Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0007265 Ras protein signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0003924 GTPase activity	IBA GO_REF:0000033	ACCEPT	Summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0090398 cellular senescence	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cellular senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: Golgi membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0003924 GTPase activity	IEA GO_REF:0000120	ACCEPT	Summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0003925 G protein activity	IEA GO_REF:0000003	ACCEPT	Summary: G protein activity is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0005525 GTP binding	IEA GO_REF:0000120	ACCEPT	Summary: GTP binding is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005794 Golgi apparatus	IEA GO_REF:0000120	ACCEPT	Summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0007165 signal transduction	IEA GO_REF:0000002	MODIFY	Summary: Signal transduction is too broad for H-Ras. Reason: H-Ras is specifically a Ras-family small GTPase in Ras protein signal transduction. Proposed replacements: Ras protein signal transduction Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0016020 membrane	IEA GO_REF:0000002	MODIFY	Summary: Membrane is too broad for H-Ras localization. Reason: H-Ras signaling depends on processed and palmitoylated localization at plasma membrane and Golgi/endomembrane compartments. Proposed replacements: plasma membrane Golgi membrane Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005515 protein binding	IPI PMID:9488663 Identification of Nore1 as a potential Ras effector.	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005654 nucleoplasm	IEA GO_REF:0000120	UNDECIDED	Summary: The current local evidence does not provide term-specific support for H-Ras localization to the nucleoplasm. Reason: Automated localization transfer requires direct compartment evidence before retaining this annotation.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: cytosol is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-uniprot.txt DR GO; GO:0005829; C:cytosol; ISO:GO_Central. file:mouse/Hras/Hras-deep-research-falcon.md Nascent Ras proteins undergo processing in cytosol/ER and further modifications enabling targeting to the inner leaflet of the plasma membrane
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of transcription by RNA polymerase II is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007265 Ras protein signal transduction	IEA GO_REF:0000107	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0008285 negative regulation of cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0010629 negative regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of gene expression is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0019003 GDP binding	IEA GO_REF:0000107	ACCEPT	Summary: GDP binding is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0030335 positive regulation of cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of cell migration is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0032956 regulation of actin cytoskeleton organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of actin cytoskeleton organization is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0042127 regulation of cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043410 positive regulation of MAPK cascade	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of MAPK cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0046330 positive regulation of JNK cascade	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of JNK cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0050679 positive regulation of epithelial cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of epithelial cell proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of ERK1 and ERK2 cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0071480 cellular response to gamma radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to gamma radiation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090303 positive regulation of wound healing	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of wound healing is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090314 positive regulation of protein targeting to membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of protein targeting to membrane is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090398 cellular senescence	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of neurotransmitter receptor localization to postsynaptic specialization membrane is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: glutamatergic synapse is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0160185 phospholipase C activator activity	IEA GO_REF:0000107	UNDECIDED	Summary: The current local evidence supports RAF, PI3K, and RalGEF effector signaling, but does not establish phospholipase C activator activity for H-Ras. Reason: Retaining this specific molecular function requires direct PLC activation evidence.
GO:1900029 positive regulation of ruffle assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of ruffle assembly is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:2000630 positive regulation of miRNA metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of miRNA metabolic process is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005794 Golgi apparatus	ISO GO_REF:0000119	ACCEPT	Summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0000164 protein phosphatase type 1 complex	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: The PP1 complex term does not describe the H-Ras core function. Reason: H-Ras may influence or associate with regulatory complexes in particular studies, but the core function is membrane-localized GDP/GTP switch signaling. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0003924 GTPase activity	ISO GO_REF:0000119	ACCEPT	Summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0005525 GTP binding	ISO GO_REF:0000119	ACCEPT	Summary: GTP binding is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005654 nucleoplasm	ISO GO_REF:0000119	UNDECIDED	Summary: The current local evidence does not provide term-specific support for H-Ras localization to the nucleoplasm. Reason: Automated localization transfer requires direct compartment evidence before retaining this annotation.
GO:0005829 cytosol	ISO GO_REF:0000119	ACCEPT	Summary: cytosol is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-uniprot.txt DR GO; GO:0005829; C:cytosol; ISO:GO_Central. file:mouse/Hras/Hras-deep-research-falcon.md Nascent Ras proteins undergo processing in cytosol/ER and further modifications enabling targeting to the inner leaflet of the plasma membrane
GO:0005886 plasma membrane	ISO GO_REF:0000096	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0006357 regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of transcription by RNA polymerase II is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007265 Ras protein signal transduction	ISO GO_REF:0000119	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0008285 negative regulation of cell population proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0010629 negative regulation of gene expression	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of gene expression is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0019003 GDP binding	ISO GO_REF:0000119	ACCEPT	Summary: GDP binding is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0030335 positive regulation of cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cell migration is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0032956 regulation of actin cytoskeleton organization	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of actin cytoskeleton organization is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0036064 ciliary basal body	ISO GO_REF:0000119	UNDECIDED	Summary: The current local evidence does not provide term-specific support for H-Ras localization to the ciliary basal body. Reason: Automated localization transfer requires direct compartment evidence before retaining this annotation.
GO:0042127 regulation of cell population proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043410 positive regulation of MAPK cascade	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of MAPK cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0044877 protein-containing complex binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: protein-containing complex binding is too generic to represent the core H-Ras molecular function; the informative biology is GTPase switch activity and effector-pathway activation. Reason: Use GTPase/GTP binding and Ras pathway terms rather than retaining a broad binding term as core. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0046330 positive regulation of JNK cascade	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of JNK cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0050679 positive regulation of epithelial cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of epithelial cell proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0051726 regulation of cell cycle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of cell cycle is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of ERK1 and ERK2 cascade is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0071480 cellular response to gamma radiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to gamma radiation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090303 positive regulation of wound healing	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of wound healing is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090314 positive regulation of protein targeting to membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of protein targeting to membrane is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090398 cellular senescence	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of neurotransmitter receptor localization to postsynaptic specialization membrane is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0098978 glutamatergic synapse	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: glutamatergic synapse is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0160185 phospholipase C activator activity	ISO GO_REF:0000119	UNDECIDED	Summary: The current local evidence supports RAF, PI3K, and RalGEF effector signaling, but does not establish phospholipase C activator activity for H-Ras. Reason: Retaining this specific molecular function requires direct PLC activation evidence.
GO:1900029 positive regulation of ruffle assembly	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of ruffle assembly is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:1905360 GTPase complex	ISO GO_REF:0000119	ACCEPT	Summary: GTPase complex is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:2000630 positive regulation of miRNA metabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of miRNA metabolic process is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005886 plasma membrane	ISO PMID:19878719 RGS14 is a multifunctional scaffold that integrates G protei...	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0090402 oncogene-induced cell senescence	IDA PMID:11551927 The ink4a/arf tumor suppressors cooperate with p21cip1/waf i...	KEEP AS NON CORE	Summary: oncogene-induced cell senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043495 protein-membrane adaptor activity	IDA PMID:16405865 Merlin inhibits growth hormone-regulated Raf-ERKs pathways b...	KEEP AS NON CORE	Summary: protein-membrane adaptor activity is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0048009 insulin-like growth factor receptor signaling pathway	ISO PMID:8828504 Comparison of the insulin and insulin-like growth factor 1 m...	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0008286 insulin receptor signaling pathway	IDA PMID:7829473 Disassembly of Son-of-sevenless proteins from Grb2 during p2...	KEEP AS NON CORE	Summary: insulin receptor signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090398 cellular senescence	IDA PMID:12878730 The p53-dependent effects of macrophage migration inhibitory...	KEEP AS NON CORE	Summary: cellular senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0090398 cellular senescence	IDA PMID:15572682 Functional genetic screen for genes involved in senescence: ...	KEEP AS NON CORE	Summary: cellular senescence is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0014044 Schwann cell development	IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ...	KEEP AS NON CORE	Summary: Schwann cell development is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0042552 myelination	IMP PMID:10704452 A dual role of erbB2 in myelination and in expansion of the ...	KEEP AS NON CORE	Summary: myelination is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0042552 myelination	IMP PMID:18760695 Neuregulin-1/ErbB signaling serves distinct functions in mye...	KEEP AS NON CORE	Summary: myelination is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007265 Ras protein signal transduction	ISO PMID:33331896 Merlin cooperates with neurofibromin and Spred1 to suppress ...	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0038133 ERBB2-ERBB3 signaling pathway	ISO PMID:11173924 Neuregulin-induced association of Sos Ras exchange protein w...	KEEP AS NON CORE	Summary: ERBB2-ERBB3 signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043495 protein-membrane adaptor activity	ISO PMID:33331896 Merlin cooperates with neurofibromin and Spred1 to suppress ...	KEEP AS NON CORE	Summary: protein-membrane adaptor activity is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0060612 adipose tissue development	IMP PMID:31408278 Silencing of lncRNA SNHG20 delays the progression of nonalco...	KEEP AS NON CORE	Summary: adipose tissue development is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0048169 regulation of long-term neuronal synaptic plasticity	IMP PMID:12427827 SynGAP regulates ERK/MAPK signaling, synaptic plasticity, an...	KEEP AS NON CORE	Summary: regulation of long-term neuronal synaptic plasticity is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005515 protein binding	IPI PMID:16954213 Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0008284 positive regulation of cell population proliferation	IPI PMID:14712229 G-protein-coupled receptor-mediated activation of rap GTPase...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007265 Ras protein signal transduction	IGI PMID:11877426 Nerve growth factor-dependent activation of the small GTPase...	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0032729 positive regulation of type II interferon production	IMP PMID:21444916 H-ras and N-ras are dispensable for T-cell development and a...	KEEP AS NON CORE	Summary: positive regulation of type II interferon production is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0042088 T-helper 1 type immune response	IMP PMID:21444916 H-ras and N-ras are dispensable for T-cell development and a...	KEEP AS NON CORE	Summary: T-helper 1 type immune response is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0042832 defense response to protozoan	IMP PMID:21444916 H-ras and N-ras are dispensable for T-cell development and a...	KEEP AS NON CORE	Summary: defense response to protozoan is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0050852 T cell receptor signaling pathway	IMP PMID:21444916 H-ras and N-ras are dispensable for T-cell development and a...	KEEP AS NON CORE	Summary: T cell receptor signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005515 protein binding	IPI PMID:23382219 Structural basis for endosomal trafficking of diverse transm...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005886 plasma membrane	ISO PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG.	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005515 protein binding	IPI PMID:8939998 RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identifi...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005515 protein binding	IPI PMID:10869344 A novel RalGEF-like protein, RGL3, as a candidate effector f...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005515 protein binding	IPI PMID:18596699 Novel type of Ras effector interaction established between t...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0097193 intrinsic apoptotic signaling pathway	IGI PMID:16954213 Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric...	KEEP AS NON CORE	Summary: intrinsic apoptotic signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005515 protein binding	IPI PMID:15235600 RabGEF1 is a negative regulator of mast cell activation and ...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005794 Golgi apparatus	ISS GO_REF:0000024	ACCEPT	Summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005886 plasma membrane	ISS GO_REF:0000024	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0010628 positive regulation of gene expression	IDA PMID:21357543 Regulation of GATA-3 expression during CD4 lineage different...	KEEP AS NON CORE	Summary: positive regulation of gene expression is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0005886 plasma membrane	TAS Reactome:R-MMU-9029152	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005886 plasma membrane	TAS Reactome:R-NUL-1250468	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005886 plasma membrane	TAS Reactome:R-NUL-1250472	ACCEPT	Summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane
GO:0005515 protein binding	IPI PMID:18604197 IQGAP3 regulates cell proliferation through the Ras/ERK sign...	MARK AS OVER ANNOTATED	Summary: protein binding records a physical association but is too generic to describe the gene product function. Reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone protein binding function; more informative molecular and pathway terms capture the biology. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0005525 GTP binding	IDA PMID:18604197 IQGAP3 regulates cell proliferation through the Ras/ERK sign...	ACCEPT	Summary: GTP binding is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0097193 intrinsic apoptotic signaling pathway	IMP PMID:16954213 Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric...	KEEP AS NON CORE	Summary: intrinsic apoptotic signaling pathway is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0046579 positive regulation of Ras protein signal transduction	ISO PMID:19029245 The protein phosphatase 2A regulatory subunits B'beta and B'...	ACCEPT	Summary: positive regulation of Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:
GO:0008284 positive regulation of cell population proliferation	IDA PMID:16478791 APC inhibits ERK pathway activation and cellular proliferati...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043524 negative regulation of neuron apoptotic process	IDA PMID:10845775 Neurofibromin negatively regulates neurotrophin signaling th...	KEEP AS NON CORE	Summary: negative regulation of neuron apoptotic process is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0043524 negative regulation of neuron apoptotic process	IGI PMID:10845775 Neurofibromin negatively regulates neurotrophin signaling th...	KEEP AS NON CORE	Summary: negative regulation of neuron apoptotic process is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007264 small GTPase-mediated signal transduction	IDA PMID:14712229 G-protein-coupled receptor-mediated activation of rap GTPase...	MODIFY	Summary: Small GTPase-mediated signaling is correct but less specific than Ras signaling for Hras. Reason: The mouse gene encodes H-Ras, so the Ras protein signal transduction term is more specific. Proposed replacements: Ras protein signal transduction Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch.
GO:0006897 endocytosis	IDA PMID:12446704 Small GTPase Rah/Rab34 is associated with membrane ruffles a...	KEEP AS NON CORE	Summary: endocytosis is a supported downstream or specialized H-Ras context. Reason: This term reflects a cell-type, disease-model, developmental, transcriptional, or phenotypic consequence of Ras signaling rather than the primary switch function. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes
GO:0007265 Ras protein signal transduction	TAS PMID:10871846 Targeted deletion of the H-ras gene decreases tumor formatio...	ACCEPT	Summary: Ras protein signal transduction is consistent with core H-Ras switch activity, effector signaling, or localization. Reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization, or immediate Ras effector pathway output. Supporting Evidence: file:mouse/Hras/Hras-deep-research-falcon.md Active (GTP-bound) HRas recruits and activates multiple effector classes:

Core Functions

Functions as a Ras-family GDP/GTP molecular switch with intrinsic and GAP-stimulated GTPase activity.

Molecular Function:

GTPase activity

Directly Involved In:

Ras protein signal transduction

Cellular Locations:

plasma membrane Golgi membrane

Supporting Evidence:

file:mouse/Hras/Hras-deep-research-falcon.md
Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase** that acts as a **signal-transducing molecular switch**.

In the GTP-bound state, recruits RAF and other effectors to activate downstream MAPK, PI3K, and RalGEF signaling arms.

Molecular Function:

GTPase activity

Directly Involved In:

positive regulation of MAPK cascade positive regulation of ERK1 and ERK2 cascade

Cellular Locations:

plasma membrane

Supporting Evidence:

file:mouse/Hras/Hras-deep-research-falcon.md
Active (GTP-bound) HRas recruits and activates multiple effector classes:

Uses CAAX processing and reversible palmitoylation to cycle between Golgi and plasma membrane signaling compartments.

Molecular Function:

GTPase activity

Directly Involved In:

Ras protein signal transduction

Cellular Locations:

plasma membrane Golgi apparatus

Supporting Evidence:

file:mouse/Hras/Hras-deep-research-falcon.md
dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the **plasma membrane**

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10704452

A dual role of erbB2 in myelination and in expansion of the schwann cell precursor pool.

PMID:10845775

Neurofibromin negatively regulates neurotrophin signaling through p21ras in embryonic sensory neurons.

PMID:10869344

A novel RalGEF-like protein, RGL3, as a candidate effector for rit and Ras.

PMID:10871846

Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis.

PMID:11173924

Neuregulin-induced association of Sos Ras exchange protein with HER2(erbB2)/HER3(erbB3) receptor complexes in Schwann cells through a specific Grb2-HER2(erbB2) interaction.

PMID:11551927

The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis.

PMID:11877426

Nerve growth factor-dependent activation of the small GTPase Rin.

PMID:12427827

SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor.

PMID:12446704

Small GTPase Rah/Rab34 is associated with membrane ruffles and macropinosomes and promotes macropinosome formation.

PMID:12878730

The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.

PMID:14712229

G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway.

PMID:15235600

RabGEF1 is a negative regulator of mast cell activation and skin inflammation.

PMID:15572682

Functional genetic screen for genes involved in senescence: role of Tid1, a homologue of the Drosophila tumor suppressor l(2)tid, in senescence and cell survival.

PMID:16405865

Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein.

PMID:16478791

APC inhibits ERK pathway activation and cellular proliferation induced by RAS.

PMID:16954213

Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell death.

PMID:17724343

Spatial regulation of Raf kinase signaling by RKTG.

PMID:18596699

Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II.

PMID:18604197

IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade.

PMID:18760695

Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system.

PMID:19029245

The protein phosphatase 2A regulatory subunits B'beta and B'delta mediate sustained TrkA neurotrophin receptor autophosphorylation and neuronal differentiation.

PMID:19878719

RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways.

PMID:21357543

Regulation of GATA-3 expression during CD4 lineage differentiation.

PMID:21444916

H-ras and N-ras are dispensable for T-cell development and activation but critical for protective Th1 immunity.

PMID:23382219

Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.

PMID:31408278

Silencing of lncRNA SNHG20 delays the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma via regulating liver Kupffer cells polarization.

PMID:33331896

Merlin cooperates with neurofibromin and Spred1 to suppress the Ras-Erk pathway.

PMID:7829473

Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desensitization by insulin.

PMID:8828504

Comparison of the insulin and insulin-like growth factor 1 mitogenic intracellular signaling pathways.

PMID:8939998

RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG.

PMID:9488663

Identification of Nore1 as a potential Ras effector.

Reactome:R-MMU-9029152

Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2:p-Y-Crkl:p-Y-Shc1:Grb2-1:Sos1,p-Y-Vav1 mediates exchange of GDP for GTP bound to Ras

Reactome:R-NUL-1250468

Ras guanyl-nucleotide exchange mediated by Sos1 in complex with GRB2 and P-Erbb2mut

Reactome:R-NUL-1250472

Ras guanyl-nucleotide exchange mediated by Sos1 bound to GRB2 in complex with P-Shc1:P-Erbb2mut

file:mouse/Hras/Hras-deep-research-falcon.md

Falcon deep research summary for mouse Hras

Suggested Experiments

Experiment: Quantitatively compare wild-type and palmitoylation-defective H-Ras rescue in Hras/Nras-deficient mouse cells for RAF, PI3K, and RalGEF pathway activation.

Hypothesis: H-Ras pathway output depends on Golgi-plasma membrane cycling and cannot be inferred from generic cytosolic Ras activity.

Type: Allelic rescue and pathway phosphoproteomics

Deep Research

Falcon

(Hras-deep-research-falcon.md)

Research Report: Mouse **Hras** (UniProt **Q61411**) — Functional Annotation, Pathways, Localization, and Recent Advances Falcon Edison Scientific Literature 51 citations 2026-05-03T13:32:59.242908

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Mouse Hras (UniProt Q61411) — Functional Annotation, Pathways, Localization, and Recent Advances

Scope and target verification (critical identity check)

The UniProt accession Q61411 corresponds to Mus musculus Hras, encoding the classical Ras-family small GTPase H-Ras (“transforming protein p21”), a P-loop NTPase that functions as a membrane-localized GDP/GTP molecular switch and signals through canonical Ras effector pathways. Mechanistic literature describing CAAX processing (farnesylation → RCE1 cleavage → ICMT methylation) and dual palmitoylation that drives Golgi-to–plasma membrane trafficking is consistent with the defining properties of H-Ras and matches the UniProt description you provided. (nair2023regulationofrasgtpase pages 6-8, nair2023regulationofrasgtpase pages 1-2, ren2023rab27bcontrolspalmitoylationdependent pages 1-2)

1. Key concepts and definitions (current understanding)

1.1 HRas as a “molecular switch” small GTPase

H-Ras proteins cycle between an inactive GDP-bound state and an active GTP-bound state; conformational changes in switch I/II determine effector binding and downstream pathway activation. Activation is promoted by guanine nucleotide exchange factors (GEFs) (e.g., SOS family; RasGRP/RasGRF), while inactivation is accelerated by GTPase-activating proteins (GAPs). This GDP/GTP cycling framework is central to functional annotation of mouse HRas as a signaling node rather than a metabolic enzyme with diverse small-molecule substrates. (nair2023regulationofrasgtpase pages 1-2, healy2024mediatingkinaseactivity pages 2-3)

1.2 Enzymatic activity and “substrate specificity” for HRas

Functionally, HRas is a GTPase whose catalytic cycle uses GTP as substrate (hydrolyzed to GDP + Pi) and whose “specificity” is primarily defined by:
- Nucleotide state (GDP vs GTP), and
- Protein–protein interactions with regulators (GEFs/GAPs) and effectors (e.g., RAF, PI3K, RalGEFs), mediated by switch I/II surfaces.
This mode of specificity contrasts with classical enzymes (e.g., kinases) and is important for accurate annotation. (nair2023regulationofrasgtpase pages 1-2, mozzarelli2024functionalandstructural pages 6-7)

2. Molecular function, processing, and subcellular localization

2.1 CAAX processing and prenylation-dependent membrane association

H-Ras contains a C-terminal CAAX motif that is processed by:
1) Farnesyltransferase (FTase) addition of a 15-carbon farnesyl group,
2) RCE1 cleavage of the AAX residues,
3) ICMT carboxyl-methylation.
These steps are required to generate a hydrophobic C-terminus competent for membrane interactions and subsequent trafficking. (Apr 2023 review; https://doi.org/10.3390/kinasesphosphatases1020007) (nair2023regulationofrasgtpase pages 6-8)

2.2 HRas palmitoylation and Golgi-to–plasma membrane cycling

A defining feature of H-Ras (vs KRas4B) is reliance on reversible palmitoylation rather than a strong polybasic tail to achieve stable plasma membrane localization.

Residue-level information: H-Ras undergoes dual palmitoylation at Cys181 and Cys184 (Golgi), and this palmitoylation is reversible; cycling of palmitoylation/depalmitoylation mediates redistribution among Golgi, plasma membrane, and endomembranes. (Apr 2023; https://doi.org/10.3390/kinasesphosphatases1020007) (nair2023regulationofrasgtpase pages 6-8)

Mechanistic emphasis from recent JCI perspective: CAAX prenylation is necessary but not sufficient for plasma-membrane delivery; palmitoylation can increase membrane affinity by approximately ~100-fold compared with prenylation alone, underscoring why palmitoylation is functionally central to HRas signaling location. (Jun 2023; https://doi.org/10.1172/jci171104) (yu2023mechanismsforregulation pages 1-2)

2.3 Cellular compartments where HRas acts

Functional signaling from HRas is tightly coupled to its membrane compartmentalization:
- Nascent Ras proteins undergo processing in cytosol/ER and further modifications enabling targeting to the inner leaflet of the plasma membrane, described as a primary signaling platform. (Apr 2023; https://doi.org/10.3390/kinasesphosphatases1020007) (nair2023regulationofrasgtpase pages 1-2)
- HRas and NRas traffic to the Golgi for palmitoylation by the ZDHHC9–GOLGA7 palmitoyltransferase complex before reaching the plasma membrane. (Jun 2023; https://doi.org/10.1172/jci165510) (ren2023rab27bcontrolspalmitoylationdependent pages 1-2)

3. Downstream pathways and effector mechanisms

3.1 Canonical effector arms

Active (GTP-bound) HRas recruits and activates multiple effector classes:
- RAF kinases → MEK → ERK (MAPK cascade)
- PI3K → AKT signaling
- RalGEFs (e.g., RalGDS family) → Ral signaling
These are consistently described as major Ras-mediated kinase pathway outputs and are central to pathway-level annotation. (healy2024mediatingkinaseactivity pages 2-3, mozzarelli2024functionalandstructural pages 6-7)

Recent synthesis emphasizes that Ras effector coupling is not a single uniform “binds RAF” event, but depends on specific interfaces and membrane geometry:
- RAF activation: besides RAF’s Ras-binding domain (RBD), the cysteine-rich domain (CRD) interacts with Ras interswitch/α5 regions and membranes; mutations at the Ras–CRD interface can substantially reduce CRAF activation without strongly changing binding strength, implying a coupling mechanism beyond affinity alone. (Aug 2024; https://doi.org/10.1016/j.molcel.2024.06.027) (mozzarelli2024functionalandstructural pages 6-7)
- PI3K interaction: Ras–PI3K engagement is GTP-dependent and generally weaker than Ras–RAF binding; HRAS contacts PI3Kγ through switch I/II, with switch II contacting the catalytic domain. (Aug 2024; https://doi.org/10.1016/j.molcel.2024.06.027) (mozzarelli2024functionalandstructural pages 6-7)
- RalGEF branch: RalGDS-family effectors engage Ras mainly through switch I; these mechanistic distinctions support annotating HRas as a hub that can route signals into multiple arms depending on context. (Aug 2024; https://doi.org/10.1016/j.molcel.2024.06.027) (mozzarelli2024functionalandstructural pages 6-7)

4. Regulation beyond lipidation: additional PTMs and signal tuning

HRas is further regulated by post-translational modifications that alter localization and nucleotide cycling:
- Ubiquitination: mono/di-ubiquitination can sequester HRas to endocytic compartments and impair RAF1 recruitment/MAPK signaling; site-specific effects include Lys117 ubiquitination increasing nucleotide exchange and GTP loading, whereas other sites (e.g., Lys63) can stabilize endosomal association and modulate signaling. (Apr 2023; https://doi.org/10.3390/kinasesphosphatases1020007) (nair2023regulationofrasgtpase pages 6-8)
- Nitrosylation: nitrosylation at Cys118 by NOS is described to activate ERK/MAPK signaling. (Apr 2023; https://doi.org/10.3390/kinasesphosphatases1020007) (nair2023regulationofrasgtpase pages 6-8)

These mechanisms refine functional annotation: HRas output is controlled not only by GEF/GAP cycling but also by membrane routing and PTMs that change where and how long HRas remains signaling-competent. (nair2023regulationofrasgtpase pages 6-8)

5. Mouse genetics: in vivo evidence for HRas function

5.1 Activating knock-in alleles model RASopathies (Costello syndrome) and map pathway causality

HrasG12S/+ knock-in: skin inflammation and MAPK output

A knock-in Costello syndrome model (HrasG12S/+) shows susceptibility to house-dust-mite–induced atopic-dermatitis-like lesions, with mechanistic linkage to ERK activation and epithelial cytokines.

Quantitative examples (from the reported experiments): baseline serum IgE was elevated in HrasG12S/+ vs WT (reported means ± SD: 654 ± 348 ng/mL vs 261 ± 152.2 ng/mL; P = 0.039). Increased p-ERK–positive epidermal cells and increased IL-33 were observed, and MEK inhibition (PD0325901) ameliorated symptoms and reduced p-ERK/IL-33, supporting a causal HRas→MEK→ERK mechanism in this tissue response. (Aug 2020; https://doi.org/10.1038/s41419-020-02845-8) (katata2020costellosyndromemodel pages 1-2)

HrasG12V knock-in: skeletal myopathy rescued by MEK inhibition

In an HrasG12V knock-in model, skeletal myopathy is linked to hyperactive Ras/MAPK (and PI3K/AKT) signaling; the phenotype is reversible with MEK inhibition.

Quantitative examples:
- RNA-seq in gastrocnemius: 487 DEGs (n=3) at fold change ≥1.5 and P≤0.05; multiple GO enrichments were significant (e.g., carbohydrate metabolism P=0.0004; lipid metabolism P=0.006). (tidyman2022mekinhibitormediatedrescueof pages 8-9)
- In vitro primary myoblast differentiation: PD0325901 1 µM rescued differentiation (n=5; P<0.01), whereas PI3K inhibitor GDC0941 1 µM caused detachment/cell death. (tidyman2022mekinhibitormediatedrescueof pages 8-9)
- In vivo: daily PD0325901 for 28 days in 3-month-old mice normalized Ras/MAPK signaling by western blot and rescued muscle structural/functional measures (e.g., myofiber CSA, muscle weight, grip strength). (Sep 2022; https://doi.org/10.1242/dmm.049166) (tidyman2022mekinhibitormediatedrescueof pages 8-9)

These knock-in models provide high-confidence in vivo evidence that hyperactive HRas drives phenotypes predominantly through the RAF–MEK–ERK axis, and that pharmacologic pathway inhibition can reverse disease-associated outputs (a “real-world” implementation of pathway annotation). (tidyman2022mekinhibitormediatedrescueof pages 8-9, katata2020costellosyndromemodel pages 1-2)

5.2 Loss-of-function context and Ras isoform compensation: Hras/Nras double knockout

A key mouse genetics insight is that HRas function can be buffered by other Ras isoforms; nevertheless, combined removal of HRas and NRas reveals essential, non-redundant physiological roles.

Perinatal lethality and lung maturation: Hras/Nras double knockout mice display very high perinatal mortality from respiratory failure within 24–48 h; at birth expected Mendelian representation is ~25%, but survival at weaning (P21) is 5–6-fold lower than near birth, and neonates show 15–20% reduced body weight. Dexamethasone partially mitigated lung maturation defects and extended survival up to 6 days. (Nov 2019; https://doi.org/10.1038/s41419-019-2075-2) (fuentesmateos2019concomitantdeletionof pages 1-2)
RASopathy-like adult phenotype in survivors and mechanistic KRAS compensation: a 2024 follow-up reports that rare adult survivors show craniofacial abnormalities, thrombocytopenia/bleeding anomalies, reduced platelet activation, and organ hyperplasia; mechanistically these alterations are accompanied by increased KRAS-GTP in multiple tissues/cells, supporting a compensation-driven mechanism that can itself become pathological. (Jun 2024; https://doi.org/10.1186/s12964-024-01717-4) (fuentesmateos2024combinedhrasand pages 1-2)

6. Recent developments and latest research (prioritizing 2023–2024)

6.1 2023–2024: trafficking/PTM regulation as therapeutic logic

Recent JCI work highlights that manipulating Ras palmitoylation/trafficking (e.g., via palmitoyltransferase complexes and upstream regulators) can suppress Ras output by preventing plasma membrane localization, emphasizing localization as a functional requirement rather than a descriptive feature. (Jun 2023; https://doi.org/10.1172/jci165510; Jun 2023; https://doi.org/10.1172/jci171104) (ren2023rab27bcontrolspalmitoylationdependent pages 1-2, yu2023mechanismsforregulation pages 1-2)

6.2 2024: effector structural insights refine pathway annotation

The 2024 Molecular Cell review clarifies that RAF activation requires coordinated RBD/CRD and membrane interactions, while PI3K and RalGEF interfaces engage distinct switch surfaces; this improves mechanistic specificity for HRas functional annotation and explains pathway selectivity. (Aug 2024; https://doi.org/10.1016/j.molcel.2024.06.027) (mozzarelli2024functionalandstructural pages 6-7)

6.3 2023–2024: direct Ras targeting and druggability (context relevant to HRas)

Although much direct inhibitor development focuses on human KRAS, these studies are still informative for HRas structure–function:
- A 2024 Cell study reports targeting Ras-family GTPases through a conserved cryptic pocket and includes an inhibitor-bound H-Ras(G12C) structure, supporting the concept that HRas has exploitable conformational pockets tied to its switch-state biology. (Oct 2024; https://doi.org/10.1016/j.cell.2024.08.017) (bhattarai2026recentbreakthroughsin pages 5-7)
- 2023–2024 reviews summarize expanding modalities (noncovalent pocket ligands, active-state inhibitors, macromolecular binders) and emphasize allele/context dependence; one review notes KRAS G12C ~12% of KRAS mutations and provides cohort-scale mutation counts (HRAS N=178; NRAS N=517; KRAS N=3,752 in one compilation), framing why different Ras isoforms and alleles have distinct therapeutic trajectories. (Sep 2024; https://doi.org/10.3389/fphar.2024.1441938; May 2023; https://doi.org/10.1038/s41392-023-01441-4) (healy2024mediatingkinaseactivity pages 12-13, healy2024mediatingkinaseactivity pages 3-6, yin2023targetingsmallgtpases pages 1-2)

7. Current applications and real-world implementations

7.1 In vivo pathway intervention in HRas-driven phenotypes

Mouse knock-in models demonstrate that MEK inhibition (PD0325901) can reverse both signaling readouts and organismal phenotypes (dermatitis-like inflammation; skeletal myopathy). These are direct implementations of pathway knowledge and validate RAF–MEK–ERK as a causal HRas output axis in vivo. (katata2020costellosyndromemodel pages 1-2, tidyman2022mekinhibitormediatedrescueof pages 8-9)

7.2 Targeting Ras membrane association and PTM pathways

Multiple recent sources frame Ras lipidation and trafficking as actionable:
- PTM-centric modulation (prenylation/palmitoylation/trafficking) is argued to be therapeutically attractive because membrane association is required for signaling. (yu2023mechanismsforregulation pages 1-2, ren2023rab27bcontrolspalmitoylationdependent pages 1-2)
- A 2023 review reports a high-affinity PDE6δ inhibitor example (Deltarasin KD = 7.6 ± 1.3 nM) as a chemical strategy to displace farnesylated Ras from membranes (discussed mainly for KRAS but mechanistically tied to prenylated Ras biology). (May 2023; https://doi.org/10.1038/s41392-023-01441-4) (yin2023targetingsmallgtpases pages 16-17)

8. Expert synthesis: primary functional statement for annotation

Primary function: Mouse HRas encodes a membrane-anchored, Ras-family small GTPase that acts as a signal-transducing molecular switch. In its GTP-bound state, HRas recruits effectors (RAF, PI3K, RalGEFs) to activate MAPK/PI3K/Ral signaling; in its GDP-bound state it is inactive. Activity is regulated by GEFs and GAPs and is inseparable from subcellular localization.

Where it acts: HRas signaling depends on lipid modifications and trafficking—CAAX farnesylation/RCE1 cleavage/ICMT methylation enable membrane competence, while dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling to the plasma membrane, the major signaling platform. Additional PTMs (ubiquitination, nitrosylation) tune localization and signaling strength. (nair2023regulationofrasgtpase pages 6-8, nair2023regulationofrasgtpase pages 1-2, ren2023rab27bcontrolspalmitoylationdependent pages 1-2, mozzarelli2024functionalandstructural pages 6-7)

Evidence maps (tables)

The following tables summarize the evidence base for HRas functional annotation and highlight 2023–2024 advances.

Functional aspect	Key details	Evidence type	Key citations with year, DOI URL, and citation id
GTPase cycle / core biochemical function	Mouse Hras encodes classical H-Ras, a Ras-family small GTPase that functions as a GDP/GTP molecular switch. The G domain contains switch I/II regions that change conformation between GDP- and GTP-bound states and mediate effector binding. Activation is promoted by GEFs such as SOS/RasGRP/RasGRF family proteins; inactivation is accelerated by GAPs. Signaling output depends on the GTP-bound, membrane-associated state.	Recent review / mechanistic synthesis	Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 1-2); Healy et al. 2024, https://doi.org/10.3389/fphar.2024.1441938 (healy2024mediatingkinaseactivity pages 2-3); Patel 2023, https://doi.org/10.17863/cam.95441 (patel2023investigatingtherole pages 18-21)
Post-translational modifications (CAAX processing)	HRas carries a C-terminal CAAX motif that undergoes farnesylation by FTase, proteolytic -AAX removal by RCE1, and carboxyl-methylation by ICMT; these steps occur before stable membrane targeting. Prenylation is necessary but not sufficient for plasma-membrane signaling.	Recent review / PTM-focused review	Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 6-8); Yu & Qian 2023, https://doi.org/10.1172/jci171104 (yu2023mechanismsforregulation pages 1-2); Ren et al. 2023, https://doi.org/10.1172/jci165510 (ren2023rab27bcontrolspalmitoylationdependent pages 1-2)
Palmitoylation / membrane affinity	HRas is dually palmitoylated at C181 and C184 in the Golgi; reversible depalmitoylation supports cycling between Golgi, plasma membrane, and endomembranes. Palmitoylation greatly increases membrane affinity and is essential for productive signaling from the plasma membrane.	Recent review / biochemical trafficking review	Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 6-8); Yu & Qian 2023, https://doi.org/10.1172/jci171104 (yu2023mechanismsforregulation pages 1-2); Patel 2023, https://doi.org/10.17863/cam.95441 (patel2023investigatingtherole pages 18-21)
Trafficking / subcellular localization	Newly synthesized HRas is processed in the cytosol/ER, then traffics to the Golgi for palmitoylation, followed by delivery to the inner leaflet of the plasma membrane, the principal signaling platform. HRas can also signal from Golgi/endomembrane pools, and dynamic palmitoylation-depalmitoylation regulates redistribution among compartments.	Review plus compartmentalized signaling study	Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 1-2); Santra et al. 2019, https://doi.org/10.1016/j.celrep.2019.02.038 (bhattarai2026recentbreakthroughsin pages 5-7); Ren et al. 2023, https://doi.org/10.1172/jci165510 (ren2023rab27bcontrolspalmitoylationdependent pages 1-2)
Downstream effectors / pathways	GTP-bound HRas engages canonical Ras effectors including RAF kinases to drive RAF-MEK-ERK signaling, PI3K catalytic subunits to activate PI3K-AKT signaling, and RalGEF family proteins to stimulate Ral signaling. Effector recognition depends on the exposed switch regions in the active conformation.	Recent effector review / pathway review	Mozzarelli et al. 2024, https://doi.org/10.1016/j.molcel.2024.06.027 (healy2024mediatingkinaseactivity pages 12-13); Healy et al. 2024, https://doi.org/10.3389/fphar.2024.1441938 (healy2024mediatingkinaseactivity pages 2-3); Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 6-8)
Additional regulatory PTMs	HRas regulation extends beyond lipidation: ubiquitination can relocalize HRas to endosomes and modulate Raf/MAPK output; Lys117 ubiquitination can enhance nucleotide exchange/GTP loading; nitrosylation at Cys118 can activate ERK/MAPK signaling.	PTM review / mechanistic synthesis	Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 6-8); Weatherdon 2024, https://doi.org/10.17863/cam.107595 (weatherdon2024proteiniscreensidentify pages 25-28)
Mouse model: HrasG12S/+ Costello syndrome skin phenotype	Activating HrasG12S/+ knock-in mice are predisposed to house dust mite–induced atopic dermatitis-like disease with impaired barrier function, elevated IgE, increased p-ERK-positive epidermal cells, and increased IL-33/Th2-type cytokine responses, linking mutant Hras to MAPK-driven epidermal inflammation.	Primary mouse knock-in study	Katata et al. 2020, https://doi.org/10.1038/s41419-020-02845-8 (katata2020costellosyndromemodel pages 1-2)
Mouse model: HrasG12V Costello syndrome muscle phenotype	HrasG12V knock-in mice show skeletal myopathy, reduced muscle mass/strength, hyperactive Ras/MAPK and PI3K/AKT signaling, and reduced p38 signaling. In vitro and in vivo MEK inhibition rescues major aspects of the phenotype, supporting MAPK hyperactivation as a principal pathogenic mechanism.	Primary mouse knock-in study	Tidyman et al. 2022, https://doi.org/10.1242/dmm.049166 (tidyman2022mekinhibitormediatedrescueof pages 1-2, tidyman2022mekinhibitormediatedrescueof pages 8-9)
Mouse model: HrasG12S/+ metabolic phenotype	HrasG12S/+ mice on high-fat diet are resistant to diet-induced obesity yet develop impaired hepatic energy homeostasis, microvesicular steatosis, hypoketosis during fasting, and accumulation of long-chain acylcarnitines, implicating oncogenic Hras in systemic metabolic regulation.	Primary mouse knock-in study	Oba et al. 2018, https://doi.org/10.1016/j.ebiom.2017.11.029 (oba2018micewithan pages 1-3)
Mouse loss-of-function context	Single-gene HRAS loss is partly buffered by other Ras isoforms, but combined Hras/Nras ablation causes severe developmental defects: high perinatal lethality from respiratory failure, delayed lung maturation, and in surviving adults a RASopathy-like phenotype with craniofacial abnormalities, thrombocytopenia, bleeding defects, splenic/heart changes, and increased KRAS-GTP. This indicates nonredundant physiological contributions of Hras that are partly masked by Ras-family compensation.	Primary mouse knockout studies	Fuentes-Mateos et al. 2019, https://doi.org/10.1038/s41419-019-2075-2 (fuentesmateos2019concomitantdeletionof pages 1-2); Fuentes-Mateos et al. 2024, https://doi.org/10.1186/s12964-024-01717-4 (fuentesmateos2024combinedhrasand pages 1-2)
Therapeutic / experimental interventions	MEK inhibition (PD0325901) reduced p-ERK signaling and improved Hras-driven mouse phenotypes in skin inflammation and skeletal muscle disease, validating RAF-MEK-ERK as a major actionable downstream axis. More broadly, HRas biology supports intervention at PTM-dependent membrane targeting (farnesylation/palmitoylation) or downstream effector pathways.	Primary intervention studies plus recent reviews	Katata et al. 2020, https://doi.org/10.1038/s41419-020-02845-8 (katata2020costellosyndromemodel pages 1-2); Tidyman et al. 2022, https://doi.org/10.1242/dmm.049166 (tidyman2022mekinhibitormediatedrescueof pages 8-9); Yu & Qian 2023, https://doi.org/10.1172/jci171104 (yu2023mechanismsforregulation pages 1-2)

Table: This table summarizes the core functional annotation of mouse HRas (UniProt Q61411), including its biochemical switch function, PTMs, localization, downstream pathways, and informative mouse models. It is useful as a compact evidence map linking mechanistic understanding to primary in vivo studies and recent reviews.

Development area	2023-2024 key finding	Why it matters for mouse HRas functional annotation	Source (publication date, DOI URL, citation id)
Palmitoylation / trafficking regulation	2023 work identified a RAB27B-ZDHHC9 regulatory axis that controls palmitoylation-dependent Ras trafficking to the plasma membrane and downstream ERK output in leukemia models; companion 2023 commentary emphasized that prenylation is necessary but insufficient, and that palmitoylation can increase membrane affinity by ~100-fold. Although the strongest direct evidence in these papers is for NRAS, the mechanism is explicitly framed as relevant to palmitoylated RAS proteins including HRAS.	Supports annotating mouse HRas as a membrane-trafficked signaling GTPase whose function depends on CAAX processing plus reversible palmitoylation, especially Golgi-to-plasma-membrane cycling rather than simple constitutive membrane residence. This is directly relevant to where HRas acts in the cell and why localization is integral to its signaling role.	Jun 2023, https://doi.org/10.1172/jci165510 (ren2023rab27bcontrolspalmitoylationdependent pages 1-2); Jun 2023, https://doi.org/10.1172/jci171104 (yu2023mechanismsforregulation pages 1-2)
Effector structural insights: RAF CRD	A 2024 Molecular Cell review synthesized structural evidence that RAF activation depends not only on the canonical Ras-binding domain (RBD) but also on the cysteine-rich domain (CRD), which contacts the Ras interswitch/α5 region and membranes. Mutations at the Ras-CRD interface can markedly reduce CRAF activation even with limited effects on binding strength.	Refines annotation of HRas from a generic “MAPK activator” to a spatially organized membrane signal transducer whose active conformation and membrane orientation govern productive RAF activation. For mouse HRas, this supports precise pathway annotation to RAF-MEK-ERK with membrane-context dependence.	Aug 2024, https://doi.org/10.1016/j.molcel.2024.06.027 (mozzarelli2024functionalandstructural pages 6-7)
Effector structural insights: PI3Kγ interface	2024 review evidence indicates Ras-PI3K interaction is GTP-dependent but weaker than RAF binding; HRAS engages PI3Kγ through switch I/II, with switch II making direct contact with the catalytic domain.	Supports annotating mouse HRas as an upstream activator of PI3K signaling, but with effector-specific interaction geometry distinct from RAF. This improves specificity of functional annotation beyond “binds PI3K” by linking activation to the GTP-bound switch regions.	Aug 2024, https://doi.org/10.1016/j.molcel.2024.06.027 (mozzarelli2024functionalandstructural pages 6-7)
Effector structural insights: RalGDS / RalGEF branch	2024 structural synthesis reports that RALGDS family effectors engage Ras primarily through switch I, and KRAS-RGL1 complexes are predominantly 1:1 dimers in solution with slow tetramerization behavior.	Reinforces that HRas should be annotated not only to MAPK and PI3K pathways but also to the RalGEF branch of Ras signaling. It also emphasizes that different effectors read distinct surfaces of active Ras, helping explain pathway selectivity in vivo.	Aug 2024, https://doi.org/10.1016/j.molcel.2024.06.027 (mozzarelli2024functionalandstructural pages 6-7)
Direct Ras targeting / cryptic pocket druggability	A 2024 Cell study demonstrated that Ras-, Rho-, and Rab-family GTPases can be targeted through a conserved cryptic pocket, and included structural work with inhibitor-bound H-Ras(G12C). Parallel 2024/2023 reviews highlight growing exploitation of transient switch-region pockets and allosteric conformations for direct Ras inhibition.	Even though most compounds are developed for oncogenic human Ras alleles, these studies are highly informative for mouse HRas annotation because they validate that HRas possesses exploitable conformational pockets linked to switch-state biology. This strengthens structure-function inference for the GTPase domain of mouse Hras.	Oct 2024, https://doi.org/10.1016/j.cell.2024.08.017 (bhattarai2026recentbreakthroughsin pages 5-7); May 2023, https://doi.org/10.1038/s41392-023-01441-4 (yin2023targetingsmallgtpases pages 1-2)
Direct targeting advances beyond G12C	2024 reviews summarize noncovalent switch-II-pocket ligands, pan-RAS-active compounds, and active-state inhibitors such as RMC-6236; they also note emerging chemistry for non-cysteine mutants (e.g., G12S/G12R-directed strategies) and examples of tumor regressions in xenograft models.	Important for mouse HRas because they show that Ras function is not only genetically inferable but chemically perturbable at the level of nucleotide state and effector coupling. This helps interpret HRas as a dynamic switch protein with separable biochemical states rather than an undruggable scaffold.	Sep 2024, https://doi.org/10.3389/fphar.2024.1441938 (healy2024mediatingkinaseactivity pages 12-13, healy2024mediatingkinaseactivity pages 20-20); May 2023, https://doi.org/10.1038/s41392-023-01441-4 (yin2023targetingsmallgtpases pages 14-16)
Macromolecular Ras binders / effector competition	2023 review evidence highlights cyclic peptides, monobodies, DARPins, affimers, and miniproteins that bind switch-region pockets or block effector engagement, with reported affinities reaching nanomolar to picomolar ranges in some systems.	These studies underscore that the key functional surface of HRas is the effector-binding switch interface. For annotation, this supports describing HRas as a signaling hub whose primary biochemical role is regulated effector recruitment rather than broad enzymatic catalysis on diverse substrates.	May 2023, https://doi.org/10.1038/s41392-023-01441-4 (yin2023targetingsmallgtpases pages 14-16)
Pathway / therapy context	2024 pathway-focused reviews emphasize that Ras-mutant signaling is highly allele- and context-dependent, with differential routing through MAPK, PI3K, and Ral pathways; they highlight individualized therapeutic strategies and resistance mechanisms as key current themes.	For mouse HRas annotation, this argues against overly broad pleiotropic descriptions and favors pathway-centered annotation: HRas primarily relays receptor-derived signals through canonical effector arms, with output shaped by localization, mutation state, and effector availability.	Sep 2024, https://doi.org/10.3389/fphar.2024.1441938 (healy2024mediatingkinaseactivity pages 2-3, healy2024mediatingkinaseactivity pages 12-13); Aug 2024, https://doi.org/10.1016/j.molcel.2024.06.027 (mozzarelli2024functionalandstructural pages 6-7)

Table: This table summarizes the most relevant 2023-2024 advances for interpreting mouse HRas function, spanning membrane trafficking, effector structural biology, and direct Ras targeting. It is useful for linking recent mechanistic discoveries to precise functional annotation of UniProt Q61411.

Limitations and evidence gaps

Several recent 2023–2024 sources are high-quality reviews or mechanistic papers not strictly mouse-Hras-specific; they inform mouse HRas by strong homology and shared Ras isoform processing principles, but direct residue-by-residue validation in mouse tissues can require additional isoform-specific primary studies.
The provided evidence set does not include a dedicated 2023–2024 mouse-Hras-specific biochemical kinetics paper reporting intrinsic GTP hydrolysis rates or nucleotide exchange rates for mouse HRas; accordingly, this report focuses on the well-supported switch-model and PTM/localization-dependent signaling mechanisms.

Key URLs (selected)

Nair & Saha. 2023-04. Regulation of Ras-GTPase Signaling and Localization by Post-Translational Modifications. https://doi.org/10.3390/kinasesphosphatases1020007 (nair2023regulationofrasgtpase pages 6-8, nair2023regulationofrasgtpase pages 1-2)
Yu & Qian. 2023-06. Mechanisms for regulation of RAS palmitoylation and plasma membrane trafficking in hematopoietic malignancies. https://doi.org/10.1172/jci171104 (yu2023mechanismsforregulation pages 1-2)
Ren et al. 2023-06. RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. https://doi.org/10.1172/jci165510 (ren2023rab27bcontrolspalmitoylationdependent pages 1-2)
Mozzarelli et al. 2024-08. Functional and structural insights into RAS effector proteins. https://doi.org/10.1016/j.molcel.2024.06.027 (mozzarelli2024functionalandstructural pages 6-7)
Fuentes-Mateos et al. 2024-06. Combined HRAS and NRAS ablation induces a RASopathy phenotype in mice. https://doi.org/10.1186/s12964-024-01717-4 (fuentesmateos2024combinedhrasand pages 1-2)
Katata et al. 2020-08. Costello syndrome model mice with a Hras G12S mutation… atopic dermatitis. https://doi.org/10.1038/s41419-020-02845-8 (katata2020costellosyndromemodel pages 1-2)
Tidyman et al. 2022-09. MEK-inhibitor-mediated rescue… Hras mutation… mouse model. https://doi.org/10.1242/dmm.049166 (tidyman2022mekinhibitormediatedrescueof pages 8-9)
Healy et al. 2024-09. Mediating kinase activity in Ras-mutant cancer…. https://doi.org/10.3389/fphar.2024.1441938 (healy2024mediatingkinaseactivity pages 12-13)

References

(nair2023regulationofrasgtpase pages 6-8): Arathi Nair and Bhaskar Saha. Regulation of ras-gtpase signaling and localization by post-translational modifications. Kinases and Phosphatases, 1:97-116, Apr 2023. URL: https://doi.org/10.3390/kinasesphosphatases1020007, doi:10.3390/kinasesphosphatases1020007. This article has 7 citations.
(nair2023regulationofrasgtpase pages 1-2): Arathi Nair and Bhaskar Saha. Regulation of ras-gtpase signaling and localization by post-translational modifications. Kinases and Phosphatases, 1:97-116, Apr 2023. URL: https://doi.org/10.3390/kinasesphosphatases1020007, doi:10.3390/kinasesphosphatases1020007. This article has 7 citations.
(ren2023rab27bcontrolspalmitoylationdependent pages 1-2): Jian-Gang Ren, Bowen Xing, Kaosheng Lv, Rachel A. O’Keefe, Mengfang Wu, Ruoxing Wang, Kaylyn M. Bauer, Arevik Ghazaryan, George M. Burslem, Jing Zhang, Ryan M. O’Connell, Vinodh Pillai, Elizabeth O. Hexner, Mark R. Philips, and Wei Tong. Rab27b controls palmitoylation-dependent nras trafficking and signaling in myeloid leukemia. The Journal of Clinical Investigation, Jun 2023. URL: https://doi.org/10.1172/jci165510, doi:10.1172/jci165510. This article has 52 citations.
(healy2024mediatingkinaseactivity pages 2-3): Fiona M. Healy, Amy L. Turner, Vanessa Marensi, and David J. MacEwan. Mediating kinase activity in ras-mutant cancer: potential for an individualised approach? Frontiers in Pharmacology, Sep 2024. URL: https://doi.org/10.3389/fphar.2024.1441938, doi:10.3389/fphar.2024.1441938. This article has 0 citations.
(mozzarelli2024functionalandstructural pages 6-7): Alessandro M. Mozzarelli, Dhirendra K. Simanshu, and Pau Castel. Functional and structural insights into ras effector proteins. Molecular Cell, 84:2807-2821, Aug 2024. URL: https://doi.org/10.1016/j.molcel.2024.06.027, doi:10.1016/j.molcel.2024.06.027. This article has 35 citations and is from a highest quality peer-reviewed journal.
(yu2023mechanismsforregulation pages 1-2): Fang Yu and Zhijian Qian. Mechanisms for regulation of ras palmitoylation and plasma membrane trafficking in hematopoietic malignancies. The Journal of Clinical Investigation, Jun 2023. URL: https://doi.org/10.1172/jci171104, doi:10.1172/jci171104. This article has 19 citations.
(katata2020costellosyndromemodel pages 1-2): Yu Katata, Shin-ichi Inoue, Atsuko Asao, Shuhei Kobayashi, Hitoshi Terui, Aya Inoue-Shibui, Taiki Abe, Tetsuya Niihori, Setsuya Aiba, Naoto Ishii, Shigeo Kure, and Yoko Aoki. Costello syndrome model mice with a hras g12s mutation are susceptible to develop house dust mite-induced atopic dermatitis. Cell Death & Disease, Aug 2020. URL: https://doi.org/10.1038/s41419-020-02845-8, doi:10.1038/s41419-020-02845-8. This article has 8 citations and is from a peer-reviewed journal.
(tidyman2022mekinhibitormediatedrescueof pages 8-9): William E. Tidyman, Alice F. Goodwin, Yoshiko Maeda, Ophir D. Klein, and Katherine A. Rauen. Mek-inhibitor-mediated rescue of skeletal myopathy caused by activating hras mutation in a costello syndrome mouse model. Disease Models & Mechanisms, Sep 2022. URL: https://doi.org/10.1242/dmm.049166, doi:10.1242/dmm.049166. This article has 26 citations and is from a domain leading peer-reviewed journal.
(fuentesmateos2019concomitantdeletionof pages 1-2): Rocío Fuentes-Mateos, David Jimeno, Carmela Gómez, Nuria Calzada, Alberto Fernández-Medarde, and Eugenio Santos. Concomitant deletion of hras and nras leads to pulmonary immaturity, respiratory failure and neonatal death in mice. Cell Death & Disease, Nov 2019. URL: https://doi.org/10.1038/s41419-019-2075-2, doi:10.1038/s41419-019-2075-2. This article has 15 citations and is from a peer-reviewed journal.
(fuentesmateos2024combinedhrasand pages 1-2): Rocío Fuentes-Mateos, Rósula García-Navas, Cristina Fernández-Infante, Luis Hernández-Cano, Nuria Calzada-Nieto, Andrea Olarte-San Juan, Carmen Guerrero, Eugenio Santos, and Alberto Fernández-Medarde. Combined hras and nras ablation induces a rasopathy phenotype in mice. Cell Communication and Signaling : CCS, Jun 2024. URL: https://doi.org/10.1186/s12964-024-01717-4, doi:10.1186/s12964-024-01717-4. This article has 4 citations.
(bhattarai2026recentbreakthroughsin pages 5-7): Nisha Bhattarai and Matthias Buck. Recent breakthroughs in understanding the allosteric features of ras gtpases and their effector and regulatory protein interactions, enabling drug design. Current Opinion in Structural Biology, 96:103183, Feb 2026. URL: https://doi.org/10.1016/j.sbi.2025.103183, doi:10.1016/j.sbi.2025.103183. This article has 0 citations and is from a peer-reviewed journal.
(healy2024mediatingkinaseactivity pages 12-13): Fiona M. Healy, Amy L. Turner, Vanessa Marensi, and David J. MacEwan. Mediating kinase activity in ras-mutant cancer: potential for an individualised approach? Frontiers in Pharmacology, Sep 2024. URL: https://doi.org/10.3389/fphar.2024.1441938, doi:10.3389/fphar.2024.1441938. This article has 0 citations.
(healy2024mediatingkinaseactivity pages 3-6): Fiona M. Healy, Amy L. Turner, Vanessa Marensi, and David J. MacEwan. Mediating kinase activity in ras-mutant cancer: potential for an individualised approach? Frontiers in Pharmacology, Sep 2024. URL: https://doi.org/10.3389/fphar.2024.1441938, doi:10.3389/fphar.2024.1441938. This article has 0 citations.
(yin2023targetingsmallgtpases pages 1-2): Guowei Yin, Jing Huang, Johnny Petela, Hongmei Jiang, Yuetong Zhang, Siqi Gong, Jiaxin Wu, Bei Liu, Jianyou Shi, and Yijun Gao. Targeting small gtpases: emerging grasps on previously untamable targets, pioneered by kras. Signal Transduction and Targeted Therapy, May 2023. URL: https://doi.org/10.1038/s41392-023-01441-4, doi:10.1038/s41392-023-01441-4. This article has 90 citations and is from a peer-reviewed journal.
(yin2023targetingsmallgtpases pages 16-17): Guowei Yin, Jing Huang, Johnny Petela, Hongmei Jiang, Yuetong Zhang, Siqi Gong, Jiaxin Wu, Bei Liu, Jianyou Shi, and Yijun Gao. Targeting small gtpases: emerging grasps on previously untamable targets, pioneered by kras. Signal Transduction and Targeted Therapy, May 2023. URL: https://doi.org/10.1038/s41392-023-01441-4, doi:10.1038/s41392-023-01441-4. This article has 90 citations and is from a peer-reviewed journal.
(patel2023investigatingtherole pages 18-21): Khushali Patel. Investigating the role of oncogenic kras g12 mutations in cell signalling. Dissertation, Mar 2023. URL: https://doi.org/10.17863/cam.95441, doi:10.17863/cam.95441. This article has 0 citations.
(weatherdon2024proteiniscreensidentify pages 25-28): Laura Jane Weatherdon. Proteini screens identify orp9 as a novel regulator of kras-driven signalling. Dissertation, Apr 2024. URL: https://doi.org/10.17863/cam.107595, doi:10.17863/cam.107595. This article has 0 citations.
(tidyman2022mekinhibitormediatedrescueof pages 1-2): William E. Tidyman, Alice F. Goodwin, Yoshiko Maeda, Ophir D. Klein, and Katherine A. Rauen. Mek-inhibitor-mediated rescue of skeletal myopathy caused by activating hras mutation in a costello syndrome mouse model. Disease Models & Mechanisms, Sep 2022. URL: https://doi.org/10.1242/dmm.049166, doi:10.1242/dmm.049166. This article has 26 citations and is from a domain leading peer-reviewed journal.
(oba2018micewithan pages 1-3): Daiju Oba, Shin-ichi Inoue, Sachiko Miyagawa-Tomita, Yasumi Nakashima, Tetsuya Niihori, Seiji Yamaguchi, Yoichi Matsubara, and Yoko Aoki. Mice with an oncogenic hras mutation are resistant to high-fat diet-induced obesity and exhibit impaired hepatic energy homeostasis. EBioMedicine, 27:138-150, Jan 2018. URL: https://doi.org/10.1016/j.ebiom.2017.11.029, doi:10.1016/j.ebiom.2017.11.029. This article has 50 citations and is from a peer-reviewed journal.
(healy2024mediatingkinaseactivity pages 20-20): Fiona M. Healy, Amy L. Turner, Vanessa Marensi, and David J. MacEwan. Mediating kinase activity in ras-mutant cancer: potential for an individualised approach? Frontiers in Pharmacology, Sep 2024. URL: https://doi.org/10.3389/fphar.2024.1441938, doi:10.3389/fphar.2024.1441938. This article has 0 citations.
(yin2023targetingsmallgtpases pages 14-16): Guowei Yin, Jing Huang, Johnny Petela, Hongmei Jiang, Yuetong Zhang, Siqi Gong, Jiaxin Wu, Bei Liu, Jianyou Shi, and Yijun Gao. Targeting small gtpases: emerging grasps on previously untamable targets, pioneered by kras. Signal Transduction and Targeted Therapy, May 2023. URL: https://doi.org/10.1038/s41392-023-01441-4, doi:10.1038/s41392-023-01441-4. This article has 90 citations and is from a peer-reviewed journal.

Citations

nair2023regulationofrasgtpase pages 6-8
yu2023mechanismsforregulation pages 1-2
nair2023regulationofrasgtpase pages 1-2
mozzarelli2024functionalandstructural pages 6-7
katata2020costellosyndromemodel pages 1-2
tidyman2022mekinhibitormediatedrescueof pages 8-9
fuentesmateos2019concomitantdeletionof pages 1-2
fuentesmateos2024combinedhrasand pages 1-2
bhattarai2026recentbreakthroughsin pages 5-7
yin2023targetingsmallgtpases pages 16-17
healy2024mediatingkinaseactivity pages 2-3
patel2023investigatingtherole pages 18-21
healy2024mediatingkinaseactivity pages 12-13
weatherdon2024proteiniscreensidentify pages 25-28
oba2018micewithan pages 1-3
yin2023targetingsmallgtpases pages 1-2
yin2023targetingsmallgtpases pages 14-16
healy2024mediatingkinaseactivity pages 3-6
tidyman2022mekinhibitormediatedrescueof pages 1-2
healy2024mediatingkinaseactivity pages 20-20
https://doi.org/10.3390/kinasesphosphatases1020007
https://doi.org/10.1172/jci171104
https://doi.org/10.1172/jci165510
https://doi.org/10.1016/j.molcel.2024.06.027
https://doi.org/10.1038/s41419-020-02845-8
https://doi.org/10.1242/dmm.049166
https://doi.org/10.1038/s41419-019-2075-2
https://doi.org/10.1186/s12964-024-01717-4
https://doi.org/10.1172/jci165510;
https://doi.org/10.1016/j.cell.2024.08.017
https://doi.org/10.3389/fphar.2024.1441938;
https://doi.org/10.1038/s41392-023-01441-4
https://doi.org/10.3389/fphar.2024.1441938
https://doi.org/10.17863/cam.95441
https://doi.org/10.1016/j.celrep.2019.02.038
https://doi.org/10.17863/cam.107595
https://doi.org/10.1016/j.ebiom.2017.11.029
https://doi.org/10.3390/kinasesphosphatases1020007,
https://doi.org/10.1172/jci165510,
https://doi.org/10.3389/fphar.2024.1441938,
https://doi.org/10.1016/j.molcel.2024.06.027,
https://doi.org/10.1172/jci171104,
https://doi.org/10.1038/s41419-020-02845-8,
https://doi.org/10.1242/dmm.049166,
https://doi.org/10.1038/s41419-019-2075-2,
https://doi.org/10.1186/s12964-024-01717-4,
https://doi.org/10.1016/j.sbi.2025.103183,
https://doi.org/10.1038/s41392-023-01441-4,
https://doi.org/10.17863/cam.95441,
https://doi.org/10.17863/cam.107595,
https://doi.org/10.1016/j.ebiom.2017.11.029,

📄 View Raw YAML

id: Q61411
gene_symbol: Hras
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: Hras encodes the membrane-anchored Ras-family small GTPase H-Ras, a GDP/GTP molecular
  switch that relays receptor-derived signals to RAF-MEK-ERK, PI3K, RalGEF, and related effector
  pathways. Core function is GTP binding/hydrolysis and GTP-state-dependent effector recruitment
  at plasma-membrane and Golgi/endomembrane compartments after CAAX processing and reversible
  palmitoylation. Proliferation, senescence, differentiation, neural, immune, and wound-response
  phenotypes are curated as downstream or specialized contexts unless the annotation directly
  describes Ras switch activity or membrane-localized Ras signal transduction.
alternative_products:
- name: 1 (p21, H-Ras4A)
  id: Q61411-1
- name: 2 (p19, H-RasIDX)
  id: Q61411-2
  sequence_note: VSP_041598
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:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  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: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat
    orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs
    using Ensembl Compara
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human
    orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10704452
  title: A dual role of erbB2 in myelination and in expansion of the schwann cell precursor
    pool.
  findings: []
- id: PMID:10845775
  title: Neurofibromin negatively regulates neurotrophin signaling through p21ras in embryonic
    sensory neurons.
  findings: []
- id: PMID:10869344
  title: A novel RalGEF-like protein, RGL3, as a candidate effector for rit and Ras.
  findings: []
- id: PMID:10871846
  title: Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis.
  findings: []
- id: PMID:11173924
  title: Neuregulin-induced association of Sos Ras exchange protein with HER2(erbB2)/HER3(erbB3)
    receptor complexes in Schwann cells through a specific Grb2-HER2(erbB2) interaction.
  findings: []
- id: PMID:11551927
  title: The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse
    epidermal differentiation, senescence, and carcinogenesis.
  findings: []
- id: PMID:11877426
  title: Nerve growth factor-dependent activation of the small GTPase Rin.
  findings: []
- id: PMID:12427827
  title: SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex
    with postsynaptic density 95 and NMDA receptor.
  findings: []
- id: PMID:12446704
  title: Small GTPase Rah/Rab34 is associated with membrane ruffles and macropinosomes and
    promotes macropinosome formation.
  findings: []
- id: PMID:12878730
  title: The p53-dependent effects of macrophage migration inhibitory factor revealed by gene
    targeting.
  findings: []
- id: PMID:14712229
  title: 'G-protein-coupled receptor-mediated activation of rap GTPases: characterization
    of a novel Galphai regulated pathway.'
  findings: []
- id: PMID:15235600
  title: RabGEF1 is a negative regulator of mast cell activation and skin inflammation.
  findings: []
- id: PMID:15572682
  title: 'Functional genetic screen for genes involved in senescence: role of Tid1, a homologue
    of the Drosophila tumor suppressor l(2)tid, in senescence and cell survival.'
  findings: []
- id: PMID:16405865
  title: Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein.
  findings: []
- id: PMID:16478791
  title: APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
  findings: []
- id: PMID:16954213
  title: Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell death.
  findings: []
- id: PMID:17724343
  title: Spatial regulation of Raf kinase signaling by RKTG.
  findings: []
- id: PMID:18596699
  title: Novel type of Ras effector interaction established between tumour suppressor NORE1A
    and Ras switch II.
  findings: []
- id: PMID:18604197
  title: IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade.
  findings: []
- id: PMID:18760695
  title: Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral
    and central nervous system.
  findings: []
- id: PMID:19029245
  title: The protein phosphatase 2A regulatory subunits B'beta and B'delta mediate sustained
    TrkA neurotrophin receptor autophosphorylation and neuronal differentiation.
  findings: []
- id: PMID:19878719
  title: RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase
    signalling pathways.
  findings: []
- id: PMID:21357543
  title: Regulation of GATA-3 expression during CD4 lineage differentiation.
  findings: []
- id: PMID:21444916
  title: H-ras and N-ras are dispensable for T-cell development and activation but critical
    for protective Th1 immunity.
  findings: []
- id: PMID:23382219
  title: Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM
    proteins.
  findings: []
- id: PMID:31408278
  title: Silencing of lncRNA SNHG20 delays the progression of nonalcoholic fatty liver disease
    to hepatocellular carcinoma via regulating liver Kupffer cells polarization.
  findings: []
- id: PMID:33331896
  title: Merlin cooperates with neurofibromin and Spred1 to suppress the Ras-Erk pathway.
  findings: []
- id: PMID:7829473
  title: Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desensitization
    by insulin.
  findings: []
- id: PMID:8828504
  title: Comparison of the insulin and insulin-like growth factor 1 mitogenic intracellular
    signaling pathways.
  findings: []
- id: PMID:8939998
  title: RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic
    GDI protein interacting with the small GTP-binding proteins RhoB and RhoG.
  findings: []
- id: PMID:9488663
  title: Identification of Nore1 as a potential Ras effector.
  findings: []
- id: Reactome:R-MMU-9029152
  title: Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2:p-Y-Crkl:p-Y-Shc1:Grb2-1:Sos1,p-Y-Vav1 mediates
    exchange of GDP for GTP bound to Ras
  findings: []
- id: Reactome:R-NUL-1250468
  title: Ras guanyl-nucleotide exchange mediated by Sos1 in complex with GRB2 and P-Erbb2mut
  findings: []
- id: Reactome:R-NUL-1250472
  title: Ras guanyl-nucleotide exchange mediated by Sos1 bound to GRB2 in complex with P-Shc1:P-Erbb2mut
  findings: []
- id: file:mouse/Hras/Hras-deep-research-falcon.md
  title: Falcon deep research summary for mouse Hras
  findings: []
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cellular senescence is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Golgi membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: G protein activity is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: GTP binding is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Signal transduction is too broad for H-Ras.
    action: MODIFY
    reason: H-Ras is specifically a Ras-family small GTPase in Ras protein signal transduction.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
    proposed_replacement_terms:
    - &id001
      id: GO:0007265
      label: Ras protein signal transduction
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Membrane is too broad for H-Ras localization.
    action: MODIFY
    reason: H-Ras signaling depends on processed and palmitoylated localization at plasma
      membrane and Golgi/endomembrane compartments.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    - id: GO:0000139
      label: Golgi membrane
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9488663
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: The current local evidence does not provide term-specific support for H-Ras
      localization to the nucleoplasm.
    action: UNDECIDED
    reason: Automated localization transfer requires direct compartment evidence before retaining
      this annotation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytosol is consistent with core H-Ras switch activity, effector signaling, or
      localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-uniprot.txt
      supporting_text: 'DR   GO; GO:0005829; C:cytosol; ISO:GO_Central.'
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Nascent Ras proteins undergo processing in cytosol/ER and further modifications
        enabling targeting to the **inner leaflet of the plasma membrane**
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of transcription by RNA polymerase II is a supported downstream or
      specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of gene expression is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: GDP binding is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell migration is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of actin cytoskeleton organization is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of cell population proliferation is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of MAPK cascade is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of transcription by RNA polymerase II is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0046330
    label: positive regulation of JNK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of JNK cascade is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of epithelial cell proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is consistent with core H-Ras switch
      activity, effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0071480
    label: cellular response to gamma radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to gamma radiation is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090303
    label: positive regulation of wound healing
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of wound healing is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090314
    label: positive regulation of protein targeting to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein targeting to membrane is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular senescence is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0098696
    label: regulation of neurotransmitter receptor localization to postsynaptic specialization
      membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of neurotransmitter receptor localization to postsynaptic specialization
      membrane is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: glutamatergic synapse is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0160185
    label: phospholipase C activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: The current local evidence supports RAF, PI3K, and RalGEF effector signaling,
      but does not establish phospholipase C activator activity for H-Ras.
    action: UNDECIDED
    reason: Retaining this specific molecular function requires direct PLC activation evidence.
- term:
    id: GO:1900029
    label: positive regulation of ruffle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of ruffle assembly is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:2000630
    label: positive regulation of miRNA metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of miRNA metabolic process is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0000164
    label: protein phosphatase type 1 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The PP1 complex term does not describe the H-Ras core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: H-Ras may influence or associate with regulatory complexes in particular studies,
      but the core function is membrane-localized GDP/GTP switch signaling.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: GTPase activity is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: GTP binding is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The current local evidence does not provide term-specific support for H-Ras
      localization to the nucleoplasm.
    action: UNDECIDED
    reason: Automated localization transfer requires direct compartment evidence before retaining
      this annotation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytosol is consistent with core H-Ras switch activity, effector signaling, or
      localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-uniprot.txt
      supporting_text: 'DR   GO; GO:0005829; C:cytosol; ISO:GO_Central.'
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Nascent Ras proteins undergo processing in cytosol/ER and further modifications
        enabling targeting to the **inner leaflet of the plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of transcription by RNA polymerase II is a supported downstream or
      specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of gene expression is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: GDP binding is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell migration is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of actin cytoskeleton organization is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The current local evidence does not provide term-specific support for H-Ras
      localization to the ciliary basal body.
    action: UNDECIDED
    reason: Automated localization transfer requires direct compartment evidence before retaining
      this annotation.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of cell population proliferation is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of MAPK cascade is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein-containing complex binding is too generic to represent the core H-Ras
      molecular function; the informative biology is GTPase switch activity and effector-pathway
      activation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Use GTPase/GTP binding and Ras pathway terms rather than retaining a broad binding
      term as core.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of transcription by RNA polymerase II is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0046330
    label: positive regulation of JNK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of JNK cascade is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of epithelial cell proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of cell cycle is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is consistent with core H-Ras switch
      activity, effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0071480
    label: cellular response to gamma radiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to gamma radiation is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090303
    label: positive regulation of wound healing
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of wound healing is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090314
    label: positive regulation of protein targeting to membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein targeting to membrane is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular senescence is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0098696
    label: regulation of neurotransmitter receptor localization to postsynaptic specialization
      membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of neurotransmitter receptor localization to postsynaptic specialization
      membrane is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: glutamatergic synapse is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0160185
    label: phospholipase C activator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The current local evidence supports RAF, PI3K, and RalGEF effector signaling,
      but does not establish phospholipase C activator activity for H-Ras.
    action: UNDECIDED
    reason: Retaining this specific molecular function requires direct PLC activation evidence.
- term:
    id: GO:1900029
    label: positive regulation of ruffle assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of ruffle assembly is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:1905360
    label: GTPase complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: GTPase complex is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:2000630
    label: positive regulation of miRNA metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of miRNA metabolic process is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:19878719
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0090402
    label: oncogene-induced cell senescence
  evidence_type: IDA
  original_reference_id: PMID:11551927
  review:
    summary: oncogene-induced cell senescence is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043495
    label: protein-membrane adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:16405865
  review:
    summary: protein-membrane adaptor activity is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:8828504
  review:
    summary: insulin-like growth factor receptor signaling pathway is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:7829473
  review:
    summary: insulin receptor signaling pathway is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IDA
  original_reference_id: PMID:12878730
  review:
    summary: cellular senescence is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IDA
  original_reference_id: PMID:15572682
  review:
    summary: cellular senescence is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0014044
    label: Schwann cell development
  evidence_type: IMP
  original_reference_id: PMID:10704452
  review:
    summary: Schwann cell development is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0042552
    label: myelination
  evidence_type: IMP
  original_reference_id: PMID:10704452
  review:
    summary: myelination is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0042552
    label: myelination
  evidence_type: IMP
  original_reference_id: PMID:18760695
  review:
    summary: myelination is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: ISO
  original_reference_id: PMID:33331896
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0038133
    label: ERBB2-ERBB3 signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:11173924
  review:
    summary: ERBB2-ERBB3 signaling pathway is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043495
    label: protein-membrane adaptor activity
  evidence_type: ISO
  original_reference_id: PMID:33331896
  review:
    summary: protein-membrane adaptor activity is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0060612
    label: adipose tissue development
  evidence_type: IMP
  original_reference_id: PMID:31408278
  review:
    summary: adipose tissue development is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0048169
    label: regulation of long-term neuronal synaptic plasticity
  evidence_type: IMP
  original_reference_id: PMID:12427827
  review:
    summary: regulation of long-term neuronal synaptic plasticity is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16954213
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IPI
  original_reference_id: PMID:14712229
  review:
    summary: positive regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IGI
  original_reference_id: PMID:11877426
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0032729
    label: positive regulation of type II interferon production
  evidence_type: IMP
  original_reference_id: PMID:21444916
  review:
    summary: positive regulation of type II interferon production is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0042088
    label: T-helper 1 type immune response
  evidence_type: IMP
  original_reference_id: PMID:21444916
  review:
    summary: T-helper 1 type immune response is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0042832
    label: defense response to protozoan
  evidence_type: IMP
  original_reference_id: PMID:21444916
  review:
    summary: defense response to protozoan is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0050852
    label: T cell receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:21444916
  review:
    summary: T cell receptor signaling pathway is a supported downstream or specialized H-Ras
      context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23382219
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:17724343
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8939998
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10869344
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18596699
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:16954213
  review:
    summary: intrinsic apoptotic signaling pathway is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15235600
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Golgi apparatus is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:21357543
  review:
    summary: positive regulation of gene expression is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9029152
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-1250468
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-1250472
  review:
    summary: plasma membrane is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
        to the **plasma membrane**
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18604197
  review:
    summary: protein binding records a physical association but is too generic to describe
      the gene product function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports regulated signaling-complex assembly, not a meaningful standalone
      protein binding function; more informative molecular and pathway terms capture the biology.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:18604197
  review:
    summary: GTP binding is consistent with core H-Ras switch activity, effector signaling,
      or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:16954213
  review:
    summary: intrinsic apoptotic signaling pathway is a supported downstream or specialized
      H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0046579
    label: positive regulation of Ras protein signal transduction
  evidence_type: ISO
  original_reference_id: PMID:19029245
  review:
    summary: positive regulation of Ras protein signal transduction is consistent with core
      H-Ras switch activity, effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:16478791
  review:
    summary: positive regulation of cell population proliferation is a supported downstream
      or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043524
    label: negative regulation of neuron apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:10845775
  review:
    summary: negative regulation of neuron apoptotic process is a supported downstream or
      specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0043524
    label: negative regulation of neuron apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:10845775
  review:
    summary: negative regulation of neuron apoptotic process is a supported downstream or
      specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007264
    label: small GTPase-mediated signal transduction
  evidence_type: IDA
  original_reference_id: PMID:14712229
  review:
    summary: Small GTPase-mediated signaling is correct but less specific than Ras signaling
      for Hras.
    action: MODIFY
    reason: The mouse gene encodes H-Ras, so the Ras protein signal transduction term is more
      specific.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
        that acts as a **signal-transducing molecular switch**.
    proposed_replacement_terms:
    - *id001
- term:
    id: GO:0006897
    label: endocytosis
  evidence_type: IDA
  original_reference_id: PMID:12446704
  review:
    summary: endocytosis is a supported downstream or specialized H-Ras context.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a cell-type, disease-model, developmental, transcriptional,
      or phenotypic consequence of Ras signaling rather than the primary switch function.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: Mouse knock-in models demonstrate that **MEK inhibition (PD0325901)**
        can reverse both signaling readouts and organismal phenotypes
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: TAS
  original_reference_id: PMID:10871846
  review:
    summary: Ras protein signal transduction is consistent with core H-Ras switch activity,
      effector signaling, or localization.
    action: ACCEPT
    reason: The term directly captures H-Ras guanine nucleotide cycling, membrane localization,
      or immediate Ras effector pathway output.
    supported_by:
    - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
      supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
core_functions:
- description: Functions as a Ras-family GDP/GTP molecular switch with intrinsic and GAP-stimulated
    GTPase activity.
  molecular_function: &id002
    id: GO:0003924
    label: GTPase activity
  directly_involved_in:
  - *id001
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0000139
    label: Golgi membrane
  supported_by:
  - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
    supporting_text: Mouse **HRas** encodes a membrane-anchored, Ras-family **small GTPase**
      that acts as a **signal-transducing molecular switch**.
- description: In the GTP-bound state, recruits RAF and other effectors to activate downstream
    MAPK, PI3K, and RalGEF signaling arms.
  molecular_function: *id002
  directly_involved_in:
  - id: GO:0043410
    label: positive regulation of MAPK cascade
  - id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
    supporting_text: 'Active (GTP-bound) HRas recruits and activates multiple effector classes:'
- description: Uses CAAX processing and reversible palmitoylation to cycle between Golgi and
    plasma membrane signaling compartments.
  molecular_function: *id002
  directly_involved_in:
  - id: GO:0007265
    label: Ras protein signal transduction
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005794
    label: Golgi apparatus
  supported_by:
  - reference_id: file:mouse/Hras/Hras-deep-research-falcon.md
    supporting_text: dual palmitoylation (C181/C184) supports Golgi retention/exit and cycling
      to the **plasma membrane**
proposed_new_terms: []
suggested_questions:
- question: Which Hras developmental and neuronal annotations reflect direct H-Ras activity
    versus compensation or redundancy with Nras/Kras?
- question: Should Hras membrane-trafficking annotations distinguish Golgi palmitoylation
    from plasma-membrane signaling compartments?
suggested_experiments:
- description: Quantitatively compare wild-type and palmitoylation-defective H-Ras rescue
    in Hras/Nras-deficient mouse cells for RAF, PI3K, and RalGEF pathway activation.
  hypothesis: H-Ras pathway output depends on Golgi-plasma membrane cycling and cannot be
    inferred from generic cytosolic Ras activity.
  experiment_type: Allelic rescue and pathway phosphoproteomics

Hras

Gene Description

Existing Annotations Review

Core Functions

Functions as a Ras-family GDP/GTP molecular switch with intrinsic and GAP-stimulated GTPase activity.

In the GTP-bound state, recruits RAF and other effectors to activate downstream MAPK, PI3K, and RalGEF signaling arms.

Uses CAAX processing and reversible palmitoylation to cycle between Golgi and plasma membrane signaling compartments.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Mouse Hras (UniProt Q61411) — Functional Annotation, Pathways, Localization, and Recent Advances

Scope and target verification (critical identity check)

1. Key concepts and definitions (current understanding)

1.1 HRas as a “molecular switch” small GTPase

1.2 Enzymatic activity and “substrate specificity” for HRas

2. Molecular function, processing, and subcellular localization

2.1 CAAX processing and prenylation-dependent membrane association

2.2 HRas palmitoylation and Golgi-to–plasma membrane cycling

2.3 Cellular compartments where HRas acts

3. Downstream pathways and effector mechanisms

3.1 Canonical effector arms

3.2 2024 structural/functional refinement of effector interactions

4. Regulation beyond lipidation: additional PTMs and signal tuning

5. Mouse genetics: in vivo evidence for HRas function

5.1 Activating knock-in alleles model RASopathies (Costello syndrome) and map pathway causality

HrasG12S/+ knock-in: skin inflammation and MAPK output

HrasG12V knock-in: skeletal myopathy rescued by MEK inhibition

5.2 Loss-of-function context and Ras isoform compensation: Hras/Nras double knockout

6. Recent developments and latest research (prioritizing 2023–2024)

6.1 2023–2024: trafficking/PTM regulation as therapeutic logic

6.2 2024: effector structural insights refine pathway annotation

6.3 2023–2024: direct Ras targeting and druggability (context relevant to HRas)

7. Current applications and real-world implementations

7.1 In vivo pathway intervention in HRas-driven phenotypes

7.2 Targeting Ras membrane association and PTM pathways

8. Expert synthesis: primary functional statement for annotation

Evidence maps (tables)

Limitations and evidence gaps

Key URLs (selected)

Citations

📄 View Raw YAML