gbpC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004672 protein kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: GbpC contains a MAP3K-like serine/threonine protein kinase domain that constitutes the functional output of the protein. A kinase-dead mutant fails to rescue chemotaxis, confirming catalytic relevance. This is a core molecular function, though the more specific serine/threonine child term is preferable. Reason: The kinase domain is experimentally essential for GbpC activity in vivo, making protein kinase activity a genuine core function of this Roco protein. Supporting Evidence: PMID:18703517 Mutants that lack a functional guanine exchange factor (GEF), Roc, or kinase domain are inactive in vivo PMID:18703517 a four-step intramolecular activation mechanism of the Roco protein GbpC: cGMP binding to the cyclic nucleotide-binding domains, activation of the GEF domain, GDP/GTP exchange of Roc, and activation of the MAPKKK domain
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: GbpC is predominantly cytoplasmic in resting cells and only translocates to the cell boundary upon stimulation. Cytoplasmic localization is well supported by direct evidence for this gene product. Reason: Direct experimental data show GbpC resides in the cytoplasm of resting cells, consistent with the IBA inference. Supporting Evidence: PMID:22119747 In resting cells, the protein is present in the cytoplasm, but GbpC rapidly translocates to the cell boundary upon stimulation with the chemoattractant cAMP
GO:0007165 signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GbpC is a bona fide signal transducer (the cGMP effector of chemotactic signaling), so this annotation is correct but very general. More specific child terms (intracellular signal transduction, regulation of chemotaxis) capture its role better. Reason: The term is accurate but too high-level to represent the specific cGMP signaling role; retained as non-core in favor of more precise process terms. Supporting Evidence: PMID:22119747 cGMP-mediated GbpC activation is essential for the proper regulation of myosin II during chemotaxis
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based inference of protein kinase activity from the kinase domain. Redundant with the IBA annotation but consistent with the experimentally validated MAP3K-like kinase domain. Reason: The protein kinase domain is present and functionally essential; the IEA inference is correct. Supporting Evidence: PMID:18703517 Mutants that lack a functional guanine exchange factor (GEF), Roc, or kinase domain are inactive in vivo
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: The GbpC kinase domain is a serine/threonine (MAP3K-like, TKL family) kinase per UniProt EC 2.7.11.1 and domain analysis. This more specific MF term accurately captures the catalytic output of GbpC. Reason: Serine/threonine protein kinase activity is the precise molecular function of the GbpC kinase domain and a core function of the protein. Supporting Evidence: PMID:12011437 GbpC contains the following nine domains (in order): leucine-rich repeats, Ras, MEK kinase, Ras guanine nucleotide exchange factor N-terminal (RasGEF-N), DEP, RasGEF, cGMP-binding, GRAM, and a second cGMP-binding domain PMID:18703517 a four-step intramolecular activation mechanism of the Roco protein GbpC: cGMP binding to the cyclic nucleotide-binding domains, activation of the GEF domain, GDP/GTP exchange of Roc, and activation of the MAPKKK domain
GO:0005085 guanyl-nucleotide exchange factor activity	IEA GO_REF:0000002	ACCEPT	Summary: GbpC contains a RasGEF (CDC25) domain that has been directly shown to accelerate GDP/GTP exchange on its own Roc domain. The IEA inference is confirmed by direct biochemical evidence. Reason: GEF activity is a core, experimentally demonstrated molecular function of the internal RasGEF domain of GbpC. Supporting Evidence: PMID:18703517 the RasGEF domain of GbpC specifically accelerates the GDP/GTP exchange of the Roc domain
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding is inferred from the kinase domain. It is a correct supporting molecular function underlying the kinase activity but is not itself a distinctive core function. Reason: ATP binding is a generic cofactor-binding activity intrinsic to the kinase domain; correct but subsidiary to the kinase activity annotation. Supporting Evidence: PMID:18703517 Mutants that lack a functional guanine exchange factor (GEF), Roc, or kinase domain are inactive in vivo
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning inference of cytoplasmic localization, consistent with direct evidence that GbpC is cytoplasmic in resting cells. Reason: Cytoplasmic localization is well established for GbpC by direct experimental evidence. Supporting Evidence: PMID:22119747 In resting cells, the protein is present in the cytoplasm, but GbpC rapidly translocates to the cell boundary upon stimulation with the chemoattractant cAMP
GO:0007264 small GTPase-mediated signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: GbpC harbors a Ras-like Roc GTPase domain that cycles between GDP- and GTP-bound states within its intramolecular cascade, so small GTPase-mediated signaling is mechanistically relevant. This is an accurate but mechanistic sub-aspect rather than the top-level function. Reason: The intramolecular Roc GTPase switch is central to GbpC mechanism, but this process term is best retained as non-core relative to the cGMP/kinase output. Supporting Evidence: PMID:18703517 the RasGEF domain of GbpC specifically accelerates the GDP/GTP exchange of the Roc domain
GO:0035556 intracellular signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: GbpC transduces the intracellular cGMP signal, so intracellular signal transduction is an appropriate process annotation. Reason: Correct and more informative than bare signal transduction, but still a general process term relative to the specific chemotaxis/polarity roles. Supporting Evidence: PMID:22119747 cGMP-mediated GbpC activation is essential for the proper regulation of myosin II during chemotaxis
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea/EC-based inference of serine kinase activity, consistent with the Ser/Thr kinase (EC 2.7.11.1) MAP3K-like domain of GbpC. Reason: Serine kinase activity accurately reflects the catalytic activity of the GbpC kinase domain. Supporting Evidence: PMID:18703517 a four-step intramolecular activation mechanism of the Roco protein GbpC: cGMP binding to the cyclic nucleotide-binding domains, activation of the GEF domain, GDP/GTP exchange of Roc, and activation of the MAPKKK domain
GO:0019887 protein kinase regulator activity	IMP PMID:16546177 Myosin light chain kinase A is activated by cGMP-dependent a...	KEEP AS NON CORE	Summary: Loss of GbpC (or of cGMP) abrogates chemotaxis-induced activation of myosin light chain kinase A (MLCK-A). GbpC is thus genetically required for MLCK-A activation, but this is most likely an upstream/indirect effect (via the GbpC kinase cascade) rather than GbpC directly acting as a kinase-regulator module. Reason: The IMP evidence supports a requirement of GbpC for MLCK-A activation, but the relationship is upstream and probably indirect; retained as non-core rather than a direct core molecular function. Supporting Evidence: PMID:16546177 MLCK-A activation during chemotaxis is highly responsive to cellular cGMP levels and the cGMP-binding protein GbpC
GO:0007163 establishment or maintenance of cell polarity	IMP PMID:15827084 RasGEF-containing proteins GbpC and GbpD have differential e...	ACCEPT	Summary: gbpC-null cells fail to polarize effectively in a chemoattractant gradient, establishing a direct role for GbpC in chemotactic cell polarity through myosin II. Reason: Strong loss-of-function evidence directly links GbpC to establishment of cell polarity during chemotaxis; a core biological role. Supporting Evidence: PMID:15827084 gbpC-null cells display strongly reduced chemotaxis, because they are unable to polarise effectively in a chemotactic gradient PMID:15827084 cGMP activates GbpC, mediating the chemoattractant-induced establishment of cell polarity through myosin
GO:0005737 cytoplasm	IDA PMID:22119747 Multiple regulatory mechanisms for the Dictyostelium Roco pr...	ACCEPT	Summary: Direct localization evidence shows GbpC is present in the cytoplasm of resting cells before chemoattractant-induced translocation. Reason: Direct imaging demonstrates cytoplasmic localization of GbpC in resting cells. Supporting Evidence: PMID:22119747 In resting cells, the protein is present in the cytoplasm, but GbpC rapidly translocates to the cell boundary upon stimulation with the chemoattractant cAMP
GO:0005886 plasma membrane	IMP PMID:22119747 Multiple regulatory mechanisms for the Dictyostelium Roco pr...	ACCEPT	Summary: Upon cAMP stimulation or osmotic shock GbpC translocates to the plasma membrane via its GRAM domain; GRAM-domain mutations disrupt membrane association and GbpC function. This is a genuine stimulus-dependent localization. Reason: Both localization and GRAM-domain mutant analysis support plasma-membrane association as a functionally important localization of GbpC. Supporting Evidence: PMID:22119747 the protein localizes toward the plasma membrane and actin cytoskeleton PMID:22119747 cAMP induces a GRAM-dependent translocation of GbpC toward the plasma membrane and cell cortex
GO:0005938 cell cortex	IDA PMID:22119747 Multiple regulatory mechanisms for the Dictyostelium Roco pr...	ACCEPT	Summary: After stimulation GbpC enriches in the F-actin-rich cell cortex, where it is thought to phosphorylate effector proteins. Directly supported localization. Reason: Direct evidence places stimulated GbpC at the cell cortex, consistent with its role in cortical myosin regulation. Supporting Evidence: PMID:22119747 cAMP induces a GRAM-dependent translocation of GbpC toward the plasma membrane and cell cortex
GO:0031252 cell leading edge	IDA PMID:19346484 Switching direction in electric-signal-induced cell migratio...	UNDECIDED	Summary: This paper reports that GCase- and PI3K-pathway signaling components localize at the leading edge during electrotaxis, but the cached text does not explicitly document GbpC-specific leading-edge localization (GbpC is classically associated with the cell rear/retraction). Cannot verify the GbpC-specific claim from the available text. Reason: The full text may contain GbpC-specific localization imaging not captured in the cached article; leading-edge localization is not clearly attributable to GbpC from the accessible text, so no confident action is taken.
GO:0032060 bleb assembly	IGI PMID:26317626 Microtubule-Mediated Inositol Lipid Signaling Plays Critical...	KEEP AS NON CORE	Summary: In a genetic (mutant) blebbing screen, gbpC/gbpD-deficient cells extended blebs more frequently than wild type, indicating GbpC acts within the regulation of bleb-based protrusion. A specialized, non-core process role. Reason: Genetic evidence supports GbpC involvement in regulating blebbing, but this is a peripheral process relative to the core cGMP/kinase signaling function. Supporting Evidence: PMID:26317626 cells deficient in gbpC-/gbpD (guanylate cyclases), pkgB (serine/threonine-protein kinase), iplA (Ca2+ channel), or pi3k (phosphatidylinositol 3-kinase) extended blebs more frequently than wild type cells
GO:0005085 guanyl-nucleotide exchange factor activity	IDA PMID:18703517 Intramolecular activation mechanism of the Dictyostelium LRR...	ACCEPT	Summary: Direct in vitro nucleotide-exchange assays show the isolated GbpC RasGEF domain specifically accelerates GDP/GTP exchange on its own Roc domain (and not on other Ras/Rap proteins). This is the strongest evidence for the GEF core function. Reason: Direct biochemical demonstration of specific GEF activity toward the Roc domain; a core molecular function of GbpC. Supporting Evidence: PMID:18703517 the RasGEF domain of GbpC specifically accelerates the GDP/GTP exchange of the Roc domain
GO:0051602 response to electrical stimulus	IMP PMID:19346484 Switching direction in electric-signal-induced cell migratio...	KEEP AS NON CORE	Summary: Genetic modulation of GbpC (with guanylyl cyclases) can reverse the preferred migration direction during electrotaxis, implicating GbpC in the cellular response to a direct-current electric field. A specialized process role. Reason: GbpC contributes to electrotaxis directionality via the cGMP pathway, but this is a context-specific process rather than a core function. Supporting Evidence: PMID:19346484 the preferential direction of migration during electrotaxis in Dictyostelium cells can be reversed by genetically modulating both guanylyl cyclases (GCases) and the cyclic guanosine monophosphate (cGMP)-binding protein C (GbpC)
GO:0030553 cGMP binding	IMP PMID:12011437 Identification of four candidate cGMP targets in Dictyosteli...	ACCEPT	Summary: Disruption of gbpC eliminates all high-affinity cGMP-binding activity in the soluble cell fraction, establishing GbpC as the principal high-affinity cGMP receptor in Dictyostelium. This is a defining core molecular function. Reason: GbpC accounts for the cell's high-affinity cGMP binding; cGMP binding is the central input function of this cGMP effector. Supporting Evidence: PMID:12011437 Disruption of the gbpC gene results in loss of all high-affinity cGMP-binding activity present in the soluble cellular fraction PMID:18703517 Because GbpC is the only high affinity cGMP-target in Dictyostelium
GO:0005543 phospholipid binding	IDA PMID:22119747 Multiple regulatory mechanisms for the Dictyostelium Roco pr...	KEEP AS NON CORE	Summary: The GbpC GRAM domain binds various phospholipids in vitro and mediates membrane association. A real molecular function underlying stimulus-dependent membrane targeting, but subsidiary to the cGMP/kinase signaling core. Reason: Phospholipid binding by the GRAM domain is directly demonstrated and functionally relevant for localization, but serves the membrane-targeting mechanism rather than being a top-level output function. Supporting Evidence: PMID:22119747 the GRAM domain itself associates with cellular membranes and binds various phospholipids in vitro
GO:0005525 GTP binding	IDA PMID:22119747 Multiple regulatory mechanisms for the Dictyostelium Roco pr...	ACCEPT	Summary: The Ras-like Roc domain of GbpC binds GTP; GTP-agarose pulldowns and P-loop (K342N) mutagenesis confirmed that GTP binding is mediated by the Roc domain. Intrinsic to the intramolecular Roc GTPase switch. Reason: Direct evidence shows GbpC binds GTP through its Roc domain, a core mechanistic activity of this Roco protein. Supporting Evidence: PMID:18703517 confirming that GTP binding is mediated by the Roc domain
GO:0030553 cGMP binding	IDA PMID:18673369 The Legionella pneumophila phosphatidylinositol-4 phosphate-...	ACCEPT	Summary: cGMP binding is a well-established core function of GbpC (it is the only high-affinity cGMP target in Dictyostelium). However, the cited reference PMID:18673369 is a Legionella pneumophila SidC study unrelated to GbpC, so the identifier appears mis-attributed. The function itself is correct and supported by the GbpC literature. Reason: The cGMP-binding function is genuine and central; the annotation is retained but the original reference is mis-cited (see reference_review for PMID:18673369). Support is provided from the correct GbpC literature. Supporting Evidence: PMID:18703517 Because GbpC is the only high affinity cGMP-target in Dictyostelium PMID:12011437 Disruption of the gbpC gene results in loss of all high-affinity cGMP-binding activity present in the soluble cellular fraction
GO:0046579 positive regulation of Ras protein signal transduction	IDA PMID:18703517 Intramolecular activation mechanism of the Dictyostelium LRR...	ACCEPT	Summary: The GbpC RasGEF domain positively regulates the GbpC Ras-like Roc domain by catalyzing GDP/GTP exchange, driving it into the active GTP-bound state. A directly demonstrated regulatory role in (intramolecular) Ras-type signaling. Reason: Direct evidence shows GbpC GEF activity positively regulates its Roc (Ras-like) GTPase, consistent with this process term. Supporting Evidence: PMID:18703517 the RasGEF domain of GbpC specifically accelerates the GDP/GTP exchange of the Roc domain
GO:0050920 regulation of chemotaxis	IMP PMID:18673369 The Legionella pneumophila phosphatidylinositol-4 phosphate-...	ACCEPT	Summary: GbpC is a key regulator of Dictyostelium chemotaxis via the cGMP pathway, a well-supported function. The cited reference PMID:18673369, however, is a Legionella SidC paper unrelated to GbpC and appears mis-attributed; the same function is properly supported by PMID:15827084. Reason: Regulation of chemotaxis is a genuine core process for GbpC; the annotation is retained but the original reference is mis-cited (see reference_review for PMID:18673369), with support drawn from the correct GbpC study. Supporting Evidence: PMID:15827084 gbpC-null cells display strongly reduced chemotaxis, because they are unable to polarise effectively in a chemotactic gradient
GO:0031589 cell-substrate adhesion	IMP PMID:15827084 RasGEF-containing proteins GbpC and GbpD have differential e...	UNDECIDED	Summary: In this paper the increased-adhesion / substrate-attached-pseudopod phenotype is attributed to GbpD (and its overexpression), not to GbpC, whose phenotype is reduced chemotaxis/polarity. The cached abstract does not document a GbpC-specific adhesion phenotype, so this annotation cannot be verified from the accessible text. Reason: The adhesion phenotype in this study is associated with the paralog GbpD; a GbpC-specific cell-substrate adhesion role is not verifiable from the available text. Per policy the experimental IMP annotation is not overruled, but it is left undecided pending full-text confirmation.
GO:0050920 regulation of chemotaxis	IMP PMID:15827084 RasGEF-containing proteins GbpC and GbpD have differential e...	ACCEPT	Summary: gbpC-null cells show strongly reduced chemotaxis due to failed polarization, directly demonstrating that GbpC regulates chemotaxis through the cGMP/myosin II pathway. A core biological role. Reason: Loss-of-function evidence firmly establishes GbpC as a regulator of chemotaxis. Supporting Evidence: PMID:15827084 gbpC-null cells display strongly reduced chemotaxis, because they are unable to polarise effectively in a chemotactic gradient PMID:22119747 cGMP-mediated GbpC activation is essential for the proper regulation of myosin II during chemotaxis

Gene Description

Existing Annotations Review

Core Functions

GbpC is the principal high-affinity intracellular cGMP receptor in Dictyostelium; cGMP binding to its tandem cyclic-nucleotide-binding domains is the sensing event that initiates the intramolecular signaling cascade controlling chemotaxis.

GbpC contains an internal RasGEF (CDC25) domain that specifically catalyzes GDP/GTP exchange on its own Ras-like Roc GTPase domain, converting the cGMP-binding signal into activation of the Roc GTPase within a single polypeptide.

References

Suggested Questions for Experts

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