carA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004930 G protein-coupled receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that cAR1 is a G protein-coupled receptor is correct and central to its function. cAR1 is a canonical seven-transmembrane serpentine receptor that couples to heterotrimeric G proteins. Reason: cAR1 is a bona fide GPCR; direct evidence shows it catalyzes the heterotrimeric G-protein cycle upon cAMP binding. This is a core molecular function, though the more specific cAMP/chemoattractant receptor terms better capture the ligand. Supporting Evidence: PMID:11264536 occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: cAR1 is a multi-pass plasma-membrane receptor, confirmed by direct subcellular localization studies. Phylogenetic inference of plasma membrane localization is correct. Reason: The plasma membrane origin of cAR1-enriched fractions was confirmed by cell-surface biotinylation and immunoelectron microscopy; this is where cAR1 binds extracellular cAMP and signals. Supporting Evidence: PMID:9168471 Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	MODIFY	Summary: cAR1 activates adenylyl cyclase (ACA) via heterotrimeric G proteins as part of the cAMP relay. This IBA term is correct; a more specific child term for cAMP-receptor signaling exists and is used elsewhere in this record. Reason: The essence is correct, but the cAMP-receptor-specific child term GO:0140582 (used by multiple experimental annotations here) more precisely captures cAR1 signaling. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000560943 · PANTHER node for the Dictyostelium cAMP-receptor (cAR) family SUPPORTS SOURCE BUT NOT TARGET The adenylate-cyclase-activating signaling role is real for cAR1, but a cAMP-receptor-specific child term captures cAR1 more precisely than the generic GPCR parent dictyBase:DDB_G0273397 · Dictyostelium aggregation-stage cAR paralog SUPPORTS SOURCE BUT NOT TARGET Source paralog genuinely couples to adenylate cyclase; the term is correct but too general for cAR1 Proposed replacements: adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway Supporting Evidence: PMID:9578623 assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization
GO:0004888 transmembrane signaling receptor activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: A correct but general parent of GPCR/cAMP receptor activity. cAR1 is a transmembrane signaling receptor, but more informative child terms apply. Reason: Accurate but non-specific; the core function is better represented by cAMP receptor activity and G protein-coupled chemoattractant receptor activity. Supporting Evidence: PMID:11264536 occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO inference of GPCR activity, duplicating the IBA annotation and consistent with cAR1 being a serpentine GPCR. Reason: cAR1 is a canonical GPCR; this electronic annotation is correct and corroborated by direct evidence of G-protein activation. Supporting Evidence: PMID:11264536 occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0007165 signal transduction	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: A very general process term. cAR1 is a signal transduction receptor, but far more specific pathway terms are available and used here. Reason: Correct but uninformative; retained as non-core because specific cAMP-receptor signaling terms better represent the function. Supporting Evidence: PMID:1849108 cAR1-mediated signal transduction controls the development of Dictyostelium
GO:0007166 cell surface receptor signaling pathway	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct general parent term. cAR1 is a cell-surface receptor that initiates signaling, but a more specific GPCR/cAMP-receptor term is preferable. Reason: Accurate but non-specific; specific cAMP receptor signaling terms are used as core. Supporting Evidence: PMID:1849108 cAR1, a G-protein-linked surface cAMP receptor, plays a central role in the development of Dictyostelium
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: cAR1 signals via a G protein-coupled receptor pathway, which is accurate. This term is a parent of the specific adenylate cyclase-activating cAMP receptor pathway used for the experimental annotations. Reason: Accurate but general; the specific GO:0140582 term better captures cAR1's core signaling role. Supporting Evidence: PMID:7949426 cAR1, coupled by a typical heterotrimeric G-protein to intracellular effectors
GO:0016020 membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cAR1 is an integral membrane protein; this general term is correct but subsumed by the more specific plasma membrane annotation. Reason: Accurate but non-specific relative to the plasma membrane localization that is directly supported. Supporting Evidence: PMID:9168471 Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation
GO:0030552 cAMP binding	IEA GO_REF:0000002	ACCEPT	Summary: cAR1 binds extracellular cAMP with nanomolar affinity; direct ligand binding is well established. This InterPro2GO annotation is correct. Reason: cAMP binding is the defining ligand-recognition activity of cAR1, supported by direct binding assays. Supporting Evidence: PMID:1648967 The affinity of the expressed cAR1 was similar to that of the endogenous receptors in aggregation stage cells
GO:0035589 G protein-coupled purinergic nucleotide receptor signaling pathway	IEA GO_REF:0000108	REMOVE	Summary: This electronically inferred term classifies cAR1 signaling as purinergic nucleotide receptor signaling. cAR1 is a cAMP receptor whose signaling is distinct from classical purinergic (P2X/P2Y) receptor pathways; this is an over-propagation from automated inter-ontology inference. Reason: cAR1 is not a purinergic (ATP/ADP/UTP) receptor; it recognizes the second-messenger-derived chemoattractant cAMP. Its signaling is captured accurately by the cAMP receptor / adenylate cyclase-activating cAMP receptor terms. This IEA (GO_REF:0000108, logical inference) mislabels the pathway and should be removed.
GO:1904776 regulation of protein localization to cell cortex	IGI PMID:40934557 The Ras association domain of DydA as a specific reporter of...	KEEP AS NON CORE	Summary: cAR1 (Car1/3) and G-protein signaling are required for chemoattractant- induced cortical/leading-edge translocation of a RasG biosensor, placing cAR1 upstream of cortical protein localization during chemotaxis. Reason: A valid downstream developmental/chemotactic consequence of cAR1 signaling rather than its core molecular function. Supporting Evidence: PMID:40934557 This localization required GPCR Car1/3 and G-protein signaling
GO:0010856 adenylate cyclase activator activity	IMP PMID:9578623 Switching of chemoattractant receptors programs development ...	KEEP AS NON CORE	Summary: cAR1 activates adenylyl cyclase (ACA) as part of the cAMP relay. The activation is receptor-mediated and G-protein-dependent (indirect) rather than cAR1 acting directly on the cyclase, so this MF is best treated as non-core. Reason: cAR1 mediates activation of adenylyl cyclase, but does so indirectly via heterotrimeric G proteins; the direct molecular function is receptor/cAMP binding. Retained as non-core. Supporting Evidence: PMID:9578623 assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization
GO:0030295 protein kinase activator activity	IMP PMID:8670837 Dual role of cAMP and involvement of both G-proteins and ras...	KEEP AS NON CORE	Summary: cAMP binding to cAR1 stimulates activation of the MAP kinase ERK2, but this occurs through a G-protein/Ras-dependent cascade, not by cAR1 directly binding and activating a kinase. Reason: The kinase activation is an indirect downstream effect of cAR1 signaling; the core molecular function is receptor/ligand binding. Retained as non-core. Supporting Evidence: PMID:8670837 Binding of extracellular cAMP to cAMP receptor 1, a G-protein coupled cell surface receptor, transiently stimulates phosphorylation, activation and nuclear translocation of ERK2
GO:0140295 pathogen-derived receptor ligand activity	IDA PMID:37866633 The Legionella autoinducer LAI-1 is delivered by outer membr...	REMOVE	Summary: This annotation assigns cAR1 a pathogen-derived receptor ligand activity. cAR1 is a host cell-surface receptor, not a pathogen-derived ligand, and the cited study (Legionella LAI-1 delivered via outer membrane vesicles, which inhibit Dictyostelium migration) does not mention cAR1 in its full text. Reason: The molecular function is biologically inverted for cAR1 (a receptor cannot have receptor-ligand activity), and the full text of PMID:37866633 does not implicate cAR1 as the ligand or receptor for LAI-1. This appears to be a curation/mapping error rather than a supportable function.
GO:0140676 oscillatory cAMP signaling	IDA PMID:37921687 Collective signalling drives rapid jumping between cell stat...	ACCEPT	Summary: cAR1 is the receptor that detects the collective, oscillatory cAMP signals that coordinate the developmental gene-expression jump during aggregation. Oscillatory cAMP signaling is a central role of cAR1. Reason: cAR1 mediates the cell's response to collective oscillations of cAMP; this oscillatory cAMP signaling is a core aspect of cAR1 function during aggregation. Supporting Evidence: PMID:37921687 the jump coincides with the onset of collective oscillations of cAMP
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:8280098 Phospholipase C in Dictyostelium discoideum. Identification ...	ACCEPT	Summary: Genetic evidence links cAR1 and its G proteins to cAMP-regulated signaling (here, dual regulation of phospholipase C), consistent with cAR1 operating the G protein-coupled cAMP receptor signaling pathway. Reason: cAR1 is a core component of the surface cAMP receptor / G-protein signaling module; the paper directly implicates cAR1 with a G protein in cAMP signal transduction. Supporting Evidence: PMID:8280098 The inhibitory pathway is composed of the surface receptor cAR1 and the G-protein G1
GO:0070371 ERK1 and ERK2 cascade	IMP PMID:8670837 Dual role of cAMP and involvement of both G-proteins and ras...	ACCEPT	Summary: cAMP binding to cAR1 transiently activates ERK2 in a G-protein-dependent manner, placing cAR1 upstream of the ERK cascade during chemotactic signaling. Reason: Directly supported by the finding that cAR1 activation stimulates ERK2 phosphorylation, activation and nuclear translocation, a genuine downstream signaling role. Supporting Evidence: PMID:8670837 Binding of extracellular cAMP to cAMP receptor 1, a G-protein coupled cell surface receptor, transiently stimulates phosphorylation, activation and nuclear translocation of ERK2
GO:0030695 GTPase regulator activity	IDA PMID:21103944 Chemoattractant-mediated Rap1 activation requires GPCR/G pro...	KEEP AS NON CORE	Summary: As a GPCR, cAR1 acts as a guanine-nucleotide exchange factor for heterotrimeric G proteins and is required for chemoattractant-mediated activation of the small GTPase Rap1. Its GTPase-regulator role is receptor- driven and largely mediated through the heterotrimeric G proteins. Reason: cAR1 regulates GTPase cycling indirectly as part of its GPCR function; the core molecular activity is receptor/cAMP binding. Retained as non-core. Supporting Evidence: PMID:21103944 The rapid Rap1 activation upon cAMP chemoattractant stimulation was absent in cells lacking chemoattractant cAMP receptors cAR1/cAR3
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IDA PMID:8999903 Random mutagenesis of the cAMP chemoattractant receptor, cAR...	ACCEPT	Summary: Mutagenesis of cAR1 directly demonstrates its role in transducing extracellular cAMP signals via G-protein-dependent (and independent) mechanisms, the core cAMP receptor signaling pathway. Reason: Direct experimental evidence that cAR1 mediates cAMP signal transduction; a core process for this receptor. Supporting Evidence: PMID:8999903 The cAMP chemoattractant receptor, cAR1, of Dictyostelium transduces extracellular cAMP signals via G protein-dependent and G protein-independent mechanisms
GO:0005829 cytosol	IDA PMID:21541374 Quantification of GPCR internalization by single-molecule mi...	KEEP AS NON CORE	Summary: Single-molecule imaging shows the fraction of cytosolic cAR1 increases after persistent agonist stimulation, reflecting phosphorylation-dependent receptor internalization rather than a steady-state cytosolic pool. Reason: The cytosolic signal represents internalized receptor during desensitization, not the site of the receptor's core signaling function (the plasma membrane). Retained as non-core. Supporting Evidence: PMID:21541374 the fraction of cytosolic receptors increases after persistent agonist stimulation
GO:0031252 cell leading edge	IDA PMID:18469015 A spatially restricted increase in receptor mobility is invo...	ACCEPT	Summary: Single-molecule microscopy shows an agonist-induced increase in cAR1 mobility at the leading edge of chemotaxing cells, contributing to directional sensing. cAR1 is active at the leading edge. Reason: Directly supported localization of active cAR1 to the leading edge during chemotaxis, a functionally important site. Supporting Evidence: PMID:18469015 an agonist-induced increase in the mobile fraction of cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum cells
GO:0031152 aggregation involved in sorocarp development	IMP PMID:15507682 A rapid and efficient method to generate multiple gene disru...	ACCEPT	Summary: cAR1 is essential for the aggregation stage of Dictyostelium development; cAR1 nulls fail to aggregate. Aggregation is a core biological process for cAR1. Reason: cAR1-mediated cAMP signaling drives the chemotactic aggregation of starving cells into a multicellular mound; loss of cAR1 arrests development in early aggregation. Supporting Evidence: PMID:1849108 fail to bind or sense cAMP and arrest in early development
GO:0031152 aggregation involved in sorocarp development	IMP PMID:17630977 Regulation of G protein-coupled cAMP receptor activation by ...	ACCEPT	Summary: cAR1 is essential for multicellular development; constitutively active Ile-104 mutants block development, confirming cAR1's role in aggregation-stage development. Reason: Directly supported requirement of properly regulated cAR1 for the aggregation/development program. Supporting Evidence: PMID:17630977 cAR1, a G protein-coupled cAMP receptor, is essential for multicellular development of Dictyostelium
GO:0031152 aggregation involved in sorocarp development	IEP PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo...	KEEP AS NON CORE	Summary: cAR1/carA is expressed during the aggregation phase when starving cells communicate via extracellular cAMP. Expression-pattern evidence is consistent with, but weaker than, the mutant-based support for a role in aggregation. Reason: IEP (expression) evidence corroborates the aggregation role established by mutant studies; retained as non-core given the weaker evidence type. Supporting Evidence: PMID:25887420 communicate via extracellular cAMP, aggregate by tens of thousands and develop into multicellular organisms
GO:0097696 cell surface receptor signaling pathway via STAT	IMP PMID:9670017 Developmentally and spatially regulated activation of a Dict...	ACCEPT	Summary: Extracellular cAMP acting through cAR1 rapidly induces tyrosine phosphorylation and nuclear translocation of Dd-STAT, a G protein-independent signaling output of the receptor. Reason: Directly supported role of cAR1 in mediating STAT (Dd-STAT) activation, a genuine signaling pathway downstream of the receptor. Supporting Evidence: PMID:9670017 The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1
GO:0005886 plasma membrane	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: cAR1 is a plasma-membrane chemoattractant receptor; this is a well-established, traceable statement in the chemoattractant-signaling literature. Reason: Plasma membrane is the functional location of cAR1, corroborated by direct biochemical/microscopy evidence. Supporting Evidence: PMID:9168471 Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation
GO:0005886 plasma membrane	IDA PMID:9168471 Identification of detergent-resistant plasma membrane microd...	ACCEPT	Summary: cAR1 is enriched in detergent-resistant plasma-membrane microdomains; the plasma membrane origin was directly confirmed by surface biotinylation and immunoelectron microscopy. Reason: Direct experimental confirmation of cAR1's plasma membrane localization, the site of its receptor function. Supporting Evidence: PMID:9168471 Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation
GO:0005515 protein binding	IPI PMID:25143405 Arrestins function in cAR1 GPCR-mediated signaling and cAR1 ...	KEEP AS NON CORE	Summary: cAR1 physically interacts with arrestin domain-containing proteins (AdcC); activation of cAR1 recruits AdcC to the membrane and links the receptor to periodic ERK2 activation and internalization. The bare protein binding term is uninformative. Reason: The specific interaction (arrestin binding regulating cAR1 signaling and internalization) is informative, but the generic GO:0005515 term does not convey function; retained as non-core. A more specific arrestin-binding molecular function would be preferable. Supporting Evidence: PMID:25143405 activation of cAR1 promotes the transient membrane recruitment of AdcC and interaction with cAR1
GO:0005769 early endosome	IDA PMID:7628637 Localization of cyclic-AMP receptors with acidosomes in Dict...	KEEP AS NON CORE	Summary: Internalized cAR1 localizes with acidosomes, which the authors argue are analogous to early/recycling endosomes and may be a site for recycling of internalized receptors. Reason: Endosomal localization reflects receptor trafficking/recycling after internalization rather than the core plasma-membrane signaling function. Retained as non-core. Supporting Evidence: PMID:7628637 acidosomes contain abundant receptors for cyclic AMP (CAR1) and that it may be the site for recycling of internalized receptors
GO:0009986 cell surface	IDA PMID:15507682 A rapid and efficient method to generate multiple gene disru...	ACCEPT	Summary: cAR1 is a cell-surface cAMP receptor, consistent with its plasma-membrane localization and function in sensing extracellular cAMP. Reason: cAR1 acts at the cell surface where it binds extracellular cAMP; corroborated by its description as a surface cAMP receptor. Supporting Evidence: PMID:1849108 cAR1, a G-protein-linked surface cAMP receptor, plays a central role in the development of Dictyostelium
GO:0006935 chemotaxis	IMP PMID:15507682 A rapid and efficient method to generate multiple gene disru...	ACCEPT	Summary: cAR1 mediates chemotaxis toward cAMP, the defining behavioral response it controls during aggregation. Reason: cAR1 is required for directed migration up cAMP gradients; chemotaxis is a core biological process for the receptor. Supporting Evidence: PMID:9578623 assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization
GO:0006935 chemotaxis	IGI PMID:9578623 Switching of chemoattractant receptors programs development ...	ACCEPT	Summary: Genetic complementation of car1-/car3- cells with cAR1 restores chemotaxis, confirming cAR1's role in chemotactic responses to cAMP. Reason: cAR1 mediates chemotaxis to cAMP; a core biological process directly tested by receptor expression assays. Supporting Evidence: PMID:9578623 assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization
GO:0023058 adaptation of signaling pathway	IMP PMID:23902692 Phosphorylation of chemoattractant receptors regulates chemo...	ACCEPT	Summary: Agonist-induced phosphorylation of cAR1 is required for adaptation of adenylyl cyclase responses and for proper long-range oscillatory cAMP wave production, a signaling-adaptation function. Reason: Non-phosphorylatable cAR1 mutants fail to adapt adenylyl cyclase and lose directional chemotaxis, directly demonstrating cAR1's role in signaling adaptation. Supporting Evidence: PMID:23902692 receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin response
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IDA PMID:11264536 Receptor-mediated activation of heterotrimeric G-proteins in...	ACCEPT	Summary: FRET imaging in living cells shows chemoattractant (cAMP) binding to the receptor drives dissociation/reassociation of the heterotrimeric G protein, directly demonstrating the cAMP receptor signaling pathway. Reason: Direct in vivo evidence that cAR1 catalyzes the G-protein cycle upon cAMP binding; core to cAMP receptor signaling. Supporting Evidence: PMID:11264536 The G-protein heterotrimer rapidly dissociated and reassociated upon addition and removal of chemoattractant
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IMP PMID:7949426 Two cAMP receptors activate common signaling pathways in Dic...	ACCEPT	Summary: cAR1 is the primary receptor mediating cAMP responses (cAMP relay, cGMP synthesis) coupled through a heterotrimeric G protein; car1- cells have strongly reduced responses. Reason: Genetic evidence that cAR1 normally mediates cAMP-relay and other responses via a heterotrimeric G protein; core cAMP receptor signaling. Supporting Evidence: PMID:7949426 Dictyostelium cells respond to cAMP using one such receptor, cAR1, coupled by a typical heterotrimeric G-protein to intracellular effectors
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	IGI PMID:7949426 Two cAMP receptors activate common signaling pathways in Dic...	ACCEPT	Summary: Double car1-/car3- deletion abolishes cAMP sensitivity, and cAR1 and cAR3 act redundantly through the same G protein, confirming cAR1's role in the cAMP receptor signaling pathway. Reason: Genetic interaction evidence that cAR1 (with cAR3) mediates cAMP signaling via a shared heterotrimeric G protein. Supporting Evidence: PMID:7949426 both interact with the same heterotrimeric G-protein to mediate these and other responses
GO:1903013 response to differentiation-inducing factor 1	HDA PMID:25518940 The Dictyostelium prestalk inducer differentiation-inducing ...	KEEP AS NON CORE	Summary: Phosphoproteomic analysis shows the cAMP receptor is rapidly dephosphorylated in response to DIF-1, reflecting cross-talk/antagonism between DIF-1 and cAMP signaling. Reason: cAR1's dephosphorylation in response to DIF-1 is a regulatory cross-talk response, not a core function of the receptor. Retained as non-core. Supporting Evidence: PMID:25518940 the rapid dephosphorylation of the cAMP receptor that we observe in response to DIF-1
GO:0001637 G protein-coupled chemoattractant receptor activity	IDA PMID:11264536 Receptor-mediated activation of heterotrimeric G-proteins in...	ACCEPT	Summary: cAR1 is the G protein-coupled receptor for the chemoattractant cAMP; occupied receptors directly catalyze the G-protein cycle as shown by live-cell FRET. This is a core molecular function. Reason: Directly supported chemoattractant GPCR activity coupling cAMP detection to heterotrimeric G-protein activation. Supporting Evidence: PMID:11264536 occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0001646 cAMP receptor activity	IDA PMID:9578623 Switching of chemoattractant receptors programs development ...	ACCEPT	Summary: cAR1 is the founding member of the Dictyostelium cAMP receptor family and functions as a cAMP receptor; direct expression/complementation assays confirm this activity. This is the core molecular function. Reason: Directly supported cAMP receptor activity; the defining function of cAR1. Supporting Evidence: PMID:9578623 The cAMP chemoattractant receptor family of Dictyostelium discoideum is composed of four receptors (cAR1-cAR4)
GO:0001646 cAMP receptor activity	IGI PMID:9578623 Switching of chemoattractant receptors programs development ...	ACCEPT	Summary: Complementation of receptor-null cells with cAR1 restores cAMP responses, genetically confirming cAR1 cAMP receptor activity. Reason: cAMP receptor activity is the core molecular function of cAR1; supported by genetic complementation. Supporting Evidence: PMID:9578623 The cAMP chemoattractant receptor family of Dictyostelium discoideum is composed of four receptors (cAR1-cAR4)
GO:0010225 response to UV-C	IDA PMID:25858552 Response of Dictyostelium discoideum to UV-C and involvement...	KEEP AS NON CORE	Summary: carA/car1 is among the developmentally regulated genes whose expression was examined during the UV-C response of Dictyostelium; this is a stress- response context rather than a core receptor function. Reason: cAR1 involvement here reflects developmental gene-expression changes under UV-C stress, not the receptor's core molecular role. Retained as non-core. Supporting Evidence: PMID:25858552 Expression of developmentally regulated genes yakA, car1, aca, csA, regA, ctnA, ctnB, gp24, hspD and dsn were analysed using semiquantitative RT-PCR
GO:0030552 cAMP binding	IDA PMID:15507682 A rapid and efficient method to generate multiple gene disru...	ACCEPT	Summary: cAR1 directly binds extracellular cAMP; ligand binding is the receptor's defining biochemical activity, well documented across many studies. Reason: cAMP binding is a core molecular function of cAR1, supported by direct binding measurements. Supporting Evidence: PMID:1648967 The affinity of the expressed cAR1 was similar to that of the endogenous receptors in aggregation stage cells
GO:0030552 cAMP binding	IDA PMID:1648967 Overexpression of the cAMP receptor 1 in growing Dictyosteli...	ACCEPT	Summary: Direct binding assays show cAR1 binds cAMP with nanomolar affinity (two affinity states, Kd ~30 and 300 nM), matching endogenous aggregation-stage receptors. Reason: Direct measurement of cAR1 cAMP binding affinity; a core molecular function. Supporting Evidence: PMID:1648967 two affinity states with Kd's of PMID:1648967 The affinity of the expressed cAR1 was similar to that of the endogenous receptors in aggregation stage cells
GO:0030552 cAMP binding	IMP PMID:17630977 Regulation of G protein-coupled cAMP receptor activation by ...	ACCEPT	Summary: Ile-104 substitutions in cAR1 dramatically alter the receptor's cAMP affinity, demonstrating that cAR1 binds cAMP and that this residue tunes ligand affinity. Reason: Mutational evidence directly implicating cAR1 in cAMP binding (affinity modulation); core molecular function. Supporting Evidence: PMID:17630977 all Ile(104) substitutions, except for the most conservative, dramatically elevated the receptor's cAMP affinity
GO:0030552 cAMP binding	IDA PMID:8999903 Random mutagenesis of the cAMP chemoattractant receptor, cAR...	ACCEPT	Summary: Random mutagenesis identified cAR1 mutants with altered cAMP binding (including conditional binding defects), directly demonstrating cAR1 cAMP binding activity. Reason: Direct biochemical evidence for cAR1 cAMP binding; core molecular function. Supporting Evidence: PMID:8999903 One class had a conditional defect in cAMP binding that was reversed by high salt
GO:0030552 cAMP binding	IMP PMID:9578623 Switching of chemoattractant receptors programs development ...	ACCEPT	Summary: cAR1 and related receptors sense different concentration ranges of cAMP; mutations altering ligand recognition confirm cAR1 cAMP binding activity. Reason: Mutational evidence that cAR1 binds cAMP; core molecular function. Supporting Evidence: PMID:9578623 various receptors and mutants sense different concentration ranges of cAMP
GO:1904643 response to curcumin	IDA PMID:26449461 Curcumin inhibits development and cell adhesion in Dictyoste...	KEEP AS NON CORE	Summary: Curcumin delays Dictyostelium chemotaxis, adhesion and development. This is a chemical/developmental response of the organism rather than a core cAR1 molecular function. Reason: cAR1's involvement reflects curcumin's inhibitory effect on cAMP-driven chemotaxis and development, a stimulus-response phenotype rather than a core receptor function. Retained as non-core. Supporting Evidence: PMID:26449461 This resulted in delayed chemotaxis, adhesion, and development of the organism
GO:1902168 response to catechin	IDA PMID:23516620 The green tea catechin epigallocatechin gallate (EGCG) block...	KEEP AS NON CORE	Summary: The green-tea catechin EGCG reduces random movement and chemotaxis of Dictyostelium and stalls development, a chemical-response phenotype affecting cAMP-driven chemotaxis. Reason: Reflects a stimulus-response (catechin) effect on chemotaxis/development rather than a core cAR1 molecular function. Retained as non-core. Supporting Evidence: PMID:23516620 EGCG reduces both random movement and chemotaxis of Dictyostelium amoebae
GO:0050764 regulation of phagocytosis	IMP PMID:17905919 Developmental commitment in Dictyostelium discoideum.	KEEP AS NON CORE	Summary: Extracellular cAMP pulses (sensed via cAR1) are sufficient to induce developmental commitment and the loss of phagocytosis in starving cells, placing cAR1 signaling upstream of phagocytosis regulation. Reason: Down-regulation of phagocytosis is a developmental consequence of cAMP and cAR1 signaling during commitment, not a core receptor function. Retained as non-core. Supporting Evidence: PMID:17905919 cAMP pulses are sufficient to induce both commitment and the loss of phagocytosis in starving cells
GO:0002029 desensitization of G protein-coupled receptor signaling pathway	IMP PMID:15574880 Constitutively active G protein-coupled receptor mutants blo...	ACCEPT	Summary: cAR1-mediated pathways undergo adaptation/desensitization; constitutively active DN mutants block development by turning on natural adaptation mechanisms, implicating cAR1 in GPCR desensitization. Reason: Directly supported role of cAR1 in adaptation/desensitization of its signaling; a genuine regulatory process for the receptor. Supporting Evidence: PMID:15574880 The activation of multiple pathways by cAR1 is transient because of poorly defined adaptation mechanisms
GO:0008277 regulation of G protein-coupled receptor signaling pathway	IDA PMID:11264536 Receptor-mediated activation of heterotrimeric G-proteins in...	KEEP AS NON CORE	Summary: Live-cell FRET shows that G-protein activation by occupied cAR1 reaches a steady state and does not decline even as responses adapt, informing how cAR1 GPCR signaling is regulated. Reason: Captures regulation of cAR1's own GPCR signaling (adaptation occurring downstream of the receptor); a regulatory aspect retained as non-core relative to the core receptor activity. Supporting Evidence: PMID:11264536 adaptation occurs at another point in the signaling pathway, and occupied receptors, whether or not they are phosphorylated, catalyze the G-protein cycle
GO:0031152 aggregation involved in sorocarp development	IMP PMID:1849108 Gene targeting of the aggregation stage cAMP receptor cAR1 i...	ACCEPT	Summary: Gene targeting shows cAR1-null mutants fail to bind/sense cAMP and arrest in early development, proving cAR1-mediated signaling controls the aggregation stage of development. Reason: Definitive genetic evidence that cAR1 is required for aggregation-stage development; a core biological process. Supporting Evidence: PMID:1849108 fail to bind or sense cAMP and arrest in early development PMID:1849108 cAR1-mediated signal transduction controls the development of Dictyostelium

📄 View Raw YAML

id: P13773
gene_symbol: carA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: Cyclic AMP receptor 1 (cAR1, encoded by carA) is a seven-transmembrane,
  serpentine G protein-coupled receptor (GPCR) of the cAMP receptor (cAR) family in
  the social amoeba Dictyostelium discoideum. It resides in the plasma membrane and
  binds extracellular cAMP, the chemoattractant that coordinates the transition from
  a unicellular to a multicellular organism. Upon cAMP binding, cAR1 couples to
  heterotrimeric G proteins (notably Galpha2 and the single Gbeta) to activate
  downstream effectors including adenylyl cyclase (ACA), guanylyl cyclase,
  phospholipase C, the ERK2/MAP kinase cascade, PI3K, and Ras/Rap1 GTPases, driving
  directed chemotaxis toward cAMP and the pulsatile cAMP relay that propagates
  oscillatory cAMP waves during aggregation. cAR1 also signals through G
  protein-independent routes, including rapid activation of the STAT-family
  transcription factor Dd-STAT. cAR1 is the first of four sequentially expressed cAMP
  receptors (cAR1-cAR4); it is expressed predominantly during early aggregation, and
  its loss arrests development at the onset of aggregation. Receptor signaling is
  attenuated by agonist-induced phosphorylation of C-terminal serine clusters and by
  arrestin-mediated internalization, mechanisms that underlie adaptation and
  desensitization and directional sensing during chemotaxis. cAR1 concentrates at the
  leading edge of chemotaxing cells and in detergent-resistant plasma-membrane
  microdomains, and internalized receptor traffics through early/recycling endosomal
  (acidosome) compartments.
existing_annotations:
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference that cAR1 is a G protein-coupled receptor is
      correct and central to its function. cAR1 is a canonical seven-transmembrane
      serpentine receptor that couples to heterotrimeric G proteins.
    action: ACCEPT
    reason: cAR1 is a bona fide GPCR; direct evidence shows it catalyzes the
      heterotrimeric G-protein cycle upon cAMP binding. This is a core molecular
      function, though the more specific cAMP/chemoattractant receptor terms better
      capture the ligand.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated,
        catalyze the G-protein cycle
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: cAR1 is a multi-pass plasma-membrane receptor, confirmed by direct
      subcellular localization studies. Phylogenetic inference of plasma membrane
      localization is correct.
    action: ACCEPT
    reason: The plasma membrane origin of cAR1-enriched fractions was confirmed by
      cell-surface biotinylation and immunoelectron microscopy; this is where cAR1
      binds extracellular cAMP and signals.
    supported_by:
    - reference_id: PMID:9168471
      supporting_text: Cell surface biotinylation and preembedding immunoelectron
        microscopy both confirmed the plasma membrane origin of this preparation
- term:
    id: GO:0007189
    label: adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: cAR1 activates adenylyl cyclase (ACA) via heterotrimeric G proteins as
      part of the cAMP relay. This IBA term is correct; a more specific child term
      for cAMP-receptor signaling exists and is used elsewhere in this record.
    action: MODIFY
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - GRANULARITY_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000560943
        source_label: "PANTHER node for the Dictyostelium cAMP-receptor (cAR) family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "The adenylate-cyclase-activating signaling role is real for cAR1, but a cAMP-receptor-specific child term captures cAR1 more precisely than the generic GPCR parent"
      - source_id: dictyBase:DDB_G0273397
        source_label: "Dictyostelium aggregation-stage cAR paralog"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Source paralog genuinely couples to adenylate cyclase; the term is correct but too general for cAR1"
    reason: The essence is correct, but the cAMP-receptor-specific child term
      GO:0140582 (used by multiple experimental annotations here) more precisely
      captures cAR1 signaling.
    proposed_replacement_terms:
    - id: GO:0140582
      label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
        pathway
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis,
        activation of adenylyl cyclase and actin polymerization
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: A correct but general parent of GPCR/cAMP receptor activity. cAR1 is a
      transmembrane signaling receptor, but more informative child terms apply.
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-specific; the core function is better represented by
      cAMP receptor activity and G protein-coupled chemoattractant receptor activity.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated,
        catalyze the G-protein cycle
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO inference of GPCR activity, duplicating the IBA annotation
      and consistent with cAR1 being a serpentine GPCR.
    action: ACCEPT
    reason: cAR1 is a canonical GPCR; this electronic annotation is correct and
      corroborated by direct evidence of G-protein activation.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated,
        catalyze the G-protein cycle
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: A very general process term. cAR1 is a signal transduction receptor, but
      far more specific pathway terms are available and used here.
    action: KEEP_AS_NON_CORE
    reason: Correct but uninformative; retained as non-core because specific
      cAMP-receptor signaling terms better represent the function.
    supported_by:
    - reference_id: PMID:1849108
      supporting_text: cAR1-mediated signal transduction controls the development of
        Dictyostelium
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Correct general parent term. cAR1 is a cell-surface receptor that
      initiates signaling, but a more specific GPCR/cAMP-receptor term is preferable.
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-specific; specific cAMP receptor signaling terms are
      used as core.
    supported_by:
    - reference_id: PMID:1849108
      supporting_text: cAR1, a G-protein-linked surface cAMP receptor, plays a central
        role in the development of Dictyostelium
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: cAR1 signals via a G protein-coupled receptor pathway, which is accurate.
      This term is a parent of the specific adenylate cyclase-activating cAMP receptor
      pathway used for the experimental annotations.
    action: KEEP_AS_NON_CORE
    reason: Accurate but general; the specific GO:0140582 term better captures cAR1's
      core signaling role.
    supported_by:
    - reference_id: PMID:7949426
      supporting_text: cAR1, coupled by a typical heterotrimeric G-protein to
        intracellular effectors
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: cAR1 is an integral membrane protein; this general term is correct but
      subsumed by the more specific plasma membrane annotation.
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-specific relative to the plasma membrane localization
      that is directly supported.
    supported_by:
    - reference_id: PMID:9168471
      supporting_text: Cell surface biotinylation and preembedding immunoelectron
        microscopy both confirmed the plasma membrane origin of this preparation
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: cAR1 binds extracellular cAMP with nanomolar affinity; direct ligand
      binding is well established. This InterPro2GO annotation is correct.
    action: ACCEPT
    reason: cAMP binding is the defining ligand-recognition activity of cAR1,
      supported by direct binding assays.
    supported_by:
    - reference_id: PMID:1648967
      supporting_text: The affinity of the expressed cAR1 was similar to that of the
        endogenous receptors in aggregation stage cells
- term:
    id: GO:0035589
    label: G protein-coupled purinergic nucleotide receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: This electronically inferred term classifies cAR1 signaling as
      purinergic nucleotide receptor signaling. cAR1 is a cAMP receptor whose
      signaling is distinct from classical purinergic (P2X/P2Y) receptor pathways;
      this is an over-propagation from automated inter-ontology inference.
    action: REMOVE
    reason: cAR1 is not a purinergic (ATP/ADP/UTP) receptor; it recognizes the
      second-messenger-derived chemoattractant cAMP. Its signaling is captured
      accurately by the cAMP receptor / adenylate cyclase-activating cAMP receptor
      terms. This IEA (GO_REF:0000108, logical inference) mislabels the pathway and
      should be removed.
- term:
    id: GO:1904776
    label: regulation of protein localization to cell cortex
  evidence_type: IGI
  original_reference_id: PMID:40934557
  qualifier: acts_upstream_of_or_within
  review:
    summary: cAR1 (Car1/3) and G-protein signaling are required for chemoattractant-
      induced cortical/leading-edge translocation of a RasG biosensor, placing cAR1
      upstream of cortical protein localization during chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: A valid downstream developmental/chemotactic consequence of cAR1
      signaling rather than its core molecular function.
    supported_by:
    - reference_id: PMID:40934557
      supporting_text: This localization required GPCR Car1/3 and G-protein signaling
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IMP
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: cAR1 activates adenylyl cyclase (ACA) as part of the cAMP relay. The
      activation is receptor-mediated and G-protein-dependent (indirect) rather than
      cAR1 acting directly on the cyclase, so this MF is best treated as non-core.
    action: KEEP_AS_NON_CORE
    reason: cAR1 mediates activation of adenylyl cyclase, but does so indirectly via
      heterotrimeric G proteins; the direct molecular function is receptor/cAMP
      binding. Retained as non-core.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis,
        activation of adenylyl cyclase and actin polymerization
- term:
    id: GO:0030295
    label: protein kinase activator activity
  evidence_type: IMP
  original_reference_id: PMID:8670837
  qualifier: enables
  review:
    summary: cAMP binding to cAR1 stimulates activation of the MAP kinase ERK2, but
      this occurs through a G-protein/Ras-dependent cascade, not by cAR1 directly
      binding and activating a kinase.
    action: KEEP_AS_NON_CORE
    reason: The kinase activation is an indirect downstream effect of cAR1 signaling;
      the core molecular function is receptor/ligand binding. Retained as non-core.
    supported_by:
    - reference_id: PMID:8670837
      supporting_text: Binding of extracellular cAMP to cAMP receptor 1, a G-protein
        coupled cell surface receptor, transiently stimulates phosphorylation,
        activation and nuclear translocation of ERK2
- term:
    id: GO:0140295
    label: pathogen-derived receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:37866633
  qualifier: enables
  review:
    summary: This annotation assigns cAR1 a pathogen-derived receptor ligand activity.
      cAR1 is a host cell-surface receptor, not a pathogen-derived ligand, and the
      cited study (Legionella LAI-1 delivered via outer membrane vesicles, which
      inhibit Dictyostelium migration) does not mention cAR1 in its full text.
    action: REMOVE
    reason: The molecular function is biologically inverted for cAR1 (a receptor
      cannot have receptor-ligand activity), and the full text of PMID:37866633 does
      not implicate cAR1 as the ligand or receptor for LAI-1. This appears to be a
      curation/mapping error rather than a supportable function.
- term:
    id: GO:0140676
    label: oscillatory cAMP signaling
  evidence_type: IDA
  original_reference_id: PMID:37921687
  qualifier: involved_in
  review:
    summary: cAR1 is the receptor that detects the collective, oscillatory cAMP
      signals that coordinate the developmental gene-expression jump during
      aggregation. Oscillatory cAMP signaling is a central role of cAR1.
    action: ACCEPT
    reason: cAR1 mediates the cell's response to collective oscillations of cAMP; this
      oscillatory cAMP signaling is a core aspect of cAR1 function during aggregation.
    supported_by:
    - reference_id: PMID:37921687
      supporting_text: the jump coincides with the onset of collective oscillations
        of cAMP
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IMP
  original_reference_id: PMID:8280098
  qualifier: involved_in
  review:
    summary: Genetic evidence links cAR1 and its G proteins to cAMP-regulated
      signaling (here, dual regulation of phospholipase C), consistent with cAR1
      operating the G protein-coupled cAMP receptor signaling pathway.
    action: ACCEPT
    reason: cAR1 is a core component of the surface cAMP receptor / G-protein
      signaling module; the paper directly implicates cAR1 with a G protein in cAMP
      signal transduction.
    supported_by:
    - reference_id: PMID:8280098
      supporting_text: The inhibitory pathway is composed of the surface receptor cAR1
        and the G-protein G1
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: IMP
  original_reference_id: PMID:8670837
  qualifier: involved_in
  review:
    summary: cAMP binding to cAR1 transiently activates ERK2 in a G-protein-dependent
      manner, placing cAR1 upstream of the ERK cascade during chemotactic signaling.
    action: ACCEPT
    reason: Directly supported by the finding that cAR1 activation stimulates ERK2
      phosphorylation, activation and nuclear translocation, a genuine downstream
      signaling role.
    supported_by:
    - reference_id: PMID:8670837
      supporting_text: Binding of extracellular cAMP to cAMP receptor 1, a G-protein
        coupled cell surface receptor, transiently stimulates phosphorylation,
        activation and nuclear translocation of ERK2
- term:
    id: GO:0030695
    label: GTPase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:21103944
  qualifier: enables
  review:
    summary: As a GPCR, cAR1 acts as a guanine-nucleotide exchange factor for
      heterotrimeric G proteins and is required for chemoattractant-mediated
      activation of the small GTPase Rap1. Its GTPase-regulator role is receptor-
      driven and largely mediated through the heterotrimeric G proteins.
    action: KEEP_AS_NON_CORE
    reason: cAR1 regulates GTPase cycling indirectly as part of its GPCR function;
      the core molecular activity is receptor/cAMP binding. Retained as non-core.
    supported_by:
    - reference_id: PMID:21103944
      supporting_text: The rapid Rap1 activation upon cAMP chemoattractant stimulation
        was absent in cells lacking chemoattractant cAMP receptors cAR1/cAR3
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IDA
  original_reference_id: PMID:8999903
  qualifier: involved_in
  review:
    summary: Mutagenesis of cAR1 directly demonstrates its role in transducing
      extracellular cAMP signals via G-protein-dependent (and independent)
      mechanisms, the core cAMP receptor signaling pathway.
    action: ACCEPT
    reason: Direct experimental evidence that cAR1 mediates cAMP signal transduction;
      a core process for this receptor.
    supported_by:
    - reference_id: PMID:8999903
      supporting_text: The cAMP chemoattractant receptor, cAR1, of Dictyostelium
        transduces extracellular cAMP signals via G protein-dependent and G
        protein-independent mechanisms
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:21541374
  qualifier: located_in
  review:
    summary: Single-molecule imaging shows the fraction of cytosolic cAR1 increases
      after persistent agonist stimulation, reflecting phosphorylation-dependent
      receptor internalization rather than a steady-state cytosolic pool.
    action: KEEP_AS_NON_CORE
    reason: The cytosolic signal represents internalized receptor during
      desensitization, not the site of the receptor's core signaling function (the
      plasma membrane). Retained as non-core.
    supported_by:
    - reference_id: PMID:21541374
      supporting_text: the fraction of cytosolic receptors increases after persistent
        agonist stimulation
- term:
    id: GO:0031252
    label: cell leading edge
  evidence_type: IDA
  original_reference_id: PMID:18469015
  qualifier: is_active_in
  review:
    summary: Single-molecule microscopy shows an agonist-induced increase in cAR1
      mobility at the leading edge of chemotaxing cells, contributing to directional
      sensing. cAR1 is active at the leading edge.
    action: ACCEPT
    reason: Directly supported localization of active cAR1 to the leading edge during
      chemotaxis, a functionally important site.
    supported_by:
    - reference_id: PMID:18469015
      supporting_text: an agonist-induced increase in the mobile fraction of
        cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum
        cells
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:15507682
  qualifier: involved_in
  review:
    summary: cAR1 is essential for the aggregation stage of Dictyostelium
      development; cAR1 nulls fail to aggregate. Aggregation is a core biological
      process for cAR1.
    action: ACCEPT
    reason: cAR1-mediated cAMP signaling drives the chemotactic aggregation of
      starving cells into a multicellular mound; loss of cAR1 arrests development in
      early aggregation.
    supported_by:
    - reference_id: PMID:1849108
      supporting_text: fail to bind or sense cAMP and arrest in early development
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:17630977
  qualifier: involved_in
  review:
    summary: cAR1 is essential for multicellular development; constitutively active
      Ile-104 mutants block development, confirming cAR1's role in aggregation-stage
      development.
    action: ACCEPT
    reason: Directly supported requirement of properly regulated cAR1 for the
      aggregation/development program.
    supported_by:
    - reference_id: PMID:17630977
      supporting_text: cAR1, a G protein-coupled cAMP receptor, is essential for
        multicellular development of Dictyostelium
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: involved_in
  review:
    summary: cAR1/carA is expressed during the aggregation phase when starving cells
      communicate via extracellular cAMP. Expression-pattern evidence is consistent
      with, but weaker than, the mutant-based support for a role in aggregation.
    action: KEEP_AS_NON_CORE
    reason: IEP (expression) evidence corroborates the aggregation role established by
      mutant studies; retained as non-core given the weaker evidence type.
    supported_by:
    - reference_id: PMID:25887420
      supporting_text: communicate via extracellular cAMP, aggregate by tens of
        thousands and develop into multicellular organisms
- term:
    id: GO:0097696
    label: cell surface receptor signaling pathway via STAT
  evidence_type: IMP
  original_reference_id: PMID:9670017
  qualifier: involved_in
  review:
    summary: Extracellular cAMP acting through cAR1 rapidly induces tyrosine
      phosphorylation and nuclear translocation of Dd-STAT, a G protein-independent
      signaling output of the receptor.
    action: ACCEPT
    reason: Directly supported role of cAR1 in mediating STAT (Dd-STAT) activation, a
      genuine signaling pathway downstream of the receptor.
    supported_by:
    - reference_id: PMID:9670017
      supporting_text: The tyrosine phosphorylation and nuclear localization of
        Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine
        cAMP receptor cAR1
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: is_active_in
  review:
    summary: cAR1 is a plasma-membrane chemoattractant receptor; this is a
      well-established, traceable statement in the chemoattractant-signaling
      literature.
    action: ACCEPT
    reason: Plasma membrane is the functional location of cAR1, corroborated by
      direct biochemical/microscopy evidence.
    supported_by:
    - reference_id: PMID:9168471
      supporting_text: Cell surface biotinylation and preembedding immunoelectron
        microscopy both confirmed the plasma membrane origin of this preparation
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9168471
  qualifier: is_active_in
  review:
    summary: cAR1 is enriched in detergent-resistant plasma-membrane microdomains;
      the plasma membrane origin was directly confirmed by surface biotinylation and
      immunoelectron microscopy.
    action: ACCEPT
    reason: Direct experimental confirmation of cAR1's plasma membrane localization,
      the site of its receptor function.
    supported_by:
    - reference_id: PMID:9168471
      supporting_text: Cell surface biotinylation and preembedding immunoelectron
        microscopy both confirmed the plasma membrane origin of this preparation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25143405
  qualifier: enables
  review:
    summary: cAR1 physically interacts with arrestin domain-containing proteins
      (AdcC); activation of cAR1 recruits AdcC to the membrane and links the receptor
      to periodic ERK2 activation and internalization. The bare protein binding term
      is uninformative.
    action: KEEP_AS_NON_CORE
    reason: The specific interaction (arrestin binding regulating cAR1 signaling and
      internalization) is informative, but the generic GO:0005515 term does not
      convey function; retained as non-core. A more specific arrestin-binding
      molecular function would be preferable.
    supported_by:
    - reference_id: PMID:25143405
      supporting_text: activation of cAR1 promotes the transient membrane recruitment
        of AdcC and interaction with cAR1
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:7628637
  qualifier: located_in
  review:
    summary: Internalized cAR1 localizes with acidosomes, which the authors argue are
      analogous to early/recycling endosomes and may be a site for recycling of
      internalized receptors.
    action: KEEP_AS_NON_CORE
    reason: Endosomal localization reflects receptor trafficking/recycling after
      internalization rather than the core plasma-membrane signaling function.
      Retained as non-core.
    supported_by:
    - reference_id: PMID:7628637
      supporting_text: acidosomes contain abundant receptors for cyclic AMP (CAR1) and
        that it may be the site for recycling of internalized receptors
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:15507682
  qualifier: is_active_in
  review:
    summary: cAR1 is a cell-surface cAMP receptor, consistent with its plasma-membrane
      localization and function in sensing extracellular cAMP.
    action: ACCEPT
    reason: cAR1 acts at the cell surface where it binds extracellular cAMP;
      corroborated by its description as a surface cAMP receptor.
    supported_by:
    - reference_id: PMID:1849108
      supporting_text: cAR1, a G-protein-linked surface cAMP receptor, plays a central
        role in the development of Dictyostelium
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: IMP
  original_reference_id: PMID:15507682
  qualifier: involved_in
  review:
    summary: cAR1 mediates chemotaxis toward cAMP, the defining behavioral response
      it controls during aggregation.
    action: ACCEPT
    reason: cAR1 is required for directed migration up cAMP gradients; chemotaxis is a
      core biological process for the receptor.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis,
        activation of adenylyl cyclase and actin polymerization
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: IGI
  original_reference_id: PMID:9578623
  qualifier: involved_in
  review:
    summary: Genetic complementation of car1-/car3- cells with cAR1 restores
      chemotaxis, confirming cAR1's role in chemotactic responses to cAMP.
    action: ACCEPT
    reason: cAR1 mediates chemotaxis to cAMP; a core biological process directly
      tested by receptor expression assays.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis,
        activation of adenylyl cyclase and actin polymerization
- term:
    id: GO:0023058
    label: adaptation of signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:23902692
  qualifier: involved_in
  review:
    summary: Agonist-induced phosphorylation of cAR1 is required for adaptation of
      adenylyl cyclase responses and for proper long-range oscillatory cAMP wave
      production, a signaling-adaptation function.
    action: ACCEPT
    reason: Non-phosphorylatable cAR1 mutants fail to adapt adenylyl cyclase and lose
      directional chemotaxis, directly demonstrating cAR1's role in signaling
      adaptation.
    supported_by:
    - reference_id: PMID:23902692
      supporting_text: receptor phosphorylation is required to regulate adenylyl
        cyclase adaptation, long-range oscillatory cAMP wave production and
        cytoskeletal actin response
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: involved_in
  review:
    summary: FRET imaging in living cells shows chemoattractant (cAMP) binding to the
      receptor drives dissociation/reassociation of the heterotrimeric G protein,
      directly demonstrating the cAMP receptor signaling pathway.
    action: ACCEPT
    reason: Direct in vivo evidence that cAR1 catalyzes the G-protein cycle upon cAMP
      binding; core to cAMP receptor signaling.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: The G-protein heterotrimer rapidly dissociated and reassociated
        upon addition and removal of chemoattractant
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IMP
  original_reference_id: PMID:7949426
  qualifier: involved_in
  review:
    summary: cAR1 is the primary receptor mediating cAMP responses (cAMP relay, cGMP
      synthesis) coupled through a heterotrimeric G protein; car1- cells have
      strongly reduced responses.
    action: ACCEPT
    reason: Genetic evidence that cAR1 normally mediates cAMP-relay and other
      responses via a heterotrimeric G protein; core cAMP receptor signaling.
    supported_by:
    - reference_id: PMID:7949426
      supporting_text: Dictyostelium cells respond to cAMP using one such receptor,
        cAR1, coupled by a typical heterotrimeric G-protein to intracellular effectors
- term:
    id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  evidence_type: IGI
  original_reference_id: PMID:7949426
  qualifier: involved_in
  review:
    summary: Double car1-/car3- deletion abolishes cAMP sensitivity, and cAR1 and
      cAR3 act redundantly through the same G protein, confirming cAR1's role in the
      cAMP receptor signaling pathway.
    action: ACCEPT
    reason: Genetic interaction evidence that cAR1 (with cAR3) mediates cAMP signaling
      via a shared heterotrimeric G protein.
    supported_by:
    - reference_id: PMID:7949426
      supporting_text: both interact with the same heterotrimeric G-protein to mediate
        these and other responses
- term:
    id: GO:1903013
    label: response to differentiation-inducing factor 1
  evidence_type: HDA
  original_reference_id: PMID:25518940
  qualifier: involved_in
  review:
    summary: Phosphoproteomic analysis shows the cAMP receptor is rapidly
      dephosphorylated in response to DIF-1, reflecting cross-talk/antagonism between
      DIF-1 and cAMP signaling.
    action: KEEP_AS_NON_CORE
    reason: cAR1's dephosphorylation in response to DIF-1 is a regulatory cross-talk
      response, not a core function of the receptor. Retained as non-core.
    supported_by:
    - reference_id: PMID:25518940
      supporting_text: the rapid dephosphorylation of the cAMP receptor that we
        observe in response to DIF-1
- term:
    id: GO:0001637
    label: G protein-coupled chemoattractant receptor activity
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: enables
  review:
    summary: cAR1 is the G protein-coupled receptor for the chemoattractant cAMP;
      occupied receptors directly catalyze the G-protein cycle as shown by live-cell
      FRET. This is a core molecular function.
    action: ACCEPT
    reason: Directly supported chemoattractant GPCR activity coupling cAMP detection
      to heterotrimeric G-protein activation.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: occupied receptors, whether or not they are phosphorylated,
        catalyze the G-protein cycle
- term:
    id: GO:0001646
    label: cAMP receptor activity
  evidence_type: IDA
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: cAR1 is the founding member of the Dictyostelium cAMP receptor family
      and functions as a cAMP receptor; direct expression/complementation assays
      confirm this activity. This is the core molecular function.
    action: ACCEPT
    reason: Directly supported cAMP receptor activity; the defining function of cAR1.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: The cAMP chemoattractant receptor family of Dictyostelium
        discoideum is composed of four receptors (cAR1-cAR4)
- term:
    id: GO:0001646
    label: cAMP receptor activity
  evidence_type: IGI
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: Complementation of receptor-null cells with cAR1 restores cAMP responses,
      genetically confirming cAR1 cAMP receptor activity.
    action: ACCEPT
    reason: cAMP receptor activity is the core molecular function of cAR1; supported
      by genetic complementation.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: The cAMP chemoattractant receptor family of Dictyostelium
        discoideum is composed of four receptors (cAR1-cAR4)
- term:
    id: GO:0010225
    label: response to UV-C
  evidence_type: IDA
  original_reference_id: PMID:25858552
  qualifier: acts_upstream_of_or_within
  review:
    summary: carA/car1 is among the developmentally regulated genes whose expression
      was examined during the UV-C response of Dictyostelium; this is a stress-
      response context rather than a core receptor function.
    action: KEEP_AS_NON_CORE
    reason: cAR1 involvement here reflects developmental gene-expression changes under
      UV-C stress, not the receptor's core molecular role. Retained as non-core.
    supported_by:
    - reference_id: PMID:25858552
      supporting_text: 'Expression of developmentally regulated genes yakA, car1, aca,
        csA, regA, ctnA, ctnB, gp24, hspD and dsn were analysed using semiquantitative
        RT-PCR'
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:15507682
  qualifier: enables
  review:
    summary: cAR1 directly binds extracellular cAMP; ligand binding is the receptor's
      defining biochemical activity, well documented across many studies.
    action: ACCEPT
    reason: cAMP binding is a core molecular function of cAR1, supported by direct
      binding measurements.
    supported_by:
    - reference_id: PMID:1648967
      supporting_text: The affinity of the expressed cAR1 was similar to that of the
        endogenous receptors in aggregation stage cells
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:1648967
  qualifier: enables
  review:
    summary: Direct binding assays show cAR1 binds cAMP with nanomolar affinity (two
      affinity states, Kd ~30 and 300 nM), matching endogenous aggregation-stage
      receptors.
    action: ACCEPT
    reason: Direct measurement of cAR1 cAMP binding affinity; a core molecular
      function.
    supported_by:
    - reference_id: PMID:1648967
      supporting_text: two affinity states with Kd's of
    - reference_id: PMID:1648967
      supporting_text: The affinity of the expressed cAR1 was similar to that of the
        endogenous receptors in aggregation stage cells
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IMP
  original_reference_id: PMID:17630977
  qualifier: enables
  review:
    summary: Ile-104 substitutions in cAR1 dramatically alter the receptor's cAMP
      affinity, demonstrating that cAR1 binds cAMP and that this residue tunes ligand
      affinity.
    action: ACCEPT
    reason: Mutational evidence directly implicating cAR1 in cAMP binding (affinity
      modulation); core molecular function.
    supported_by:
    - reference_id: PMID:17630977
      supporting_text: all Ile(104) substitutions, except for the most conservative,
        dramatically elevated the receptor's cAMP affinity
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:8999903
  qualifier: enables
  review:
    summary: Random mutagenesis identified cAR1 mutants with altered cAMP binding
      (including conditional binding defects), directly demonstrating cAR1 cAMP
      binding activity.
    action: ACCEPT
    reason: Direct biochemical evidence for cAR1 cAMP binding; core molecular
      function.
    supported_by:
    - reference_id: PMID:8999903
      supporting_text: One class had a conditional defect in cAMP binding that was
        reversed by high salt
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IMP
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: cAR1 and related receptors sense different concentration ranges of cAMP;
      mutations altering ligand recognition confirm cAR1 cAMP binding activity.
    action: ACCEPT
    reason: Mutational evidence that cAR1 binds cAMP; core molecular function.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: various receptors and mutants sense different concentration
        ranges of cAMP
- term:
    id: GO:1904643
    label: response to curcumin
  evidence_type: IDA
  original_reference_id: PMID:26449461
  qualifier: involved_in
  review:
    summary: Curcumin delays Dictyostelium chemotaxis, adhesion and development. This
      is a chemical/developmental response of the organism rather than a core cAR1
      molecular function.
    action: KEEP_AS_NON_CORE
    reason: cAR1's involvement reflects curcumin's inhibitory effect on cAMP-driven
      chemotaxis and development, a stimulus-response phenotype rather than a core
      receptor function. Retained as non-core.
    supported_by:
    - reference_id: PMID:26449461
      supporting_text: This resulted in delayed chemotaxis, adhesion, and development
        of the organism
- term:
    id: GO:1902168
    label: response to catechin
  evidence_type: IDA
  original_reference_id: PMID:23516620
  qualifier: involved_in
  review:
    summary: The green-tea catechin EGCG reduces random movement and chemotaxis of
      Dictyostelium and stalls development, a chemical-response phenotype affecting
      cAMP-driven chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: Reflects a stimulus-response (catechin) effect on chemotaxis/development
      rather than a core cAR1 molecular function. Retained as non-core.
    supported_by:
    - reference_id: PMID:23516620
      supporting_text: EGCG reduces both random movement and chemotaxis of
        Dictyostelium amoebae
- term:
    id: GO:0050764
    label: regulation of phagocytosis
  evidence_type: IMP
  original_reference_id: PMID:17905919
  qualifier: acts_upstream_of_or_within
  review:
    summary: Extracellular cAMP pulses (sensed via cAR1) are sufficient to induce
      developmental commitment and the loss of phagocytosis in starving cells,
      placing cAR1 signaling upstream of phagocytosis regulation.
    action: KEEP_AS_NON_CORE
    reason: Down-regulation of phagocytosis is a developmental consequence of cAMP and
      cAR1 signaling during commitment, not a core receptor function. Retained as
      non-core.
    supported_by:
    - reference_id: PMID:17905919
      supporting_text: cAMP pulses are sufficient to induce both commitment and the
        loss of phagocytosis in starving cells
- term:
    id: GO:0002029
    label: desensitization of G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15574880
  qualifier: involved_in
  review:
    summary: cAR1-mediated pathways undergo adaptation/desensitization;
      constitutively active DN mutants block development by turning on natural
      adaptation mechanisms, implicating cAR1 in GPCR desensitization.
    action: ACCEPT
    reason: Directly supported role of cAR1 in adaptation/desensitization of its
      signaling; a genuine regulatory process for the receptor.
    supported_by:
    - reference_id: PMID:15574880
      supporting_text: The activation of multiple pathways by cAR1 is transient
        because of poorly defined adaptation mechanisms
- term:
    id: GO:0008277
    label: regulation of G protein-coupled receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:11264536
  qualifier: involved_in
  review:
    summary: Live-cell FRET shows that G-protein activation by occupied cAR1 reaches a
      steady state and does not decline even as responses adapt, informing how cAR1
      GPCR signaling is regulated.
    action: KEEP_AS_NON_CORE
    reason: Captures regulation of cAR1's own GPCR signaling (adaptation occurring
      downstream of the receptor); a regulatory aspect retained as non-core relative
      to the core receptor activity.
    supported_by:
    - reference_id: PMID:11264536
      supporting_text: adaptation occurs at another point in the signaling pathway,
        and occupied receptors, whether or not they are phosphorylated, catalyze the
        G-protein cycle
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:1849108
  qualifier: involved_in
  review:
    summary: Gene targeting shows cAR1-null mutants fail to bind/sense cAMP and arrest
      in early development, proving cAR1-mediated signaling controls the aggregation
      stage of development.
    action: ACCEPT
    reason: Definitive genetic evidence that cAR1 is required for aggregation-stage
      development; a core biological process.
    supported_by:
    - reference_id: PMID:1849108
      supporting_text: fail to bind or sense cAMP and arrest in early development
    - reference_id: PMID:1849108
      supporting_text: cAR1-mediated signal transduction controls the development of
        Dictyostelium
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:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  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:11264536
  title: Receptor-mediated activation of heterotrimeric G-proteins in living cells.
  findings:
  - statement: Occupied cAR1, whether or not phosphorylated, catalyzes the
      heterotrimeric G-protein cycle, with rapid dissociation/reassociation on cAMP
      addition/removal.
    supporting_text: occupied receptors, whether or not they are phosphorylated,
      catalyze the G-protein cycle
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; live-cell FRET directly demonstrates cAR1-driven
      heterotrimeric G-protein activation.
- id: PMID:15473840
  title: Chemoattractant signaling in dictyostelium discoideum.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Authoritative review of chemoattractant (cAR1) signaling; supports
      the plasma-membrane receptor framing though it is secondary literature.
- id: PMID:15507682
  title: A rapid and efficient method to generate multiple gene disruptions in Dictyostelium
    discoideum using a single selectable marker and the Cre-loxP system.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Primarily a Cre-loxP methods paper; cached full text lacks a results
      section describing cAR1 function. The cAR1 annotations attributed to it are
      corroborated here by other primary references.
- id: PMID:15574880
  title: Constitutively active G protein-coupled receptor mutants block dictyostelium
    development.
  findings:
  - statement: cAR1 is a GPCR for cAMP required for multicellular development; its
      pathway activation is transient due to adaptation.
    supporting_text: The activation of multiple pathways by cAR1 is transient because
      of poorly defined adaptation mechanisms
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; dominant-negative cAR1 mutants directly implicate
      the receptor in adaptation/desensitization.
- id: PMID:1648967
  title: Overexpression of the cAMP receptor 1 in growing Dictyostelium cells.
  findings:
  - statement: cAR1 binds cAMP with nanomolar affinity (two affinity states, Kd ~30
      and 300 nM).
    supporting_text: two affinity states with Kd's of
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; provides direct cAMP binding-affinity measurements
      for cAR1.
- id: PMID:17630977
  title: Regulation of G protein-coupled cAMP receptor activation by a hydrophobic
    residue in transmembrane helix 3.
  findings:
  - statement: cAR1 is essential for multicellular development; Ile-104 substitutions
      elevate cAMP affinity and can lock the receptor active.
    supporting_text: cAR1, a G protein-coupled cAMP receptor, is essential for
      multicellular development of Dictyostelium
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; mutational analysis of cAR1 activation and cAMP
      affinity.
- id: PMID:17905919
  title: Developmental commitment in Dictyostelium discoideum.
  findings:
  - statement: cAMP pulses induce developmental commitment and loss of phagocytosis
      in starving cells.
    supporting_text: cAMP pulses are sufficient to induce both commitment and the
      loss of phagocytosis in starving cells
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; links cAMP signaling to phagocytosis regulation
      during commitment.
- id: PMID:18469015
  title: A spatially restricted increase in receptor mobility is involved in directional
    sensing during Dictyostelium discoideum chemotaxis.
  findings:
  - statement: Agonist stimulation increases the mobile fraction of cAMP receptor at
      the leading edge, contributing to directional sensing.
    supporting_text: an agonist-induced increase in the mobile fraction of
      cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; single-molecule evidence for cAR1 dynamics at the
      leading edge.
- id: PMID:1849108
  title: Gene targeting of the aggregation stage cAMP receptor cAR1 in Dictyostelium.
  findings:
  - statement: cAR1-null mutants fail to bind or sense cAMP and arrest in early
      development, proving cAR1 controls development.
    supporting_text: fail to bind or sense cAMP and arrest in early development
  - statement: cAR1-mediated signal transduction controls Dictyostelium development.
    supporting_text: cAR1-mediated signal transduction controls the development of
      Dictyostelium
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; foundational gene-targeting evidence for cAR1's
      essential developmental role.
- id: PMID:21103944
  title: Chemoattractant-mediated Rap1 activation requires GPCR/G proteins.
  findings:
  - statement: Chemoattractant-induced Rap1 activation requires cAR1/cAR3 and Galpha2.
    supporting_text: The rapid Rap1 activation upon cAMP chemoattractant stimulation
      was absent in cells lacking chemoattractant cAMP receptors cAR1/cAR3
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; places cAR1 upstream of Rap1 GTPase activation.
- id: PMID:21541374
  title: Quantification of GPCR internalization by single-molecule microscopy in living
    cells.
  findings:
  - statement: Persistent agonist stimulation increases the cytosolic fraction of
      cAR1 via phosphorylation-dependent internalization.
    supporting_text: the fraction of cytosolic receptors increases after persistent
      agonist stimulation
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; documents cAR1 internalization/trafficking.
- id: PMID:23516620
  title: The green tea catechin epigallocatechin gallate (EGCG) blocks cell motility,
    chemotaxis and development in Dictyostelium discoideum.
  findings:
  - statement: EGCG reduces random movement and chemotaxis of Dictyostelium amoebae.
    supporting_text: EGCG reduces both random movement and chemotaxis of Dictyostelium
      amoebae
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified; catechin effect on chemotaxis/development, an
      indirect cAR1-related phenotype.
- id: PMID:23902692
  title: Phosphorylation of chemoattractant receptors regulates chemotaxis, actin
    reorganization and signal relay.
  findings:
  - statement: cAR1 phosphorylation is required for adenylyl cyclase adaptation and
      oscillatory cAMP wave production.
    supporting_text: receptor phosphorylation is required to regulate adenylyl cyclase
      adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin
      response
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; directly ties cAR1 phosphorylation to adaptation
      and signal relay.
- id: PMID:25143405
  title: Arrestins function in cAR1 GPCR-mediated signaling and cAR1 internalization
    in the development of Dictyostelium discoideum.
  findings:
  - statement: Activation of cAR1 recruits arrestin AdcC to the membrane and links the
      receptor to periodic ERK2 activation and internalization.
    supporting_text: activation of cAR1 promotes the transient membrane recruitment of
      AdcC and interaction with cAR1
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; defines a specific cAR1 protein-protein interaction
      (arrestin) regulating signaling/internalization.
- id: PMID:25518940
  title: The Dictyostelium prestalk inducer differentiation-inducing factor-1 (DIF-1)
    triggers unexpectedly complex global phosphorylation changes.
  findings:
  - statement: DIF-1 rapidly dephosphorylates the cAMP receptor, reflecting DIF-1/cAMP
      signaling antagonism.
    supporting_text: the rapid dephosphorylation of the cAMP receptor that we observe
      in response to DIF-1
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified; phosphoproteomic cross-talk finding, peripheral to
      core cAR1 function.
- id: PMID:25858552
  title: Response of Dictyostelium discoideum to UV-C and involvement of poly (ADP-ribose)
    polymerase.
  findings:
  - statement: carA/car1 expression was analysed among developmentally regulated genes
      in the UV-C response.
    supporting_text: 'Expression of developmentally regulated genes yakA, car1, aca,
      csA, regA, ctnA, ctnB, gp24, hspD and dsn were analysed using semiquantitative
      RT-PCR'
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified; car1 appears only as one of many developmental
      marker genes examined under UV-C.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings:
  - statement: Starving cells communicate via extracellular cAMP and aggregate into
      multicellular organisms.
    supporting_text: communicate via extracellular cAMP, aggregate by tens of thousands
      and develop into multicellular organisms
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified; transcriptome study providing expression-context
      support for cAR1's aggregation role.
- id: PMID:26449461
  title: 'Curcumin inhibits development and cell adhesion in Dictyostelium discoideum:
    Implications for YakA signaling and GST enzyme function.'
  findings:
  - statement: Curcumin delays chemotaxis, adhesion and development in Dictyostelium.
    supporting_text: This resulted in delayed chemotaxis, adhesion, and development of
      the organism
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified; chemical-response phenotype, indirectly related to
      cAR1-driven chemotaxis.
- id: PMID:37866633
  title: The Legionella autoinducer LAI-1 is delivered by outer membrane vesicles
    to promote interbacterial and interkingdom signaling.
  findings:
  - statement: Legionella LAI-1, delivered via outer membrane vesicles, inhibits
      Dictyostelium migration; the paper does not identify cAR1 as a receptor or
      ligand.
    supporting_text: inhibit the migration of Dictyostelium discoideum amoeba
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: Full text does not mention cAR1; the GO:0140295 pathogen-derived
      receptor ligand activity annotation to cAR1 appears to be a curation/mapping
      error and is recommended for removal.
- id: PMID:37921687
  title: Collective signalling drives rapid jumping between cell states.
  findings:
  - statement: A global gene-expression jump coincides with the onset of collective
      oscillations of cAMP, sensed via cAR1.
    supporting_text: the jump coincides with the onset of collective oscillations of
      cAMP
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; supports cAR1's role in responding to oscillatory
      cAMP signaling.
- id: PMID:40934557
  title: The Ras association domain of DydA as a specific reporter of activated RasG
    in Dictyostelium.
  findings:
  - statement: Chemoattractant-induced cortical/leading-edge RasG activation requires
      GPCR Car1/3 and G-protein signaling.
    supporting_text: This localization required GPCR Car1/3 and G-protein signaling
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; places cAR1 upstream of cortical RasG activation
      during chemotaxis.
- id: PMID:7628637
  title: Localization of cyclic-AMP receptors with acidosomes in Dictyostelium discoideum.
  findings:
  - statement: Internalized cAR1 localizes with acidosomes, proposed to be early/
      recycling endosome-like compartments.
    supporting_text: acidosomes contain abundant receptors for cyclic AMP (CAR1) and
      that it may be the site for recycling of internalized receptors
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; supports endosomal/trafficking localization of
      internalized cAR1.
- id: PMID:7949426
  title: Two cAMP receptors activate common signaling pathways in Dictyostelium.
  findings:
  - statement: cAR1 is coupled by a heterotrimeric G protein to intracellular
      effectors and normally mediates cAMP responses; cAR1/cAR3 are partially
      redundant.
    supporting_text: cAR1, coupled by a typical heterotrimeric G-protein to
      intracellular effectors
  - statement: cAR1 and cAR3 interact with the same heterotrimeric G protein.
    supporting_text: both interact with the same heterotrimeric G-protein to mediate
      these and other responses
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; establishes cAR1 as the primary cAMP receptor and
      its G-protein coupling.
- id: PMID:8280098
  title: Phospholipase C in Dictyostelium discoideum. Identification of stimulatory
    and inhibitory surface receptors and G-proteins.
  findings:
  - statement: cAR1 (with G-protein G1) forms the inhibitory arm of dual PLC
      regulation by cAMP.
    supporting_text: The inhibitory pathway is composed of the surface receptor cAR1
      and the G-protein G1
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified; genetic/biochemical evidence coupling cAR1 to a
      G protein in cAMP signaling.
- id: PMID:8670837
  title: Dual role of cAMP and involvement of both G-proteins and ras in regulation
    of ERK2 in Dictyostelium discoideum.
  findings:
  - statement: cAMP binding to cAR1 transiently activates ERK2 in a
      G-protein-dependent manner.
    supporting_text: Binding of extracellular cAMP to cAMP receptor 1, a G-protein
      coupled cell surface receptor, transiently stimulates phosphorylation,
      activation and nuclear translocation of ERK2
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; directly links cAR1 to the ERK2 cascade.
- id: PMID:8999903
  title: Random mutagenesis of the cAMP chemoattractant receptor, cAR1, of Dictyostelium.
    Mutant classes that cause discrete shifts in agonist affinity and lock the receptor
    in a novel activational intermediate.
  findings:
  - statement: cAR1 transduces extracellular cAMP via G protein-dependent and
      -independent mechanisms; mutants alter cAMP binding.
    supporting_text: The cAMP chemoattractant receptor, cAR1, of Dictyostelium
      transduces extracellular cAMP signals via G protein-dependent and G
      protein-independent mechanisms
  - statement: A mutant class showed a conditional cAMP-binding defect reversed by
      high salt.
    supporting_text: One class had a conditional defect in cAMP binding that was
      reversed by high salt
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; structure-function mutagenesis of cAR1 cAMP binding
      and signaling.
- id: PMID:9168471
  title: 'Identification of detergent-resistant plasma membrane microdomains in dictyostelium:
    enrichment of signal transduction proteins.'
  findings:
  - statement: cAR1 is enriched in detergent-resistant plasma-membrane microdomains,
      confirmed as plasma-membrane in origin.
    supporting_text: Cell surface biotinylation and preembedding immunoelectron
      microscopy both confirmed the plasma membrane origin of this preparation
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; direct evidence for cAR1 plasma-membrane
      localization.
- id: PMID:9578623
  title: 'Switching of chemoattractant receptors programs development and morphogenesis
    in Dictyostelium: receptor subtypes activate common responses at different agonist
    concentrations.'
  findings:
  - statement: cAR1 is the first of four sequentially expressed cAMP receptors and
      mediates chemotaxis, adenylyl cyclase activation and actin polymerization.
    supporting_text: assessed the capacity of each to mediate chemotaxis, activation
      of adenylyl cyclase and actin polymerization
  - statement: The Dictyostelium cAMP receptor family comprises four receptors
      (cAR1-cAR4) expressed sequentially during development.
    supporting_text: The cAMP chemoattractant receptor family of Dictyostelium
      discoideum is composed of four receptors (cAR1-cAR4)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; defines cAR1 within the cAR family and its core
      response repertoire.
- id: PMID:9670017
  title: Developmentally and spatially regulated activation of a Dictyostelium STAT
    protein by a serpentine receptor.
  findings:
  - statement: Extracellular cAMP acting through cAR1 rapidly induces Dd-STAT tyrosine
      phosphorylation and nuclear translocation.
    supporting_text: The tyrosine phosphorylation and nuclear localization of Dd-STAT
      are induced very rapidly by extracellular cAMP through the serpentine cAMP
      receptor cAR1
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; establishes cAR1's G protein-independent STAT
      activation pathway.
core_functions:
- description: cAR1 is the cell-surface cAMP receptor that binds extracellular cAMP,
    the chemoattractant coordinating aggregation. Acting as a seven-transmembrane
    GPCR at the plasma membrane, cAR1 detects cAMP to drive directed chemotaxis and
    the developmental aggregation program.
  molecular_function:
    id: GO:0001646
    label: cAMP receptor activity
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0031252
    label: cell leading edge
  directly_involved_in:
  - id: GO:0006935
    label: chemotaxis
  - id: GO:0031152
    label: aggregation involved in sorocarp development
  supported_by:
  - reference_id: PMID:9578623
    supporting_text: The cAMP chemoattractant receptor family of Dictyostelium
      discoideum is composed of four receptors (cAR1-cAR4)
  - reference_id: PMID:1849108
    supporting_text: fail to bind or sense cAMP and arrest in early development
- description: As a G protein-coupled chemoattractant receptor, cAR1 couples cAMP
    detection to activation of heterotrimeric G proteins (Galpha2/Gbeta), catalyzing
    the G-protein cycle to trigger the adenylate cyclase-activating cAMP receptor
    signaling pathway (the cAMP relay) and downstream effectors during aggregation.
  molecular_function:
    id: GO:0001637
    label: G protein-coupled chemoattractant receptor activity
  locations:
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0140582
    label: adenylate cyclase-activating G protein-coupled cAMP receptor signaling
      pathway
  supported_by:
  - reference_id: PMID:11264536
    supporting_text: occupied receptors, whether or not they are phosphorylated,
      catalyze the G-protein cycle
  - reference_id: PMID:7949426
    supporting_text: cAR1, coupled by a typical heterotrimeric G-protein to
      intracellular effectors
- description: cAR1 directly binds the extracellular chemoattractant cAMP with
    nanomolar affinity at the plasma membrane; this ligand-binding activity is the
    biochemical basis for its receptor function and is tunable by mutations in the
    transmembrane core.
  molecular_function:
    id: GO:0030552
    label: cAMP binding
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:1648967
    supporting_text: The affinity of the expressed cAR1 was similar to that of the
      endogenous receptors in aggregation stage cells
  - reference_id: PMID:8999903
    supporting_text: One class had a conditional defect in cAMP binding that was
      reversed by high salt

Gene Description

Existing Annotations Review

Core Functions

cAR1 is the cell-surface cAMP receptor that binds extracellular cAMP, the chemoattractant coordinating aggregation. Acting as a seven-transmembrane GPCR at the plasma membrane, cAR1 detects cAMP to drive directed chemotaxis and the developmental aggregation program.

cAR1 directly binds the extracellular chemoattractant cAMP with nanomolar affinity at the plasma membrane; this ligand-binding activity is the biochemical basis for its receptor function and is tunable by mutations in the transmembrane core.

References

📄 View Raw YAML