carD

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004930 G protein-coupled receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: CAR4 is a bona fide seven-transmembrane G protein-coupled receptor of the Dictyostelium cAR family, and its signaling is mediated by G proteins. Phylogenetic inference to GPCR activity is correct and represents a core molecular function. Reason: The primary literature explicitly describes CAR4 as a cell-surface, G protein-linked cAMP receptor whose activity is mediated by G proteins, and the UniProt topology confirms a canonical 7TM architecture. GPCR activity is a correct and central molecular function. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: As a cell-surface GPCR, CAR4 is active at the plasma membrane. This is a correct core localization. Reason: CAR4 is described as a cell-surface receptor and is predicted to be a multi-pass membrane protein; the plasma membrane is where a chemoattractant cAMP receptor acts. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Retain the ancestral cyclase-activating GPCR output as non-core, distinct from the best characterized CAR4/GSK3 developmental branch. Reason: PTHR23112 places GO:0007189 at PTN000560943 with fungal and Dictyostelium experimental descendants. The focused OpenScientist report confirms that published receptor-comparison assays directly tested cAR1/cAR2/cAR3, while the 1997 extension to all cARs explicitly includes unpublished observations. That distinction is valid, and the observation is not treated as a published CAR4 assay. However, the report finds no CAR4-specific loss and incorrectly treats target experimental absence and a different signaling branch as sufficient to diagnose paralog carry-over. GSK3 antagonism does not imply inhibition or loss of adenylyl cyclase. Retain the curated ancestral inference as non-core; direct CAR4 cyclase activity remains unverified. PMID:1333842 supplies published homolog-level evidence for G-alpha-2-dependent activation by more than one cAMP receptor; it is not presented as a direct cAR4 assay. Supporting Evidence: PMID:9284050 all of the CARs may be capable of adenylyl cyclase activation ( Pupillo et al. 1992 ; A.R. Kimmel, unpubl.) PMID:1333842 cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2.
GO:0004888 transmembrane signaling receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: A correct but general parent term for CAR4's receptor activity. The more specific cAMP receptor activity (GO:0001646) better captures the ligand specificity. Reason: CAR4 is a transmembrane signaling receptor; the term is accurate. It is a general ancestor of the more informative cAMP receptor activity annotation, which is also present. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based GPCR activity annotation, consistent with the IBA annotation and the experimental characterization of CAR4 as a G protein-linked cAMP receptor. Reason: Correct core molecular function, supported by both the GPCR domain architecture and the primary literature describing G protein-linked signaling. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0007165 signal transduction	IEA GO_REF:0000117	ACCEPT	Summary: Correct but very general process term. CAR4 transduces extracellular cAMP signals; more specific GPCR signaling pathway terms are also annotated. Reason: CAR4 is a signal-transducing receptor. The term is accurate though general; the more specific GPCR signaling pathway annotation is preferable for capturing the mechanism. Supporting Evidence: PMID:2722797 the cell surface receptors participate in the transduction of the cAMP signal during chemotaxis and cell differentiation
GO:0007166 cell surface receptor signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: CAR4 is a cell-surface receptor that initiates intracellular signaling in response to extracellular cAMP. Correct process annotation. Reason: Accurate for a cell-surface cAMP GPCR; this is a parent of the more specific G protein-coupled receptor signaling pathway term. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: CAR4 signals through heterotrimeric G proteins, making this the most appropriate specific process term for its signaling role. Reason: The activity of the receptor is explicitly mediated by G proteins, so GPCR signaling pathway is the correct core process. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0016020 membrane	IEA GO_REF:0000120	ACCEPT	Summary: Correct but general localization. CAR4 is a multi-pass membrane protein; the more specific plasma membrane annotation is also present. Reason: CAR4 is predicted to be a multi-pass membrane protein and is a cell-surface receptor. Membrane is accurate; plasma membrane is the more informative term. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0030552 cAMP binding	IEA GO_REF:0000002	ACCEPT	Summary: cAMP binding is the defining ligand-recognition activity of the cAR receptor family and is a core molecular function of CAR4. Reason: The receptor binds extracellular cAMP as its ligand; this activity is supported by both the InterPro domain and direct biochemical study of the cell surface cAMP receptors. Supporting Evidence: PMID:2722797 cAMP is probably bound to the surface receptors in the anti conformation in a hydrophobic cleft of the receptor
GO:0035589 G protein-coupled purinergic nucleotide receptor signaling pathway	IEA GO_REF:0000108	ACCEPT	Summary: The GO definition includes GPCR signaling initiated by an extracellular purine nucleotide. Extracellular cAMP signaling through CAR4 satisfies this scope. Reason: QuickGO defines GO:0035589 by extracellular purine-nucleotide activation and does not restrict it to ATP/ADP-binding P2Y receptors. cAMP is a purine nucleotide, and CAR4 is a G protein-linked cAMP receptor. The old removal incorrectly substituted a narrower P2-receptor interpretation for the ontology definition; retain the logical inference. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0008160 protein tyrosine phosphatase activator activity	TAS PMID:12408804 Receptor-dependent and tyrosine phosphatase-mediated inhibit...	KEEP AS NON CORE	Summary: CAR4 signaling activates a protein tyrosine phosphatase that inhibits GSK3 to control cell-fate choice. This captures a real, receptor-dependent regulatory relationship, but as a direct molecular function of the receptor it is an over-interpretation, because CAR4 regulates the phosphatase indirectly through G protein signaling rather than acting as a direct enzyme activator. Reason: The essence is supported by the primary paper (CAR4 regulates a tyrosine phosphatase that inhibits GSK3), and it is an important downstream mechanism for patterning. However, this is a signaling-mediated regulatory role rather than a direct catalytic-activator molecular function of the receptor, so it is retained as non-core. Supporting Evidence: PMID:12408804 We now show that CAR4 regulates a tyrosine phosphatase that inhibits GSK3 activity
GO:0005886 plasma membrane	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: Plasma membrane localization of the cAMP chemoattractant receptors, consistent with the IBA plasma membrane annotation and CAR4's cell-surface character. Reason: CAR4 is a cell-surface cAMP receptor; the plasma membrane is the correct core localization. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0010628 positive regulation of gene expression	IMP PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	KEEP AS NON CORE	Summary: car4 null mutants show significantly reduced prestalk gene expression, indicating CAR4 normally promotes expression of prestalk-specific genes during late development. This is a downstream developmental regulatory role. Reason: Supported by the loss-of-function phenotype (reduced prestalk gene expression in car4 nulls). This is a pleiotropic downstream developmental consequence of CAR4 signaling, not the receptor's core molecular function, so it is retained as non-core. Supporting Evidence: PMID:7958880 Prestalk gene expression is significantly reduced in car4 nulls, whereas prespore-specific markers are overexpressed and detected in zones normally restricted to prestalk cells
GO:0010629 negative regulation of gene expression	IMP PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	KEEP AS NON CORE	Summary: In car4 nulls, prespore-specific markers are overexpressed and appear in zones normally restricted to prestalk cells, indicating CAR4 normally restricts (negatively regulates) prespore gene expression in the prestalk domain. A downstream developmental regulatory role. Reason: Supported by the loss-of-function phenotype (ectopic overexpression of prespore markers in car4 nulls). This is a spatial patterning consequence of CAR4 signaling rather than the core molecular function. Supporting Evidence: PMID:7958880 Prestalk gene expression is significantly reduced in car4 nulls, whereas prespore-specific markers are overexpressed and detected in zones normally restricted to prestalk cells
GO:0001646 cAMP receptor activity	ISS PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	ACCEPT	Summary: cAMP receptor activity is the defining, core molecular function of CAR4, inferred by sequence similarity to the founding cAR1 receptor (P13773) and consistent with its experimental characterization. Reason: CAR4 is a member of the cAR family of cAMP receptors and was characterized as a cell-surface cAMP receptor; cAMP receptor activity is the correct and central molecular function. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0030552 cAMP binding	ISS PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	ACCEPT	Summary: cAMP binding, inferred by similarity to cAR1, is the ligand-recognition component of CAR4's receptor function and is a core molecular activity. Reason: Ligand binding is intrinsic to cAMP receptor activity; the annotation is correct and complements the cAMP receptor activity term. Supporting Evidence: PMID:2722797 cAMP is probably bound to the surface receptors in the anti conformation in a hydrophobic cleft of the receptor
GO:0007165 signal transduction	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: General signal transduction annotation from a chemoattractant-signaling review. Correct but less informative than the GPCR signaling pathway terms. Reason: CAR4 transduces extracellular cAMP signals; the term is accurate though general. 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 study of the Dictyostelium cell-surface cAMP receptors demonstrated cAMP binding in a hydrophobic cleft. cAMP binding is a core molecular activity of CAR4 as a cAMP receptor. Reason: Experimental (IDA) support for cAMP binding by the cell-surface receptors. This ligand-binding activity is intrinsic to CAR4's core function as a cAMP receptor. Supporting Evidence: PMID:2722797 cAMP is probably bound to the surface receptors in the anti conformation in a hydrophobic cleft of the receptor
GO:0030154 cell differentiation	IMP PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	ACCEPT	Summary: CAR4 signaling controls prestalk/prespore cell-type differentiation during late Dictyostelium development. Reason: The car4-null phenotype directly establishes this role, which is the principal characterized biological purpose of the late-stage receptor and is already included in the core-function synthesis. Retain as core rather than treating cell differentiation as an incidental downstream phenotype. Supporting Evidence: PMID:7958880 cAMP signaling is required for pattern formation and cellular differentiation during late Dictyostelium development
GO:0031154 culmination involved in sorocarp development	IMP PMID:7958880 The cAMP receptor CAR4 regulates axial patterning and cellul...	KEEP AS NON CORE	Summary: CAR4 is expressed from tip elongation through culmination and car4 nulls show patterning defects that persist in terminally differentiated fruiting bodies, consistent with a role in late (culmination-stage) morphogenesis. Reason: Supported by expression timing and the terminal-stage patterning phenotype. This is a downstream developmental role of CAR4 rather than its core molecular function. Supporting Evidence: PMID:7958880 CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination
GO:0001646 cAMP receptor activity	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: cAMP receptor activity annotation from a chemoattractant-signaling review, consistent with the ISS annotation. Core molecular function. Reason: cAMP receptor activity is the defining, core molecular function of CAR4. Supporting Evidence: PMID:7958880 the gene for a new cell-surface, G protein-linked cAMP receptor
GO:0030552 cAMP binding	TAS PMID:15473840 Chemoattractant signaling in dictyostelium discoideum.	ACCEPT	Summary: cAMP binding annotation from a chemoattractant-signaling review; consistent with the direct and inferred cAMP binding annotations. Core ligand-recognition activity. Reason: Ligand binding is intrinsic to CAR4's cAMP receptor function; the annotation is correct. Supporting Evidence: PMID:2722797 cAMP is probably bound to the surface receptors in the anti conformation in a hydrophobic cleft of the receptor

Gene Description

Existing Annotations Review

Core Functions

CAR4 is a seven-transmembrane G protein-coupled receptor that binds extracellular cAMP at the plasma membrane and, through heterotrimeric G proteins, transduces the cAMP signal to control late-development cell-type patterning and differentiation.

References

Deep Research

OpenScientist

📚 Additional Documentation

Notes

📄 View Raw YAML