acbA

id: Q5FXM5
gene_symbol: acbA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: AcbA is a small (84-residue) acyl-CoA-binding protein of the conserved
  ACBP family in Dictyostelium discoideum. Like its animal and plant homologs it
  binds medium- to long-chain acyl-CoA esters (e.g. palmitoyl-CoA) with high affinity
  in a 1:1 stoichiometry, a housekeeping activity linked to intracellular acyl-CoA
  transport and lipid (including sphingolipid) metabolism. AcbA has a second,
  signaling role during multicellular development. It is unconventionally secreted
  from prespore cells via a vesicular, NSF- and GRASP-dependent pathway, and the
  extracellular protein is proteolytically cleaved by the prestalk surface protease
  TagC to release the peptide SDF-2 (spore differentiation factor 2). SDF-2 acts as
  a ligand for the membrane histidine kinase DhkA; ligand binding inhibits the
  DhkA-RdeA-RegA phosphorelay, raising cAMP and PKA activity and triggering rapid,
  synchronous encapsulation of prespore cells during culmination. Loss of AcbA
  abolishes SDF-2 activity and greatly reduces viable spore formation in a
  non-cell-autonomous manner.
existing_annotations:
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) inference that AcbA participates in fatty acid/lipid
      metabolism. This is consistent with the conserved acyl-CoA-binding activity of
      the ACBP family, which shuttles acyl-CoA esters and is implicated in membrane
      lipid and sphingolipid metabolism. It is a genuine but secondary role relative
      to the well-characterized developmental signaling function.
    action: KEEP_AS_NON_CORE
    reason: AcbA does bind acyl-CoA and is linked to lipid/sphingolipid metabolism,
      so the broad metabolic process term is defensible, but in Dictyostelium the
      gene is chiefly studied and functionally important as the precursor of the
      SDF-2 sporulation signal. This general metabolic term is kept as a non-core
      annotation.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: This small protein binds C 14 -C 22 acyl-CoA esters and is
        involved in membrane mobilization
    - reference_id: PMID:17878305
      supporting_text: acbA encodes an acyl-CoA binding protein, which is involved in
        sphingolipid metabolism and in developmental intercellular signaling
- term:
    id: GO:0000062
    label: fatty-acyl-CoA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of fatty-acyl-CoA binding, the defining and
      conserved molecular function of the ACBP family. This is directly confirmed
      experimentally for Dictyostelium AcbA and represents a core molecular function.
    action: ACCEPT
    reason: Acyl-CoA binding is the conserved, defining activity of the ACBP family
      and is experimentally validated for AcbA (palmitoyl-CoA binding, Kd ~0.35 uM,
      1:1 stoichiometry). The IBA inference is correct and core.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio
- term:
    id: GO:0000062
    label: fatty-acyl-CoA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic annotation of fatty-acyl-CoA binding from the
      Acyl-CoA-binding protein domain (IPR000582/IPR035984). Correct and consistent
      with direct experimental evidence.
    action: ACCEPT
    reason: The InterPro domain-based inference of acyl-CoA binding matches the
      experimentally demonstrated core molecular function of AcbA.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio
- term:
    id: GO:0004860
    label: protein kinase inhibitor activity
  evidence_type: IMP
  original_reference_id: PMID:15897458
  qualifier: enables
  review:
    summary: This annotation reflects the mechanism of the SDF-2 peptide derived from
      AcbA. SDF-2 binds the histidine kinase DhkA and inhibits its kinase activity
      and phosphorelay, as shown in a heterologous yeast assay. The activity is thus
      a real, experimentally supported property mediated by the SDF-2 cleavage
      product rather than a function of full-length acyl-CoA-bound AcbA.
    action: KEEP_AS_NON_CORE
    reason: Direct evidence (yeast reconstitution) shows SDF-2 ligand binding
      inhibits the DhkA histidine kinase. This is the mechanistic basis of the
      sporulation signal, but as an inhibitor-of-a-specific-receptor-kinase activity
      it is a downstream property of the processed peptide; it is kept as non-core
      relative to the acyl-CoA-binding molecular function.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: ligand binding to the SDF-2 receptor histidine kinase, DhkA,
        inhibits phosphorelay, which can account for its ability to induce rapid
        sporulation
    - reference_id: PMID:15897458
      supporting_text: It appears that DhkA functions as a constitutive kinase in
        yeast that is inhibited upon ligand binding
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IDA
  original_reference_id: PMID:15897458
  qualifier: involved_in
  review:
    summary: AcbA is the precursor that is proteolytically processed to generate the
      active SDF-2 peptide. Trypsin (in vitro) and the TagC protease (in vivo) cleave
      AcbA to release SDF-2, which triggers sporulation. This precursor-processing
      event is central to AcbA biology and is directly demonstrated.
    action: ACCEPT
    reason: Direct experimental evidence shows AcbA is proteolytically cleaved to
      produce SDF-2. Processing of the AcbA precursor into its bioactive peptide is a
      core part of its signaling function.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: AcbA is released from prespore cells and proteolytically
        cleaved by prestalk cells to generate SDF-2, which then triggers rapid
        sporulation of prespore cells
    - reference_id: PMID:20472692
      supporting_text: During culmination, extracellular AcbA is rapidly cleaved by
        the TagC protease that is exposed on the surface of prestalk cells
- term:
    id: GO:0030435
    label: sporulation resulting in formation of a cellular spore
  evidence_type: IMP
  original_reference_id: PMID:15897458
  qualifier: involved_in
  review:
    summary: acbA disruption abolishes SDF-2 activity and reduces viable spore
      formation by ~90 percent; the defect is non-cell-autonomous and rescued in
      chimeras with wild-type cells, consistent with loss of an intercellular
      sporulation signal. This is a core developmental role.
    action: ACCEPT
    reason: Loss-of-function directly demonstrates that AcbA (via SDF-2) is required
      for efficient spore formation. This is a well-supported core biological process.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: Mutants lacking AcbA sporulate well only when developed in
        chimeras with WT cells
    - reference_id: PMID:15897458
      supporting_text: the peptide signal spore differentiation factor 2 (SDF-2) is
        processed from acyl-CoA binding protein, AcbA
- 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) inference from a developmental RNA-seq time
      course. acbA transcript dynamics are consistent with a housekeeping role in
      vegetative growth and a signaling role in terminal (culmination-stage) spore
      differentiation. The evidence is correlative expression timing rather than a
      direct functional assay of culmination.
    action: KEEP_AS_NON_CORE
    reason: SDF-2 signaling does act during culmination, so the term is biologically
      plausible, but the supporting evidence here is only transcript-timing
      correlation. Kept as a non-core annotation; the core sporulation role is
      captured by the IMP annotation.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: The expression profile of acbA was consistent with its known
        housekeeping function during vegetative growth, and a signaling function in
        terminal spore differentiation
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IMP
  original_reference_id: PMID:20472692
  qualifier: located_in
  review:
    summary: AcbA accumulates in membrane-bound vesicles at the cortex of prespore
      cells just prior to sporulation, as shown by immunofluorescence; these cortical
      vesicles are secretion intermediates that disappear upon stimulated release.
    action: ACCEPT
    reason: Direct localization evidence places AcbA-containing vesicles at the cell
      cortex prior to secretion. This is a valid, experimentally supported location.
    supported_by:
    - reference_id: PMID:20472692
      supporting_text: AcbA is localized in vesicles that accumulate in the cortex of
        prespore cells just prior to sporulation
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IMP
  original_reference_id: PMID:20472692
  qualifier: located_in
  review:
    summary: A portion of AcbA is concentrated in membrane-bound vesicles that serve
      as intermediates in its unconventional secretion; acyl-CoA binding is required
      for inclusion of AcbA into these vesicles.
    action: ACCEPT
    reason: Directly demonstrated localization of AcbA to secretory vesicles. This is
      a valid location annotation central to the unconventional secretion pathway.
    supported_by:
    - reference_id: PMID:20472692
      supporting_text: a portion of AcbA is concentrated in membrane-bound vesicles
        that appear near the plasma membrane just prior to release
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IMP
  original_reference_id: PMID:17878305
  qualifier: acts_upstream_of_or_within
  review:
    summary: This annotation derives from a cisplatin-sensitivity screen in which an
      acbA mutant showed altered drug sensitivity. The paper attributes the effect to
      AcbA's role in sphingolipid metabolism (a known modulator of cisplatin
      sensitivity), not to a direct role in the DNA damage response. Framing the
      altered cisplatin sensitivity as DNA damage response over-interprets the
      evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The mutant phenotype is altered cisplatin sensitivity, mechanistically
      linked to sphingolipid metabolism rather than to a bona fide DNA damage
      response. The term is not flatly wrong (cisplatin is a DNA-damaging agent) but
      it over-annotates AcbA's role, which is metabolic/lipid-signaling.
    supported_by:
    - reference_id: PMID:17878305
      supporting_text: Mutations in five cisplatin response genes (sgkB, csbA, acbA,
        smlA, and atg8) resulted in altered drug sensitivity
    - reference_id: PMID:17878305
      supporting_text: acbA encodes an acyl-CoA binding protein, which is involved in
        sphingolipid metabolism and in developmental intercellular signaling
- term:
    id: GO:0000062
    label: fatty-acyl-CoA binding
  evidence_type: IDA
  original_reference_id: PMID:15897458
  qualifier: enables
  review:
    summary: Direct biochemical evidence that recombinant AcbA binds palmitoyl-CoA in
      a 1:1 molar ratio with an apparent Kd of ~0.35 uM, comparable to mammalian and
      plant ACBP homologs. This is the core, defining molecular function.
    action: ACCEPT
    reason: High-quality direct binding assay establishes fatty-acyl-CoA binding as
      the core molecular function of AcbA. Trypsin treatment abolished binding,
      confirming the intact ACB domain is required.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IMP
  original_reference_id: PMID:15897458
  qualifier: located_in
  review:
    summary: AcbA is unconventionally secreted and reaches the extracellular space,
      where the intact protein is cleaved by the prestalk surface protease TagC to
      generate SDF-2. Extracellular localization is integral to its signaling role.
    action: ACCEPT
    reason: AcbA is released from prespore cells into the extracellular medium, where
      it is processed into SDF-2. Extracellular localization is directly supported.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: AcbA is released from prespore cells and proteolytically
        cleaved by prestalk cells to generate SDF-2, which then triggers rapid
        sporulation of prespore cells
    - reference_id: PMID:20472692
      supporting_text: The acyl coenzyme A (CoA) binding protein AcbA is secreted
        unconventionally and processed into spore differentiation factor 2 (SDF-2)
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IGI
  original_reference_id: PMID:15897458
  qualifier: enables
  review:
    summary: Genetic-interaction-based annotation (with DhkA, UniProtKB:Q54U87)
      reflecting that the AcbA-derived SDF-2 peptide acts as a ligand for the
      membrane histidine kinase DhkA. The interaction is functionally documented, but
      protein kinase binding is a low-information term; the informative activity is
      captured by the protein kinase inhibitor / receptor-ligand relationship.
    action: KEEP_AS_NON_CORE
    reason: SDF-2 binds the DhkA histidine kinase to trigger sporulation, so binding
      to a protein kinase is supported. The bare protein kinase binding term is
      uninformative on its own and is retained as non-core; the mechanistic effect
      (kinase inhibition) is annotated separately.
    supported_by:
    - reference_id: PMID:15897458
      supporting_text: ligand binding to the SDF-2 receptor histidine kinase, DhkA,
        inhibits phosphorelay, which can account for its ability to induce rapid
        sporulation
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: PMID:15897458
  title: Peptide signaling during terminal differentiation of Dictyostelium.
  findings:
  - statement: The peptide sporulation signal SDF-2 is generated by proteolytic
      processing of the acyl-CoA-binding protein AcbA.
    supporting_text: the peptide signal spore differentiation factor 2 (SDF-2) is
      processed from acyl-CoA binding protein, AcbA
  - statement: Recombinant AcbA binds palmitoyl-CoA in a 1:1 molar ratio.
    supporting_text: AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio
  - statement: AcbA-null mutants fail to make SDF-2 and are rescued in chimeras with
      wild-type cells, indicating a non-cell-autonomous intercellular signal.
    supporting_text: Mutants lacking AcbA sporulate well only when developed in
      chimeras with WT cells
  - statement: SDF-2 acts as a ligand for the histidine kinase DhkA, inhibiting its
      phosphorelay to induce rapid sporulation.
    supporting_text: ligand binding to the SDF-2 receptor histidine kinase, DhkA,
      inhibits phosphorelay, which can account for its ability to induce rapid
      sporulation
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary paper establishing AcbA as the SDF-2 precursor, its
      acyl-CoA binding, the acbA-null sporulation defect, and the DhkA kinase-
      inhibition mechanism. Full text available and quotes verified against it.
- id: PMID:17878305
  title: Global transcriptional responses to cisplatin in Dictyostelium discoideum
    identify potential drug targets.
  findings:
  - statement: An acbA mutant shows altered cisplatin sensitivity, linking AcbA to
      sphingolipid metabolism-dependent drug response rather than to a direct DNA
      damage response.
    supporting_text: Mutations in five cisplatin response genes (sgkB, csbA, acbA,
      smlA, and atg8) resulted in altered drug sensitivity
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Cisplatin-sensitivity screen; the acbA phenotype is attributed to
      sphingolipid metabolism, supporting a metabolic role but not a bona fide DNA
      damage response annotation.
- id: PMID:20472692
  title: Unconventional secretion of AcbA in Dictyostelium discoideum through a vesicular
    intermediate.
  findings:
  - statement: AcbA is unconventionally secreted and processed into SDF-2.
    supporting_text: The acyl coenzyme A (CoA) binding protein AcbA is secreted
      unconventionally and processed into spore differentiation factor 2 (SDF-2)
  - statement: AcbA localizes to cortical membrane-bound vesicles in prespore cells
      that act as secretion intermediates.
    supporting_text: AcbA is localized in vesicles that accumulate in the cortex of
      prespore cells just prior to sporulation
  - statement: Extracellular AcbA is cleaved by the prestalk surface protease TagC
      during culmination.
    supporting_text: During culmination, extracellular AcbA is rapidly cleaved by the
      TagC protease that is exposed on the surface of prestalk cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the vesicular, NSF/GRASP-dependent unconventional
      secretion route and cortical vesicle localization of AcbA; quotes verified.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: acbA expression dynamics fit a vegetative housekeeping role plus a
      late-development spore-differentiation signaling role.
    supporting_text: The expression profile of acbA was consistent with its known
      housekeeping function during vegetative growth, and a signaling function in
      terminal spore differentiation
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Developmental RNA-seq time course; provides expression-pattern
      (IEP) support consistent with AcbA's dual metabolic/signaling roles.
core_functions:
- description: AcbA binds medium- to long-chain fatty-acyl-CoA esters (e.g.
    palmitoyl-CoA) with high affinity and 1:1 stoichiometry through its conserved ACB
    domain, functioning in intracellular acyl-CoA transport/sequestration and lipid
    (including sphingolipid) metabolism. This is the conserved, defining molecular
    function of the ACBP family.
  molecular_function:
    id: GO:0000062
    label: fatty-acyl-CoA binding
  directly_involved_in:
  - id: GO:0006631
    label: fatty acid metabolic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:15897458
    supporting_text: AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio
  - reference_id: PMID:15897458
    supporting_text: This small protein binds C 14 -C 22 acyl-CoA esters and is
      involved in membrane mobilization
- description: AcbA serves as the precursor of the intercellular sporulation signal
    SDF-2. The protein is unconventionally secreted from prespore cells and cleaved
    extracellularly by the prestalk protease TagC to release SDF-2, which acts as a
    secreted peptide ligand for the histidine kinase DhkA, inhibiting its
    DhkA-RdeA-RegA phosphorelay, elevating PKA activity and triggering rapid,
    synchronous encapsulation of prespore cells during culmination. The molecular
    function of the processed signal is best captured as receptor ligand activity
    (SDF-2 binding DhkA); the GOA-annotated protein-kinase-inhibitor activity
    describes the downstream consequence and is retained non-core.
  molecular_function:
    id: GO:0048018
    label: receptor ligand activity
  directly_involved_in:
  - id: GO:0030435
    label: sporulation resulting in formation of a cellular spore
  - id: GO:0016485
    label: protein processing
  locations:
  - id: GO:0005576
    label: extracellular region
  supported_by:
  - reference_id: PMID:15897458
    supporting_text: ligand binding to the SDF-2 receptor histidine kinase, DhkA,
      inhibits phosphorelay, which can account for its ability to induce rapid
      sporulation
  - reference_id: PMID:15897458
    supporting_text: AcbA is released from prespore cells and proteolytically cleaved
      by prestalk cells to generate SDF-2, which then triggers rapid sporulation of
      prespore cells