HRAS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: HRAS is membrane-targeted and signals from the plasma membrane. Reason: Plasma membrane localization is central to HRAS signaling, supported by CAAX processing and palmitoylation-dependent trafficking. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS contains a C-terminal CAAX motif that is post-translationally processed by a canonical sequence: farnesylation → AAX proteolysis (RCE1) → carboxymethylation (ICMT).
GO:0007265 Ras protein signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: HRAS is a canonical Ras-family GTPase that mediates Ras protein signal transduction. Reason: Ras protein signal transduction is the core biological process for HRAS as a GDP/GTP-regulated molecular switch. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins (including HRAS) are GTP hydrolases that function as binary molecular switches: GDP-bound is “OFF,” GTP-bound is “ON,” and the ON state supports binding to downstream effector proteins.
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: HRAS signaling can promote proliferation, but this is a downstream and context-dependent outcome rather than the core HRAS molecular function. Reason: Proliferation is a canonical outcome of Ras signaling in some cellular contexts, but it depends on cell type, stimulus duration, feedback, and mutant versus wild-type HRAS state. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS-ERK signaling dynamics can bias proliferation versus differentiation outputs, but these outcomes depend strongly on cell type and signaling kinetics.
GO:0003924 GTPase activity	IBA GO_REF:0000033	ACCEPT	Summary: HRAS has intrinsic GTPase activity. Reason: GTP hydrolysis is the core molecular switch activity of HRAS. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Intrinsic GTPase activity is accelerated by GAPs, while GEFs promote GDP→GTP exchange.
GO:0090398 cellular senescence	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Cellular senescence is a context-dependent outcome of oncogenic Ras signaling rather than the primary normal function of HRAS. Reason: Senescence evidence is strongly tied to oncogenic Ras expression and should not be treated as the core function of wild-type HRAS. Supporting Evidence: PMID:9054499 Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest. file:human/HRAS/HRAS-deep-research-falcon.md Apoptosis/senescence: generally non-core default for HRAS
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: Golgi membrane localization is part of HRAS lipidation-dependent membrane trafficking. Reason: HRAS is processed and trafficked through ER/Golgi membranes before plasma membrane localization. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Palmitoylation provides the “second signal” for HRAS membrane targeting beyond prenylation and supports vesicular transport from Golgi→plasma membrane; palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane.
GO:0000165 MAPK cascade	IEA GO_REF:0000117	ACCEPT	Summary: HRAS activates signaling through the RAF-MEK-ERK MAPK cascade. Reason: MAPK cascade signaling is a proximal canonical Ras output, although distal phenotypic outcomes should be curated separately. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins sit at the apex of the RAF–MEK–ERK (MAPK) cascade, and Ras-effector binding directly routes signals into MAPK outputs.
GO:0003924 GTPase activity	IEA GO_REF:0000002	ACCEPT	Summary: HRAS has intrinsic GTPase activity. Reason: GTPase activity is the core catalytic molecular function of HRAS. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Intrinsic GTPase activity is accelerated by GAPs, while GEFs promote GDP→GTP exchange.
GO:0003925 G protein activity	IEA GO_REF:0000003	MODIFY	Summary: HRAS is a small monomeric GTPase rather than a heterotrimeric G protein; the more precise annotation is GTPase activity. Reason: GO:0003925 can cover Ras-family GTPases, but the annotation should use GO:0003924 because it captures the catalytic GTP-hydrolysis function more precisely. Proposed replacements: GTPase activity Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.
GO:0005525 GTP binding	IEA GO_REF:0000120	ACCEPT	Summary: HRAS binds guanine nucleotides as part of its GDP/GTP switch mechanism. Reason: GTP binding is a core molecular function for Ras-family GTPases. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.
GO:0005634 nucleus	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Nuclear localization is not characteristic of the canonical farnesylated, membrane-anchored H-Ras p21 isoform. Reason: The mature p21 H-Ras is targeted to the plasma membrane and Golgi/endomembranes via CAAX prenylation and palmitoylation; nuclear localization is reported mainly for the minor alternatively spliced p19 (H-RasIDX) isoform, so a general nuclear CC annotation over-projects onto the main gene product. Supporting Evidence: PMID:14500341 Both the endogenous and the transiently expressed p19 protein are detected in COS-1 and HeLa cells and show nuclear diffuse and speckled patterns as well as cytoplasmic localization.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: A broad cytoplasm annotation is consistent with HRAS biology but less informative than its specific membrane locations. Reason: Newly synthesized and a fraction of HRAS exists in the cytoplasm prior to membrane targeting, and the p19 isoform shows cytoplasmic localization; however, the functionally meaningful locations are plasma membrane and Golgi/endomembrane, so the generic cytoplasm term is retained as non-core. Supporting Evidence: PMID:14500341 Both the endogenous and the transiently expressed p19 protein are detected in COS-1 and HeLa cells and show nuclear diffuse and speckled patterns as well as cytoplasmic localization.
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: Golgi localization is supported by HRAS membrane trafficking and palmitoylation cycles. Reason: HRAS cycles through Golgi membranes as part of its lipidation-dependent targeting to signaling membranes. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Palmitoylation provides the “second signal” for HRAS membrane targeting beyond prenylation and supports vesicular transport from Golgi→plasma membrane; palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: HRAS localizes to the plasma membrane for Ras signaling. Reason: Plasma membrane localization is a core cellular context for HRAS signal-transduction function. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Plasma membrane localization \| HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0007165 signal transduction	IEA GO_REF:0000002	MODIFY	Summary: The annotation captures the broad signaling role of HRAS, but Ras protein signal transduction is more informative. Reason: HRAS is specifically a Ras-family signal-transduction GTPase, so the existing broad signal transduction term should be replaced with the specific Ras protein signal transduction term. Proposed replacements: Ras protein signal transduction Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Ras protein signal transduction \| HRAS is one of the canonical RAS proteins acting upstream of multiple effector pathways in Ras signal transduction.
GO:0016020 membrane	IEA GO_REF:0000002	MODIFY	Summary: HRAS is membrane-associated, but the generic membrane term is less informative than its specific plasma membrane and Golgi membrane annotations. Reason: HRAS lipidation targets it to specific membranes; the broad membrane term should be replaced with the more precise plasma membrane location that is central to its signaling. Proposed replacements: plasma membrane Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Perinuclear localization is consistent with HRAS pools at the Golgi and perinuclear endomembranes during lipidation-dependent trafficking. Reason: HRAS cycles through Golgi/recycling endosomes, which lie in the perinuclear region, so this localization is plausible but secondary to the plasma membrane and Golgi membrane annotations. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane
GO:0005515 protein binding	IPI PMID:11335720 Prenylated Rab acceptor protein is a receptor for prenylated...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with PRA1/prenylated Rab acceptor (a receptor for prenylated small GTPases). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:11857081 The putative tumor suppressor RASSF1A homodimerizes and hete...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RASSF1A/NORE1 Ras-GTP binding proteins. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RAF kinase (two-hybrid interactions). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:12628188 Structural evidence for feedback activation by Ras.GTP of th...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras-GEF SOS (feedback Ras-GTP activation site). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:14724641 Ras regulates assembly of mitogenic signalling complexes thr...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the effector IMP in mitogenic signalling complexes. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:15507210 Structural analysis of autoinhibition in the Ras activator S...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (autoinhibition). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:15886098 RIN1 is an ABL tyrosine kinase activator and a regulator of ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the ABL activator/effector RIN1. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:16316996 The RAP1 guanine nucleotide exchange factor Epac2 couples cy...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the RAP1 GEF Epac2. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:16698549 GTP-Ras disrupts the intramolecular complex of C1 and RA dom...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with NORE1/RASSF5 (C1 and RA domains). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:16810318 Release of RASSF1C from the nucleus by Daxx degradation link...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RASSF1C (DNA-damage/JNK context). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:17084389 Catalytic competence of the Ras-GEF domain of hSos1 requires...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras-GEF hSos1 (REM domain). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:17540175 Binding of ras to phosphoinositide 3-kinase p110alpha is req...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with PI3K p110alpha (Ras-driven tumorigenesis). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:18073111 Transformation efficiency of RasQ61 mutants linked to struct...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RAF in the context of RasQ61 mutant transformation. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:18273062 A novel switch region regulates H-ras membrane orientation a...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a switch-region partner regulating H-Ras membrane orientation. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:18454158 Membrane-dependent signal integration by the Ras activator S...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (membrane signal integration). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:18596699 Novel type of Ras effector interaction established between t...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the tumour-suppressor effector NORE1A via Ras switch II. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:19063885 Regulation of growth and survival of activated T cells by ce...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with cell-transducing Ras inhibitors. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:19141281 Differences in flexibility underlie functional differences i...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activators SOS and RasGRF1. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:19222999 Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathwa...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with FKBP38 (Rheb/mTORC1 pathway reassessment). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:19696784 Nucleocytoplasmic transport of Alp7/TACC organizes spatiotem...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a partner identified in a fission-yeast TACC study. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:20080631 Ras membrane orientation and nanodomain localization generat...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with partners affecting Ras membrane orientation/nanodomain localization. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:20133692 Role of the histone domain in the autoinhibition and activat...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (histone domain autoinhibition). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:20133694 Allosteric gating of Son of sevenless activity by the histon...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (allosteric gating by histone domain). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:20178605 Genetic and functional characterization of putative Ras/Raf ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with putative Ras/Raf interaction inhibitors. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:20936779 A human MAP kinase interactome.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with MAP kinase interactome partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:22020336 p37δ is a new isoform of PI3K p110δ that increases cell prol...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with PI3K p110delta isoform p37delta. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:22169110 Nilotinib and MEK inhibitors induce synthetic lethality thro...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RAF in drug-resistant CML (paradoxical activation). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:24412244 Charting the molecular links between driver and susceptibili...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with driver/susceptibility partners in colorectal cancer. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:24441586 Integrated RAS signaling defined by parallel NMR detection o...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with effectors and regulators detected by parallel NMR. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with Raf-1 and MST2/Hippo signalling partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with endogenous pathway partners profiled by proximity ligation. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:25684575 Allosteric effects of the oncogenic RasQ61L mutant on Raf-RB...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with Raf-RBD (oncogenic RasQ61L allosteric effects). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:26165597 The RAS-Binding Domain of Human BRAF Protein Serine/Threonin...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the BRAF Ras-binding domain. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:26635368 Interaction between a Domain of the Negative Regulator of th...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with neurofibromin GAP-related domain/SPRED1 (Legius/NF1 context). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with protein-community partners from a large interactome map. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RAS-isoform interactome partners (PIP5K1A study). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:30518913 UBIAD1 suppresses the proliferation of bladder carcinoma cel...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with UBIAD1 (H-Ras C-terminal trafficking). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:31209342 GGTase3 is a newly identified geranylgeranyltransferase targ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a substrate context in a geranylgeranyltransferase study. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with neurodegenerative-disease network partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with cell-specific interactome partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:34591612 A protein interaction landscape of breast cancer.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with breast-cancer interactome partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with head and neck cancer interactome partners. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with mutation-directed neo-interaction partners in cancer. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with isoform-specific, nucleotide-dependent RAS interactors. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with partners from multimodal cell maps. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-termi...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the c-Raf-1 amino-terminal regulatory domain. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:8670882 Identification of a novel Rac1-interacting protein involved ...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a Rac1-interacting membrane-ruffling protein. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the effector RIN1. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:9447984 Regulation of Sos activity by intramolecular interactions.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (intramolecular regulation). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:9488663 Identification of Nore1 as a potential Ras effector.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the potential Ras effector Nore1. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:9690470 The structural basis of the activation of Ras by Sos.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the Ras GEF SOS (activation mechanism). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI P01112-2 PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with binary interactome partners (isoform P01112-2). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0007265 Ras protein signal transduction	IEA GO_REF:0000107	ACCEPT	Summary: HRAS is directly involved in Ras protein signal transduction. Reason: This is the core biological process for the HRAS GTPase switch. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md “Ras protein signal transduction” and “positive regulation of MAPK cascade” are generally core for HRAS, but very specific outcome terms (e.g., “cell cycle progression” as a default) should be restricted to contexts with strong, direct, wild-type evidence.
GO:0008286 insulin receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: HRAS acts downstream of receptor tyrosine kinases including the insulin receptor, but this is one specific RTK input among many rather than a core HRAS-defining process. Reason: RAS GTPases relay signals from multiple growth-factor/RTK inputs (EGFR, insulin receptor, etc.) into the MAPK and PI3K pathways; the insulin receptor pathway is a legitimate but non-core context for HRAS, while the core annotation is the general Ras protein signal transduction. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins sit at the apex of the RAF–MEK–ERK (MAPK) cascade, and Ras-effector binding directly routes signals into MAPK outputs.
GO:0014044 Schwann cell development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Schwann cell development is a distal developmental outcome and is not a core HRAS molecular function annotation. Reason: This automated IEA row appears to over-project broad Ras-family or pathway-derived developmental biology onto HRAS; there is no direct evidence in this review that wild-type HRAS is a proximal regulator of Schwann cell development specifically. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md 2) Avoid overly broad BP terms (e.g., generic “cancer,” “development,” “cell cycle,” “transcriptional regulation,” “immune/inflammatory processes”) unless there is direct mechanistic evidence placing wild-type HRAS as a proximal regulator rather than a downstream correlate. Large interactome datasets include false positives and many context-specific interactors.
GO:0042552 myelination	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Myelination is a distal developmental outcome and is not supported as a core HRAS annotation. Reason: This automated IEA row appears to over-project broad Ras-family or pathway-derived developmental biology onto HRAS; HRAS mutations can cause developmental phenotypes, but that does not make myelination a proximal wild-type HRAS function for GO annotation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Do not transfer oncogenic mutant phenotypes to wild-type HRAS GO BP terms by default.
GO:0043495 protein-membrane adaptor activity	IEA GO_REF:0000107	REMOVE	Summary: HRAS is a lipid-modified small GTPase, not a protein-membrane adaptor. Reason: HRAS membrane association is mediated by its own CAAX processing and palmitoylation; that trafficking mechanism should not be represented as protein-membrane adaptor activity. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Membrane targeting by CAAX prenylation and palmitoylation \| HRAS uses CAAX farnesylation, AAX cleavage, carboxymethylation, and reversible palmitoylation as the core membrane-targeting logic.
GO:0060612 adipose tissue development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Adipose tissue development is too distal to represent the core function of HRAS. Reason: This automated IEA row appears to over-project broad Ras-family or pathway-derived developmental biology onto HRAS; direct evidence that wild-type HRAS is a proximal regulator of adipose tissue development was not identified in this review. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md 2) Avoid overly broad BP terms (e.g., generic “cancer,” “development,” “cell cycle,” “transcriptional regulation,” “immune/inflammatory processes”) unless there is direct mechanistic evidence placing wild-type HRAS as a proximal regulator rather than a downstream correlate. Large interactome datasets include false positives and many context-specific interactors.
GO:0046579 positive regulation of Ras protein signal transduction	NAS PMID:35831509 Structure-function analysis of the SHOC2-MRAS-PP1C holophosp...	KEEP AS NON CORE	Summary: HRAS participates in positive feedback loops within RAS-ERK signaling (e.g., via SHOC2-MRAS-PP1C-mediated RAF dephosphorylation), but the cited study focuses on the MRAS-containing holophosphatase rather than HRAS directly. Reason: Positive regulation of Ras signal transduction is biologically reasonable for HRAS (Ras-GTP can feedback-activate SOS), but the supporting reference (PMID:35831509) characterizes the SHOC2-MRAS-PP1C complex; the annotation is plausible at the pathway level but not a direct, core HRAS molecular function. The core process is captured by GO:0007265. Supporting Evidence: PMID:35831509 Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. file:human/HRAS/HRAS-deep-research-falcon.md A key GO-relevant principle is that bona fide Ras effectors must bind RAS in a nucleotide-dependent manner (GTP-bound)
GO:0006357 regulation of transcription by RNA polymerase II	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	MARK AS OVER ANNOTATED	Summary: This transcription annotation is based on a downstream oncogenic Ras model and should not be treated as a direct HRAS function. Reason: PMID:23027131 describes oncogenic Ras regulation of Wnt4/miR-24 and motility phenotypes, which are distal transcriptional consequences rather than a direct normal molecular function of HRAS. Supporting Evidence: PMID:23027131 By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling. file:human/HRAS/HRAS-deep-research-falcon.md 2) Avoid overly broad BP terms (e.g., generic “cancer,” “development,” “cell cycle,” “transcriptional regulation,” “immune/inflammatory processes”) unless there is direct mechanistic evidence placing wild-type HRAS as a proximal regulator rather than a downstream correlate. Large interactome datasets include false positives and many context-specific interactors.
GO:0007265 Ras protein signal transduction	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	ACCEPT	Summary: The paper uses oncogenic Ras, but the annotation to Ras protein signal transduction is consistent with HRAS biology. Reason: HRAS's proximal role in Ras protein signal transduction is core, even though distal phenotypes from this particular study require caution. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Ras protein signal transduction \| HRAS is one of the canonical RAS proteins acting upstream of multiple effector pathways in Ras signal transduction.
GO:0042127 regulation of cell population proliferation	IDA PMID:9054499 Oncogenic ras provokes premature cell senescence associated ...	KEEP AS NON CORE	Summary: Oncogenic Ras regulates proliferation/senescence outcomes, but this is not a core wild-type HRAS function. Reason: The supporting paper uses oncogenic Ras and shows growth arrest/senescence in primary cells, making this a context-dependent downstream outcome. Supporting Evidence: PMID:9054499 Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest.
GO:0000165 MAPK cascade	TAS Reactome:R-HSA-5673001	ACCEPT	Summary: HRAS signals through the RAF-MEK-ERK MAPK cascade. Reason: MAPK signaling is a proximal canonical output of HRAS-GTP effector binding. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins sit at the apex of the RAF–MEK–ERK (MAPK) cascade, and Ras-effector binding directly routes signals into MAPK outputs.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: Nucleoplasmic localization is not characteristic of the membrane-anchored p21 H-Ras and likely derives from high-throughput localization data or the minor p19 isoform. Reason: The mature, lipidated H-Ras is targeted to plasma membrane and Golgi/endomembranes; nucleoplasmic localization is reported mainly for the alternatively spliced p19 (H-RasIDX), so a nucleoplasm CC term over-projects onto the canonical gene product. Supporting Evidence: PMID:14500341 Both the endogenous and the transiently expressed p19 protein are detected in COS-1 and HeLa cells and show nuclear diffuse and speckled patterns as well as cytoplasmic localization.
GO:0005829 cytosol	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: A cytosolic pool of HRAS exists transiently before and during membrane targeting. Reason: Newly synthesized HRAS and the p19 isoform can be cytosolic, so the annotation is acceptable, but the functionally important locations are the plasma membrane and Golgi/endomembranes. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0043410 positive regulation of MAPK cascade	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	ACCEPT	Summary: HRAS positively regulates MAPK cascade signaling. Reason: Positive regulation of MAPK cascade is a proximal canonical Ras output, although PMID:23027131 itself is an oncogenic Ras model and distal phenotypes should be reviewed cautiously. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md “Ras protein signal transduction” and “positive regulation of MAPK cascade” are generally core for HRAS, but very specific outcome terms (e.g., “cell cycle progression” as a default) should be restricted to contexts with strong, direct, wild-type evidence. file:human/HRAS/HRAS-deep-research-falcon.md Positive regulation of MAPK cascade \| RAS signaling is funneled strongly into RAF-MEK-ERK, and HRAS contributes to ERK output and MAPK signaling dynamics.
GO:0003924 GTPase activity	TAS Reactome:R-HSA-9649736	ACCEPT	Summary: HRAS has intrinsic GTPase activity. Reason: GTP hydrolysis is the core molecular switch activity of HRAS. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Intrinsic GTPase activity is accelerated by GAPs, while GEFs promote GDP→GTP exchange.
GO:0160185 phospholipase C activator activity	IDA PMID:11022048 Regulation of a novel human phospholipase C, PLCepsilon, thr...	KEEP AS NON CORE	Summary: HRAS can directly activate PLCepsilon in a GTP-dependent manner. Reason: This is a well-supported specific effector activity, but it represents one downstream branch rather than the core HRAS molecular function. Supporting Evidence: PMID:11022048 The Ras-associating domain of PLCepsilon specifically binds to the GTP-bound forms of Ha-Ras and Rap1A. PMID:11022048 These results indicate that Ras directly regulates phosphoinositide breakdown through membrane targeting of PLCepsilon.
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IDA PMID:12202034 Ras and Rap control AMPA receptor trafficking during synapti...	KEEP AS NON CORE	Summary: Ras relays NMDA-R/CaMKII signaling to drive synaptic delivery of AMPA receptors during long-term potentiation, a neuron-specific downstream output of Ras signaling. Reason: This is a well-supported but cell-type-specific (postsynaptic) function that is a distal consequence of Ras-MAPK signaling rather than the core molecular switch function of HRAS. Supporting Evidence: PMID:12202034 Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery of AMPA-Rs during long-term potentiation.
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IMP PMID:12202034 Ras and Rap control AMPA receptor trafficking during synapti...	KEEP AS NON CORE	Summary: Perturbation of Ras alters synaptic AMPA receptor delivery during LTP, supporting a non-core synaptic-plasticity role. Reason: The IMP evidence supports a neuron-specific role downstream of Ras-MAPK signaling; it is a legitimate process annotation but non-core relative to the GTPase/signal-transduction function of HRAS. Supporting Evidence: PMID:12202034 Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery of AMPA-Rs during long-term potentiation.
GO:0098978 glutamatergic synapse	IDA PMID:12202034 Ras and Rap control AMPA receptor trafficking during synapti...	KEEP AS NON CORE	Summary: HRAS functions in postsynaptic signaling at glutamatergic synapses during synaptic plasticity. Reason: The glutamatergic synapse location reflects a neuron-specific context for Ras signaling and is a valid but non-core localization relative to plasma membrane and Golgi. Supporting Evidence: PMID:12202034 we examine the small GTPases Ras and Rap in the postsynaptic signaling underlying synaptic plasticity
GO:0098978 glutamatergic synapse	IMP PMID:12202034 Ras and Rap control AMPA receptor trafficking during synapti...	KEEP AS NON CORE	Summary: Manipulation of Ras at glutamatergic synapses alters AMPA receptor trafficking during plasticity. Reason: This synapse-localization annotation is supported but represents a neuron-specific context rather than a core HRAS localization. Supporting Evidence: PMID:12202034 we examine the small GTPases Ras and Rap in the postsynaptic signaling underlying synaptic plasticity
GO:0032956 regulation of actin cytoskeleton organization	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	KEEP AS NON CORE	Summary: This is a downstream motility phenotype from an oncogenic Ras model, not a core HRAS function. Reason: The annotation is biologically plausible as a distal Ras signaling output, but it should be marked non-core because the evidence is from malignant transformation/oncogenic Ras context. Supporting Evidence: PMID:23027131 Wnt4 interferes with Ras-induced actin cytoskeleton reorganization through non-canonical pathways, by altering the balance between the activation of different Rho-family small guanosine triphosphatases (GTPases).
GO:0051726 regulation of cell cycle	IDA PMID:9054499 Oncogenic ras provokes premature cell senescence associated ...	KEEP AS NON CORE	Summary: Cell-cycle arrest is a downstream outcome of oncogenic Ras-induced senescence. Reason: This annotation is supported as a context-specific oncogenic Ras outcome but should not be represented as the core normal function of HRAS. Supporting Evidence: PMID:9054499 The arrest induced by ras is accompanied by accumulation of p53 and p16, and is phenotypically indistinguishable from cellular senescence.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9647994	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802834	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802908	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802918	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802922	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802924	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802925	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802926	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802937	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802941	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802942	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802943	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6803233	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6803234	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6803240	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8936731	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9651280	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-9647980	ACCEPT	Summary: HRAS transits and cycles through Golgi membranes during palmitoylation-dependent trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-9647982	ACCEPT	Summary: HRAS transits and cycles through Golgi membranes during palmitoylation-dependent trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9647978	ACCEPT	Summary: Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9647999	ACCEPT	Summary: Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1168636	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1225951	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1225957	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1250383	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1306972	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1433471	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-170986	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-177938	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-177945	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-186834	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-210977	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2179407	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2424477	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-392054	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5218845	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5621573	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5624486	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5624492	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5624494	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5637806	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5637808	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654392	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654402	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654413	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654426	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654600	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654618	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654647	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5654663	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655241	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655277	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655326	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5655347	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5658231	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5658435	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672950	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672965	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672966	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672969	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672972	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672973	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672978	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5672980	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5674018	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5674022	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5675417	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5675431	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5675433	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802837	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8851827	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8851877	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8851899	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8941613	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8941618	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8941623	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8941628	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8981353	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8981355	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9607304	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9632906	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9632918	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9634418	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9647980	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9649733	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9649735	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9649736	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9653108	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656209	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656211	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656212	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656213	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656214	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9656215	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9657599	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9657603	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9657606	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9657608	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9658253	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9660557	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9664991	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665009	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665404	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665408	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665700	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665707	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9670436	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9672163	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9672170	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9695853	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9703441	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9647977	ACCEPT	Summary: Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9647982	ACCEPT	Summary: Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0005829 cytosol	TAS Reactome:R-HSA-9647978	KEEP AS NON CORE	Summary: A cytosolic pool of HRAS exists prior to and during membrane targeting, consistent with this Reactome reaction location. Reason: This Reactome TAS row places a HRAS reaction in the cytosol, consistent with the soluble/pre-membrane pool; the location is valid but non-core relative to the plasma membrane and Golgi/endomembranes. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0090314 positive regulation of protein targeting to membrane	IMP PMID:11022048 Regulation of a novel human phospholipase C, PLCepsilon, thr...	KEEP AS NON CORE	Summary: GTP-bound HRAS recruits PLCepsilon to the membrane, promoting membrane targeting of this effector. Reason: This is a specific, well-supported consequence of HRAS-GTP binding the PLCepsilon RA domain and recruiting it to membranes, but it is one effector branch rather than the core HRAS molecular function. Supporting Evidence: PMID:11022048 These results indicate that Ras directly regulates phosphoinositide breakdown through membrane targeting of PLCepsilon.
GO:0071480 cellular response to gamma radiation	IDA PMID:16213212 Regulation of p53 translation and induction after DNA damage...	MARK AS OVER ANNOTATED	Summary: The cited reference concerns RPL26/nucleolin control of p53 translation after irradiation and does not establish a direct, proximal HRAS role in the gamma-radiation response. Reason: PMID:16213212 focuses on p53 translational induction by RPL26 and nucleolin after DNA damage; there is no direct evidence here that wild-type HRAS is a proximal mediator of the cellular response to gamma radiation, so this is a distal/indirect over-annotation. Supporting Evidence: PMID:16213212 Ribosomal protein L26 (RPL26) and nucleolin were found to bind to the 5' untranslated region (UTR) of p53 mRNA and to control p53 translation and induction after DNA damage.
GO:0003924 GTPase activity	IMP PMID:9230043 Regional polysterism in the GTP-bound form of the human c-Ha...	ACCEPT	Summary: HRAS has intrinsic GTPase activity, a core property of this small GTPase switch. Reason: Intrinsic GTP hydrolysis is the defining catalytic function of HRAS and is well established structurally and biochemically; this is a core molecular function. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Intrinsic GTPase activity is accelerated by GAPs, while GEFs promote GDP→GTP exchange.
GO:0005525 GTP binding	IMP PMID:9230043 Regional polysterism in the GTP-bound form of the human c-Ha...	ACCEPT	Summary: HRAS binds GTP with high affinity as part of its nucleotide-dependent switch. Reason: GTP binding is a core molecular function of HRAS, well supported by structural studies of the GTP-bound conformation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.
GO:0019003 GDP binding	IMP PMID:8142349 Solution structure and dynamics of ras p21.GDP determined by...	ACCEPT	Summary: HRAS binds GDP in its inactive state, completing the GDP/GTP switch cycle. Reason: GDP binding (the OFF state of the switch) is a core molecular function of HRAS, demonstrated by NMR structural studies of the GDP-bound form. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins (including HRAS) are GTP hydrolases that function as binary molecular switches: GDP-bound is “OFF,” GTP-bound is “ON,”
GO:0019003 GDP binding	IMP PMID:9230043 Regional polysterism in the GTP-bound form of the human c-Ha...	ACCEPT	Summary: HRAS binds GDP in its inactive state, completing the GDP/GTP switch cycle. Reason: GDP binding is a core molecular function of HRAS; this duplicate IMP annotation is consistent with the GDP/GTP switch model. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins (including HRAS) are GTP hydrolases that function as binary molecular switches: GDP-bound is “OFF,” GTP-bound is “ON,”
GO:0003924 GTPase activity	IDA PMID:9178006 Mechanism of activation of the Caenorhabditis elegans ras ho...	ACCEPT	Summary: HRAS has intrinsic GTPase activity (inferred from the conserved let-60 Ras activation study). Reason: GTP hydrolysis is the core catalytic molecular function of HRAS and is conserved across the Ras family. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Intrinsic GTPase activity is accelerated by GAPs, while GEFs promote GDP→GTP exchange.
GO:0005886 plasma membrane	IDA PMID:17724343 Spatial regulation of Raf kinase signaling by RKTG.	ACCEPT	Summary: HRAS localizes to the plasma membrane, where its signaling is spatially regulated (e.g., by RKTG). Reason: Direct evidence supports plasma membrane localization, the principal signaling location of mature, lipidated HRAS. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-4093331	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-4093339	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802914	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802915	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802916	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802919	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6802921	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6803230	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8936676	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005886 plasma membrane	TAS Reactome:R-NUL-9617449	ACCEPT	Summary: The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions. Reason: This is a bulk Reactome TAS localization row placing HRAS in a membrane compartment consistent with its established lipidation-dependent trafficking and signaling; the location is correct and accepted. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005515 protein binding	IPI PMID:11598133 Nedd4 regulates ubiquitination and stability of the guanine-...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the GEF CNrasGEF (Nedd4 regulation). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:10608844 RA-GEF, a novel Rap1A guanine nucleotide exchange factor con...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RA-GEF, a Rap1A/Ras-associating GEF. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0010629 negative regulation of gene expression	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	MARK AS OVER ANNOTATED	Summary: Negative regulation of gene expression is a distal transcriptional output from an oncogenic Ras transformation model (Wnt4/miR-24 axis). Reason: PMID:23027131 uses oncogenic Ras-induced malignant transformation; transcriptional/gene-expression changes are distal consequences rather than a proximal, direct molecular function of wild-type HRAS. Supporting Evidence: PMID:23027131 By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling.
GO:0030335 positive regulation of cell migration	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	KEEP AS NON CORE	Summary: Promotion of cell migration is a downstream motility phenotype of oncogenic Ras signaling. Reason: Cell migration is a plausible distal Ras output but is documented here in an oncogenic transformation context; it is non-core relative to the HRAS switch function. Supporting Evidence: PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	MARK AS OVER ANNOTATED	Summary: Positive transcriptional regulation is a distal output from an oncogenic Ras transformation model. Reason: Transcriptional activation in this study is a downstream consequence of oncogenic Ras signaling, not a direct, proximal HRAS molecular function. Supporting Evidence: PMID:23027131 By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling.
GO:0090303 positive regulation of wound healing	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	MARK AS OVER ANNOTATED	Summary: Wound-healing regulation is a distal phenotype inferred from oncogenic Ras-driven motility assays. Reason: This is a far-downstream phenotypic readout of oncogenic Ras-induced cell motility rather than a proximal, mechanistically supported function of wild-type HRAS. Supporting Evidence: PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.
GO:1900029 positive regulation of ruffle assembly	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	KEEP AS NON CORE	Summary: Ruffle assembly is a cytoskeletal output of oncogenic Ras signaling via Rho-family GTPases. Reason: Membrane ruffling downstream of Ras-driven actin remodeling is plausible but indirect (mediated by Rho-family GTPases) and documented in an oncogenic context, so it is non-core. Supporting Evidence: PMID:23027131 Wnt4 interferes with Ras-induced actin cytoskeleton reorganization through non-canonical pathways, by altering the balance between the activation of different Rho-family small guanosine triphosphatases (GTPases).
GO:2000630 positive regulation of miRNA metabolic process	IDA PMID:23027131 Wnt4 inhibits cell motility induced by oncogenic Ras.	MARK AS OVER ANNOTATED	Summary: Regulation of miR-24 is a distal transcriptional/RNA output from an oncogenic Ras transformation model. Reason: miRNA metabolic regulation here is a downstream consequence of oncogenic Ras signaling rather than a direct, proximal HRAS molecular function. Supporting Evidence: PMID:23027131 By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling.
GO:0005515 protein binding	IPI PMID:10369681 Aiolos transcription factor controls cell death in T cells b...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a partner reported in an Aiolos/Bcl-2 T-cell study. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:22065586 Oncogenic Ras and B-Raf proteins positively regulate death r...	MARK AS OVER ANNOTATED	Summary: Oncogenic Ras induces DR5 transcription via ERK/JNK and downstream transcription factors (CHOP, Elk1, c-Jun), a distal transcriptional output. Reason: Transcriptional regulation of DR5 here is several steps downstream of oncogenic Ras signaling and mediated by ERK/JNK and multiple transcription factors, so it is not a proximal, direct HRAS function. Supporting Evidence: PMID:22065586 Ras induces DR5 expression through co-activation of ERK/RSK and JNK signaling pathways and subsequent cooperative effects among the transcriptional factors CHOP, Elk1, and c-Jun to enhance DR5 gene transcription.
GO:0046330 positive regulation of JNK cascade	IDA PMID:22065586 Oncogenic Ras and B-Raf proteins positively regulate death r...	KEEP AS NON CORE	Summary: Oncogenic Ras can co-activate the JNK signaling cascade. Reason: JNK activation is a recognized but secondary/context-dependent Ras output (relative to the canonical RAF-MEK-ERK cascade) and is documented here in an oncogenic context, so it is non-core. Supporting Evidence: PMID:22065586 Ras induces DR5 expression through co-activation of ERK/RSK and JNK signaling pathways
GO:0070374 positive regulation of ERK1 and ERK2 cascade	IDA PMID:22065586 Oncogenic Ras and B-Raf proteins positively regulate death r...	ACCEPT	Summary: HRAS positively regulates the ERK1/ERK2 cascade, a core proximal Ras output. Reason: Activation of the ERK1/2 (RAF-MEK-ERK) cascade is the canonical, proximal signaling output of HRAS-GTP and is a core process annotation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS signaling is funneled strongly into RAF-MEK-ERK, and HRAS contributes to ERK output and MAPK signaling dynamics.
GO:0005515 protein binding	IPI PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a reported physical interaction partner. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005525 GTP binding	IDA PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren...	ACCEPT	Summary: HRAS binds GTP, a core molecular function of this small GTPase. Reason: GTP binding is a core, well-established molecular function of HRAS as a nucleotide-dependent switch. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.
GO:0005794 Golgi apparatus	IDA PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren...	ACCEPT	Summary: The canonical p21 H-Ras localizes to Golgi membranes during lipidation-dependent trafficking. Reason: Golgi localization is consistent with HRAS palmitoylation cycles and ER/Golgi processing; this is a valid localization annotation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md palmitoylation is reversible/dynamic, supporting HRAS cycling between Golgi and plasma membrane
GO:0005886 plasma membrane	IDA PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren...	ACCEPT	Summary: The canonical p21 H-Ras localizes to the plasma membrane. Reason: Plasma membrane localization is the principal signaling location of mature lipidated HRAS. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0005794 Golgi apparatus	IDA PMID:21968647 PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparat...	ACCEPT	Summary: HRAS localizes to and signals from the Golgi apparatus, where PAQR10/PAQR11 promote its Golgi localization and ERK activation. Reason: Golgi localization and Golgi-based Ras signaling are directly supported; this is a valid HRAS localization annotation. Supporting Evidence: PMID:21968647 Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B.
GO:0005886 plasma membrane	IDA PMID:21968647 PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparat...	ACCEPT	Summary: HRAS localizes to the plasma membrane in addition to the Golgi pool. Reason: Plasma membrane localization is the principal signaling location of HRAS and is consistent with this study of Golgi vs PM Ras pools. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0090398 cellular senescence	IDA PMID:9054499 Oncogenic ras provokes premature cell senescence associated ...	KEEP AS NON CORE	Summary: Oncogenic Ras induces premature senescence in primary cells, a context-dependent outcome. Reason: The senescence evidence comes from oncogenic Ras overexpression in primary cells and should not be treated as a core function of wild-type HRAS. Supporting Evidence: PMID:9054499 Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest.
GO:0005515 protein binding	IPI PMID:11980706 The complex of Arl2-GTP and PDE delta: from structure to fun...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with a partner reported in an Arl2-GTP/PDEdelta study. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0050679 positive regulation of epithelial cell proliferation	IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost...	KEEP AS NON CORE	Summary: Activation of Ras (via DAB2IP/RasGAP loss) promotes prostate epithelial proliferation and metastasis, a downstream cancer-context phenotype. Reason: Epithelial proliferation here arises from loss of the RasGAP DAB2IP in a metastatic prostate cancer model; it is a context-dependent downstream output rather than a core wild-type HRAS function. Supporting Evidence: PMID:20154697 loss of the Ras GTPase-activating protein (RasGAP) gene DAB2IP induces metastatic prostate cancer in an orthotopic mouse tumor model.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:9765203 Premature senescence involving p53 and p16 is activated in r...	KEEP AS NON CORE	Summary: Sustained Ras/MEK-MAPK signaling can promote proliferation, a context-dependent downstream outcome. Reason: Proliferation is a canonical but context-dependent Ras output; the cited study links constitutive MEK/MAPK signaling to proliferation/senescence depending on context, so it is non-core. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS-ERK signaling dynamics can bias proliferation versus differentiation outputs, but these outcomes depend strongly on cell type and signaling kinetics.
GO:0043410 positive regulation of MAPK cascade	IDA PMID:9765203 Premature senescence involving p53 and p16 is activated in r...	ACCEPT	Summary: HRAS positively regulates the MAPK cascade, a core proximal Ras output. Reason: Positive regulation of the MAPK (RAF-MEK-ERK) cascade is the canonical proximal signaling output of HRAS-GTP and is a core process. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md RAS proteins sit at the apex of the RAF–MEK–ERK (MAPK) cascade, and Ras-effector binding directly routes signals into MAPK outputs.
GO:0005525 GTP binding	IDA PMID:17260967 GTP binding is essential to the protein kinase activity of L...	ACCEPT	Summary: HRAS binds GTP; the cited reference uses HRAS as a reference Ras-like GTP binding protein when characterizing the LRRK2 ROC domain. Reason: GTP binding is a core, well-established molecular function of HRAS, regardless of the comparative context of the citing paper. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.
GO:0008285 negative regulation of cell population proliferation	IDA PMID:9054499 Oncogenic ras provokes premature cell senescence associated ...	KEEP AS NON CORE	Summary: Oncogenic Ras can negatively regulate proliferation by triggering premature senescence/G1 arrest in primary cells. Reason: This anti-proliferative (senescence) output is an oncogenic-Ras, context-dependent phenotype in primary cells and is not a core wild-type HRAS function. Supporting Evidence: PMID:9054499 The arrest induced by ras is accompanied by accumulation of p53 and p16, and is phenotypically indistinguishable from cellular senescence.
GO:0005515 protein binding	IPI PMID:11022048 Regulation of a novel human phospholipase C, PLCepsilon, thr...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with the effector PLCepsilon (Ras-associating domain). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:2122974 Modulation of guanine nucleotides bound to Ras in NIH3T3 cel...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with GTPase-activating protein (GAP) modulating Ras nucleotide state. Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0005515 protein binding	IPI PMID:9219684 The Ras-RasGAP complex: structural basis for GTPase activati...	MARK AS OVER ANNOTATED	Summary: This IPI annotation records a physical interaction of HRAS with RasGAP (Ras-RasGAP complex structure). Reason: The bare 'protein binding' (GO:0005515) term is uninformative for a hub GTPase like HRAS; where the interaction reflects a bona fide, nucleotide-state-dependent effector or regulator engagement it would be better captured by a specific binding term, and many large-scale interactome hits lack mechanistic validation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.
GO:0007165 signal transduction	NAS PMID:8607982 Ras-related proteins in signal transduction and growth contr...	MODIFY	Summary: HRAS transmits signals from growth factor receptors into downstream kinase cascades; the more specific term is Ras protein signal transduction. Reason: The broad signal transduction term should be replaced with the specific Ras protein signal transduction term, which the cited review explicitly describes. Proposed replacements: Ras protein signal transduction Supporting Evidence: PMID:8607982 The ras p21 protooncogene products, H-ras, K-ras, and N-ras, transmit signals from growth factor receptors to a cascade of protein kinases that begins with the Raf protooncogene product.
GO:0009887 animal organ morphogenesis	TAS PMID:10848592 Involvement of Ras and Ral in chemotactic migration of skele...	MARK AS OVER ANNOTATED	Summary: Organ morphogenesis is a distal developmental phenotype inferred from Ras/Ral involvement in myoblast chemotaxis and muscle development. Reason: The cited study addresses Ras/Ral control of growth-factor-driven myoblast chemotaxis; organ morphogenesis is a far-downstream developmental outcome, not a proximal, direct HRAS molecular function. Supporting Evidence: PMID:10848592 Expression of a dominant-negative mutant of Ras inhibited chemotaxis of C2C12 myoblasts in response to basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and insulin-like growth factor 1 (IGF-1), key regulators of limb muscle development and skeletal muscle regeneration.
GO:0005737 cytoplasm	TAS PMID:10842192 Increased oxidative stress with gene alteration in urinary b...	KEEP AS NON CORE	Summary: A generic cytoplasm localization, consistent with the soluble/pre-membrane pool of HRAS. Reason: Cytoplasmic localization is plausible for a fraction of HRAS, but the functionally meaningful locations are the plasma membrane and Golgi/endomembranes; this generic term is non-core. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md prenylation drives nascent Ras proteins to ER and Golgi before subsequent trafficking to the plasma membrane
GO:0005886 plasma membrane	TAS PMID:9020890 Ras activation in platelets after stimulation of the thrombi...	ACCEPT	Summary: Ras localizes to the plasma membrane in platelets, consistent with its lipidation-dependent membrane targeting. Reason: Plasma membrane localization is the principal signaling location of mature HRAS and is directly observed here. Supporting Evidence: PMID:9020890 Immunofluorescence studies indicated that Ras was present in a peripheral rim pattern in fixed, permeabilized platelets, suggesting an intracellular, plasma membrane location.
GO:0005886 plasma membrane	TAS PMID:9880516 A non-farnesylated Ha-Ras protein can be palmitoylated and t...	ACCEPT	Summary: Lipidated H-Ras localizes to the plasma membrane; palmitoylation can target H-Ras to the membrane even without farnesylation. Reason: Plasma membrane localization driven by H-Ras lipid modifications is a core localization annotation. Supporting Evidence: file:human/HRAS/HRAS-deep-research-falcon.md HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
GO:0006935 chemotaxis	TAS PMID:10848592 Involvement of Ras and Ral in chemotactic migration of skele...	KEEP AS NON CORE	Summary: Ras (with Ral) contributes to growth-factor-induced chemotactic migration of skeletal myoblasts, a cell-type-specific downstream output. Reason: Chemotaxis is a plausible distal output of Ras signaling but is context-specific (myoblasts, via a Ras-Ral branch independent of MEK/PI3K here), so it is non-core relative to the GTPase switch function. Supporting Evidence: PMID:10848592 Here, we demonstrate that Ras is involved also in the chemotactic response of skeletal myoblasts.
GO:0007166 cell surface receptor signaling pathway	TAS PMID:9020890 Ras activation in platelets after stimulation of the thrombi...	KEEP AS NON CORE	Summary: HRAS is activated downstream of cell-surface receptors (e.g., thrombin and thromboxane A2 receptors) in platelets. Reason: Acting downstream of cell-surface receptors is consistent with HRAS biology, but this broad process is a context for, rather than a more specific statement of, the core Ras protein signal transduction function. Supporting Evidence: PMID:9020890 Activation of platelets with the thrombin receptor peptide42-50, the prostaglandin H2/thromboxane A2 mimetic U46619 or phorbol 12-myristate 13-acetate induced a rapid increase in GTP-bound, activated Ras.

GO aspect	Suggested GO term label (plain English)	Evidence summary (1 sentence)	Key caveats	Supporting source
MF	GTP binding	HRAS is a canonical RAS small GTPase that binds GDP/GTP with high affinity and functions as a nucleotide-dependent molecular switch.	Core, well established	Smith 2023, DOI:10.1002/bies.202300088; Mozzarelli et al. 2024, DOI:10.1016/j.molcel.2024.06.027 (smith2023definingbonefide pages 1-2, mozzarelli2024functionalandstructural pages 1-3)
MF	Small monomeric GTPase activity / GTP hydrolysis	HRAS has intrinsic GTPase activity, with GAPs accelerating hydrolysis and GEFs promoting GDP-to-GTP exchange.	Do not infer mutant behavior to WT	Smith 2023, DOI:10.1002/bies.202300088; Kolch et al. 2023, DOI:10.1042/bcj20220234 (smith2023definingbonefide pages 1-2, kolch2023dynamicregulationof pages 15-16)
MF	Effector binding (GTP-dependent)	Bona fide HRAS effectors bind preferentially to the GTP-bound switch-region conformation rather than GDP-bound HRAS.	Require direct, nucleotide-dependent evidence	Smith 2023, DOI:10.1002/bies.202300088; Adariani et al. 2021, DOI:10.1016/j.jbc.2021.100626 (smith2023definingbonefide pages 1-2, adariani2021acomprehensiveanalysis pages 1-4)
MF	RAF1 / CRAF binding	Direct binding studies support high-affinity HRAS interaction with RAF-family RBDs, including CRAF/RAF1.	Prefer specific partner term over generic protein binding	Nakhaeizadeh et al. 2016, DOI:10.1371/journal.pone.0167145; Sydor et al. 1998, PMID:9760267 (nakhaeizadeh2016theraseffectorinterface pages 6-7, nakhaeizadeh2016theraseffectorinterface pages 19-20)
MF	RALGDS binding	HRAS directly binds the RALGDS RA domain in a GTP-dependent manner, supporting specific effector-binding annotation.	Affinity lower than RAF; context matters	Nakhaeizadeh et al. 2016, DOI:10.1371/journal.pone.0167145; Vetter et al. 1999, PMID:10371160 (nakhaeizadeh2016theraseffectorinterface pages 6-7, nakhaeizadeh2016theraseffectorinterface pages 19-20)
MF	RASSF5 binding	HRAS directly binds RASSF5/NORE1A RA-domain-containing effectors, involving switch-region contacts.	Use specific evidence; not all RASSF family equal	Nakhaeizadeh et al. 2016, DOI:10.1371/journal.pone.0167145; Stieglitz et al. 2008, DOI:10.1038/emboj.2008.125, PMID:18596699 (nakhaeizadeh2016theraseffectorinterface pages 6-7, nakhaeizadeh2016theraseffectorinterface pages 19-20)
MF	PI3K binding	HRAS can bind PI3K RBD-containing catalytic subunits, but measured affinity is substantially weaker than for RAF/RASSF5.	Keep as specific, possibly non-core partner binding	Nakhaeizadeh et al. 2016, DOI:10.1371/journal.pone.0167145; Smith 2023, DOI:10.1002/bies.202300088 (nakhaeizadeh2016theraseffectorinterface pages 6-7, smith2023definingbonefide pages 3-3)
BP	Ras protein signal transduction	HRAS is one of the canonical RAS proteins acting upstream of multiple effector pathways in Ras signal transduction.	Core BP term	Kolch et al. 2023, DOI:10.1042/bcj20220234 (kolch2023dynamicregulationof pages 1-2)
BP	Positive regulation of MAPK cascade	RAS signaling is funneled strongly into RAF-MEK-ERK, and HRAS contributes to ERK output and MAPK signaling dynamics.	Core but avoid over-specific phenotypes from mutants	Kolch et al. 2023, DOI:10.1042/bcj20220234 (kolch2023dynamicregulationof pages 12-13, kolch2023dynamicregulationof pages 11-11)
BP	PI3K-AKT pathway activation	PI3K is a recognized RAS effector pathway, especially engaged at higher RAS-GTP levels and in some oncogenic contexts.	Core Ras output, but context dependent for HRAS-specific strength	Kolch et al. 2023, DOI:10.1042/bcj20220234; Smith 2023, DOI:10.1002/bies.202300088 (kolch2023dynamicregulationof pages 11-11, smith2023definingbonefide pages 1-2)
BP	Ral signaling via RalGDS	High-affinity RAS effectors include RALGDS/RGL2, supporting HRAS participation in Ral GTPase signaling.	Reasonable pathway annotation if direct HRAS evidence retained	Kolch et al. 2023, DOI:10.1042/bcj20220234 (kolch2023dynamicregulationof pages 11-11)
BP	Regulation of proliferation or differentiation	RAS-ERK signaling dynamics can bias proliferation versus differentiation outputs, but these outcomes depend strongly on cell type and signaling kinetics.	Usually non-core/context specific	Kolch et al. 2023, DOI:10.1042/bcj20220234 (kolch2023dynamicregulationof pages 1-2, kolch2023dynamicregulationof pages 13-14)
BP	Apoptosis / senescence regulation	Pro- or anti-apoptotic outputs can arise through pathway competition (e.g., RAF1-MEK versus MST2) and mutant/kinetic context rather than constitutive normal HRAS function.	Flag for review, not default core	Kolch et al. 2023, DOI:10.1042/bcj20220234 (kolch2023dynamicregulationof pages 13-14, kolch2023dynamicregulationof pages 15-16)
CC	Plasma membrane localization	HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.	Core CC term	Choy et al. 1999, DOI:10.1016/S0092-8674(00)80607-8; Wright & Philips 2006, DOI:10.1194/jlr.R600004-JLR200 (choy1999endomembranetraffickingof pages 1-2, wright2006thematicreviewseries pages 2-3)
CC	Golgi apparatus localization / trafficking	HRAS transits ER/Golgi during post-CAAX processing and palmitoylation, and cycles between Golgi and plasma membrane.	Core trafficking/localization term	Choy et al. 1999, DOI:10.1016/S0092-8674(00)80607-8; Lynch et al. 2015, DOI:10.1002/jcp.24779 (choy1999endomembranetraffickingof pages 1-2, lynch2015thedifferentialpalmitoylation pages 1-3)
CC	Recycling endosome localization	Palmitoylated HRAS has been reported on recycling endosomes as a waypoint in post-Golgi trafficking to the plasma membrane.	Useful but less core than PM/Golgi	Taguchi & Misaki 2011, DOI:10.4161/sgtp.2.2.15245 (taguchi2011palmitoylationpilotsras pages 1-3)
CC	Membrane targeting by CAAX prenylation and palmitoylation	HRAS uses CAAX farnesylation, AAX cleavage, carboxymethylation, and reversible palmitoylation as the core membrane-targeting logic.	PTM mechanism, not a location term by itself	Wright & Philips 2006, DOI:10.1194/jlr.R600004-JLR200; Berthiaume 2002, DOI:10.1126/stke.2002.152.pe41 (wright2006thematicreviewseries pages 2-3, berthiaume2002insiderinformationhow pages 1-2)
Avoid/flag for review	Generic protein binding	Broad protein-binding annotation adds little value when specific effector binding terms are available with direct evidence.	Over-annotation risk	Mozzarelli et al. 2024, DOI:10.1016/j.molcel.2024.06.027; Smith 2023, DOI:10.1002/bies.202300088 (mozzarelli2024functionalandstructural pages 1-3, smith2023definingbonefide pages 1-2)
Avoid/flag for review	Broad cancer/development/cell cycle terms from oncogenic mutants	Many mutant RAS phenotypes reflect constitutive signaling, network rewiring, or overexpression and should not be transferred wholesale to normal HRAS GO annotations.	Mutant/overexpression confound	Kolch et al. 2023, DOI:10.1042/bcj20220234; Smith 2023, DOI:10.1002/bies.202300088 (kolch2023dynamicregulationof pages 14-15, smith2023definingbonefide pages 1-2)
Avoid/flag for review	Transcriptional regulation, immune/inflammatory, or other distal phenotypes	High-throughput interactomics and downstream phenotypes often show context-specific rewiring and false positives, so distal process terms need direct mechanistic evidence.	Indirect/context-specific	Kolch et al. 2023, DOI:10.1042/bcj20220234; Mozzarelli et al. 2024, DOI:10.1016/j.molcel.2024.06.027 (kolch2023dynamicregulationof pages 13-14, mozzarelli2024functionalandstructural pages 1-3)

📄 View Raw YAML

id: P01112
gene_symbol: HRAS
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  HRAS encodes H-Ras, a membrane-associated small GTPase that acts as a
  GDP/GTP-regulated molecular switch in Ras signal transduction. Its core
  function is GTP binding and hydrolysis with nucleotide-state-dependent
  recruitment of effectors, especially pathways leading to RAF-MEK-ERK signaling;
  membrane targeting through CAAX processing and palmitoylation localizes H-Ras
  to plasma membrane and Golgi/endomembrane compartments. Many proliferation,
  senescence, transcription, migration, and developmental annotations are
  context-dependent downstream outcomes, often derived from oncogenic mutant or
  overexpression studies, and should not be treated as the core molecular
  function of wild-type HRAS.
alternative_products:
- name: 1 (H-Ras4A, p21)
  id: P01112-1
- name: 2 (H-RasIDX, p19)
  id: P01112-2
  sequence_note: VSP_041597
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HRAS is membrane-targeted and signals from the plasma membrane.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is central to HRAS signaling, supported by
      CAAX processing and palmitoylation-dependent trafficking.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS contains a C-terminal **CAAX motif** that is post-translationally
        processed by a canonical sequence: **farnesylation → AAX proteolysis
        (RCE1) → carboxymethylation (ICMT)**.
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HRAS is a canonical Ras-family GTPase that mediates Ras protein signal
      transduction.
    action: ACCEPT
    reason: >-
      Ras protein signal transduction is the core biological process for HRAS as
      a GDP/GTP-regulated molecular switch.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins (including HRAS) are **GTP hydrolases** that function as
        **binary molecular switches**: GDP-bound is “OFF,” GTP-bound is “ON,”
        and the ON state supports binding to downstream effector proteins.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HRAS signaling can promote proliferation, but this is a downstream and
      context-dependent outcome rather than the core HRAS molecular function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Proliferation is a canonical outcome of Ras signaling in some cellular
      contexts, but it depends on cell type, stimulus duration, feedback, and
      mutant versus wild-type HRAS state.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS-ERK signaling dynamics can bias proliferation versus
        differentiation outputs, but these outcomes depend strongly on cell
        type and signaling kinetics.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HRAS has intrinsic GTPase activity.
    action: ACCEPT
    reason: >-
      GTP hydrolysis is the core molecular switch activity of HRAS.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Intrinsic GTPase activity is **accelerated by GAPs**, while **GEFs
        promote GDP→GTP exchange**.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Cellular senescence is a context-dependent outcome of oncogenic Ras
      signaling rather than the primary normal function of HRAS.
    action: KEEP_AS_NON_CORE
    reason: >-
      Senescence evidence is strongly tied to oncogenic Ras expression and
      should not be treated as the core function of wild-type HRAS.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: >-
        Here we show that expression of oncogenic ras in primary human or rodent
        cells results in a permanent G1 arrest.
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Apoptosis/senescence: generally non-core default for HRAS
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Golgi membrane localization is part of HRAS lipidation-dependent membrane
      trafficking.
    action: ACCEPT
    reason: >-
      HRAS is processed and trafficked through ER/Golgi membranes before plasma
      membrane localization.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Palmitoylation provides the “second signal” for HRAS membrane targeting
        beyond prenylation and supports vesicular transport from
        **Golgi→plasma membrane**; palmitoylation is **reversible/dynamic**,
        supporting HRAS cycling between Golgi and plasma membrane.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      HRAS activates signaling through the RAF-MEK-ERK MAPK cascade.
    action: ACCEPT
    reason: >-
      MAPK cascade signaling is a proximal canonical Ras output, although
      distal phenotypic outcomes should be curated separately.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins sit at the apex of the **RAF–MEK–ERK (MAPK) cascade**, and
        Ras-effector binding directly routes signals into MAPK outputs.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      HRAS has intrinsic GTPase activity.
    action: ACCEPT
    reason: >-
      GTPase activity is the core catalytic molecular function of HRAS.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Intrinsic GTPase activity is **accelerated by GAPs**, while **GEFs
        promote GDP→GTP exchange**.
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: >-
      HRAS is a small monomeric GTPase rather than a heterotrimeric G protein;
      the more precise annotation is GTPase activity.
    action: MODIFY
    reason: >-
      GO:0003925 can cover Ras-family GTPases, but the annotation should use
      GO:0003924 because it captures the catalytic GTP-hydrolysis function more
      precisely.
    proposed_replacement_terms:
    - id: GO:0003924
      label: GTPase activity
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS is a canonical RAS small GTPase that binds GDP/GTP with high
        affinity and functions as a nucleotide-dependent molecular switch.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      HRAS binds guanine nucleotides as part of its GDP/GTP switch mechanism.
    action: ACCEPT
    reason: >-
      GTP binding is a core molecular function for Ras-family GTPases.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS is a canonical RAS small GTPase that binds GDP/GTP with high
        affinity and functions as a nucleotide-dependent molecular switch.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Nuclear localization is not characteristic of the canonical farnesylated,
      membrane-anchored H-Ras p21 isoform.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The mature p21 H-Ras is targeted to the plasma membrane and
      Golgi/endomembranes via CAAX prenylation and palmitoylation; nuclear
      localization is reported mainly for the minor alternatively spliced p19
      (H-RasIDX) isoform, so a general nuclear CC annotation over-projects onto
      the main gene product.
    supported_by:
    - reference_id: PMID:14500341
      supporting_text: >-
        Both the endogenous and the transiently expressed p19 protein are
        detected in COS-1 and HeLa cells and show nuclear diffuse and speckled
        patterns as well as cytoplasmic localization.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      A broad cytoplasm annotation is consistent with HRAS biology but less
      informative than its specific membrane locations.
    action: KEEP_AS_NON_CORE
    reason: >-
      Newly synthesized and a fraction of HRAS exists in the cytoplasm prior to
      membrane targeting, and the p19 isoform shows cytoplasmic localization;
      however, the functionally meaningful locations are plasma membrane and
      Golgi/endomembrane, so the generic cytoplasm term is retained as non-core.
    supported_by:
    - reference_id: PMID:14500341
      supporting_text: >-
        Both the endogenous and the transiently expressed p19 protein are
        detected in COS-1 and HeLa cells and show nuclear diffuse and speckled
        patterns as well as cytoplasmic localization.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Golgi localization is supported by HRAS membrane trafficking and
      palmitoylation cycles.
    action: ACCEPT
    reason: >-
      HRAS cycles through Golgi membranes as part of its lipidation-dependent
      targeting to signaling membranes.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Palmitoylation provides the “second signal” for HRAS membrane targeting
        beyond prenylation and supports vesicular transport from
        **Golgi→plasma membrane**; palmitoylation is **reversible/dynamic**,
        supporting HRAS cycling between Golgi and plasma membrane.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      HRAS localizes to the plasma membrane for Ras signaling.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is a core cellular context for HRAS
      signal-transduction function.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Plasma membrane localization | HRAS membrane association is essential
        for signaling, with lipid modifications enabling stable plasma membrane
        localization.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      The annotation captures the broad signaling role of HRAS, but Ras protein
      signal transduction is more informative.
    action: MODIFY
    reason: >-
      HRAS is specifically a Ras-family signal-transduction GTPase, so the
      existing broad signal transduction term should be replaced with the
      specific Ras protein signal transduction term.
    proposed_replacement_terms:
    - id: GO:0007265
      label: Ras protein signal transduction
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Ras protein signal transduction | HRAS is one of the canonical RAS
        proteins acting upstream of multiple effector pathways in Ras signal
        transduction.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      HRAS is membrane-associated, but the generic membrane term is less
      informative than its specific plasma membrane and Golgi membrane
      annotations.
    action: MODIFY
    reason: >-
      HRAS lipidation targets it to specific membranes; the broad membrane term
      should be replaced with the more precise plasma membrane location that is
      central to its signaling.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid
        modifications enabling stable plasma membrane localization.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Perinuclear localization is consistent with HRAS pools at the Golgi and
      perinuclear endomembranes during lipidation-dependent trafficking.
    action: KEEP_AS_NON_CORE
    reason: >-
      HRAS cycles through Golgi/recycling endosomes, which lie in the
      perinuclear region, so this localization is plausible but secondary to the
      plasma membrane and Golgi membrane annotations.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        palmitoylation is **reversible/dynamic**, supporting HRAS cycling
        between Golgi and plasma membrane
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11335720
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with PRA1/prenylated Rab acceptor (a receptor for prenylated small GTPases).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11857081
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RASSF1A/NORE1 Ras-GTP binding proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12620389
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RAF kinase (two-hybrid interactions).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12628188
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras-GEF SOS (feedback Ras-GTP activation site).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14724641
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the effector IMP in mitogenic signalling complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15507210
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (autoinhibition).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15886098
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the ABL activator/effector RIN1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16316996
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the RAP1 GEF Epac2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16698549
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with NORE1/RASSF5 (C1 and RA domains).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16810318
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RASSF1C (DNA-damage/JNK context).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17084389
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras-GEF hSos1 (REM domain).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17540175
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with PI3K p110alpha (Ras-driven tumorigenesis).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18073111
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RAF in the context of RasQ61 mutant transformation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18273062
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a switch-region partner regulating H-Ras membrane orientation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18454158
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (membrane signal integration).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18596699
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the tumour-suppressor effector NORE1A via Ras switch II.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19063885
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with cell-transducing Ras inhibitors.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19141281
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activators SOS and RasGRF1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19222999
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with FKBP38 (Rheb/mTORC1 pathway reassessment).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19696784
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a partner identified in a fission-yeast TACC study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080631
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with partners affecting Ras membrane orientation/nanodomain localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20133692
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (histone domain autoinhibition).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20133694
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (allosteric gating by histone domain).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20178605
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with putative Ras/Raf interaction inhibitors.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20936779
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with MAP kinase interactome partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22020336
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with PI3K p110delta isoform p37delta.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22169110
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RAF in drug-resistant CML (paradoxical activation).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24412244
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with driver/susceptibility partners in colorectal cancer.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24441586
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with effectors and regulators detected by parallel NMR.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24929361
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with Raf-1 and MST2/Hippo signalling partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with endogenous pathway partners profiled by proximity ligation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25684575
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with Raf-RBD (oncogenic RasQ61L allosteric effects).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26165597
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the BRAF Ras-binding domain.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26635368
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with neurofibromin GAP-related domain/SPRED1 (Legius/NF1 context).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with protein-community partners from a large interactome map.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30194290
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RAS-isoform interactome partners (PIP5K1A study).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30518913
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with UBIAD1 (H-Ras C-terminal trafficking).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31209342
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a substrate context in a geranylgeranyltransferase study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with neurodegenerative-disease network partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with cell-specific interactome partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591612
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with breast-cancer interactome partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591642
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with head and neck cancer interactome partners.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35512704
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with mutation-directed neo-interaction partners in cancer.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35839996
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with isoform-specific, nucleotide-dependent RAS interactors.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with partners from multimodal cell maps.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8332187
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the c-Raf-1 amino-terminal regulatory domain.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8670882
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a Rac1-interacting membrane-ruffling protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9144171
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the effector RIN1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9447984
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras activator SOS (intramolecular regulation).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9488663
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the potential Ras effector Nore1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9690470
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the Ras GEF SOS (activation mechanism).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  isoform: P01112-2
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with binary interactome partners (isoform P01112-2).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      HRAS is directly involved in Ras protein signal transduction.
    action: ACCEPT
    reason: >-
      This is the core biological process for the HRAS GTPase switch.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        “Ras protein signal transduction” and “positive regulation of MAPK
        cascade” are generally **core** for HRAS, but very specific outcome
        terms (e.g., “cell cycle progression” as a default) should be
        restricted to contexts with strong, direct, wild-type evidence.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      HRAS acts downstream of receptor tyrosine kinases including the insulin
      receptor, but this is one specific RTK input among many rather than a core
      HRAS-defining process.
    action: KEEP_AS_NON_CORE
    reason: >-
      RAS GTPases relay signals from multiple growth-factor/RTK inputs (EGFR,
      insulin receptor, etc.) into the MAPK and PI3K pathways; the insulin
      receptor pathway is a legitimate but non-core context for HRAS, while the
      core annotation is the general Ras protein signal transduction.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins sit at the apex of the **RAF–MEK–ERK (MAPK) cascade**, and
        Ras-effector binding directly routes signals into MAPK outputs.
- term:
    id: GO:0014044
    label: Schwann cell development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Schwann cell development is a distal developmental outcome and is not a
      core HRAS molecular function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This automated IEA row appears to over-project broad Ras-family or
      pathway-derived developmental biology onto HRAS; there is no direct
      evidence in this review that wild-type HRAS is a proximal regulator of
      Schwann cell development specifically.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        2) **Avoid overly broad BP terms** (e.g., generic “cancer,”
        “development,” “cell cycle,” “transcriptional regulation,”
        “immune/inflammatory processes”) unless there is direct mechanistic
        evidence placing *wild-type HRAS* as a proximal regulator rather than a
        downstream correlate. Large interactome datasets include false positives
        and many context-specific interactors.
- term:
    id: GO:0042552
    label: myelination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Myelination is a distal developmental outcome and is not supported as a
      core HRAS annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This automated IEA row appears to over-project broad Ras-family or
      pathway-derived developmental biology onto HRAS; HRAS mutations can cause
      developmental phenotypes, but that does not make myelination a proximal
      wild-type HRAS function for GO annotation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Do not transfer oncogenic mutant phenotypes to wild-type HRAS GO BP
        terms by default.
- term:
    id: GO:0043495
    label: protein-membrane adaptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      HRAS is a lipid-modified small GTPase, not a protein-membrane adaptor.
    action: REMOVE
    reason: >-
      HRAS membrane association is mediated by its own CAAX processing and
      palmitoylation; that trafficking mechanism should not be represented as
      protein-membrane adaptor activity.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Membrane targeting by CAAX prenylation and palmitoylation | HRAS uses
        CAAX farnesylation, AAX cleavage, carboxymethylation, and reversible
        palmitoylation as the core membrane-targeting logic.
- term:
    id: GO:0060612
    label: adipose tissue development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Adipose tissue development is too distal to represent the core function
      of HRAS.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This automated IEA row appears to over-project broad Ras-family or
      pathway-derived developmental biology onto HRAS; direct evidence that
      wild-type HRAS is a proximal regulator of adipose tissue development was
      not identified in this review.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        2) **Avoid overly broad BP terms** (e.g., generic “cancer,”
        “development,” “cell cycle,” “transcriptional regulation,”
        “immune/inflammatory processes”) unless there is direct mechanistic
        evidence placing *wild-type HRAS* as a proximal regulator rather than a
        downstream correlate. Large interactome datasets include false positives
        and many context-specific interactors.
- term:
    id: GO:0046579
    label: positive regulation of Ras protein signal transduction
  evidence_type: NAS
  original_reference_id: PMID:35831509
  review:
    summary: >-
      HRAS participates in positive feedback loops within RAS-ERK signaling
      (e.g., via SHOC2-MRAS-PP1C-mediated RAF dephosphorylation), but the cited
      study focuses on the MRAS-containing holophosphatase rather than HRAS
      directly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Positive regulation of Ras signal transduction is biologically reasonable
      for HRAS (Ras-GTP can feedback-activate SOS), but the supporting reference
      (PMID:35831509) characterizes the SHOC2-MRAS-PP1C complex; the annotation
      is plausible at the pathway level but not a direct, core HRAS molecular
      function. The core process is captured by GO:0007265.
    supported_by:
    - reference_id: PMID:35831509
      supporting_text: >-
        Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase
        complex.
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        A key GO-relevant principle is that **bona fide Ras effectors must bind
        RAS in a nucleotide-dependent manner (GTP-bound)**
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      This transcription annotation is based on a downstream oncogenic Ras model
      and should not be treated as a direct HRAS function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PMID:23027131 describes oncogenic Ras regulation of Wnt4/miR-24 and
      motility phenotypes, which are distal transcriptional consequences rather
      than a direct normal molecular function of HRAS.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        By using a model of malignant transformation induced by Ras, we
        identified Wnt4 as an early target of Ras oncogenic signaling.
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        2) **Avoid overly broad BP terms** (e.g., generic “cancer,”
        “development,” “cell cycle,” “transcriptional regulation,”
        “immune/inflammatory processes”) unless there is direct mechanistic
        evidence placing *wild-type HRAS* as a proximal regulator rather than a
        downstream correlate. Large interactome datasets include false positives
        and many context-specific interactors.
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      The paper uses oncogenic Ras, but the annotation to Ras protein signal
      transduction is consistent with HRAS biology.
    action: ACCEPT
    reason: >-
      HRAS's proximal role in Ras protein signal transduction is core, even
      though distal phenotypes from this particular study require caution.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Ras protein signal transduction | HRAS is one of the canonical RAS
        proteins acting upstream of multiple effector pathways in Ras signal
        transduction.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:9054499
  review:
    summary: >-
      Oncogenic Ras regulates proliferation/senescence outcomes, but this is
      not a core wild-type HRAS function.
    action: KEEP_AS_NON_CORE
    reason: >-
      The supporting paper uses oncogenic Ras and shows growth arrest/senescence
      in primary cells, making this a context-dependent downstream outcome.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: >-
        Here we show that expression of oncogenic ras in primary human or rodent
        cells results in a permanent G1 arrest.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5673001
  review:
    summary: >-
      HRAS signals through the RAF-MEK-ERK MAPK cascade.
    action: ACCEPT
    reason: >-
      MAPK signaling is a proximal canonical output of HRAS-GTP effector
      binding.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins sit at the apex of the **RAF–MEK–ERK (MAPK) cascade**, and
        Ras-effector binding directly routes signals into MAPK outputs.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      Nucleoplasmic localization is not characteristic of the membrane-anchored
      p21 H-Ras and likely derives from high-throughput localization data or the
      minor p19 isoform.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The mature, lipidated H-Ras is targeted to plasma membrane and
      Golgi/endomembranes; nucleoplasmic localization is reported mainly for the
      alternatively spliced p19 (H-RasIDX), so a nucleoplasm CC term
      over-projects onto the canonical gene product.
    supported_by:
    - reference_id: PMID:14500341
      supporting_text: >-
        Both the endogenous and the transiently expressed p19 protein are
        detected in COS-1 and HeLa cells and show nuclear diffuse and speckled
        patterns as well as cytoplasmic localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      A cytosolic pool of HRAS exists transiently before and during membrane
      targeting.
    action: KEEP_AS_NON_CORE
    reason: >-
      Newly synthesized HRAS and the p19 isoform can be cytosolic, so the
      annotation is acceptable, but the functionally important locations are the
      plasma membrane and Golgi/endomembranes.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before
        subsequent trafficking to the plasma membrane
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      HRAS positively regulates MAPK cascade signaling.
    action: ACCEPT
    reason: >-
      Positive regulation of MAPK cascade is a proximal canonical Ras output,
      although PMID:23027131 itself is an oncogenic Ras model and distal
      phenotypes should be reviewed cautiously.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        “Ras protein signal transduction” and “positive regulation of MAPK
        cascade” are generally **core** for HRAS, but very specific outcome
        terms (e.g., “cell cycle progression” as a default) should be
        restricted to contexts with strong, direct, wild-type evidence.
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Positive regulation of MAPK cascade | RAS signaling is funneled strongly
        into RAF-MEK-ERK, and HRAS contributes to ERK output and MAPK signaling
        dynamics.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9649736
  review:
    summary: >-
      HRAS has intrinsic GTPase activity.
    action: ACCEPT
    reason: >-
      GTP hydrolysis is the core molecular switch activity of HRAS.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Intrinsic GTPase activity is **accelerated by GAPs**, while **GEFs
        promote GDP→GTP exchange**.
- term:
    id: GO:0160185
    label: phospholipase C activator activity
  evidence_type: IDA
  original_reference_id: PMID:11022048
  review:
    summary: >-
      HRAS can directly activate PLCepsilon in a GTP-dependent manner.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a well-supported specific effector activity, but it represents
      one downstream branch rather than the core HRAS molecular function.
    supported_by:
    - reference_id: PMID:11022048
      supporting_text: >-
        The Ras-associating domain of PLCepsilon specifically binds to the
        GTP-bound forms of Ha-Ras and Rap1A.
    - reference_id: PMID:11022048
      supporting_text: >-
        These results indicate that Ras directly regulates phosphoinositide
        breakdown through membrane targeting of PLCepsilon.
- term:
    id: GO:0098696
    label: regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
  evidence_type: IDA
  original_reference_id: PMID:12202034
  review:
    summary: >-
      Ras relays NMDA-R/CaMKII signaling to drive synaptic delivery of AMPA
      receptors during long-term potentiation, a neuron-specific downstream
      output of Ras signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a well-supported but cell-type-specific (postsynaptic) function
      that is a distal consequence of Ras-MAPK signaling rather than the core
      molecular switch function of HRAS.
    supported_by:
    - reference_id: PMID:12202034
      supporting_text: >-
        Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery
        of AMPA-Rs during long-term potentiation.
- term:
    id: GO:0098696
    label: regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
  evidence_type: IMP
  original_reference_id: PMID:12202034
  review:
    summary: >-
      Perturbation of Ras alters synaptic AMPA receptor delivery during LTP,
      supporting a non-core synaptic-plasticity role.
    action: KEEP_AS_NON_CORE
    reason: >-
      The IMP evidence supports a neuron-specific role downstream of Ras-MAPK
      signaling; it is a legitimate process annotation but non-core relative to
      the GTPase/signal-transduction function of HRAS.
    supported_by:
    - reference_id: PMID:12202034
      supporting_text: >-
        Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery
        of AMPA-Rs during long-term potentiation.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:12202034
  review:
    summary: >-
      HRAS functions in postsynaptic signaling at glutamatergic synapses during
      synaptic plasticity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The glutamatergic synapse location reflects a neuron-specific context for
      Ras signaling and is a valid but non-core localization relative to plasma
      membrane and Golgi.
    supported_by:
    - reference_id: PMID:12202034
      supporting_text: >-
        we examine the small GTPases Ras and Rap in the postsynaptic signaling
        underlying synaptic plasticity
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IMP
  original_reference_id: PMID:12202034
  review:
    summary: >-
      Manipulation of Ras at glutamatergic synapses alters AMPA receptor
      trafficking during plasticity.
    action: KEEP_AS_NON_CORE
    reason: >-
      This synapse-localization annotation is supported but represents a
      neuron-specific context rather than a core HRAS localization.
    supported_by:
    - reference_id: PMID:12202034
      supporting_text: >-
        we examine the small GTPases Ras and Rap in the postsynaptic signaling
        underlying synaptic plasticity
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      This is a downstream motility phenotype from an oncogenic Ras model, not a
      core HRAS function.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is biologically plausible as a distal Ras signaling output,
      but it should be marked non-core because the evidence is from malignant
      transformation/oncogenic Ras context.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        Wnt4 interferes with Ras-induced actin cytoskeleton reorganization
        through non-canonical pathways, by altering the balance between the
        activation of different Rho-family small guanosine triphosphatases
        (GTPases).
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: IDA
  original_reference_id: PMID:9054499
  review:
    summary: >-
      Cell-cycle arrest is a downstream outcome of oncogenic Ras-induced
      senescence.
    action: KEEP_AS_NON_CORE
    reason: >-
      This annotation is supported as a context-specific oncogenic Ras outcome
      but should not be represented as the core normal function of HRAS.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: >-
        The arrest induced by ras is accompanied by accumulation of p53 and p16,
        and is phenotypically indistinguishable from cellular senescence.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647994
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802834
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802908
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802918
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802922
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802924
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802925
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802926
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802937
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802941
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802942
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802943
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803233
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803234
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803240
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8936731
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9651280
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647980
  review:
    summary: >-
      HRAS transits and cycles through Golgi membranes during palmitoylation-dependent trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        palmitoylation is **reversible/dynamic**, supporting HRAS cycling between Golgi and plasma membrane
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647982
  review:
    summary: >-
      HRAS transits and cycles through Golgi membranes during palmitoylation-dependent trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        palmitoylation is **reversible/dynamic**, supporting HRAS cycling between Golgi and plasma membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647978
  review:
    summary: >-
      Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before subsequent trafficking to the plasma membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647999
  review:
    summary: >-
      Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before subsequent trafficking to the plasma membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1168636
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1225951
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1225957
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1250383
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1306972
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1433471
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-170986
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-177938
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-177945
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-186834
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-210977
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2179407
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2424477
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-392054
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5218845
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5621573
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624486
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624492
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624494
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5637806
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5637808
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654392
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654402
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654413
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654426
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654600
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654618
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654647
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5654663
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5655241
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5655277
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5655326
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5655347
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5658231
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5658435
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672950
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672965
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672966
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672969
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672972
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672973
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672978
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672980
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674018
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5674022
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675417
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675431
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5675433
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802837
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8851827
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8851877
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8851899
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8941613
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8941618
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8941623
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8941628
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8981353
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8981355
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9607304
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9632906
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9632918
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9634418
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647980
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9649733
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9649735
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9649736
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9653108
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656209
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656211
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656212
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656213
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656214
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9656215
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657599
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657603
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657606
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9657608
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9658253
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9660557
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9664991
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9665009
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9665404
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9665408
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9665700
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9665707
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670436
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9672163
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9672170
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9695853
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9703441
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647977
  review:
    summary: >-
      Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before subsequent trafficking to the plasma membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647982
  review:
    summary: >-
      Newly prenylated HRAS is processed at the ER membrane (RCE1/ICMT) before onward trafficking, consistent with this Reactome location.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before subsequent trafficking to the plasma membrane
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9647978
  review:
    summary: >-
      A cytosolic pool of HRAS exists prior to and during membrane targeting, consistent with this Reactome reaction location.
    action: KEEP_AS_NON_CORE
    reason: >-
      This Reactome TAS row places a HRAS reaction in the cytosol, consistent
      with the soluble/pre-membrane pool; the location is valid but non-core
      relative to the plasma membrane and Golgi/endomembranes.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before subsequent trafficking to the plasma membrane
- term:
    id: GO:0090314
    label: positive regulation of protein targeting to membrane
  evidence_type: IMP
  original_reference_id: PMID:11022048
  review:
    summary: >-
      GTP-bound HRAS recruits PLCepsilon to the membrane, promoting membrane
      targeting of this effector.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a specific, well-supported consequence of HRAS-GTP binding the
      PLCepsilon RA domain and recruiting it to membranes, but it is one
      effector branch rather than the core HRAS molecular function.
    supported_by:
    - reference_id: PMID:11022048
      supporting_text: >-
        These results indicate that Ras directly regulates phosphoinositide
        breakdown through membrane targeting of PLCepsilon.
- term:
    id: GO:0071480
    label: cellular response to gamma radiation
  evidence_type: IDA
  original_reference_id: PMID:16213212
  review:
    summary: >-
      The cited reference concerns RPL26/nucleolin control of p53 translation
      after irradiation and does not establish a direct, proximal HRAS role in
      the gamma-radiation response.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PMID:16213212 focuses on p53 translational induction by RPL26 and
      nucleolin after DNA damage; there is no direct evidence here that
      wild-type HRAS is a proximal mediator of the cellular response to gamma
      radiation, so this is a distal/indirect over-annotation.
    supported_by:
    - reference_id: PMID:16213212
      supporting_text: >-
        Ribosomal protein L26 (RPL26) and nucleolin were found to bind to the 5'
        untranslated region (UTR) of p53 mRNA and to control p53 translation and
        induction after DNA damage.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IMP
  original_reference_id: PMID:9230043
  review:
    summary: >-
      HRAS has intrinsic GTPase activity, a core property of this small GTPase
      switch.
    action: ACCEPT
    reason: >-
      Intrinsic GTP hydrolysis is the defining catalytic function of HRAS and is
      well established structurally and biochemically; this is a core molecular
      function.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Intrinsic GTPase activity is **accelerated by GAPs**, while **GEFs
        promote GDP→GTP exchange**.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IMP
  original_reference_id: PMID:9230043
  review:
    summary: >-
      HRAS binds GTP with high affinity as part of its nucleotide-dependent
      switch.
    action: ACCEPT
    reason: >-
      GTP binding is a core molecular function of HRAS, well supported by
      structural studies of the GTP-bound conformation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS is a canonical RAS small GTPase that binds GDP/GTP with high
        affinity and functions as a nucleotide-dependent molecular switch.
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: IMP
  original_reference_id: PMID:8142349
  review:
    summary: >-
      HRAS binds GDP in its inactive state, completing the GDP/GTP switch cycle.
    action: ACCEPT
    reason: >-
      GDP binding (the OFF state of the switch) is a core molecular function of
      HRAS, demonstrated by NMR structural studies of the GDP-bound form.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins (including HRAS) are **GTP hydrolases** that function as
        **binary molecular switches**: GDP-bound is “OFF,” GTP-bound is “ON,”
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: IMP
  original_reference_id: PMID:9230043
  review:
    summary: >-
      HRAS binds GDP in its inactive state, completing the GDP/GTP switch cycle.
    action: ACCEPT
    reason: >-
      GDP binding is a core molecular function of HRAS; this duplicate IMP
      annotation is consistent with the GDP/GTP switch model.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins (including HRAS) are **GTP hydrolases** that function as
        **binary molecular switches**: GDP-bound is “OFF,” GTP-bound is “ON,”
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:9178006
  review:
    summary: >-
      HRAS has intrinsic GTPase activity (inferred from the conserved let-60 Ras
      activation study).
    action: ACCEPT
    reason: >-
      GTP hydrolysis is the core catalytic molecular function of HRAS and is
      conserved across the Ras family.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Intrinsic GTPase activity is **accelerated by GAPs**, while **GEFs
        promote GDP→GTP exchange**.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17724343
  review:
    summary: >-
      HRAS localizes to the plasma membrane, where its signaling is spatially
      regulated (e.g., by RKTG).
    action: ACCEPT
    reason: >-
      Direct evidence supports plasma membrane localization, the principal
      signaling location of mature, lipidated HRAS.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid
        modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4093331
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4093339
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802914
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802915
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802916
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802919
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6802921
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6803230
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8936676
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9617449
  review:
    summary: >-
      The plasma membrane is the principal signaling location of mature, lipidated HRAS, consistent with these Reactome RAS-pathway reactions.
    action: ACCEPT
    reason: >-
      This is a bulk Reactome TAS localization row placing HRAS in a membrane
      compartment consistent with its established lipidation-dependent
      trafficking and signaling; the location is correct and accepted.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11598133
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the GEF CNrasGEF (Nedd4 regulation).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10608844
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RA-GEF, a Rap1A/Ras-associating GEF.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Negative regulation of gene expression is a distal transcriptional output
      from an oncogenic Ras transformation model (Wnt4/miR-24 axis).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PMID:23027131 uses oncogenic Ras-induced malignant transformation;
      transcriptional/gene-expression changes are distal consequences rather
      than a proximal, direct molecular function of wild-type HRAS.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        By using a model of malignant transformation induced by Ras, we
        identified Wnt4 as an early target of Ras oncogenic signaling.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Promotion of cell migration is a downstream motility phenotype of
      oncogenic Ras signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell migration is a plausible distal Ras output but is documented here in
      an oncogenic transformation context; it is non-core relative to the HRAS
      switch function.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        Wnt4 inhibits cell motility induced by oncogenic Ras.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Positive transcriptional regulation is a distal output from an oncogenic
      Ras transformation model.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Transcriptional activation in this study is a downstream consequence of
      oncogenic Ras signaling, not a direct, proximal HRAS molecular function.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        By using a model of malignant transformation induced by Ras, we
        identified Wnt4 as an early target of Ras oncogenic signaling.
- term:
    id: GO:0090303
    label: positive regulation of wound healing
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Wound-healing regulation is a distal phenotype inferred from oncogenic
      Ras-driven motility assays.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a far-downstream phenotypic readout of oncogenic Ras-induced cell
      motility rather than a proximal, mechanistically supported function of
      wild-type HRAS.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        Wnt4 inhibits cell motility induced by oncogenic Ras.
- term:
    id: GO:1900029
    label: positive regulation of ruffle assembly
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Ruffle assembly is a cytoskeletal output of oncogenic Ras signaling via
      Rho-family GTPases.
    action: KEEP_AS_NON_CORE
    reason: >-
      Membrane ruffling downstream of Ras-driven actin remodeling is plausible
      but indirect (mediated by Rho-family GTPases) and documented in an
      oncogenic context, so it is non-core.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        Wnt4 interferes with Ras-induced actin cytoskeleton reorganization
        through non-canonical pathways, by altering the balance between the
        activation of different Rho-family small guanosine triphosphatases
        (GTPases).
- term:
    id: GO:2000630
    label: positive regulation of miRNA metabolic process
  evidence_type: IDA
  original_reference_id: PMID:23027131
  review:
    summary: >-
      Regulation of miR-24 is a distal transcriptional/RNA output from an
      oncogenic Ras transformation model.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      miRNA metabolic regulation here is a downstream consequence of oncogenic
      Ras signaling rather than a direct, proximal HRAS molecular function.
    supported_by:
    - reference_id: PMID:23027131
      supporting_text: >-
        By using a model of malignant transformation induced by Ras, we
        identified Wnt4 as an early target of Ras oncogenic signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10369681
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a partner reported in an Aiolos/Bcl-2 T-cell study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:22065586
  review:
    summary: >-
      Oncogenic Ras induces DR5 transcription via ERK/JNK and downstream
      transcription factors (CHOP, Elk1, c-Jun), a distal transcriptional
      output.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Transcriptional regulation of DR5 here is several steps downstream of
      oncogenic Ras signaling and mediated by ERK/JNK and multiple
      transcription factors, so it is not a proximal, direct HRAS function.
    supported_by:
    - reference_id: PMID:22065586
      supporting_text: >-
        Ras induces DR5 expression through co-activation of ERK/RSK and JNK
        signaling pathways and subsequent cooperative effects among the
        transcriptional factors CHOP, Elk1, and c-Jun to enhance DR5 gene
        transcription.
- term:
    id: GO:0046330
    label: positive regulation of JNK cascade
  evidence_type: IDA
  original_reference_id: PMID:22065586
  review:
    summary: >-
      Oncogenic Ras can co-activate the JNK signaling cascade.
    action: KEEP_AS_NON_CORE
    reason: >-
      JNK activation is a recognized but secondary/context-dependent Ras output
      (relative to the canonical RAF-MEK-ERK cascade) and is documented here in
      an oncogenic context, so it is non-core.
    supported_by:
    - reference_id: PMID:22065586
      supporting_text: >-
        Ras induces DR5 expression through co-activation of ERK/RSK and JNK
        signaling pathways
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IDA
  original_reference_id: PMID:22065586
  review:
    summary: >-
      HRAS positively regulates the ERK1/ERK2 cascade, a core proximal Ras
      output.
    action: ACCEPT
    reason: >-
      Activation of the ERK1/2 (RAF-MEK-ERK) cascade is the canonical, proximal
      signaling output of HRAS-GTP and is a core process annotation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS signaling is funneled strongly into RAF-MEK-ERK, and HRAS
        contributes to ERK output and MAPK signaling dynamics.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14500341
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a reported physical interaction partner.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:14500341
  review:
    summary: >-
      HRAS binds GTP, a core molecular function of this small GTPase.
    action: ACCEPT
    reason: >-
      GTP binding is a core, well-established molecular function of HRAS as a
      nucleotide-dependent switch.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS is a canonical RAS small GTPase that binds GDP/GTP with high
        affinity and functions as a nucleotide-dependent molecular switch.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:14500341
  review:
    summary: >-
      The canonical p21 H-Ras localizes to Golgi membranes during
      lipidation-dependent trafficking.
    action: ACCEPT
    reason: >-
      Golgi localization is consistent with HRAS palmitoylation cycles and
      ER/Golgi processing; this is a valid localization annotation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        palmitoylation is **reversible/dynamic**, supporting HRAS cycling
        between Golgi and plasma membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:14500341
  review:
    summary: >-
      The canonical p21 H-Ras localizes to the plasma membrane.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is the principal signaling location of mature
      lipidated HRAS.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid
        modifications enabling stable plasma membrane localization.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:21968647
  review:
    summary: >-
      HRAS localizes to and signals from the Golgi apparatus, where PAQR10/PAQR11
      promote its Golgi localization and ERK activation.
    action: ACCEPT
    reason: >-
      Golgi localization and Golgi-based Ras signaling are directly supported;
      this is a valid HRAS localization annotation.
    supported_by:
    - reference_id: PMID:21968647
      supporting_text: >-
        Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of
        HRas, NRas and KRas4A, but not KRas4B.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:21968647
  review:
    summary: >-
      HRAS localizes to the plasma membrane in addition to the Golgi pool.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is the principal signaling location of HRAS
      and is consistent with this study of Golgi vs PM Ras pools.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid
        modifications enabling stable plasma membrane localization.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IDA
  original_reference_id: PMID:9054499
  review:
    summary: >-
      Oncogenic Ras induces premature senescence in primary cells, a
      context-dependent outcome.
    action: KEEP_AS_NON_CORE
    reason: >-
      The senescence evidence comes from oncogenic Ras overexpression in primary
      cells and should not be treated as a core function of wild-type HRAS.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: >-
        Here we show that expression of oncogenic ras in primary human or rodent
        cells results in a permanent G1 arrest.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11980706
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with a partner reported in an Arl2-GTP/PDEdelta study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:20154697
  review:
    summary: >-
      Activation of Ras (via DAB2IP/RasGAP loss) promotes prostate epithelial
      proliferation and metastasis, a downstream cancer-context phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Epithelial proliferation here arises from loss of the RasGAP DAB2IP in a
      metastatic prostate cancer model; it is a context-dependent downstream
      output rather than a core wild-type HRAS function.
    supported_by:
    - reference_id: PMID:20154697
      supporting_text: >-
        loss of the Ras GTPase-activating protein (RasGAP) gene DAB2IP induces
        metastatic prostate cancer in an orthotopic mouse tumor model.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:9765203
  review:
    summary: >-
      Sustained Ras/MEK-MAPK signaling can promote proliferation, a
      context-dependent downstream outcome.
    action: KEEP_AS_NON_CORE
    reason: >-
      Proliferation is a canonical but context-dependent Ras output; the cited
      study links constitutive MEK/MAPK signaling to proliferation/senescence
      depending on context, so it is non-core.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS-ERK signaling dynamics can bias proliferation versus differentiation
        outputs, but these outcomes depend strongly on cell type and signaling
        kinetics.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IDA
  original_reference_id: PMID:9765203
  review:
    summary: >-
      HRAS positively regulates the MAPK cascade, a core proximal Ras output.
    action: ACCEPT
    reason: >-
      Positive regulation of the MAPK (RAF-MEK-ERK) cascade is the canonical
      proximal signaling output of HRAS-GTP and is a core process.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        RAS proteins sit at the apex of the **RAF–MEK–ERK (MAPK) cascade**, and
        Ras-effector binding directly routes signals into MAPK outputs.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:17260967
  review:
    summary: >-
      HRAS binds GTP; the cited reference uses HRAS as a reference Ras-like GTP
      binding protein when characterizing the LRRK2 ROC domain.
    action: ACCEPT
    reason: >-
      GTP binding is a core, well-established molecular function of HRAS,
      regardless of the comparative context of the citing paper.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS is a canonical RAS small GTPase that binds GDP/GTP with high
        affinity and functions as a nucleotide-dependent molecular switch.
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:9054499
  review:
    summary: >-
      Oncogenic Ras can negatively regulate proliferation by triggering
      premature senescence/G1 arrest in primary cells.
    action: KEEP_AS_NON_CORE
    reason: >-
      This anti-proliferative (senescence) output is an oncogenic-Ras,
      context-dependent phenotype in primary cells and is not a core wild-type
      HRAS function.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: >-
        The arrest induced by ras is accompanied by accumulation of p53 and p16,
        and is phenotypically indistinguishable from cellular senescence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11022048
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with the effector PLCepsilon (Ras-associating domain).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:2122974
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with GTPase-activating protein (GAP) modulating Ras nucleotide state.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9219684
  review:
    summary: >-
      This IPI annotation records a physical interaction of HRAS with RasGAP (Ras-RasGAP complex structure).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The bare 'protein binding' (GO:0005515) term is uninformative for a hub
      GTPase like HRAS; where the interaction reflects a bona fide,
      nucleotide-state-dependent effector or regulator engagement it would be
      better captured by a specific binding term, and many large-scale
      interactome hits lack mechanistic validation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        Broad protein-binding annotation adds little value when specific effector
        binding terms are available with direct evidence.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: NAS
  original_reference_id: PMID:8607982
  review:
    summary: >-
      HRAS transmits signals from growth factor receptors into downstream kinase
      cascades; the more specific term is Ras protein signal transduction.
    action: MODIFY
    reason: >-
      The broad signal transduction term should be replaced with the specific
      Ras protein signal transduction term, which the cited review explicitly
      describes.
    proposed_replacement_terms:
    - id: GO:0007265
      label: Ras protein signal transduction
    supported_by:
    - reference_id: PMID:8607982
      supporting_text: >-
        The ras p21 protooncogene products, H-ras, K-ras, and N-ras, transmit
        signals from growth factor receptors to a cascade of protein kinases
        that begins with the Raf protooncogene product.
- term:
    id: GO:0009887
    label: animal organ morphogenesis
  evidence_type: TAS
  original_reference_id: PMID:10848592
  review:
    summary: >-
      Organ morphogenesis is a distal developmental phenotype inferred from
      Ras/Ral involvement in myoblast chemotaxis and muscle development.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The cited study addresses Ras/Ral control of growth-factor-driven myoblast
      chemotaxis; organ morphogenesis is a far-downstream developmental outcome,
      not a proximal, direct HRAS molecular function.
    supported_by:
    - reference_id: PMID:10848592
      supporting_text: >-
        Expression of a dominant-negative mutant of Ras inhibited chemotaxis of
        C2C12 myoblasts in response to basic fibroblast growth factor (bFGF),
        hepatocyte growth factor (HGF), and insulin-like growth factor 1
        (IGF-1), key regulators of limb muscle development and skeletal muscle
        regeneration.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:10842192
  review:
    summary: >-
      A generic cytoplasm localization, consistent with the soluble/pre-membrane
      pool of HRAS.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cytoplasmic localization is plausible for a fraction of HRAS, but the
      functionally meaningful locations are the plasma membrane and
      Golgi/endomembranes; this generic term is non-core.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        prenylation drives nascent Ras proteins to **ER and Golgi** before
        subsequent trafficking to the plasma membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:9020890
  review:
    summary: >-
      Ras localizes to the plasma membrane in platelets, consistent with its
      lipidation-dependent membrane targeting.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is the principal signaling location of mature
      HRAS and is directly observed here.
    supported_by:
    - reference_id: PMID:9020890
      supporting_text: >-
        Immunofluorescence studies indicated that Ras was present in a
        peripheral rim pattern in fixed, permeabilized platelets, suggesting an
        intracellular, plasma membrane location.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:9880516
  review:
    summary: >-
      Lipidated H-Ras localizes to the plasma membrane; palmitoylation can
      target H-Ras to the membrane even without farnesylation.
    action: ACCEPT
    reason: >-
      Plasma membrane localization driven by H-Ras lipid modifications is a core
      localization annotation.
    supported_by:
    - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
      supporting_text: >-
        HRAS membrane association is essential for signaling, with lipid
        modifications enabling stable plasma membrane localization.
- term:
    id: GO:0006935
    label: chemotaxis
  evidence_type: TAS
  original_reference_id: PMID:10848592
  review:
    summary: >-
      Ras (with Ral) contributes to growth-factor-induced chemotactic migration
      of skeletal myoblasts, a cell-type-specific downstream output.
    action: KEEP_AS_NON_CORE
    reason: >-
      Chemotaxis is a plausible distal output of Ras signaling but is
      context-specific (myoblasts, via a Ras-Ral branch independent of MEK/PI3K
      here), so it is non-core relative to the GTPase switch function.
    supported_by:
    - reference_id: PMID:10848592
      supporting_text: >-
        Here, we demonstrate that Ras is involved also in the chemotactic
        response of skeletal myoblasts.
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: TAS
  original_reference_id: PMID:9020890
  review:
    summary: >-
      HRAS is activated downstream of cell-surface receptors (e.g., thrombin and
      thromboxane A2 receptors) in platelets.
    action: KEEP_AS_NON_CORE
    reason: >-
      Acting downstream of cell-surface receptors is consistent with HRAS
      biology, but this broad process is a context for, rather than a more
      specific statement of, the core Ras protein signal transduction function.
    supported_by:
    - reference_id: PMID:9020890
      supporting_text: >-
        Activation of platelets with the thrombin receptor peptide42-50, the
        prostaglandin H2/thromboxane A2 mimetic U46619 or phorbol 12-myristate
        13-acetate induced a rapid increase in GTP-bound, activated Ras.
references:
- id: file:human/HRAS/HRAS-deep-research-falcon.md
  title: Falcon deep research synthesis for human HRAS
  findings:
  - statement: >-
      HRAS is a small GTPase molecular switch whose core GO annotations should
      prioritize GTP binding, GTPase activity, Ras protein signal transduction,
      positive regulation of MAPK cascade, and plasma membrane/Golgi membrane
      localization, while distal oncogenic mutant phenotypes should be curated
      conservatively.
    supporting_text: >-
      “Ras protein signal transduction” and “positive regulation of MAPK
      cascade” are generally **core** for HRAS, but very specific outcome terms
      (e.g., “cell cycle progression” as a default) should be restricted to
      contexts with strong, direct, wild-type evidence.
- id: GO_REF:0000002
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000003
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000033
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000044
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000052
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000107
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000117
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000120
  title: 'TODO: Fetch title'
  findings: []
- id: PMID:10369681
  title: Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization.
  findings: []
- id: PMID:10608844
  title: RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved
    between nematode and humans.
  findings: []
- id: PMID:10842192
  title: Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident.
  findings: []
- id: PMID:10848592
  title: Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts.
  findings: []
- id: PMID:11022048
  title: Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras.
  findings: []
- id: PMID:11335720
  title: Prenylated Rab acceptor protein is a receptor for prenylated small GTPases.
  findings: []
- id: PMID:11598133
  title: Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange factor CNrasGEF.
  findings: []
- id: PMID:11857081
  title: The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1.
  findings: []
- id: PMID:11980706
  title: 'The complex of Arl2-GTP and PDE delta: from structure to function.'
  findings: []
- id: PMID:12202034
  title: Ras and Rap control AMPA receptor trafficking during synaptic plasticity.
  findings: []
- id: PMID:12620389
  title: Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis.
  findings: []
- id: PMID:12628188
  title: Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS.
  findings: []
- id: PMID:14500341
  title: Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm
    and nucleus.
  findings: []
- id: PMID:14724641
  title: Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP.
  findings: []
- id: PMID:15507210
  title: Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  findings: []
- id: PMID:15886098
  title: RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration.
  findings: []
- id: PMID:16213212
  title: Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin.
  findings: []
- id: PMID:16316996
  title: The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane.
  findings: []
- id: PMID:16698549
  title: GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1.
  findings: []
- id: PMID:16810318
  title: Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation.
  findings: []
- id: PMID:17084389
  title: Catalytic competence of the Ras-GEF domain of hSos1 requires intra-REM domain interactions mediated by phenylalanine
    577.
  findings: []
- id: PMID:17260967
  title: GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease.
  findings: []
- id: PMID:17540175
  title: Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice.
  findings: []
- id: PMID:17724343
  title: Spatial regulation of Raf kinase signaling by RKTG.
  findings: []
- id: PMID:18073111
  title: Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of
    Raf.
  findings: []
- id: PMID:18273062
  title: A novel switch region regulates H-ras membrane orientation and signal output.
  findings: []
- id: PMID:18454158
  title: Membrane-dependent signal integration by the Ras activator Son of sevenless.
  findings: []
- id: PMID:18596699
  title: Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II.
  findings: []
- id: PMID:19063885
  title: Regulation of growth and survival of activated T cells by cell-transducing inhibitors of Ras.
  findings: []
- id: PMID:19141281
  title: Differences in flexibility underlie functional differences in the Ras activators son of sevenless and Ras guanine
    nucleotide releasing factor 1.
  findings: []
- id: PMID:19222999
  title: Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway.
  findings: []
- id: PMID:19696784
  title: Nucleocytoplasmic transport of Alp7/TACC organizes spatiotemporal microtubule formation in fission yeast.
  findings: []
- id: PMID:20080631
  title: Ras membrane orientation and nanodomain localization generate isoform diversity.
  findings: []
- id: PMID:20133692
  title: Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.
  findings: []
- id: PMID:20133694
  title: Allosteric gating of Son of sevenless activity by the histone domain.
  findings: []
- id: PMID:20154697
  title: An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear
    factor-kappaB.
  findings: []
- id: PMID:20178605
  title: Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells.
  findings: []
- id: PMID:20936779
  title: A human MAP kinase interactome.
  findings: []
- id: PMID:2122974
  title: Modulation of guanine nucleotides bound to Ras in NIH3T3 cells by oncogenes, growth factors, and the GTPase activating
    protein (GAP).
  findings: []
- id: PMID:21968647
  title: PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus.
  findings: []
- id: PMID:22020336
  title: p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors.
  findings: []
- id: PMID:22065586
  title: Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and
    JNK signaling.
  findings: []
- id: PMID:22169110
  title: Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic
    myeloid leukemia.
  findings: []
- id: PMID:23027131
  title: Wnt4 inhibits cell motility induced by oncogenic Ras.
  findings: []
- id: PMID:24412244
  title: Charting the molecular links between driver and susceptibility genes in colorectal cancer.
  findings: []
- id: PMID:24441586
  title: Integrated RAS signaling defined by parallel NMR detection of effectors and regulators.
  findings: []
- id: PMID:24929361
  title: Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling.
  findings: []
- id: PMID:25241761
  title: Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a
    pathway network.
  findings: []
- id: PMID:25684575
  title: Allosteric effects of the oncogenic RasQ61L mutant on Raf-RBD.
  findings: []
- id: PMID:26165597
  title: The RAS-Binding Domain of Human BRAF Protein Serine/Threonine Kinase Exhibits Allosteric Conformational Changes upon
    Binding HRAS.
  findings: []
- id: PMID:26635368
  title: Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating
    Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:30194290
  title: Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability.
  findings: []
- id: PMID:30518913
  title: UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via
    interaction with the C-terminal domain of H-Ras.
  findings: []
- id: PMID:31209342
  title: GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation
    in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34591612
  title: A protein interaction landscape of breast cancer.
  findings: []
- id: PMID:34591642
  title: A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
  findings: []
- id: PMID:35512704
  title: Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
  findings: []
- id: PMID:35831509
  title: Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.
  findings: []
- id: PMID:35839996
  title: A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8142349
  title: Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy.
  findings: []
- id: PMID:8332187
  title: Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1.
  findings: []
- id: PMID:8607982
  title: Ras-related proteins in signal transduction and growth control.
  findings: []
- id: PMID:8670882
  title: Identification of a novel Rac1-interacting protein involved in membrane ruffling.
  findings: []
- id: PMID:9020890
  title: Ras activation in platelets after stimulation of the thrombin receptor, thromboxane A2 receptor or protein kinase
    C.
  findings: []
- id: PMID:9054499
  title: Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
  findings: []
- id: PMID:9144171
  title: Protein binding and signaling properties of RIN1 suggest a unique effector function.
  findings: []
- id: PMID:9178006
  title: Mechanism of activation of the Caenorhabditis elegans ras homologue let-60 by a novel, temperature-sensitive, gain-of-function
    mutation.
  findings: []
- id: PMID:9219684
  title: 'The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.'
  findings: []
- id: PMID:9230043
  title: Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein.
  findings: []
- id: PMID:9447984
  title: Regulation of Sos activity by intramolecular interactions.
  findings: []
- id: PMID:9488663
  title: Identification of Nore1 as a potential Ras effector.
  findings: []
- id: PMID:9690470
  title: The structural basis of the activation of Ras by Sos.
  findings: []
- id: PMID:9765203
  title: Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling.
  findings: []
- id: PMID:9880516
  title: A non-farnesylated Ha-Ras protein can be palmitoylated and trigger potent differentiation and transformation.
  findings: []
- id: Reactome:R-HSA-1168636
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1225951
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1225957
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1250383
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1306972
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-1433471
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-170986
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-177938
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-177945
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-186834
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-210977
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-2179407
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-2424477
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-392054
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-4093331
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core_functions:
- molecular_function:
    id: GO:0003924
    label: GTPase activity
  description: >-
    HRAS is a small monomeric GTPase that binds GDP/GTP and hydrolyzes GTP to
    operate as a molecular switch. In its GTP-bound state it recruits effectors
    that transmit Ras signaling, especially through RAF-MEK-ERK/MAPK pathways.
    Membrane targeting through CAAX processing and palmitoylation places this
    switch primarily at the plasma membrane and Golgi/endomembrane
    compartments. Proliferation, senescence, motility, and transcriptional
    outputs are downstream, context-dependent consequences rather than the core
    molecular function.
  directly_involved_in:
  - id: GO:0007265
    label: Ras protein signal transduction
  - id: GO:0043410
    label: positive regulation of MAPK cascade
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0000139
    label: Golgi membrane
  supported_by:
  - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
    supporting_text: >-
      RAS proteins (including HRAS) are **GTP hydrolases** that function as
      **binary molecular switches**: GDP-bound is “OFF,” GTP-bound is “ON,” and
      the ON state supports binding to downstream effector proteins.
- molecular_function:
    id: GO:0005525
    label: GTP binding
  description: >-
    HRAS binding to GTP/GDP is co-equal with GTP hydrolysis in the Ras molecular
    switch: GDP-bound HRAS is inactive, while GTP-bound HRAS recruits effectors
    that route signals into MAPK and other Ras effector pathways.
  directly_involved_in:
  - id: GO:0007265
    label: Ras protein signal transduction
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0000139
    label: Golgi membrane
  supported_by:
  - reference_id: file:human/HRAS/HRAS-deep-research-falcon.md
    supporting_text: >-
      GTP binding | HRAS is a canonical RAS small GTPase that binds GDP/GTP
      with high affinity and functions as a nucleotide-dependent molecular
      switch.
proposed_new_terms: []
suggested_questions:
- question: >-
    Which HRAS effector interactions in the GOA set are supported by direct
    GTP-state-dependent binding and should be converted from generic protein
    binding to specific effector-binding annotations?
- question: >-
    Which distal proliferation, transcription, migration, or developmental
    annotations are based on oncogenic mutant HRAS rather than normal wild-type
    HRAS signaling?
- question: >-
    Should HRAS compartment-specific signaling from plasma membrane, Golgi, and
    recycling endosome be represented with separate non-core localization or
    process annotations?
suggested_experiments:
- description: >-
    Curate the generic protein-binding rows by mapping each interactor to
    nucleotide-state-dependent effector evidence and replacing supported rows
    with specific binding terms where available.
- description: >-
    Compare wild-type HRAS and oncogenic HRAS alleles in controlled cell systems
    for MAPK, PI3K, PLCepsilon, senescence, and transcriptional outputs to
    distinguish core signaling from mutant-specific phenotypes.
- description: >-
    Use live-cell imaging with palmitoylation/prenylation mutants to separate
    plasma membrane, Golgi, and recycling-endosome pools and their contribution
    to effector activation.

Gene Description

Existing Annotations Review

Core Functions

HRAS binding to GTP/GDP is co-equal with GTP hydrolysis in the Ras molecular switch: GDP-bound HRAS is inactive, while GTP-bound HRAS recruits effectors that route signals into MAPK and other Ras effector pathways.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Concise GO annotation research report: Human HRAS (UniProt P01112, GTPase HRas)

Scope and intent

1) Key concepts and definitions (current understanding)

1.1 Core MF: small GTPase molecular switch

1.2 Switch regions and nucleotide-dependent effector binding

2) Cellular Component: membrane targeting and localization (CAAX processing, palmitoylation; PM/Golgi/endosomes)

2.1 CAAX-driven prenylation and ER/Golgi processing (core)

2.2 Palmitoylation-mediated membrane affinity, Golgi localization, and trafficking (core)

2.3 Recycling endosome localization (supported but typically non-core)

3) Biological Process: Ras signal transduction and downstream pathways; core vs non-core outcomes

3.1 Core BP: Ras protein signal transduction; MAPK activation

3.2 PI3K–AKT pathway as a canonical Ras output (core, with context qualifiers)

3.3 RalGDS/Ral pathway and RASSF pathways (core Ras outputs)

3.4 Apoptosis/senescence: generally non-core default for HRAS

4) Effector/protein-binding annotations: specificity and evidence strength

4.1 Prefer specific effector binding terms over generic “protein binding”

4.2 Quantitative binding data (helps prevent over-annotation)

4.3 Primary effector-binding literature identifiers (PMID/DOI)

5) Recent developments (prioritize 2023–2024)

5.1 2024 expert synthesis of effector biology and annotation caveats

5.2 2023 expert analysis of Ras dynamics and interactomics uncertainty

6) Current applications / real-world implementations (GO-relevant)

7) Statistics / quantitative data relevant for curation decisions

8) Over-annotation risks and caveats (especially mutants/overexpression)

9) Recommended GO annotation elements (summary table)

References (URLs / dates)

Citations

📚 Additional Documentation

Notes

HRAS notes

📄 View Raw YAML