ecmA

id: Q54YG2
gene_symbol: ecmA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: EcmA (also known as ST430 or Dd63) is a large, secreted, cysteine-rich
  extracellular matrix glycoprotein of the social amoeba Dictyostelium discoideum.
  The mature protein is dominated by dozens of tandem Cys-rich repeats
  (the Dictyostelium "CT"/Dicty_CTDC repeat) and carries a cleaved N-terminal signal
  peptide and numerous N-glycosylation sites, consistent with secretion into the
  extracellular space. EcmA is deposited as a structural constituent of the developmental
  extracellular matrix, contributing to the slime sheath that surrounds the migrating
  slug (pseudoplasmodium) and to the cellulose-rich stalk-tube matrix formed during
  culmination. Its expression is essentially confined to prestalk cells, chiefly the
  anterior-most prestalk zone, and is induced by the chlorinated stalk morphogen DIF-1
  (differentiation-inducing factor). Because of this tightly regulated, cell-type-restricted
  expression, ecmA is a classic molecular marker for prestalk cell differentiation and
  is widely used (often as an ecmA/ecmAO promoter reporter) to follow prestalk fate,
  cell sorting, and morphogenesis in the Dictyostelium developmental cycle.
existing_annotations:
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetically inferred localization to the extracellular matrix. This
      is consistent with direct proteomic and experimental evidence that EcmA is a
      structural component of the Dictyostelium developmental ECM (slime sheath / stalk
      tube), and represents a core aspect of the protein.
    action: ACCEPT
    reason: EcmA is a secreted extracellular-matrix protein; ECM localization is directly
      supported by proteomic profiling of the slime sheath, so the IBA inference is
      corroborated by primary evidence.
    supported_by:
    - reference_id: PMID:26152465
      supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
        discoidin II)
- term:
    id: GO:0099120
    label: socially cooperative development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference that EcmA participates in the multicellular (social)
      developmental program. EcmA is indeed a prestalk-expressed ECM protein deposited
      during slug and fruiting-body morphogenesis, so involvement in cooperative development
      is reasonable, but this is a very general process term that does not capture the
      protein's specific structural role.
    action: KEEP_AS_NON_CORE
    reason: EcmA contributes to development only as a downstream structural ECM constituent
      of prestalk-derived matrix; the broad "socially cooperative development" term is
      correct in spirit but too general to represent the core molecular function.
    supported_by:
    - reference_id: PMID:41057014
      supporting_text: During multicellular development, the ecmA and ecmB genes encode
        extracellular matrix proteins, which are mainly expressed in the most anterior
        prestalk cells of slugs and can regulate the morphogenesis of Dictyostelium
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation from the UniProt "Secreted" subcellular location.
      EcmA has a cleaved signal peptide and is a bona fide secreted ECM protein, so
      extracellular localization is correct.
    action: ACCEPT
    reason: The UniProt record documents a signal peptide and secreted location, and
      the protein is experimentally recovered from the extracellular slime sheath;
      extracellular-region localization is well supported.
    supported_by:
    - reference_id: PMID:26152465
      supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
        discoidin II)
- term:
    id: GO:0009642
    label: response to light intensity
  evidence_type: HEP
  original_reference_id: PMID:41057014
  qualifier: acts_upstream_of_or_within
  review:
    summary: High-throughput expression (HEP) annotation reflecting that ecmA transcript
      levels increase upon light exposure during the unicellular-to-multicellular transition.
      This captures the transcriptional responsiveness of the prestalk marker to light,
      not a mechanistic role for the EcmA protein in phototransduction.
    action: KEEP_AS_NON_CORE
    reason: The annotation is based on ecmA being upregulated by light, i.e. it is a
      downstream transcriptional readout of prestalk differentiation, which is known
      to be light-sensitive. EcmA is a structural ECM protein and does not itself mediate
      the light response, so this is retained as a non-core, expression-based association.
    supported_by:
    - reference_id: PMID:41057014
      supporting_text: Our findings revealed that both of ecmA and ecmB genes are upregulated
        when exposed to light
- term:
    id: GO:0099120
    label: socially cooperative development
  evidence_type: IDA
  original_reference_id: PMID:38561423
  qualifier: involved_in
  review:
    summary: Direct assay annotation from a study of prestalk-like cell positioning
      during Dictyostelium development, in which ecmA (as an ecmAO reporter) was used
      as the prestalk cell-type marker and its expression tracked differentiation and
      de-differentiation. The annotation places EcmA within the cooperative developmental
      program.
    action: KEEP_AS_NON_CORE
    reason: Per curation policy this experimental (IDA) annotation is retained. However,
      EcmA participates in cooperative development as a downstream, prestalk-restricted
      structural ECM constituent and differentiation marker, so the very general process
      term is best marked non-core rather than as the protein's core function.
    supported_by:
    - reference_id: PMID:38561423
      supporting_text: Refed (RF) cells harbored prespore (pspA-GFP, green) and prestalk
        (ecmAO-RFP, magenta) markers.
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:26152465
  qualifier: located_in
  review:
    summary: High-throughput direct-assay (proteomic) localization of EcmA to the Dictyostelium
      extracellular matrix (slime sheath). LC/MS/MS of slug ECM recovered EcmA among
      the expected structural components, providing strong evidence for ECM localization.
    action: ACCEPT
    reason: EcmA was directly identified by mass spectrometry in the purified slug ECM
      (slime sheath), confirming that the extracellular matrix is its site of deposition.
      This is a core localization for the protein.
    supported_by:
    - reference_id: PMID:26152465
      supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
        discoidin II)
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: acts_upstream_of_or_within
  review:
    summary: Expression-pattern (IEP) annotation. In the developmental transcriptome,
      ecmA is induced during late development and upregulated dramatically around culmination
      (16-18 h), coincident with stalk/fruiting-body formation, consistent with a role
      for the prestalk ECM protein during culmination.
    action: KEEP_AS_NON_CORE
    reason: The annotation rests on ecmA's culmination-phase expression as a prestalk
      gene rather than on a demonstrated mechanistic requirement of the EcmA protein
      for culmination. EcmA contributes to stalk-tube matrix formation, so involvement
      in culmination is plausible but retained as non-core given the expression-based
      evidence.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: Expression of the prestalk genes ecmA, ecmB and ecmF ([19,36],
        could be detected as early as 12 h, but were up-regulated more dramatically
        between 16 h and 18 h
- term:
    id: GO:1902168
    label: response to catechin
  evidence_type: IDA
  original_reference_id: PMID:23516620
  qualifier: involved_in
  review:
    summary: Annotation derived from a study showing that the green-tea catechin EGCG
      blocks Dictyostelium development, with near-complete loss of prestalk-specific
      ecmA (and prespore pspA) expression in treated cells. This reflects that ecmA
      expression is suppressed when development is blocked by catechin, not that EcmA
      has a dedicated function in a catechin-response pathway.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence is that ecmA transcription is downregulated as a nonspecific
      consequence of EGCG-induced developmental arrest (a general differentiation-marker
      readout), not that EcmA functions in "response to catechin." Treating this as a
      biological function of the protein over-interprets a downstream transcriptional
      effect.
    supported_by:
    - reference_id: PMID:23516620
      supporting_text: we detected almost no expression of prespore specific pspA and
        prestalk specific ecmA genes in EGCG treated cells at 10 to 12 h into starvation
- term:
    id: GO:0005198
    label: structural molecule activity
  evidence_type: TAS
  original_reference_id: PMID:8016318
  qualifier: enables
  review:
    summary: Traceable-author annotation assigning EcmA a structural molecule activity.
      As a secreted, Cys-rich repeat glycoprotein deposited in the slime sheath and
      stalk-tube matrix, EcmA acts as a structural constituent of the developmental
      ECM; this is the best representation of its core molecular function.
    action: ACCEPT
    reason: EcmA is an abundant structural ECM protein with no known catalytic activity;
      structural molecule activity correctly captures its core molecular role as a
      matrix building block.
    supported_by:
    - reference_id: PMID:41057014
      supporting_text: During multicellular development, the ecmA and ecmB genes encode
        extracellular matrix proteins, which are mainly expressed in the most anterior
        prestalk cells of slugs and can regulate the morphogenesis of Dictyostelium
- term:
    id: GO:0030198
    label: extracellular matrix organization
  evidence_type: TAS
  original_reference_id: PMID:8016318
  qualifier: acts_upstream_of_or_within
  review:
    summary: Traceable-author annotation that EcmA participates in organizing the extracellular
      matrix. As a structural constituent deposited into the slime sheath and stalk
      tube, EcmA contributes to assembly/organization of the developmental ECM.
    action: ACCEPT
    reason: EcmA is deposited into and helps constitute the developmental ECM whose
      assembly accompanies slug and stalk morphogenesis; extracellular matrix organization
      is an appropriate biological-process annotation for a core matrix component.
    supported_by:
    - reference_id: PMID:41057014
      supporting_text: During multicellular development, the ecmA and ecmB genes encode
        extracellular matrix proteins, which are mainly expressed in the most anterior
        prestalk cells of slugs and can regulate the morphogenesis of Dictyostelium
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: TAS
  original_reference_id: PMID:8016318
  qualifier: located_in
  review:
    summary: Traceable-author localization of EcmA to the extracellular matrix, consistent
      with all other evidence (proteomic recovery from the slime sheath, secreted status).
      This is a core localization.
    action: ACCEPT
    reason: ECM localization of EcmA is corroborated by direct proteomic evidence and
      its secreted nature; the TAS annotation is accurate.
    supported_by:
    - reference_id: PMID:26152465
      supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
        discoidin II)
references:
- 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: PMID:23516620
  title: The green tea catechin epigallocatechin gallate (EGCG) blocks cell motility,
    chemotaxis and development in Dictyostelium discoideum.
  findings:
  - statement: EGCG treatment abolishes expression of the prestalk marker ecmA (and
      prespore pspA), reflecting a block of Dictyostelium differentiation rather than
      a specific catechin-response function of EcmA.
    supporting_text: we detected almost no expression of prespore specific pspA and
      prestalk specific ecmA genes in EGCG treated cells at 10 to 12 h into starvation
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Citation verified against cached full text; supports that ecmA expression
      is suppressed under EGCG-induced developmental arrest. Does not establish a
      dedicated EcmA role in catechin response, hence the over-annotation call.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: ecmA is a prestalk gene strongly upregulated during late development
      (16-18 h), coincident with culmination and fruiting-body formation.
    supporting_text: Expression of the prestalk genes ecmA, ecmB and ecmF ([19,36],
      could be detected as early as 12 h, but were up-regulated more dramatically
      between 16 h and 18 h
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached full text confirms culmination-phase induction of ecmA;
      supports the IEP culmination annotation as an expression-based association.
- id: PMID:26152465
  title: Proteomic profiling of the extracellular matrix (slime sheath) of Dictyostelium
    discoideum.
  findings:
  - statement: LC/MS/MS of purified slug extracellular matrix (slime sheath) directly
      identified EcmA as an expected structural ECM component.
    supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
      discoidin II)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Directly demonstrates EcmA presence in the developmental ECM proteome,
      anchoring the extracellular-matrix localization annotations.
- id: PMID:38561423
  title: Prestalk-like positioning of de-differentiated cells in the social amoeba
    Dictyostelium discoideum.
  findings:
  - statement: ecmA (via an ecmAO reporter) is used as the prestalk cell-type marker
      to track differentiation, sorting, and de-differentiation during development.
    supporting_text: Refed (RF) cells harbored prespore (pspA-GFP, green) and prestalk
      (ecmAO-RFP, magenta) markers.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Confirms ecmA's use as a prestalk marker within the cooperative
      developmental program; supports the developmental (non-core) annotation.
- id: PMID:41057014
  title: Transcriptomic and metabolomic insights into light-mediated unicellular-to-multicellular
    transition in Dictyostelium discoideum.
  findings:
  - statement: ecmA and ecmB encode extracellular matrix proteins expressed mainly
      in anterior prestalk cells and are transcriptionally upregulated by light.
    supporting_text: During multicellular development, the ecmA and ecmB genes encode
      extracellular matrix proteins, which are mainly expressed in the most anterior
      prestalk cells of slugs and can regulate the morphogenesis of Dictyostelium
  - statement: Light exposure upregulates ecmA (and ecmB) transcript levels.
    supporting_text: Our findings revealed that both of ecmA and ecmB genes are upregulated
      when exposed to light
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached full text describes EcmA as a prestalk ECM protein and
      documents its light-induced upregulation; supports both the structural/ECM
      framing and the light-response (non-core) annotation.
- id: PMID:8016318
  title: Prestalk cell-differentiation and movement during the morphogenesis of Dictyostelium
    discoideum.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: Abstract-only review (full_text_available:false in cache); cited by
      dictyBase as TAS for EcmA structural/ECM annotations, which are independently
      corroborated by proteomic evidence. Supporting quotes for these annotations are
      drawn from other cached full-text sources.
core_functions:
- description: EcmA is a secreted, cysteine-rich repeat glycoprotein that acts as a
    structural constituent of the Dictyostelium developmental extracellular matrix.
    Deposited by prestalk cells into the slime sheath surrounding the slug and into
    the stalk-tube matrix during culmination, it contributes to the mechanical integrity
    and organization of the ECM that supports multicellular morphogenesis.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
  locations:
  - id: GO:0031012
    label: extracellular matrix
  - id: GO:0005576
    label: extracellular region
  directly_involved_in:
  - id: GO:0030198
    label: extracellular matrix organization
  supported_by:
  - reference_id: PMID:26152465
    supporting_text: identified numerous expected (e.g. EcmA, EcmD, discoidin I,
      discoidin II)
  - reference_id: PMID:41057014
    supporting_text: During multicellular development, the ecmA and ecmB genes encode
      extracellular matrix proteins, which are mainly expressed in the most anterior
      prestalk cells of slugs and can regulate the morphogenesis of Dictyostelium