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What Do We Mean By "RAS Pathway"?

October 22, 2014, by Frank McCormick

Frank McCormick, Ph.D.

Dr. Frank McCormick directs the research efforts of the RAS Initiative at FNLCR.

Dear all,

We are planning a paper that presents a RAS-centric view of the data in TCGA.  This will be a collaboration between Gaddy Getz and colleagues at the Broad, and Bob Stephens and colleagues at the Frederick National Lab and others. The aim is to provide a synopsis of expression patterns, mutations and copy number changes, and several other parameters relevant to the RAS pathway across the  different tumor types.

As you all know, this pathway can be defined in various ways. For purposes of interrogating TCGA data we have used gene names from the Broad Tumor Portal. Some may not be familiar to you. For example, I hadn’t realized that ARHGAP35, which is mutated at quite a high frequency, is actually  p190RhoGAP, made popular by Jeff Settleman. Matt Meyerson kindly pointed this out to me.

 

ras pathway genes

The diagram shows 118 genes arranged in 36 groups containing one to eleven genes per group.  The proteins represented by gene names in a group are thought to carry out similar, but probably not identical, functions. Gene names separated by periods represent proteins believed to form physical complexes. At the top of the diagram "growth factors" signal through receptors and messengers to the three RAS proteins. The RAS proteins in turn signal through three alternative pathways to affect many downstream targets including TP53, RB1, and MTOR.  Arrows represent activation signals, dotted  "T" lines represent inhibitory signals. The bracket connecting KSR1 and KSR2 to the RAF, MAP2K, and MAPK genes represents a scaffolding function.

Anyway, we'd be very grateful  if you could send suggestions for genes that we missed or errors in the pathway diagram.  Any other suggestions for making this effort more useful would be welcome, particularly in the context of how to best share the TCGA data in the most useful way possible.

Provide your feedback by commenting below or email me at SolveRAS@nih.gov.

Cheers,

Frank

 

Gene Names, Cognate Proteins, and Aliases in the RAS Pathway

The table comprises the name of each human gene in the RAS Pathway diagram,  the name of the cognate protein for each gene, and gene aliases (alternative names).  The aliases in bold are gene names more commonly used by RAS researchers.

Gene name Protein name from Uniprot or BioGPS Alternative gene names from BioGPS
AKT1 RAC-alpha serine/threonine-protein kinase AKT, CWS6, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA
AKT2 RAC-beta serine/threonine-protein kinase  HIHGHH, PKBB, PKBBETA, PRKBB, RAC-BETA
AKT3 RAC-gamma serine/threonine-protein kinase MPPH, MPPH2, PKB-GAMMA, PKBG, PRKBG, RAC-PK-gamma, RAC-gamma, STK-2
ALK Anaplastic lymphoma receptor tyrosine kinase; ALK tyrosine kinase receptor CD246, NBLST3
ARAF Serine/threonine-protein kinase A-Raf  A-RAF, ARAF1, PKS2, RAFA1
ARHGAP35 Rho GTPase-activating protein 35  GRF-1, GRLF1, P190-A, P190A, p190ARhoGAP, p190RhoGAP
BRAF Serine/threonine-protein kinase B-raf  B-RAF1, BRAF1, NS7, RAFB1
CCND1 Cyclin D1 BCL1, D11S287E, PRAD1, U21B31
CDK4 Cyclin-dependent kinase 4 CMM3, PSK-J3
CDK6 Cyclin-dependent kinase 6 PLSTIRE
DUSP1 Dual specificity phosphatase 1 CL100, HVH1, MKP-1, MKP1, PTPN10
DUSP2 Dual specificity phosphatase 2 PAC-1, PAC1
DUSP3 Dual specificity phosphatase 3 VHR
DUSP4 Dual specificity phosphatase 4 HVH2, MKP-2, MKP2, TYP
DUSP5 Dual specificity phosphatase 5 DUSP, HVH3
DUSP6 Dual specificity phosphatase 6 HH19, MKP3, PYST1
EGFR Epidermal growth factor receptor ERBB, ERBB1, HER1, PIG61, mENA
EIF4EBP1 Eukaryotic translation initiation factor 4E-binding protein 1  4E-BP1, 4EBP1, BP-1, PHAS-I
ERBB2 Receptor tyrosine-protein kinase erbB-2 CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1
ETS1 v-ets avian erythroblastosis virus E26 oncogene homolog 1 ETS-1, EWSR2, p54
ETS2 v-ets avian erythroblastosis virus E26 oncogene homolog 2 ETS2IT1
FGFR1 Fibroblast growth factor receptor 1 BFGFR, CD331, CEK, FGFBR, FGFR-1, FLG, FLT-2, FLT2, HBGFR, HH2, HRTFDS, KAL2, N-SAM, OGD, bFGF-R-1
FGFR2 Fibroblast growth factor receptor 2 BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25
FGFR3 Fibroblast growth factor receptor 3 CH, CD333, CEK2, HSFGFR3EX, JTK4
FGFR4 Fibroblast growth factor receptor 4 CD334, JTK2, TKF
FOS FBJ murine osteosarcoma viral oncogene homolog AP-1, C-FOS, p55
GRB2 Growth factor receptor-bound protein 2  ASH, EGFRBP-GRB2, Grb3-3, MST084, MSTP084, NCKAP2
HRAS GTPase HRas C-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV, HRAS1, RASH1, p21ras
JUN Jun proto-oncogene AP-1, AP1, c-Jun
KRAS GTPase KRas C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, KI-RAS, KRAS1, KRAS2, NS, NS3, RASK2
KSR1 Kinase suppressor of Ras 1  KSR, RSU2
KSR2 Kinase suppressor of Ras 2 [none]
MAP2K1 Dual specificity mitogen-activated protein kinase kinase 1 CFC3, MAPKK1, MEK1, MKK1, PRKMK1
MAP2K2 Dual specificity mitogen-activated protein kinase kinase 2 CFC4, MAPKK2, MEK2, MKK2, PRKMK2
MAPK1 Mitogen-activated protein kinase 1  ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK
MAPK3 Mitogen-activated protein kinase 3 ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK
MDM2 MDM2 proto-oncogene, E3 ubiquitin protein ligase ACTFS, HDMX, hdm2
MET MET proto-oncogene, receptor tyrosine kinase; hepatocyte growth factor receptor AUTS9, HGFR, RCCP2, c-Met
MLST8 MTOR associated protein, LST8 homolog (S. cerevisiae) GBL, GbetaL, LST8, POP3, WAT1
MTOR Mechanistic target of rapamycin (serine/threonine kinase) FRAP, FRAP1, FRAP2, RAFT1, RAPT1
NF1 Neurofibromin NFNS, VRNF, WSS
NRAS GTPase NRas ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6
PAK1 p21 protein (Cdc42/Rac)-activated kinase 1 PAKalpha
PAK2 p21 protein (Cdc42/Rac)-activated kinase 2 PAK65, PAKgamma
PAK3 p21 protein (Cdc42/Rac)-activated kinase 3  CDKN1A, MRX30, MRX47, OPHN3, PAK3beta, bPAK, hPAK3
PAK4 p21 protein (Cdc42/Rac)-activated kinase 4 [none]
PDGFRA Platelet-derived growth factor receptor alpha CD140A, PDGFR-2, PDGFR2, RHEPDGFRA
PDGFRB Platelet-derived growth factor receptor beta CD140B, IBGC4, IMF1, JTK12, PDGFR, PDGFR-1, PDGFR1
PDPK1 3-phosphoinositide-dependent protein kinase 1  PDK1, PDPK2, PRO0461
PIK3CA Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform  CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, p110-alpha
PIK3CB Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform  P110BETA, PI3K, PI3KBETA, PIK3C1
PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta APDS, IMD14, P110DELTA, PI3K, p110D
PIK3R1 Phosphatidylinositol 3-kinase regulatory subunit alpha AGM7, GRB1, p85, p85-ALPHA
PIK3R2 Phosphatidylinositol 3-kinase regulatory subunit beta MPPH, MPPH1, P85B, p85, p85-BETA
PIK3R3 Phosphatidylinositol 3-kinase regulatory subunit gamma p55, p55-GAMMA
PIK3R4 Phosphoinositide 3-kinase regulatory subunit 4  VPS15, p150
PIK3R5 Phosphoinositide 3-kinase regulatory subunit 5 F730038I15Rik, FOAP-2, P101-PI3K, p101
PIK3R6 Phosphoinositide 3-kinase regulatory subunit 6   C17orf38, HsT41028, p84 PIKAP, p87(PIKAP), p87PIKAP
PRKAA1 5'-AMP-activated protein kinase catalytic subunit alpha-1 AMPK, AMPKa1
PRKAA2 5'-AMP-activated protein kinase catalytic subunit alpha-2   AMPK, AMPK2, AMPKa2, PRKAA
PRKAB1 5'-AMP-activated protein kinase subunit beta-1   AMPK, HAMPKb
PRKAB2 5'-AMP-activated protein kinase subunit beta-2 [none]
PRKAG1 Protein kinase, AMP-activated, gamma 1 non-catalytic subunit AMPKG
PRKAG2 Protein kinase, AMP-activated, gamma 2 non-catalytic subunit AAKG, AAKG2, CMH6, H91620p, WPWS
PRKAG3 Protein kinase, AMP-activated, gamma 3 non-catalytic subunit AMPKG3
PTEN Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN 10q23del, BZS, CWS1, DEC, GLM2, MHAM, MMAC1, PTEN1, TEP1
RAC1 Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) Rac-1, TC-25, p21-Rac1
RAC2 Ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) EN-7, Gx, HSPC022, p21-Rac2
RAC3 Ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [none]
RAF1 RAF proto-oncogene serine/threonine-protein kinase CMD1NN, CRAF, NS5, Raf-1, c-Raf
RALA Ras-related protein Ral-A RAL
RALB Ras-related protein Ral-B [none]
RALGDS Ral guanine nucleotide dissociation stimulator   RGDS, RGF, RalGEF
RASA1 Ras GTPase-activating protein 1  CM-AVM, CMAVM, GAP, PKWS, RASA, RASGAP, p120GAP, p120RASGAP
RASA2 Ras GTPase-activating protein 2 GAP1M
RASA3 Ras GTPase-activating protein 3 GAP1IP4BP, GAPIII
RASAL1 RasGAP-activating-like protein 1  RASAL
RASAL2 Ras GTPase-activating protein nGAP  NGAP
RASAL3 RAS protein activator like-3  [none]
RASGRF2 Ras-specific guanine nucleotide-releasing factor 2 GRF2, RAS-GRF2
RASGRP1 RAS guanyl-releasing protein 1 CALDAG-GEFI, CALDAG-GEFII, RASGRP, V, hRasGRP1
RASGRP2 RAS guanyl-releasing protein 2 CALDAG-GEFI, CDC25L
RASGRP3 Ras guanyl-releasing protein 3  GRP3, KIAA0846
RASGRP4 RAS guanyl-releasing protein 4 [none]
RB1 Retinoblastoma 1 OSRC, PPP1R130, RB, p105-Rb, pRb, pp110
RHEB Ras Homolog Enriched In Brain, GTP-binding protein Rheb RHEB2
RHOA Ras homolog family member A ARH12, ARHA, RHO12, RHOH12
RHOB Ras homolog family member B ARH6, ARHB, MST081, MSTP081, RHOH6
RHOC Ras homolog family member C ARH9, ARHC, H9, RHOH9
ROCK1 Rho-associated, coiled-coil containing protein kinase 1 P160ROCK, ROCK-I
ROCK2 Rho-associated, coiled-coil containing protein kinase 2 ROCK-II
ROS1 ROS proto-oncogene 1 , receptor tyrosine kinase MCF3, ROS, c-ros-1
RPS6KA1 Ribosomal protein S6 kinase alpha-1   MAPKAPK1A, RSK1
RPS6KA2 Ribosomal protein S6 kinase alpha-2   HU-2, MAPKAPK1C, RSK, RSK3, S6K-alpha, S6K-alpha2, p90-RSK3, pp90RSK3
RPS6KA3 Ribosomal protein S6 kinase alpha-3   CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK, RSK2, S6K-alpha3, p90-RSK2, pp90RSK2
RPS6KA4 Ribosomal protein S6 kinase alpha-4   MSK2, RSK-B
RPS6KA5 Ribosomal protein S6 kinase alpha-5 MSK1, MSPK1, RLPK
RPS6KA6 Ribosomal protein S6 kinase alpha-6 PP90RSK4, RSK4
RPTOR Regulatory associated protein of MTOR, complex 1 KOG1, Mip1
SHC1 SHC (Src homology 2 domain containing) transforming protein 1 SHC, SHCA
SHC2 SHC (Src homology 2 domain containing) transforming protein 2 SCK, SHCB, SLI
SHC3 SHC (Src homology 2 domain containing) transforming protein 3 N-Shc, NSHC, RAI, SHCC
SHC4 SHC (Src homology 2 domain containing) transforming protein 4 RaLP, SHCD
SOS1 Son of sevenless homolog 1 GF1, GGF1, GINGF, HGF, NS4
SOS2 Son of sevenless homolog 2 [none]
SPRED1 Sprouty-related, EVH1 domain-containing protein 1 NFLS, PPP1R147, hSpred1, spred-1
SPRED2 Sprouty-related, EVH1 domain-containing protein 2  Spred-2
SPRED3 Sprouty-related, EVH1 domain-containing protein 3  Eve-3, spred-3
SPRY1 Protein sprouty homolog 1  hSPRY1
SPRY2 Protein sprouty homolog 2  hSPRY2
SPRY3 Protein sprouty homolog 3 HSPRY3, spry-3
SPRY4 Protein sprouty homolog 4   HH17
STK11 Serine/threonine-protein kinase STK11 LKB1, PJS, hLKB1
TIAM1 T-lymphoma invasion and metastasis-inducing protein 1 [none]
TIAM2 T-lymphoma invasion and metastasis-inducing protein 2 STEF, TIAM-2
TP53 tumor protein p53 BCC7, LFS1, P53, TRP53
TSC1 Tuberous Sclerosis 1, Hamartin LAM, TSC
TSC2 Tuberous Sclerosis 2,  Tuberin LAM, PPP1R160, TSC4

 

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