KRAS encodes a membrane-associated Ras-family small GTPase that functions as a GDP/GTP molecular switch in receptor-driven signal transduction. In the GTP-bound state KRAS recruits effectors including RAF-family kinases and PI3Kalpha to activate downstream MAPK and PI3K-AKT-mTOR signaling; intrinsic and GAP-stimulated GTP hydrolysis return KRAS to the GDP-bound inactive state. KRAS4A and KRAS4B differ in their C-terminal hypervariable regions and membrane-targeting mechanisms, but both depend on lipid modification and membrane localization for signaling. Oncogenic and rasopathy variants alter nucleotide cycling, GAP responsiveness, effector interactions, or localization, producing context-dependent effects on proliferation, survival, senescence, and gene expression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005886
plasma membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
Both isoforms are farnesylated at the CAAX cysteine and further processed (RCE1 cleavage and ICMT methylation) in the ER, enabling membrane association. KRAS4B lacks palmitoylatable cysteines and instead uses a lysine-rich polybasic HVR (reported net charge +8) to electrostatically stabilize plasma membrane association with anionic lipids.
|
|
GO:0007265
Ras protein signal transduction
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA annotation for Ras protein signal transduction. KRAS participates directly in Ras signaling through SOS-mediated activation and effector engagement.
Reason: This process annotation is appropriate for KRAS, whose active GTP-bound form transmits receptor inputs to downstream pathways including RAF-MEK-ERK and PI3K-AKT-mTOR.
Supporting Evidence:
PMID:38188543
SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of KRAS
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
file:human/KRAS/KRAS-deep-research-falcon.md
Primary structural evidence for Ras activation by SOS comes from the crystal structure of Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a nucleotide-free state, a mechanistic basis for GEF-driven exchange.
|
|
GO:0008284
positive regulation of cell population proliferation
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: KRAS signaling can promote cell proliferation through MAPK and PI3K effector pathways, but proliferation is a downstream cellular outcome rather than the molecular core function.
Reason: The annotation is biologically plausible and supported by pathway literature, but it should not be treated as the core activity of KRAS.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
PMID:39788953
Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway
|
|
GO:0003924
GTPase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
Reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Reactome:R-HSA-9649736
RAS proteins have weak intrinsic GTPase activity in the absence of other effectors
file:human/KRAS/KRAS-deep-research-falcon.md
**KRAS is a Ras-family small GTPase** that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in **switch I/II** regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state.
|
|
GO:0000165
MAPK cascade
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: KRAS participates in the RAF/MAP kinase cascade by recruiting and activating RAF-family kinases when GTP-bound.
Reason: Reactome and structural work support active KRAS as an upstream activator of the RAF-MEK-ERK MAPK cascade.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
|
|
GO:0003924
GTPase activity
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
Reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Reactome:R-HSA-9649736
RAS proteins have weak intrinsic GTPase activity in the absence of other effectors
file:human/KRAS/KRAS-deep-research-falcon.md
**KRAS is a Ras-family small GTPase** that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in **switch I/II** regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state.
|
|
GO:0003925
G protein activity
|
IEA
GO_REF:0000003 |
MODIFY |
Summary: KRAS functions as a small monomeric G protein that switches between GDP-bound inactive and GTP-bound active states.
Reason: The integrated falcon DR guidance explicitly recommends the more specific GTPase activity term (GO:0003924) over the generic G protein activity term for KRAS. GO:0003924 is already separately annotated for KRAS with IBA, IEA, EXP, TAS, and IMP evidence (all ACCEPT), so MODIFY replaces this generic IEA term with the established specific term.
Proposed replacements:
GTPase activity
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Alternates between an inactive form bound to GDP and an active form bound to GTP
file:human/KRAS/KRAS-deep-research-falcon.md
Use "GTPase activity," not broad "G protein activity"; mutant-impaired hydrolysis should not redefine WT function. Prefer specific MF terms (GTP binding, GDP binding, GTPase activity) over generic "G protein activity/protein binding."
|
|
GO:0005525
GTP binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: KRAS binds GTP as the active nucleotide state of the Ras molecular switch.
Reason: GTP binding is essential to KRAS activation and downstream effector recruitment.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Alternates between an inactive form bound to GDP and an active form bound to GTP
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS is a Ras-family small GTPase that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in switch I/II regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state. A primary structural and functional demonstration of Ras effector engagement is the Ras–PI3Kγ complex: PI3Kγ is directly activated by GTP-loaded Ras, and the structure shows Ras uses switch I/II to bind the PI3Kγ Ras-binding domain.
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: IEA annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0007165
signal transduction
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: The generic signal transduction annotation reflects KRAS signaling but is less informative than Ras-specific signaling terms.
Reason: KRAS should be annotated to Ras protein signal transduction rather than broad signal transduction when the domain and pathway evidence are Ras-specific.
Proposed replacements:
Ras protein signal transduction
Supporting Evidence:
PMID:38188543
SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of KRAS
|
|
GO:0012505
endomembrane system
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: KRAS, especially K-Ras4a under SIRT2-regulated lysine defatty-acylation, can localize to endomembrane compartments.
Reason: Endomembrane localization is supported by K-Ras4a acylation experiments and by UniProt subcellular-location curation.
Supporting Evidence:
PMID:29239724
SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular delivery to the plasma membrane.
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000002 |
MARK AS OVER ANNOTATED |
Summary: The generic membrane annotation is directionally correct for lipid-anchored KRAS but lacks the useful subcellular specificity available from curated evidence.
Reason: KRAS has more specific and better-supported plasma membrane, cytoplasmic-side-of-plasma-membrane, endomembrane, and cytosolic localization annotations. Generic membrane should not be used as an informative KRAS localization.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
|
|
GO:0005515
protein binding
|
IPI
PMID:12732644 RASSF2 is a novel K-Ras-specific effector and potential tumo... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005515
protein binding
|
IPI
PMID:25416956 A proteome-scale map of the human interactome network. |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005515
protein binding
|
IPI
PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005515
protein binding
|
IPI
PMID:30194290 Interrogating the protein interactomes of RAS isoforms ident... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005515
protein binding
|
IPI
PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0001889
liver development
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The liver development annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0007249
canonical NF-kappaB signal transduction
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The canonical NF-kappaB signal transduction annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0007565
female pregnancy
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The female pregnancy annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0009629
response to gravity
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The response to gravity annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0019002
GMP binding
|
IEA
GO_REF:0000107 |
MODIFY |
Summary: This orthology-transferred GMP binding annotation does not match the established KRAS nucleotide cycle, which is GDP/GTP based.
Reason: KRAS is characterized as a GDP/GTP-binding small GTPase. GMP binding is not the physiologically informative ligand state for KRAS and should be replaced by the specific GDP and GTP binding terms.
Proposed replacements:
GTP binding
GDP binding
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
|
|
GO:0019003
GDP binding
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: KRAS binds GDP as the inactive nucleotide state of the Ras molecular switch.
Reason: GDP binding is a normal part of the KRAS regulatory cycle and is supported by the UniProt activity-regulation statement.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Alternates between an inactive form bound to GDP and an active form bound to GTP
|
|
GO:0019221
cytokine-mediated signaling pathway
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The cytokine-mediated signaling pathway annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0030275
LRR domain binding
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: KRAS can interact with LRR-containing SHOC2 in the SHOC2-PP1C-RAS regulatory system, but LRR domain binding is not the core KRAS molecular function.
Reason: The orthology-transferred MF term overemphasizes one regulator interaction. The functional consequence is better represented by Ras/MAPK signaling annotations.
Supporting Evidence:
PMID:36175670
The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind SHOC2
|
|
GO:0035900
response to isolation stress
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The response to isolation stress annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0051384
response to glucocorticoid
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The response to glucocorticoid annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0051385
response to mineralocorticoid
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The response to mineralocorticoid annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0051450
myoblast proliferation
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The myoblast proliferation annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:0060038
cardiac muscle cell proliferation
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The cardiac muscle cell proliferation annotation is an orthology-transferred high-level biological-process term and is not directly supported as a specific human KRAS function in the reviewed evidence.
Reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation. They overstate the direct functional role of KRAS.
|
|
GO:2000774
positive regulation of cellular senescence
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: RAS pathway activation can be associated with cellular senescence in oncogene-stress contexts, but this is a context-dependent downstream outcome.
Reason: The term should not be considered core for KRAS; it reflects a cellular response to signaling intensity and context rather than the conserved molecular role.
|
|
GO:0005515
protein binding
|
IPI
PMID:23524970 Desmoglein-1/Erbin interaction suppresses ERK activation to ... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005737
cytoplasm
|
IDA
PMID:23524970 Desmoglein-1/Erbin interaction suppresses ERK activation to ... |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:23524970 Desmoglein-1/Erbin interaction suppresses ERK activation to ... |
ACCEPT |
Summary: IDA annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0007265
Ras protein signal transduction
|
IDA
PMID:38188543 Studying early structural changes in SOS1 mediated KRAS acti... |
ACCEPT |
Summary: IDA annotation for Ras protein signal transduction. KRAS participates directly in Ras signaling through SOS-mediated activation and effector engagement.
Reason: This process annotation is appropriate for KRAS, whose active GTP-bound form transmits receptor inputs to downstream pathways including RAF-MEK-ERK and PI3K-AKT-mTOR.
Supporting Evidence:
PMID:38188543
SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of KRAS
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
file:human/KRAS/KRAS-deep-research-falcon.md
Primary structural evidence for Ras activation by SOS comes from the crystal structure of Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a nucleotide-free state, a mechanistic basis for GEF-driven exchange.
|
|
GO:0032008
positive regulation of TOR signaling
|
NAS
PMID:39788953 Structural insights into isoform-specific RAS-PI3Kα interact... |
KEEP AS NON CORE |
Summary: RAS-PI3Kalpha interaction can amplify PI3K-AKT-mTOR signaling, placing KRAS upstream of TOR pathway activation in some contexts.
Reason: This is a supported effector branch but not the primary core function; KRAS is best represented first as a membrane-associated small GTPase in Ras/MAPK signaling.
Supporting Evidence:
PMID:39788953
Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway
|
|
GO:0042127
regulation of cell population proliferation
|
NAS
PMID:38188543 Studying early structural changes in SOS1 mediated KRAS acti... |
KEEP AS NON CORE |
Summary: KRAS signaling can promote cell proliferation through MAPK and PI3K effector pathways, but proliferation is a downstream cellular outcome rather than the molecular core function.
Reason: The annotation is biologically plausible and supported by pathway literature, but it should not be treated as the core activity of KRAS.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
PMID:39788953
Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway
|
|
GO:0043069
negative regulation of programmed cell death
|
NAS
PMID:39788953 Structural insights into isoform-specific RAS-PI3Kα interact... |
MARK AS OVER ANNOTATED |
Summary: Negative regulation of programmed cell death can occur downstream of RAS effector pathways, especially through PI3K-AKT survival signaling, but the annotation is broad.
Reason: The cited PI3Kalpha structural work supports RAS-PI3K pathway activation, not a direct KRAS role in the general programmed cell death process.
Supporting Evidence:
PMID:39788953
Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway
|
|
GO:0043410
positive regulation of MAPK cascade
|
NAS
PMID:33608534 KRAS interaction with RAF1 RAS-binding domain and cysteine-r... |
ACCEPT |
Summary: KRAS positively regulates the MAPK cascade through direct active-RAS interaction with RAF-family kinases.
Reason: This is an accurate pathway-level annotation for the canonical KRAS effector branch.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
|
|
GO:1902554
serine/threonine protein kinase complex
|
IPI
PMID:33608534 KRAS interaction with RAF1 RAS-binding domain and cysteine-r... |
MARK AS OVER ANNOTATED |
Summary: The cited RAF1 structural work supports KRAS binding to RAF regulatory domains during RAF activation, not stable membership in a serine/threonine protein kinase complex.
Reason: KRAS is an upstream small GTPase effector-binding partner for RAF; representing it as part of a kinase complex overstates a transient signaling interaction.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
|
|
GO:1905360
GTPase complex
|
IPI
PMID:39043660 Allosteric nanobodies to study the interactions between SOS1... |
MARK AS OVER ANNOTATED |
Summary: The GTPase complex annotation is based on a structural interaction context rather than evidence that KRAS is a stable component of a native cellular complex.
Reason: KRAS forms transient complexes with GEFs, GAPs, effectors, inhibitors, and structural binders. A generic GTPase complex cellular-component term is not informative as a gene-level KRAS annotation.
|
|
GO:0000164
protein phosphatase type 1 complex
|
IPI
PMID:36175670 Structure of the SHOC2-MRAS-PP1C complex provides insights i... |
MARK AS OVER ANNOTATED |
Summary: SHOC2-MRAS-PP1C studies show that canonical RAS proteins, including KRAS, can bind this regulatory phosphatase system with lower affinity than MRAS.
Reason: The core complex is SHOC2-MRAS-PP1C. Assigning KRAS as part of a protein phosphatase type 1 complex overstates a non-core, weaker regulatory interaction.
Supporting Evidence:
PMID:36175670
The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind SHOC2
|
|
GO:0046579
positive regulation of Ras protein signal transduction
|
NAS
PMID:35831509 Structure-function analysis of the SHOC2-MRAS-PP1C holophosp... |
MODIFY |
Summary: This annotation captures KRAS-dependent positive signaling but frames the role as regulation of Ras signaling rather than direct participation in the Ras/MAPK pathway.
Reason: The evidence is better represented by KRAS involvement in Ras protein signal transduction and positive regulation of the MAPK cascade.
Proposed replacements:
Ras protein signal transduction
positive regulation of MAPK cascade
Supporting Evidence:
PMID:36175670
The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind SHOC2
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
|
|
GO:0000165
MAPK cascade
|
TAS
Reactome:R-HSA-5673001 |
ACCEPT |
Summary: KRAS participates in the RAF/MAP kinase cascade by recruiting and activating RAF-family kinases when GTP-bound.
Reason: Reactome and structural work support active KRAS as an upstream activator of the RAF-MEK-ERK MAPK cascade.
Supporting Evidence:
Reactome:R-HSA-5673001
GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation
PMID:33608534
Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
|
|
GO:0005829
cytosol
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0003924
GTPase activity
|
EXP
PMID:20949621 Germline KRAS mutations cause aberrant biochemical and physi... |
ACCEPT |
Summary: EXP annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
Reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Reactome:R-HSA-9649736
RAS proteins have weak intrinsic GTPase activity in the absence of other effectors
file:human/KRAS/KRAS-deep-research-falcon.md
A widely cited expert synthesis reports Ras intrinsic hydrolysis is slow (kcat ≈ 2×10−4 s−1), but it is a real enzymatic activity central to the molecular switch. GAPs accelerate Ras hydrolysis (reported up to ~10^5-fold in expert synthesis) and do so by complementing the active site, including an external arginine ("arginine finger") concept.
|
|
GO:0005886
plasma membrane
|
EXP
PMID:29239724 SIRT2 and lysine fatty acylation regulate the transforming a... |
ACCEPT |
Summary: EXP annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0012505
endomembrane system
|
EXP
PMID:29239724 SIRT2 and lysine fatty acylation regulate the transforming a... |
ACCEPT |
Summary: KRAS, especially K-Ras4a under SIRT2-regulated lysine defatty-acylation, can localize to endomembrane compartments.
Reason: Endomembrane localization is supported by K-Ras4a acylation experiments and by UniProt subcellular-location curation.
Supporting Evidence:
PMID:29239724
SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular delivery to the plasma membrane.
|
|
GO:0003924
GTPase activity
|
TAS
Reactome:R-HSA-9649736 |
ACCEPT |
Summary: TAS annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
Reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Reactome:R-HSA-9649736
RAS proteins have weak intrinsic GTPase activity in the absence of other effectors
file:human/KRAS/KRAS-deep-research-falcon.md
**KRAS is a Ras-family small GTPase** that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in **switch I/II** regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state.
|
|
GO:0009898
cytoplasmic side of plasma membrane
|
IDA
PMID:23698361 Small molecule inhibition of the KRAS-PDEδ interaction impai... |
ACCEPT |
Summary: KRAS localizes to the cytoplasmic side of the plasma membrane through C-terminal lipid modification and membrane-targeting motifs.
Reason: This is the most precise cellular-component annotation for signaling-competent membrane-associated KRAS.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0003924
GTPase activity
|
IMP
PMID:26037647 Biochemical and Structural Analysis of Common Cancer-Associa... |
ACCEPT |
Summary: IMP annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
Reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Reactome:R-HSA-9649736
RAS proteins have weak intrinsic GTPase activity in the absence of other effectors
file:human/KRAS/KRAS-deep-research-falcon.md
**KRAS is a Ras-family small GTPase** that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in **switch I/II** regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state.
|
|
GO:0005515
protein binding
|
IPI
PMID:24415755 The chaperone protein SmgGDS interacts with small GTPases en... |
REMOVE |
Summary: This protein binding annotation records a physical interaction, but GO:0005515 is too generic to describe KRAS function.
Reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization annotations rather than a generic protein binding MF term.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9674816 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9654521 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9654523 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9654525 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9654533 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005741
mitochondrial outer membrane
|
TAS
Reactome:R-HSA-9653592 |
KEEP AS NON CORE |
Summary: Reactome places phosphorylated KRAS4B at the mitochondrial outer membrane in a regulated trafficking/signaling context.
Reason: This is context-specific and isoform/modification-state dependent, so it should be kept as non-core rather than treated as a general KRAS localization.
|
|
GO:0005741
mitochondrial outer membrane
|
TAS
Reactome:R-HSA-9653595 |
KEEP AS NON CORE |
Summary: Reactome places phosphorylated KRAS4B at the mitochondrial outer membrane in a regulated trafficking/signaling context.
Reason: This is context-specific and isoform/modification-state dependent, so it should be kept as non-core rather than treated as a general KRAS localization.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9653503 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9653592 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9651280 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802834 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802908 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802918 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802922 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802924 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802925 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802926 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802937 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802941 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802942 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802943 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6803233 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6803234 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6803240 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8936731 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9647977 |
KEEP AS NON CORE |
Summary: ER membrane annotations reflect CAAX processing and maturation reactions for farnesylated RAS proteins in Reactome.
Reason: The ER membrane is relevant to RAS processing but is not the primary location of signaling-competent KRAS.
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9647978 |
KEEP AS NON CORE |
Summary: ER membrane annotations reflect CAAX processing and maturation reactions for farnesylated RAS proteins in Reactome.
Reason: The ER membrane is relevant to RAS processing but is not the primary location of signaling-competent KRAS.
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9647999 |
KEEP AS NON CORE |
Summary: ER membrane annotations reflect CAAX processing and maturation reactions for farnesylated RAS proteins in Reactome.
Reason: The ER membrane is relevant to RAS processing but is not the primary location of signaling-competent KRAS.
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9649732 |
KEEP AS NON CORE |
Summary: ER membrane annotations reflect CAAX processing and maturation reactions for farnesylated RAS proteins in Reactome.
Reason: The ER membrane is relevant to RAS processing but is not the primary location of signaling-competent KRAS.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9647978 |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9647980 |
KEEP AS NON CORE |
Summary: Golgi membrane localization is relevant to RAS membrane trafficking and palmitoylation cycles, especially for the K-Ras4A isoform.
Reason: This is a plausible trafficking/maturation localization but not the primary signaling location for KRAS.
Supporting Evidence:
Reactome:R-HSA-9647980
mature RAS proteins translocate to the plasma membrane
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular delivery to the plasma membrane.
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9647982 |
KEEP AS NON CORE |
Summary: Golgi membrane localization is relevant to RAS membrane trafficking and palmitoylation cycles, especially for the K-Ras4A isoform.
Reason: This is a plausible trafficking/maturation localization but not the primary signaling location for KRAS.
Supporting Evidence:
Reactome:R-HSA-9647980
mature RAS proteins translocate to the plasma membrane
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular delivery to the plasma membrane.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1168636 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1225951 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1225957 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1250383 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1306972 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-1433471 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-170986 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-177938 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-177945 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-186834 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-210977 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2179407 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-2424477 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-392054 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5218845 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5621573 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5624486 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5624492 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5624494 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5637806 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5637808 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654392 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654402 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654413 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654426 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654600 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654618 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654647 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5654663 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5655241 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5655277 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5655326 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5655347 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5658231 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5658435 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672950 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672965 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672966 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672969 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672972 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672973 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672978 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672980 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5674018 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5674022 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5675417 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5675431 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5675433 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802837 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8851827 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8851877 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8851899 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8941613 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8941618 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8941623 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8941628 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8981353 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8981355 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9607304 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9632906 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9632918 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9634418 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9647980 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9647994 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9649733 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9649735 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9649736 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9653108 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656209 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656211 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656212 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656213 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656214 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9656215 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9657599 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9657603 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9657606 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9657608 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9658253 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9664991 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9665009 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9665404 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9665408 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9665700 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9665707 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9670436 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9672163 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9672170 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9695853 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9703441 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9647982 |
KEEP AS NON CORE |
Summary: ER membrane annotations reflect CAAX processing and maturation reactions for farnesylated RAS proteins in Reactome.
Reason: The ER membrane is relevant to RAS processing but is not the primary location of signaling-competent KRAS.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9649732 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9653585 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9654521 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9654533 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0044877
protein-containing complex binding
|
IDA
PMID:23209302 KIF14 negatively regulates Rap1a-Radil signaling during brea... |
REMOVE |
Summary: The protein-containing complex binding annotation is broad and the cited paper is not KRAS-centered; it does not clarify KRAS molecular function.
Reason: This generic binding term is not useful for KRAS and appears to come from a broad complex-binding assertion rather than evidence for a specific KRAS activity.
|
|
GO:0005737
cytoplasm
|
IDA
PMID:23698361 Small molecule inhibition of the KRAS-PDEδ interaction impai... |
ACCEPT |
Summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including PDEdelta-mediated solubilization of farnesylated KRAS.
Reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is supported as part of its trafficking and recycling cycle.
Supporting Evidence:
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
file:human/KRAS/KRAS-deep-research-falcon.md
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
|
|
GO:0005925
focal adhesion
|
HDA
PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... |
MARK AS OVER ANNOTATED |
Summary: The focal adhesion annotation comes from high-throughput proteomic detection rather than targeted KRAS localization evidence.
Reason: Focal adhesion is not a supported core or well-established localization for KRAS in the reviewed evidence.
|
|
GO:0016020
membrane
|
HDA
PMID:19946888 Defining the membrane proteome of NK cells. |
MARK AS OVER ANNOTATED |
Summary: The generic membrane annotation is directionally correct for lipid-anchored KRAS but lacks the useful subcellular specificity available from curated evidence.
Reason: KRAS has more specific and better-supported plasma membrane, cytoplasmic-side-of-plasma-membrane, endomembrane, and cytosolic localization annotations. Generic membrane should not be used as an informative KRAS localization.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802914 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802915 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802916 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802919 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6802921 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6803230 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8936676 |
ACCEPT |
Summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions at the cytoplasmic face of the plasma membrane.
Reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work, K-Ras4a acylation work, and many Reactome RAS pathway events.
Supporting Evidence:
file:human/KRAS/KRAS-uniprot.txt
Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor
PMID:23698361
Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ
|
|
GO:0010628
positive regulation of gene expression
|
IMP
PMID:22065586 Oncogenic Ras and B-Raf proteins positively regulate death r... |
MARK AS OVER ANNOTATED |
Summary: Oncogenic Ras can increase expression of specific genes such as DR5 through ERK/JNK-dependent transcription factor activation.
Reason: The evidence concerns oncogenic Ras/B-Raf regulation of a specific death receptor transcriptional response. The broad gene expression term is a downstream, mutant/context-dependent outcome rather than a general KRAS function.
|
Q: Which KRAS4A and KRAS4B functions should be represented as isoform-specific GO annotations rather than gene-level annotations?
Q: Should SHOC2-PP1C complex annotations be restricted to MRAS, or should weak H/K/NRAS interactions support non-core annotations?
Q: Can KRAS mitochondrial outer membrane localization be curated as a modification- or isoform-specific function rather than a general localization?
Q: Should pathway-level proliferation, senescence, and programmed cell death annotations be retained for KRAS or replaced by more direct Ras/MAPK and PI3K pathway terms?
Experiment: Endogenous isoform-specific tagging or proteomics to quantify KRAS4A and KRAS4B localization across plasma membrane, Golgi, ER, endomembrane, cytosol, and mitochondria.
Hypothesis: Gene-level KRAS localization annotations conflate distinct KRAS4A and KRAS4B trafficking mechanisms.
Experiment: Compare endogenous KRAS, NRAS, HRAS, and MRAS binding to SHOC2-PP1C under matched nucleotide-loading and membrane conditions.
Hypothesis: Canonical RAS isoforms bind SHOC2-PP1C weakly relative to MRAS and should not receive core phosphatase-complex component annotations.
Experiment: Use pathway-resolved KRAS perturbation with rescue by GTPase, effector-binding, and localization mutants to separate direct MAPK/PI3K signaling from downstream proliferation and gene-expression outcomes.
Hypothesis: Most broad biological-process annotations for KRAS are downstream consequences of Ras effector signaling rather than direct gene-level functions.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Concise GO annotation research for human KRAS / UniProt P01116 (K-Ras isoforms KRAS4A and KRAS4B). Focus only on GO-relevant evidence: core molecular function as a Ras-family small GTPase with GDP/GTP binding and GTP hydrolysis; GEF/GAP-regulated nucleotide cycling; effector binding in the GTP-bound state; core biological processes Ras protein signal transduction, MAPK cascade/positive regulation of MAPK cascade, PI3K/AKT/mTOR signaling where directly supported; isoform-specific membrane targeting of KRAS4A and KRAS4B including farnesylation, palmitoylation/fatty acylation, polybasic region, PDEdelta-mediated trafficking, plasma membrane/endosomal/Golgi localization; distinguish wild-type KRAS core function from oncogenic mutant phenotypes, cancer, proliferation, senescence, apoptosis, transcription, development, and immune/metabolic downstream outcomes; evaluate generic protein binding, G protein activity vs GTPase activity, protein-membrane adaptor activity, and over-annotation risks from pathway membership or mutant studies. Include PMID/DOI citations and keep under 1500 words.
This report summarizes GO-relevant evidence for the wild-type (WT) KRAS molecular switch function (GDP/GTP cycling, effector engagement) and isoform-specific membrane targeting of KRAS4A versus KRAS4B. It explicitly avoids over-annotation from (i) pathway membership, (ii) overexpression systems, and (iii) oncogenic-mutant phenotypes unless the claim is a direct biochemical consequence of the mutation that is relevant to the core switch mechanism. Recent expert reviews emphasize that a “bona fide” RAS effector must bind directly and nucleotide-dependently and alter effector activity, and that domain presence (e.g., an RBD/RA motif) is insufficient without experimental validation. (smith2023definingbonefide pages 1-2, mozzarelli2024functionalandstructural pages 1-3)
KRAS is a Ras-family small GTPase that functions as a GDP/GTP-regulated switch. GTP binding induces conformational changes in switch I/II regions enabling effector recognition, while GTP hydrolysis returns KRAS to the GDP-bound state. (jesus2023targetingkrasin pages 2-4, ahearn2012regulatingtheregulator pages 2-4, pacold2000crystalstructureand pages 1-2)
GEF/GAP-regulated nucleotide cycling is central to KRAS function: GEFs (e.g., SOS) promote GDP release and GTP loading; GAPs accelerate hydrolysis, in part via an “arginine finger” mechanism. (nair2023regulationofrasgtpase pages 1-2, boriacksjodin1998thestructuralbasis pages 1-2, hall2001structurebasedmutagenesisreveals pages 1-2, scheffzek1998gtpaseactivatingproteinshelping pages 1-2)
Effector definition and over-annotation risk (2023–2024): Reviews stress that many proteins labeled “effectors” lack mechanistic proof (nucleotide dependence + functional consequence), and that kinetics/competition among effectors and local concentrations shape outputs—critical for avoiding BP over-annotation from correlation. (smith2023definingbonefide pages 1-2, mozzarelli2024functionalandstructural pages 1-3)
Mutant-specific biochemical bias (2023–2024): Recent analyses summarize that different KRAS hotspot variants can differ in intrinsic hydrolysis and RAF affinity, producing variant-dependent pathway bias; therefore “KRAS activates X pathway” statements require direct evidence in the relevant context and should not be inferred from a single mutant or tumor dataset. (mondal2024krasmutationsubtypes pages 10-12, jani2024insightintostructural pages 16-17)
A widely cited expert synthesis reports Ras intrinsic hydrolysis is slow (kcat ≈ 2×10−4 s−1), but it is a real enzymatic activity central to the molecular switch. (ahearn2012regulatingtheregulator pages 2-4)
GAPs accelerate Ras hydrolysis (reported up to ~10^5-fold in expert synthesis) and do so by complementing the active site, including an external arginine (“arginine finger”) concept; importantly, Gly12 oncogenic mutants are classically noted to resist such stimulation. (ahearn2012regulatingtheregulator pages 2-4, scheffzek1998gtpaseactivatingproteinshelping pages 1-2)
Primary structural evidence for Ras activation by SOS comes from the crystal structure of Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a nucleotide-free state, a mechanistic basis for GEF-driven exchange. (Boriack-Sjodin et al., Nature 1998-07; DOI/URL: https://doi.org/10.1038/28548) (boriacksjodin1998thestructuralbasis pages 1-2)
Structure-guided mutagenesis further shows distinct roles for Ras switch I vs switch II: switch II interactions largely anchor Ras to SOS, while switch I perturbation disrupts the nucleotide-binding site to promote GDP dissociation. (Hall et al., JBC 2001-07; DOI/URL: https://doi.org/10.1074/jbc.M101727200) (hall2001structurebasedmutagenesisreveals pages 1-2)
A primary structural and functional demonstration of Ras effector engagement is the Ras–PI3Kγ complex: PI3Kγ is directly activated by GTP-loaded Ras, and the structure shows Ras uses switch I/II to bind the PI3Kγ Ras-binding domain. (Pacold et al., Cell 2000-12; DOI/URL: https://doi.org/10.1016/S0092-8674(00)00196-3) (pacold2000crystalstructureand pages 1-2)
Ras protein signal transduction is the safest high-level BP annotation because it directly follows from nucleotide cycling and effector engagement (WT function). (nair2023regulationofrasgtpase pages 1-2, jesus2023targetingkrasin pages 4-6)
Positive regulation of MAPK cascade (RAS→RAF→MEK→ERK): Reviews of KRAS mechanism and signaling connect KRAS-GTP effector binding to RAF-family activation and MAPK signaling; however, expert cautions emphasize that “pathway membership” or overexpression is insufficient, and that effector engagement is limited by a single RBD-binding site per RAS at a given time. (jesus2023targetingkrasin pages 4-6)
PI3K signaling / PI3K–AKT–mTOR signaling: Direct biochemical/structural evidence supports Ras→PI3K effector binding and activation (PI3Kγ is a clear case). Extending to downstream AKT/mTOR should be done only where direct KRAS–PI3K effector evidence and context-specific functional readouts exist, not solely from tumor omics or mutant phenotypes. (pacold2000crystalstructureand pages 1-2, jesus2023targetingkrasin pages 4-6)
KRAS4A and KRAS4B differ almost exclusively in their C-terminal hypervariable region (HVR), which controls membrane binding, trafficking routes, and compartmental signaling. (Rossi et al., Biochem Soc Trans 2023-05; DOI/URL: https://doi.org/10.1042/bst20221347) (rossi2023differentialfunctionsof pages 9-10)
Shared CAAX processing and farnesylation: Both isoforms are farnesylated at the CAAX cysteine and further processed (RCE1 cleavage and ICMT methylation) in the ER, enabling membrane association. (Cox et al., Clin Cancer Res 2015-04; DOI/URL: https://doi.org/10.1158/1078-0432.CCR-14-3214) (cox2015targetingrasmembrane pages 2-4)
KRAS4A palmitoylation / fatty-acylation: KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi “affinity trap” promoting vesicular delivery to the plasma membrane. (Ahearn et al., Nat Rev Mol Cell Biol 2012-12; DOI/URL: https://doi.org/10.1038/nrm3255) (ahearn2012regulatingtheregulator pages 5-7)
KRAS4B polybasic region: KRAS4B lacks palmitoylatable cysteines and instead uses a lysine-rich polybasic HVR (reported net charge +8) to electrostatically stabilize plasma membrane association with anionic lipids. (ahearn2012regulatingtheregulator pages 5-7)
PDE6D (PDEδ) trafficking/chaperoning: KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold. (kaya2023characterizationofnovel pages 23-27)
A curated schematic comparing KRAS4A vs KRAS4B trafficking and compartmental localization (including PDE6D for KRAS4B and palmitoylation cycling for KRAS4A) is available in the Rossi 2023 review. (rossi2023differentialfunctionsof media 2c8748fc)
Oncogenic KRAS mutations (e.g., G12/G13/Q61) can reduce intrinsic and/or GAP-stimulated hydrolysis and shift conformational state populations, thereby sustaining effector engagement; however, downstream phenotypes (proliferation, senescence, apoptosis, transcriptional programs, developmental and immune/metabolic outcomes) are highly context dependent and often derived from mutant/overexpression models. These should not be propagated as WT KRAS GO BP annotations without direct WT evidence. (jesus2023targetingkrasin pages 4-6, mondal2024krasmutationsubtypes pages 10-12, jani2024insightintostructural pages 16-17, mozzarelli2024functionalandstructural pages 22-23)
Therapeutic strategies targeting membrane association/trafficking (e.g., CAAX processing inhibitors, PDE6D inhibitors) and effector interaction surfaces demonstrate that localization and effector engagement are mechanistically separable axes of KRAS biology; this reinforces the need for GO annotations to separate core MF (GTPase switch) from contextual disease phenotypes. (cox2015targetingrasmembrane pages 2-4, kaya2023characterizationofnovel pages 23-27)
Effector landscape: prediction-based summaries report 56 RBD-containing Ras effectors, and emphasize that each RAS molecule has one RBD-binding site such that only one effector binds at a time. (jesus2023targetingkrasin pages 4-6)
Cancer context: KRAS mutations are reported as present in ~22% of cancers (contextual prevalence, not a functional annotation). (smith2023definingbonefide pages 1-2)
PDAC context: in a compiled dataset (n=1552), >90% of PDAC tumors harbor KRAS mutations; the majority are at G12 (90%) and Q61 (7%), with reported G12D 36–45%, G12V 28–39%, G12R 12–21%, and G12C 0–4%. (jesus2023targetingkrasin pages 4-6)
| GO aspect | Recommended GO term label | Evidence summary (1 line) | Key refs (DOI/URL + year; PMID if explicit) | Annotation cautions |
|---|---|---|---|---|
| MF | GTP binding | KRAS is a Ras-family small GTPase whose active state is GTP-bound, with switch I/II conformational changes underlying signaling competence (jesus2023targetingkrasin pages 2-4, ahearn2012regulatingtheregulator pages 2-4, kewagamang2024therelationshipbetween pages 25-28) | Boriack-Sjodin et al. 1998, https://doi.org/10.1038/28548; Jesus et al. 2023, https://doi.org/10.3390/cancers15205015 | Prefer specific nucleotide binding over generic “G protein activity”; do not infer altered affinity from oncogenic mutants alone. |
| MF | GDP binding | KRAS also binds GDP as the inactive nucleotide-bound state; GDP/GTP cycling is the core switch mechanism (jesus2023targetingkrasin pages 2-4, nair2023regulationofrasgtpase pages 1-2, kewagamang2024therelationshipbetween pages 25-28) | Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007; Jesus et al. 2023, https://doi.org/10.3390/cancers15205015 | Annotate GDP binding separately from GTPase activity; avoid conflating inactive GDP-bound state with loss of function. |
| MF | GTPase activity | Ras has intrinsic GTP hydrolysis activity; catalytic turnover is low but real, central to KRAS molecular function (mozzarelli2024functionalandstructural pages 1-3, ahearn2012regulatingtheregulator pages 5-7, ahearn2012regulatingtheregulator pages 2-4) | Mozzarelli et al. 2024, https://doi.org/10.1016/j.molcel.2024.06.027; Ahearn et al. 2012, https://doi.org/10.1038/nrm3255 | Use “GTPase activity,” not broad “G protein activity”; mutant-impaired hydrolysis should not redefine WT function. |
| MF | Ras guanine nucleotide exchange factor binding / GEF-regulated nucleotide exchange | SOS binds nucleotide-free Ras and distorts switch regions to promote GDP release and GTP loading, establishing GEF-regulated cycling (boriacksjodin1998thestructuralbasis pages 1-2, hall2001structurebasedmutagenesisreveals pages 1-2) | Boriack-Sjodin et al. 1998, https://doi.org/10.1038/28548; Hall et al. 2001, https://doi.org/10.1074/jbc.M101727200 | Evidence supports regulation by GEFs; avoid annotating KRAS itself as a GEF. Use direct biochemical/structural evidence, not pathway membership. |
| MF | Ras GTPase-activating protein binding / GAP-stimulated GTP hydrolysis | GAPs accelerate KRAS hydrolysis by complementing the active site with an arginine finger; oncogenic codon-12 mutants resist this stimulation (ahearn2012regulatingtheregulator pages 2-4, scheffzek1998gtpaseactivatingproteinshelping pages 1-2) | Scheffzek et al. 1998, https://doi.org/10.1016/S0968-0004(98)01224-9; Ahearn et al. 2012, https://doi.org/10.1038/nrm3255 | Good support for GAP-regulated hydrolysis, but avoid mutant-centric annotations as WT properties; do not annotate generic “protein binding.” |
| MF | Effector binding (RAF/PI3K) in GTP-bound state | Bona fide effectors must bind GTP-bound Ras directly and change effector activity; structural work shows Ras·GTP engages PI3Kγ through switch I/II (smith2023definingbonefide pages 1-2, mozzarelli2024functionalandstructural pages 1-3, pacold2000crystalstructureand pages 1-2) | Smith 2023, https://doi.org/10.1002/bies.202300088; Mozzarelli et al. 2024, https://doi.org/10.1016/j.molcel.2024.06.027; Pacold et al. 2000, https://doi.org/10.1016/S0092-8674(00)00196-3 | Avoid annotating generic “protein binding”; require nucleotide dependence and functional consequence. Presence of an RBD/RA domain alone is insufficient. |
| BP | Ras protein signal transduction | Core WT role is Ras signal transduction via nucleotide cycling and effector engagement downstream of receptor inputs (jesus2023targetingkrasin pages 2-4, nair2023regulationofrasgtpase pages 1-2, jesus2023targetingkrasin pages 4-6) | Nair & Saha 2023, https://doi.org/10.3390/kinasesphosphatases1020007; Jesus et al. 2023, https://doi.org/10.3390/cancers15205015 | This is the safest high-level BP term; avoid importing cancer, proliferation, apoptosis, immune, or metabolic outcomes from mutant studies. |
| BP | Positive regulation of MAPK cascade | KRAS-GTP directly engages RAF-family effectors, supporting upstream positive regulation of the RAF-MEK-ERK/MAPK cascade (jesus2023targetingkrasin pages 4-6, ahearn2012regulatingtheregulator pages 2-4) | Jesus et al. 2023, https://doi.org/10.3390/cancers15205015; Ahearn et al. 2012, https://doi.org/10.1038/nrm3255 | Use when direct KRAS→RAF/MAPK evidence is available; avoid assigning all downstream transcriptional/developmental outputs to KRAS WT core function. |
| BP | PI3K signaling / positive regulation of PI3K-AKT-mTOR signaling | Ras directly binds and activates PI3Kγ structurally and biochemically, supporting PI3K pathway annotation where direct effector evidence exists (jesus2023targetingkrasin pages 4-6, pacold2000crystalstructureand pages 1-2) | Pacold et al. 2000, https://doi.org/10.1016/S0092-8674(00)00196-3; Jesus et al. 2023, https://doi.org/10.3390/cancers15205015 | Prefer direct Ras–PI3K evidence; be cautious with broad AKT/mTOR annotations inferred only from mutant tumors or indirect pathway studies. |
| BP | Protein prenylation / farnesylation-dependent membrane targeting | All KRAS isoforms undergo CAAX processing with farnesylation, followed by RCE1/ICMT processing, enabling membrane association (cox2015targetingrasmembrane pages 2-4, ahearn2012regulatingtheregulator pages 5-7) | Cox et al. 2015, https://doi.org/10.1158/1078-0432.CCR-14-3214; Ahearn et al. 2012, https://doi.org/10.1038/nrm3255 | This is primarily PTM/localization biology, not a unique signaling output; avoid overextending to disease phenotypes. |
| BP | Protein palmitoylation / fatty-acylation (KRAS4A-specific) | KRAS4A, unlike KRAS4B, carries a palmitoylatable cysteine and can undergo reversible acylation that promotes Golgi-dependent trafficking (rossi2023differentialfunctionsof pages 9-10, cox2015targetingrasmembrane pages 2-4, ahearn2012regulatingtheregulator pages 5-7) | Rossi et al. 2023, https://doi.org/10.1042/BST20221347; Cox et al. 2015, https://doi.org/10.1158/1078-0432.CCR-14-3214; Ahearn et al. 2012, https://doi.org/10.1038/nrm3255 | Isoform-specific: do not propagate palmitoylation to KRAS4B. Some fatty-acylation studies use oncogenic constructs; keep WT/isoform boundaries clear. |
| CC | Plasma membrane | KRAS signaling-competent pools localize predominantly to the inner leaflet of the plasma membrane; KRAS4B uses its polybasic HVR, KRAS4A uses lipidation plus HVR features (rossi2023differentialfunctionsof pages 9-10, cox2015targetingrasmembrane pages 2-4, ahearn2012regulatingtheregulator pages 5-7) | Rossi et al. 2023, https://doi.org/10.1042/BST20221347; Cox et al. 2015, https://doi.org/10.1158/1078-0432.CCR-14-3214 | Strong CC annotation is justified, but avoid assuming exclusive PM residence because KRAS also traffics through endomembranes. |
| CC | Golgi / endosome / ER membranes | KRAS cycles through endomembranes: KRAS4A via palmitoylation-dependent Golgi trafficking; KRAS4B can shuttle among ER/Golgi/endosomal membranes during solubilization and recycling (rossi2023differentialfunctionsof pages 9-10, cox2015targetingrasmembrane pages 2-4, rossi2023differentialfunctionsof media 2c8748fc) | Rossi et al. 2023, https://doi.org/10.1042/BST20221347; Cox et al. 2015, https://doi.org/10.1158/1078-0432.CCR-14-3214 | Use broader endomembrane/Golgi annotations cautiously and preferably with isoform-resolved evidence; localization may be transient and context dependent. |
| BP/CC | PDE6D-mediated trafficking / prenyl-dependent solubilization | PDE6D binds the KRAS prenyl group and supports solubilization/trafficking of especially KRAS4B between endomembranes and the plasma membrane; affinity is reduced >35-fold without carboxymethylation and >6-fold by S181E phosphomimic (rossi2023differentialfunctionsof pages 9-10, kaya2023characterizationofnovel pages 23-27) | Rossi et al. 2023, https://doi.org/10.1042/BST20221347; quantitative summary citing Dharmaiah et al. 2016 in pqac-00000025 | Useful for trafficking/localization curation, but avoid annotating KRAS as having “protein-membrane adaptor activity.” This is transport/chaperone-assisted localization, not an intrinsic adaptor MF. |
Table: This table maps GO-relevant functions, processes, and localizations for human KRAS (P01116) to concise evidence summaries and key sources. It is designed to support careful annotation while flagging common over-annotation risks, especially from mutant or generic pathway data.
1) Prefer specific MF terms (GTP binding, GDP binding, GTPase activity) over generic “G protein activity/protein binding.” (ahearn2012regulatingtheregulator pages 2-4, smith2023definingbonefide pages 1-2)
2) Add regulatory interaction terms (GEF/GAP-related) only with direct mechanistic evidence (e.g., SOS structural/functional evidence). (boriacksjodin1998thestructuralbasis pages 1-2, hall2001structurebasedmutagenesisreveals pages 1-2, scheffzek1998gtpaseactivatingproteinshelping pages 1-2)
3) Annotate MAPK/PI3K processes when supported by direct effector interaction/activation evidence; avoid inferring broad downstream phenotypes from mutant tumor biology. (pacold2000crystalstructureand pages 1-2, jesus2023targetingkrasin pages 4-6, mozzarelli2024functionalandstructural pages 22-23)
4) Use isoform-specific CC/BP annotations for KRAS4A palmitoylation trafficking vs KRAS4B polybasic/PDE6D-mediated trafficking; do not propagate palmitoylation to KRAS4B. (ahearn2012regulatingtheregulator pages 5-7, kaya2023characterizationofnovel pages 23-27, rossi2023differentialfunctionsof media 2c8748fc)
References
(smith2023definingbonefide pages 1-2): Matthew J. Smith. Defining bone fide effectors of ras gtpases. BioEssays, Jul 2023. URL: https://doi.org/10.1002/bies.202300088, doi:10.1002/bies.202300088. This article has 11 citations and is from a peer-reviewed journal.
(mozzarelli2024functionalandstructural pages 1-3): Alessandro M. Mozzarelli, Dhirendra K. Simanshu, and Pau Castel. Functional and structural insights into ras effector proteins. Molecular Cell, 84:2807-2821, Aug 2024. URL: https://doi.org/10.1016/j.molcel.2024.06.027, doi:10.1016/j.molcel.2024.06.027. This article has 35 citations and is from a highest quality peer-reviewed journal.
(jesus2023targetingkrasin pages 2-4): Victor Hugo Fonseca de Jesus, Maria Cecília Mathias-Machado, João Paulo Fogacci de Farias, Marcelo Porfirio Sunagua Aruquipa, Alexandre A. Jácome, and Renata D’Alpino Peixoto. Targeting kras in pancreatic ductal adenocarcinoma: the long road to cure. Cancers, 15:5015, Oct 2023. URL: https://doi.org/10.3390/cancers15205015, doi:10.3390/cancers15205015. This article has 42 citations.
(ahearn2012regulatingtheregulator pages 2-4): Ian M. Ahearn, Kevin Haigis, Dafna Bar-Sagi, and Mark R. Philips. Regulating the regulator: post-translational modification of ras. Nature Reviews Molecular Cell Biology, 13:39-51, Dec 2012. URL: https://doi.org/10.1038/nrm3255, doi:10.1038/nrm3255. This article has 749 citations and is from a domain leading peer-reviewed journal.
(pacold2000crystalstructureand pages 1-2): Michael E. Pacold, Sabine Suire, Olga Perisic, Samuel Lara-Gonzalez, Colin T. Davis, Edward H. Walker, Phillip T. Hawkins, Len Stephens, John F. Eccleston, and Roger L. Williams. Crystal structure and functional analysis of ras binding to its effector phosphoinositide 3-kinase γ. Cell, 103:931-944, Dec 2000. URL: https://doi.org/10.1016/s0092-8674(00)00196-3, doi:10.1016/s0092-8674(00)00196-3. This article has 843 citations and is from a highest quality peer-reviewed journal.
(nair2023regulationofrasgtpase pages 1-2): Arathi Nair and Bhaskar Saha. Regulation of ras-gtpase signaling and localization by post-translational modifications. Kinases and Phosphatases, 1:97-116, Apr 2023. URL: https://doi.org/10.3390/kinasesphosphatases1020007, doi:10.3390/kinasesphosphatases1020007. This article has 7 citations.
(boriacksjodin1998thestructuralbasis pages 1-2): P. Ann Boriack-Sjodin, S. Mariana Margarit, Dafna Bar-Sagi, and John Kuriyan. The structural basis of the activation of ras by sos. Nature, 394:337-343, Jul 1998. URL: https://doi.org/10.1038/28548, doi:10.1038/28548. This article has 1134 citations and is from a highest quality peer-reviewed journal.
(hall2001structurebasedmutagenesisreveals pages 1-2): Brian E. Hall, Shao Song Yang, P. Ann Boriack-Sjodin, John Kuriyan, and Dafna Bar-Sagi. Structure-based mutagenesis reveals distinct functions for ras switch 1 and switch 2 in sos-catalyzed guanine nucleotide exchange*. The Journal of Biological Chemistry, 276:27629-27637, Jul 2001. URL: https://doi.org/10.1074/jbc.m101727200, doi:10.1074/jbc.m101727200. This article has 181 citations.
(scheffzek1998gtpaseactivatingproteinshelping pages 1-2): Klaus Scheffzek, Mohammad Reza Ahmadian, and Alfred Wittinghofer. Gtpase-activating proteins: helping hands to complement an active site. Trends in biochemical sciences, 23 7:257-62, Jul 1998. URL: https://doi.org/10.1016/s0968-0004(98)01224-9, doi:10.1016/s0968-0004(98)01224-9. This article has 590 citations and is from a domain leading peer-reviewed journal.
(mondal2024krasmutationsubtypes pages 10-12): Koushik Mondal, Mahesh Kumar Posa, Revathi P. Shenoy, and Susanta Roychoudhury. Kras mutation subtypes and their association with other driver mutations in oncogenic pathways. Cells, 13:1221, Jul 2024. URL: https://doi.org/10.3390/cells13141221, doi:10.3390/cells13141221. This article has 45 citations.
(jani2024insightintostructural pages 16-17): Vinod Jani, Uddhavesh Sonavane, and Rajendra Joshi. Insight into structural dynamics involved in activation mechanism of full length kras wild type and p-loop mutants. Heliyon, 10:e36161, Aug 2024. URL: https://doi.org/10.1016/j.heliyon.2024.e36161, doi:10.1016/j.heliyon.2024.e36161. This article has 7 citations.
(jesus2023targetingkrasin pages 4-6): Victor Hugo Fonseca de Jesus, Maria Cecília Mathias-Machado, João Paulo Fogacci de Farias, Marcelo Porfirio Sunagua Aruquipa, Alexandre A. Jácome, and Renata D’Alpino Peixoto. Targeting kras in pancreatic ductal adenocarcinoma: the long road to cure. Cancers, 15:5015, Oct 2023. URL: https://doi.org/10.3390/cancers15205015, doi:10.3390/cancers15205015. This article has 42 citations.
(rossi2023differentialfunctionsof pages 9-10): Juan Kochen Rossi, Cristina Nuevo-Tapioles, and Mark R. Philips. Differential functions of the kras splice variants. Biochemical Society transactions, 51:1191-1199, May 2023. URL: https://doi.org/10.1042/bst20221347, doi:10.1042/bst20221347. This article has 9 citations and is from a peer-reviewed journal.
(cox2015targetingrasmembrane pages 2-4): Adrienne D. Cox, Channing J. Der, and Mark R. Philips. Targeting ras membrane association: back to the future for anti-ras drug discovery? Clinical Cancer Research, 21:1819-1827, Apr 2015. URL: https://doi.org/10.1158/1078-0432.ccr-14-3214, doi:10.1158/1078-0432.ccr-14-3214. This article has 448 citations and is from a highest quality peer-reviewed journal.
(ahearn2012regulatingtheregulator pages 5-7): Ian M. Ahearn, Kevin Haigis, Dafna Bar-Sagi, and Mark R. Philips. Regulating the regulator: post-translational modification of ras. Nature Reviews Molecular Cell Biology, 13:39-51, Dec 2012. URL: https://doi.org/10.1038/nrm3255, doi:10.1038/nrm3255. This article has 749 citations and is from a domain leading peer-reviewed journal.
(kaya2023characterizationofnovel pages 23-27): P KAYA. Characterization of novel inhibitors of the trafficking chaperone pde6d. Unknown journal, 2023.
(rossi2023differentialfunctionsof media 2c8748fc): Juan Kochen Rossi, Cristina Nuevo-Tapioles, and Mark R. Philips. Differential functions of the kras splice variants. Biochemical Society transactions, 51:1191-1199, May 2023. URL: https://doi.org/10.1042/bst20221347, doi:10.1042/bst20221347. This article has 9 citations and is from a peer-reviewed journal.
(mozzarelli2024functionalandstructural pages 22-23): Alessandro M. Mozzarelli, Dhirendra K. Simanshu, and Pau Castel. Functional and structural insights into ras effector proteins. Molecular Cell, 84:2807-2821, Aug 2024. URL: https://doi.org/10.1016/j.molcel.2024.06.027, doi:10.1016/j.molcel.2024.06.027. This article has 35 citations and is from a highest quality peer-reviewed journal.
(kewagamang2024therelationshipbetween pages 25-28): K Kewagamang. The relationship between oncogenic kras and wild-type ras activity and signaling. Unknown journal, 2024.
Initial review date: 2026-05-02
KRAS is a Ras-family small GTPase. UniProt describes human KRAS as binding GDP/GTP
and having intrinsic GTPase activity, with the catalytic reaction GTP + H2O -> GDP
+ phosphate. It cycles between GDP-bound inactive and GTP-bound active states and
is regulated by GEFs and GAPs [file:human/KRAS/KRAS-uniprot.txt, "Ras proteins
bind GDP/GTP and possess intrinsic GTPase activity"; "Alternates between an
inactive form bound to GDP and an active form bound to GTP"].
KRAS membrane localization is central to function. UniProt places KRAS at the cell
membrane, cytoplasmic side, endomembrane system, and cytosol [file:human/KRAS/KRAS-uniprot.txt,
"Cell membrane ... Lipid-anchor"; "Endomembrane system"; "Cytoplasm, cytosol"].
PDEdelta regulates correct localization of farnesylated KRAS and supports the cytosolic
trafficking pool [PMID:23698361 Small molecule inhibition of the KRAS-PDEdelta
interaction impairs oncogenic KRAS signalling, "Correct localization and signalling
by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ"].
KRAS4A and KRAS4B differ in C-terminal targeting mechanisms. K-Ras4A is regulated by
lysine fatty acylation; SIRT2-mediated removal of lysine acylation promotes
endomembrane localization and ARAF interaction [PMID:29239724 SIRT2 and lysine fatty
acylation regulate the transforming activity of K-Ras4a, "SIRT2-mediated lysine
defatty-acylation promotes endomembrane localization of K-Ras4a"].
KRAS participates directly in Ras protein signal transduction. SOS1 facilitates
GDP-to-GTP exchange on KRAS [PMID:38188543 Studying early structural changes in SOS1
mediated KRAS activation mechanism, "SOS1 facilitates the exchange of GDP to GTP
thereby leading to activation of KRAS"]. GTP-bound RAS recruits RAF and promotes RAF
activation in the RAF-MEK-ERK cascade [Reactome:R-HSA-5673001 RAF/MAP kinase cascade,
"GTP-bound RAS recruits RAF"; PMID:33608534 KRAS interaction with RAF1 RAS-binding
domain and cysteine-rich domain provides insights into RAS-mediated RAF activation,
"Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active"].
RAS-PI3Kalpha interaction also supports PI3K-AKT-mTOR signaling [PMID:39788953
Structural insights into isoform-specific RAS-PI3Kalpha interactions and the role of
RAS in PI3Kalpha activation, "activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway"].
Core annotations are GTPase activity, G protein activity/GTP-GDP switch behavior, Ras
protein signal transduction, and MAPK cascade activation at membranes. Plasma membrane,
cytoplasmic side of plasma membrane, endomembrane system, cytosol/cytoplasm, Golgi,
ER, and mitochondrial outer membrane annotations were handled according to how directly
they support KRAS signaling versus trafficking or isoform/modification-specific biology.
Generic protein binding annotations were removed. They record real interactions in some
cases, but GO:0005515 does not describe KRAS function and is explicitly discouraged by
the project guidelines.
High-level phenotype/process annotations such as liver development, pregnancy, hormone
responses, response to gravity/isolation stress, and cell-type proliferation were marked
as over-annotated unless they had direct pathway support. Proliferation, TOR signaling,
and senescence were retained as non-core where they reflect plausible downstream outcomes
of KRAS effector signaling.
just fetch-gene human KRAS hit NCBI HTTP 429 errors for several PMIDs. I retried
PMID:20949621, PMID:22065586, PMID:35831509, and PMID:39043660 but the fetch still
failed. I updated their reference titles from accessible web/PubMed or structural
database metadata and marked findings as full-text unavailable where needed. These
failed cached publications should be refreshed later with just fetch-gene-pmids human KRAS
or targeted just fetch-pmid retries.
Backfilled KRAS-deep-research-falcon.md on 2026-05-13. The Falcon synthesis
corroborates the already-complete review: KRAS core function is the wild-type GDP/GTP
molecular switch with GTP hydrolysis, GEF/GAP-regulated cycling, and GTP-bound effector
engagement [file:human/KRAS/KRAS-deep-research-falcon.md, "This report summarizes
GO-relevant evidence for the wild-type (WT) KRAS molecular switch function
(GDP/GTP cycling, effector engagement) and isoform-specific membrane targeting of
KRAS4A versus KRAS4B."]. It also reinforces the existing conservative handling of
generic protein binding and broad mutant/cancer outcomes: broad downstream phenotypes
should not be propagated without direct wild-type evidence [file:human/KRAS/KRAS-deep-research-falcon.md,
"It explicitly avoids over-annotation from (i) pathway membership, (ii) overexpression
systems, and (iii) oncogenic-mutant phenotypes unless the claim is a direct biochemical
consequence of the mutation that is relevant to the core switch mechanism."].
id: P01116
gene_symbol: KRAS
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: 'KRAS encodes a membrane-associated Ras-family small GTPase that functions as a GDP/GTP molecular
switch in receptor-driven signal transduction. In the GTP-bound state KRAS recruits effectors including
RAF-family kinases and PI3Kalpha to activate downstream MAPK and PI3K-AKT-mTOR signaling; intrinsic
and GAP-stimulated GTP hydrolysis return KRAS to the GDP-bound inactive state. KRAS4A and KRAS4B differ
in their C-terminal hypervariable regions and membrane-targeting mechanisms, but both depend on lipid
modification and membrane localization for signaling. Oncogenic and rasopathy variants alter nucleotide
cycling, GAP responsiveness, effector interactions, or localization, producing context-dependent effects
on proliferation, survival, senescence, and gene expression.'
alternative_products:
- name: 2A (K-Ras4A {ECO:0000303|PubMed:29239724})
id: P01116-1
description: KRAS4A isoform with a distinct C-terminal hypervariable region. It uses
farnesylation, Cys180 palmitoylation, and lysine fatty acylation to control plasma membrane and
endomembrane localization; SIRT2-dependent lysine defatty-acylation promotes endomembrane
localization and ARAF interaction.
- name: 2B (K-Ras4B)
id: P01116-2, P01118-1
sequence_note: VSP_011140, VSP_011141
description: KRAS4B isoform with a polybasic C-terminal hypervariable region. Farnesylation and
the polybasic region support plasma membrane association, while PDEdelta-mediated solubilization
and recycling help maintain KRAS4B spatial organization.
existing_annotations:
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- &id005
reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361,
ECO:0000269|PubMed:29239724}; Lipid-anchor
- &id004
reference_id: PMID:23698361
supporting_text: Correct localization and signalling by farnesylated KRAS is regulated by the
prenyl-binding protein PDEδ
- &id014
reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
Both isoforms are farnesylated at the CAAX cysteine and further processed (RCE1 cleavage
and ICMT methylation) in the ER, enabling membrane association. KRAS4B lacks palmitoylatable
cysteines and instead uses a lysine-rich polybasic HVR (reported net charge +8) to
electrostatically stabilize plasma membrane association with anionic lipids.
- term:
id: GO:0007265
label: Ras protein signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA annotation for Ras protein signal transduction. KRAS participates directly in Ras
signaling through SOS-mediated activation and effector engagement.
action: ACCEPT
reason: This process annotation is appropriate for KRAS, whose active GTP-bound form transmits
receptor inputs to downstream pathways including RAF-MEK-ERK and PI3K-AKT-mTOR.
supported_by:
- &id006
reference_id: PMID:38188543
supporting_text: SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of
KRAS
- &id001
reference_id: Reactome:R-HSA-5673001
supporting_text: GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its
dimerization and activation
- &id002
reference_id: PMID:33608534
supporting_text: Active RAS recruits RAF to the membrane where RAF dimerizes and becomes
active
- &id015
reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
Primary structural evidence for Ras activation by SOS comes from the crystal structure of
Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a
nucleotide-free state, a mechanistic basis for GEF-driven exchange.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: KRAS signaling can promote cell proliferation through MAPK and PI3K effector pathways,
but proliferation is a downstream cellular outcome rather than the molecular core function.
action: KEEP_AS_NON_CORE
reason: The annotation is biologically plausible and supported by pathway literature, but it
should not be treated as the core activity of KRAS.
supported_by:
- *id001
- *id002
- &id008
reference_id: PMID:39788953
supporting_text: Their interaction plays a crucial role in activating PI3Kα and amplifying the
PI3K-AKT-mTOR pathway
- term:
id: GO:0003924
label: GTPase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with
intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
action: ACCEPT
reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic
GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central
catalytic activity.
supported_by: &id003
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
- reference_id: Reactome:R-HSA-9649736
supporting_text: RAS proteins have weak intrinsic GTPase activity in the absence of other
effectors
- reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
**KRAS is a Ras-family small GTPase** that functions as a GDP/GTP-regulated
switch. GTP binding induces conformational changes in **switch I/II** regions
enabling effector recognition, while GTP hydrolysis returns KRAS to the
GDP-bound state.
- term:
id: GO:0000165
label: MAPK cascade
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: KRAS participates in the RAF/MAP kinase cascade by recruiting and activating RAF-family
kinases when GTP-bound.
action: ACCEPT
reason: Reactome and structural work support active KRAS as an upstream activator of the
RAF-MEK-ERK MAPK cascade.
supported_by: &id010
- *id001
- *id002
- term:
id: GO:0003924
label: GTPase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: IEA annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with
intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
action: ACCEPT
reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic
GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central
catalytic activity.
supported_by: *id003
- term:
id: GO:0003925
label: G protein activity
evidence_type: IEA
original_reference_id: GO_REF:0000003
review:
summary: KRAS functions as a small monomeric G protein that switches between GDP-bound inactive
and GTP-bound active states.
action: MODIFY
reason: The integrated falcon DR guidance explicitly recommends the more specific GTPase
activity term (GO:0003924) over the generic G protein activity term for KRAS. GO:0003924 is
already separately annotated for KRAS with IBA, IEA, EXP, TAS, and IMP evidence (all ACCEPT),
so MODIFY replaces this generic IEA term with the established specific term.
proposed_replacement_terms:
- id: GO:0003924
label: GTPase activity
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Alternates between an inactive form bound to GDP and an active form bound to
GTP
- reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
Use "GTPase activity," not broad "G protein activity"; mutant-impaired hydrolysis should
not redefine WT function. Prefer specific MF terms (GTP binding, GDP binding, GTPase
activity) over generic "G protein activity/protein binding."
- term:
id: GO:0005525
label: GTP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: KRAS binds GTP as the active nucleotide state of the Ras molecular switch.
action: ACCEPT
reason: GTP binding is essential to KRAS activation and downstream effector recruitment.
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Alternates between an inactive form bound to GDP and an active form bound to
GTP
- reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
KRAS is a Ras-family small GTPase that functions as a GDP/GTP-regulated switch. GTP binding
induces conformational changes in switch I/II regions enabling effector recognition, while
GTP hydrolysis returns KRAS to the GDP-bound state. A primary structural and functional
demonstration of Ras effector engagement is the Ras–PI3Kγ complex: PI3Kγ is directly
activated by GTP-loaded Ras, and the structure shows Ras uses switch I/II to bind the
PI3Kγ Ras-binding domain.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: &id007
- *id004
- &id017
reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group
and support trafficking between endomembranes and plasma membrane. Quantitatively summarized
evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by
>35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: IEA annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0007165
label: signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: The generic signal transduction annotation reflects KRAS signaling but is less
informative than Ras-specific signaling terms.
action: MODIFY
reason: KRAS should be annotated to Ras protein signal transduction rather than broad signal
transduction when the domain and pathway evidence are Ras-specific.
proposed_replacement_terms:
- id: GO:0007265
label: Ras protein signal transduction
supported_by:
- *id006
- term:
id: GO:0012505
label: endomembrane system
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: KRAS, especially K-Ras4a under SIRT2-regulated lysine defatty-acylation, can localize
to endomembrane compartments.
action: ACCEPT
reason: Endomembrane localization is supported by K-Ras4a acylation experiments and by UniProt
subcellular-location curation.
supported_by: &id013
- reference_id: PMID:29239724
supporting_text: SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of
K-Ras4a
- reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent
Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase
membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular
delivery to the plasma membrane.
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: The generic membrane annotation is directionally correct for lipid-anchored KRAS but
lacks the useful subcellular specificity available from curated evidence.
action: MARK_AS_OVER_ANNOTATED
reason: KRAS has more specific and better-supported plasma membrane,
cytoplasmic-side-of-plasma-membrane, endomembrane, and cytosolic localization annotations.
Generic membrane should not be used as an informative KRAS localization.
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361,
ECO:0000269|PubMed:29239724}; Lipid-anchor
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12732644
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25852190
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:30194290
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31980649
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0001889
label: liver development
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The liver development annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0007249
label: canonical NF-kappaB signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The canonical NF-kappaB signal transduction annotation is an orthology-transferred
high-level biological-process term and is not directly supported as a specific human KRAS
function in the reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0007565
label: female pregnancy
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The female pregnancy annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0009629
label: response to gravity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The response to gravity annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0019002
label: GMP binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: This orthology-transferred GMP binding annotation does not match the established KRAS
nucleotide cycle, which is GDP/GTP based.
action: MODIFY
reason: KRAS is characterized as a GDP/GTP-binding small GTPase. GMP binding is not the
physiologically informative ligand state for KRAS and should be replaced by the specific GDP
and GTP binding terms.
proposed_replacement_terms:
- id: GO:0005525
label: GTP binding
- id: GO:0019003
label: GDP binding
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
- term:
id: GO:0019003
label: GDP binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: KRAS binds GDP as the inactive nucleotide state of the Ras molecular switch.
action: ACCEPT
reason: GDP binding is a normal part of the KRAS regulatory cycle and is supported by the
UniProt activity-regulation statement.
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Alternates between an inactive form bound to GDP and an active form bound to
GTP
- term:
id: GO:0019221
label: cytokine-mediated signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The cytokine-mediated signaling pathway annotation is an orthology-transferred
high-level biological-process term and is not directly supported as a specific human KRAS
function in the reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0030275
label: LRR domain binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: KRAS can interact with LRR-containing SHOC2 in the SHOC2-PP1C-RAS regulatory system,
but LRR domain binding is not the core KRAS molecular function.
action: MARK_AS_OVER_ANNOTATED
reason: The orthology-transferred MF term overemphasizes one regulator interaction. The
functional consequence is better represented by Ras/MAPK signaling annotations.
supported_by: &id011
- &id012
reference_id: PMID:36175670
supporting_text: The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind
SHOC2
- term:
id: GO:0035900
label: response to isolation stress
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The response to isolation stress annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0051384
label: response to glucocorticoid
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The response to glucocorticoid annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0051385
label: response to mineralocorticoid
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The response to mineralocorticoid annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0051450
label: myoblast proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The myoblast proliferation annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:0060038
label: cardiac muscle cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The cardiac muscle cell proliferation annotation is an orthology-transferred high-level
biological-process term and is not directly supported as a specific human KRAS function in the
reviewed evidence.
action: MARK_AS_OVER_ANNOTATED
reason: These developmental, stress, hormone, cytokine, or cell-type proliferation terms are
likely indirect consequences of Ras pathway perturbation or non-human phenotype propagation.
They overstate the direct functional role of KRAS.
- term:
id: GO:2000774
label: positive regulation of cellular senescence
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: RAS pathway activation can be associated with cellular senescence in oncogene-stress
contexts, but this is a context-dependent downstream outcome.
action: KEEP_AS_NON_CORE
reason: The term should not be considered core for KRAS; it reflects a cellular response to
signaling intensity and context rather than the conserved molecular role.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23524970
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:23524970
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:23524970
review:
summary: IDA annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0007265
label: Ras protein signal transduction
evidence_type: IDA
original_reference_id: PMID:38188543
review:
summary: IDA annotation for Ras protein signal transduction. KRAS participates directly in Ras
signaling through SOS-mediated activation and effector engagement.
action: ACCEPT
reason: This process annotation is appropriate for KRAS, whose active GTP-bound form transmits
receptor inputs to downstream pathways including RAF-MEK-ERK and PI3K-AKT-mTOR.
supported_by:
- *id006
- *id001
- *id002
- *id015
- term:
id: GO:0032008
label: positive regulation of TOR signaling
evidence_type: NAS
original_reference_id: PMID:39788953
review:
summary: RAS-PI3Kalpha interaction can amplify PI3K-AKT-mTOR signaling, placing KRAS upstream of
TOR pathway activation in some contexts.
action: KEEP_AS_NON_CORE
reason: This is a supported effector branch but not the primary core function; KRAS is best
represented first as a membrane-associated small GTPase in Ras/MAPK signaling.
supported_by: &id009
- *id008
- term:
id: GO:0042127
label: regulation of cell population proliferation
evidence_type: NAS
original_reference_id: PMID:38188543
review:
summary: KRAS signaling can promote cell proliferation through MAPK and PI3K effector pathways,
but proliferation is a downstream cellular outcome rather than the molecular core function.
action: KEEP_AS_NON_CORE
reason: The annotation is biologically plausible and supported by pathway literature, but it
should not be treated as the core activity of KRAS.
supported_by:
- *id001
- *id002
- *id008
- term:
id: GO:0043069
label: negative regulation of programmed cell death
evidence_type: NAS
original_reference_id: PMID:39788953
review:
summary: Negative regulation of programmed cell death can occur downstream of RAS effector
pathways, especially through PI3K-AKT survival signaling, but the annotation is broad.
action: MARK_AS_OVER_ANNOTATED
reason: The cited PI3Kalpha structural work supports RAS-PI3K pathway activation, not a direct
KRAS role in the general programmed cell death process.
supported_by: *id009
- term:
id: GO:0043410
label: positive regulation of MAPK cascade
evidence_type: NAS
original_reference_id: PMID:33608534
review:
summary: KRAS positively regulates the MAPK cascade through direct active-RAS interaction with
RAF-family kinases.
action: ACCEPT
reason: This is an accurate pathway-level annotation for the canonical KRAS effector branch.
supported_by: *id010
- term:
id: GO:1902554
label: serine/threonine protein kinase complex
evidence_type: IPI
original_reference_id: PMID:33608534
review:
summary: The cited RAF1 structural work supports KRAS binding to RAF regulatory domains during
RAF activation, not stable membership in a serine/threonine protein kinase complex.
action: MARK_AS_OVER_ANNOTATED
reason: KRAS is an upstream small GTPase effector-binding partner for RAF; representing it as
part of a kinase complex overstates a transient signaling interaction.
supported_by: *id010
- term:
id: GO:1905360
label: GTPase complex
evidence_type: IPI
original_reference_id: PMID:39043660
review:
summary: The GTPase complex annotation is based on a structural interaction context rather than
evidence that KRAS is a stable component of a native cellular complex.
action: MARK_AS_OVER_ANNOTATED
reason: KRAS forms transient complexes with GEFs, GAPs, effectors, inhibitors, and structural
binders. A generic GTPase complex cellular-component term is not informative as a gene-level
KRAS annotation.
- term:
id: GO:0000164
label: protein phosphatase type 1 complex
evidence_type: IPI
original_reference_id: PMID:36175670
review:
summary: SHOC2-MRAS-PP1C studies show that canonical RAS proteins, including KRAS, can bind this
regulatory phosphatase system with lower affinity than MRAS.
action: MARK_AS_OVER_ANNOTATED
reason: The core complex is SHOC2-MRAS-PP1C. Assigning KRAS as part of a protein phosphatase
type 1 complex overstates a non-core, weaker regulatory interaction.
supported_by: *id011
- term:
id: GO:0046579
label: positive regulation of Ras protein signal transduction
evidence_type: NAS
original_reference_id: PMID:35831509
review:
summary: This annotation captures KRAS-dependent positive signaling but frames the role as
regulation of Ras signaling rather than direct participation in the Ras/MAPK pathway.
action: MODIFY
reason: The evidence is better represented by KRAS involvement in Ras protein signal
transduction and positive regulation of the MAPK cascade.
proposed_replacement_terms:
- id: GO:0007265
label: Ras protein signal transduction
- id: GO:0043410
label: positive regulation of MAPK cascade
supported_by:
- *id012
- *id001
- *id002
- term:
id: GO:0000165
label: MAPK cascade
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5673001
review:
summary: KRAS participates in the RAF/MAP kinase cascade by recruiting and activating RAF-family
kinases when GTP-bound.
action: ACCEPT
reason: Reactome and structural work support active KRAS as an upstream activator of the
RAF-MEK-ERK MAPK cascade.
supported_by: *id010
- term:
id: GO:0005829
label: cytosol
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0003924
label: GTPase activity
evidence_type: EXP
original_reference_id: PMID:20949621
review:
summary: EXP annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with
intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
action: ACCEPT
reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic
GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central
catalytic activity.
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
- reference_id: Reactome:R-HSA-9649736
supporting_text: RAS proteins have weak intrinsic GTPase activity in the absence of other
effectors
- reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
A widely cited expert synthesis reports Ras intrinsic hydrolysis is slow (kcat ≈ 2×10−4
s−1), but it is a real enzymatic activity central to the molecular switch. GAPs accelerate
Ras hydrolysis (reported up to ~10^5-fold in expert synthesis) and do so by complementing
the active site, including an external arginine ("arginine finger") concept.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: EXP
original_reference_id: PMID:29239724
review:
summary: EXP annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0012505
label: endomembrane system
evidence_type: EXP
original_reference_id: PMID:29239724
review:
summary: KRAS, especially K-Ras4a under SIRT2-regulated lysine defatty-acylation, can localize
to endomembrane compartments.
action: ACCEPT
reason: Endomembrane localization is supported by K-Ras4a acylation experiments and by UniProt
subcellular-location curation.
supported_by: *id013
- term:
id: GO:0003924
label: GTPase activity
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649736
review:
summary: TAS annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with
intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
action: ACCEPT
reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic
GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central
catalytic activity.
supported_by: *id003
- term:
id: GO:0009898
label: cytoplasmic side of plasma membrane
evidence_type: IDA
original_reference_id: PMID:23698361
review:
summary: KRAS localizes to the cytoplasmic side of the plasma membrane through C-terminal lipid
modification and membrane-targeting motifs.
action: ACCEPT
reason: This is the most precise cellular-component annotation for signaling-competent
membrane-associated KRAS.
supported_by:
- *id005
- *id004
- term:
id: GO:0003924
label: GTPase activity
evidence_type: IMP
original_reference_id: PMID:26037647
review:
summary: IMP annotation for KRAS GTPase activity. KRAS is a Ras-family small GTPase with
intrinsic GTP hydrolysis activity and GAP-stimulated hydrolysis.
action: ACCEPT
reason: This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic
GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central
catalytic activity.
supported_by: *id003
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24415755
review:
summary: This protein binding annotation records a physical interaction, but GO:0005515 is too
generic to describe KRAS function.
action: REMOVE
reason: Protein binding is specifically uninformative for KRAS. Specific effector/regulator
interactions should support Ras signaling, MAPK cascade, PI3K signaling, or localization
annotations rather than a generic protein binding MF term.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9674816
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654521
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654523
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654525
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654533
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005741
label: mitochondrial outer membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653592
review:
summary: Reactome places phosphorylated KRAS4B at the mitochondrial outer membrane in a
regulated trafficking/signaling context.
action: KEEP_AS_NON_CORE
reason: This is context-specific and isoform/modification-state dependent, so it should be kept
as non-core rather than treated as a general KRAS localization.
- term:
id: GO:0005741
label: mitochondrial outer membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653595
review:
summary: Reactome places phosphorylated KRAS4B at the mitochondrial outer membrane in a
regulated trafficking/signaling context.
action: KEEP_AS_NON_CORE
reason: This is context-specific and isoform/modification-state dependent, so it should be kept
as non-core rather than treated as a general KRAS localization.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653503
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653592
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9651280
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802834
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802908
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802918
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802922
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802924
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802925
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802926
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802937
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802941
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802942
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802943
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6803233
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6803234
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6803240
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8936731
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647977
review:
summary: ER membrane annotations reflect CAAX processing and maturation reactions for
farnesylated RAS proteins in Reactome.
action: KEEP_AS_NON_CORE
reason: The ER membrane is relevant to RAS processing but is not the primary location of
signaling-competent KRAS.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647978
review:
summary: ER membrane annotations reflect CAAX processing and maturation reactions for
farnesylated RAS proteins in Reactome.
action: KEEP_AS_NON_CORE
reason: The ER membrane is relevant to RAS processing but is not the primary location of
signaling-competent KRAS.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647999
review:
summary: ER membrane annotations reflect CAAX processing and maturation reactions for
farnesylated RAS proteins in Reactome.
action: KEEP_AS_NON_CORE
reason: The ER membrane is relevant to RAS processing but is not the primary location of
signaling-competent KRAS.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649732
review:
summary: ER membrane annotations reflect CAAX processing and maturation reactions for
farnesylated RAS proteins in Reactome.
action: KEEP_AS_NON_CORE
reason: The ER membrane is relevant to RAS processing but is not the primary location of
signaling-competent KRAS.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647978
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647980
review:
summary: Golgi membrane localization is relevant to RAS membrane trafficking and palmitoylation
cycles, especially for the K-Ras4A isoform.
action: KEEP_AS_NON_CORE
reason: This is a plausible trafficking/maturation localization but not the primary signaling
location for KRAS.
supported_by:
- reference_id: Reactome:R-HSA-9647980
supporting_text: mature RAS proteins translocate to the plasma membrane
- &id018
reference_id: file:human/KRAS/KRAS-deep-research-falcon.md
supporting_text: >-
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent
Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase
membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular
delivery to the plasma membrane.
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647982
review:
summary: Golgi membrane localization is relevant to RAS membrane trafficking and palmitoylation
cycles, especially for the K-Ras4A isoform.
action: KEEP_AS_NON_CORE
reason: This is a plausible trafficking/maturation localization but not the primary signaling
location for KRAS.
supported_by:
- reference_id: Reactome:R-HSA-9647980
supporting_text: mature RAS proteins translocate to the plasma membrane
- *id018
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1168636
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1225951
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1225957
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1250383
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1306972
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1433471
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-170986
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-177938
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-177945
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-186834
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-210977
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2179407
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-2424477
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-392054
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5218845
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5621573
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5624486
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5624492
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5624494
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5637806
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5637808
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654392
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654402
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654413
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654426
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654600
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654618
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654647
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5654663
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5655241
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5655277
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5655326
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5655347
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5658231
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5658435
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672950
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672965
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672966
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672969
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672972
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672973
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672978
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672980
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5674018
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5674022
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5675417
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5675431
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5675433
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802837
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8851827
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8851877
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8851899
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8941613
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8941618
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8941623
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8941628
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8981353
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8981355
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9607304
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9632906
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9632918
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9634418
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647980
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647994
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649733
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649735
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649736
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653108
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656209
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656211
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656212
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656213
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656214
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9656215
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9657599
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9657603
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9657606
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9657608
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9658253
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9664991
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9665009
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9665404
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9665408
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9665700
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9665707
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9670436
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9672163
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9672170
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9695853
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9703441
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9647982
review:
summary: ER membrane annotations reflect CAAX processing and maturation reactions for
farnesylated RAS proteins in Reactome.
action: KEEP_AS_NON_CORE
reason: The ER membrane is relevant to RAS processing but is not the primary location of
signaling-competent KRAS.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9649732
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9653585
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654521
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9654533
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0044877
label: protein-containing complex binding
evidence_type: IDA
original_reference_id: PMID:23209302
review:
summary: The protein-containing complex binding annotation is broad and the cited paper is not
KRAS-centered; it does not clarify KRAS molecular function.
action: REMOVE
reason: This generic binding term is not useful for KRAS and appears to come from a broad
complex-binding assertion rather than evidence for a specific KRAS activity.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:23698361
review:
summary: KRAS has a cytoplasmic/cytosolic pool during its membrane-trafficking cycle, including
PDEdelta-mediated solubilization of farnesylated KRAS.
action: ACCEPT
reason: Although signaling-competent KRAS is membrane-associated, cytosolic localization is
supported as part of its trafficking and recycling cycle.
supported_by: *id007
- term:
id: GO:0005925
label: focal adhesion
evidence_type: HDA
original_reference_id: PMID:21423176
review:
summary: The focal adhesion annotation comes from high-throughput proteomic detection rather
than targeted KRAS localization evidence.
action: MARK_AS_OVER_ANNOTATED
reason: Focal adhesion is not a supported core or well-established localization for KRAS in the
reviewed evidence.
- term:
id: GO:0016020
label: membrane
evidence_type: HDA
original_reference_id: PMID:19946888
review:
summary: The generic membrane annotation is directionally correct for lipid-anchored KRAS but
lacks the useful subcellular specificity available from curated evidence.
action: MARK_AS_OVER_ANNOTATED
reason: KRAS has more specific and better-supported plasma membrane,
cytoplasmic-side-of-plasma-membrane, endomembrane, and cytosolic localization annotations.
Generic membrane should not be used as an informative KRAS localization.
supported_by:
- reference_id: file:human/KRAS/KRAS-uniprot.txt
supporting_text: Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361,
ECO:0000269|PubMed:29239724}; Lipid-anchor
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802914
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802915
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802916
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802919
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6802921
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6803230
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8936676
review:
summary: TAS annotation for plasma membrane localization. KRAS is lipid-anchored and functions
at the cytoplasmic face of the plasma membrane.
action: ACCEPT
reason: Plasma membrane localization is well supported by UniProt, PDEdelta localization work,
K-Ras4a acylation work, and many Reactome RAS pathway events.
supported_by:
- *id005
- *id004
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:22065586
review:
summary: Oncogenic Ras can increase expression of specific genes such as DR5 through
ERK/JNK-dependent transcription factor activation.
action: MARK_AS_OVER_ANNOTATED
reason: The evidence concerns oncogenic Ras/B-Raf regulation of a specific death receptor
transcriptional response. The broad gene expression term is a downstream,
mutant/context-dependent outcome rather than a general KRAS function.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000003
title: Gene Ontology annotation based on Enzyme Commission mapping
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: PMID:12732644
title: RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor.
findings: []
- id: PMID:19946888
title: Defining the membrane proteome of NK cells.
findings: []
- id: PMID:20949621
title: 'Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental
disorders.'
findings:
- statement: Biochemical analysis of germline KRAS variants supports altered nucleotide exchange,
GAP-stimulated hydrolysis, and effector interactions.
full_text_unavailable: true
- id: PMID:21423176
title: Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in
negative regulation of focal adhesion maturation.
findings: []
- id: PMID:22065586
title: 'Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation
of ERK and JNK signaling'
findings:
- statement: Oncogenic Ras can induce DR5 expression through ERK/RSK and JNK signaling, supporting
a context-specific gene-expression effect.
full_text_unavailable: true
- id: PMID:23209302
title: KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression.
findings: []
- id: PMID:23524970
title: Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal
differentiation.
findings: []
- id: PMID:23698361
title: Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling.
findings:
- statement: PDEdelta regulates farnesylated KRAS localization and signaling.
supporting_text: Correct localization and signalling by farnesylated KRAS is regulated by the
prenyl-binding protein PDEδ
- id: PMID:24415755
title: The chaperone protein SmgGDS interacts with small GTPases entering the prenylation pathway
by recognizing the last amino acid in the CAAX motif.
findings: []
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings: []
- id: PMID:25852190
title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of
potential targets for combination therapy.
findings: []
- id: PMID:26037647
title: Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations.
findings:
- statement: Common KRAS cancer mutants were characterized for nucleotide binding,
intrinsic/GAP-stimulated GTPase activity, and RAF interaction.
supporting_text: we characterized the most common KRAS mutants biochemically for substrate
binding kinetics, intrinsic and
- id: PMID:29239724
title: SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a.
findings:
- statement: K-Ras4a has isoform-specific fatty acylation that regulates endomembrane localization
and ARAF interaction.
supporting_text: SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of
K-Ras4a
- id: PMID:30194290
title: Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a
KRAS-specific vulnerability.
findings: []
- id: PMID:31980649
title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming
levels of KRAS(G13D).
findings: []
- id: PMID:33608534
title: KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights
into RAS-mediated RAF activation.
findings:
- statement: Active KRAS binds RAF1 regulatory domains and supports RAF activation at membranes.
supporting_text: Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active
- id: PMID:35831509
title: 'Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.'
findings:
- statement: SHOC2-MRAS-PP1C is a RAF/MAPK regulatory holophosphatase complex; original
publication could not be cached because NCBI returned HTTP 429.
full_text_unavailable: true
- id: PMID:36175670
title: Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan
syndrome.
findings:
- statement: MRAS is the preferred SHOC2-PP1C partner, while HRAS, KRAS, and NRAS can also bind
with lower affinity.
supporting_text: The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind
SHOC2
- id: PMID:38188543
title: Studying early structural changes in SOS1 mediated KRAS activation mechanism.
findings:
- statement: SOS1 facilitates GDP-to-GTP exchange on KRAS.
supporting_text: SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of
KRAS
- id: PMID:39043660
title: 'Allosteric nanobodies to study the interactions between SOS1 and RAS.'
findings:
- statement: Structural nanobody study involving KRAS; publication could not be cached because
NCBI returned HTTP 429.
full_text_unavailable: true
- id: PMID:39788953
title: Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in
PI3Kα activation.
findings:
- statement: RAS interaction with PI3Kalpha activates/amplifies PI3K-AKT-mTOR signaling.
supporting_text: Their interaction plays a crucial role in activating PI3Kα and amplifying the
PI3K-AKT-mTOR pathway
- id: Reactome:R-HSA-1168636
title: p-RasGRP1,3:DAG cause RAS to exchange GDP for GTP
findings: []
- id: Reactome:R-HSA-1225951
title: SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with
ligand-responsive p-6Y-EGFR mutants)
findings: []
- id: Reactome:R-HSA-1225957
title: SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with
phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)
findings: []
- id: Reactome:R-HSA-1250383
title: RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and
p-Y349,350-SHC1:p-ERBB4
findings: []
- id: Reactome:R-HSA-1306972
title: RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with
phosphorylated ERBB4:ERBB2 heterodimers
findings: []
- id: Reactome:R-HSA-1433471
title: Activation of RAS by p-KIT bound SOS1
findings: []
- id: Reactome:R-HSA-170986
title: Ral-GDS binds to Ras-GTP
findings: []
- id: Reactome:R-HSA-177938
title: SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)
findings: []
- id: Reactome:R-HSA-177945
title: SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)
findings: []
- id: Reactome:R-HSA-186834
title: SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)
findings: []
- id: Reactome:R-HSA-210977
title: Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos)
findings: []
- id: Reactome:R-HSA-2179407
title: SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated)
findings: []
- id: Reactome:R-HSA-2424477
title: SOS mediated nucleotide exchange of RAS (SHC)
findings: []
- id: Reactome:R-HSA-392054
title: NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras
findings: []
- id: Reactome:R-HSA-5218845
title: p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate
findings: []
- id: Reactome:R-HSA-5621573
title: CD209 activate GTPase RAS
findings: []
- id: Reactome:R-HSA-5624486
title: SFKs phosphorylates RAF1 on Y340,Y341
findings: []
- id: Reactome:R-HSA-5624492
title: PAK phosphorylates p21 RAF1 on S338
findings: []
- id: Reactome:R-HSA-5624494
title: RAF1 binds p21 RAS:GTP
findings: []
- id: Reactome:R-HSA-5637806
title: SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFRvIII)
findings: []
- id: Reactome:R-HSA-5637808
title: SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with
phosphorylated SHC1 and p-EGFRvIII)
findings: []
- id: Reactome:R-HSA-5654392
title: Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654402
title: Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654413
title: Activated FGFR3:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654426
title: Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654600
title: Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654618
title: Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654647
title: Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5654663
title: Activated FGFR4:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5655241
title: Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5655277
title: Activated FGFR3 point, translocation and fusion mutants:p-FRS2:GRB2:SOS1 activates RAS
nucleotide exchange
findings: []
- id: Reactome:R-HSA-5655326
title: Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5655347
title: Activated FGFR4 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5658231
title: RAS GAPs stimulate RAS GTPase activity
findings: []
- id: Reactome:R-HSA-5658435
title: RAS GAPs bind RAS:GTP
findings: []
- id: Reactome:R-HSA-5672950
title: '"Activator" RAF:YWHAB dimer binds RAS:GTP'
findings: []
- id: Reactome:R-HSA-5672965
title: RAS GEFs promote RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-5672966
title: RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers
findings: []
- id: Reactome:R-HSA-5672969
title: Phosphorylation of RAF
findings: []
- id: Reactome:R-HSA-5672972
title: MAP2Ks and MAPKs bind to the activated RAF complex
findings: []
- id: Reactome:R-HSA-5672973
title: MAP2Ks phosphorylate MAPKs
findings: []
- id: Reactome:R-HSA-5672978
title: RAF phosphorylates MAP2K dimer
findings: []
- id: Reactome:R-HSA-5672980
title: Dissociation of RAS:RAF complex
findings: []
- id: Reactome:R-HSA-5673001
title: RAF/MAP kinase cascade
findings:
- statement: GTP-bound RAS recruits RAF and promotes RAF activation in the MAPK cascade.
supporting_text: GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its
dimerization and activation
- id: Reactome:R-HSA-5674018
title: BRAP binds RAS:GTP
findings: []
- id: Reactome:R-HSA-5674022
title: BRAP autoubiquitinates
findings: []
- id: Reactome:R-HSA-5675417
title: PEBP1 binds activated RAF1
findings: []
- id: Reactome:R-HSA-5675431
title: PP2A dephosphorylates RAF1
findings: []
- id: Reactome:R-HSA-5675433
title: PP5 dephosphorylates RAF1 S338
findings: []
- id: Reactome:R-HSA-6802834
title: RAS GTPase mutants don't hydrolyze GTP
findings: []
- id: Reactome:R-HSA-6802837
title: Loss-of-function NF1 variants don't stimulate RAS GTPase activity
findings: []
- id: Reactome:R-HSA-6802908
title: RAS mutants bind inactive RAF
findings: []
- id: Reactome:R-HSA-6802914
title: RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs
findings: []
- id: Reactome:R-HSA-6802915
title: Moderate kinase activity BRAF mutants bind RAS:GTP
findings: []
- id: Reactome:R-HSA-6802916
title: RAF is phosphorylated downstream of moderate kinase activity BRAF mutants
findings: []
- id: Reactome:R-HSA-6802918
title: Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants
findings: []
- id: Reactome:R-HSA-6802919
title: RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks
findings: []
- id: Reactome:R-HSA-6802921
title: Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants
findings: []
- id: Reactome:R-HSA-6802922
title: Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS
findings: []
- id: Reactome:R-HSA-6802924
title: RAF is phosphorylated downstream of oncogenic RAS
findings: []
- id: Reactome:R-HSA-6802925
title: Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs
findings: []
- id: Reactome:R-HSA-6802926
title: Mutant RAS:p-RAF complexes phosphorylate MAP2Ks
findings: []
- id: Reactome:R-HSA-6802937
title: Inactive BRAF mutants bind mutant RAS:GTP
findings: []
- id: Reactome:R-HSA-6802941
title: RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
findings: []
- id: Reactome:R-HSA-6802942
title: RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
findings: []
- id: Reactome:R-HSA-6802943
title: RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks
findings: []
- id: Reactome:R-HSA-6803230
title: Dissociation of moderate activity BRAF complexes
findings: []
- id: Reactome:R-HSA-6803233
title: Dissociation of oncogenic RAS:RAF complex
findings: []
- id: Reactome:R-HSA-6803234
title: Dissociation of paradoxically activated RAS:BRAF complexes
findings: []
- id: Reactome:R-HSA-6803240
title: Homo- or heterodimerization of RAF downstream of mutant RAS
findings: []
- id: Reactome:R-HSA-8851827
title: RAS guanyl nucleotide exchange by MET-bound GRB2:SOS1
findings: []
- id: Reactome:R-HSA-8851877
title: RAS guanyl nucleotide exchange by SOS1 associated with RANBP9 and MET
findings: []
- id: Reactome:R-HSA-8851899
title: RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET
findings: []
- id: Reactome:R-HSA-8936676
title: Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize
findings: []
- id: Reactome:R-HSA-8936731
title: Inactive BRAF mutants:mutant RAS:GTP bind RAF1
findings: []
- id: Reactome:R-HSA-8941613
title: Activated FGFR4:p-FRS:p-PTPN11 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-8941618
title: Activated FGFR2:p-FRS:p-PTPN11 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-8941623
title: Activated FGFR1:p-FRS:p-PTPN11 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-8941628
title: Activated FGFR3:p-FRS:p-PTPN11 activates RAS nucleotide exchange
findings: []
- id: Reactome:R-HSA-8981353
title: RASA1 stimulates RAS GTPase activity
findings: []
- id: Reactome:R-HSA-8981355
title: RASA1 binds RAS:GTP
findings: []
- id: Reactome:R-HSA-9607304
title: SOS1-mediated nucleotide exchange of RAS downstream of FLT3
findings: []
- id: Reactome:R-HSA-9632906
title: PRKCZ recruits RAS in response to estrogen stimulation
findings: []
- id: Reactome:R-HSA-9632918
title: PRKCZ stimulates RAS nucleotide exchange in response to estrogen
findings: []
- id: Reactome:R-HSA-9634418
title: RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2
homodimer:p-SHC1
findings: []
- id: Reactome:R-HSA-9647977
title: ICMT methylates S-Farn RAS proteins
findings: []
- id: Reactome:R-HSA-9647978
title: pro-RAS proteins are farnesylated
findings: []
- id: Reactome:R-HSA-9647980
title: mature RAS proteins translocate to plasma membrane
findings:
- statement: RAS post-translational processing supports plasma membrane translocation.
supporting_text: After farnesylation, C-terminal proteolysis, carboxymethylation and
palmitoylation
- id: Reactome:R-HSA-9647982
title: S-farn Me-HRAS, -NRAS and -KRAS4A are palmitoylated
findings: []
- id: Reactome:R-HSA-9647994
title: RAS proteins are depalmitoylated
findings: []
- id: Reactome:R-HSA-9647999
title: RCE1 cleaves S-Farn proRAS proteins
findings: []
- id: Reactome:R-HSA-9649732
title: Mature S-Farn-Me KRAS4B translocates to plasma membrane
findings: []
- id: Reactome:R-HSA-9649733
title: mature p21 RAS binds GDP
findings: []
- id: Reactome:R-HSA-9649735
title: Intrinsic nucleotide exchange on RAS
findings: []
- id: Reactome:R-HSA-9649736
title: RAS intrinsic GTPase activity hydrolyzes GTP to GDP
findings:
- statement: RAS proteins have weak intrinsic GTPase activity that is stimulated by GAP proteins.
supporting_text: RAS proteins have weak intrinsic GTPase activity in the absence of other
effectors
- id: Reactome:R-HSA-9651280
title: RAS GAP mutants aren't stimulated by GAPs
findings: []
- id: Reactome:R-HSA-9653108
title: Raf dimer inhibitors bind RAF heterodimers
findings: []
- id: Reactome:R-HSA-9653503
title: KRAS4B is phosphorylated on serine 181
findings: []
- id: Reactome:R-HSA-9653585
title: S-Farn-Me KRAS4B binds calmodulin
findings: []
- id: Reactome:R-HSA-9653592
title: pS181-S-Farn-Me KRAS4B translocates to the outer mitochondrial membrane
findings: []
- id: Reactome:R-HSA-9653595
title: pS181-S-Farn-Me KRAS4B binds BCL2L1
findings: []
- id: Reactome:R-HSA-9654521
title: Calmodulin dissociates KRAS4B from the plasma membrane
findings: []
- id: Reactome:R-HSA-9654523
title: ARL2:GTP bind PDE6D on KRAS4B
findings: []
- id: Reactome:R-HSA-9654525
title: PDE6D binds S-Farn-Me KRAS4B:CALM:4 Ca2+
findings: []
- id: Reactome:R-HSA-9654533
title: KRAS4B recycles to the plasma membrane
findings: []
- id: Reactome:R-HSA-9656209
title: Dissociation of RAS:RAF1 mutant complex
findings: []
- id: Reactome:R-HSA-9656211
title: MAP2Ks and MAPKs bind to the activated mutant RAF1 complex
findings: []
- id: Reactome:R-HSA-9656212
title: Phosphorylation of RAF1 mutants
findings: []
- id: Reactome:R-HSA-9656213
title: RAF1 mutants show enhanced heterodimerization with BRAF
findings: []
- id: Reactome:R-HSA-9656214
title: MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants
findings: []
- id: Reactome:R-HSA-9656215
title: RAF1 mutant complexes phosphorylate MAP2K dimer
findings: []
- id: Reactome:R-HSA-9657599
title: Dual mechanism MAP2K inhibitors bind MAP2Ks
findings: []
- id: Reactome:R-HSA-9657603
title: Dual mechanism MAPK inhibitors bind MAPKs
findings: []
- id: Reactome:R-HSA-9657606
title: Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks
findings: []
- id: Reactome:R-HSA-9657608
title: Single mechanism MAPK inhibitors bind phosphorylated MAPK
findings: []
- id: Reactome:R-HSA-9658253
title: RAS:GTP binds PI3K
findings: []
- id: Reactome:R-HSA-9664991
title: RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
findings: []
- id: Reactome:R-HSA-9665009
title: RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR
findings: []
- id: Reactome:R-HSA-9665404
title: RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD
mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1
findings: []
- id: Reactome:R-HSA-9665408
title: RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR
through GRB2
findings: []
- id: Reactome:R-HSA-9665700
title: RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants
findings: []
- id: Reactome:R-HSA-9665707
title: RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and
EGFR
findings: []
- id: Reactome:R-HSA-9670436
title: p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS
findings: []
- id: Reactome:R-HSA-9672163
title: SOS-mediated nucleotide exchange on RAS downstream of PDGFRA extracellular domain dimers
findings: []
- id: Reactome:R-HSA-9672170
title: SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors
findings: []
- id: Reactome:R-HSA-9674816
title: p-Y546,Y584-PTPN11 (in CSF3
dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS
findings: []
- id: Reactome:R-HSA-9695853
title: FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS
findings: []
- id: Reactome:R-HSA-9703441
title: SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants
findings: []
- id: file:human/KRAS/KRAS-uniprot.txt
title: UniProt record for human KRAS (P01116)
findings:
- statement: KRAS binds GDP/GTP and has intrinsic GTPase activity.
supporting_text: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
- statement: KRAS cycles between GDP-bound inactive and GTP-bound active forms.
supporting_text: Alternates between an inactive form bound to GDP and an active form bound to
GTP
- statement: KRAS localizes to the cell membrane, endomembrane system, and cytosol.
supporting_text: Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361,
ECO:0000269|PubMed:29239724}; Lipid-anchor
- id: file:human/KRAS/KRAS-deep-research-falcon.md
title: Falcon deep research report on KRAS
findings:
- statement: KRAS intrinsic GTP hydrolysis is slow but real, with kcat ≈ 2×10^-4 s^-1, and is
the central enzymatic activity of the molecular switch.
supporting_text: >-
A widely cited expert synthesis reports Ras intrinsic hydrolysis is slow (kcat ≈ 2×10−4
s−1), but it is a real enzymatic activity central to the molecular switch.
- statement: GAPs accelerate KRAS GTP hydrolysis up to ~10^5-fold via an arginine finger
mechanism; oncogenic Gly12 mutants resist this stimulation.
supporting_text: >-
GAPs accelerate Ras hydrolysis (reported up to ~10^5-fold in expert synthesis) and do so by
complementing the active site, including an external arginine ("arginine finger") concept;
importantly, Gly12 oncogenic mutants are classically noted to resist such stimulation.
- statement: SOS-mediated nucleotide exchange proceeds via stabilization of a nucleotide-free
Ras intermediate, established by the crystal structure of Ras–SOS complex.
supporting_text: >-
Primary structural evidence for Ras activation by SOS comes from the crystal structure of
Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a
nucleotide-free state, a mechanistic basis for GEF-driven exchange.
- statement: Switch I and switch II play distinct roles in SOS-catalyzed nucleotide exchange,
with switch II anchoring Ras to SOS and switch I perturbation promoting GDP dissociation.
supporting_text: >-
Structure-guided mutagenesis further shows distinct roles for Ras switch I vs switch II:
switch II interactions largely anchor Ras to SOS, while switch I perturbation disrupts the
nucleotide-binding site to promote GDP dissociation.
- statement: GTP-loaded Ras directly engages effectors via switch I/II; the Ras–PI3Kγ crystal
structure is a primary demonstration of nucleotide-dependent effector binding.
supporting_text: >-
A primary structural and functional demonstration of Ras effector engagement is the
Ras–PI3Kγ complex: PI3Kγ is directly activated by GTP-loaded Ras, and the structure shows
Ras uses switch I/II to bind the PI3Kγ Ras-binding domain.
- statement: KRAS4A palmitoylation at Cys180 enables reversible Golgi trafficking; combined
farnesylation and palmitoylation increases membrane affinity by >100-fold.
supporting_text: >-
KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent
Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase
membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular
delivery to the plasma membrane.
- statement: KRAS4B uses a polybasic HVR (net charge +8) for electrostatic plasma membrane
association, distinct from KRAS4A's palmitoylation-dependent mechanism.
supporting_text: >-
KRAS4B lacks palmitoylatable cysteines and instead uses a lysine-rich polybasic HVR
(reported net charge +8) to electrostatically stabilize plasma membrane association with
anionic lipids.
- statement: PDE6D binds the KRAS4B prenyl group to support endomembrane-to-plasma-membrane
trafficking; carboxymethylation loss reduces PDE6D affinity >35-fold.
supporting_text: >-
KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and
support trafficking between endomembranes and plasma membrane. Quantitatively summarized
evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by
>35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold.
- statement: Downstream phenotypes from KRAS (proliferation, senescence, apoptosis, transcription,
development) are context-dependent and mostly derived from mutant/overexpression models and
should not be propagated as WT KRAS GO annotations without direct WT evidence.
supporting_text: >-
Downstream phenotypes (proliferation, senescence, apoptosis, transcriptional programs,
developmental and immune/metabolic outcomes) are highly context dependent and often derived
from mutant/overexpression models. These should not be propagated as WT KRAS GO BP
annotations without direct WT evidence.
core_functions:
- molecular_function:
id: GO:0003924
label: GTPase activity
description: KRAS is a Ras-family small GTPase with intrinsic GTP hydrolysis activity. Its active
GTP-bound state is turned off by intrinsic and GAP-stimulated hydrolysis to GDP, making
nucleotide cycling the central molecular switch for KRAS function.
supported_by: *id003
locations:
- id: GO:0009898
label: cytoplasmic side of plasma membrane
- id: GO:0012505
label: endomembrane system
directly_involved_in:
- id: GO:0007265
label: Ras protein signal transduction
- molecular_function:
id: GO:0005525
label: GTP binding
description: GTP-bound KRAS recruits RAF-family kinases and other effectors to propagate
downstream signaling, most prominently the RAF-MEK-ERK MAPK cascade and PI3K-AKT-mTOR branch.
supported_by:
- *id001
- *id002
- *id008
locations:
- id: GO:0005886
label: plasma membrane
directly_involved_in:
- id: GO:0000165
label: MAPK cascade
proposed_new_terms: []
suggested_questions:
- question: Which KRAS4A and KRAS4B functions should be represented as isoform-specific GO
annotations rather than gene-level annotations?
- question: Should SHOC2-PP1C complex annotations be restricted to MRAS, or should weak H/K/NRAS
interactions support non-core annotations?
- question: Can KRAS mitochondrial outer membrane localization be curated as a modification- or
isoform-specific function rather than a general localization?
- question: Should pathway-level proliferation, senescence, and programmed cell death annotations be
retained for KRAS or replaced by more direct Ras/MAPK and PI3K pathway terms?
suggested_experiments:
- description: Endogenous isoform-specific tagging or proteomics to quantify KRAS4A and KRAS4B
localization across plasma membrane, Golgi, ER, endomembrane, cytosol, and mitochondria.
hypothesis: Gene-level KRAS localization annotations conflate distinct KRAS4A and KRAS4B
trafficking mechanisms.
- description: Compare endogenous KRAS, NRAS, HRAS, and MRAS binding to SHOC2-PP1C under matched
nucleotide-loading and membrane conditions.
hypothesis: Canonical RAS isoforms bind SHOC2-PP1C weakly relative to MRAS and should not receive
core phosphatase-complex component annotations.
- description: Use pathway-resolved KRAS perturbation with rescue by GTPase, effector-binding, and
localization mutants to separate direct MAPK/PI3K signaling from downstream proliferation and
gene-expression outcomes.
hypothesis: Most broad biological-process annotations for KRAS are downstream consequences of Ras
effector signaling rather than direct gene-level functions.