting its
      CRM1-dependent nuclear export.
    supporting_text: Dd-STATc becomes tyrosine phosphorylated, dimerises and
      accumulates in the nuclei of Dictyostelium cells exposed to DIF
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes that STATc nuclear accumulation is regulated at the
      level of nuclear export. Cached record is abstract-only.
- id: PMID:12771188
  title: A STAT-regulated, stress-induced signalling pathway in Dictyostelium.
  findings:
  - statement: Hyperosmotic stress, heat shock and oxidative stress activate STATc,
      which then functions as a transcriptional activator of stress-response genes.
    supporting_text: hyperosmotic stress, heat shock and oxidative stress also
      activate Dd-STATc
  - statement: Osmotic-stress induction of the target genes gapA and rtoA is entirely
      dependent on STATc.
    supporting_text: Osmotic stress induction of gapA and rtoA is entirely dependent
      on Dd-STATc
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes STATc as a stress-activated transcriptional activator
      controlling specific target genes.
- id: PMID:17517120
  title: STATc is a key regulator of the transcriptional response to hyperosmotic
    shock.
  findings:
  - statement: Approximately 20% of hyperosmotically regulated genes depend on STATc,
      making it a major regulator of the osmotic stress transcriptome.
    supporting_text: Approximately 20% of the differentially regulated genes were
      dependent on the presence of STATc
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Genome-wide (microarray) evidence for STATc's central role in the
      hyperosmotic transcriptional response; full text available.
- id: PMID:18305004
  title: Evidence that DIF-1 and hyper-osmotic stress activate a Dictyostelium STAT
    by inhibiting a specific protein tyrosine phosphatase.
  findings:
  - statement: The protein tyrosine phosphatase PTP3 directly binds STATc and
      dephosphorylates it; DIF-1 and osmotic stress activate STATc by inhibiting
      PTP3.
    supporting_text: the protein tyrosine phosphatase PTP3 interacts directly with
      STATc
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Identifies PTP3 as the STATc-inactivating phosphatase and the basis
      of the STATc protein binding IPI; full text available.
- id: PMID:22699506
  title: Identification of the kinase that activates a nonmetazoan STAT gives insights
    into the evolution of phosphotyrosine-SH2 domain signaling.
  findings:
  - statement: The tyrosine-kinase-like enzyme Pyk2 phosphorylates STATc on Tyr922
      and forms a constitutive complex with STATc via its SH2 domain.
    supporting_text: Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes with
      STATc both in vitro and in vivo
  - statement: Dictyostelium lacks metazoan tyrosine kinase orthologs; TKL enzymes
      substitute for JAK-like STATc activation.
    supporting_text: There are no orthologs of the animal tyrosine kinases, but there
      are very many tyrosine kinase-like kinases (TKLs)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Identifies Pyk2 as a STATc-activating kinase and supports use of a
      STAT (non-JAK) signaling term. Cached record is abstract-only.
- id: PMID:22944283
  title: The calcineurin dependent transcription factor TacA is involved in development
    and the stress response of Dictyostelium discoideum.
  findings:
  - statement: STATc mediates a well-known Dictyostelium stress response pathway,
      distinct from the calcineurin/TacA pathway.
    supporting_text: TacA is involved in the stress response of D. discoideum during
      development in a separate pathway to the well-known stress response in
      Dictyostelium via STATc
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Primarily a TacA study; corroborates STATc as the established
      stress-response pathway. Basis of the STATc osmotic/cation stress IMP
      annotations; cached record is abstract-only.
- id: PMID:24267687
  title: The arrestin-domain containing protein AdcA is a response element to stress.
  findings:
  - statement: STATc-dependent transcription is required for the timely
      dephosphorylation of the stress element AdcA.
    supporting_text: STATc-dependent transcriptional activity is involved for the
      timely dephosphorylation of AdcA in
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Links STATc-dependent transcription to regulation of the cellular
      stress response via AdcA; full text available.
- id: PMID:24587195
  title: Identification of the protein kinases Pyk3 and Phg2 as regulators of the
    STATc-mediated response to hyperosmolarity.
  findings:
  - statement: The STATc stress pathway includes a positive feedback loop
      upregulating STATc and STATc-regulated genes; Pyk3 and Phg2 modulate STATc
      phosphorylation.
    supporting_text: The STATc stress signalling pathway feeds back on itself by
      upregulating the expression of STATc and STATc-regulated genes
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes STATc-dependent positive regulation of gene expression
      and additional upstream kinases; full text available.
- id: PMID:25143406
  title: Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced
    STAT activation pathways.
  findings:
  - statement: Pyk2 and Pyk3 redundantly phosphorylate STATc; their autophosphorylation
      sites bind the STATc SH2 domain to enable further kinase action.
    supporting_text: The site(s) that are generated bind the SH2 domain of STATc, and
      then STATc becomes the target of further kinase action
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the Pyk2/Pyk3 kinase-STATc SH2 interaction; basis of the
      protein binding IPI; full text available.
- id: PMID:25518940
  title: The Dictyostelium prestalk inducer differentiation-inducing factor-1 (DIF-1)
    triggers unexpectedly complex global phosphorylation changes.
  findings:
  - statement: Global phosphoproteomics confirms STATc is rapidly phosphorylated
      after DIF-1 exposure.
    supporting_text: STATc is rapidly phosphorylated after exposure to DIF-1
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput phosphoproteomic support for STATc activation by
      DIF-1; full text available.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: dstC (statC) shows a graded developmental expression trajectory.
    supporting_text: dstC continued on a more graded trajectory
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Developmental transcriptome study; basis of the IEP sorocarp
      development annotation via expression pattern; full text available.
core_functions:
- description: STATc is a latent, signal-activated DNA-binding transcription factor.
    Upon DIF-1 or stress-induced tyrosine phosphorylation and dimerization it
    accumulates in the nucleus and regulates RNA polymerase II transcription of
    specific target genes, acting both as a repressor (restricting graded ecmA
    prestalk-gene expression) and as an activator (driving hyperosmotic
    stress-response genes such as gapA and rtoA).
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:11336701
    supporting_text: Dd-STATc also functions as a repressor, which directs graded
      expression of the ecmA gene in different prestalk cell populations
  - reference_id: PMID:12771188
    supporting_text: These data show that Dd-STATc functions as a transcriptional
      activator in a stress-response pathway
- description: Through its SH2 domain, STATc binds phosphotyrosine residues on the
    tyrosine-kinase-like enzymes Pyk2/Pyk3, which phosphorylate STATc on Tyr922 to
    activate it. This phosphotyrosine-SH2 interaction with its activating kinase is a
    core molecular feature of STATc signaling in the absence of a metazoan JAK.
  molecular_function:
    id: GO:1990782
    label: protein tyrosine kinase binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:22699506
    supporting_text: the STATc-Pyk2 complex is formed constitutively by an
      interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2
  - reference_id: PMID:25143406
    supporting_text: The site(s) that are generated bind the SH2 domain of STATc, and
      then STATc becomes the target of further kinase action

Gene Description

Existing Annotations Review

Core Functions

References

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