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... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with PRA1/RABAC1 (Q9Z0S9, rat), a receptor for prenylated small GTPases. Reason: Bare protein binding is uninformative. PRA1 binds the prenylated C terminus of many small GTPases; no specific HRAS molecular function beyond binding is supported. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. Supporting Evidence: PMID:11335720 Prenylated Rab acceptor protein is a receptor for prenylated small GTPases |
| GO:0005515 protein binding | IPI PMID:11857081 The putative tumor suppressor RASSF1A homodimerizes and hete... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with the Ras-GTP-binding RASSF effectors NORE1/RASSF5 and RASSF1A. Reason: Bare protein binding is uninformative. RASSF proteins are non-catalytic Ras-association- domain effectors, and no GO term specific to binding them (from the GTPase side) conveys more than the process annotations already present. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 and ARAF in an exhaustive yeast two-hybrid analysis. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:12620389 Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:12628188 Structural evidence for feedback activation by Ras.GTP of th... | MODIFY | Summary: IPI (crystallographic and solution) evidence that Ras-GTP binds a distal allosteric site on the GEF SOS1 and increases SOS-catalysed nucleotide release. Reason: Bare protein binding is uninformative. The paper shows that HRAS-GTP acts as an allosteric activator of its own GEF (positive feedback), which is better represented by molecular function activator activity (non-covalent activation of a target's activity). Proposed replacements: molecular function activator activity Supporting Evidence: PMID:12628188 Ras.GTP forms ternary complexes with SOS(cat) in solution and increases significantly the rate of SOS(cat)-stimulated nucleotide release from Ras |
| GO:0005515 protein binding | IPI PMID:14724641 Ras regulates assembly of mitogenic signalling complexes thr... | MODIFY | Summary: IPI evidence that HRAS binds the Ras effector IMP/BRAP (Q7Z569), a Ras-responsive E3 ubiquitin ligase. Reason: Bare protein binding is uninformative. IMP/BRAP is a RING E3 ubiquitin ligase whose auto- polyubiquitination is triggered by activated Ras, so the interaction is better captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:14724641 IMP is a Ras-responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination |
| GO:0005515 protein binding | IPI PMID:15507210 Structural analysis of autoinhibition in the Ras activator S... | MODIFY | Summary: IPI (structural/biochemical) evidence that Ras binds the allosteric site of SOS1 and converts SOS from low to high activity forms. Reason: Bare protein binding is uninformative. The paper describes Ras-GTP as an allosteric activator of SOS1, better captured by molecular function activator activity. Proposed replacements: molecular function activator activity Supporting Evidence: PMID:15507210 The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged |
| GO:0005515 protein binding | IPI PMID:15886098 RIN1 is an ABL tyrosine kinase activator and a regulator of ... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RIN1 (Q13671), a Ras effector that activates ABL kinases and acts as a RAB5 GEF. Reason: Bare protein binding is uninformative. RIN1 is a non-catalytic (with respect to Ras) effector; HRAS itself has no more specific molecular function in this interaction than GTP-dependent effector engagement, already covered by Ras signaling annotations. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:16316996 The RAP1 guanine nucleotide exchange factor Epac2 couples cy... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with Epac2/RAPGEF4 (Q9EQZ6, mouse). Reason: Bare protein binding is uninformative. Epac2 is a RAP1 GEF recruited to the plasma membrane by Ras; no more specific HRAS molecular function is established by this interaction. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:16698549 GTP-Ras disrupts the intramolecular complex of C1 and RA dom... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with NORE1/RASSF5 (Q5EBH1). Reason: Bare protein binding is uninformative. NORE1 is a non-catalytic Ras-association-domain effector; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:16810318 Release of RASSF1C from the nucleus by Daxx degradation link... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RASSF1C (Q9NS23-4). Reason: Bare protein binding is uninformative. RASSF1C is a non-catalytic Ras-association-domain protein; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:17084389 Catalytic competence of the Ras-GEF domain of hSos1 requires... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with SOS1 (Q07889). Reason: Bare protein binding is uninformative. In this study Ras is the substrate of the SOS1 catalytic (Ras-GEF) module; the relationship is captured by SOS1 guanyl-nucleotide exchange factor activity, not by an HRAS molecular function. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:17540175 Binding of ras to phosphoinositide 3-kinase p110alpha is req... | MODIFY | Summary: IPI evidence that Ras binds the PI3K catalytic subunit p110alpha (PIK3CA, P42337) via its Ras-binding domain. Reason: Bare protein binding is uninformative. Ras engagement of the p110alpha Ras-binding domain is a defined effector interaction with a lipid kinase, better captured by phosphatidylinositol 3-kinase binding. Proposed replacements: phosphatidylinositol 3-kinase binding Supporting Evidence: PMID:17540175 Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice |
| GO:0005515 protein binding | IPI PMID:18073111 Transformation efficiency of RasQ61 mutants linked to struct... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049); the study relates RasQ61 mutant switch-region structure to transformation in the presence of Raf. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:18073111 Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:18273062 A novel switch region regulates H-ras membrane orientation a... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of H-ras membrane orientation and signal output. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:18454158 Membrane-dependent signal integration by the Ras activator S... | MODIFY | Summary: IPI evidence that membrane-tethered Ras binds both the catalytic and the distal allosteric site of SOS1 (and RASGRF1 is listed as a partner). Reason: Bare protein binding is uninformative. Ras binding at the SOS allosteric site anchors and activates SOS(cat), which is better captured by molecular function activator activity. Proposed replacements: molecular function activator activity Supporting Evidence: PMID:18454158 SOS has two binding sites for Ras, one of which is an allosteric site that is distal to the active site |
| GO:0005515 protein binding | IPI PMID:18596699 Novel type of Ras effector interaction established between t... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RASSF5/NORE1 (Q5EBH1, Q8WWW0). Reason: Bare protein binding is uninformative. NORE1 is a non-catalytic Ras-association-domain effector; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:19063885 Regulation of growth and survival of activated T cells by ce... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of cell- transducing Ras inhibitors. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:19141281 Differences in flexibility underlie functional differences i... | MODIFY | Summary: IPI evidence for Ras binding to SOS1 (and RASGRF1), in a study of the allosteric activation of Sos by Ras. Reason: Bare protein binding is uninformative. Sos is inactive without Ras bound at its distal allosteric site, so the Ras side of this interaction is an activator function, better captured by molecular function activator activity. Proposed replacements: molecular function activator activity Supporting Evidence: PMID:19141281 The Ras-specific nucleotide exchange factor Son of sevenless (Sos) is inactive without Ras bound to a distal allosteric site |
| GO:0005515 protein binding | IPI PMID:19222999 Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathwa... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 and RALA (P04049, P11233) in a biochemical study of the Rheb/FKBP38 interaction. The cached abstract does not describe the HRAS assays (likely Ras-RAF control interactions); the curator-recorded HRAS-RAF1 binding is well established.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:19696784 Nucleocytoplasmic transport of Alp7/TACC organizes spatiotem... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049). The cached abstract (fission yeast Alp7/TACC) does not describe the HRAS assay, which may have been a control interaction; the curator-recorded HRAS-RAF1 binding is well established and is deferred to.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:20080631 Ras membrane orientation and nanodomain localization generat... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049); the Ras binding domain of C-Raf recognizes H-ras membrane orientation. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20080631 The orientation of the G domain of H-ras with respect to the plane of the plasma membrane is recognized by the Ras binding domain of C-Raf PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:20133692 Role of the histone domain in the autoinhibition and activat... | MODIFY | Summary: IPI evidence for Ras binding SOS1 in a structural/kinetic study of SOS autoinhibition by its histone and DH-PH domains. Reason: Bare protein binding is uninformative. SOS is inactive unless Ras is bound at its allosteric site, so the Ras side of this interaction is better captured by molecular function activator activity. Proposed replacements: molecular function activator activity Supporting Evidence: PMID:20133692 SOS is inactive unless Ras is bound to an allosteric site on SOS |
| GO:0005515 protein binding | IPI PMID:20133694 Allosteric gating of Son of sevenless activity by the histon... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of Sos histone-domain gating of Ras activation (Ras-GTP likely assayed by RAF RBD binding). Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:20178605 Genetic and functional characterization of putative Ras/Raf ... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of putative Ras/Raf interaction inhibitors. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20178605 Genetic and functional characterization of putative Ras/Raf interaction inhibitors PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: IPI evidence for physical interaction of HRAS with the Ral GEFs RGL2, RALGDS and RGL1 (O15211, Q12967, Q9NZL6). Reason: Bare protein binding is uninformative. RalGEFs are non-catalytic (with respect to Ras) RA- domain effectors; no more specific HRAS molecular function term applies. The interaction was detected in a large-scale interactome screen. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:22020336 p37Ξ΄ is a new isoform of PI3K p110Ξ΄ that increases cell prol... | MODIFY | Summary: IPI evidence that HRAS binds PIK3CD p110delta and its truncated isoform p37delta (O00329, O00329-2), which retains part of the RAS-binding domain. Reason: Bare protein binding is uninformative. Ras binding to the Ras-binding domain of a PI3K catalytic subunit is better captured by phosphatidylinositol 3-kinase binding. Proposed replacements: phosphatidylinositol 3-kinase binding Supporting Evidence: PMID:22020336 Despite the truncated RAS-binding domain, p37Ξ΄ bound to RAS |
| GO:0005515 protein binding | IPI PMID:22169110 Nilotinib and MEK inhibitors induce synthetic lethality thro... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of paradoxical RAF activation in CML. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with SMAD4 and FBXW7 (Q13485, Q969H0). Reason: Bare protein binding is uninformative. These partners were detected in a large-scale driver/susceptibility interaction map; no specific HRAS molecular function is established. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:24441586 Integrated RAS signaling defined by parallel NMR detection o... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with ARAF, BRAF, RALGDS, RIN1 and RGL1 effector Ras-binding domains, detected by parallel NMR. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24441586 specifically altering interactions with RAL GTPase-specific GEFs and RAF kinases PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049) in a study of Raf-1/MST2 interaction switches. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24929361 Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RALGDS (Q12967). Reason: Bare protein binding is uninformative. RALGDS is a non-catalytic (with respect to Ras) RA- domain effector; no more specific HRAS molecular function term applies. The interaction was detected in a large-scale interactome screen. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:25684575 Allosteric effects of the oncogenic RasQ61L mutant on Raf-RB... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049); the study analyses allosteric effects of RasQ61L on the Raf-RBD. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25684575 The CR1 contains two Ras binding domains: the Ras Binding Domain, Raf-RBD (residues 51-131), which binds Ras with an affinity of 18 nM PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:26165597 The RAS-Binding Domain of Human BRAF Protein Serine/Threonin... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with BRAF (P15056); crystal structures of the BRAF RBD bound to HRAS. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:26165597 The RAS-Binding Domain of Human BRAF Protein Serine/Threonine Kinase Exhibits Allosteric Conformational Changes upon Binding HRAS PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:26635368 Interaction between a Domain of the Negative Regulator of th... | MODIFY | Summary: IPI evidence for HRAS binding neurofibromin (NF1, P21359), the Ras GTPase-activating protein, in a study of the SPRED1-NF1 GAP-related domain interaction. Reason: Bare protein binding is uninformative. NF1 is a Ras GAP whose GAP-related domain acts on HRAS; the interaction is better captured as GTPase activating protein binding. Proposed replacements: GTPase activating protein binding Supporting Evidence: PMID:26635368 GTPase-activating Protein-related Domain of Neurofibromin |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with BRAF and RIN1 (P15056, Q13671). The interaction was detected in a large-scale interactome screen.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident... | MODIFY | Summary: IPI (proximity-labeling interactome) evidence for HRAS association with RAF1, BRAF, NF1, RALA and other proteins. Reason: Bare protein binding is uninformative. The partners include the RAF effector kinases, captured by protein kinase binding, and the Ras GAP NF1, captured by GTPase activating protein binding; other hits lack functional characterization. Proposed replacements: protein kinase binding GTPase activating protein binding Supporting Evidence: PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:30518913 UBIAD1 suppresses the proliferation of bladder carcinoma cel... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with UBIAD1 (Q9Y5Z9), which binds the H-Ras C-terminal domain and regulates its trafficking. Reason: Bare protein binding is uninformative. UBIAD1 is a prenyltransferase, but the interaction is not with its catalytic function; no specific HRAS molecular function is established. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:31209342 GGTase3 is a newly identified geranylgeranyltransferase targ... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with the farnesyltransferase/GGTase alpha subunit FNTA (P49354). Reason: Bare protein binding is uninformative. HRAS is a substrate of protein farnesyltransferase; this enzyme-substrate relationship belongs on the enzyme (has input) rather than as an HRAS molecular function. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with numerous proteins in a neurodegenerative-disease yeast two-hybrid interactome map. Reason: Bare protein binding is uninformative. The hits lack functional characterization. The interaction was detected in a large-scale interactome screen. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with BRAF, RAP1GDS1, RIN1 and RGL1 (BioPlex). The interaction was detected in a large-scale interactome screen.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RGL2, RAF1, ARAF and RIN1. The interaction was detected in a large-scale interactome screen.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RGL2, RAF1, ARAF, BRAF and RIN1. The interaction was detected in a large-scale interactome screen.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with BRAF, SMAD4 and FBXW7. The interaction was detected in a large-scale interactome screen.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:35839996 A Proteomic Approach Identifies Isoform-Specific and Nucleot... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1, ARAF, BRAF, FNTA, RAP1GDS1, RADIL and others in a nucleotide-dependent RAS interactome study. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:35839996 The RADILβRAS interactions were nearly identical to the known RAS effector RAF1 with one interesting difference PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RAP1GDS1 and RIN1 (P52306, Q13671). Reason: Bare protein binding is uninformative. These partners lack a more specific HRAS molecular function term. The interaction was detected in a large-scale interactome screen. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-termi... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049); normal and oncogenic p21ras bind the amino-terminal regulatory domain of c-Raf-1. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:8670882 Identification of a novel Rac1-interacting protein involved ... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 (P04049). The cached abstract (POR1/Rac1) does not describe the HRAS assay, likely a Ras-Raf control interaction; the curator-recorded HRAS-RAF1 binding is well established and is deferred to.. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 PMID:30194290 Among these were the well-described RAS effectors ARAF, BRAF, and RAF1 (CRAF), which directly bind to activated RAS through a Ras-binding domain |
| GO:0005515 protein binding | IPI PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u... | MODIFY | Summary: IPI evidence for physical interaction of HRAS with RAF1 and RIN1 (P04049, Q13671) in a study of RIN1 effector function. Reason: Bare protein binding is uninformative. The interaction partners include RAF-family serine/threonine kinases, which GTP-bound RAS engages through their Ras-binding domain as the canonical MAPK-pathway effector interaction, so the evidence is better captured by protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:9144171 Human RIN1 was first characterized as a RAS binding protein PMID:8332187 Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1 |
| GO:0005515 protein binding | IPI PMID:9447984 Regulation of Sos activity by intramolecular interactions. | REMOVE | Summary: IPI evidence for physical interaction of HRAS with SOS1 (Q07889). Reason: Bare protein binding is uninformative. Here Ras binding is assayed as the substrate of the hSos1 catalytic domain; the relationship is captured by SOS1 guanyl-nucleotide exchange factor activity, not by an HRAS molecular function. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:9488663 Identification of Nore1 as a potential Ras effector. | REMOVE | Summary: IPI evidence for physical interaction of HRAS with NORE1/RASSF5 (Q8WWW0). Reason: Bare protein binding is uninformative. NORE1 is a non-catalytic Ras-association-domain effector; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:9690470 The structural basis of the activation of Ras by Sos. | REMOVE | Summary: IPI evidence for physical interaction of HRAS with SOS1 (Q07889); crystal structure of H-Ras bound to the Sos exchange region. Reason: Bare protein binding is uninformative. In this complex Ras is the substrate whose nucleotide is released by Sos; the relationship is captured by SOS1 guanyl-nucleotide exchange factor activity, not by an HRAS molecular function. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI P01112-2 PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RAP1GDS1 isoform (P52306-5), tested with HRAS isoform p19 (P01112-2) in the HuRI binary interactome. Reason: Bare protein binding is uninformative. No specific molecular function is established. The interaction was detected in a large-scale interactome screen. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| 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 | KEEP AS NON CORE | Summary: Protein-membrane adaptor activity (IEA), transferred from rat Hras; membrane-anchored Ras-GTP recruits effectors such as Raf to the plasma membrane. Reason: The term describes bringing a protein to a membrane, which is what membrane-anchored, GTP-bound Ras does when it recruits effectors: UniProt records, from published experiments, that activated HRAS interacts with phospholipase C epsilon (PLCE1) and recruits it to the plasma membrane, and Raf kinases are recruited in the same way. The term does not refer to the lipid modifications that anchor HRAS itself, which is how the row had been read. The row is transferred from rat Hras, annotated by direct assay from a paper on merlin and the growth hormone-regulated Raf-ERK pathway (PMID:16405865); its abstract does not mention Ras and the full text is not available here, so that assay was not checked and the row does not rest on it. Effector recruitment follows from GTP-dependent effector binding by membrane-bound Ras and is secondary to the GTPase switch that this review treats as core, so the row is kept as non-core. 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. file:human/HRAS/HRAS-uniprot.txt constitutively activated; interacts and recruits PLCE1 to |
| 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-... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with CNrasGEF/RAPGEF2 (Q9Y4G8). Reason: Bare protein binding is uninformative. RAPGEF2 is an RA-domain-containing GEF for Rap1; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| GO:0005515 protein binding | IPI PMID:10608844 RA-GEF, a novel Rap1A guanine nucleotide exchange factor con... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RA-GEF/RAPGEF2 (Q9Y4G8). Reason: Bare protein binding is uninformative. RAPGEF2 is an RA-domain-containing GEF for Rap1; no more specific HRAS molecular function term applies. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| 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... | MODIFY | Summary: IPI evidence (two-hybrid and co-immunoprecipitation) that Ras binds the transcription factor Aiolos (IKZF3, Q9UKT9), with IL-2-induced Aiolos phosphorylation required for dissociation from Ras. Reason: Bare protein binding is uninformative. The partner is a DNA-binding transcription factor whose localization is controlled by Ras association, so DNA-binding transcription factor binding is the more informative term. This is a peripheral, non-core interaction. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:10369681 The Ras-Aiolos interaction was confirmed in vitro and in vivo by co-immunoprecipitation |
| 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... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with RACK1 (P63244), reported for the p19/H-RasIDX splice isoform. Reason: Bare protein binding is uninformative. RACK1 is a scaffold protein; no specific HRAS molecular function is established by this interaction. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| 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... | REMOVE | Summary: IPI evidence for physical interaction of HRAS with PDE6D (O43924), the prenyl-binding delta subunit. Reason: Bare protein binding is uninformative. PDEdelta is a prenyl-binding solubilizing factor; the relationship is a lipid-anchor chaperone interaction without a more specific HRAS molecular function. Removal does not mean the interaction is false; it reflects the lack of functional information carried by bare GO:0005515, and the interaction remains recorded in the interaction databases and UniProt. |
| 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... | MODIFY | Summary: IPI evidence that GTP-bound Ha-Ras binds the Ras-associating domain of phospholipase C epsilon (PLCE1, Q9P212) and stimulates its PIP2-hydrolysing activity. Reason: Bare protein binding is uninformative. PLCepsilon is an enzyme effector of Ras, so the interaction is better captured as enzyme binding. Proposed replacements: enzyme binding Supporting Evidence: PMID:11022048 The Ras-associating domain of PLCepsilon specifically binds to the GTP-bound forms of Ha- Ras and Rap1A |
| GO:0005515 protein binding | IPI PMID:2122974 Modulation of guanine nucleotides bound to Ras in NIH3T3 cel... | MODIFY | Summary: IPI evidence relating Ras to the GTPase activating protein p120GAP (RASA1, P20936), whose overexpression reduces Ras-GTP levels in cells. Reason: Bare protein binding is uninformative. RASA1 is a Ras GAP, so the interaction is better captured as GTPase activating protein binding. Proposed replacements: GTPase activating protein binding Supporting Evidence: PMID:2122974 Ras biochemical activity involves regulation of a GTP/GDP cycle and the GTPase activating protein (GAP) |
| GO:0005515 protein binding | IPI PMID:9219684 The Ras-RasGAP complex: structural basis for GTPase activati... | MODIFY | Summary: IPI (crystal structure) evidence that GDP-bound H-Ras forms a complex with the GTPase- activating domain of p120GAP (RASA1). Reason: Bare protein binding is uninformative. The structure shows HRAS engaging its GAP, better captured as GTPase activating protein binding. Proposed replacements: GTPase activating protein binding Supporting Evidence: PMID:9219684 The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras |
| 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. |
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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.
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