acaA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004016 adenylate cyclase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of adenylate cyclase activity is correct and strongly corroborated by direct enzymatic assays on ACA. This is the core molecular function of the gene product. Reason: ACA is a bona fide adenylyl cyclase (EC 4.6.1.1) responsible for cAMP synthesis during aggregation; the IBA inference agrees with multiple direct experimental annotations. Supporting Evidence: PMID:1348970 has little detectable adenylyl cyclase activity and fails to aggregate
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: ACA is a multi-pass plasma membrane enzyme and functions at the plasma membrane, as confirmed by direct biochemical fractionation. Reason: ACA is an integral plasma membrane protein enriched in plasma membrane microdomains; the phylogenetic localization inference is well supported. Supporting Evidence: PMID:9168471 adenylate cyclase (ACA), were specifically localized in these structures
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: ACA is activated downstream of the cAMP receptor cAR1 via heterotrimeric G proteins, placing it centrally in this signaling pathway. Reason: ACA activation is receptor- and G protein-regulated and it synthesizes the cAMP that relays the chemotactic signal; this is a core biological process. Supporting Evidence: PMID:16267269 which synthesizes the chemoattractant cAMP, is essential to relay the signal to
GO:0006171 cAMP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: ACA synthesizes cAMP; cAMP biosynthetic process is a core biological process for this enzyme. Reason: Directly supported by the catalytic activity (ATP to cAMP) and by loss of cAMP synthesis in aca- mutants. Supporting Evidence: PMID:1348970 has little detectable adenylyl cyclase activity and fails to aggregate
GO:0001931 uropod	IEA GO_REF:0000044	ACCEPT	Summary: In polarized cells ACA becomes highly enriched at the uropod; this localization is directly documented. Reason: UniProt subcellular-location mapping to uropod is confirmed by experimental localization of ACA to the uropod of aggregating cells. Supporting Evidence: PMID:26315268 The localization of adenylyl cyclase A (ACA) to uropod of cells is required for the stream formation
GO:0004016 adenylate cyclase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated RHEA/EC mapping to adenylate cyclase activity, consistent with the experimentally established catalytic activity. Reason: EC 4.6.1.1 mapping is correct; ACA catalyzes ATP to 3',5'-cyclic AMP. Supporting Evidence: PMID:1348970 has little detectable adenylyl cyclase activity and fails to aggregate
GO:0009190 cyclic nucleotide biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but general parent of cAMP biosynthetic process. The specific child (cAMP biosynthetic process) better captures ACA function. Reason: InterPro2GO inference is accurate but non-specific; the more informative term cAMP biosynthetic process is already annotated.
GO:0016020 membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Correct but general. ACA is a membrane protein, but plasma membrane and uropod membrane are the informative, well-supported locations. Reason: Generic membrane is subsumed by the more specific plasma membrane and uropod membrane annotations.
GO:0016849 phosphorus-oxygen lyase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but general parent of adenylate cyclase activity. Adenylyl cyclases are phosphorus-oxygen lyases (EC 4.6.1.-), but the specific term is more informative. Reason: InterPro2GO parent-level MF term; the specific child adenylate cyclase activity (GO:0004016) is the informative function.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: General signaling term. ACA does participate in signal transduction (cAMP relay) but more specific pathway terms are annotated. Reason: Broad InterPro2GO term subsumed by the specific adenylate cyclase-activating GPCR signaling annotations.
GO:0060359 response to ammonium ion	IDA PMID:41406008 Extracellular adenosine deamination primes tip organizer dev...	KEEP AS NON CORE	Summary: ACA-derived cAMP feeds a cascade in which extracellular cAMP is converted to adenosine and then to ammonia during tip organizer development. This is a peripheral, developmentally contextual role. Reason: ACA supplies the cAMP upstream of the adenosine/ammonia cascade; the link is indirect and not a core function. Supporting Evidence: PMID:41406008 the consecutive transformation of extracellular cAMP to adenosine, and adenosine to ammonia
GO:1903561 extracellular vesicle	IDA PMID:19047467 Collective cell migration requires vesicular trafficking for...	ACCEPT	Summary: Migrating cells shed ACA-containing vesicles, consistent with an extracellular-vesicle localization documented by direct imaging. Reason: ACA is found on secreted vesicles that relay the chemoattractant to trailing cells, a well-supported part of the ACA trafficking story. Supporting Evidence: PMID:19047467 leave behind ACA-containing vesicles
GO:0046686 response to cadmium ion	HEP PMID:39874878 Exploring the mechanisms of cadmium tolerance and bioaccumul...	MARK AS OVER ANNOTATED	Summary: This annotation derives from a high-throughput transcriptomic study of cadmium tolerance in which acaA appears among differentially expressed genes. It reflects a general stress transcriptional response, not a specific ACA function. Reason: HEP evidence from a genome-wide expression screen; there is no indication that ACA has a dedicated role in cadmium response beyond being a regulated developmental gene. Supporting Evidence: PMID:39874878 key genes involved in metal transport, detoxification, and stress response
GO:0004016 adenylate cyclase activity	IDA PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	ACCEPT	Summary: Direct assay of the adenylyl cyclase activation pathway supports ACA adenylate cyclase activity in the context of Ras/Rap1 signaling. Reason: Experimental support for ACA catalytic activity; core molecular function. Supporting Evidence: PMID:18180289 the adenylyl cyclase activation pathway in the rasC
GO:1902351 response to imidacloprid	IEP PMID:36716868 The neonicotinoid insecticide imidacloprid has unexpected ef...	MARK AS OVER ANNOTATED	Summary: Derived from a transcriptome study of imidacloprid effects on Dictyostelium; acaA appears as an expression-regulated gene. This is a general environmental stress response rather than a specific ACA function. Reason: IEP annotation from a broad toxicant-response expression profile; not indicative of a dedicated ACA role in imidacloprid response. Supporting Evidence: PMID:36716868 imidacloprid affected
GO:0031254 cell trailing edge	IDA PMID:16267269 Phosphoinositide 3-kinase activity controls the chemoattract...	ACCEPT	Summary: ACA is asymmetrically localized to the rear (trailing edge) of polarized chemotaxing cells, where it relays cAMP to following cells. Reason: Rear/trailing-edge enrichment of ACA is a well-documented and functionally important localization. Supporting Evidence: PMID:19047467 the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells
GO:0031254 cell trailing edge	IDA PMID:29618632 Adenylyl cyclase A mRNA localized at the back of cells is ac...	ACCEPT	Summary: ACA protein is locally translated and active at the back of chemotaxing cells, supporting trailing-edge activity. Reason: Live-cell imaging shows ACA mRNA transport and local translation at the cell rear, confirming trailing-edge localization and activity. Supporting Evidence: PMID:29618632 local translation of ACA-YFP occurs at the back of cells
GO:0005886 plasma membrane	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: Review-based assertion of plasma membrane localization, consistent with ACA being an integral plasma membrane cyclase. Reason: Plasma membrane localization is well established from primary biochemical evidence. Supporting Evidence: PMID:9168471 adenylate cyclase (ACA), were specifically localized in these structures
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:28302905 Protein kinase A regulates the Ras, Rap1 and TORC2 pathways ...	ACCEPT	Summary: ACA-mediated intracellular cAMP production lies at the heart of this cAMP receptor signaling pathway, which is modulated by PKA via RasG/Rap1/TORC2. Reason: Mutant analysis places ACA-mediated cAMP production centrally in the cAR1/G-protein/cAMP signaling network; core biological process. Supporting Evidence: PMID:28302905 these pathways control the ACA-mediated production of intracellular cAMP
GO:0031259 uropod membrane	IDA PMID:26315268 Adenylyl cyclase localization to the uropod of aggregating D...	ACCEPT	Summary: ACA is enriched and active at the uropod membrane of polarized cells, a localization required for stream formation. Reason: Directly demonstrated uropod-membrane localization of ACA that is required for streaming. Supporting Evidence: PMID:26315268 The localization of adenylyl cyclase A (ACA) to uropod of cells is required for the stream formation
GO:0031271 lateral pseudopodium assembly	IMP PMID:15821137 Intracellular role of adenylyl cyclase in regulation of late...	ACCEPT	Summary: Intracellular cAMP from ACA is required to suppress lateral pseudopods during chemotaxis; aca- cells fail to suppress them. Reason: Mutant phenotype directly implicates ACA-derived cAMP in the control of lateral pseudopod formation. Supporting Evidence: PMID:15821137 defective in suppressing lateral pseudopods in response to a spatial gradient of cAMP
GO:0031259 uropod membrane	IDA PMID:19047467 Collective cell migration requires vesicular trafficking for...	ACCEPT	Summary: ACA accumulates at the rear/uropod membrane via vesicular trafficking, consistent with its head-to-tail signal relay role. Reason: Directly documented rear/uropod localization of ACA-containing structures. Supporting Evidence: PMID:19047467 the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells
GO:0031152 aggregation involved in sorocarp development	IMP PMID:1348970 Structurally distinct and stage-specific adenylyl cyclase ge...	ACCEPT	Summary: aca- mutants fail to aggregate, establishing ACA as essential for the aggregation stage of Dictyostelium development. This is a core process. Reason: Classic gene-disruption phenotype (no cAMP synthesis and failure to aggregate); central developmental role. Supporting Evidence: PMID:1348970 has little detectable adenylyl cyclase activity and fails to aggregate
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:20670432 KeaA, a Dictyostelium Kelch-domain protein that regulates th...	KEEP AS NON CORE	Summary: This annotation comes from a study of the Kelch-domain regulator KeaA showing that cAMP production and detection after stress requires KeaA; the link to ACA in this pathway is indirect. Reason: Supports ACA involvement in cAMP signaling in a stress/development context but via an indirect (KeaA-focused) genetic experiment. Supporting Evidence: PMID:20670432 keaA is necessary for the production and detection of cAMP
GO:0010225 response to UV-C	IDA PMID:25858552 Response of Dictyostelium discoideum to UV-C and involvement...	MARK AS OVER ANNOTATED	Summary: aca is one of several developmentally regulated genes whose expression was profiled by RT-PCR after UV-C exposure; it is used here as a developmental marker rather than a functional effector of UV response. Reason: Annotation reflects aca expression change in a marker-gene panel, not a dedicated role of ACA in the UV-C response. Supporting Evidence: PMID:25858552 yakA, car1, aca, csA, regA
GO:0031285 regulation of sorocarp stalk cell differentiation	IMP PMID:28057864 Adenylate cyclase A acting on PKA mediates induction of stal...	ACCEPT	Summary: Tip-expressed ACA produces the cAMP that, via PKA, induces stalk gene expression downstream of c-di-GMP at the organizer. ACA is required for c-di-GMP-induced stalk formation. Reason: Genetic and pharmacological evidence shows ACA is required for c-di-GMP-induced stalk gene transcription, a genuine later-development role. Supporting Evidence: PMID:28057864 the more widely expressed DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk genes
GO:0061939 c-di-GMP signaling	IMP PMID:28057864 Adenylate cyclase A acting on PKA mediates induction of stal...	KEEP AS NON CORE	Summary: ACA acts as a downstream effector within the c-di-GMP signaling pathway (DgcA activates ACA, which acts on PKA). Its role is as an intermediary rather than a core c-di-GMP signaling component. Reason: ACA is downstream of the diguanylate cyclase DgcA in transmitting the c-di-GMP signal; a real but non-core, context-specific role. Supporting Evidence: PMID:28057864 the more widely expressed DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk genes
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IMP PMID:1348970 Structurally distinct and stage-specific adenylyl cyclase ge...	ACCEPT	Summary: aca- disruption abolishes receptor/G protein-regulated adenylyl cyclase activity, confirming ACA's role in this signaling pathway. Reason: Restoration of receptor- and guanine nucleotide-regulated adenylyl cyclase activity by ACA expression confirms pathway involvement. Supporting Evidence: PMID:1348970 ACA expression restores receptor and guanine nucleotide-regulated adenylyl cyclase activity
GO:0010042 response to manganese ion	IDA PMID:108168 The effect of divalent cations on aggregation of Dictyosteli...	KEEP AS NON CORE	Summary: Manganese directly stimulates adenylyl cyclase activity and can overcome Ca2+ inhibition, reflecting divalent-cation regulation of the enzyme rather than a developmental process per se. Reason: Reflects genuine biochemical regulation of ACA activity by Mn2+, but is a peripheral/regulatory property, not a core evolved function. Supporting Evidence: PMID:108168 was shown to directly stimulate adenyl cyclase
GO:0005771 multivesicular body	IDA PMID:19047467 Collective cell migration requires vesicular trafficking for...	ACCEPT	Summary: ACA-containing vesicles are secreted as multivesicular bodies during collective migration, supporting this localization. Reason: Directly imaged ACA in multivesicular-body structures shed by migrating cells. Supporting Evidence: PMID:19047467 likely secreted as multivesicular bodies
GO:0071944 cell periphery	IDA PMID:19047467 Collective cell migration requires vesicular trafficking for...	KEEP AS NON CORE	Summary: General peripheral localization; the informative locations (plasma membrane, uropod membrane, trailing edge) are separately annotated. Reason: Broad cell periphery term subsumed by more specific plasma membrane/uropod annotations. Supporting Evidence: PMID:19047467 the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells
GO:0097708 intracellular vesicle	IDA PMID:19047467 Collective cell migration requires vesicular trafficking for...	ACCEPT	Summary: ACA is carried on intracellular vesicles that traffic to the cell rear, a well-supported part of the ACA relay mechanism. Reason: Directly documented association of ACA with intracellular vesicular structures. Supporting Evidence: PMID:26315268 ACA-YFP is mainly associated with intracellular vesicular structures
GO:0004016 adenylate cyclase activity	IMP PMID:1348970 Structurally distinct and stage-specific adenylyl cyclase ge...	ACCEPT	Summary: Gene disruption abolishes detectable adenylyl cyclase activity, directly attributing the activity to ACA. Reason: Loss-of-function evidence for ACA adenylate cyclase activity; core molecular function. Supporting Evidence: PMID:1348970 has little detectable adenylyl cyclase activity and fails to aggregate
GO:0010447 response to acidic pH	IDA PMID:7883072 Regulation of Dictyostelium adenylylcyclases by morphogen-in...	KEEP AS NON CORE	Summary: Weak acids that lower cytosolic pH inhibit ACA activity, reflecting the pH dependence of the enzyme rather than a dedicated developmental process. Reason: Captures biochemical pH-sensitivity of ACA activity; a regulatory/peripheral property, not a core function. Supporting Evidence: PMID:7883072 weak acids inhibit both ACA and ACG permanently
GO:1904643 response to curcumin	IDA PMID:26449461 Curcumin inhibits development and cell adhesion in Dictyoste...	KEEP AS NON CORE	Summary: Curcumin suppresses YakA-pathway developmental genes and delays development; any effect on acaA is part of a broad developmental/stress response rather than a specific ACA function. Reason: Peripheral chemical-response annotation reflecting curcumin's general effects on the developmental program.
GO:0031410 cytoplasmic vesicle	IDA PMID:26315268 Adenylyl cyclase localization to the uropod of aggregating D...	ACCEPT	Summary: ACA associates with cytoplasmic (intracellular) vesicles that are trafficked to the plasma membrane at the cell rear. Reason: Directly documented ACA localization to vesicular structures during trafficking. Supporting Evidence: PMID:26315268 ACA-YFP is mainly associated with intracellular vesicular structures
GO:0005886 plasma membrane	IDA PMID:9168471 Identification of detergent-resistant plasma membrane microd...	ACCEPT	Summary: ACA is directly localized to plasma membrane microdomains (CHIFF) enriched in signal transduction proteins. Reason: Primary biochemical evidence for plasma membrane localization of ACA; core localization. Supporting Evidence: PMID:9168471 adenylate cyclase (ACA), were specifically localized in these structures
GO:0010628 positive regulation of gene expression	IMP PMID:23473502 Robustness of self-organizing chemoattractant field arising ...	KEEP AS NON CORE	Summary: ACA-generated cAMP oscillations drive developmental gene expression (for example of cAMP-relay components). The connection to gene expression is indirect, via the cAMP signal. Reason: Downstream, indirect effect of ACA-derived cAMP on developmental gene expression; not a core molecular function.
GO:0031000 response to caffeine	IDA PMID:22928977 Regulation of multiple tip formation by caffeine in cellular...	KEEP AS NON CORE	Summary: Caffeine (an adenosine antagonist) lowers AcaA levels and cAMP, contributing to multiple-tip formation; this reflects modulation of ACA by caffeine rather than a dedicated ACA function. Reason: Reflects caffeine-induced reduction of ACA levels affecting the cAMP gradient; a peripheral chemical-response context. Supporting Evidence: PMID:22928977 Caffeine decreases adenyl cyclase-A (AcaA) levels
GO:1902168 response to catechin	IDA PMID:23516620 The green tea catechin epigallocatechin gallate (EGCG) block...	KEEP AS NON CORE	Summary: EGCG (a green-tea catechin) blocks Dictyostelium motility, chemotaxis and development; any ACA involvement is part of a broad effect on the cAMP-driven developmental program. Reason: Peripheral chemical-response annotation; not a core ACA function.
GO:0004016 adenylate cyclase activity	IDA PMID:8619862 Tetrahydropterins interfere with the G protein pathway in Di...	ACCEPT	Summary: Loss of adenylyl cyclase activation upon G protein inhibition supports ACA adenylate cyclase activity within the G protein pathway. Reason: Experimental support linking ACA adenylate cyclase activity to G protein activation; core molecular function. Supporting Evidence: PMID:8619862 a loss of adenylyl cyclase activation
GO:0030435 sporulation resulting in formation of a cellular spore	IGI PMID:9582274 Evidence that the RdeA protein is a component of a multistep...	KEEP AS NON CORE	Summary: Genetic interaction with the phosphorelay component RdeA implicates ACA/cAMP-PKA signaling in the timing of development and sporulation. This is a later-development, non-core role. Reason: Supports a role for ACA-derived cAMP signaling in developmental timing/sporulation through the RdeA phosphorelay, but peripheral to the core aggregation function. Supporting Evidence: PMID:9582274 RdeA is part of a multistep phosphorelay system that modulates the rate of development
GO:0007015 actin filament organization	IMP PMID:15821137 Intracellular role of adenylyl cyclase in regulation of late...	KEEP AS NON CORE	Summary: aca- cells show altered pseudopod behavior and cell shape during chemotaxis; effects on actin organization are indirect consequences of lost intracellular cAMP signaling. Reason: Indirect, downstream effect of ACA on the actin cytoskeleton via cAMP-regulated chemotactic behavior; not a core function. Supporting Evidence: PMID:15821137 adenylyl cyclase play an intracellular role in the chemotactic response
GO:0008360 regulation of cell shape	IMP PMID:15821137 Intracellular role of adenylyl cyclase in regulation of late...	KEEP AS NON CORE	Summary: Loss of ACA impairs polarity and shape control during chemotaxis; this is an indirect consequence of disrupted intracellular cAMP signaling. Reason: Downstream phenotypic effect of ACA loss on cell shape; peripheral to the core catalytic/relay function. Supporting Evidence: PMID:15821137 adenylyl cyclase play an intracellular role in the chemotactic response
GO:0050920 regulation of chemotaxis	IMP PMID:15821137 Intracellular role of adenylyl cyclase in regulation of late...	KEEP AS NON CORE	Summary: Intracellular cAMP produced by ACA is required for normal chemotactic behavior (suppression of lateral pseudopods, chemotaxis in natural cAMP waves). Reason: ACA-derived cAMP regulates chemotactic responsiveness; an important but downstream/regulatory role rather than the core catalytic function. Supporting Evidence: PMID:15821137 adenylyl cyclase play an intracellular role in the chemotactic response
GO:0004016 adenylate cyclase activity	IDA PMID:10556070 An adenylyl cyclase that functions during late development o...	ACCEPT	Summary: Direct experimental annotation of ACA adenylate cyclase activity by dictyBase curators. Adenylate cyclase activity is firmly established for this gene product. Reason: Core molecular function, corroborated by numerous direct assays; defer to the experimental curation.
GO:0004016 adenylate cyclase activity	IDA PMID:15507682 A rapid and efficient method to generate multiple gene disru...	ACCEPT	Summary: Direct experimental annotation of ACA adenylate cyclase activity by dictyBase curators. Reason: Core molecular function of ACA; consistent with all other direct enzymatic evidence.

Gene Description

Existing Annotations Review

Core Functions

References

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