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.
| 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 β AAX proteolysis (RCE1) β 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 βOFF,β GTP-bound is βON,β 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 GDPβGTP 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 βsecond signalβ for HRAS membrane targeting beyond prenylation and supports vesicular transport from **Golgiβplasma 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 **RAFβMEKβERK (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 GDPβGTP 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 βsecond signalβ for HRAS membrane targeting beyond prenylation and supports vesicular transport from **Golgiβplasma 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 p37Ξ΄ is a new isoform of PI3K p110Ξ΄ 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 βRas protein signal transductionβ and βpositive regulation of MAPK cascadeβ are generally **core** for HRAS, but very specific outcome terms (e.g., βcell cycle progressionβ 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 **RAFβMEKβERK (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 βcancer,β βdevelopment,β βcell cycle,β βtranscriptional regulation,β βimmune/inflammatory processesβ) 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 βcancer,β βdevelopment,β βcell cycle,β βtranscriptional regulation,β βimmune/inflammatory processesβ) 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 βcancer,β βdevelopment,β βcell cycle,β βtranscriptional regulation,β βimmune/inflammatory processesβ) 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 **RAFβMEKβERK (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 βRas protein signal transductionβ and βpositive regulation of MAPK cascadeβ are generally **core** for HRAS, but very specific outcome terms (e.g., βcell cycle progressionβ 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 GDPβGTP 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 GDPβGTP 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 βOFF,β GTP-bound is βON,β |
| 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 βOFF,β GTP-bound is βON,β |
| 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 GDPβGTP 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 **RAFβMEKβERK (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. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: 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?
Q: Which distal proliferation, transcription, migration, or developmental annotations are based on oncogenic mutant HRAS rather than normal wild-type HRAS signaling?
Q: Should HRAS compartment-specific signaling from plasma membrane, Golgi, and recycling endosome be represented with separate non-core localization or process annotations?
Experiment: 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.
Experiment: 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.
Experiment: Use live-cell imaging with palmitoylation/prenylation mutants to separate plasma membrane, Golgi, and recycling-endosome pools and their contribution to effector activation.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)