Protein RAS* map

Identifiers
HUGO:HRAS, HUGO:KRAS, HUGO:NRAS
NRAS proto-oncogene, GTPase
HUGO:NRAS hgnc_id:HGNC:7989 HGNC:7989 ENTREZ:4893 UNIPROT:P01111
KRAS proto-oncogene, GTPase
HUGO:KRAS hgnc_id:HGNC:6407 HGNC:6407 ENTREZ:3845 UNIPROT:P01116
HRas proto-oncogene, GTPase
HUGO:HRAS hgnc_id:HGNC:5173 HGNC:5173 ENTREZ:3265 UNIPROT:P01112
v-Ha-ras Harvey rat sarcoma viral oncogene homolog
HRAS1
HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112
v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
KRAS2 "v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog"
HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116
neuroblastoma RAS viral (v-ras) oncogene homolog
HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111
RAS p21 protein activator (GTPase activating protein) 1
HUGO:RASA1 HGNC:9871 ENTREZ:5921 UNIPROT:P20936 GENECARDS:RASA1 REACTOME:63760 KEGG:5921 ATLASONC:GC_RASA1 WIKI:RASA1
RAS p21 protein activator 2
HUGO:RASA2 HGNC:9872 ENTREZ:5922 UNIPROT:Q15283 GENECARDS:RASA2 KEGG:5922 ATLASONC:GC_RASA2 WIKI:RASA2
RAS p21 protein activator 3
HUGO:RASA3 HGNC:20331 ENTREZ:22821 UNIPROT:Q14644 GENECARDS:RASA3 KEGG:22821 ATLASONC:GC_RASA3 WIKI:RASA3
RAS p21 protein activator 4
HUGO:RASA4 HGNC:23181 ENTREZ:10156 UNIPROT:O43374 GENECARDS:RASA4 KEGG:10156 WIKI:RASA4
HUGO:HRAS HGNC:5173 ENTREZ:3265 UNIPROT:P01112 GENECARDS:HRAS REACTOME:62718 KEGG:3265 ATLASONC:HRASID108 WIKI:HRAS
HUGO:KRAS HGNC:6407 ENTREZ:3845 UNIPROT:P01116 GENECARDS:KRAS REACTOME:62720 KEGG:3845 ATLASONC:KRASID91 WIKI:KRAS
HUGO:NRAS HGNC:7989 ENTREZ:4893 UNIPROT:P01111 GENECARDS:NRAS REACTOME:62726 KEGG:4893 ATLASONC:NRASID92 WIKI:NRAS

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
 Cancer Associated Fibroblasts  map  / CORE  map
HMC:EVADING_GROWTH_SUPPRESSORS
 Survival  map  / MAPK  map
 Survival  map  / HEDGEHOG  map
 Survival  map  / PI3K_AKT_MTOR  map

References
CASCADE:FGF
CASCADE:EGFR
GASCADE:IGF1R
PMID:12419216
FGF activares RAS in fibroblasts
PMID:16227978
Ras GTPases comprise a large family of mostly membrane-resident proteins that shuttle between an inactive GDP-bound and active GTP-bound conformation105. The best-characterized family members are K-Ras, H-Ras and N-Ras.
RasGTP can bind to a number of effector molecules, including the serine/threonine kinase Raf, phosphatidylinositol 3-kinase, RalGDS and others106. RasGTP recruits these proteins to the membrane compartment, which is crucial for their activation and signalling function. All three Raf family members, A-Raf, B-Raf and Raf-1, bind RasGTP as the first step in their activation process. Whereas RasGTP association might suffice to activate B-Raf, both Raf-1 and A-Raf undergo a complex series of activation steps that have not been entirely elucidated and involve changes in phosphorylation levels and protein interactions. For recent reviews on Raf isoforms and their activation mechanisms see Refs 1???3. All Raf isoforms can activate MAPK and ERK kinase (MEK) by phosphorylating two serines in the MEK ACTIVATION LOOP,
PMID:10567412; PMID:15567848
EGFR activates ERK via GRB2/SOS/RAS/RAF pathway
RasGDP binds to Sos and RasGTP is generated. RasGTP keeps Sos inactive enhancing duration and amplitude of the output.
RasGRP1 activates Golgi-associated Ras on this compartment.
K-Ras is found exclusively at the PM. H- and N-Ras are also present in endomembrane compartments such as the endoplasmic reticulum and the Golgi apparatus.
Processed K-Ras is confined primarily to the PM; however when its polybasic region is phosphorylated or targeted by Ca2+/calmodulin K-Ras relocalises to other endomembrane compartments including Golgi endoplasmic reticulum and mitochondria. In contrast H-Ras and N-Ras constantly shuttle between the Golgi and PM as a result of a constitutive depalmitoylation/repalmitoylation cycle.
H-Ras but not K-Ras signalling was dependent on endocytosis.
PMID:17496910 PMID:16488589 PMID:12782630 PMID:17496910 PMID:19615955
PMID:21102635

RAS*@Plasma Membrane

References
su_mpk1_mpk1_re67( Survival  map ):
Calcium activates the Ras GAP CAPRI (RASA4) that translocates to the PM and downregulates any Ras that is activated on this compartment by the exchange factor SOS.
PMID:16488589
su_mpk1_mpk1_re9( Survival  map ):
Sos mediates Ras activation. Interaction of Sos with Ras induces the formation of RasGTP from RasGDP.
Spry is induced by activated ERK through phosphorylation on Tyr55. It positively regulates EGFR signalling by sequestering Cbl whereas it negatively regulates FGFR signalling by sequestering Grb2 from FSR2.
PMID:17496910 PMID:15173823
su_mpk1_mpk1_re285( Survival  map ):
RasGRP1 activates Golgi-associated Ras on this compartment.

RAS*@Cytoplasm

References
su_akt1_s_akt1_re6( Survival  map ):
PMID:15534002
PMID:9779982
PMID:14585353
su_akt1_s_akt1_re11( Survival  map ):
PMID:15584861
PMID:10648629

RAS*@Cytosol

References
s_shh1_re98:( Survival  map ) PMID:18829525
s_akt1_re6( Survival  map ):
PMID:15534002
PMID:9779982
PMID:14585353
s_akt1_re11( Survival  map ):
PMID:15584861
PMID:10648629

Modifications:
In compartment: Cytoplasm
  1. RAS*@Cytoplasm map
In compartment: Cytosol
  1. RAS*@Cytosol map
In compartment: Plasma Membrane
  1. RAS*@Plasma Membrane map
Participates in complexes:
In compartment: Cytoplasm
  1. GRB2:​MAP3K1|​pho:​RAS*|​pho:​RTK*:​SOS*@Cytoplasm map
  2. GRB2:​MAP3K2_3*|​pho:​RAS*|​pho:​RTK*:​SOS*@Cytoplasm map
In compartment: Cytosol
  1. GDP:​RAS*@Cytosol map
  2. GTP:​RAS*@Cytosol map
In compartment: Endosome
  1. GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map
In compartment: Golgi Apparatus
  1. Ca2+:​DAG:​RAS*|​pho:​RASGRP1@Golgi Apparatus map
  2. Ca2+:​DAG:​RAF1|​pho:​RAS*|​pho:​RASGRP1@Golgi Apparatus map
In compartment: Late Endosomes
  1. GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  2. GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  3. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
In compartment: Lipid Raft
  1. RAS*:​p110*:​p85*@Lipid Raft map
  2. GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map
In compartment: Plasma Membrane
  1. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  2. BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  3. GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  4. BRAF|​pho:​GRB2:​KSR1-NTER*:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  5. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  6. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
Participates in reactions:
As Reactant or Product:
  1. GDP:​RAS*@Cytosol map → map GTP:​RAS*@Cytosol map
  2. GDP:​RAS*@Cytosol map → map GTP:​RAS*@Cytosol map
  3. GDP:​RAS*@Cytosol map + GTP@Cytosol map → map GTP:​RAS*@Cytosol map + GDP@Cytosol map
  4. p110*:​p85*@Cytoplasm map + GRB2:​SOS*@Cytoplasm map + PI3,4,5-P3@Lipid Raft map + RTK*@Cytoplasm map + GF@default map + RAS*@Cytoplasm map + GAB1|​Y977_pho|​Y989_pho@Cytoplasm map → map GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map
  5. GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map → map Ubiquitination@Cytoplasm map
  6. GAB1|​Y977_pho|​Y989_pho:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Lipid Raft map → map GAB1:​GF:​GRB2:​PI3,4,5-P3:​RAS*:​RTK*|​pho|​pho|​hm2:​SOS*:​p110*:​p85*@Endosome map
  7. RAS activation@Cytoplasm map → map RAS*@Cytoplasm map
  8. p110*:​p85*@Cytoplasm map + RAS*@Cytoplasm map → map RAS*:​p110*:​p85*@Lipid Raft map
  9. RAF1@Cytoplasm map + GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  10. GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + RAF1|​pho@Mitochondria map
  11. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + BRAF@Cytoplasm map → map BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  12. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + MAP3K1@Cytoplasm map → map GRB2:​MAP3K1|​pho:​RAS*|​pho:​RTK*:​SOS*@Cytoplasm map
  13. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + MAP3K2_3*@Cytoplasm map → map GRB2:​MAP3K2_3*|​pho:​RAS*|​pho:​RTK*:​SOS*@Cytoplasm map
  14. BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + KSR1:​MEK*@Cytoplasm map → map BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  15. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*@Cytoplasm map → map BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  16. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + LAMTOR2:​MEK*:​MP1*@Late Endosomes map → map GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  17. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map → map GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*@Cytoplasm map + RAF1@Cytoplasm map
  18. RAF1@Cytoplasm map + GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map → map GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  19. ERK*@Cytoplasm map + GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map → map ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  20. RAS*@Plasma Membrane map + Ca2+:​DAG:​RASGRP1@Golgi Apparatus map → map Ca2+:​DAG:​RAS*|​pho:​RASGRP1@Golgi Apparatus map
  21. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map KSR1:​MEK*@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*|​pho|​pho@Cytoplasm map
  22. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map BRAF|​pho:​GRB2:​KSR1-NTER*:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + KSR1-CTER*:​MEK*@Cytoplasm map
  23. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map → map GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*|​pho|​pho@Cytoplasm map
  24. RAF1@Cytoplasm map + Ca2+:​DAG:​RAS*|​pho:​RASGRP1@Golgi Apparatus map → map Ca2+:​DAG:​RAF1|​pho:​RAS*|​pho:​RASGRP1@Golgi Apparatus map
  25. GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map RAS*@Plasma Membrane map + GRB2:​RTK*:​SOS*@Plasma Membrane map
  26. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map → map ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  27. RAS*@Plasma Membrane map + GRB2:​RTK*:​SOS*@Plasma Membrane map → map GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  28. RAS activation@Cytosol map → map RAS*@Cytosol map
As Catalyser:
  1. GDP:​RAF1@Cytosol map → map GTP:​RAF1@Cytosol map
  2. RAF*@Cytosol map → map RAF*@Cytosol map
  3. PtdIns(4,5)-P2@Lipid Raft map → map PI3,4,5-P3@Lipid Raft map
  4. MAP2K4@Cytoplasm map → map MAP2K4|​pho|​pho@Cytoplasm map
  5. MAP2K7@Cytoplasm map → map MAP2K7|​pho|​pho@Cytoplasm map
  6. MAP2K6@Cytoplasm map → map MAP2K6|​pho|​pho@Cytoplasm map
  7. MEK*@Cytoplasm map → map MEK*|​pho|​pho@Cytoplasm map
  8. IMP*:​KSR1:​MEK*@Cytoplasm map → map IMP*@Cytoplasm map + KSR1:​MEK*@Cytoplasm map
  9. ERK*:​MEK*:​SEF*@Golgi Apparatus map → map ERK*|​pho|​pho:​MEK*|​pho|​pho:​SEF*@Cytoplasm map
  10. SUFU@Cytosol map + SIL*@Cytosol map → map SIL*:​SUFU@Cytosol map