carB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004930 G protein-coupled receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: cAR2 is a bona fide seven-transmembrane G protein-coupled receptor for cAMP whose responses are mediated by heterotrimeric G proteins. This is a core molecular function and the phylogenetic inference is well supported by direct characterization of the Dictyostelium cAR family. Reason: cAR2 belongs to the cAMP receptor GPCR family, has seven predicted transmembrane helices, and signals via G proteins, consistent with GPCR activity as a core function. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: As a cell-surface cAMP receptor with seven transmembrane domains, cAR2 is active in the plasma membrane. This is a core localization for the receptor. Reason: cAR2 is a multi-pass cell-surface receptor; plasma membrane is where it binds extracellular cAMP and transduces signal. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: When expressed, cAR2 can mediate activation of adenylyl cyclase, so participation in an adenylate cyclase-activating GPCR signaling pathway is supported experimentally and by phylogenetic inference from the cAR family. Reason: cAR2 couples cAMP binding to adenylyl cyclase activation via G proteins, as directly shown for the receptor subtype. 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	MODIFY	Summary: This is a correct but non-specific parent of G protein-coupled receptor activity. A more informative, already-curated child term (GO:0004930) captures the same function more precisely. Reason: The general transmembrane signaling receptor activity term is subsumed by the more specific GPCR activity that is separately annotated; replace with the specific term. Proposed replacements: G protein-coupled receptor activity Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic annotation of GPCR activity from the cAMP receptor domain signature. This agrees with the IBA and experimental evidence and is a core molecular function. Reason: cAR2 is a member of the Dictyostelium cAMP receptor GPCR family; GPCR activity is correct and core. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0007165 signal transduction	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Correct but very general. cAR2 does participate in signal transduction, but a more specific GPCR signaling pathway term better captures its role. Reason: Signal transduction is a high-level parent of the specific GPCR signaling pathway annotations; retain as non-core context. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0007166 cell surface receptor signaling pathway	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but a general parent of G protein-coupled receptor signaling pathway, which is the more precise annotation for cAR2. Reason: cAR2 is a cell-surface receptor, but the more specific GPCR signaling pathway term is preferred; retain this as non-core. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: cAR2 transduces extracellular cAMP through a G protein-coupled receptor signaling pathway. This is a core biological process for the receptor. Reason: cAR2 signaling is mediated by G proteins, placing it squarely in the GPCR signaling pathway. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: Correct but non-specific. cAR2 is a plasma membrane cell-surface receptor; the more specific plasma membrane term is preferred. Reason: Generic membrane localization should be replaced by the specific plasma membrane term appropriate for a cell-surface receptor. Proposed replacements: plasma membrane Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0030552 cAMP binding	IEA GO_REF:0000002	ACCEPT	Summary: cAR2 binds cAMP as its ligand. This InterPro-based electronic annotation is consistent with direct binding measurements and is a core molecular function. Reason: Direct [3H]cAMP binding to cAR2 has been demonstrated; cAMP binding is the defining ligand-recognition activity of the receptor. Supporting Evidence: PMID:1537842 We have expressed three receptor subtypes, cAR1, cAR2, and cAR3, in growing cells and have investigated their affinity and pharmacological specificity in a series of [3H]cAMP binding studies.
GO:0035589 G protein-coupled purinergic nucleotide receptor signaling pathway	IEA GO_REF:0000108	REMOVE	Summary: This term was assigned by an automated inter-ontology logical inference from cAMP receptor activity. The Dictyostelium cAR receptors are cyclic-AMP chemoattractant receptors, not purinergic (ATP/ADP/adenosine) nucleotide receptors in the sense captured by this term. The mapping mischaracterizes the receptor's signaling pathway. Reason: This is an over-propagated electronic inference. cAR2 responds to the diffusible second messenger cAMP as a developmental chemoattractant; it is not a purinergic nucleotide receptor. The GPCR signaling pathway term already captures its role correctly without the misleading purinergic classification. Supporting Evidence: PMID:2722797 the cell surface receptors participate in the transduction of the cAMP signal during chemotaxis and cell differentiation
GO:0009642 response to light intensity	HEP PMID:41057014 Transcriptomic and metabolomic insights into light-mediated ...	KEEP AS NON CORE	Summary: A high-throughput expression annotation. carB transcript is down-regulated under dark relative to light in a transcriptomic study of the light-mediated unicellular-to-multicellular transition. This reflects transcriptional responsiveness rather than a core molecular function of the receptor. Reason: The evidence is expression-level (HEP), showing carB is among genes down-regulated in the dark; it is a peripheral developmental/environmental response, not a core function. Supporting Evidence: PMID:41057014 some downregulated genes including adenylate cyclase (acrA) and cyclic AMP receptor (CarB) could reduce the cell aggregation during dark incubation
GO:0010854 adenylate cyclase regulator activity	IMP PMID:9578623 Switching of chemoattractant receptors programs development ...	ACCEPT	Summary: Functional expression experiments showed cAR2 can mediate activation of adenylyl cyclase, consistent with the receptor acting as an upstream regulator of adenylyl cyclase through its G protein coupling. Supported by experimental (IMP) evidence. Reason: cAR2 was directly shown to mediate adenylyl cyclase activation when expressed, supporting an adenylate cyclase regulator activity as part of its signaling output. Supporting Evidence: PMID:9578623 assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization
GO:0005886 plasma membrane	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: cAR2 is a cell-surface cAMP receptor located in the plasma membrane. This is a core localization and is consistent with its multi-pass membrane architecture. Reason: As a seven-transmembrane cell-surface receptor, cAR2 resides in the plasma membrane where it binds extracellular cAMP. Supporting Evidence: PMID:8436297 The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains.
GO:0007165 signal transduction	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	KEEP AS NON CORE	Summary: Correct but very general. cAR2 participates in signal transduction, more precisely as a GPCR signaling pathway component. Reason: High-level parent term; retained as non-core context alongside the specific GPCR signaling pathway annotation. Supporting Evidence: PMID:2722797 the cell surface receptors participate in the transduction of the cAMP signal during chemotaxis and cell differentiation
GO:0030552 cAMP binding	IDA PMID:2722797 The cyclic nucleotide specificity of eight cAMP-binding prot...	ACCEPT	Summary: Direct biochemical analysis of Dictyostelium cell-surface cAMP receptors (including cAR2) demonstrated cAMP binding and characterized their nucleotide specificity. cAMP binding is the defining ligand-recognition activity of cAR2. Reason: Experimental (IDA) evidence for cAMP binding by the cell-surface receptor family; this is a core molecular function. Supporting Evidence: PMID:2722797 Eight forms of cAMP-binding proteins have been described in this organism: four forms of a cell surface receptor
GO:0010628 positive regulation of gene expression	IEP PMID:8436297 CAR2, a prestalk cAMP receptor required for normal tip forma...	KEEP AS NON CORE	Summary: cAR2 signaling influences the developmental gene-expression program. Loss of cAR2 alters cell-type gene expression (over-expression of prespore markers), indicating cAR2 acts upstream of developmental gene regulation. This is a downstream developmental consequence rather than a core molecular function. Reason: The receptor regulates expression of developmentally regulated genes as a downstream effect of signaling; retain as non-core developmental context. Supporting Evidence: PMID:8436297 they exhibit an enhanced expression of prespore-specific mRNA
GO:0010629 negative regulation of gene expression	IEP PMID:8436297 CAR2, a prestalk cAMP receptor required for normal tip forma...	KEEP AS NON CORE	Summary: In wild-type aggregates cAR2 normally restrains prespore-specific gene expression; the enhanced prespore mRNA in cAR2-null cells indicates cAR2 acts upstream of negative regulation of these genes. A downstream developmental effect, not a core molecular function. Reason: Derepression of prespore markers in the mutant implies cAR2 normally contributes to negative regulation of that gene set; retain as non-core. Supporting Evidence: PMID:8436297 they exhibit an enhanced expression of prespore-specific mRNA
GO:0030552 cAMP binding	IDA PMID:1537842 The cyclic nucleotide specificity of three cAMP receptors in...	ACCEPT	Summary: Direct [3H]cAMP binding studies of expressed cAR2 demonstrated cAMP binding, with cAR2 showing much lower/less-detectable affinity than cAR1 in physiological buffer (measurable only in ammonium sulfate). cAMP binding is a core molecular function. Reason: Experimental (IDA) demonstration of cAMP binding by cAR2; the low apparent affinity distinguishes it from cAR1 but binding is genuine and core. Supporting Evidence: PMID:1537842 there was one affinity state of 4 nM for cAR1 and 11 nM for cAR2
GO:0031154 culmination involved in sorocarp development	IMP PMID:8436297 CAR2, a prestalk cAMP receptor required for normal tip forma...	KEEP AS NON CORE	Summary: cAR2-null cells arrest at the tight-mound stage and fail normal tip formation and late development, so cAR2 is required for progression toward culmination and fruiting-body (sorocarp) formation. This is a multicellular developmental role rather than a core molecular function. Reason: Loss-of-function experimental evidence links cAR2 to late multicellular morphogenesis/culmination; retained as a non-core developmental process. Supporting Evidence: PMID:8436297 detained at the tight mound stage
GO:0001646 cAMP receptor activity	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: cAMP receptor activity is the most precise molecular-function description of cAR2 as a cell-surface receptor that binds extracellular cAMP and transduces the signal via G proteins. This is the primary core function. Reason: cAR2 is a defining member of the Dictyostelium cAMP receptor family; cAMP receptor activity is the correct, specific core molecular function. Supporting Evidence: PMID:2722797 the cell surface receptors participate in the transduction of the cAMP signal during chemotaxis and cell differentiation

Gene Description

Existing Annotations Review

Core Functions

cAR2 is a cell-surface, seven-transmembrane G protein-coupled receptor that binds extracellular cAMP and transduces the signal through heterotrimeric G proteins at the plasma membrane. It is a comparatively low/atypical-affinity member of the cAR family expressed after aggregation in prestalk cells.

Through its G protein coupling, cAR2 acts upstream as a regulator of adenylyl cyclase, mediating cAMP-triggered adenylyl cyclase activation as part of the developmental signaling relay.

References

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