RasG (DdrasG) is the most abundant Ras subfamily small GTPase in growing Dictyostelium discoideum and the closest amoebozoan relative of mammalian K-Ras. Like other Ras proteins it is a C-terminally prenylated, plasma-membrane-anchored molecular switch that cycles between an inactive GDP-bound and an active GTP-bound state, controlled by guanine-nucleotide exchange factors (RasGEFs such as GefR/Aimless) and GTPase-activating proteins (RasGAPs such as NF1, IqgC, C2GAP1 and the Leep2 complex). Upon chemoattractant (folate or cAMP) stimulation, RasG is rapidly and transiently activated at the leading edge and cell cortex, where GTP-loaded RasG binds and activates class I phosphatidylinositol 3-kinase to generate PIP3, driving F-actin-based pseudopod formation, directional sensing and cell motility. RasG is a principal regulator of chemotaxis, random motility and cell polarity, cytokinesis, macropinocytosis and phagocytosis, engaging effectors including PI3K, the Diaphanous-related formin ForG, the NDR/LATS kinase NdrC, TORC2, the Ras-interacting protein RIP3/RipA and the MRL-family adaptor DydA. Its functions overlap partly with the paralogs RasC (more specialized for cAMP relay and adenylyl cyclase activation) and RasD (which can substitute for RasG in cytokinesis).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0003924
GTPase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference that RasG has intrinsic GTPase activity. This is the defining catalytic property of a Ras-family small GTPase and is directly supported for RasG (EC 3.6.5.2, GTP hydrolysis inactivates the switch).
Reason: RasG is a bona fide Ras GTPase that hydrolyzes GTP to GDP; the intrinsic GTPase activity is a core molecular function and is well conserved across the family.
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: Phylogenetic inference of plasma membrane localization, corroborated by direct imaging of GFP-RasG uniformly distributed along the plasma membrane and activated at the cortex/leading edge.
Reason: RasG is prenylated and anchored to the cytoplasmic face of the plasma membrane, where it is activated and signals; this is a core localization.
Supporting Evidence:
PMID:15534002
GFP-RasG displayed uniform localization along the plasma membrane and cytosol
|
|
GO:0007264
small GTPase-mediated signal transduction
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference that RasG participates in small GTPase-mediated signal transduction. This is the core signaling role of RasG as a molecular switch relaying chemoattractant signals to PI3K and other effectors.
Reason: RasG functions as a GTP/GDP molecular switch in signal transduction, a core function directly demonstrated experimentally.
Supporting Evidence:
PMID:15534002
Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity
|
|
GO:0000281
mitotic cytokinesis
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference of a cytokinesis role, strongly corroborated by RasG null cells becoming multinucleate in suspension.
Reason: RasG is required for normal cytokinesis; rasG-null cells fail to complete cytokinesis and become multinucleate in shaken suspension. This is a core function.
Supporting Evidence:
PMID:9245789
rasG- cells are unable to perform normal cytokinesis, becoming multinucleate when grown in suspension culture
|
|
GO:0044351
macropinocytosis
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetic inference of a macropinocytosis role, strongly supported by genetic evidence that RasG is a major regulator of macropinocytosis.
Reason: RasG is one of the key Ras proteins driving macropinocytosis in Dictyostelium; a core function.
Supporting Evidence:
PMID:38263885
RasG is a major regulator of macropinocytosis in Dictyostelium discoideum
|
|
GO:0003924
GTPase activity
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO inference of GTPase activity from the Ras small-GTPase domain. Correct and core.
Reason: The Ras/P-loop GTPase domain confers intrinsic GTP hydrolysis, a core molecular function of RasG.
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:0003925
G protein activity
|
IEA
GO_REF:0000003 |
ACCEPT |
Summary: EC-based inference of GTP-hydrolyzing G protein activity. RasG is a monomeric guanine-nucleotide-binding signal transducer, so this MF is correct and core (GO:0003925 encompasses small monomeric GTPases).
Reason: RasG acts as a nucleotide-dependent molecular switch/signal transducer; G protein activity is a core molecular function directly demonstrated by GTP-loading (RBD pulldown) assays.
Supporting Evidence:
PMID:15143344
the Ras-binding domain (RBD) of mammalian Raf1 was capable of binding to the activated form of RasG
|
|
GO:0005525
GTP binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro2GO inference of GTP binding from the Ras domain. Core and directly supported (GTP-bound RasG is captured by Raf1-RBD pulldowns).
Reason: RasG binds GTP/GDP through its conserved P-loop; a core molecular function.
Supporting Evidence:
PMID:15143344
the Ras-binding domain (RBD) of mammalian Raf1 was capable of binding to the activated form of RasG
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: UniProt subcellular-location mapping to plasma membrane, consistent with the lipid-anchored, membrane-associated nature of RasG and with direct imaging.
Reason: RasG is a prenylated plasma-membrane-anchored GTPase; correct core localization.
Supporting Evidence:
PMID:15534002
GFP-RasG displayed uniform localization along the plasma membrane and cytosol
|
|
GO:0007165
signal transduction
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: Generic signal transduction inferred from the Ras domain. Correct but far less informative than the more specific small GTPase-mediated signal transduction annotation also present.
Reason: This is a high-level parent term; the specific child term GO:0007264 (small GTPase-mediated signal transduction) better captures RasG function, so this general term is retained but non-core.
Supporting Evidence:
PMID:15534002
Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: Generic membrane localization inferred from the domain. Correct but a high-level parent of the specific plasma membrane annotation.
Reason: Uninformative parent term; the specific term plasma membrane GO:0005886 is the appropriate core localization.
Supporting Evidence:
PMID:15534002
GFP-RasG displayed uniform localization along the plasma membrane and cytosol
|
|
GO:0005515
protein binding
|
IPI
PMID:40934557 The Ras association domain of DydA as a specific reporter of... |
KEEP AS NON CORE |
Summary: Captures the interaction between activated RasG and the RA1 domain of the effector DydA, used as a RasG-specific biosensor. Bare protein binding is uninformative; the biologically relevant point is effector engagement by GTP-RasG.
Reason: Documents a real RasG-effector interaction (RA1:DydA reporter) but the generic protein binding term conveys no specific function; retained as non-core.
Supporting Evidence:
PMID:40934557
RA1 preferentially binds RasG over other Ras isoforms and Rap1
|
|
GO:0019887
protein kinase regulator activity
|
IDA
PMID:9551080 Negative influence of RasG on chemoattractant-induced ERK2 p... |
KEEP AS NON CORE |
Summary: Based on the observation that constitutively activated RasG inhibits chemoattractant-induced ERK2 activating phosphorylation. This indicates RasG influences a MAP kinase, but the effect is negative and likely indirect rather than a direct kinase-regulator activity.
Reason: RasG modulates ERK2 phosphorylation, but the relationship is indirect and the more precise, directly-supported effector MF is PI3K regulation (GO:0035014). Retained as non-core.
Supporting Evidence:
PMID:9551080
Activating phosphorylation is markedly inhibited in strains overexpressing the constitutively activated RasG protein
|
|
GO:0140220
pathogen-containing vacuole
|
HDA
PMID:39458259 Francisella novicida-Containing Vacuole within Dictyostelium... |
KEEP AS NON CORE |
Summary: RasG was detected by proteomics of purified Francisella-containing vacuoles. This is an incidental high-throughput co-purification with an endomembrane compartment rather than a core RasG function; the proteome is dominated by Rab-family GTPases.
Reason: Bulk proteomic detection of a membrane-anchored GTPase on a pathogen vacuole reflects membrane trafficking during uptake, not a dedicated RasG role; retained as non-core.
Supporting Evidence:
PMID:39458259
Proteomic analyses revealed 689 proteins, including 13 small GTPases of the Rab family
|
|
GO:0019954
asexual reproduction
|
IMP
PMID:10906762 Mediation of cell-substratum adhesion by RasG in Dictyosteli... |
KEEP AS NON CORE |
Summary: RasG affects growth and phagocytosis of vegetative cells; dictyBase maps such growth/proliferation phenotypes to asexual reproduction. This is a broad developmental-cycle term rather than a specific molecular role.
Reason: The annotation reflects RasG's contribution to vegetative growth/uptake captured under a broad life-cycle term; retained as non-core.
Supporting Evidence:
PMID:10906762
RasG is crucial for Dictyostelium cell-substratum adhesion during growth and that RasG may play a role in adhesion-mediated phagocytosis
|
|
GO:0031589
cell-substrate adhesion
|
IMP
PMID:10906762 Mediation of cell-substratum adhesion by RasG in Dictyosteli... |
ACCEPT |
Summary: Expression of activated RasG(G12T) makes cells markedly more adherent to the substratum, and rasG-null cells adhere abnormally, establishing RasG as a regulator of cell-substratum adhesion.
Reason: RasG activity controls cell-substratum adhesion, a well-supported and core aspect of RasG-regulated cytoskeletal/adhesion behavior.
Supporting Evidence:
PMID:10906762
RasG is crucial for Dictyostelium cell-substratum adhesion during growth and that RasG may play a role in adhesion-mediated phagocytosis
|
|
GO:0010811
positive regulation of cell-substrate adhesion
|
IMP
PMID:39789437 The IQGAP-related RasGAP IqgC regulates cell-substratum adhe... |
KEEP AS NON CORE |
Summary: This study centers on the RasGAP IqgC and RapA in adhesion regulation. RasG's positive role in substratum adhesion is established more directly by activated-RasG experiments, so this annotation is retained but treated as a supporting, non-core adhesion role.
Reason: The cited paper primarily addresses IqgC/RapA; the positive regulation of adhesion by active RasG is supported (activated RasG increases adhesion) but the adhesion axis is one of several downstream RasG processes, retained as non-core.
Supporting Evidence:
PMID:10906762
which causes cells to become significantly more adherent to the substratum than are wild type cells
|
|
GO:1905301
regulation of macropinocytosis
|
IGI
PMID:38888895 Leep2A and Leep2B function as a RasGAP complex to regulate m... |
ACCEPT |
Summary: The Leep2A/Leep2B RasGAP complex fine-tunes Ras activity to control macropinosome formation, placing RasG within the regulatory network of macropinocytosis.
Reason: RasG activity is a central input controlling macropinocytosis; regulation of macropinocytosis is a core aspect of RasG function.
Supporting Evidence:
PMID:38888895
At the center of this signaling network are Ras GTPases, whose activation potently stimulates macropinocytosis
|
|
GO:0005515
protein binding
|
IPI
PMID:38888895 Leep2A and Leep2B function as a RasGAP complex to regulate m... |
KEEP AS NON CORE |
Summary: Captures binding between RasG and the Leep2 RasGAP complex. Bare protein binding is uninformative; the meaningful relationship is that Leep2 acts as a GAP on Ras GTPases including RasG.
Reason: Documents a real RasG-regulator (RasGAP) interaction but via an uninformative term; retained as non-core.
Supporting Evidence:
PMID:38888895
it modulates macropinosome formation by regulating the activities of three Ras family small GTPases
|
|
GO:0001891
phagocytic cup
|
IDA
PMID:38263885 IqgC is a potent regulator of macropinocytosis in the presen... |
ACCEPT |
Summary: Active RasG localizes to forming endocytic (macropinocytic/phagocytic) cups, where it recruits the RasGAP IqgC. RasG marks the cup membrane during large-scale endocytosis.
Reason: RasG is enriched at nascent endocytic cups, a core site of its action in macropinocytosis/phagocytosis.
Supporting Evidence:
PMID:38263885
interaction with RasG is indispensable for the recruitment of IqgC to forming macropinocytic cups
|
|
GO:0032880
regulation of protein localization
|
IMP
PMID:38263885 IqgC is a potent regulator of macropinocytosis in the presen... |
ACCEPT |
Summary: Recruitment/loading of the RasGAP IqgC onto macropinosomes requires RasG, so RasG controls the localization of this effector protein.
Reason: RasG governs the membrane recruitment of downstream partners (e.g. IqgC) at endocytic structures; a genuine regulatory function.
Supporting Evidence:
PMID:38263885
its loading to macropinosomes is dependent on RasG
|
|
GO:0140986
G protein-coupled chemorepellent receptor signaling pathway
|
IMP
PMID:34788129 A chemorepellent inhibits local Ras activation to inhibit ps... |
KEEP AS NON CORE |
Summary: The chemorepellent AprA locally inhibits Ras cortical activation acting through, among others, RasG, to bias cell movement away from the source. RasG participates in this chemorepulsion pathway.
Reason: RasG is a node in AprA chemorepulsion signaling, but this is a context-specific developmental/behavioral role rather than a core RasG function.
Supporting Evidence:
PMID:34788129
Ras protein RasG, protein kinase B, the p21-activated kinase PakD, and the extracellular signal-regulated kinase Erk1
|
|
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: Delineation of the AprA chemorepulsion pathway showed it uses a subset of chemoattraction components including Ras. RasG contributes to chemorepellent signaling.
Reason: Participation in AprA chemorepulsion is a specialized behavioral role, retained as non-core.
Supporting Evidence:
PMID:30462573
AprA uses a subset of chemoattraction signal transduction pathways including Ras, protein kinase A, target of rapamycin
|
|
GO:0007188
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
|
IMP
PMID:15143344 Chemoattractant-induced Ras activation during Dictyostelium ... |
KEEP AS NON CORE |
Summary: During aggregation, cAMP acting via its GPCR triggers rapid, transient RasG activation. RasG is thus part of chemoattractant-GPCR signaling, though adenylyl cyclase (ACA) activation is more strongly dependent on the paralog RasC.
Reason: RasG is activated downstream of the cAMP GPCR, but the adenylate cyclase-modulating branch is predominantly a RasC function; retained as non-core for RasG.
Supporting Evidence:
PMID:15143344
RasC and RasG showed a rapid and transient activation when aggregation-competent cells were stimulated with the chemoattractant cAMP
|
|
GO:0051593
response to folic acid
|
IGI
PMID:23132928 Delineating the core regulatory elements crucial for directe... |
ACCEPT |
Summary: RasG (and RasC) are activated in response to folic acid and are required for full Ras/PI3K responses during folate-directed migration of vegetative cells.
Reason: Folate is the key vegetative chemoattractant and RasG is a core mediator of the folic-acid response; a core function.
Supporting Evidence:
PMID:23132928
Ras and phosphoinositide 3-kinase activity were significantly decreased in Ras G and Ras C/G nulls
|
|
GO:0140220
pathogen-containing vacuole
|
HDA
PMID:18980612 Proteome analysis of Legionella vacuoles purified by magneti... |
KEEP AS NON CORE |
Summary: RasG was recovered in proteomic analyses of purified Legionella- containing vacuoles, which are dominated by Arf/Rab GTPases. This is an incidental co-purification during endocytic trafficking, not a dedicated RasG role.
Reason: Bulk proteomic detection on a pathogen vacuole reflects membrane trafficking; retained as non-core.
Supporting Evidence:
PMID:18980612
revealed 566 host proteins, including known LCV components, such as the small GTPases Arf1, Rab1 and Rab7
|
|
GO:0003925
G protein activity
|
IDA
PMID:15352238 The identification of Dictyostelium phosphoproteins altered ... |
ACCEPT |
Summary: Uses the constitutively activated (GTP-locked) RasG(G12T) to probe downstream phosphorylation, consistent with RasG acting as an active G protein/signal transducer.
Reason: RasG functions as a nucleotide-dependent G protein switch; a core molecular function.
Supporting Evidence:
PMID:15352238
the effect of activated RasG, RasG(G12T), expression on the phosphorylation state of Dictyostelium proteins
|
|
GO:0035014
phosphatidylinositol 3-kinase regulator activity
|
IMP
PMID:23132928 Delineating the core regulatory elements crucial for directe... |
ACCEPT |
Summary: Loss of RasG (and RasC/G) strongly reduces PI3K activity, demonstrating that RasG is a positive regulator/activator of class I PI3K, its best-defined effector.
Reason: RasG activation of PI3K to produce PIP3 is a central, directly-supported core molecular function.
Supporting Evidence:
PMID:23132928
Ras and phosphoinositide 3-kinase activity were significantly decreased in Ras G and Ras C/G nulls
|
|
GO:0050927
positive regulation of positive chemotaxis
|
IMP
PMID:10725225 Functional overlap of the dictyostelium RasG, RasD and RasB ... |
ACCEPT |
Summary: rasG disruption reduces motility and chemotactic behavior; RasG promotes directed movement toward chemoattractants.
Reason: RasG positively promotes chemotaxis/motility, a core function.
Supporting Evidence:
PMID:10725225
a defect in cytokinesis, reduced motility and reduced growth
|
|
GO:0046587
positive regulation of calcium-dependent cell-cell adhesion
|
IMP
PMID:16622066 An activated Ras protein alters cell adhesion by dephosphory... |
KEEP AS NON CORE |
Summary: Activated RasG increases DdCAD-1-dependent cell-cell cohesion during early development by reducing DdCAD-1 phosphorylation and increasing its surface localization. This is a developmental adhesion role.
Reason: RasG modulates DdCAD-1-mediated cell-cell adhesion during early development, a specialized developmental process rather than the core RasG function.
Supporting Evidence:
PMID:16622066
cells expressing RasG(G12T) exhibited increased cell-cell cohesion, concomitant with reduced levels of DdCAD-1 phosphorylation
|
|
GO:0072697
protein localization to cell cortex
|
IMP
PMID:16622066 An activated Ras protein alters cell adhesion by dephosphory... |
KEEP AS NON CORE |
Summary: Activated RasG increases localization of the adhesion molecule DdCAD-1 at the cell surface/cortex, so RasG influences cortical protein localization in a developmental adhesion context.
Reason: This reflects RasG control of DdCAD-1 surface localization during early development, a specialized non-core role.
Supporting Evidence:
PMID:16622066
was correlated with increased localization of DdCAD-1 at the cell surface
|
|
GO:0000281
mitotic cytokinesis
|
IMP
PMID:10725225 Functional overlap of the dictyostelium RasG, RasD and RasB ... |
ACCEPT |
Summary: rasG disruption causes a cytokinesis defect, one of the principal phenotypes of rasG-null cells.
Reason: RasG is required for normal cytokinesis; a core function.
Supporting Evidence:
PMID:10725225
a defect in cytokinesis, reduced motility and reduced growth
|
|
GO:0051248
negative regulation of protein metabolic process
|
IDA
PMID:10725225 Functional overlap of the dictyostelium RasG, RasD and RasB ... |
KEEP AS NON CORE |
Summary: RasG negatively regulates the levels of the paralogous RasD (and RasB) protein in vegetative cells. This is a regulatory cross-talk between paralogs rather than a broad protein-metabolism role.
Reason: The evidence supports RasG-dependent negative control of RasD/RasB protein levels; retained under this broad term as non-core.
Supporting Evidence:
PMID:10725225
RasD protein levels are negatively regulated in vegetative cells by RasG
|
|
GO:0019887
protein kinase regulator activity
|
IDA
PMID:15534002 Localized Ras signaling at the leading edge regulates PI3K, ... |
KEEP AS NON CORE |
Summary: RasG activation stimulates PI3K and hence Akt/PKB activation. The direct effector is PI3K (a lipid kinase); regulation of the protein kinase PKB is downstream and indirect.
Reason: The precise, directly-supported effector MF is PI3K regulation (GO:0035014); the more general protein kinase regulator activity is retained as non-core.
Supporting Evidence:
PMID:15534002
chemoattractant-induced Akt/PKB activation was decreased in rasG null cells
|
|
GO:0031252
cell leading edge
|
IDA
PMID:15534002 Localized Ras signaling at the leading edge regulates PI3K, ... |
ACCEPT |
Summary: A GFP-RBD biosensor shows Ras activation localized to the leading edge of chemotaxing cells, where RasG acts to establish the front.
Reason: RasG is activated at, and acts from, the cell leading edge; a core site of action.
Supporting Evidence:
PMID:15534002
Ras activation occurs at the leading edge of chemotaxing cells
|
|
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IMP
PMID:15534002 Localized Ras signaling at the leading edge regulates PI3K, ... |
ACCEPT |
Summary: RasG activation is required for chemoattractant-induced PI3K/Akt(PKB) activation; rasG-null cells show decreased Akt/PKB activation.
Reason: Positive regulation of PI3K/PKB signaling is a core downstream output of RasG.
Supporting Evidence:
PMID:15534002
chemoattractant-induced Akt/PKB activation was decreased in rasG null cells
|
|
GO:0010629
negative regulation of gene expression
|
IMP
PMID:8754814 Overexpression of an activated rasG gene during growth block... |
KEEP AS NON CORE |
Summary: Overexpression of activated rasG-G12T during growth blocks initiation of development and represses early developmental genes (car1, pde). This is a gain-of-function developmental effect.
Reason: The effect on early gene expression reflects a developmental consequence of constitutive RasG activation rather than a core RasG function.
Supporting Evidence:
PMID:8754814
the expression of car1 and pde, genes that are normally induced soon after the initiation of development, was repressed
|
|
GO:0003925
G protein activity
|
IDA
PMID:17380187 Cyclic AMP signalling in Dictyostelium: G-proteins activate ... |
ACCEPT |
Summary: RasG is directly shown to be activated (GTP-loaded) in response to cAMP, acting as a G protein switch, with RasGEFR as its specific activator.
Reason: RasG acts as a nucleotide-dependent G protein/signal transducer; a core molecular function.
Supporting Evidence:
PMID:17380187
During Dictyostelium development, RasC and RasG are activated in response to cyclic AMP
|
|
GO:0140220
pathogen-containing vacuole
|
HDA
PMID:28183814 Comparative Proteomics of Purified Pathogen Vacuoles Correla... |
KEEP AS NON CORE |
Summary: Comparative proteomics of Legionella-containing vacuoles highlighted the small GTPase Rap1; RasG detection here is an incidental co-purification during endocytic trafficking rather than a specific RasG function.
Reason: Bulk proteomic co-purification on a pathogen vacuole; retained as non-core.
Supporting Evidence:
PMID:28183814
The small GTPase Rap1 was identified on D. discoideum LCVs containing strain Lp02 but not the
|
|
GO:0044354
macropinosome
|
IDA
PMID:27821733 A Diaphanous-related formin links Ras signaling directly to ... |
ACCEPT |
Summary: Active RasG is present on macropinosomes/endocytic cups where it directly regulates the formin ForG during large-scale endocytosis.
Reason: The macropinosome membrane is a core site of RasG action in macropinocytosis/phagocytosis.
Supporting Evidence:
PMID:27821733
ForG is directly regulated in large-scale endocytosis by RasB and RasG, which are highly related to the human proto-oncogene KRas
|
|
GO:0005515
protein binding
|
IPI
PMID:10473630 A novel Ras-interacting protein required for chemotaxis and ... |
KEEP AS NON CORE |
Summary: Captures the interaction of activated RasG with the Ras-interacting protein RIP3 (RipA), an effector required for chemotaxis and cAMP signal relay. Bare protein binding is uninformative.
Reason: Documents a real RasG-effector interaction (RIP3/RipA) but via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:10473630
RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement
|
|
GO:0005515
protein binding
|
IPI
PMID:15194808 Phg2, a kinase involved in adhesion and focal site modeling ... |
KEEP AS NON CORE |
Summary: Relates to Phg2, an adhesion-linked serine/threonine kinase carrying a Ras-binding domain. The interaction is captured by an uninformative protein binding term.
Reason: Documents a Ras-effector (Phg2 RBD) association but via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:15194808
PHG2 encodes a novel serine/threonine kinase with a ras-binding domain
|
|
GO:0005515
protein binding
|
IPI
PMID:20089846 A Rap/phosphatidylinositol 3-kinase pathway controls pseudop... |
KEEP AS NON CORE |
Summary: This study concerns a GbpD/Rap1/PI3K pathway controlling pseudopod formation and cell-substrate adhesion; the associated interaction is captured by an uninformative protein binding term.
Reason: Retained interaction annotation via a non-specific term in a Rap/PI3K adhesion context; non-core.
Supporting Evidence:
PMID:20089846
Rap1 directly binds to the Ras binding domain of PI3K
|
|
GO:0005515
protein binding
|
IPI
PMID:23135995 Daydreamer, a Ras effector and GSK-3 substrate, is important... |
KEEP AS NON CORE |
Summary: Captures the interaction with DydA (Daydreamer), an MRL-family Ras effector required for directional sensing and cell motility. Bare protein binding is uninformative.
Reason: Documents a RasG-effector interaction (DydA) but via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:23135995
DydA is a putative Ras effector that is required for cell polarization and directional movement during chemotaxis
|
|
GO:0005515
protein binding
|
IPI
PMID:24986648 Regulation of a LATS-homolog by Ras GTPases is important for... |
KEEP AS NON CORE |
Summary: Captures binding of the NDR/LATS-homolog kinase NdrC to activated RasG (and RasB), an interaction important for control of cell division. Bare protein binding is uninformative.
Reason: Documents a RasG-effector interaction (NdrC) via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:24986648
Further in vitro pull-down assays showed that NdrC binds RasG and RasB, and to a lesser extent RasC and Rap1
|
|
GO:0005515
protein binding
|
IPI
PMID:27172998 The small GTPases Ras and Rap1 bind to and control TORC2 act... |
KEEP AS NON CORE |
Summary: Relates to binding of Ras (and Rap1) to the TORC2 complex; in this study the strongest Ras-TOR interaction is via the paralog RasC. The generic protein binding term is uninformative.
Reason: Documents Ras-TORC2 association via a non-specific term (the study emphasizes RasC); retained as non-core.
Supporting Evidence:
PMID:27172998
Ras and Rap1 bind to and control TORC2 activity
|
|
GO:0005515
protein binding
|
IPI
PMID:27821733 A Diaphanous-related formin links Ras signaling directly to ... |
KEEP AS NON CORE |
Summary: Captures binding of activated RasG (and RasB) to the Diaphanous-related formin ForG, linking Ras signaling directly to actin assembly. Bare protein binding is uninformative.
Reason: Documents a RasG-effector interaction (ForG) via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:27821733
ForG is directly regulated in large-scale endocytosis by RasB and RasG, which are highly related to the human proto-oncogene KRas
|
|
GO:0005515
protein binding
|
IPI
PMID:29109256 GPCR-controlled membrane recruitment of negative regulator C... |
KEEP AS NON CORE |
Summary: Relates to the RasGAP C2GAP1, a negative regulator of Ras signaling that is recruited to the leading edge. Bare protein binding is uninformative.
Reason: Documents a RasG-regulator (RasGAP) interaction via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:29109256
C2GAP1, which localizes at the leading edge of chemotaxing cells and is activated by and essential for GPCR-mediated Ras signaling
|
|
GO:0005525
GTP binding
|
IDA
PMID:15143344 Chemoattractant-induced Ras activation during Dictyostelium ... |
ACCEPT |
Summary: Direct assay of the GTP-bound (activated) form of RasG using a Raf1-RBD pulldown demonstrates GTP binding.
Reason: GTP binding is a core molecular function directly demonstrated for RasG.
Supporting Evidence:
PMID:15143344
the Ras-binding domain (RBD) of mammalian Raf1 was capable of binding to the activated form of RasG
|
|
GO:0005811
lipid droplet
|
HDA
PMID:24036346 Dictyostelium lipid droplets host novel proteins. |
KEEP AS NON CORE |
Summary: RasG was recovered in proteomic characterization of Dictyostelium lipid droplets. This is an incidental co-purification of a membrane-anchored protein, not a dedicated lipid-droplet function.
Reason: Bulk proteomic detection on lipid droplets; retained as non-core.
Supporting Evidence:
PMID:24036346
Among the novel protein components are LdpA, a protein specific to Dictyostelium, and Net4
|
|
GO:0005938
cell cortex
|
IDA
PMID:24986648 Regulation of a LATS-homolog by Ras GTPases is important for... |
ACCEPT |
Summary: Activated RasG is a cortical/membrane-associated GTPase; the NdrC study localizes Ras activity to the cortex in the context of cell-division control.
Reason: The cell cortex is a core site of RasG activity, consistent with its membrane anchoring and leading-edge/cortical activation.
Supporting Evidence:
PMID:24986648
In cells lacking NdrC, the levels of activated RasB and RasG are up-regulated
|
|
GO:0009898
cytoplasmic side of plasma membrane
|
IDA
PMID:27821733 A Diaphanous-related formin links Ras signaling directly to ... |
ACCEPT |
Summary: RasG is prenylated and anchored to the cytoplasmic face of the plasma membrane, from which it signals to effectors such as ForG.
Reason: Consistent with the lipid-anchored orientation of RasG at the inner leaflet of the plasma membrane; a core localization.
Supporting Evidence:
PMID:27821733
ForG is directly regulated in large-scale endocytosis by RasB and RasG, which are highly related to the human proto-oncogene KRas
|
|
GO:0010856
adenylate cyclase activator activity
|
IGI
PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras... |
KEEP AS NON CORE |
Summary: In doubly-disrupted rasC/rasG cells, adenylyl cyclase (ACA) signaling is lost; however, ACA activation is predominantly a RasC-dependent process, with RasG contributing largely to the chemotactic branch.
Reason: RasG contributes to cAMP-signaling pathways, but adenylyl cyclase activation is chiefly a RasC role; retained as non-core for RasG.
Supporting Evidence:
PMID:18180289
RasG and RasC are the only two Ras subfamily proteins that directly control these pathways
|
|
GO:0019900
kinase binding
|
IPI
PMID:10473630 A novel Ras-interacting protein required for chemotaxis and ... |
KEEP AS NON CORE |
Summary: Relates to the RasG-RIP3(RipA) interaction. RIP3 is a Ras-interacting protein involved in guanylyl cyclase-linked chemotaxis signaling; the kinase binding term is only weakly informative here.
Reason: Documents a RasG partner interaction; the specific molecular meaning is better captured as effector binding, so retained as non-core.
Supporting Evidence:
PMID:10473630
RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement
|
|
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-null cells, identifying RasG/RasC as the presumptive GTPases required, in a developmental cAMP-signaling context.
Reason: RasG contributes to guanylyl cyclase activation in the aggregation-stage cAMP pathway; a developmental-signaling role retained as non-core.
Supporting Evidence:
PMID:18180289
in vitro guanylyl cyclase activation is also abolished in the rasC
|
|
GO:0030250
guanylate cyclase activator activity
|
IGI
PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras... |
KEEP AS NON CORE |
Summary: Same finding via genetic interaction; guanylyl cyclase activation requires RasG/RasC during aggregation.
Reason: Developmental cAMP-pathway contribution; retained as non-core.
Supporting Evidence:
PMID:18180289
identifies RasG/RasC as the presumptive monomeric GTPases required for this activation
|
|
GO:0031982
vesicle
|
IDA
PMID:19589376 Nanovesicles released by Dictyostelium cells: a potential ca... |
KEEP AS NON CORE |
Summary: RasG was reported among proteins of Dictyostelium-released nanovesicles, a preparation dominated by actin and actin-related proteins. This is an incidental co-purification.
Reason: Bulk proteomic detection in released vesicles; not a core RasG function.
Supporting Evidence:
PMID:19589376
A proteomic analysis reveals a predominance of actin and actin-related proteins
|
|
GO:0043130
ubiquitin binding
|
IDA
PMID:24338482 Degradation of activated K-Ras orthologue via K-Ras-specific... |
MARK AS OVER ANNOTATED |
Summary: This study shows that activated RasG is itself targeted for degradation by polyubiquitination at K-Ras-equivalent C-terminal lysines. Being a substrate of ubiquitination is not the same as possessing a ubiquitin-binding molecular function.
Reason: The evidence demonstrates that RasG is polyubiquitinated (a substrate), which does not support a ubiquitin-binding molecular function; the term appears to over-interpret a modification event.
Supporting Evidence:
PMID:24338482
RasG, the Dictyostelium orthologue of K-Ras, is targeted for degradation by polyubiquitination
|
|
GO:0043548
phosphatidylinositol 3-kinase binding
|
IPI
PMID:23843627 Two distinct functions for PI3-kinases in macropinocytosis. |
ACCEPT |
Summary: Binding assays show RasG interacts most strongly with PI3K1/2 and PI3K4, directly engaging its principal effector, class I PI3-kinase.
Reason: Direct binding of GTP-RasG to PI3K is a core, mechanistically informative molecular function underlying macropinocytosis and chemotaxis.
Supporting Evidence:
PMID:23843627
RasG and RasS interact most strongly with PI3K1/2 and PI3K4
|
|
GO:0045335
phagocytic vesicle
|
HDA
PMID:16926386 Proteomics fingerprinting of phagosome maturation and eviden... |
KEEP AS NON CORE |
Summary: RasG was among the many signal-transduction proteins detected by proteomic fingerprinting of maturing Dictyostelium phagosomes. Consistent with a role in phagocytosis, though the detection itself is high-throughput.
Reason: Proteomic detection on phagosomes supports involvement in phagocytosis but is an incidental localization here; retained as non-core.
Supporting Evidence:
PMID:16926386
we identified 179 phagosomal proteins in the amoeba Dictyostelium, including components of signal transduction, membrane traffic, and the cytoskeleton
|
|
GO:0005886
plasma membrane
|
IDA
PMID:15534002 Localized Ras signaling at the leading edge regulates PI3K, ... |
ACCEPT |
Summary: Direct imaging shows GFP-RasG along the plasma membrane and Ras activity (GFP-RBD) at the plasma membrane/leading edge upon stimulation.
Reason: RasG acts at the plasma membrane; a core localization directly supported.
Supporting Evidence:
PMID:15534002
GFP-RasG displayed uniform localization along the plasma membrane and cytosol
|
|
GO:0044351
macropinocytosis
|
IMP
PMID:30967009 Function of small GTPases in Dictyostelium macropinocytosis. |
ACCEPT |
Summary: Genetic analysis identifies RasG (with RasS) as a key Ras protein driving macropinocytosis, which is stimulated by persistent Ras activation.
Reason: RasG is a core driver of macropinocytosis.
Supporting Evidence:
PMID:30967009
macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved
|
|
GO:1901262
negative regulation of sorocarp spore cell differentiation
|
IMP
PMID:11222145 Expression of activated Ras during Dictyostelium development... |
KEEP AS NON CORE |
Summary: Developmental expression of activated rasG in prespore cells causes their transdifferentiation into prestalk cells, altering cell fate. This is a gain-of-function developmental effect.
Reason: Reflects a developmental cell-fate consequence of activated RasG rather than a core RasG molecular function; retained as non-core.
Supporting Evidence:
PMID:11222145
the expression of activated rasG in prespore cells results in their transdifferentiation into prestalk cells
|
|
GO:0006909
phagocytosis
|
IMP
PMID:10906762 Mediation of cell-substratum adhesion by RasG in Dictyosteli... |
ACCEPT |
Summary: Expression of activated RasG reduces bacterial engulfment (phagocytosis) when cells are adhered, indicating RasG regulates phagocytosis.
Reason: RasG regulates phagocytosis, a core RasG-dependent uptake process closely related to macropinocytosis.
Supporting Evidence:
PMID:10906762
engulf fewer bacteria on filter surfaces, indicating a defect in phagocytosis when cells are adhered
|
|
GO:0046847
filopodium assembly
|
IMP
PMID:10906762 Mediation of cell-substratum adhesion by RasG in Dictyosteli... |
ACCEPT |
Summary: RasG activity influences filopodial number; activated RasG dramatically reduces filopodia, and rasG-null cells show abnormal, excessive filopodia, indicating RasG regulates filopodium formation.
Reason: RasG regulates filopodium/actin-protrusion assembly, a core cytoskeletal function.
Supporting Evidence:
PMID:10906762
The expression of the activated RasG also dramatically reduces the number of filopodia on the cell surface
|
|
GO:0007015
actin filament organization
|
IMP
PMID:9245789 Dictyostelium RasG is required for normal motility and cytok... |
ACCEPT |
Summary: rasG-null cells show a wide range of actin cytoskeleton defects including loss of polarity, absence of normal lamellipodia and aberrant filopodia, establishing RasG as a regulator of actin organization.
Reason: Control of the actin cytoskeleton is a principal, core function of RasG.
Supporting Evidence:
PMID:9245789
they exhibit defective cell movement and a wide range of defects in the control of the actin cytoskeleton, including a loss of cell polarity, absence of normal lamellipodia
|
|
GO:0005515
protein binding
|
IPI
PMID:30622175 IQGAP-related protein IqgC suppresses Ras signaling during l... |
KEEP AS NON CORE |
Summary: Captures binding of the RasGAP IqgC to active RasG. Bare protein binding is uninformative; the meaningful relationship is that IqgC is a RasG-specific GAP.
Reason: Documents a RasG-regulator (RasGAP) interaction via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:30622175
IqgC interacts with active RasG and exhibits RasGAP activity toward this GTPase
|
|
GO:0005515
protein binding
|
IPI
PMID:27009206 The novel RacE-binding protein GflB sharpens Ras activity at... |
KEEP AS NON CORE |
Summary: Relates to GflB, a RacE-binding protein with Ras GEF and Rho GAP domains that sharpens Ras activity at the leading edge. The interaction is captured by an uninformative protein binding term.
Reason: Documents a Ras-regulator (GflB) interaction via a non-specific term; retained as non-core.
Supporting Evidence:
PMID:27009206
GflB balances the activation of Ras and Rho GTPases, which enables cells to precisely orient signaling events
|
|
GO:1905169
regulation of protein localization to phagocytic vesicle
|
IMP
PMID:27821733 A Diaphanous-related formin links Ras signaling directly to ... |
ACCEPT |
Summary: RasG directly regulates the formin ForG at endocytic cups, controlling its recruitment/activity during phagocytosis and macropinocytosis.
Reason: RasG governs recruitment of actin-assembly machinery to phagocytic/ macropinocytic vesicles; a core function at endocytic structures.
Supporting Evidence:
PMID:27821733
ForG is directly regulated in large-scale endocytosis by RasB and RasG, which are highly related to the human proto-oncogene KRas
|
|
GO:0051591
response to cAMP
|
IDA
PMID:2049874 Ras-related genes in Dictyostelium discoideum. |
KEEP AS NON CORE |
Summary: An early characterization of Dictyostelium ras genes noting DdrasG expression in vegetative cells and early development. Support for a specific cAMP-response molecular role is limited in this reference.
Reason: RasG is activated in response to cAMP during aggregation (better established by later work); this early reference supports developmental expression, retained as non-core.
Supporting Evidence:
PMID:2049874
DdrasG is expressed in vegetative cells and during early development
|
|
GO:0019954
asexual reproduction
|
IGI
PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras... |
KEEP AS NON CORE |
Summary: RasG/RasC control cAMP signaling required for the multicellular (asexual) developmental cycle; captured under a broad life-cycle term.
Reason: Broad life-cycle term reflecting RasG's developmental-signaling contribution; retained as non-core.
Supporting Evidence:
PMID:18180289
RasG and RasC are the only two Ras subfamily proteins that directly control these pathways
|
|
GO:1903666
positive regulation of asexual reproduction
|
IMP
PMID:10725225 Functional overlap of the dictyostelium RasG, RasD and RasB ... |
KEEP AS NON CORE |
Summary: RasG supports vegetative growth and cell division underlying asexual reproduction; captured under a broad life-cycle term.
Reason: Broad life-cycle term reflecting RasG's role in growth/division; retained as non-core.
Supporting Evidence:
PMID:10725225
a defect in cytokinesis, reduced motility and reduced growth
|
|
GO:0043326
chemotaxis to folate
|
IMP
PMID:24742374 RasG signaling is important for optimal folate chemotaxis in... |
ACCEPT |
Summary: RasG is required for optimal folate chemotaxis, particularly in weak gradients, in both axenic and bacterially grown cells.
Reason: Folate chemotaxis is a core vegetative behavior of RasG.
Supporting Evidence:
PMID:24742374
Both axenic and bacterially grown cells require RasG for optimal folate chemotaxis, particularly in weak gradients
|
|
GO:0000281
mitotic cytokinesis
|
IMP
PMID:20833893 Ras proteins have multiple functions in vegetative cells of ... |
ACCEPT |
Summary: Cytokinesis is one of three distinct RasG functions in vegetative cells; RasD can fully substitute for RasG in cytokinesis but RasC cannot.
Reason: RasG is required for cytokinesis; a core function.
Supporting Evidence:
PMID:20833893
RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension
|
|
GO:0043326
chemotaxis to folate
|
IMP
PMID:20833893 Ras proteins have multiple functions in vegetative cells of ... |
ACCEPT |
Summary: Folate chemotaxis is a distinct RasG function; RasC can partially, but RasD cannot, substitute for RasG in folate chemotaxis.
Reason: RasG is a core mediator of folate chemotaxis.
Supporting Evidence:
PMID:20833893
for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect
|
|
GO:0044351
macropinocytosis
|
IMP
PMID:23843627 Two distinct functions for PI3-kinases in macropinocytosis. |
ACCEPT |
Summary: Single rasG mutants have severe macropinocytosis defects; RasG works with PI3K1/2 and PI3K4 to drive macropinocytosis.
Reason: RasG is a core driver of macropinocytosis through PI3K.
Supporting Evidence:
PMID:23843627
single mutants of either Ras have severe macropinocytosis defects
|
|
GO:0043327
chemotaxis to cAMP
|
IGI
PMID:18180289 Rap1 activation in response to cAMP occurs downstream of ras... |
ACCEPT |
Summary: RasG is required for cAMP chemotactic signaling during aggregation; cAMP-driven chemotaxis is abolished in rasC/rasG-null cells.
Reason: RasG is the more important Ras for cAMP chemotaxis; a core chemotactic function.
Supporting Evidence:
PMID:18180289
there was negligible signaling through both the cAMP chemotactic pathway and the adenylyl cyclase activation pathway
|
|
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: RasG positively regulates PI3K/PKB signaling downstream of cAMP; Rap1 activation (downstream of PI3K-linked signaling) is abolished in rasG-null cells.
Reason: Positive regulation of PI3K/PKB signaling is a core downstream output of RasG.
Supporting Evidence:
PMID:18180289
Rap1 activation was totally abolished in
|
|
GO:0031152
aggregation involved in sorocarp development
|
IMP
PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep... |
KEEP AS NON CORE |
Summary: rasG inactivation delays aggregation and reduces early gene expression, showing RasG contributes to the aggregation stage of development.
Reason: RasG participates in developmental aggregation, a specialized developmental process rather than a core vegetative function.
Supporting Evidence:
PMID:16885420
Insertional inactivation of the rasG gene resulted in delayed aggregation and a partial inhibition of early gene expression
|
|
GO:0031152
aggregation involved in sorocarp development
|
IGI
PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep... |
KEEP AS NON CORE |
Summary: Comparison of rasG-, rasC- and rasC-rasG- strains shows overlapping Ras contributions to aggregation; RasG participates in the aggregation stage.
Reason: Developmental aggregation role; retained as non-core.
Supporting Evidence:
PMID:16885420
Insertional inactivation of the rasG gene resulted in delayed aggregation and a partial inhibition of early gene expression
|
|
GO:0043327
chemotaxis to cAMP
|
IMP
PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep... |
ACCEPT |
Summary: Signal transduction through RasG is more important than RasC for cAMP chemotaxis; chemotaxis is reduced in rasG-null cells.
Reason: RasG is a core mediator of cAMP chemotaxis.
Supporting Evidence:
PMID:16885420
signal transduction through RasG is more important in chemotaxis and early gene expression
|
|
GO:0043327
chemotaxis to cAMP
|
IGI
PMID:16885420 Delineation of the roles played by RasG and RasC in cAMP-dep... |
ACCEPT |
Summary: Genetic comparison confirms RasG is the predominant Ras for cAMP chemotaxis, with partial functional overlap with RasC.
Reason: RasG is a core mediator of cAMP chemotaxis.
Supporting Evidence:
PMID:16885420
Both chemotaxis and ACA activation were reduced in the rasG- cells, but the effect on chemotaxis was more pronounced
|
|
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: RasG signaling positively contributes to the chemotactic (PI3K/PKB) arm of the cAMP response during aggregation.
Reason: Positive regulation of PI3K/PKB signaling is a core downstream output of RasG.
Supporting Evidence:
PMID:16885420
signal transduction through RasG is more important in chemotaxis and early gene expression
|
|
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 data support RasG positively regulating the chemotactic PI3K/PKB branch of cAMP signaling.
Reason: Positive regulation of PI3K/PKB signaling is a core downstream output of RasG.
Supporting Evidence:
PMID:16885420
Both chemotaxis and ACA activation were reduced in the rasG- cells, but the effect on chemotaxis was more pronounced
|
|
GO:0000281
mitotic cytokinesis
|
IMP
PMID:16822579 Cell motility and SCAR localisation in axenically growing Di... |
ACCEPT |
Summary: In studies of motility and SCAR localization across strains, Ras protein knockouts (including rasG) produce phenotypes during vegetative growth, consistent with the established RasG cytokinesis requirement.
Reason: RasG is required for cytokinesis (well established across multiple studies); a core function.
Supporting Evidence:
PMID:9245789
rasG- cells are unable to perform normal cytokinesis, becoming multinucleate when grown in suspension culture
|
|
GO:0000902
cell morphogenesis
|
IMP
PMID:16822579 Cell motility and SCAR localisation in axenically growing Di... |
ACCEPT |
Summary: Ras (including rasG) mutations alter cell morphology/motility during vegetative growth, consistent with RasG control of cell shape via the actin cytoskeleton.
Reason: RasG shapes cell morphology through actin/polarity control; a core function (loss of polarity and abnormal shape in rasG-null cells).
Supporting Evidence:
PMID:16822579
knockouts of members of the SCAR complex and Ras proteins, cause different phenotypes during vegetative growth in different parental strains
|
|
GO:0031589
cell-substrate adhesion
|
IMP
PMID:16822579 Cell motility and SCAR localisation in axenically growing Di... |
ACCEPT |
Summary: Consistent with RasG's established role in substratum adhesion; Ras mutants show altered vegetative-growth phenotypes including adhesion/motility behavior.
Reason: RasG regulates cell-substratum adhesion; a core function supported most directly by activated-RasG adhesion experiments.
Supporting Evidence:
PMID:10906762
which causes cells to become significantly more adherent to the substratum than are wild type cells
|
id: P15064
gene_symbol: rasG
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:44689
label: Dictyostelium discoideum
description: RasG (DdrasG) is the most abundant Ras subfamily small GTPase in
growing Dictyostelium discoideum and the closest amoebozoan relative of
mammalian K-Ras. Like other Ras proteins it is a C-terminally prenylated,
plasma-membrane-anchored molecular switch that cycles between an inactive
GDP-bound and an active GTP-bound state, controlled by guanine-nucleotide
exchange factors (RasGEFs such as GefR/Aimless) and GTPase-activating proteins
(RasGAPs such as NF1, IqgC, C2GAP1 and the Leep2 complex). Upon chemoattractant
(folate or cAMP) stimulation, RasG is rapidly and transiently activated at the
leading edge and cell cortex, where GTP-loaded RasG binds and activates class I
phosphatidylinositol 3-kinase to generate PIP3, driving F-actin-based pseudopod
formation, directional sensing and cell motility. RasG is a principal regulator
of chemotaxis, random motility and cell polarity, cytokinesis, macropinocytosis
and phagocytosis, engaging effectors including PI3K, the Diaphanous-related
formin ForG, the NDR/LATS kinase NdrC, TORC2, the Ras-interacting protein
RIP3/RipA and the MRL-family adaptor DydA. Its functions overlap partly with the
paralogs RasC (more specialized for cAMP relay and adenylyl cyclase activation)
and RasD (which can substitute for RasG in cytokinesis).
existing_annotations:
- term:
id: GO:0003924
label: GTPase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: Phylogenetic inference that RasG has intrinsic GTPase activity. This
is the defining catalytic property of a Ras-family small GTPase and is
directly supported for RasG (EC 3.6.5.2, GTP hydrolysis inactivates the
switch).
action: ACCEPT
reason: RasG is a bona fide Ras GTPase that hydrolyzes GTP to GDP; the intrinsic
GTPase activity is a core molecular function and is well conserved across the
family.
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: Phylogenetic inference of plasma membrane localization, corroborated by
direct imaging of GFP-RasG uniformly distributed along the plasma membrane and
activated at the cortex/leading edge.
action: ACCEPT
reason: RasG is prenylated and anchored to the cytoplasmic face of the plasma
membrane, where it is activated and signals; this is a core localization.
supported_by:
- reference_id: PMID:15534002
supporting_text: GFP-RasG displayed uniform localization along the plasma
membrane and cytosol
- term:
id: GO:0007264
label: small GTPase-mediated signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Phylogenetic inference that RasG participates in small GTPase-mediated
signal transduction. This is the core signaling role of RasG as a molecular
switch relaying chemoattractant signals to PI3K and other effectors.
action: ACCEPT
reason: RasG functions as a GTP/GDP molecular switch in signal transduction, a
core function directly demonstrated experimentally.
supported_by:
- reference_id: PMID:15534002
supporting_text: Ras is rapidly and transiently activated in response to
chemoattractant stimulation and regulates PI3K activity
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Phylogenetic inference of a cytokinesis role, strongly corroborated by
RasG null cells becoming multinucleate in suspension.
action: ACCEPT
reason: RasG is required for normal cytokinesis; rasG-null cells fail to complete
cytokinesis and become multinucleate in shaken suspension. This is a core
function.
supported_by:
- reference_id: PMID:9245789
supporting_text: rasG- cells are unable to perform normal cytokinesis,
becoming multinucleate when grown in suspension culture
- term:
id: GO:0044351
label: macropinocytosis
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Phylogenetic inference of a macropinocytosis role, strongly supported by
genetic evidence that RasG is a major regulator of macropinocytosis.
action: ACCEPT
reason: RasG is one of the key Ras proteins driving macropinocytosis in
Dictyostelium; a core function.
supported_by:
- reference_id: PMID:38263885
supporting_text: RasG is a major regulator of macropinocytosis in Dictyostelium
discoideum
- 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 Ras small-GTPase
domain. Correct and core.
action: ACCEPT
reason: The Ras/P-loop GTPase domain confers intrinsic GTP hydrolysis, a core
molecular function of RasG.
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:0003925
label: G protein activity
evidence_type: IEA
original_reference_id: GO_REF:0000003
qualifier: enables
review:
summary: EC-based inference of GTP-hydrolyzing G protein activity. RasG is a
monomeric guanine-nucleotide-binding signal transducer, so this MF is correct
and core (GO:0003925 encompasses small monomeric GTPases).
action: ACCEPT
reason: RasG acts as a nucleotide-dependent molecular switch/signal transducer;
G protein activity is a core molecular function directly demonstrated by
GTP-loading (RBD pulldown) assays.
supported_by:
- reference_id: PMID:15143344
supporting_text: the Ras-binding domain (RBD) of mammalian Raf1 was capable of
binding to the activated form of RasG
- term:
id: GO:0005525
label: GTP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: InterPro2GO inference of GTP binding from the Ras domain. Core and
directly supported (GTP-bound RasG is captured by Raf1-RBD pulldowns).
action: ACCEPT
reason: RasG binds GTP/GDP through its conserved P-loop; a core molecular
function.
supported_by:
- reference_id: PMID:15143344
supporting_text: the Ras-binding domain (RBD) of mammalian Raf1 was capable of
binding to the activated form of RasG
- 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 lipid-anchored, membrane-associated nature of RasG and with direct imaging.
action: ACCEPT
reason: RasG is a prenylated plasma-membrane-anchored GTPase; correct core
localization.
supported_by:
- reference_id: PMID:15534002
supporting_text: GFP-RasG displayed uniform localization along the plasma
membrane and cytosol
- term:
id: GO:0007165
label: signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: Generic signal transduction inferred from the Ras domain. Correct but
far less informative than the more specific small GTPase-mediated signal
transduction annotation also present.
action: KEEP_AS_NON_CORE
reason: This is a high-level parent term; the specific child term GO:0007264
(small GTPase-mediated signal transduction) better captures RasG function, so
this general term is retained but non-core.
supported_by:
- reference_id: PMID:15534002
supporting_text: Ras is rapidly and transiently activated in response to
chemoattractant stimulation and regulates PI3K activity
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: located_in
review:
summary: Generic membrane localization inferred from the domain. Correct but a
high-level parent of the specific plasma membrane annotation.
action: KEEP_AS_NON_CORE
reason: Uninformative parent term; the specific term plasma membrane GO:0005886
is the appropriate core localization.
supported_by:
- reference_id: PMID:15534002
supporting_text: GFP-RasG displayed uniform localization along the plasma
membrane and cytosol
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:40934557
qualifier: enables
review:
summary: Captures the interaction between activated RasG and the RA1 domain of
the effector DydA, used as a RasG-specific biosensor. Bare protein binding is
uninformative; the biologically relevant point is effector engagement by
GTP-RasG.
action: KEEP_AS_NON_CORE
reason: Documents a real RasG-effector interaction (RA1:DydA reporter) but the
generic protein binding term conveys no specific function; retained as
non-core.
supported_by:
- reference_id: PMID:40934557
supporting_text: RA1 preferentially binds RasG over other Ras isoforms and Rap1
- term:
id: GO:0019887
label: protein kinase regulator activity
evidence_type: IDA
original_reference_id: PMID:9551080
qualifier: enables
review:
summary: Based on the observation that constitutively activated RasG inhibits
chemoattractant-induced ERK2 activating phosphorylation. This indicates RasG
influences a MAP kinase, but the effect is negative and likely indirect rather
than a direct kinase-regulator activity.
action: KEEP_AS_NON_CORE
reason: RasG modulates ERK2 phosphorylation, but the relationship is indirect and
the more precise, directly-supported effector MF is PI3K regulation
(GO:0035014). Retained as non-core.
supported_by:
- reference_id: PMID:9551080
supporting_text: Activating phosphorylation is markedly inhibited in strains
overexpressing the constitutively activated RasG protein
- term:
id: GO:0140220
label: pathogen-containing vacuole
evidence_type: HDA
original_reference_id: PMID:39458259
qualifier: located_in
review:
summary: RasG was detected by proteomics of purified Francisella-containing
vacuoles. This is an incidental high-throughput co-purification with an
endomembrane compartment rather than a core RasG function; the proteome is
dominated by Rab-family GTPases.
action: KEEP_AS_NON_CORE
reason: Bulk proteomic detection of a membrane-anchored GTPase on a pathogen
vacuole reflects membrane trafficking during uptake, not a dedicated RasG
role; retained as non-core.
supported_by:
- reference_id: PMID:39458259
supporting_text: Proteomic analyses revealed 689 proteins, including 13 small
GTPases of the Rab family
- term:
id: GO:0019954
label: asexual reproduction
evidence_type: IMP
original_reference_id: PMID:10906762
qualifier: acts_upstream_of_or_within
review:
summary: RasG affects growth and phagocytosis of vegetative cells; dictyBase maps
such growth/proliferation phenotypes to asexual reproduction. This is a broad
developmental-cycle term rather than a specific molecular role.
action: KEEP_AS_NON_CORE
reason: The annotation reflects RasG's contribution to vegetative growth/uptake
captured under a broad life-cycle term; retained as non-core.
supported_by:
- reference_id: PMID:10906762
supporting_text: RasG is crucial for Dictyostelium cell-substratum adhesion
during growth and that RasG may play a role in adhesion-mediated phagocytosis
- term:
id: GO:0031589
label: cell-substrate adhesion
evidence_type: IMP
original_reference_id: PMID:10906762
qualifier: acts_upstream_of_or_within
review:
summary: Expression of activated RasG(G12T) makes cells markedly more adherent to
the substratum, and rasG-null cells adhere abnormally, establishing RasG as a
regulator of cell-substratum adhesion.
action: ACCEPT
reason: RasG activity controls cell-substratum adhesion, a well-supported and
core aspect of RasG-regulated cytoskeletal/adhesion behavior.
supported_by:
- reference_id: PMID:10906762
supporting_text: RasG is crucial for Dictyostelium cell-substratum adhesion
during growth and that RasG may play a role in adhesion-mediated phagocytosis
- term:
id: GO:0010811
label: positive regulation of cell-substrate adhesion
evidence_type: IMP
original_reference_id: PMID:39789437
qualifier: acts_upstream_of_or_within
review:
summary: This study centers on the RasGAP IqgC and RapA in adhesion regulation.
RasG's positive role in substratum adhesion is established more directly by
activated-RasG experiments, so this annotation is retained but treated as a
supporting, non-core adhesion role.
action: KEEP_AS_NON_CORE
reason: The cited paper primarily addresses IqgC/RapA; the positive regulation of
adhesion by active RasG is supported (activated RasG increases adhesion) but
the adhesion axis is one of several downstream RasG processes, retained as
non-core.
supported_by:
- reference_id: PMID:10906762
supporting_text: which causes cells to become significantly more adherent to
the substratum than are wild type cells
- term:
id: GO:1905301
label: regulation of macropinocytosis
evidence_type: IGI
original_reference_id: PMID:38888895
qualifier: involved_in
review:
summary: The Leep2A/Leep2B RasGAP complex fine-tunes Ras activity to control
macropinosome formation, placing RasG within the regulatory network of
macropinocytosis.
action: ACCEPT
reason: RasG activity is a central input controlling macropinocytosis; regulation
of macropinocytosis is a core aspect of RasG function.
supported_by:
- reference_id: PMID:38888895
supporting_text: At the center of this signaling network are Ras GTPases, whose
activation potently stimulates macropinocytosis
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:38888895
qualifier: enables
review:
summary: Captures binding between RasG and the Leep2 RasGAP complex. Bare protein
binding is uninformative; the meaningful relationship is that Leep2 acts as a
GAP on Ras GTPases including RasG.
action: KEEP_AS_NON_CORE
reason: Documents a real RasG-regulator (RasGAP) interaction but via an
uninformative term; retained as non-core.
supported_by:
- reference_id: PMID:38888895
supporting_text: it modulates macropinosome formation by regulating the
activities of three Ras family small GTPases
- term:
id: GO:0001891
label: phagocytic cup
evidence_type: IDA
original_reference_id: PMID:38263885
qualifier: located_in
review:
summary: Active RasG localizes to forming endocytic (macropinocytic/phagocytic)
cups, where it recruits the RasGAP IqgC. RasG marks the cup membrane during
large-scale endocytosis.
action: ACCEPT
reason: RasG is enriched at nascent endocytic cups, a core site of its action in
macropinocytosis/phagocytosis.
supported_by:
- reference_id: PMID:38263885
supporting_text: interaction with RasG is indispensable for the recruitment of
IqgC to forming macropinocytic cups
- term:
id: GO:0032880
label: regulation of protein localization
evidence_type: IMP
original_reference_id: PMID:38263885
qualifier: acts_upstream_of_or_within
review:
summary: Recruitment/loading of the RasGAP IqgC onto macropinosomes requires
RasG, so RasG controls the localization of this effector protein.
action: ACCEPT
reason: RasG governs the membrane recruitment of downstream partners (e.g. IqgC)
at endocytic structures; a genuine regulatory function.
supported_by:
- reference_id: PMID:38263885
supporting_text: its loading to macropinosomes is dependent on RasG
- term:
id: GO:0140986
label: G protein-coupled chemorepellent receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:34788129
qualifier: involved_in
review:
summary: The chemorepellent AprA locally inhibits Ras cortical activation acting
through, among others, RasG, to bias cell movement away from the source. RasG
participates in this chemorepulsion pathway.
action: KEEP_AS_NON_CORE
reason: RasG is a node in AprA chemorepulsion signaling, but this is a
context-specific developmental/behavioral role rather than a core RasG
function.
supported_by:
- reference_id: PMID:34788129
supporting_text: Ras protein RasG, protein kinase B, the p21-activated kinase
PakD, and the extracellular signal-regulated kinase Erk1
- term:
id: GO:0140986
label: G protein-coupled chemorepellent receptor signaling pathway
evidence_type: IGI
original_reference_id: PMID:30462573
qualifier: acts_upstream_of_or_within
review:
summary: Delineation of the AprA chemorepulsion pathway showed it uses a subset
of chemoattraction components including Ras. RasG contributes to chemorepellent
signaling.
action: KEEP_AS_NON_CORE
reason: Participation in AprA chemorepulsion is a specialized behavioral role,
retained as non-core.
supported_by:
- reference_id: PMID:30462573
supporting_text: AprA uses a subset of chemoattraction signal transduction
pathways including Ras, protein kinase A, target of rapamycin
- 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: During aggregation, cAMP acting via its GPCR triggers rapid, transient
RasG activation. RasG is thus part of chemoattractant-GPCR signaling, though
adenylyl cyclase (ACA) activation is more strongly dependent on the paralog
RasC.
action: KEEP_AS_NON_CORE
reason: RasG is activated downstream of the cAMP GPCR, but the adenylate
cyclase-modulating branch is predominantly a RasC function; retained as
non-core for RasG.
supported_by:
- reference_id: PMID:15143344
supporting_text: RasC and RasG showed a rapid and transient activation when
aggregation-competent cells were stimulated with the chemoattractant cAMP
- term:
id: GO:0051593
label: response to folic acid
evidence_type: IGI
original_reference_id: PMID:23132928
qualifier: involved_in
review:
summary: RasG (and RasC) are activated in response to folic acid and are required
for full Ras/PI3K responses during folate-directed migration of vegetative
cells.
action: ACCEPT
reason: Folate is the key vegetative chemoattractant and RasG is a core mediator
of the folic-acid response; a core function.
supported_by:
- reference_id: PMID:23132928
supporting_text: Ras and phosphoinositide 3-kinase activity were significantly
decreased in Ras G and Ras C/G nulls
- term:
id: GO:0140220
label: pathogen-containing vacuole
evidence_type: HDA
original_reference_id: PMID:18980612
qualifier: part_of
review:
summary: RasG was recovered in proteomic analyses of purified Legionella-
containing vacuoles, which are dominated by Arf/Rab GTPases. This is an
incidental co-purification during endocytic trafficking, not a dedicated RasG
role.
action: KEEP_AS_NON_CORE
reason: Bulk proteomic detection on a pathogen vacuole reflects membrane
trafficking; retained as non-core.
supported_by:
- reference_id: PMID:18980612
supporting_text: revealed 566 host proteins, including known LCV components,
such as the small GTPases Arf1, Rab1 and Rab7
- term:
id: GO:0003925
label: G protein activity
evidence_type: IDA
original_reference_id: PMID:15352238
qualifier: enables
review:
summary: Uses the constitutively activated (GTP-locked) RasG(G12T) to probe
downstream phosphorylation, consistent with RasG acting as an active G
protein/signal transducer.
action: ACCEPT
reason: RasG functions as a nucleotide-dependent G protein switch; a core
molecular function.
supported_by:
- reference_id: PMID:15352238
supporting_text: the effect of activated RasG, RasG(G12T), expression on the
phosphorylation state of Dictyostelium proteins
- term:
id: GO:0035014
label: phosphatidylinositol 3-kinase regulator activity
evidence_type: IMP
original_reference_id: PMID:23132928
qualifier: enables
review:
summary: Loss of RasG (and RasC/G) strongly reduces PI3K activity, demonstrating
that RasG is a positive regulator/activator of class I PI3K, its best-defined
effector.
action: ACCEPT
reason: RasG activation of PI3K to produce PIP3 is a central, directly-supported
core molecular function.
supported_by:
- reference_id: PMID:23132928
supporting_text: Ras and phosphoinositide 3-kinase activity were significantly
decreased in Ras G and Ras C/G nulls
- term:
id: GO:0050927
label: positive regulation of positive chemotaxis
evidence_type: IMP
original_reference_id: PMID:10725225
qualifier: involved_in
review:
summary: rasG disruption reduces motility and chemotactic behavior; RasG promotes
directed movement toward chemoattractants.
action: ACCEPT
reason: RasG positively promotes chemotaxis/motility, a core function.
supported_by:
- reference_id: PMID:10725225
supporting_text: a defect in cytokinesis, reduced motility and reduced growth
- term:
id: GO:0046587
label: positive regulation of calcium-dependent cell-cell adhesion
evidence_type: IMP
original_reference_id: PMID:16622066
qualifier: involved_in
review:
summary: Activated RasG increases DdCAD-1-dependent cell-cell cohesion during
early development by reducing DdCAD-1 phosphorylation and increasing its
surface localization. This is a developmental adhesion role.
action: KEEP_AS_NON_CORE
reason: RasG modulates DdCAD-1-mediated cell-cell adhesion during early
development, a specialized developmental process rather than the core RasG
function.
supported_by:
- reference_id: PMID:16622066
supporting_text: cells expressing RasG(G12T) exhibited increased cell-cell
cohesion, concomitant with reduced levels of DdCAD-1 phosphorylation
- term:
id: GO:0072697
label: protein localization to cell cortex
evidence_type: IMP
original_reference_id: PMID:16622066
qualifier: acts_upstream_of_or_within
review:
summary: Activated RasG increases localization of the adhesion molecule DdCAD-1
at the cell surface/cortex, so RasG influences cortical protein localization in
a developmental adhesion context.
action: KEEP_AS_NON_CORE
reason: This reflects RasG control of DdCAD-1 surface localization during early
development, a specialized non-core role.
supported_by:
- reference_id: PMID:16622066
supporting_text: was correlated with increased localization of DdCAD-1 at the
cell surface
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:10725225
qualifier: involved_in
review:
summary: rasG disruption causes a cytokinesis defect, one of the principal
phenotypes of rasG-null cells.
action: ACCEPT
reason: RasG is required for normal cytokinesis; a core function.
supported_by:
- reference_id: PMID:10725225
supporting_text: a defect in cytokinesis, reduced motility and reduced growth
- term:
id: GO:0051248
label: negative regulation of protein metabolic process
evidence_type: IDA
original_reference_id: PMID:10725225
qualifier: involved_in
review:
summary: RasG negatively regulates the levels of the paralogous RasD (and RasB)
protein in vegetative cells. This is a regulatory cross-talk between paralogs
rather than a broad protein-metabolism role.
action: KEEP_AS_NON_CORE
reason: The evidence supports RasG-dependent negative control of RasD/RasB
protein levels; retained under this broad term as non-core.
supported_by:
- reference_id: PMID:10725225
supporting_text: RasD protein levels are negatively regulated in vegetative
cells by RasG
- term:
id: GO:0019887
label: protein kinase regulator activity
evidence_type: IDA
original_reference_id: PMID:15534002
qualifier: enables
review:
summary: RasG activation stimulates PI3K and hence Akt/PKB activation. The direct
effector is PI3K (a lipid kinase); regulation of the protein kinase PKB is
downstream and indirect.
action: KEEP_AS_NON_CORE
reason: The precise, directly-supported effector MF is PI3K regulation
(GO:0035014); the more general protein kinase regulator activity is retained as
non-core.
supported_by:
- reference_id: PMID:15534002
supporting_text: chemoattractant-induced Akt/PKB activation was decreased in
rasG null cells
- term:
id: GO:0031252
label: cell leading edge
evidence_type: IDA
original_reference_id: PMID:15534002
qualifier: is_active_in
review:
summary: A GFP-RBD biosensor shows Ras activation localized to the leading edge
of chemotaxing cells, where RasG acts to establish the front.
action: ACCEPT
reason: RasG is activated at, and acts from, the cell leading edge; a core site
of action.
supported_by:
- reference_id: PMID:15534002
supporting_text: Ras activation occurs at the leading edge of chemotaxing cells
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction
evidence_type: IMP
original_reference_id: PMID:15534002
qualifier: involved_in
review:
summary: RasG activation is required for chemoattractant-induced PI3K/Akt(PKB)
activation; rasG-null cells show decreased Akt/PKB activation.
action: ACCEPT
reason: Positive regulation of PI3K/PKB signaling is a core downstream output of
RasG.
supported_by:
- reference_id: PMID:15534002
supporting_text: chemoattractant-induced Akt/PKB activation was decreased in
rasG null cells
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:8754814
qualifier: acts_upstream_of_or_within
review:
summary: Overexpression of activated rasG-G12T during growth blocks initiation of
development and represses early developmental genes (car1, pde). This is a
gain-of-function developmental effect.
action: KEEP_AS_NON_CORE
reason: The effect on early gene expression reflects a developmental consequence
of constitutive RasG activation rather than a core RasG function.
supported_by:
- reference_id: PMID:8754814
supporting_text: the expression of car1 and pde, genes that are normally
induced soon after the initiation of development, was repressed
- term:
id: GO:0003925
label: G protein activity
evidence_type: IDA
original_reference_id: PMID:17380187
qualifier: enables
review:
summary: RasG is directly shown to be activated (GTP-loaded) in response to cAMP,
acting as a G protein switch, with RasGEFR as its specific activator.
action: ACCEPT
reason: RasG acts as a nucleotide-dependent G protein/signal transducer; a core
molecular function.
supported_by:
- reference_id: PMID:17380187
supporting_text: During Dictyostelium development, RasC and RasG are activated
in response to cyclic AMP
- term:
id: GO:0140220
label: pathogen-containing vacuole
evidence_type: HDA
original_reference_id: PMID:28183814
qualifier: part_of
review:
summary: Comparative proteomics of Legionella-containing vacuoles highlighted the
small GTPase Rap1; RasG detection here is an incidental co-purification during
endocytic trafficking rather than a specific RasG function.
action: KEEP_AS_NON_CORE
reason: Bulk proteomic co-purification on a pathogen vacuole; retained as
non-core.
supported_by:
- reference_id: PMID:28183814
supporting_text: The small GTPase Rap1 was identified on D. discoideum LCVs
containing strain Lp02 but not the
- term:
id: GO:0044354
label: macropinosome
evidence_type: IDA
original_reference_id: PMID:27821733
qualifier: part_of
review:
summary: Active RasG is present on macropinosomes/endocytic cups where it
directly regulates the formin ForG during large-scale endocytosis.
action: ACCEPT
reason: The macropinosome membrane is a core site of RasG action in
macropinocytosis/phagocytosis.
supported_by:
- reference_id: PMID:27821733
supporting_text: ForG is directly regulated in large-scale endocytosis by RasB
and RasG, which are highly related to the human proto-oncogene KRas
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10473630
qualifier: enables
review:
summary: Captures the interaction of activated RasG with the Ras-interacting
protein RIP3 (RipA), an effector required for chemotaxis and cAMP signal relay.
Bare protein binding is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents a real RasG-effector interaction (RIP3/RipA) but via a
non-specific term; retained as non-core.
supported_by:
- reference_id: PMID:10473630
supporting_text: RIP3 preferentially interacts with an activated form of the
Dictyostelium Ras protein RasG, which itself is important for cell movement
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15194808
qualifier: enables
review:
summary: Relates to Phg2, an adhesion-linked serine/threonine kinase carrying a
Ras-binding domain. The interaction is captured by an uninformative protein
binding term.
action: KEEP_AS_NON_CORE
reason: Documents a Ras-effector (Phg2 RBD) association but via a non-specific
term; retained as non-core.
supported_by:
- reference_id: PMID:15194808
supporting_text: PHG2 encodes a novel serine/threonine kinase with a
ras-binding domain
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20089846
qualifier: enables
review:
summary: This study concerns a GbpD/Rap1/PI3K pathway controlling pseudopod
formation and cell-substrate adhesion; the associated interaction is captured
by an uninformative protein binding term.
action: KEEP_AS_NON_CORE
reason: Retained interaction annotation via a non-specific term in a Rap/PI3K
adhesion context; non-core.
supported_by:
- reference_id: PMID:20089846
supporting_text: Rap1 directly binds to the Ras binding domain of PI3K
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23135995
qualifier: enables
review:
summary: Captures the interaction with DydA (Daydreamer), an MRL-family Ras
effector required for directional sensing and cell motility. Bare protein
binding is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents a RasG-effector interaction (DydA) but via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:23135995
supporting_text: DydA is a putative Ras effector that is required for cell
polarization and directional movement during chemotaxis
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24986648
qualifier: enables
review:
summary: Captures binding of the NDR/LATS-homolog kinase NdrC to activated RasG
(and RasB), an interaction important for control of cell division. Bare protein
binding is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents a RasG-effector interaction (NdrC) via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:24986648
supporting_text: Further in vitro pull-down assays showed that NdrC binds RasG
and RasB, and to a lesser extent RasC and Rap1
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27172998
qualifier: enables
review:
summary: Relates to binding of Ras (and Rap1) to the TORC2 complex; in this study
the strongest Ras-TOR interaction is via the paralog RasC. The generic protein
binding term is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents Ras-TORC2 association via a non-specific term (the study
emphasizes RasC); retained as non-core.
supported_by:
- reference_id: PMID:27172998
supporting_text: Ras and Rap1 bind to and control TORC2 activity
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27821733
qualifier: enables
review:
summary: Captures binding of activated RasG (and RasB) to the Diaphanous-related
formin ForG, linking Ras signaling directly to actin assembly. Bare protein
binding is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents a RasG-effector interaction (ForG) via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:27821733
supporting_text: ForG is directly regulated in large-scale endocytosis by RasB
and RasG, which are highly related to the human proto-oncogene KRas
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:29109256
qualifier: enables
review:
summary: Relates to the RasGAP C2GAP1, a negative regulator of Ras signaling that
is recruited to the leading edge. Bare protein binding is uninformative.
action: KEEP_AS_NON_CORE
reason: Documents a RasG-regulator (RasGAP) interaction via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:29109256
supporting_text: C2GAP1, which localizes at the leading edge of chemotaxing
cells and is activated by and essential for GPCR-mediated Ras signaling
- term:
id: GO:0005525
label: GTP binding
evidence_type: IDA
original_reference_id: PMID:15143344
qualifier: enables
review:
summary: Direct assay of the GTP-bound (activated) form of RasG using a Raf1-RBD
pulldown demonstrates GTP binding.
action: ACCEPT
reason: GTP binding is a core molecular function directly demonstrated for RasG.
supported_by:
- reference_id: PMID:15143344
supporting_text: the Ras-binding domain (RBD) of mammalian Raf1 was capable of
binding to the activated form of RasG
- term:
id: GO:0005811
label: lipid droplet
evidence_type: HDA
original_reference_id: PMID:24036346
qualifier: part_of
review:
summary: RasG was recovered in proteomic characterization of Dictyostelium lipid
droplets. This is an incidental co-purification of a membrane-anchored protein,
not a dedicated lipid-droplet function.
action: KEEP_AS_NON_CORE
reason: Bulk proteomic detection on lipid droplets; retained as non-core.
supported_by:
- reference_id: PMID:24036346
supporting_text: Among the novel protein components are LdpA, a protein
specific to Dictyostelium, and Net4
- term:
id: GO:0005938
label: cell cortex
evidence_type: IDA
original_reference_id: PMID:24986648
qualifier: part_of
review:
summary: Activated RasG is a cortical/membrane-associated GTPase; the NdrC study
localizes Ras activity to the cortex in the context of cell-division control.
action: ACCEPT
reason: The cell cortex is a core site of RasG activity, consistent with its
membrane anchoring and leading-edge/cortical activation.
supported_by:
- reference_id: PMID:24986648
supporting_text: In cells lacking NdrC, the levels of activated RasB and RasG
are up-regulated
- term:
id: GO:0009898
label: cytoplasmic side of plasma membrane
evidence_type: IDA
original_reference_id: PMID:27821733
qualifier: is_active_in
review:
summary: RasG is prenylated and anchored to the cytoplasmic face of the plasma
membrane, from which it signals to effectors such as ForG.
action: ACCEPT
reason: Consistent with the lipid-anchored orientation of RasG at the inner
leaflet of the plasma membrane; a core localization.
supported_by:
- reference_id: PMID:27821733
supporting_text: ForG is directly regulated in large-scale endocytosis by RasB
and RasG, which are highly related to the human proto-oncogene KRas
- term:
id: GO:0010856
label: adenylate cyclase activator activity
evidence_type: IGI
original_reference_id: PMID:18180289
qualifier: enables
review:
summary: In doubly-disrupted rasC/rasG cells, adenylyl cyclase (ACA) signaling is
lost; however, ACA activation is predominantly a RasC-dependent process, with
RasG contributing largely to the chemotactic branch.
action: KEEP_AS_NON_CORE
reason: RasG contributes to cAMP-signaling pathways, but adenylyl cyclase
activation is chiefly a RasC role; retained as non-core for RasG.
supported_by:
- reference_id: PMID:18180289
supporting_text: RasG and RasC are the only two Ras subfamily proteins that
directly control these pathways
- term:
id: GO:0019900
label: kinase binding
evidence_type: IPI
original_reference_id: PMID:10473630
qualifier: enables
review:
summary: Relates to the RasG-RIP3(RipA) interaction. RIP3 is a Ras-interacting
protein involved in guanylyl cyclase-linked chemotaxis signaling; the kinase
binding term is only weakly informative here.
action: KEEP_AS_NON_CORE
reason: Documents a RasG partner interaction; the specific molecular meaning is
better captured as effector binding, so retained as non-core.
supported_by:
- reference_id: PMID:10473630
supporting_text: RIP3 preferentially interacts with an activated form of the
Dictyostelium Ras protein RasG, which itself is important for cell movement
- 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-null
cells, identifying RasG/RasC as the presumptive GTPases required, in a
developmental cAMP-signaling context.
action: KEEP_AS_NON_CORE
reason: RasG contributes to guanylyl cyclase activation in the aggregation-stage
cAMP pathway; a developmental-signaling role retained as non-core.
supported_by:
- reference_id: PMID:18180289
supporting_text: in vitro guanylyl cyclase activation is also abolished in the
rasC
- term:
id: GO:0030250
label: guanylate cyclase activator activity
evidence_type: IGI
original_reference_id: PMID:18180289
qualifier: enables
review:
summary: Same finding via genetic interaction; guanylyl cyclase activation
requires RasG/RasC during aggregation.
action: KEEP_AS_NON_CORE
reason: Developmental cAMP-pathway contribution; retained as non-core.
supported_by:
- reference_id: PMID:18180289
supporting_text: identifies RasG/RasC as the presumptive monomeric GTPases
required for this activation
- term:
id: GO:0031982
label: vesicle
evidence_type: IDA
original_reference_id: PMID:19589376
qualifier: part_of
review:
summary: RasG was reported among proteins of Dictyostelium-released nanovesicles,
a preparation dominated by actin and actin-related proteins. This is an
incidental co-purification.
action: KEEP_AS_NON_CORE
reason: Bulk proteomic detection in released vesicles; not a core RasG function.
supported_by:
- reference_id: PMID:19589376
supporting_text: A proteomic analysis reveals a predominance of actin and
actin-related proteins
- term:
id: GO:0043130
label: ubiquitin binding
evidence_type: IDA
original_reference_id: PMID:24338482
qualifier: enables
review:
summary: This study shows that activated RasG is itself targeted for degradation
by polyubiquitination at K-Ras-equivalent C-terminal lysines. Being a substrate
of ubiquitination is not the same as possessing a ubiquitin-binding molecular
function.
action: MARK_AS_OVER_ANNOTATED
reason: The evidence demonstrates that RasG is polyubiquitinated (a substrate),
which does not support a ubiquitin-binding molecular function; the term appears
to over-interpret a modification event.
supported_by:
- reference_id: PMID:24338482
supporting_text: RasG, the Dictyostelium orthologue of K-Ras, is targeted for
degradation by polyubiquitination
- term:
id: GO:0043548
label: phosphatidylinositol 3-kinase binding
evidence_type: IPI
original_reference_id: PMID:23843627
qualifier: enables
review:
summary: Binding assays show RasG interacts most strongly with PI3K1/2 and PI3K4,
directly engaging its principal effector, class I PI3-kinase.
action: ACCEPT
reason: Direct binding of GTP-RasG to PI3K is a core, mechanistically informative
molecular function underlying macropinocytosis and chemotaxis.
supported_by:
- reference_id: PMID:23843627
supporting_text: RasG and RasS interact most strongly with PI3K1/2 and PI3K4
- term:
id: GO:0045335
label: phagocytic vesicle
evidence_type: HDA
original_reference_id: PMID:16926386
qualifier: part_of
review:
summary: RasG was among the many signal-transduction proteins detected by
proteomic fingerprinting of maturing Dictyostelium phagosomes. Consistent with
a role in phagocytosis, though the detection itself is high-throughput.
action: KEEP_AS_NON_CORE
reason: Proteomic detection on phagosomes supports involvement in phagocytosis
but is an incidental localization here; retained as non-core.
supported_by:
- reference_id: PMID:16926386
supporting_text: we identified 179 phagosomal proteins in the amoeba
Dictyostelium, including components of signal transduction, membrane traffic,
and the cytoskeleton
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:15534002
qualifier: is_active_in
review:
summary: Direct imaging shows GFP-RasG along the plasma membrane and Ras activity
(GFP-RBD) at the plasma membrane/leading edge upon stimulation.
action: ACCEPT
reason: RasG acts at the plasma membrane; a core localization directly supported.
supported_by:
- reference_id: PMID:15534002
supporting_text: GFP-RasG displayed uniform localization along the plasma
membrane and cytosol
- term:
id: GO:0044351
label: macropinocytosis
evidence_type: IMP
original_reference_id: PMID:30967009
qualifier: acts_upstream_of_or_within
review:
summary: Genetic analysis identifies RasG (with RasS) as a key Ras protein
driving macropinocytosis, which is stimulated by persistent Ras activation.
action: ACCEPT
reason: RasG is a core driver of macropinocytosis.
supported_by:
- reference_id: PMID:30967009
supporting_text: macropinocytosis is stimulated by persistent Ras activation and
genetic analysis suggests that RasG and RasS are the key Ras proteins involved
- term:
id: GO:1901262
label: negative regulation of sorocarp spore cell differentiation
evidence_type: IMP
original_reference_id: PMID:11222145
qualifier: acts_upstream_of_or_within
review:
summary: Developmental expression of activated rasG in prespore cells causes their
transdifferentiation into prestalk cells, altering cell fate. This is a
gain-of-function developmental effect.
action: KEEP_AS_NON_CORE
reason: Reflects a developmental cell-fate consequence of activated RasG rather
than a core RasG molecular function; retained as non-core.
supported_by:
- reference_id: PMID:11222145
supporting_text: the expression of activated rasG in prespore cells results in
their transdifferentiation into prestalk cells
- term:
id: GO:0006909
label: phagocytosis
evidence_type: IMP
original_reference_id: PMID:10906762
qualifier: acts_upstream_of_or_within
review:
summary: Expression of activated RasG reduces bacterial engulfment (phagocytosis)
when cells are adhered, indicating RasG regulates phagocytosis.
action: ACCEPT
reason: RasG regulates phagocytosis, a core RasG-dependent uptake process closely
related to macropinocytosis.
supported_by:
- reference_id: PMID:10906762
supporting_text: engulf fewer bacteria on filter surfaces, indicating a defect
in phagocytosis when cells are adhered
- term:
id: GO:0046847
label: filopodium assembly
evidence_type: IMP
original_reference_id: PMID:10906762
qualifier: acts_upstream_of_or_within
review:
summary: RasG activity influences filopodial number; activated RasG dramatically
reduces filopodia, and rasG-null cells show abnormal, excessive filopodia,
indicating RasG regulates filopodium formation.
action: ACCEPT
reason: RasG regulates filopodium/actin-protrusion assembly, a core cytoskeletal
function.
supported_by:
- reference_id: PMID:10906762
supporting_text: The expression of the activated RasG also dramatically reduces
the number of filopodia on the cell surface
- term:
id: GO:0007015
label: actin filament organization
evidence_type: IMP
original_reference_id: PMID:9245789
qualifier: acts_upstream_of_or_within
review:
summary: rasG-null cells show a wide range of actin cytoskeleton defects including
loss of polarity, absence of normal lamellipodia and aberrant filopodia,
establishing RasG as a regulator of actin organization.
action: ACCEPT
reason: Control of the actin cytoskeleton is a principal, core function of RasG.
supported_by:
- reference_id: PMID:9245789
supporting_text: they exhibit defective cell movement and a wide range of
defects in the control of the actin cytoskeleton, including a loss of cell
polarity, absence of normal lamellipodia
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:30622175
qualifier: enables
review:
summary: Captures binding of the RasGAP IqgC to active RasG. Bare protein binding
is uninformative; the meaningful relationship is that IqgC is a RasG-specific
GAP.
action: KEEP_AS_NON_CORE
reason: Documents a RasG-regulator (RasGAP) interaction via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:30622175
supporting_text: IqgC interacts with active RasG and exhibits RasGAP activity
toward this GTPase
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27009206
qualifier: enables
review:
summary: Relates to GflB, a RacE-binding protein with Ras GEF and Rho GAP domains
that sharpens Ras activity at the leading edge. The interaction is captured by
an uninformative protein binding term.
action: KEEP_AS_NON_CORE
reason: Documents a Ras-regulator (GflB) interaction via a non-specific term;
retained as non-core.
supported_by:
- reference_id: PMID:27009206
supporting_text: GflB balances the activation of Ras and Rho GTPases, which
enables cells to precisely orient signaling events
- term:
id: GO:1905169
label: regulation of protein localization to phagocytic vesicle
evidence_type: IMP
original_reference_id: PMID:27821733
qualifier: acts_upstream_of_or_within
review:
summary: RasG directly regulates the formin ForG at endocytic cups, controlling
its recruitment/activity during phagocytosis and macropinocytosis.
action: ACCEPT
reason: RasG governs recruitment of actin-assembly machinery to phagocytic/
macropinocytic vesicles; a core function at endocytic structures.
supported_by:
- reference_id: PMID:27821733
supporting_text: ForG is directly regulated in large-scale endocytosis by RasB
and RasG, which are highly related to the human proto-oncogene KRas
- term:
id: GO:0051591
label: response to cAMP
evidence_type: IDA
original_reference_id: PMID:2049874
qualifier: involved_in
review:
summary: An early characterization of Dictyostelium ras genes noting DdrasG
expression in vegetative cells and early development. Support for a specific
cAMP-response molecular role is limited in this reference.
action: KEEP_AS_NON_CORE
reason: RasG is activated in response to cAMP during aggregation (better
established by later work); this early reference supports developmental
expression, retained as non-core.
supported_by:
- reference_id: PMID:2049874
supporting_text: DdrasG is expressed in vegetative cells and during early
development
- term:
id: GO:0019954
label: asexual reproduction
evidence_type: IGI
original_reference_id: PMID:18180289
qualifier: acts_upstream_of_or_within
review:
summary: RasG/RasC control cAMP signaling required for the multicellular (asexual)
developmental cycle; captured under a broad life-cycle term.
action: KEEP_AS_NON_CORE
reason: Broad life-cycle term reflecting RasG's developmental-signaling
contribution; retained as non-core.
supported_by:
- reference_id: PMID:18180289
supporting_text: RasG and RasC are the only two Ras subfamily proteins that
directly control these pathways
- term:
id: GO:1903666
label: positive regulation of asexual reproduction
evidence_type: IMP
original_reference_id: PMID:10725225
qualifier: acts_upstream_of_or_within
review:
summary: RasG supports vegetative growth and cell division underlying asexual
reproduction; captured under a broad life-cycle term.
action: KEEP_AS_NON_CORE
reason: Broad life-cycle term reflecting RasG's role in growth/division; retained
as non-core.
supported_by:
- reference_id: PMID:10725225
supporting_text: a defect in cytokinesis, reduced motility and reduced growth
- term:
id: GO:0043326
label: chemotaxis to folate
evidence_type: IMP
original_reference_id: PMID:24742374
qualifier: acts_upstream_of_or_within
review:
summary: RasG is required for optimal folate chemotaxis, particularly in weak
gradients, in both axenic and bacterially grown cells.
action: ACCEPT
reason: Folate chemotaxis is a core vegetative behavior of RasG.
supported_by:
- reference_id: PMID:24742374
supporting_text: Both axenic and bacterially grown cells require RasG for
optimal folate chemotaxis, particularly in weak gradients
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:20833893
qualifier: acts_upstream_of_or_within
review:
summary: Cytokinesis is one of three distinct RasG functions in vegetative cells;
RasD can fully substitute for RasG in cytokinesis but RasC cannot.
action: ACCEPT
reason: RasG is required for cytokinesis; a core function.
supported_by:
- reference_id: PMID:20833893
supporting_text: RasD is capable of totally substituting for RasG for
cytokinesis and growth in suspension
- term:
id: GO:0043326
label: chemotaxis to folate
evidence_type: IMP
original_reference_id: PMID:20833893
qualifier: acts_upstream_of_or_within
review:
summary: Folate chemotaxis is a distinct RasG function; RasC can partially, but
RasD cannot, substitute for RasG in folate chemotaxis.
action: ACCEPT
reason: RasG is a core mediator of folate chemotaxis.
supported_by:
- reference_id: PMID:20833893
supporting_text: for chemotaxis to folate, RasC is capable of partially
substituting for RasG, but RasD is totally without effect
- term:
id: GO:0044351
label: macropinocytosis
evidence_type: IMP
original_reference_id: PMID:23843627
qualifier: acts_upstream_of_or_within
review:
summary: Single rasG mutants have severe macropinocytosis defects; RasG works
with PI3K1/2 and PI3K4 to drive macropinocytosis.
action: ACCEPT
reason: RasG is a core driver of macropinocytosis through PI3K.
supported_by:
- reference_id: PMID:23843627
supporting_text: single mutants of either Ras have severe macropinocytosis
defects
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IGI
original_reference_id: PMID:18180289
qualifier: acts_upstream_of_or_within
review:
summary: RasG is required for cAMP chemotactic signaling during aggregation;
cAMP-driven chemotaxis is abolished in rasC/rasG-null cells.
action: ACCEPT
reason: RasG is the more important Ras for cAMP chemotaxis; a core chemotactic
function.
supported_by:
- reference_id: PMID:18180289
supporting_text: there was negligible signaling through both the cAMP
chemotactic pathway and the adenylyl cyclase activation pathway
- 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: RasG positively regulates PI3K/PKB signaling downstream of cAMP; Rap1
activation (downstream of PI3K-linked signaling) is abolished in rasG-null
cells.
action: ACCEPT
reason: Positive regulation of PI3K/PKB signaling is a core downstream output of
RasG.
supported_by:
- reference_id: PMID:18180289
supporting_text: Rap1 activation was totally abolished in
- 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: rasG inactivation delays aggregation and reduces early gene expression,
showing RasG contributes to the aggregation stage of development.
action: KEEP_AS_NON_CORE
reason: RasG participates in developmental aggregation, a specialized
developmental process rather than a core vegetative function.
supported_by:
- reference_id: PMID:16885420
supporting_text: Insertional inactivation of the rasG gene resulted in delayed
aggregation and a partial inhibition of early gene expression
- 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: Comparison of rasG-, rasC- and rasC-rasG- strains shows overlapping Ras
contributions to aggregation; RasG participates in the aggregation stage.
action: KEEP_AS_NON_CORE
reason: Developmental aggregation role; retained as non-core.
supported_by:
- reference_id: PMID:16885420
supporting_text: Insertional inactivation of the rasG gene resulted in delayed
aggregation and a partial inhibition of early gene expression
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IMP
original_reference_id: PMID:16885420
qualifier: acts_upstream_of_or_within
review:
summary: Signal transduction through RasG is more important than RasC for cAMP
chemotaxis; chemotaxis is reduced in rasG-null cells.
action: ACCEPT
reason: RasG is a core mediator of cAMP chemotaxis.
supported_by:
- reference_id: PMID:16885420
supporting_text: signal transduction through RasG is more important in
chemotaxis and early gene expression
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IGI
original_reference_id: PMID:16885420
qualifier: acts_upstream_of_or_within
review:
summary: Genetic comparison confirms RasG is the predominant Ras for cAMP
chemotaxis, with partial functional overlap with RasC.
action: ACCEPT
reason: RasG is a core mediator of cAMP chemotaxis.
supported_by:
- reference_id: PMID:16885420
supporting_text: Both chemotaxis and ACA activation were reduced in the rasG-
cells, but the effect on chemotaxis was more pronounced
- 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: RasG signaling positively contributes to the chemotactic (PI3K/PKB) arm
of the cAMP response during aggregation.
action: ACCEPT
reason: Positive regulation of PI3K/PKB signaling is a core downstream output of
RasG.
supported_by:
- reference_id: PMID:16885420
supporting_text: signal transduction through RasG is more important in
chemotaxis and early gene expression
- 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 data support RasG positively regulating the
chemotactic PI3K/PKB branch of cAMP signaling.
action: ACCEPT
reason: Positive regulation of PI3K/PKB signaling is a core downstream output of
RasG.
supported_by:
- reference_id: PMID:16885420
supporting_text: Both chemotaxis and ACA activation were reduced in the rasG-
cells, but the effect on chemotaxis was more pronounced
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:16822579
qualifier: acts_upstream_of_or_within
review:
summary: In studies of motility and SCAR localization across strains, Ras protein
knockouts (including rasG) produce phenotypes during vegetative growth,
consistent with the established RasG cytokinesis requirement.
action: ACCEPT
reason: RasG is required for cytokinesis (well established across multiple
studies); a core function.
supported_by:
- reference_id: PMID:9245789
supporting_text: rasG- cells are unable to perform normal cytokinesis,
becoming multinucleate when grown in suspension culture
- term:
id: GO:0000902
label: cell morphogenesis
evidence_type: IMP
original_reference_id: PMID:16822579
qualifier: acts_upstream_of_or_within
review:
summary: Ras (including rasG) mutations alter cell morphology/motility during
vegetative growth, consistent with RasG control of cell shape via the actin
cytoskeleton.
action: ACCEPT
reason: RasG shapes cell morphology through actin/polarity control; a core
function (loss of polarity and abnormal shape in rasG-null cells).
supported_by:
- reference_id: PMID:16822579
supporting_text: knockouts of members of the SCAR complex and Ras proteins,
cause different phenotypes during vegetative growth in different parental
strains
- term:
id: GO:0031589
label: cell-substrate adhesion
evidence_type: IMP
original_reference_id: PMID:16822579
qualifier: acts_upstream_of_or_within
review:
summary: Consistent with RasG's established role in substratum adhesion; Ras
mutants show altered vegetative-growth phenotypes including adhesion/motility
behavior.
action: ACCEPT
reason: RasG regulates cell-substratum adhesion; a core function supported most
directly by activated-RasG adhesion experiments.
supported_by:
- reference_id: PMID:10906762
supporting_text: which causes cells to become significantly more adherent to
the substratum than are wild type cells
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:10473630
title: A novel Ras-interacting protein required for chemotaxis and cyclic adenosine
monophosphate signal relay in Dictyostelium.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; RIP3/RipA preferentially binds activated RasG and
links chemotaxis and cAMP signal relay.
- id: PMID:10725225
title: Functional overlap of the dictyostelium RasG, RasD and RasB proteins.
findings: []
- id: PMID:10906762
title: Mediation of cell-substratum adhesion by RasG in Dictyostelium.
findings: []
- id: PMID:11222145
title: Expression of activated Ras during Dictyostelium development alters cell
localization and changes cell fate.
findings: []
- id: PMID:15143344
title: Chemoattractant-induced Ras activation during Dictyostelium aggregation.
findings: []
- id: PMID:15194808
title: Phg2, a kinase involved in adhesion and focal site modeling in Dictyostelium.
findings: []
- id: PMID:15352238
title: The identification of Dictyostelium phosphoproteins altered in response to
the activation of RasG.
findings: []
- id: PMID:15534002
title: Localized Ras signaling at the leading edge regulates PI3K, cell polarity,
and directional cell movement.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified full text; establishes leading-edge RasG activation
driving PI3K and directional movement (GFP-RasG plasma membrane localization,
reduced Akt/PKB in rasG null).
- id: PMID:16622066
title: An activated Ras protein alters cell adhesion by dephosphorylating Dictyostelium
DdCAD-1.
findings: []
- id: PMID:16822579
title: Cell motility and SCAR localisation in axenically growing Dictyostelium cells.
findings: []
- 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: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; RasG is more important for cAMP chemotaxis and
early gene expression while RasC is more important for adenylyl cyclase
activation.
- id: PMID:16926386
title: Proteomics fingerprinting of phagosome maturation and evidence for the role
of a Galpha during uptake.
findings: []
- id: PMID:17380187
title: 'Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras
pathways using specific RasGEFs.'
findings: []
- id: PMID:18180289
title: Rap1 activation in response to cAMP occurs downstream of ras activation during
Dictyostelium aggregation.
findings: []
- id: PMID:18980612
title: Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation
reveals secretory and endosomal GTPases.
findings: []
- id: PMID:19589376
title: 'Nanovesicles released by Dictyostelium cells: a potential carrier for drug
delivery.'
findings: []
- id: PMID:20089846
title: A Rap/phosphatidylinositol 3-kinase pathway controls pseudopod formation
[corrected].
findings: []
- id: PMID:2049874
title: Ras-related genes in Dictyostelium discoideum.
findings: []
- id: PMID:20833893
title: Ras proteins have multiple functions in vegetative cells of Dictyostelium.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; defines three distinct non-overlapping RasG
functions in vegetative cells (cytokinesis, folate chemotaxis, actin/random
motility).
- id: PMID:23132928
title: Delineating the core regulatory elements crucial for directed cell migration
by examining folic-acid-mediated responses.
findings: []
- id: PMID:23135995
title: Daydreamer, a Ras effector and GSK-3 substrate, is important for directional
sensing and cell motility.
findings: []
- id: PMID:23843627
title: Two distinct functions for PI3-kinases in macropinocytosis.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; RasG binds PI3K1/2 and PI3K4, and single rasG
mutants have severe macropinocytosis defects.
- id: PMID:24036346
title: Dictyostelium lipid droplets host novel proteins.
findings: []
- id: PMID:24338482
title: Degradation of activated K-Ras orthologue via K-Ras-specific lysine residues
is required for cytokinesis.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: PubMed-verified; shows RasG is polyubiquitinated/degraded (a
substrate), which does not support a ubiquitin-binding molecular function.
- id: PMID:24742374
title: RasG signaling is important for optimal folate chemotaxis in Dictyostelium.
findings: []
- id: PMID:24986648
title: Regulation of a LATS-homolog by Ras GTPases is important for the control
of cell division.
findings: []
- id: PMID:27009206
title: The novel RacE-binding protein GflB sharpens Ras activity at the leading
edge of migrating cells.
findings: []
- id: PMID:27172998
title: The small GTPases Ras and Rap1 bind to and control TORC2 activity.
findings: []
- id: PMID:27821733
title: A Diaphanous-related formin links Ras signaling directly to actin assembly
in macropinocytosis and phagocytosis.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; RasG (and RasB) directly regulate the formin ForG
at endocytic cups, linking Ras to actin assembly in large-scale endocytosis.
- id: PMID:28183814
title: Comparative Proteomics of Purified Pathogen Vacuoles Correlates Intracellular
Replication of Legionella pneumophila with the Small GTPase Ras-related protein
1 (Rap1).
findings: []
- id: PMID:29109256
title: GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally
inhibits Ras signaling for adaptation and long-range chemotaxis.
findings: []
- id: PMID:30462573
title: An endogenous chemorepellent directs cell movement by inhibiting pseudopods
at one side of cells.
findings: []
- id: PMID:30622175
title: IQGAP-related protein IqgC suppresses Ras signaling during large-scale endocytosis.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; IqgC is a RasG-specific GAP that interacts with
active RasG during macropinocytosis and phagocytosis.
- id: PMID:30967009
title: Function of small GTPases in Dictyostelium macropinocytosis.
findings: []
- id: PMID:34788129
title: A chemorepellent inhibits local Ras activation to inhibit pseudopod formation
to bias cell movement away from the chemorepellent.
findings: []
- id: PMID:38263885
title: IqgC is a potent regulator of macropinocytosis in the presence of NF1 and
its loading to macropinosomes is dependent on RasG.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified; RasG is a major regulator of macropinocytosis and
recruits IqgC to forming macropinocytic cups.
- id: PMID:38888895
title: Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome
formation.
findings: []
- id: PMID:39458259
title: 'Francisella novicida-Containing Vacuole within Dictyostelium discoideum:
Isolation and Proteomic Characterization.'
findings: []
- id: PMID:39789437
title: The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium
discoideum.
findings: []
- id: PMID:40934557
title: The Ras association domain of DydA as a specific reporter of activated RasG
in Dictyostelium.
findings: []
- id: PMID:8754814
title: Overexpression of an activated rasG gene during growth blocks the initiation
of Dictyostelium development.
findings: []
- id: PMID:9245789
title: Dictyostelium RasG is required for normal motility and cytokinesis, but not
growth.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified full text; rasG-null cells have defective motility,
actin/polarity defects, and fail cytokinesis (become multinucleate in
suspension).
- id: PMID:9551080
title: Negative influence of RasG on chemoattractant-induced ERK2 phosphorylation
in Dictyostelium.
findings: []
core_functions:
- description: RasG is a plasma-membrane-anchored Ras small GTPase that acts as a
nucleotide-dependent molecular switch. Upon chemoattractant (folate/cAMP)
stimulation it is rapidly and transiently loaded with GTP at the cell cortex and
leading edge, where active RasG transduces the signal to downstream effectors;
its intrinsic GTPase activity (accelerated by RasGAPs such as IqgC, C2GAP1,
Leep2 and NF1) resets the switch.
molecular_function:
id: GO:0003925
label: G protein activity
locations:
- id: GO:0005886
label: plasma membrane
- id: GO:0031252
label: cell leading edge
- id: GO:0009898
label: cytoplasmic side of plasma membrane
directly_involved_in:
- id: GO:0007264
label: small GTPase-mediated signal transduction
supported_by:
- reference_id: PMID:15534002
supporting_text: Ras is rapidly and transiently activated in response to
chemoattractant stimulation and regulates PI3K activity
- reference_id: PMID:15143344
supporting_text: the Ras-binding domain (RBD) of mammalian Raf1 was capable of
binding to the activated form of RasG
- description: Active GTP-RasG binds and activates class I phosphatidylinositol
3-kinase (PI3K1/2, PI3K4), generating a localized PIP3 patch at the leading
edge/cortex that drives F-actin-based pseudopod formation, directional sensing
and PKB(Akt) activation. This RasG-PI3K axis underlies chemotaxis (to folate and
cAMP), random motility, cell polarity and macropinocytosis.
molecular_function:
id: GO:0035014
label: phosphatidylinositol 3-kinase regulator activity
locations:
- id: GO:0031252
label: cell leading edge
- id: GO:0044354
label: macropinosome
directly_involved_in:
- id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction
supported_by:
- reference_id: PMID:23132928
supporting_text: Ras and phosphoinositide 3-kinase activity were significantly
decreased in Ras G and Ras C/G nulls
- reference_id: PMID:15534002
supporting_text: chemoattractant-induced Akt/PKB activation was decreased in
rasG null cells
- description: RasG directly engages effectors that couple its activation to actin
remodeling and bulk endocytosis, most prominently binding class I PI3-kinases and
directly regulating the Diaphanous-related formin ForG at endocytic cups. Through
these effectors RasG is a principal driver of macropinocytosis and phagocytosis
and of the actin reorganization required for cytokinesis and cell motility.
molecular_function:
id: GO:0043548
label: phosphatidylinositol 3-kinase binding
locations:
- id: GO:0044354
label: macropinosome
- id: GO:0001891
label: phagocytic cup
directly_involved_in:
- id: GO:0044351
label: macropinocytosis
supported_by:
- reference_id: PMID:23843627
supporting_text: RasG and RasS interact most strongly with PI3K1/2 and PI3K4
- reference_id: PMID:27821733
supporting_text: ForG is directly regulated in large-scale endocytosis by RasB
and RasG, which are highly related to the human proto-oncogene KRas