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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006631 fatty acid metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:15897458 This small protein binds C 14 -C 22 acyl-CoA esters and is involved in membrane mobilization PMID:17878305 acbA encodes an acyl-CoA binding protein, which is involved in sphingolipid metabolism and in developmental intercellular signaling |
| GO:0000062 fatty-acyl-CoA binding | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:15897458 AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio |
| GO:0000062 fatty-acyl-CoA binding | IEA GO_REF:0000002 | ACCEPT | 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. Reason: The InterPro domain-based inference of acyl-CoA binding matches the experimentally demonstrated core molecular function of AcbA. Supporting Evidence: PMID:15897458 AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio |
| GO:0004860 protein kinase inhibitor activity | IMP PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:15897458 ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation PMID:15897458 It appears that DhkA functions as a constitutive kinase in yeast that is inhibited upon ligand binding |
| GO:0016485 protein processing | IDA PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | ACCEPT | 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. 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. Supporting Evidence: PMID:15897458 AcbA is released from prespore cells and proteolytically cleaved by prestalk cells to generate SDF-2, which then triggers rapid sporulation of prespore cells PMID:20472692 During culmination, extracellular AcbA is rapidly cleaved by the TagC protease that is exposed on the surface of prestalk cells |
| GO:0030435 sporulation resulting in formation of a cellular spore | IMP PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | ACCEPT | 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. 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. Supporting Evidence: PMID:15897458 Mutants lacking AcbA sporulate well only when developed in chimeras with WT cells PMID:15897458 the peptide signal spore differentiation factor 2 (SDF-2) is processed from acyl-CoA binding protein, AcbA |
| GO:0031154 culmination involved in sorocarp development | IEP PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:25887420 The expression profile of acbA was consistent with its known housekeeping function during vegetative growth, and a signaling function in terminal spore differentiation |
| GO:0005938 cell cortex | IMP PMID:20472692 Unconventional secretion of AcbA in Dictyostelium discoideum... | ACCEPT | 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. Reason: Direct localization evidence places AcbA-containing vesicles at the cell cortex prior to secretion. This is a valid, experimentally supported location. Supporting Evidence: PMID:20472692 AcbA is localized in vesicles that accumulate in the cortex of prespore cells just prior to sporulation |
| GO:0031982 vesicle | IMP PMID:20472692 Unconventional secretion of AcbA in Dictyostelium discoideum... | ACCEPT | 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. Reason: Directly demonstrated localization of AcbA to secretory vesicles. This is a valid location annotation central to the unconventional secretion pathway. Supporting Evidence: PMID:20472692 a portion of AcbA is concentrated in membrane-bound vesicles that appear near the plasma membrane just prior to release |
| GO:0006974 DNA damage response | IMP PMID:17878305 Global transcriptional responses to cisplatin in Dictyosteli... | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:17878305 Mutations in five cisplatin response genes (sgkB, csbA, acbA, smlA, and atg8) resulted in altered drug sensitivity PMID:17878305 acbA encodes an acyl-CoA binding protein, which is involved in sphingolipid metabolism and in developmental intercellular signaling |
| GO:0000062 fatty-acyl-CoA binding | IDA PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | ACCEPT | 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. 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. Supporting Evidence: PMID:15897458 AcbA was able to bind C 14 -palmitoyl-CoA in a 1:1 molar ratio |
| GO:0005576 extracellular region | IMP PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | ACCEPT | 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. Reason: AcbA is released from prespore cells into the extracellular medium, where it is processed into SDF-2. Extracellular localization is directly supported. Supporting Evidence: PMID:15897458 AcbA is released from prespore cells and proteolytically cleaved by prestalk cells to generate SDF-2, which then triggers rapid sporulation of prespore cells PMID:20472692 The acyl coenzyme A (CoA) binding protein AcbA is secreted unconventionally and processed into spore differentiation factor 2 (SDF-2) |
| GO:0019901 protein kinase binding | IGI PMID:15897458 Peptide signaling during terminal differentiation of Dictyos... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:15897458 ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)