carC

id: P35352
gene_symbol: carC
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: Cyclic AMP receptor 3 (cAR3, carC) is one of four serpentine
  seven-transmembrane G protein-coupled cAMP receptors of the social amoeba
  Dictyostelium discoideum. It is an intermediate-affinity receptor for
  extracellular cAMP that is induced at early aggregation and reaches maximal
  expression during the multicellular mound and slug stages. Like its close
  paralog cAR1 (carA), cAR3 couples through heterotrimeric G proteins (notably
  Galpha2) to intracellular effectors, triggering activation of adenylyl cyclase
  (cAMP relay), guanylyl cyclase, actin polymerization and small-GTPase (Rap1)
  signaling. Through these outputs it mediates chemotaxis toward cAMP and the
  aggregation of individual cells into a multicellular organism, and it
  contributes to the developmentally regulated gene-expression program. cAR1 and
  cAR3 are partially redundant, and cells lacking both receptors are unresponsive
  to cAMP, whereas single mutants retain substantial signaling. The receptor is a
  plasma-membrane glycoprotein whose C-terminal cytoplasmic tail can be
  phosphorylated.
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: cAR3 is a bona fide serpentine (7TM) G protein-coupled receptor of
      the Dictyostelium cAR family that signals through heterotrimeric G
      proteins. The phylogenetic inference is correct and consistent with direct
      experimental evidence.
    action: ACCEPT
    reason: cAR3 belongs to the cAMP receptor GPCR family and couples to
      heterotrimeric G proteins, as shown directly by the loss of cAMP responses
      in car1-/car3- cells and their dependence on Galpha2. The more specific MF
      is cAMP receptor activity (GO:0001646), but the general GPCR activity term
      is also correct.
    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:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: cAR3 is a multi-pass plasma-membrane receptor that senses
      extracellular cAMP at the cell surface. Plasma-membrane localization is
      correct and is the site where the receptor is active.
    action: ACCEPT
    reason: As a cell-surface cAMP receptor with seven transmembrane helices,
      cAR3 is an integral plasma-membrane protein, consistent with its role in
      detecting the extracellular chemoattractant.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- 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: cAR3 activation leads to stimulation of adenylyl cyclase (cAMP
      relay) via heterotrimeric G proteins, so participation in an adenylate
      cyclase-activating GPCR signaling pathway is correct. A cAMP-ligand
      specific child term (GO:0140582) is also annotated and is more precise.
    action: ACCEPT
    reason: Both cAR1 and cAR3 mediate cAMP relay (adenylyl cyclase activation),
      which is lost in car1-/car3- cells. The pathway annotation is well
      supported, though the cAMP-specific term GO:0140582 captures the ligand.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: activation of adenylyl cyclase
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: This InterPro2GO annotation is a correct but general parent of the
      more informative cAMP receptor activity and GPCR activity terms already
      annotated to cAR3.
    action: KEEP_AS_NON_CORE
    reason: The term is technically correct (cAR3 is a transmembrane signaling
      receptor) but is subsumed by the more specific cAMP receptor activity
      (GO:0001646) and GPCR activity (GO:0004930) annotations, so it is not the
      core function.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO assignment of GPCR activity from the cAMP receptor
      domain (IPR000848). Correct and concordant with the IBA and experimental
      evidence.
    action: ACCEPT
    reason: cAR3 is a member of the Dictyostelium cAMP GPCR family; the
      domain-based assignment of GPCR activity is accurate.
    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:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: A very general biological-process term. cAR3 is a signaling
      receptor, so this is correct but uninformative relative to the specific
      GPCR/cAMP signaling pathway terms already present.
    action: KEEP_AS_NON_CORE
    reason: Correct at a high level but far too general to represent the core
      biology; the specific pathway terms (GO:0140582, GO:0007189) are the
      informative annotations.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: activate common responses at different agonist
- 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; cAR3 is a cell-surface receptor that
      transduces an extracellular signal. Subsumed by the more specific GPCR
      signaling pathway annotations.
    action: KEEP_AS_NON_CORE
    reason: Accurate but general; the specific adenylate cyclase-activating GPCR
      cAMP receptor signaling pathway is the informative term.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- 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: cAR3 signals as a GPCR through heterotrimeric G proteins, so this
      pathway term is correct. It is a general parent of the cAMP-specific and
      adenylate cyclase-activating child terms already annotated.
    action: KEEP_AS_NON_CORE
    reason: Correct but general; the more specific cAMP receptor signaling
      pathway terms better capture the core function.
    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:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: General membrane localization inferred from the multi-pass
      membrane domain. Correct but subsumed by the more specific plasma membrane
      annotation.
    action: KEEP_AS_NON_CORE
    reason: cAR3 is an integral membrane protein, but plasma membrane
      (GO:0005886) is the specific, informative location.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Domain-based (InterPro) inference of cAMP binding, concordant with
      direct radioligand binding measurements for cAR3. This is a core molecular
      activity of the receptor.
    action: ACCEPT
    reason: cAR3 directly binds cAMP, as shown by [3H]cAMP binding studies that
      measured its affinity states; the InterPro assignment agrees with the
      experimental data.
    supported_by:
    - reference_id: PMID:1537842
      supporting_text: 20 and 500 nM for cAR3
- 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 term was assigned by automated inter-ontology logical
      inference from cAMP receptor activity. Although cAMP is chemically a purine
      nucleotide, purinergic nucleotide receptor signaling denotes the
      P1/P2-type receptor systems responding to extracellular ATP/ADP/adenosine.
      Dictyostelium cAMP chemoattractant signaling is not purinergic signaling in
      that sense.
    action: REMOVE
    reason: The annotation is a mechanical over-propagation from the
      inter-ontology mapping of cAMP receptor activity to a purinergic pathway.
      cAR3 is a cAMP chemoattractant receptor, not a purinergic (ATP/adenosine)
      receptor, so this pathway term mischaracterizes its biology.
    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: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: Cortical translocation of the RasG biosensor GFP-RA1:DydA during
      chemotaxis required cAR1/cAR3 and G-protein signaling, placing cAR3
      upstream of protein localization to the cell cortex. This is a valid but
      downstream regulatory role rather than a core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The IGI experiment shows cAR1/cAR3 are required for cortical and
      leading-edge recruitment of a downstream Ras effector reporter. cAR3 acts
      upstream of this localization through chemoattractant signaling; it is a
      genuine but non-core, context-specific role.
    supported_by:
    - reference_id: PMID:40934557
      supporting_text: This localization required GPCR Car1/3 and G-protein
        signaling
- term:
    id: GO:0005096
    label: GTPase activator activity
  evidence_type: IDA
  original_reference_id: PMID:21103944
  qualifier: enables
  review:
    summary: This paper shows that rapid Rap1 activation upon cAMP stimulation is
      absent in cells lacking cAR1/cAR3 or Galpha2, placing the receptor upstream
      of Rap1 GTPase activation. However, GTPase activator activity (GO:0005096,
      GAP activity) is a molecular function the receptor does not itself possess,
      because cAR3 is an upstream GPCR and Rap1 activation (GTP loading) is
      mediated by downstream exchange factors, not by a GAP.
    action: MARK_AS_OVER_ANNOTATED
    reason: The receptor is required for chemoattractant-induced Rap1 activation
      but does not have intrinsic GTPase activator (GAP) activity; the effect is
      indirect, transduced through G proteins and downstream regulators. The
      molecular-function assignment over-attributes an effector activity to the
      upstream receptor. Its role is better captured as involvement in the GPCR
      signaling pathway.
    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 or a subunit of the heterotrimeric G-protein complex Gα2
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: IGI
  original_reference_id: PMID:9578623
  qualifier: involved_in
  review:
    summary: cAR3, redundantly with cAR1, mediates chemotaxis toward cAMP;
      constitutively expressed cAR3 confers chemotactic responses and rescues the
      car1-/car3- defect. This is a core biological process for the receptor.
    action: ACCEPT
    reason: Directly assessed capacity of cAR3 to mediate chemotaxis, with
      genetic interaction to cAR1 (car1-/car3- double mutant). Chemotaxis toward
      cAMP is a central output of cAR3 signaling.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IMP
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: cAR3 mediates activation of adenylyl cyclase (cAMP relay), lost in
      car1-/car3- cells. However, as a GPCR it activates adenylyl cyclase
      indirectly through heterotrimeric G proteins rather than binding and
      activating the cyclase directly, so adenylate cyclase activator activity as
      a molecular function of the receptor over-attributes an effector activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: The receptor's requirement for adenylyl cyclase activation is real,
      but the activation is G-protein-mediated and indirect. The role is better
      captured by the pathway term adenylate cyclase-activating GPCR cAMP
      receptor signaling pathway (GO:0140582 and GO:0007189) than by a direct
      cyclase-activator molecular function assigned to the receptor.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: activation of adenylyl cyclase
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IGI
  original_reference_id: PMID:9578623
  qualifier: involved_in
  review:
    summary: cAR3, together with cAR1, drives the aggregation of individual
      amoebae into a multicellular organism; constitutively expressed receptors
      mediate aggregation-stage responses and rescue the car1-/car3-
      developmental defect. This is a core developmental role.
    action: ACCEPT
    reason: The receptors mediate identical responses during the aggregation
      stage and rescue the developmental defect of car1-/car3- cells, directly
      linking cAR3 to aggregation in the developmental (sorocarp) program.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: rescue the developmental defect of car1-/car3- cells
    - reference_id: PMID:9578623
      supporting_text: mediate identical responses during the aggregation stage
        of development
- 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: cAR1 and cAR3 activate common signaling pathways, including cAMP
      relay (adenylyl cyclase activation), by coupling to the same heterotrimeric
      G protein. This cAMP-ligand-specific, adenylate cyclase-activating pathway
      term is the most precise process annotation for cAR3.
    action: ACCEPT
    reason: Genetic evidence (car1- and car1-/car3- phenotypes) shows cAR3
      mediates cAMP relay through a shared G protein, precisely matching this
      pathway term.
    supported_by:
    - reference_id: PMID:7949426
      supporting_text: We conclude that the functions of the cAR1 and cAR3
        receptors are partially redundant and that both interact with the same
        heterotrimeric G-protein to mediate these and other responses
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:15473840
  qualifier: located_in
  review:
    summary: Plasma-membrane localization asserted in an authoritative review of
      chemoattractant signaling, consistent with cAR3 being a cell-surface 7TM
      receptor.
    action: ACCEPT
    reason: cAR3 is a cell-surface cAMP receptor located in the plasma membrane,
      the site of chemoattractant detection.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:2722797
  qualifier: enables
  review:
    summary: Direct ligand-specificity analysis of the Dictyostelium cell-surface
      cAMP receptors (including cAR3) demonstrating cAMP binding. cAMP binding is
      a core molecular activity of the receptor.
    action: ACCEPT
    reason: cAR3 is one of the four cell-surface cAMP receptors whose cyclic
      nucleotide binding specificity was directly characterized; cAMP binding is
      intrinsic to its receptor function.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: four forms of the cell surface receptor
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:1537842
  qualifier: enables
  review:
    summary: Direct [3H]cAMP binding assays established cAR3 affinity states
      (approximately 20 and 500 nM), confirming intermediate-affinity cAMP
      binding. Core molecular activity.
    action: ACCEPT
    reason: Radioligand binding measurements directly demonstrate cAMP binding by
      cAR3 with defined affinity states, a central feature of the receptor.
    supported_by:
    - reference_id: PMID:1537842
      supporting_text: 20 and 500 nM for cAR3
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16781008
  qualifier: enables
  review:
    summary: A yeast two-hybrid screen identified the COP9 signalosome subunit
      CSN5 as a potential interacting partner of a Dictyostelium cell-surface
      receptor. This bare protein binding term is uninformative about molecular
      function and the interaction is described as potential.
    action: KEEP_AS_NON_CORE
    reason: Per curation guidance, bare protein binding is not retained as a core
      function. The reported CSN5 interaction is a specific but preliminary
      (yeast two-hybrid, potential) finding whose functional significance for
      cAR3 is unestablished; it is kept as non-core rather than treated as a core
      molecular function.
    supported_by:
    - reference_id: PMID:16781008
      supporting_text: we have identified the CSN5 subunit as a potential
        interacting partner of a cell surface receptor of Dictyostelium
- term:
    id: GO:0001646
    label: cAMP receptor activity
  evidence_type: IDA
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: Direct evidence that cAR3 functions as a cAMP receptor, since
      constitutive expression confers cAMP-sensing responses. This is the
      defining core molecular function of the gene product.
    action: ACCEPT
    reason: cAR3 directly binds cAMP and transduces the signal as a receptor, as
      demonstrated by reconstitution of cAMP responses upon its expression. This
      is the core molecular function.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: assessed the capacity of each to mediate chemotaxis
- term:
    id: GO:0001646
    label: cAMP receptor activity
  evidence_type: IGI
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: Genetic-interaction evidence (with cAR1) supporting cAR3 cAMP
      receptor activity; the two receptors are partially redundant in cAMP
      sensing. Core molecular function.
    action: ACCEPT
    reason: The car1-/car3- double mutant loses cAMP responsiveness while single
      mutants retain it, genetically confirming cAR3 acts as a cAMP receptor
      redundantly with cAR1.
    supported_by:
    - reference_id: PMID:9578623
      supporting_text: rescue the developmental defect of car1-/car3- cells
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IMP
  original_reference_id: PMID:9578623
  qualifier: enables
  review:
    summary: Mutational/expression analysis supporting cAMP binding by cAR3 as
      part of its receptor function. Core molecular activity, concordant with the
      direct binding studies.
    action: ACCEPT
    reason: cAMP binding is intrinsic to cAR3 receptor activity and is supported
      across binding assays and functional expression studies.
    supported_by:
    - reference_id: PMID:1537842
      supporting_text: 20 and 500 nM for cAR3
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:1537842
  title: The cyclic nucleotide specificity of three cAMP receptors in Dictyostelium.
  findings:
  - statement: cAR3 binds cAMP with two affinity states (~20 and 500 nM in
      phosphate buffer), distinct from cAR1 and cAR2.
    supporting_text: there were two affinity states of about 30 and 300 nM for
      cAR1 and 20 and 500 nM for cAR3 but no detectable affinity for cAR2
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Directly measures cAR3 cAMP-binding affinity by [3H]cAMP
      binding; supports the cAMP binding annotations and intermediate-affinity
      characterization.
- id: PMID:15473840
  title: Chemoattractant signaling in dictyostelium discoideum.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Authoritative review of Dictyostelium chemoattractant (cAMP
      receptor) signaling; source of the TAS plasma-membrane annotation.
- id: PMID:16781008
  title: The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum.
  findings:
  - statement: A COP9 signalosome subunit (CSN5) was identified as a potential
      interacting partner of a Dictyostelium cell-surface receptor by yeast
      two-hybrid.
    supporting_text: we have identified the CSN5 subunit as a potential
      interacting partner of a cell surface receptor of Dictyostelium
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Basis for the IPI protein-binding annotation; the interaction
      is preliminary (potential, yeast two-hybrid) and its functional role for
      cAR3 is unestablished.
- id: PMID:21103944
  title: Chemoattractant-mediated Rap1 activation requires GPCR/G proteins.
  findings:
  - statement: Chemoattractant-induced Rap1 activation requires the cAMP
      receptors cAR1/cAR3 and the G-protein subunit Galpha2.
    supporting_text: The rapid Rap1 activation upon cAMP chemoattractant
      stimulation was absent in cells lacking chemoattractant cAMP receptors
      cAR1/cAR3 or a subunit of the heterotrimeric G-protein complex Gα2
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Places cAR1/cAR3 upstream of Rap1 activation; supports an
      upstream signaling role but not intrinsic GTPase activator (GAP) activity
      of the receptor.
- id: PMID:2722797
  title: The cyclic nucleotide specificity of eight cAMP-binding proteins in Dictyostelium
    discoideum is correlated into three groups.
  findings:
  - statement: The four forms of the Dictyostelium cell-surface cAMP receptor
      (including cAR3) form one pharmacological group of cAMP-binding proteins.
    supporting_text: four forms of the cell surface receptor
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Characterizes cell-surface cAMP receptor binding specificity;
      supports cAMP binding and cell-surface localization.
- id: PMID:40934557
  title: The Ras association domain of DydA as a specific reporter of activated RasG
    in Dictyostelium.
  findings:
  - statement: Cortical/leading-edge recruitment of the RasG biosensor
      GFP-RA1:DydA during chemotaxis requires cAR1/cAR3 and G-protein signaling.
    supporting_text: This localization required GPCR Car1/3 and G-protein
      signaling
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Basis for the regulation of protein localization to cell cortex
      IGI annotation; demonstrates cAR1/cAR3 act upstream of cortical RasG
      effector recruitment.
- id: PMID:7949426
  title: Two cAMP receptors activate common signaling pathways in Dictyostelium.
  findings:
  - statement: cAR1 and cAR3 are partially redundant and couple to the same
      heterotrimeric G protein to mediate cAMP relay and other responses.
    supporting_text: We conclude that the functions of the cAR1 and cAR3
      receptors are partially redundant and that both interact with the same
      heterotrimeric G-protein to mediate these and other responses
  - statement: car1-/car3- double-mutant cells are totally insensitive to cAMP.
    supporting_text: these lines are totally insensitive to cAMP
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes cAR3 as a G-protein-coupled cAMP receptor
      functionally redundant with cAR1 in adenylyl cyclase / cAMP-relay
      signaling.
- 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: The Dictyostelium cAMP chemoattractant receptor family comprises
      four sequentially expressed receptors (cAR1-cAR4).
    supporting_text: The cAMP chemoattractant receptor family of Dictyostelium
      discoideum is composed of four receptors (cAR1-cAR4), which are expressed
      sequentially throughout the developmental transition from a unicellular to
      a multicellular organism
  - statement: cAR3 mediates chemotaxis, adenylyl cyclase activation and actin
      polymerization and can rescue the car1-/car3- developmental defect.
    supporting_text: assessed the capacity of each to mediate chemotaxis,
      activation of adenylyl cyclase and actin polymerization, and rescue the
      developmental defect of car1-/car3- cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary functional characterization of cAR3 by
      constitutive-expression and double-mutant analysis; supports cAMP receptor
      activity, chemotaxis, aggregation and adenylyl cyclase activation.
core_functions:
- description: cAR3 is a plasma-membrane seven-transmembrane G protein-coupled
    receptor that binds extracellular cAMP and transduces the chemoattractant
    signal through heterotrimeric G proteins, functioning redundantly with cAR1
    to activate adenylyl cyclase (cAMP relay) and downstream responses during
    aggregation and multicellular development.
  molecular_function:
    id: GO:0001646
    label: cAMP 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
  - id: GO:0006935
    label: chemotaxis
  - id: GO:0031152
    label: aggregation involved in sorocarp development
  supported_by:
  - reference_id: PMID:9578623
    supporting_text: assessed the capacity of each to mediate chemotaxis,
      activation of adenylyl cyclase and actin polymerization, and rescue the
      developmental defect of car1-/car3- cells
  - reference_id: PMID:7949426
    supporting_text: both interact with the same heterotrimeric G-protein to
      mediate these and other responses
  - reference_id: PMID:1537842
    supporting_text: 20 and 500 nM for cAR3