Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.
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A constitutive de/re-palmitoylation acylation cycle drives rapid exchange of N-Ras between the plasma membrane and the Golgi apparatus.
"the specific subcellular distribution of H- and Nras guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus."
Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells.
Defining the membrane proteome of NK cells.
Ras membrane orientation and nanodomain localization generate isoform diversity.
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
ERK and PDE4 cooperate to induce RAF isoform switching in melanoma.
PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus.
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NRAS localizes to and is activated at the Golgi apparatus; Golgi-resident PAQR10/PAQR11 bind NRAS and elevate its Golgi localization and activation.
"Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B."
KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression.
MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.
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NRAS is a target of miR-146a in endothelial cells; miR-146a downregulates NRAS and attenuates angiogenesis, implicating NRAS in endothelial cell proliferation.
"which attenuated angiogenesis through downregulation of NRAS."
ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.
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ABHD17 depalmitoylase activity controls N-Ras palmitate turnover and relocalization between plasma membrane and internal membranes.
"ABHD17 catalytic activity is required for N-Ras depalmitoylation and re-localization to internal cellular membranes."
Architecture of the human interactome defines protein communities and disease networks.
Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability.
Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis.
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STK19 phosphorylates NRAS at Ser-89 to enhance binding to downstream effectors, promoting oncogenic NRAS signaling; provides direct evidence for NRAS GTPase/signal transduction function.
"STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation."
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Activating NRAS mutations are common in melanoma.
"Activating mutations in NRAS account for 20%-30% of melanoma."
GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
A reference map of the human binary protein interactome.
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.
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Active GTP-bound NRAS (like other RAS isoforms) can bind SHOC2 and PP1C to form a holophosphatase complex that promotes RAF activation and positively regulates Ras/MAPK signaling.
"SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS"
A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions.
Multimodal cell maps as a foundation for structural and functional genomics.
p-RasGRP1,3:DAG cause RAS to exchange GDP for GTP
SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants)
SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
Activation of RAS by p-KIT bound SOS1
SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)
SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)
SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)
Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos)
SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated)
SOS mediated nucleotide exchange of RAS (SHC)
NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras
p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate
CD209 activate GTPase RAS
SFKs phosphorylates RAF1 on Y340,Y341
PAK phosphorylates p21 RAF1 on S338
SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFRvIII)
SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII)
Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR3:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR4:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR3 point, translocation and fusion mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
Activated FGFR4 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange
RAS GAPs stimulate RAS GTPase activity
"Activator" RAF:YWHAB dimer binds RAS:GTP
RAS GEFs promote RAS nucleotide exchange
RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers
MAP2Ks and MAPKs bind to the activated RAF complex
MAP2Ks phosphorylate MAPKs
RAF phosphorylates MAP2K dimer
Dissociation of RAS:RAF complex
PEBP1 binds activated RAF1
PP2A dephosphorylates RAF1
PP5 dephosphorylates RAF1 S338
Exocytosis of tertiary granule membrane proteins
RAS GTPase mutants don't hydrolyze GTP
Loss-of-function NF1 variants don't stimulate RAS GTPase activity
RAS mutants bind inactive RAF
RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs
Moderate kinase activity BRAF mutants bind RAS:GTP
RAF is phosphorylated downstream of moderate kinase activity BRAF mutants
Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants
RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks
Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants
Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS
RAF is phosphorylated downstream of oncogenic RAS
Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs
Mutant RAS:p-RAF complexes phosphorylate MAP2Ks
Inactive BRAF mutants bind mutant RAS:GTP
RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks
Dissociation of moderate activity BRAF complexes
Dissociation of oncogenic RAS:RAF complex
Dissociation of paradoxically activated RAS:BRAF complexes
Homo- or heterodimerization of RAF downstream of mutant RAS
RAS guanyl nucleotide exchange by MET-bound GRB2:SOS1
RAS guanyl nucleotide exchange by SOS1 associated with RANBP9 and MET
RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET
Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize
Inactive BRAF mutants:mutant RAS:GTP bind RAF1
Activated FGFR4:p-FRS:p-PTPN11 activates RAS nucleotide exchange
Activated FGFR2:p-FRS:p-PTPN11 activates RAS nucleotide exchange
Activated FGFR1:p-FRS:p-PTPN11 activates RAS nucleotide exchange
Activated FGFR3:p-FRS:p-PTPN11 activates RAS nucleotide exchange
RASA1 stimulates RAS GTPase activity
SOS1-mediated nucleotide exchange of RAS downstream of FLT3
PRKCZ recruits RAS in response to estrogen stimulation
PRKCZ stimulates RAS nucleotide exchange in response to estrogen
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1
ICMT methylates S-Farn RAS proteins
pro-RAS proteins are farnesylated
mature RAS proteins translocate to plasma membrane
S-farn Me-HRAS, -NRAS and -KRAS4A are palmitoylated
RAS proteins are depalmitoylated
RCE1 cleaves S-Farn proRAS proteins
Intrinsic nucleotide exchange on RAS
RAS intrinsic GTPase activity hydrolyzes GTP to GDP
RAS GAP mutants aren't stimulated by GAPs
Raf dimer inhibitors bind RAF heterodimers
Dissociation of RAS:RAF1 mutant complex
MAP2Ks and MAPKs bind to the activated mutant RAF1 complex
Phosphorylation of RAF1 mutants
RAF1 mutants show enhanced heterodimerization with BRAF
MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants
RAF1 mutant complexes phosphorylate MAP2K dimer
Dual mechanism MAP2K inhibitors bind MAP2Ks
Dual mechanism MAPK inhibitors bind MAPKs
Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks
Single mechanism MAPK inhibitors bind phosphorylated MAPK
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR
RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR through GRB2
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR
p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS
SOS-mediated nucleotide exchange on RAS downstream of PDGFRA extracellular domain dimers
SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors
FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS
SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants
UniProtKB P01111 (RASN_HUMAN) GTPase NRas record
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NRAS binds GDP/GTP and possesses intrinsic GTPase activity (EC 3.6.5.2), cycling between GDP-bound inactive and GTP-bound active states under GEF/GAP control.
"Ras proteins bind GDP/GTP and possess intrinsic GTPase activity."
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NRAS is a lipid-anchored peripheral membrane protein on the cytoplasmic side of the cell membrane and Golgi apparatus membrane, shuttling between the two.
"Note=Shuttles between the plasma membrane and the Golgi apparatus."
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NRAS is farnesylated at Cys-186 and palmitoylated at Cys-181; palmitoylation by ZDHHC9-GOLGA7 and depalmitoylation by ABHD17A/B/C regulate PM-Golgi exchange.
"A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi"
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Oncogenic codon 12/13/61 mutations impair GTP hydrolysis and lock NRAS in the active GTP-bound state, transforming cells.
"Mutations which change AA 12, 13 or 61 activate the potential of Ras to transform cultured cells and are implicated in a variety of human tumors."