rasC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003924 GTPase activity	IBA GO_REF:0000033	ACCEPT	Summary: RasC is a Ras-family small GTPase with intrinsic GTPase activity that hydrolyzes bound GTP; this is a core molecular function conserved across the Ras subfamily. Reason: Intrinsic GTPase activity is a defining, well-supported feature of Ras subfamily proteins and is consistent with the UniProt record (EC 3.6.5.2) and the biochemical framing of RasC as a GDP/GTP molecular switch. Supporting Evidence: PMID:15143344 the subsequent inactivation is due to an enhancement of the intrinsic GTPase activity, which is stimulated by the GTPase-activating proteins (GAPs)
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: RasC is a prenylated (geranylgeranylated) protein anchored to the plasma membrane, where activated RasC is enriched at the leading edge of chemotaxing cells. Reason: Plasma-membrane localization is expected for a lipid-anchored Ras GTPase and is consistent with the leading-edge enrichment of active Ras in migrating cells. Supporting Evidence: PMID:20493808 active Ras is enriched at the leading edge of chemotaxing cells
GO:0007264 small GTPase-mediated signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: RasC functions as a small GTPase molecular switch transducing extracellular (chemoattractant) signals to downstream effector pathways. Reason: This is the core biological process for RasC, which relays G-protein-coupled receptor signals to adenylyl cyclase and the TORC2-PKB pathway. Supporting Evidence: PMID:17380187 Ras proteins are small, monomeric GTPases that act as crucial regulators of a number of cellular signalling pathways
GO:0000281 mitotic cytokinesis	IBA GO_REF:0000033	REMOVE	Summary: This phylogenetic (IBA) inference of a cytokinesis role is contradicted by direct experimental evidence in Dictyostelium, where loss of RasC leaves cytokinesis and the division rate essentially normal. Reason: The IBA annotation is over-propagated from Ras-family members that function in cytokinesis. In Dictyostelium, cytokinesis is regulated mainly by RasG/RasB (via NdrC), whereas rasC-null cells divide normally, so this term does not represent RasC function. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN001177391 · PANTHER node for the Ras small-GTPase family SUPPORTS SOURCE BUT NOT TARGET Mitotic cytokinesis in Dictyostelium is the role of RasG; the term is over-propagated across Ras paralogs to RasC dictyBase:DDB_G0293434 · Dictyostelium Ras-family paralog (RasG-type) SUPPORTS SOURCE BUT NOT TARGET Cytokinesis function belongs to RasG, not RasC Supporting Evidence: PMID:15878331 there was no change in the rate of cell division
GO:0044351 macropinocytosis	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: The IBA macropinocytosis inference is not supported for RasC; in Dictyostelium, RasG is the Ras protein that promotes macropinocytosis, and loss of RasC actually increases fluid-phase endocytosis rather than reducing it. Reason: RasC does not positively drive macropinocytosis; rasC-null cells show increased liquid-phase endocytosis. The term is over-propagated from RasG-like family members. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN001177391 · PANTHER node for the Ras small-GTPase family SUPPORTS SOURCE BUT NOT TARGET Macropinocytosis is driven by other Dictyostelium Ras paralogs such as RasG and RasS; rasC-null cells show increased macropinocytosis, so the positive role does not belong to RasC dictyBase:DDB_G0293434 · Dictyostelium Ras-family paralog SUPPORTS SOURCE BUT NOT TARGET Macropinocytosis role belongs to a different Ras paralog subfamily, not RasC Supporting Evidence: PMID:15878331 Cells lacking RasC also contained more protein and were larger in
GO:0003925 G protein activity	IEA GO_REF:0000003	ACCEPT	Summary: RasC is a small monomeric GTPase (G protein), consistent with the EC 3.6.5.2 mapping used for this electronic annotation. Reason: RasC is a bona fide Ras-family small GTPase functioning as a nucleotide-dependent molecular switch; the EC-to-GO mapping is appropriate. Supporting Evidence: PMID:15143344 The Ras subfamily consists of small, monomeric GTPases that act as molecular switches in cellular signalling events
GO:0005525 GTP binding	IEA GO_REF:0000002	ACCEPT	Summary: RasC binds guanine nucleotides (GTP/GDP), cycling between active GTP-bound and inactive GDP-bound states. Reason: GTP binding is a defining feature of Ras GTPases and is directly supported by the demonstration that RasC is activated (GTP-loaded) in response to cAMP. Supporting Evidence: PMID:15143344 it was shown that RasC was activated in aggregation-competent cells in response to cAMP
GO:0003924 GTPase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO inference of GTPase activity from the small-GTPase domain; correct and consistent with the IBA GTPase annotation. Reason: RasC possesses intrinsic GTPase activity as a Ras-family small GTPase. Supporting Evidence: PMID:15143344 the subsequent inactivation is due to an enhancement of the intrinsic GTPase activity, which is stimulated by the GTPase-activating proteins (GAPs)
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to plasma membrane, consistent with the C-terminal prenyl (geranylgeranyl) lipid anchor and leading-edge localization of active RasC. Reason: Membrane localization is expected for a lipid-anchored Ras GTPase; this duplicates the IBA plasma membrane annotation. Supporting Evidence: PMID:20493808 active Ras is enriched at the leading edge of chemotaxing cells
GO:0007165 signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: General signal transduction term consistent with RasC's role as a signaling GTPase; correct but non-specific relative to more informative child terms. Reason: RasC is a signaling molecular switch; the term is accurate though general. Supporting Evidence: PMID:11500376 RasC appears to function as a regulatory molecule for both the cAMP relay and the chemotactic response to cAMP.
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic membrane localization term, redundant with the more specific plasma membrane annotation. Reason: The parent term "membrane" is correct but uninformative given the specific plasma membrane localization of prenylated RasC. Supporting Evidence: PMID:20493808 active Ras is enriched at the leading edge of chemotaxing cells
GO:0071321 cellular response to cGMP	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	KEEP AS NON CORE	Summary: RasC (with RasG) is required for cAMP-induced guanylyl cyclase activation during aggregation; the connection to cGMP responses is indirect and predominantly through RasG. Reason: The genetic evidence links RasC/RasG to guanylyl cyclase activation, but cGMP signaling is predominantly a RasG function and is peripheral to RasC's core role in ACA and TORC2 activation. Supporting Evidence: PMID:18180289 guanylyl cyclase activation is also abolished in the
GO:0019887 protein kinase regulator activity	IDA PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: RasC positively regulates the activity of the PKB/Akt kinases (via TORC2), reflected in reduced Akt/PKB and ERK2 phosphorylation in rasC-null cells. Reason: RasC regulates downstream protein kinases indirectly (through TORC2), so a general "protein kinase regulator activity" molecular function is defensible but less informative than its GTPase/TORC2-activation functions. Supporting Evidence: PMID:15878331 ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response to folate
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	ACCEPT	Summary: RasC acts upstream of the PI3K/PKB (Akt) pathway; loss of RasC reduces Akt/PKB phosphorylation in response to chemoattractant. Reason: RasC is a genuine upstream activator of PKB signaling (chiefly via TORC2), a core aspect of its function during chemotaxis and aggregation. Supporting Evidence: PMID:15878331 ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response to folate PMID:11500376 RasC appears to be a central regulatory molecule acting downstream of serpentine receptor stimulation by cAMP that is required for two distinct effector pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl cyclase.
GO:0140986 G protein-coupled chemorepellent receptor signaling pathway	IGI PMID:30462573 An endogenous chemorepellent directs cell movement by inhibi...	KEEP AS NON CORE	Summary: RasC (redundantly with RasG) is required for AprA chemorepellent responses; rasC-/rasG- double mutants fail to move away from AprA. Reason: The chemorepulsion role is genuine but redundant with RasG and peripheral to RasC's principal roles in ACA and TORC2 activation. Supporting Evidence: PMID:30462573 signal transduction pathways including Ras
GO:0000165 MAPK cascade	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: RasC influences ERK2/MAPK phosphorylation in a context-dependent manner (reduced in response to folate), although for cAMP relay ERK2 activation is RasC-independent. Reason: The MAPK role is context-dependent and not RasC's core output; during cAMP relay, cAMP-induced ERK2 phosphorylation is unaffected in rasC-null cells. Supporting Evidence: PMID:15878331 ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response to folate
GO:0031932 TORC2 complex	IDA PMID:31263268 Phosphorylated Rho-GDP directly activates mTORC2 kinase towa...	KEEP AS NON CORE	Summary: Activated RasC associates with TORC2 by binding TOR and by forming a RacE-RasC-mTORC2 supercomplex, but RasC is a regulatory GTPase rather than a stoichiometric core subunit of TORC2. Reason: RasC transiently binds and activates TORC2 rather than being a constitutive subunit, so the part_of relationship overstates the association. The functional binding and activation are better captured by the TORC2-binding and positive-regulation terms. Supporting Evidence: PMID:31263268 assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
GO:1904515 positive regulation of TORC2 signaling	IDA PMID:31263268 Phosphorylated Rho-GDP directly activates mTORC2 kinase towa...	ACCEPT	Summary: GTP-bound RasC, together with phosphorylated GDP-RacE, directly stimulates mTORC2 kinase activity toward AKT. Reason: Positive regulation of TORC2 is a core RasC function, demonstrated by in vitro reconstitution of RasC-dependent mTORC2-mediated AKT phosphorylation. Supporting Evidence: PMID:31263268 assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
GO:0051593 response to folic acid	IGI PMID:23132928 Delineating the core regulatory elements crucial for directe...	KEEP AS NON CORE	Summary: RasC contributes to folic-acid-stimulated responses in vegetative cells, notably PKB substrate phosphorylation, via the TORC2 pathway. Reason: RasC participates in folate-triggered signaling but this is one of several redundant vegetative-cell roles, secondary to its core aggregation/ACA and TORC2 functions. Supporting Evidence: PMID:23132928 Ras C activates the TORC2 complex, which in turn triggers PKBA and a second PKB homolog, PKBR1
GO:0007165 signal transduction	IMP PMID:11500376 RasC is required for optimal activation of adenylyl cyclase ...	ACCEPT	Summary: RasC is a signaling GTPase required for cAMP relay and chemotactic responses during aggregation. Reason: Signal transduction is accurate for RasC, supported by the aggregation-defective phenotype of rasC-null cells and their role in cAMP signaling. Supporting Evidence: PMID:11500376 RasC appears to function as a regulatory molecule for both the cAMP relay and the chemotactic response to cAMP.
GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IMP PMID:15143344 Chemoattractant-induced Ras activation during Dictyostelium ...	ACCEPT	Summary: RasC is activated downstream of the cAMP GPCR and is required for chemoattractant-induced activation of adenylyl cyclase (the cAMP relay). Reason: This is a core function of RasC - transducing cAMP-receptor signals to adenylyl cyclase during aggregation. Supporting Evidence: PMID:15143344 it was shown that RasC was activated in aggregation-competent cells in response to cAMP PMID:17380187 RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase activation
GO:1903665 negative regulation of asexual reproduction	IMP PMID:34154396 An Autocrine Negative Feedback Loop Inhibits Dictyostelium d...	KEEP AS NON CORE	Summary: RasC is required for extracellular-polyphosphate-mediated inhibition of cell proliferation under low-nutrient conditions. Reason: RasC participates in the polyphosphate proliferation-inhibition pathway, but this is a specialized, redundant signaling role distinct from its core aggregation/TORC2 functions. Supporting Evidence: PMID:34154396 the loss of GrlD or RasC blocked the sensitivity of cells to polyphosphate
GO:0051291 protein heterooligomerization	IDA PMID:33238110 Hetero-oligomerization of Rho and Ras GTPases Connects GPCR ...	KEEP AS NON CORE	Summary: Chemoattractant stimulation induces GTP-bound RasC to hetero-oligomerize with phosphorylated GDP-bound RacE, an interaction required for mTORC2-AKT activation. Reason: The RasC-RacE hetero-oligomerization is a genuine, directly demonstrated interaction, but it is a mechanistic step in TORC2 activation rather than a stand-alone core function. Supporting Evidence: PMID:33238110 these two GTPases directly interact in cells
GO:0003925 G protein activity	IDA PMID:17380187 Cyclic AMP signalling in Dictyostelium: G-proteins activate ...	ACCEPT	Summary: RasC is a small GTPase whose GDP-to-GTP exchange is catalyzed specifically by RasGEFA, confirming its function as a nucleotide-switch G protein. Reason: Direct in vitro nucleotide-exchange and activation assays establish RasC as a functional Ras-family G protein. Supporting Evidence: PMID:17380187 RasGEFA catalysed the removal of GDP from RasC but not from other Ras subfamily proteins, confirming that RasGEFA is specific for RasC
GO:0003925 G protein activity	IMP PMID:23132928 Delineating the core regulatory elements crucial for directe...	ACCEPT	Summary: RasC functions as an activatable G protein upstream of the TORC2-PKB pathway in chemotactic responses. Reason: Consistent with the direct IDA evidence that RasC is a Ras-family G protein; this genetic annotation supports the same molecular function. Supporting Evidence: PMID:23132928 Ras C activates the TORC2 complex, which in turn triggers PKBA and a second PKB homolog, PKBR1
GO:0005515 protein binding	IPI PMID:31263268 Phosphorylated Rho-GDP directly activates mTORC2 kinase towa...	KEEP AS NON CORE	Summary: Activated RasC physically associates with the mTORC2 machinery and RacE within a signaling supercomplex. Reason: Bare "protein binding" is uninformative; the functional interaction (RasC-RacE-mTORC2 supercomplex, RasC-TOR binding) is better captured by the TORC2-binding and TORC2-activation terms. Supporting Evidence: PMID:31263268 assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
GO:0007265 Ras protein signal transduction	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	ACCEPT	Summary: RasC-mediated signal transduction affects motility, polarity, endocytosis, and chemotactic responses in vegetative and developing cells. Reason: Ras protein signal transduction is the core process RasC executes as a signaling GTPase. Supporting Evidence: PMID:15878331 loss of signal transduction through the RasC protein was found to
GO:0007265 Ras protein signal transduction	IMP PMID:20660630 Ras-mediated activation of the TORC2-PKB pathway is critical...	ACCEPT	Summary: RasC signal transduction controls the TORC2-PKB pathway governing chemotaxis. Reason: Directly supported - RasC is the upstream Ras controlling TORC2-PKB signaling during chemotaxis. Supporting Evidence: PMID:20660630 RasC is required for TORC2-mediated activation of PKB
GO:0106070 regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IMP PMID:11500376 RasC is required for optimal activation of adenylyl cyclase ...	ACCEPT	Summary: RasC regulates cAMP-receptor-mediated activation of adenylyl cyclase; rasC-null cells fail to produce cAMP in response to receptor stimulation. Reason: Regulation of the adenylyl-cyclase-activating GPCR pathway is a core RasC function underlying the cAMP relay during aggregation. Supporting Evidence: PMID:11500376 RasC appears to be a central regulatory molecule acting downstream of serpentine receptor stimulation by cAMP that is required for two distinct effector pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl cyclase.
GO:0005515 protein binding	IPI PMID:24986648 Regulation of a LATS-homolog by Ras GTPases is important for...	KEEP AS NON CORE	Summary: Activated RasC binds the LATS-family kinase NdrC via its Ras-binding domain (lower affinity than RasG/RasB). Reason: Documents a specific RasC-NdrC interaction, but as bare "protein binding" it is uninformative; the cytokinesis phenotype is driven by RasG/RasB, not RasC. Supporting Evidence: PMID:24986648 NdrC was the only protein that bound RasC in the yeast two-hybrid screen
GO:0005515 protein binding	IPI PMID:26424797 PP2A/B56 and GSK3/Ras suppress PKB activity during Dictyoste...	KEEP AS NON CORE	Summary: The PP2A regulatory subunit B56 preferentially associates with the GDP-bound form of RasC (and RasD), part of a phosphatase-mediated negative regulation of PKB. Reason: A real interaction, but "protein binding" is uninformative; the functional significance is regulatory (PP2A/B56 modulating Ras and PKB activity). Supporting Evidence: PMID:26424797 GDP forms of RasC and RasD, but not with RasG in vitro
GO:0005515 protein binding	IPI PMID:27172998 The small GTPases Ras and Rap1 bind to and control TORC2 act...	KEEP AS NON CORE	Summary: Active RasC binds directly to the catalytic (FRB/kinase) domain of TOR, the proposed mechanism by which RasC activates TORC2. Reason: This specific RasC-TOR interaction is functionally important but is better represented by TORC2-binding/activation terms than by generic "protein binding". Supporting Evidence: PMID:27172998 we found that TOR kinase itself specifically co-purifies with RasCGppNHp
GO:0005515 protein binding	IPI PMID:29109256 GPCR-controlled membrane recruitment of negative regulator C...	KEEP AS NON CORE	Summary: The negative regulator C2GAP1 (a RasGAP) binds RasC in vitro, consistent with its role in terminating Ras signaling for adaptation. Reason: Documents a RasC-C2GAP1 interaction; bare "protein binding" is uninformative relative to the GAP-mediated regulation it represents. Supporting Evidence: PMID:29109256 the in vitro binding assay indicates that C2GAP1 binds both GTP- and GDP-bound Ras protein
GO:0005525 GTP binding	IDA PMID:15143344 Chemoattractant-induced Ras activation during Dictyostelium ...	ACCEPT	Summary: RasC binds and is activated by GTP; an RBD-based assay directly detected GTP-loaded (active) RasC upon cAMP stimulation. Reason: Direct experimental demonstration of RasC nucleotide binding/activation supports the GTP-binding molecular function. Supporting Evidence: PMID:15143344 it was shown that RasC was activated in aggregation-competent cells in response to cAMP
GO:0005811 lipid droplet	HDA PMID:24036346 Dictyostelium lipid droplets host novel proteins.	MARK AS OVER ANNOTATED	Summary: RasC was recovered in a high-throughput lipid-droplet proteome, but its established localization is the plasma membrane/leading edge; lipid-droplet association likely reflects the shared lipid-anchor/membrane biochemistry rather than a functional role. Reason: High-throughput organelle proteomes frequently capture membrane-anchored proteins as background. There is no functional evidence for RasC acting at lipid droplets, whose biology is unrelated to Ras chemotactic signaling. Supporting Evidence: PMID:24036346 Among the novel protein components are LdpA, a protein specific to Dictyostelium
GO:0010856 adenylate cyclase activator activity	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	ACCEPT	Summary: RasC (with RasG) is required for cAMP-receptor-mediated activation of adenylyl cyclase during aggregation, with RasC being the more important of the two for ACA activation. Reason: Activation of adenylyl cyclase is a core RasC function underlying the cAMP relay; RasC/RasG are the presumptive GTPases required for cyclase activation. Supporting Evidence: PMID:18180289 proteins that are necessary for optimum cAMP signaling PMID:17380187 RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase activation
GO:0030250 guanylate cyclase activator activity	IMP PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	KEEP AS NON CORE	Summary: In vitro guanylyl cyclase activation is abolished in rasC-/rasG- cells, identifying RasC/RasG as required for cyclase activation; however, RasG predominates for the cGMP branch. Reason: RasC contributes to guanylyl cyclase activation but this is largely a RasG-dominated function and secondary to RasC's principal ACA/TORC2 roles. Supporting Evidence: PMID:18180289 guanylyl cyclase activation is also abolished in the
GO:0030250 guanylate cyclase activator activity	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	KEEP AS NON CORE	Summary: Genetic-interaction evidence that RasC (with RasG) is required for guanylyl cyclase activation; duplicate of the IMP annotation. Reason: Same rationale as the paired IMP annotation - a redundant, RasG-dominated function. Supporting Evidence: PMID:18180289 guanylyl cyclase activation is also abolished in the
GO:0031252 cell leading edge	IC PMID:20493808 A Ras signaling complex controls the RasC-TORC2 pathway and ...	ACCEPT	Summary: Active RasC signaling (RasC-TORC2) is localized to the leading edge of chemotaxing cells, where the Sca1/RasGEF complex promotes local RasC activation. Reason: Leading-edge localization of active RasC signaling is a core spatial feature underlying directed migration. Supporting Evidence: PMID:20493808 active Ras is enriched at the leading edge of chemotaxing cells
GO:0031982 vesicle	IDA PMID:19589376 Nanovesicles released by Dictyostelium cells: a potential ca...	MARK AS OVER ANNOTATED	Summary: RasC was detected among proteins of secreted Dictyostelium nanovesicles (a proteome dominated by actin and endosomal markers); this does not reflect a functional vesicle role. Reason: Recovery in a released-nanovesicle proteome is expected for a membrane-anchored protein and does not indicate a dedicated vesicle function; RasC acts at the plasma membrane/leading edge. Supporting Evidence: PMID:19589376 A proteomic analysis reveals a predominance of actin and actin-related proteins.
GO:0051602 response to electrical stimulus	IMP PMID:26012633 A large-scale screen reveals genes that mediate electrotaxis...	KEEP AS NON CORE	Summary: rasC was identified among genes affecting electrotaxis in a large-scale screen; the specific mechanistic role is not defined. Reason: A screen-level hit indicating involvement in electrotaxis, but peripheral to RasC's characterized core functions and without detailed mechanistic support in the accessible text.
GO:1904841 TORC2 complex binding	IDA PMID:20660630 Ras-mediated activation of the TORC2-PKB pathway is critical...	ACCEPT	Summary: TORC2 binds specifically to the activated (GTP-bound) form of RasC, as shown by co-immunoprecipitation with the TORC2 component Rip3. Reason: Direct binding of activated RasC to TORC2 is a core molecular function central to RasC-mediated PKB activation and chemotaxis. Supporting Evidence: PMID:20660630 This result shows that RasC and TORC2 interact in a regulated fashion
GO:0005515 protein binding	IPI PMID:27009206 The novel RacE-binding protein GflB sharpens Ras activity at...	KEEP AS NON CORE	Summary: The RacE-binding, RhoGAP/RasGEF-domain protein GflB binds RasC (and RasG), linking directional sensing to Ras/Rho activity at the leading edge. Reason: A real RasC-GflB interaction, but bare "protein binding" is uninformative and GflB's characterized activity is chiefly on RasG/Rac. Supporting Evidence: PMID:27009206 GflB also binds to Ras GTPases
GO:0110094 polyphosphate-mediated signaling	IMP PMID:28584190 Extracellular polyphosphate signals through Ras and Akt to p...	KEEP AS NON CORE	Summary: RasC (with Akt/PKB) mediates extracellular-polyphosphate signaling that primes cells for development and inhibits the proteasome. Reason: RasC participates in polyphosphate signaling, but this is a specialized branch secondary to its core aggregation and TORC2 roles. Supporting Evidence: PMID:28584190 mediated by Akt proteins and RasC in Dictyostelium
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:20660630 Ras-mediated activation of the TORC2-PKB pathway is critical...	ACCEPT	Summary: RasC positively regulates PKB activation, primarily through TORC2-mediated phosphorylation of PKBR1/PKBA (largely PIP3-independent). Reason: Positive regulation of PKB signaling is a core RasC output; RasC deletion reduces, and activated RasC prolongs, PKB phosphorylation. Supporting Evidence: PMID:20660630 RasC is required for TORC2-mediated activation of PKB
GO:0061122 positive regulation of positive chemotaxis to cAMP	IMP PMID:20660630 Ras-mediated activation of the TORC2-PKB pathway is critical...	KEEP AS NON CORE	Summary: Proper temporal control of RasC-TORC2-PKBR1 signaling is required for efficient directed migration toward cAMP; dysregulated RasC impairs chemotaxis. Reason: RasC contributes to cAMP chemotaxis via TORC2, but chemotactic gradient sensing is dominated by RasG/PI3K; RasC's contribution here is modulatory. Supporting Evidence: PMID:20660630 RasC is required for TORC2-mediated activation of PKB
GO:1904515 positive regulation of TORC2 signaling	IMP PMID:20660630 Ras-mediated activation of the TORC2-PKB pathway is critical...	ACCEPT	Summary: RasC is required for and, when constitutively active, prolongs TORC2-mediated PKB signaling. Reason: Positive regulation of TORC2 is a core RasC function established by genetic and in vitro reconstitution evidence. Supporting Evidence: PMID:20660630 RasC is required for TORC2-mediated activation of PKB
GO:0048870 cell motility	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: Vegetative rasC-null cells show reduced random motility and are less polarized, indicating a role for RasC in cell motility. Reason: RasC affects motility, but the dominant motility/polarity regulator among the Ras proteins is RasG; RasC's contribution is partial. Supporting Evidence: PMID:15878331 reduced random motility, were less polarized and had altered F-actin
GO:0019954 asexual reproduction	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	KEEP AS NON CORE	Summary: RasC is required (with RasG) for aggregation, the developmental process that leads to asexual sporulation. Reason: The link to asexual reproduction is via RasC's role in aggregation/cAMP signaling rather than a distinct reproductive function. Supporting Evidence: PMID:18180289 proteins that are necessary for optimum cAMP signaling
GO:0043326 chemotaxis to folate	IGI PMID:20833893 Ras proteins have multiple functions in vegetative cells of ...	KEEP AS NON CORE	Summary: RasC can partially substitute for RasG in folate chemotaxis; rasC-/rasG- cells are completely incapable of folate chemotaxis. Reason: RasC contributes to folate chemotaxis but redundantly with (and secondarily to) RasG. Supporting Evidence: PMID:20833893 to folate, RasC is capable of partially substituting for RasG
GO:0043327 chemotaxis to cAMP	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	KEEP AS NON CORE	Summary: RasC (with RasG) is required for optimal cAMP signaling that underlies chemotaxis during aggregation. Reason: RasC contributes to cAMP chemotaxis but the chemotactic branch is predominantly RasG-dependent; RasC's core role is ACA activation. Supporting Evidence: PMID:18180289 proteins that are necessary for optimum cAMP signaling
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras...	ACCEPT	Summary: RasC (with RasG) acts upstream of PKB activation during cAMP signaling. Reason: Positive regulation of PKB activation is a core RasC output during cAMP signaling, consistent with the reduced PKB phosphorylation of rasC-null cells. Supporting Evidence: PMID:18180289 proteins that are necessary for optimum cAMP signaling
GO:0031152 aggregation involved in sorocarp development	IMP PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep...	ACCEPT	Summary: RasC is required for aggregation, controlling both cAMP relay (ACA activation) and, partly, chemotaxis during early development. Reason: Aggregation is a core developmental process requiring RasC; rasC-null cells fail to aggregate. Supporting Evidence: PMID:16885420 the Ras protein RasC is involved in both processes
GO:0031152 aggregation involved in sorocarp development	IGI PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep...	ACCEPT	Summary: Genetic-interaction evidence (RasC vs RasG) confirming RasC's role in aggregation, predominantly via ACA activation. Reason: Duplicate line of evidence for RasC's core aggregation function. Supporting Evidence: PMID:16885420 signal transduction through RasC is more important in ACA activation
GO:0043327 chemotaxis to cAMP	IMP PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep...	KEEP AS NON CORE	Summary: RasC contributes to cAMP chemotaxis, though signaling through RasG is more important for chemotaxis while RasC is more important for the cAMP relay. Reason: RasC's chemotactic contribution is secondary to RasG; its core role is ACA activation. Supporting Evidence: PMID:16885420 signal transduction through RasC is more important in ACA activation
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep...	ACCEPT	Summary: RasC contributes to cAMP-stimulated PKB phosphorylation during aggregation. Reason: Positive regulation of PKB is a core RasC output; this is consistent supporting evidence from the isogenic RasC/RasG null comparison. Supporting Evidence: PMID:16885420 signal transduction through RasC is more important in ACA activation
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep...	ACCEPT	Summary: Genetic-interaction evidence that RasC contributes to PKB activation during aggregation. Reason: Positive regulation of PKB is a core RasC output; consistent supporting evidence. Supporting Evidence: PMID:16885420 signal transduction through RasC is more important in ACA activation
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:11500376 RasC is required for optimal activation of adenylyl cyclase ...	ACCEPT	Summary: cAMP-induced Akt/PKB phosphorylation through a PI3K-dependent pathway is dramatically reduced in rasC-null cells. Reason: RasC positively regulating PKB activation is a core function, directly demonstrated by reduced Akt/PKB phosphorylation in rasC-null cells. Supporting Evidence: PMID:11500376 RasC appears to be a central regulatory molecule acting downstream of serpentine receptor stimulation by cAMP that is required for two distinct effector pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl cyclase.
GO:0031152 aggregation involved in sorocarp development	IMP PMID:16023096 The effect of the disruption of a gene encoding a PI4 kinase...	ACCEPT	Summary: Disruption of rasC produces a strain that fails to aggregate, with defects in both cAMP signal relay and chemotaxis. Reason: Core developmental phenotype - RasC is required for aggregation. Supporting Evidence: PMID:16023096 fails to aggregate with defects in both cAMP
GO:0043327 chemotaxis to cAMP	IMP PMID:16023096 The effect of the disruption of a gene encoding a PI4 kinase...	KEEP AS NON CORE	Summary: rasC-null cells are defective in cAMP chemotaxis (as part of the aggregation-negative phenotype). Reason: RasC contributes to cAMP chemotaxis but redundantly with/secondarily to RasG; its core role is ACA activation. Supporting Evidence: PMID:16023096 fails to aggregate with defects in both cAMP
GO:0001558 regulation of cell growth	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: rasC-null cells contain more protein and are larger than wild type, indicating a role for RasC in regulating cell size/growth. Reason: RasC influences vegetative cell size, but this is one of several secondary vegetative-cell phenotypes rather than a core function. Supporting Evidence: PMID:15878331 Cells lacking RasC also contained more protein and were larger in
GO:0051491 positive regulation of filopodium assembly	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: Loss of RasC alters F-actin distribution and cell polarity, consistent with a role in actin-based protrusion regulation; the abstract does not specifically detail filopodium assembly. Reason: RasC affects the actin cytoskeleton and protrusions, but a specific filopodium-assembly function is a minor aspect and only indirectly supported by the accessible abstract. Supporting Evidence: PMID:15878331 reduced random motility, were less polarized and had altered F-actin
GO:0007163 establishment or maintenance of cell polarity	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: rasC-null cells are less polarized, indicating a role for RasC in cell polarity. Reason: RasC contributes to polarity/actin organization but is not the dominant polarity regulator among Dictyostelium Ras proteins. Supporting Evidence: PMID:15878331 reduced random motility, were less polarized and had altered F-actin
GO:0030036 actin cytoskeleton organization	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: Loss of RasC alters F-actin distribution, linking RasC signaling to actin cytoskeleton organization. Reason: RasC influences the actin cytoskeleton (via TORC2-PKB and downstream effectors), a secondary consequence of its signaling rather than a direct core function. Supporting Evidence: PMID:15878331 reduced random motility, were less polarized and had altered F-actin
GO:0043326 chemotaxis to folate	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	KEEP AS NON CORE	Summary: rasC-null cells chemotax poorly to folate and show reduced folate-induced F-actin and PKB responses. Reason: RasC contributes to folate chemotaxis but redundantly with RasG; this is a vegetative-cell role secondary to RasC's core aggregation/ACA function. Supporting Evidence: PMID:15878331 chemotaxed poorly to folate
GO:0120320 lateral pseudopodium retraction	IMP PMID:15878331 Loss of the Dictyostelium RasC protein alters vegetative cel...	UNDECIDED	Summary: This specific term (lateral pseudopodium retraction) is not addressed in the accessible (abstract-only) record for this reference, which reports reduced polarity and altered F-actin but not pseudopod retraction dynamics per se. Reason: The cached publication is abstract-only and does not provide verifiable support for a specific lateral-pseudopodium-retraction function; the curator likely relied on full-text data not accessible here.
GO:0031152 aggregation involved in sorocarp development	IMP PMID:11500376 RasC is required for optimal activation of adenylyl cyclase ...	ACCEPT	Summary: Disruption of rasC generates cells incapable of aggregation, a defect restricted to the aggregation stage and rescuable by exogenous cAMP pulses. Reason: RasC's requirement for aggregation is a core developmental function directly demonstrated by the rasC-null phenotype. Supporting Evidence: PMID:11500376 generated cells incapable of aggregation

📄 View Raw YAML

id: P32253
gene_symbol: rasC
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: >-
  RasC is a member of the Ras subfamily of small monomeric GTPases in the social
  amoeba Dictyostelium discoideum. Like other Ras proteins, it cycles between an
  inactive GDP-bound and an active GTP-bound state, possesses intrinsic GTPase
  activity (EC 3.6.5.2), and is post-translationally prenylated at a C-terminal
  geranylgeranyl cysteine that anchors it to the cytoplasmic face of the plasma
  membrane. RasC is activated in response to extracellular cAMP sensed through
  G-protein-coupled cAMP receptors, via its dedicated guanine-nucleotide exchange
  factor RasGEFA (Aimless). Together with the partly redundant paralog RasG, RasC
  is a central regulator of early development. It is required for aggregation, where
  it preferentially controls activation of adenylyl cyclase (ACA) and the cAMP relay,
  and it is the principal Ras that activates the TORC2-PKB (Akt/PKBR1) pathway,
  binding the catalytic domain of TOR and forming a hetero-oligomer with
  phosphorylated GDP-bound RacE to stimulate mTORC2-mediated AKT phosphorylation.
  Through TORC2-PKB signaling, active RasC, enriched at the leading edge of
  chemotaxing cells, sets the temporal and spatial dynamics of the actin
  cytoskeleton, pseudopod formation, and directed cell migration. RasC also
  participates in additional Ras-dependent responses including folate chemotaxis and
  polyphosphate signaling, and it interacts with effectors and regulators such as the
  LATS-family kinase NdrC, the RasGAP C2GAP1, and the scaffold-associated RasGEF
  complex.
existing_annotations:
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: RasC is a Ras-family small GTPase with intrinsic GTPase activity that hydrolyzes
      bound GTP; this is a core molecular function conserved across the Ras subfamily.
    action: ACCEPT
    reason: Intrinsic GTPase activity is a defining, well-supported feature of Ras subfamily
      proteins and is consistent with the UniProt record (EC 3.6.5.2) and the biochemical
      framing of RasC as a GDP/GTP molecular switch.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: the subsequent inactivation is due to an enhancement of the intrinsic
        GTPase activity, which is stimulated by the GTPase-activating proteins (GAPs)
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: RasC is a prenylated (geranylgeranylated) protein anchored to the plasma
      membrane, where activated RasC is enriched at the leading edge of chemotaxing cells.
    action: ACCEPT
    reason: Plasma-membrane localization is expected for a lipid-anchored Ras GTPase and
      is consistent with the leading-edge enrichment of active Ras in migrating cells.
    supported_by:
    - reference_id: PMID:20493808
      supporting_text: active Ras is enriched at the leading edge of chemotaxing cells
- term:
    id: GO:0007264
    label: small GTPase-mediated signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: RasC functions as a small GTPase molecular switch transducing extracellular
      (chemoattractant) signals to downstream effector pathways.
    action: ACCEPT
    reason: This is the core biological process for RasC, which relays G-protein-coupled
      receptor signals to adenylyl cyclase and the TORC2-PKB pathway.
    supported_by:
    - reference_id: PMID:17380187
      supporting_text: Ras proteins are small, monomeric GTPases that act as crucial regulators
        of a number of cellular signalling pathways
- term:
    id: GO:0000281
    label: mitotic cytokinesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This phylogenetic (IBA) inference of a cytokinesis role is contradicted by
      direct experimental evidence in Dictyostelium, where loss of RasC leaves cytokinesis
      and the division rate essentially normal.
    action: REMOVE
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      source_entities:
      - source_id: PANTHER:PTN001177391
        source_label: "PANTHER node for the Ras small-GTPase family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Mitotic cytokinesis in Dictyostelium is the role of RasG; the term is over-propagated across Ras paralogs to RasC"
      - source_id: dictyBase:DDB_G0293434
        source_label: "Dictyostelium Ras-family paralog (RasG-type)"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Cytokinesis function belongs to RasG, not RasC"
    reason: The IBA annotation is over-propagated from Ras-family members that function
      in cytokinesis. In Dictyostelium, cytokinesis is regulated mainly by RasG/RasB (via
      NdrC), whereas rasC-null cells divide normally, so this term does not represent RasC
      function.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: there was no change in the rate of cell division
- term:
    id: GO:0044351
    label: macropinocytosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The IBA macropinocytosis inference is not supported for RasC; in Dictyostelium,
      RasG is the Ras protein that promotes macropinocytosis, and loss of RasC actually
      increases fluid-phase endocytosis rather than reducing it.
    action: MARK_AS_OVER_ANNOTATED
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      source_entities:
      - source_id: PANTHER:PTN001177391
        source_label: "PANTHER node for the Ras small-GTPase family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Macropinocytosis is driven by other Dictyostelium Ras paralogs such as RasG and RasS; rasC-null cells show increased macropinocytosis, so the positive role does not belong to RasC"
      - source_id: dictyBase:DDB_G0293434
        source_label: "Dictyostelium Ras-family paralog"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Macropinocytosis role belongs to a different Ras paralog subfamily, not RasC"
    reason: RasC does not positively drive macropinocytosis; rasC-null cells show increased
      liquid-phase endocytosis. The term is over-propagated from RasG-like family members.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: Cells lacking RasC also contained more protein and were larger in
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: RasC is a small monomeric GTPase (G protein), consistent with the EC 3.6.5.2
      mapping used for this electronic annotation.
    action: ACCEPT
    reason: RasC is a bona fide Ras-family small GTPase functioning as a nucleotide-dependent
      molecular switch; the EC-to-GO mapping is appropriate.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: The Ras subfamily consists of small, monomeric GTPases that act as
        molecular switches in cellular signalling events
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: RasC binds guanine nucleotides (GTP/GDP), cycling between active GTP-bound
      and inactive GDP-bound states.
    action: ACCEPT
    reason: GTP binding is a defining feature of Ras GTPases and is directly supported
      by the demonstration that RasC is activated (GTP-loaded) in response to cAMP.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: it was shown that RasC was activated in aggregation-competent cells
        in response to cAMP
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO inference of GTPase activity from the small-GTPase domain; correct
      and consistent with the IBA GTPase annotation.
    action: ACCEPT
    reason: RasC possesses intrinsic GTPase activity as a Ras-family small GTPase.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: the subsequent inactivation is due to an enhancement of the intrinsic
        GTPase activity, which is stimulated by the GTPase-activating proteins (GAPs)
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location mapping to plasma membrane, consistent with the
      C-terminal prenyl (geranylgeranyl) lipid anchor and leading-edge localization of
      active RasC.
    action: ACCEPT
    reason: Membrane localization is expected for a lipid-anchored Ras GTPase; this duplicates
      the IBA plasma membrane annotation.
    supported_by:
    - reference_id: PMID:20493808
      supporting_text: active Ras is enriched at the leading edge of chemotaxing cells
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: General signal transduction term consistent with RasC's role as a signaling
      GTPase; correct but non-specific relative to more informative child terms.
    action: ACCEPT
    reason: RasC is a signaling molecular switch; the term is accurate though general.
    supported_by:
    - reference_id: PMID:11500376
      supporting_text: RasC appears to function as a regulatory molecule for both the cAMP
        relay and the chemotactic response to cAMP.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: Generic membrane localization term, redundant with the more specific plasma
      membrane annotation.
    action: KEEP_AS_NON_CORE
    reason: The parent term "membrane" is correct but uninformative given the specific
      plasma membrane localization of prenylated RasC.
    supported_by:
    - reference_id: PMID:20493808
      supporting_text: active Ras is enriched at the leading edge of chemotaxing cells
- term:
    id: GO:0071321
    label: cellular response to cGMP
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC (with RasG) is required for cAMP-induced guanylyl cyclase activation
      during aggregation; the connection to cGMP responses is indirect and predominantly
      through RasG.
    action: KEEP_AS_NON_CORE
    reason: The genetic evidence links RasC/RasG to guanylyl cyclase activation, but cGMP
      signaling is predominantly a RasG function and is peripheral to RasC's core role
      in ACA and TORC2 activation.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: guanylyl cyclase activation is also abolished in the
- term:
    id: GO:0019887
    label: protein kinase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:15878331
  qualifier: enables
  review:
    summary: RasC positively regulates the activity of the PKB/Akt kinases (via TORC2),
      reflected in reduced Akt/PKB and ERK2 phosphorylation in rasC-null cells.
    action: KEEP_AS_NON_CORE
    reason: RasC regulates downstream protein kinases indirectly (through TORC2), so a
      general "protein kinase regulator activity" molecular function is defensible but
      less informative than its GTPase/TORC2-activation functions.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response
        to folate
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC acts upstream of the PI3K/PKB (Akt) pathway; loss of RasC reduces Akt/PKB
      phosphorylation in response to chemoattractant.
    action: ACCEPT
    reason: RasC is a genuine upstream activator of PKB signaling (chiefly via TORC2),
      a core aspect of its function during chemotaxis and aggregation.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response
        to folate
    - reference_id: PMID:11500376
      supporting_text: 'RasC appears to be a central regulatory molecule acting downstream
        of serpentine receptor stimulation by cAMP that is required for two distinct effector
        pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl
        cyclase.'
- term:
    id: GO:0140986
    label: G protein-coupled chemorepellent receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:30462573
  qualifier: involved_in
  review:
    summary: RasC (redundantly with RasG) is required for AprA chemorepellent responses;
      rasC-/rasG- double mutants fail to move away from AprA.
    action: KEEP_AS_NON_CORE
    reason: The chemorepulsion role is genuine but redundant with RasG and peripheral to
      RasC's principal roles in ACA and TORC2 activation.
    supported_by:
    - reference_id: PMID:30462573
      supporting_text: signal transduction pathways including Ras
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: involved_in
  review:
    summary: RasC influences ERK2/MAPK phosphorylation in a context-dependent manner (reduced
      in response to folate), although for cAMP relay ERK2 activation is RasC-independent.
    action: KEEP_AS_NON_CORE
    reason: The MAPK role is context-dependent and not RasC's core output; during cAMP
      relay, cAMP-induced ERK2 phosphorylation is unaffected in rasC-null cells.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: ERK2 phosphorylation and reduced Akt/PKB phosphorylation in response
        to folate
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IDA
  original_reference_id: PMID:31263268
  qualifier: part_of
  review:
    summary: Activated RasC associates with TORC2 by binding TOR and by forming a RacE-RasC-mTORC2
      supercomplex, but RasC is a regulatory GTPase rather than a stoichiometric core subunit
      of TORC2.
    action: KEEP_AS_NON_CORE
    reason: RasC transiently binds and activates TORC2 rather than being a constitutive
      subunit, so the part_of relationship overstates the association. The functional binding
      and activation are better captured by the TORC2-binding and positive-regulation terms.
    supported_by:
    - reference_id: PMID:31263268
      supporting_text: assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
- term:
    id: GO:1904515
    label: positive regulation of TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:31263268
  qualifier: involved_in
  review:
    summary: GTP-bound RasC, together with phosphorylated GDP-RacE, directly stimulates
      mTORC2 kinase activity toward AKT.
    action: ACCEPT
    reason: Positive regulation of TORC2 is a core RasC function, demonstrated by in vitro
      reconstitution of RasC-dependent mTORC2-mediated AKT phosphorylation.
    supported_by:
    - reference_id: PMID:31263268
      supporting_text: assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
- term:
    id: GO:0051593
    label: response to folic acid
  evidence_type: IGI
  original_reference_id: PMID:23132928
  qualifier: involved_in
  review:
    summary: RasC contributes to folic-acid-stimulated responses in vegetative cells, notably
      PKB substrate phosphorylation, via the TORC2 pathway.
    action: KEEP_AS_NON_CORE
    reason: RasC participates in folate-triggered signaling but this is one of several redundant
      vegetative-cell roles, secondary to its core aggregation/ACA and TORC2 functions.
    supported_by:
    - reference_id: PMID:23132928
      supporting_text: Ras C activates the TORC2 complex, which in turn triggers PKBA and
        a second PKB homolog, PKBR1
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IMP
  original_reference_id: PMID:11500376
  qualifier: involved_in
  review:
    summary: RasC is a signaling GTPase required for cAMP relay and chemotactic responses
      during aggregation.
    action: ACCEPT
    reason: Signal transduction is accurate for RasC, supported by the aggregation-defective
      phenotype of rasC-null cells and their role in cAMP signaling.
    supported_by:
    - reference_id: PMID:11500376
      supporting_text: RasC appears to function as a regulatory molecule for both the cAMP
        relay and the chemotactic response to cAMP.
- term:
    id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15143344
  qualifier: involved_in
  review:
    summary: RasC is activated downstream of the cAMP GPCR and is required for chemoattractant-induced
      activation of adenylyl cyclase (the cAMP relay).
    action: ACCEPT
    reason: This is a core function of RasC - transducing cAMP-receptor signals to adenylyl
      cyclase during aggregation.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: it was shown that RasC was activated in aggregation-competent cells
        in response to cAMP
    - reference_id: PMID:17380187
      supporting_text: RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase
        activation
- term:
    id: GO:1903665
    label: negative regulation of asexual reproduction
  evidence_type: IMP
  original_reference_id: PMID:34154396
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC is required for extracellular-polyphosphate-mediated inhibition of cell
      proliferation under low-nutrient conditions.
    action: KEEP_AS_NON_CORE
    reason: RasC participates in the polyphosphate proliferation-inhibition pathway, but
      this is a specialized, redundant signaling role distinct from its core aggregation/TORC2
      functions.
    supported_by:
    - reference_id: PMID:34154396
      supporting_text: the loss of GrlD or RasC blocked the sensitivity of cells to polyphosphate
- term:
    id: GO:0051291
    label: protein heterooligomerization
  evidence_type: IDA
  original_reference_id: PMID:33238110
  qualifier: involved_in
  review:
    summary: Chemoattractant stimulation induces GTP-bound RasC to hetero-oligomerize with
      phosphorylated GDP-bound RacE, an interaction required for mTORC2-AKT activation.
    action: KEEP_AS_NON_CORE
    reason: The RasC-RacE hetero-oligomerization is a genuine, directly demonstrated interaction,
      but it is a mechanistic step in TORC2 activation rather than a stand-alone core function.
    supported_by:
    - reference_id: PMID:33238110
      supporting_text: these two GTPases directly interact in cells
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IDA
  original_reference_id: PMID:17380187
  qualifier: enables
  review:
    summary: RasC is a small GTPase whose GDP-to-GTP exchange is catalyzed specifically
      by RasGEFA, confirming its function as a nucleotide-switch G protein.
    action: ACCEPT
    reason: Direct in vitro nucleotide-exchange and activation assays establish RasC as
      a functional Ras-family G protein.
    supported_by:
    - reference_id: PMID:17380187
      supporting_text: RasGEFA catalysed the removal of GDP from RasC but not from other
        Ras subfamily proteins, confirming that RasGEFA is specific for RasC
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IMP
  original_reference_id: PMID:23132928
  qualifier: enables
  review:
    summary: RasC functions as an activatable G protein upstream of the TORC2-PKB pathway
      in chemotactic responses.
    action: ACCEPT
    reason: Consistent with the direct IDA evidence that RasC is a Ras-family G protein;
      this genetic annotation supports the same molecular function.
    supported_by:
    - reference_id: PMID:23132928
      supporting_text: Ras C activates the TORC2 complex, which in turn triggers PKBA and
        a second PKB homolog, PKBR1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31263268
  qualifier: enables
  review:
    summary: Activated RasC physically associates with the mTORC2 machinery and RacE within
      a signaling supercomplex.
    action: KEEP_AS_NON_CORE
    reason: Bare "protein binding" is uninformative; the functional interaction (RasC-RacE-mTORC2
      supercomplex, RasC-TOR binding) is better captured by the TORC2-binding and TORC2-activation
      terms.
    supported_by:
    - reference_id: PMID:31263268
      supporting_text: assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates AKT
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: involved_in
  review:
    summary: RasC-mediated signal transduction affects motility, polarity, endocytosis,
      and chemotactic responses in vegetative and developing cells.
    action: ACCEPT
    reason: Ras protein signal transduction is the core process RasC executes as a signaling
      GTPase.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: loss of signal transduction through the RasC protein was found to
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IMP
  original_reference_id: PMID:20660630
  qualifier: involved_in
  review:
    summary: RasC signal transduction controls the TORC2-PKB pathway governing chemotaxis.
    action: ACCEPT
    reason: Directly supported - RasC is the upstream Ras controlling TORC2-PKB signaling
      during chemotaxis.
    supported_by:
    - reference_id: PMID:20660630
      supporting_text: RasC is required for TORC2-mediated activation of PKB
- term:
    id: GO:0106070
    label: regulation of adenylate cyclase-activating G protein-coupled receptor signaling
      pathway
  evidence_type: IMP
  original_reference_id: PMID:11500376
  qualifier: involved_in
  review:
    summary: RasC regulates cAMP-receptor-mediated activation of adenylyl cyclase; rasC-null
      cells fail to produce cAMP in response to receptor stimulation.
    action: ACCEPT
    reason: Regulation of the adenylyl-cyclase-activating GPCR pathway is a core RasC function
      underlying the cAMP relay during aggregation.
    supported_by:
    - reference_id: PMID:11500376
      supporting_text: 'RasC appears to be a central regulatory molecule acting downstream
        of serpentine receptor stimulation by cAMP that is required for two distinct effector
        pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl
        cyclase.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24986648
  qualifier: enables
  review:
    summary: Activated RasC binds the LATS-family kinase NdrC via its Ras-binding domain
      (lower affinity than RasG/RasB).
    action: KEEP_AS_NON_CORE
    reason: Documents a specific RasC-NdrC interaction, but as bare "protein binding" it
      is uninformative; the cytokinesis phenotype is driven by RasG/RasB, not RasC.
    supported_by:
    - reference_id: PMID:24986648
      supporting_text: NdrC was the only protein that bound RasC in the yeast two-hybrid
        screen
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26424797
  qualifier: enables
  review:
    summary: The PP2A regulatory subunit B56 preferentially associates with the GDP-bound
      form of RasC (and RasD), part of a phosphatase-mediated negative regulation of PKB.
    action: KEEP_AS_NON_CORE
    reason: A real interaction, but "protein binding" is uninformative; the functional
      significance is regulatory (PP2A/B56 modulating Ras and PKB activity).
    supported_by:
    - reference_id: PMID:26424797
      supporting_text: GDP forms of RasC and RasD, but not with RasG in vitro
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27172998
  qualifier: enables
  review:
    summary: Active RasC binds directly to the catalytic (FRB/kinase) domain of TOR, the
      proposed mechanism by which RasC activates TORC2.
    action: KEEP_AS_NON_CORE
    reason: This specific RasC-TOR interaction is functionally important but is better represented
      by TORC2-binding/activation terms than by generic "protein binding".
    supported_by:
    - reference_id: PMID:27172998
      supporting_text: we found that TOR kinase itself specifically co-purifies with RasCGppNHp
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29109256
  qualifier: enables
  review:
    summary: The negative regulator C2GAP1 (a RasGAP) binds RasC in vitro, consistent with
      its role in terminating Ras signaling for adaptation.
    action: KEEP_AS_NON_CORE
    reason: Documents a RasC-C2GAP1 interaction; bare "protein binding" is uninformative
      relative to the GAP-mediated regulation it represents.
    supported_by:
    - reference_id: PMID:29109256
      supporting_text: the in vitro binding assay indicates that C2GAP1 binds both GTP-
        and GDP-bound Ras protein
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:15143344
  qualifier: enables
  review:
    summary: RasC binds and is activated by GTP; an RBD-based assay directly detected GTP-loaded
      (active) RasC upon cAMP stimulation.
    action: ACCEPT
    reason: Direct experimental demonstration of RasC nucleotide binding/activation supports
      the GTP-binding molecular function.
    supported_by:
    - reference_id: PMID:15143344
      supporting_text: it was shown that RasC was activated in aggregation-competent cells
        in response to cAMP
- term:
    id: GO:0005811
    label: lipid droplet
  evidence_type: HDA
  original_reference_id: PMID:24036346
  qualifier: part_of
  review:
    summary: RasC was recovered in a high-throughput lipid-droplet proteome, but its established
      localization is the plasma membrane/leading edge; lipid-droplet association likely
      reflects the shared lipid-anchor/membrane biochemistry rather than a functional role.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput organelle proteomes frequently capture membrane-anchored proteins
      as background. There is no functional evidence for RasC acting at lipid droplets,
      whose biology is unrelated to Ras chemotactic signaling.
    supported_by:
    - reference_id: PMID:24036346
      supporting_text: Among the novel protein components are LdpA, a protein specific to
        Dictyostelium
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: enables
  review:
    summary: RasC (with RasG) is required for cAMP-receptor-mediated activation of adenylyl
      cyclase during aggregation, with RasC being the more important of the two for ACA
      activation.
    action: ACCEPT
    reason: Activation of adenylyl cyclase is a core RasC function underlying the cAMP relay;
      RasC/RasG are the presumptive GTPases required for cyclase activation.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: proteins that are necessary for optimum cAMP signaling
    - reference_id: PMID:17380187
      supporting_text: RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase
        activation
- term:
    id: GO:0030250
    label: guanylate cyclase activator activity
  evidence_type: IMP
  original_reference_id: PMID:18180289
  qualifier: enables
  review:
    summary: In vitro guanylyl cyclase activation is abolished in rasC-/rasG- cells, identifying
      RasC/RasG as required for cyclase activation; however, RasG predominates for the cGMP
      branch.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to guanylyl cyclase activation but this is largely a RasG-dominated
      function and secondary to RasC's principal ACA/TORC2 roles.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: guanylyl cyclase activation is also abolished in the
- term:
    id: GO:0030250
    label: guanylate cyclase activator activity
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: enables
  review:
    summary: Genetic-interaction evidence that RasC (with RasG) is required for guanylyl
      cyclase activation; duplicate of the IMP annotation.
    action: KEEP_AS_NON_CORE
    reason: Same rationale as the paired IMP annotation - a redundant, RasG-dominated function.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: guanylyl cyclase activation is also abolished in the
- term:
    id: GO:0031252
    label: cell leading edge
  evidence_type: IC
  original_reference_id: PMID:20493808
  qualifier: is_active_in
  review:
    summary: Active RasC signaling (RasC-TORC2) is localized to the leading edge of chemotaxing
      cells, where the Sca1/RasGEF complex promotes local RasC activation.
    action: ACCEPT
    reason: Leading-edge localization of active RasC signaling is a core spatial feature
      underlying directed migration.
    supported_by:
    - reference_id: PMID:20493808
      supporting_text: active Ras is enriched at the leading edge of chemotaxing cells
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IDA
  original_reference_id: PMID:19589376
  qualifier: part_of
  review:
    summary: RasC was detected among proteins of secreted Dictyostelium nanovesicles (a
      proteome dominated by actin and endosomal markers); this does not reflect a functional
      vesicle role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Recovery in a released-nanovesicle proteome is expected for a membrane-anchored
      protein and does not indicate a dedicated vesicle function; RasC acts at the plasma
      membrane/leading edge.
    supported_by:
    - reference_id: PMID:19589376
      supporting_text: A proteomic analysis reveals a predominance of actin and actin-related
        proteins.
- term:
    id: GO:0051602
    label: response to electrical stimulus
  evidence_type: IMP
  original_reference_id: PMID:26012633
  qualifier: acts_upstream_of_or_within
  review:
    summary: rasC was identified among genes affecting electrotaxis in a large-scale screen;
      the specific mechanistic role is not defined.
    action: KEEP_AS_NON_CORE
    reason: A screen-level hit indicating involvement in electrotaxis, but peripheral to
      RasC's characterized core functions and without detailed mechanistic support in the
      accessible text.
- term:
    id: GO:1904841
    label: TORC2 complex binding
  evidence_type: IDA
  original_reference_id: PMID:20660630
  qualifier: enables
  review:
    summary: TORC2 binds specifically to the activated (GTP-bound) form of RasC, as shown
      by co-immunoprecipitation with the TORC2 component Rip3.
    action: ACCEPT
    reason: Direct binding of activated RasC to TORC2 is a core molecular function central
      to RasC-mediated PKB activation and chemotaxis.
    supported_by:
    - reference_id: PMID:20660630
      supporting_text: This result shows that RasC and TORC2 interact in a regulated fashion
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27009206
  qualifier: enables
  review:
    summary: The RacE-binding, RhoGAP/RasGEF-domain protein GflB binds RasC (and RasG),
      linking directional sensing to Ras/Rho activity at the leading edge.
    action: KEEP_AS_NON_CORE
    reason: A real RasC-GflB interaction, but bare "protein binding" is uninformative and
      GflB's characterized activity is chiefly on RasG/Rac.
    supported_by:
    - reference_id: PMID:27009206
      supporting_text: GflB also binds to Ras GTPases
- term:
    id: GO:0110094
    label: polyphosphate-mediated signaling
  evidence_type: IMP
  original_reference_id: PMID:28584190
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC (with Akt/PKB) mediates extracellular-polyphosphate signaling that primes
      cells for development and inhibits the proteasome.
    action: KEEP_AS_NON_CORE
    reason: RasC participates in polyphosphate signaling, but this is a specialized branch
      secondary to its core aggregation and TORC2 roles.
    supported_by:
    - reference_id: PMID:28584190
      supporting_text: mediated by Akt proteins and RasC in Dictyostelium
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IMP
  original_reference_id: PMID:20660630
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC positively regulates PKB activation, primarily through TORC2-mediated
      phosphorylation of PKBR1/PKBA (largely PIP3-independent).
    action: ACCEPT
    reason: Positive regulation of PKB signaling is a core RasC output; RasC deletion reduces,
      and activated RasC prolongs, PKB phosphorylation.
    supported_by:
    - reference_id: PMID:20660630
      supporting_text: RasC is required for TORC2-mediated activation of PKB
- term:
    id: GO:0061122
    label: positive regulation of positive chemotaxis to cAMP
  evidence_type: IMP
  original_reference_id: PMID:20660630
  qualifier: acts_upstream_of_or_within
  review:
    summary: Proper temporal control of RasC-TORC2-PKBR1 signaling is required for efficient
      directed migration toward cAMP; dysregulated RasC impairs chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to cAMP chemotaxis via TORC2, but chemotactic gradient sensing
      is dominated by RasG/PI3K; RasC's contribution here is modulatory.
    supported_by:
    - reference_id: PMID:20660630
      supporting_text: RasC is required for TORC2-mediated activation of PKB
- term:
    id: GO:1904515
    label: positive regulation of TORC2 signaling
  evidence_type: IMP
  original_reference_id: PMID:20660630
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC is required for and, when constitutively active, prolongs TORC2-mediated
      PKB signaling.
    action: ACCEPT
    reason: Positive regulation of TORC2 is a core RasC function established by genetic and
      in vitro reconstitution evidence.
    supported_by:
    - reference_id: PMID:20660630
      supporting_text: RasC is required for TORC2-mediated activation of PKB
- term:
    id: GO:0048870
    label: cell motility
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: Vegetative rasC-null cells show reduced random motility and are less polarized,
      indicating a role for RasC in cell motility.
    action: KEEP_AS_NON_CORE
    reason: RasC affects motility, but the dominant motility/polarity regulator among the
      Ras proteins is RasG; RasC's contribution is partial.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: reduced random motility, were less polarized and had altered F-actin
- term:
    id: GO:0019954
    label: asexual reproduction
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC is required (with RasG) for aggregation, the developmental process that
      leads to asexual sporulation.
    action: KEEP_AS_NON_CORE
    reason: The link to asexual reproduction is via RasC's role in aggregation/cAMP signaling
      rather than a distinct reproductive function.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: proteins that are necessary for optimum cAMP signaling
- term:
    id: GO:0043326
    label: chemotaxis to folate
  evidence_type: IGI
  original_reference_id: PMID:20833893
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC can partially substitute for RasG in folate chemotaxis; rasC-/rasG- cells
      are completely incapable of folate chemotaxis.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to folate chemotaxis but redundantly with (and secondarily
      to) RasG.
    supported_by:
    - reference_id: PMID:20833893
      supporting_text: to folate, RasC is capable of partially substituting for RasG
- term:
    id: GO:0043327
    label: chemotaxis to cAMP
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC (with RasG) is required for optimal cAMP signaling that underlies chemotaxis
      during aggregation.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to cAMP chemotaxis but the chemotactic branch is predominantly
      RasG-dependent; RasC's core role is ACA activation.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: proteins that are necessary for optimum cAMP signaling
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IGI
  original_reference_id: PMID:18180289
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC (with RasG) acts upstream of PKB activation during cAMP signaling.
    action: ACCEPT
    reason: Positive regulation of PKB activation is a core RasC output during cAMP signaling,
      consistent with the reduced PKB phosphorylation of rasC-null cells.
    supported_by:
    - reference_id: PMID:18180289
      supporting_text: proteins that are necessary for optimum cAMP signaling
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:16885420
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC is required for aggregation, controlling both cAMP relay (ACA activation)
      and, partly, chemotaxis during early development.
    action: ACCEPT
    reason: Aggregation is a core developmental process requiring RasC; rasC-null cells
      fail to aggregate.
    supported_by:
    - reference_id: PMID:16885420
      supporting_text: the Ras protein RasC is involved in both processes
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IGI
  original_reference_id: PMID:16885420
  qualifier: acts_upstream_of_or_within
  review:
    summary: Genetic-interaction evidence (RasC vs RasG) confirming RasC's role in aggregation,
      predominantly via ACA activation.
    action: ACCEPT
    reason: Duplicate line of evidence for RasC's core aggregation function.
    supported_by:
    - reference_id: PMID:16885420
      supporting_text: signal transduction through RasC is more important in ACA activation
- term:
    id: GO:0043327
    label: chemotaxis to cAMP
  evidence_type: IMP
  original_reference_id: PMID:16885420
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC contributes to cAMP chemotaxis, though signaling through RasG is more
      important for chemotaxis while RasC is more important for the cAMP relay.
    action: KEEP_AS_NON_CORE
    reason: RasC's chemotactic contribution is secondary to RasG; its core role is ACA activation.
    supported_by:
    - reference_id: PMID:16885420
      supporting_text: signal transduction through RasC is more important in ACA activation
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IMP
  original_reference_id: PMID:16885420
  qualifier: acts_upstream_of_or_within
  review:
    summary: RasC contributes to cAMP-stimulated PKB phosphorylation during aggregation.
    action: ACCEPT
    reason: Positive regulation of PKB is a core RasC output; this is consistent supporting
      evidence from the isogenic RasC/RasG null comparison.
    supported_by:
    - reference_id: PMID:16885420
      supporting_text: signal transduction through RasC is more important in ACA activation
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IGI
  original_reference_id: PMID:16885420
  qualifier: acts_upstream_of_or_within
  review:
    summary: Genetic-interaction evidence that RasC contributes to PKB activation during
      aggregation.
    action: ACCEPT
    reason: Positive regulation of PKB is a core RasC output; consistent supporting evidence.
    supported_by:
    - reference_id: PMID:16885420
      supporting_text: signal transduction through RasC is more important in ACA activation
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IMP
  original_reference_id: PMID:11500376
  qualifier: acts_upstream_of_or_within
  review:
    summary: cAMP-induced Akt/PKB phosphorylation through a PI3K-dependent pathway is dramatically
      reduced in rasC-null cells.
    action: ACCEPT
    reason: RasC positively regulating PKB activation is a core function, directly demonstrated
      by reduced Akt/PKB phosphorylation in rasC-null cells.
    supported_by:
    - reference_id: PMID:11500376
      supporting_text: 'RasC appears to be a central regulatory molecule acting downstream
        of serpentine receptor stimulation by cAMP that is required for two distinct effector
        pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl
        cyclase.'
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:16023096
  qualifier: acts_upstream_of_or_within
  review:
    summary: Disruption of rasC produces a strain that fails to aggregate, with defects
      in both cAMP signal relay and chemotaxis.
    action: ACCEPT
    reason: Core developmental phenotype - RasC is required for aggregation.
    supported_by:
    - reference_id: PMID:16023096
      supporting_text: fails to aggregate with defects in both cAMP
- term:
    id: GO:0043327
    label: chemotaxis to cAMP
  evidence_type: IMP
  original_reference_id: PMID:16023096
  qualifier: acts_upstream_of_or_within
  review:
    summary: rasC-null cells are defective in cAMP chemotaxis (as part of the aggregation-negative
      phenotype).
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to cAMP chemotaxis but redundantly with/secondarily to RasG;
      its core role is ACA activation.
    supported_by:
    - reference_id: PMID:16023096
      supporting_text: fails to aggregate with defects in both cAMP
- term:
    id: GO:0001558
    label: regulation of cell growth
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: rasC-null cells contain more protein and are larger than wild type, indicating
      a role for RasC in regulating cell size/growth.
    action: KEEP_AS_NON_CORE
    reason: RasC influences vegetative cell size, but this is one of several secondary vegetative-cell
      phenotypes rather than a core function.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: Cells lacking RasC also contained more protein and were larger in
- term:
    id: GO:0051491
    label: positive regulation of filopodium assembly
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: Loss of RasC alters F-actin distribution and cell polarity, consistent with
      a role in actin-based protrusion regulation; the abstract does not specifically detail
      filopodium assembly.
    action: KEEP_AS_NON_CORE
    reason: RasC affects the actin cytoskeleton and protrusions, but a specific filopodium-assembly
      function is a minor aspect and only indirectly supported by the accessible abstract.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: reduced random motility, were less polarized and had altered F-actin
- term:
    id: GO:0007163
    label: establishment or maintenance of cell polarity
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: rasC-null cells are less polarized, indicating a role for RasC in cell polarity.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to polarity/actin organization but is not the dominant polarity
      regulator among Dictyostelium Ras proteins.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: reduced random motility, were less polarized and had altered F-actin
- term:
    id: GO:0030036
    label: actin cytoskeleton organization
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: Loss of RasC alters F-actin distribution, linking RasC signaling to actin cytoskeleton
      organization.
    action: KEEP_AS_NON_CORE
    reason: RasC influences the actin cytoskeleton (via TORC2-PKB and downstream effectors),
      a secondary consequence of its signaling rather than a direct core function.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: reduced random motility, were less polarized and had altered F-actin
- term:
    id: GO:0043326
    label: chemotaxis to folate
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: rasC-null cells chemotax poorly to folate and show reduced folate-induced F-actin
      and PKB responses.
    action: KEEP_AS_NON_CORE
    reason: RasC contributes to folate chemotaxis but redundantly with RasG; this is a vegetative-cell
      role secondary to RasC's core aggregation/ACA function.
    supported_by:
    - reference_id: PMID:15878331
      supporting_text: chemotaxed poorly to folate
- term:
    id: GO:0120320
    label: lateral pseudopodium retraction
  evidence_type: IMP
  original_reference_id: PMID:15878331
  qualifier: acts_upstream_of_or_within
  review:
    summary: This specific term (lateral pseudopodium retraction) is not addressed in the
      accessible (abstract-only) record for this reference, which reports reduced polarity
      and altered F-actin but not pseudopod retraction dynamics per se.
    action: UNDECIDED
    reason: The cached publication is abstract-only and does not provide verifiable support
      for a specific lateral-pseudopodium-retraction function; the curator likely relied
      on full-text data not accessible here.
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:11500376
  qualifier: acts_upstream_of_or_within
  review:
    summary: Disruption of rasC generates cells incapable of aggregation, a defect restricted
      to the aggregation stage and rescuable by exogenous cAMP pulses.
    action: ACCEPT
    reason: RasC's requirement for aggregation is a core developmental function directly
      demonstrated by the rasC-null phenotype.
    supported_by:
    - reference_id: PMID:11500376
      supporting_text: generated cells incapable of aggregation
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: PMID:11500376
  title: RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during
    aggregation.
  findings:
  - statement: RasC is required for aggregation and acts downstream of the cAMP receptor
      to activate both PI3K/Akt-PKB and adenylyl cyclase.
    supporting_text: 'RasC appears to be a central regulatory molecule acting downstream
      of serpentine receptor stimulation by cAMP that is required for two distinct effector
      pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl
      cyclase.'
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational rasC-null study establishing RasC's role in cAMP relay
      (ACA activation) and PKB activation during aggregation; PMID/title verified against
      the cached full text.
- id: PMID:15143344
  title: Chemoattractant-induced Ras activation during Dictyostelium aggregation.
  findings:
  - statement: RasC is rapidly and transiently activated (GTP-loaded) in aggregation-competent
      cells upon cAMP stimulation.
    supporting_text: it was shown that RasC was activated in aggregation-competent cells
      in response to cAMP
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Directly demonstrates cAMP-induced RasC activation via an RBD-binding
      assay; supports GTP-binding and G-protein activity.
- id: PMID:15878331
  title: Loss of the Dictyostelium RasC protein alters vegetative cell size, motility
    and endocytosis.
  findings:
  - statement: rasC-null vegetative cells have reduced random motility, reduced polarity,
      altered F-actin, larger size, and normal cytokinesis.
    supporting_text: reduced random motility, were less polarized and had altered F-actin
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract-only in cache; documents vegetative-cell phenotypes and shows
      cytokinesis/division rate are unaffected in rasC-null cells.
- id: PMID:16023096
  title: The effect of the disruption of a gene encoding a PI4 kinase on the developmental
    defect exhibited by Dictyostelium rasC(-) cells.
  findings:
  - statement: rasC disruption produces a strain that fails to aggregate with defects
      in both cAMP signal relay and chemotaxis.
    supporting_text: fails to aggregate with defects in both cAMP
- id: PMID:16885420
  title: Delineation of the roles played by RasG and RasC in cAMP-dependent signal
    transduction during the early development of Dictyostelium discoideum.
  findings:
  - statement: RasG is more important for chemotaxis while RasC is more important for
      adenylyl cyclase (cAMP relay) activation, with partial functional overlap.
    supporting_text: signal transduction through RasC is more important in ACA activation
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the division of labor between RasC (ACA/relay) and RasG (chemotaxis)
      using isogenic single and double null strains.
- id: PMID:17380187
  title: 'Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras
    pathways using specific RasGEFs.'
  findings:
  - statement: RasGEFA (Aimless) specifically activates RasC, and RasC is responsible
      for adenylyl cyclase activation whereas RasG regulates chemotaxis.
    supporting_text: RasGEFA catalysed the removal of GDP from RasC but not from other
      Ras subfamily proteins, confirming that RasGEFA is specific for RasC
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes RasGEFA-RasC specificity in vitro and in vivo and the
      RasC-to-ACA / RasG-to-chemotaxis division.
- id: PMID:18180289
  title: Rap1 activation in response to cAMP occurs downstream of ras activation during
    Dictyostelium aggregation.
  findings:
  - statement: RasC/RasG are the presumptive GTPases required for cAMP-induced guanylyl
      cyclase activation, and Rap1 acts downstream of the Ras proteins.
    supporting_text: guanylyl cyclase activation is also abolished in the
- id: PMID:19589376
  title: 'Nanovesicles released by Dictyostelium cells: a potential carrier for drug
    delivery.'
  findings:
  - statement: Secreted Dictyostelium nanovesicle proteome is dominated by actin and
      actin-related/endosomal proteins.
    supporting_text: A proteomic analysis reveals a predominance of actin and actin-related
      proteins.
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput vesicle proteome; RasC recovery here does not indicate
      a functional vesicle role.
- id: PMID:20493808
  title: A Ras signaling complex controls the RasC-TORC2 pathway and directed cell
    migration.
  findings:
  - statement: A Sca1/RasGEF/PP2A complex is enriched at the leading edge and controls
      RasC activation and the downstream TORC2-PKB pathway; active Ras is enriched at
      the leading edge.
    supporting_text: active Ras is enriched at the leading edge of chemotaxing cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes leading-edge, spatiotemporally controlled RasC-TORC2 signaling
      via the Sca1 scaffold complex.
- id: PMID:20660630
  title: Ras-mediated activation of the TORC2-PKB pathway is critical for chemotaxis.
  findings:
  - statement: RasC is required for and directly binds/activates TORC2, setting the temporal
      dynamics of PKBR1/PKBA phosphorylation independently of PIP3.
    supporting_text: RasC is required for TORC2-mediated activation of PKB
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Genetic plus in vitro reconstitution evidence that activated RasC is
      an upstream regulator of TORC2; TORC2 binds the activated form of RasC.
- id: PMID:20833893
  title: Ras proteins have multiple functions in vegetative cells of Dictyostelium.
  findings:
  - statement: RasC can partially substitute for RasG in folate chemotaxis, but not for
      RasG's growth/cytokinesis or random-motility functions.
    supporting_text: to folate, RasC is capable of partially substituting for RasG
- id: PMID:23132928
  title: Delineating the core regulatory elements crucial for directed cell migration
    by examining folic-acid-mediated responses.
  findings:
  - statement: RasC activates the TORC2 complex, which triggers PKBA and PKBR1, in a
      pathway parallel to RasG/PI3K during folate and cAMP responses.
    supporting_text: Ras C activates the TORC2 complex, which in turn triggers PKBA and
      a second PKB homolog, PKBR1
- id: PMID:24036346
  title: Dictyostelium lipid droplets host novel proteins.
  findings:
  - statement: High-throughput identification of the Dictyostelium lipid-droplet proteome.
    supporting_text: Among the novel protein components are LdpA, a protein specific
      to Dictyostelium
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HDA lipid-droplet proteome; RasC recovery likely reflects membrane/lipid-anchor
      background rather than a functional lipid-droplet role.
- id: PMID:24986648
  title: Regulation of a LATS-homolog by Ras GTPases is important for the control of
    cell division.
  findings:
  - statement: NdrC (LATS2 homolog) binds RasG/RasB (and less strongly RasC/Rap1); cell
      division is controlled by RasG/RasB, not by RasC.
    supporting_text: NdrC was the only protein that bound RasC in the yeast two-hybrid
      screen
- id: PMID:26012633
  title: A large-scale screen reveals genes that mediate electrotaxis in Dictyostelium
    discoideum.
  findings: []
- id: PMID:26424797
  title: PP2A/B56 and GSK3/Ras suppress PKB activity during Dictyostelium chemotaxis.
  findings:
  - statement: The PP2A regulatory subunit B56 preferentially binds GDP-bound RasC and
      RasD (not RasG) and contributes to suppression of PKB activity.
    supporting_text: GDP forms of RasC and RasD, but not with RasG in vitro
- id: PMID:27009206
  title: The novel RacE-binding protein GflB sharpens Ras activity at the leading edge
    of migrating cells.
  findings:
  - statement: GflB (a RhoGAP/RasGEF-domain protein) binds RasC and RasG and balances
      Ras/Rho activation to orient signaling toward higher chemoattractant concentrations.
    supporting_text: GflB also binds to Ras GTPases
- id: PMID:27172998
  title: The small GTPases Ras and Rap1 bind to and control TORC2 activity.
  findings:
  - statement: Active RasC binds the catalytic domain of TOR, while Rap1 binds RIP3/SIN1;
      both control TORC2 activity, with RasC playing the major role.
    supporting_text: we found that TOR kinase itself specifically co-purifies with RasCGppNHp
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Shows RasC binds TOR directly, providing a mechanism for RasC-mediated
      TORC2 activation.
- id: PMID:28584190
  title: Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium
    discoideum cells for development.
  findings:
  - statement: Polyphosphate signals through RasC and Akt to inhibit the proteasome and
      induce CsA expression, priming cells for development.
    supporting_text: mediated by Akt proteins and RasC in Dictyostelium
- id: PMID:29109256
  title: GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally
    inhibits Ras signaling for adaptation and long-range chemotaxis.
  findings:
  - statement: C2GAP1 is a RasGAP that binds Ras and locally inhibits Ras signaling for
      adaptation during chemotaxis.
    supporting_text: the in vitro binding assay indicates that C2GAP1 binds both GTP-
      and GDP-bound Ras protein
- id: PMID:30462573
  title: An endogenous chemorepellent directs cell movement by inhibiting pseudopods
    at one side of cells.
  findings:
  - statement: AprA chemorepulsion uses a subset of chemoattraction pathway components
      including Ras (RasC/RasG redundantly).
    supporting_text: signal transduction pathways including Ras
- id: PMID:31263268
  title: Phosphorylated Rho-GDP directly activates mTORC2 kinase towards AKT through
    dimerization with Ras-GTP to regulate cell migration.
  findings:
  - statement: Chemoattractant-induced phosphorylation of GDP-RacE assembles a RacE-RasC-mTORC2
      supercomplex that phosphorylates AKT.
    supporting_text: assembles the RacE-RasC-mTORC2 supercomplex that phosphorylates
      AKT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the GTP-RasC / phospho-GDP-RacE / mTORC2 mechanism of AKT activation.
- id: PMID:33238110
  title: Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT
    Signaling.
  findings:
  - statement: GTP-RasC and phosphorylated GDP-RacE directly interact and hetero-oligomerize
      to activate mTORC2 toward AKT (but not ERK).
    supporting_text: these two GTPases directly interact in cells
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the RasC-RacE hetero-oligomer as the activating input to
      mTORC2-AKT signaling.
- id: PMID:34154396
  title: An Autocrine Negative Feedback Loop Inhibits Dictyostelium discoideum Proliferation
    through Pathways Including IP3/Ca(2).
  findings:
  - statement: Under low-nutrient conditions, loss of RasC blocks polyphosphate-induced
      proliferation inhibition.
    supporting_text: the loss of GrlD or RasC blocked the sensitivity of cells to polyphosphate
core_functions:
- description: RasC is a plasma-membrane-anchored Ras-family small GTPase that acts
    as a nucleotide-dependent molecular switch, cycling between an inactive GDP-bound
    and an active GTP-bound state (with intrinsic GTPase activity), to transduce cAMP-receptor
    (GPCR) signals during Dictyostelium chemotaxis and development.
  molecular_function:
    id: GO:0003925
    label: G protein activity
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0031252
    label: cell leading edge
  directly_involved_in:
  - id: GO:0007264
    label: small GTPase-mediated signal transduction
  supported_by:
  - reference_id: PMID:17380187
    supporting_text: Ras proteins are small, monomeric GTPases that act as crucial regulators
      of a number of cellular signalling pathways
  - reference_id: PMID:15143344
    supporting_text: it was shown that RasC was activated in aggregation-competent cells
      in response to cAMP
- description: Activated RasC drives the chemoattractant-induced activation of adenylyl
    cyclase (ACA) and the cAMP relay during aggregation, functioning as the principal
    Ras protein for the cAMP signal-relay branch downstream of the cAMP GPCR and RasGEFA
    (Aimless).
  molecular_function:
    id: GO:0010856
    label: adenylate cyclase activator activity
  directly_involved_in:
  - id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  supported_by:
  - reference_id: PMID:17380187
    supporting_text: RasG regulates chemotaxis and RasC is responsible for adenylyl cyclase
      activation
  - reference_id: PMID:11500376
    supporting_text: 'RasC appears to be a central regulatory molecule acting downstream
      of serpentine receptor stimulation by cAMP that is required for two distinct effector
      pathways: the activation of Akt/PKB through PI3K and the activation of adenylyl
      cyclase.'
- description: GTP-bound RasC binds the TOR catalytic domain and, together with phosphorylated
    GDP-bound RacE, directly activates TORC2, setting the temporal and spatial dynamics
    of PKBR1/PKBA (Akt) phosphorylation that control the actin cytoskeleton and directed
    cell migration.
  molecular_function:
    id: GO:1904841
    label: TORC2 complex binding
  locations:
  - id: GO:0031252
    label: cell leading edge
  directly_involved_in:
  - id: GO:1904515
    label: positive regulation of TORC2 signaling
  supported_by:
  - reference_id: PMID:20660630
    supporting_text: RasC is required for TORC2-mediated activation of PKB
  - reference_id: PMID:27172998
    supporting_text: we found that TOR kinase itself specifically co-purifies with RasCGppNHp

Gene Description

Existing Annotations Review

Core Functions

Activated RasC drives the chemoattractant-induced activation of adenylyl cyclase (ACA) and the cAMP relay during aggregation, functioning as the principal Ras protein for the cAMP signal-relay branch downstream of the cAMP GPCR and RasGEFA (Aimless).

GTP-bound RasC binds the TOR catalytic domain and, together with phosphorylated GDP-bound RacE, directly activates TORC2, setting the temporal and spatial dynamics of PKBR1/PKBA (Akt) phosphorylation that control the actin cytoskeleton and directed cell migration.

References

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