BioPAX pathway converted from "Grb2 events in EGFR signaling" in the Reactome database. Grb2 events in EGFR signaling Grb2 events in EGFR signaling Autophosphorylation of tyrosine residues are docking sites for many downstream effectors in EGFR signaling. SH2-containing phosphotyrosine-binding domains of adaptor proteins like GRB2 is one such example. GRB2 is constitutively associated with SOS, a guanine nucleotide exchange factor of Ras. GRB2 binding to phosphorylated EGFR results in the recruitment of SOS to the plasma membrane where it comes in proximity to Ras. This mechanism has been seen to be the model for Ras activation. Authored: Castagnoli, L, 2006-10-10 13:09:34 Reviewed: Heldin, CH, 2008-02-12 09:44:02 Grb2 binds Sos Grb2 binds Sos In the cytoplasm of unstimulated cells, SOS is found in a complex with GRB2. The interaction occurs between the carboxy terminal domain of SOS and the Src homology 3 (SH3) domains of GRB2. Authored: Charalambous, M, 2005-01-07 11:17:43 Reviewed: Heldin, CH, 2008-02-12 09:44:02 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 74686 1 cytosol GO 0005829 GRB-2 - SH2 domain GRB-2 - SH2 domain GRB-2 - SH3 domain GRB-2 - SH3 domain UniProt:P62993-1 RecName: Full=Growth factor receptor-bound protein 2; AltName: Full=Adapter protein GRB2; AltName: Full=SH2/SH3 adapter GRB2; AltName: Full=Protein Ash; GN Name=GRB2; Synonyms=ASH; OS Homo sapiens (Human) ASH GRB2 FUNCTION: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. FUNCTION: Isoform GRB3-3 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. SUBUNIT: Associates with activated Tyr-phosphorylated EGF receptors and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains (By similarity). Interacts with HCV NS5A via its SH3 domains. Interacts with CBL and CBLB. Interacts with JUB and MIST (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with PRNP (By similarity). Interacts with RALGPS1 and with HCST. Interacts (via SH3 domain) with HEV ORF3 protein. INTERACTION: O92972:- (xeno); NbExp=2; IntAct=EBI-401755, EBI-710506; P26660:- (xeno); NbExp=1; IntAct=EBI-401755, EBI-706322; P27958:- (xeno); NbExp=3; IntAct=EBI-401755, EBI-706378; Q92936:-; NbExp=1; IntAct=EBI-401755, EBI-1760181; Q92937:-; NbExp=1; IntAct=EBI-401755, EBI-1760197; Q9WMX2:- (xeno); NbExp=1; IntAct=EBI-401755, EBI-710918; P00519:ABL1; NbExp=1; IntAct=EBI-401755, EBI-375543; P42684:ABL2; NbExp=1; IntAct=EBI-401755, EBI-1102694; P51816:AFF2; NbExp=1; IntAct=EBI-401755, EBI-1754468; Q15109:AGER; NbExp=1; IntAct=EBI-401755, EBI-1646426; O43918:AIRE; NbExp=1; IntAct=EBI-401755, EBI-1753081; Q9Y2D5:AKAP2; NbExp=1; IntAct=EBI-401755, EBI-1754555; Q13023:AKAP6; NbExp=1; IntAct=EBI-401755, EBI-1056102; Q01484:ANK2; NbExp=1; IntAct=EBI-401755, EBI-941975; Q9BWW9:APOL5; NbExp=1; IntAct=EBI-401755, EBI-1753592; O15085:ARHGEF11; NbExp=1; IntAct=EBI-401755, EBI-311099; Q96NS5:ASB16; NbExp=1; IntAct=EBI-401755, EBI-1751918; Q8IXJ9:ASXL1; NbExp=1; IntAct=EBI-401755, EBI-1646500; Q92934:BAD; NbExp=1; IntAct=EBI-401755, EBI-700771; P48634:BAT2; NbExp=1; IntAct=EBI-401755, EBI-347545; Q9UIF9:BAZ2A; NbExp=1; IntAct=EBI-401755, EBI-934890; O00499:BIN1; NbExp=1; IntAct=EBI-401755, EBI-719094; P51587:BRCA2; NbExp=1; IntAct=EBI-401755, EBI-79792; O60885:BRD4; NbExp=1; IntAct=EBI-401755, EBI-723869; Q9ULD4:BRPF3; NbExp=1; IntAct=EBI-401755, EBI-1753470; P13671:C6; NbExp=1; IntAct=EBI-401755, EBI-1753221; P20810:CAST; NbExp=1; IntAct=EBI-401755, EBI-1268770; P32239:CCKBR; NbExp=1; IntAct=EBI-401755, EBI-1753137; P46092:CCR10; NbExp=1; IntAct=EBI-401755, EBI-348022; P30260:CDC27; NbExp=1; IntAct=EBI-401755, EBI-994813; O76039:CDKL5; NbExp=1; IntAct=EBI-401755, EBI-1752465; Q9NYQ7:CELSR3; NbExp=1; IntAct=EBI-401755, EBI-308417; Q15027:CENTB1; NbExp=1; IntAct=EBI-401755, EBI-751746; Q9H2X0:CHRD; NbExp=1; IntAct=EBI-401755, EBI-947551; Q14008:CKAP5; NbExp=1; IntAct=EBI-401755, EBI-310585; P26992:CNTFR; NbExp=1; IntAct=EBI-401755, EBI-743758; P78357:CNTNAP1; NbExp=1; IntAct=EBI-401755, EBI-1751903; Q8WX92:COBRA1; NbExp=1; IntAct=EBI-401755, EBI-347721; P26998:CRYBB3; NbExp=1; IntAct=EBI-401755, EBI-1965681; O95319:CUGBP2; NbExp=1; IntAct=EBI-401755, EBI-949790; P25106:CXCR7; NbExp=1; IntAct=EBI-401755, EBI-1965291; P78329:CYP4F2; NbExp=1; IntAct=EBI-401755, EBI-1752413; P98082:DAB2; NbExp=1; IntAct=EBI-401755, EBI-1171238; Q14118:DAG1; NbExp=1; IntAct=EBI-401755, EBI-1755945; P14868:DARS; NbExp=1; IntAct=EBI-401755, EBI-358730; Q9ULH1:DDEF1; NbExp=1; IntAct=EBI-401755, EBI-346622; O43150:DDEF2; NbExp=1; IntAct=EBI-401755, EBI-310968; P78352:DLG4; NbExp=1; IntAct=EBI-401755, EBI-80389; O14490:DLGAP1; NbExp=1; IntAct=EBI-401755, EBI-1753207; Q9P1A6:DLGAP2; NbExp=1; IntAct=EBI-401755, EBI-1753397; O95886:DLGAP3; NbExp=1; IntAct=EBI-401755, EBI-1752541; Q9Y2H0:DLGAP4; NbExp=1; IntAct=EBI-401755, EBI-722139; Q92988:DLX4; NbExp=1; IntAct=EBI-401755, EBI-1752755; Q05193:DNM1; NbExp=2; IntAct=EBI-401755, EBI-713135; Q14185:DOCK1; NbExp=1; IntAct=EBI-401755, EBI-446740; Q8IZD9:DOCK3; NbExp=1; IntAct=EBI-401755, EBI-1752361; Q9H1R2:DUSP15; NbExp=1; IntAct=EBI-401755, EBI-1752795; Q9H8V3:ECT2; NbExp=1; IntAct=EBI-401755, EBI-1054039; O43281:EFS; NbExp=1; IntAct=EBI-401755, EBI-718488; P00533:EGFR; NbExp=2; IntAct=EBI-401755, EBI-297353; Q96KQ7:EHMT2; NbExp=1; IntAct=EBI-401755, EBI-744366; O15371:EIF3D; NbExp=1; IntAct=EBI-401755, EBI-353818; P41970:ELK3; NbExp=1; IntAct=EBI-401755, EBI-1758534; P54762:EPHB1; NbExp=1; IntAct=EBI-401755, EBI-80252; P42566:EPS15; NbExp=1; IntAct=EBI-401755, EBI-396684; Q92935:EXTL1; NbExp=1; IntAct=EBI-401755, EBI-1760167; O43909:EXTL3; NbExp=1; IntAct=EBI-401755, EBI-1754679; O00254:F2RL2; NbExp=1; IntAct=EBI-401755, EBI-1751853; Q9BQ89:FAM110A; NbExp=1; IntAct=EBI-401755, EBI-1752811; O15360:FANCA; NbExp=1; IntAct=EBI-401755, EBI-81570; P31994:FCGR2B; NbExp=1; IntAct=EBI-401755, EBI-724784; P31995:FCGR2C; NbExp=1; IntAct=EBI-401755, EBI-1396036; P21333:FLNA; NbExp=1; IntAct=EBI-401755, EBI-350432; O75369:FLNB; NbExp=1; IntAct=EBI-401755, EBI-352089; Q14315:FLNC; NbExp=1; IntAct=EBI-401755, EBI-489954; O75593:FOXH1; NbExp=1; IntAct=EBI-401755, EBI-1759806; Q92949:FOXJ1; NbExp=1; IntAct=EBI-401755, EBI-1760377; Q96I24:FUBP3; NbExp=1; IntAct=EBI-401755, EBI-954200; Q9UBS5:GABBR1; NbExp=1; IntAct=EBI-401755, EBI-724156; Q99259:GAD1; NbExp=1; IntAct=EBI-401755, EBI-743184; Q92947:GCDH; NbExp=1; IntAct=EBI-401755, EBI-1236978; P10912:GHR; NbExp=1; IntAct=EBI-401755, EBI-286316; Q9NZM4:GLTSCR1; NbExp=1; IntAct=EBI-401755, EBI-1754943; P15586:GNS; NbExp=1; IntAct=EBI-401755, EBI-1752200; Q9Y5Y3:GPR45; NbExp=1; IntAct=EBI-401755, EBI-1751869; Q13322:GRB10; NbExp=1; IntAct=EBI-401755, EBI-80275; Q9C0E4:GRIP2; NbExp=1; IntAct=EBI-401755, EBI-949557; O43708:GSTZ1; NbExp=1; IntAct=EBI-401755, EBI-748043; Q9UL51:HCN2; NbExp=1; IntAct=EBI-401755, EBI-1751885; Q6NVY1:HIBCH; NbExp=1; IntAct=EBI-401755, EBI-1965197; P05204:HMGN2; NbExp=1; IntAct=EBI-401755, EBI-1758689; Q15651:HMGN3; NbExp=1; IntAct=EBI-401755, EBI-1758705; O43390:HNRNPR; NbExp=1; IntAct=EBI-401755, EBI-713419; P31273:HOXC8; NbExp=1; IntAct=EBI-401755, EBI-1752118; P47928:ID4; NbExp=1; IntAct=EBI-401755, EBI-1754719; P31785:IL2RG; NbExp=1; IntAct=EBI-401755, EBI-80475; P26951:IL3RA; NbExp=1; IntAct=EBI-401755, EBI-1757512; Q01344:IL5RA; NbExp=1; IntAct=EBI-401755, EBI-1759442; Q9H9L3:ISG20L2; NbExp=1; IntAct=EBI-401755, EBI-751335; O60674:JAK2; NbExp=1; IntAct=EBI-401755, EBI-518647; Q92953:KCNB2; NbExp=1; IntAct=EBI-401755, EBI-1760439; Q9NS40:KCNH7; NbExp=1; IntAct=EBI-401755, EBI-1759868; Q92952:KCNN1; NbExp=1; IntAct=EBI-401755, EBI-1748210; P51787:KCNQ1; NbExp=1; IntAct=EBI-401755, EBI-359667; Q07666:KHDRBS1; NbExp=2; IntAct=EBI-401755, EBI-1364; Q92945:KHSRP; NbExp=1; IntAct=EBI-401755, EBI-1049099; Q9H1H9:KIF13A; NbExp=1; IntAct=EBI-401755, EBI-1759129; O43561:LAT; NbExp=1; IntAct=EBI-401755, EBI-1222766; P48357:LEPR; NbExp=1; IntAct=EBI-401755, EBI-518596; Q14210:LY6D; NbExp=1; IntAct=EBI-401755, EBI-1965225; Q13163:MAP2K5; NbExp=1; IntAct=EBI-401755, EBI-307294; Q92918:MAP4K1; NbExp=1; IntAct=EBI-401755, EBI-881; Q8IVH8:MAP4K3; NbExp=1; IntAct=EBI-401755, EBI-1758170; Q9Y4K4:MAP4K5; NbExp=2; IntAct=EBI-401755, EBI-1279; O60244:MED14; NbExp=1; IntAct=EBI-401755, EBI-394489; Q9H204:MED28; NbExp=3; IntAct=EBI-401755, EBI-514199; Q9NQ76:MEPE; NbExp=1; IntAct=EBI-401755, EBI-1753293; Q15746:MYLK; NbExp=1; IntAct=EBI-401755, EBI-968482; Q8NFW9:MYRIP; NbExp=1; IntAct=EBI-401755, EBI-1759414; O14513:NAP5; NbExp=1; IntAct=EBI-401755, EBI-1752508; Q86SG6:NEK8; NbExp=1; IntAct=EBI-401755, EBI-1752987; O94856:NFASC; NbExp=1; IntAct=EBI-401755, EBI-1751948; Q9Y697:NFS1; NbExp=1; IntAct=EBI-401755, EBI-1751791; P43699:NKX2-1; NbExp=1; IntAct=EBI-401755, EBI-1391923; Q96RI1:NR1H4; NbExp=1; IntAct=EBI-401755, EBI-1250177; Q13285:NR5A1; NbExp=1; IntAct=EBI-401755, EBI-874629; Q99572:P2RX7; NbExp=1; IntAct=EBI-401755, EBI-1753251; Q96RD6:PANX2; NbExp=1; IntAct=EBI-401755, EBI-1759592; P23760:PAX3; NbExp=1; IntAct=EBI-401755, EBI-1167564; Q13087:PDIA2; NbExp=1; IntAct=EBI-401755, EBI-1752525; Q92968:PEX13; NbExp=1; IntAct=EBI-401755, EBI-594849; O75167:PHACTR2; NbExp=1; IntAct=EBI-401755, EBI-1754409; O00750:PIK3C2B; NbExp=1; IntAct=EBI-401755, EBI-641107; P16885:PLCG2; NbExp=1; IntAct=EBI-401755, EBI-617403; O14939:PLD2; NbExp=2; IntAct=EBI-401755, EBI-1053996; Q9UL42:PNMA2; NbExp=1; IntAct=EBI-401755, EBI-302355; P28340:POLD1; NbExp=1; IntAct=EBI-401755, EBI-716569; Q9H9Y6:POLR1B; NbExp=1; IntAct=EBI-401755, EBI-355441; Q08209:PPP3CA; NbExp=1; IntAct=EBI-401755, EBI-352922; P16298:PPP3CB; NbExp=1; IntAct=EBI-401755, EBI-1759540; Q92954:PRG4; NbExp=1; IntAct=EBI-401755, EBI-1760455; O43900:PRICKLE3; NbExp=1; IntAct=EBI-401755, EBI-1751761; P07477:PRSS1; NbExp=1; IntAct=EBI-401755, EBI-1222902; Q99418:PSCD2; NbExp=1; IntAct=EBI-401755, EBI-448974; P29074:PTPN4; NbExp=1; IntAct=EBI-401755, EBI-710431; Q92932:PTPRN2; NbExp=1; IntAct=EBI-401755, EBI-310576; Q92927:rab1b; NbExp=1; IntAct=EBI-401755, EBI-1760045; Q92928:RAB1C; NbExp=1; IntAct=EBI-401755, EBI-1760061; Q92929:rab6b; NbExp=1; IntAct=EBI-401755, EBI-1760079; Q92930:RAB8B; NbExp=1; IntAct=EBI-401755, EBI-1760095; Q92942:RGL2; NbExp=1; IntAct=EBI-401755, EBI-1760273; Q86UR5:RIMS1; NbExp=1; IntAct=EBI-401755, EBI-1043236; Q9UQ26:RIMS2; NbExp=1; IntAct=EBI-401755, EBI-1756749; Q8TB24:RIN3; NbExp=1; IntAct=EBI-401755, EBI-1570523; Q92963:RIT1; NbExp=1; IntAct=EBI-401755, EBI-365845; Q99578:RIT2; NbExp=1; IntAct=EBI-401755, EBI-365914; Q9NRR4:RNASEN; NbExp=1; IntAct=EBI-401755, EBI-528367; Q8IWN7:RP1L1; NbExp=1; IntAct=EBI-401755, EBI-1757848; P26373:RPL13; NbExp=1; IntAct=EBI-401755, EBI-356849; P78345:RPP38; NbExp=1; IntAct=EBI-401755, EBI-366493; Q8IZ73:RPUSD2; NbExp=1; IntAct=EBI-401755, EBI-1965305; P10301:RRAS; NbExp=1; IntAct=EBI-401755, EBI-968703; P21817:RYR1; NbExp=1; IntAct=EBI-401755, EBI-1221290; Q96GP6:SCARF2; NbExp=1; IntAct=EBI-401755, EBI-1752088; O75326:SEMA7A; NbExp=1; IntAct=EBI-401755, EBI-1753538; Q9NZV5:SEPN1; NbExp=1; IntAct=EBI-401755, EBI-1751965; Q15427:SF3B4; NbExp=1; IntAct=EBI-401755, EBI-348469; Q9UPX8:SHANK2; NbExp=1; IntAct=EBI-401755, EBI-1570571; Q9BYB0:SHANK3; NbExp=1; IntAct=EBI-401755, EBI-1752330; Q13796:SHROOM2; NbExp=1; IntAct=EBI-401755, EBI-1644065; Q9UHI7:SLC23A1; NbExp=1; IntAct=EBI-401755, EBI-1759386; O60721:SLC24A1; NbExp=1; IntAct=EBI-401755, EBI-1753504; Q92959:SLCO2A1; NbExp=1; IntAct=EBI-401755, EBI-1760532; P84022:SMAD3; NbExp=1; IntAct=EBI-401755, EBI-347161; Q92922:SMARCC1; NbExp=1; IntAct=EBI-401755, EBI-355653; Q8TAQ2:SMARCC2; NbExp=1; IntAct=EBI-401755, EBI-357418; Q96GM5:SMARCD1; NbExp=1; IntAct=EBI-401755, EBI-358489; Q92925:SMARCD2; NbExp=1; IntAct=EBI-401755, EBI-358441; Q92926:SMARCD3; NbExp=1; IntAct=EBI-401755, EBI-1760029; Q92966:SNAPC3; NbExp=1; IntAct=EBI-401755, EBI-1760638; Q9UMY4:SNX12; NbExp=1; IntAct=EBI-401755, EBI-1752602; Q15036:SNX17; NbExp=1; IntAct=EBI-401755, EBI-1752620; O60493:SNX3; NbExp=1; IntAct=EBI-401755, EBI-727209; Q9UNH6:SNX7; NbExp=1; IntAct=EBI-401755, EBI-751422; Q9Y5X2:SNX8; NbExp=1; IntAct=EBI-401755, EBI-1752557; Q07889:SOS1; NbExp=3; IntAct=EBI-401755, EBI-297487; Q07890:SOS2; NbExp=3; IntAct=EBI-401755, EBI-298181; P08047:SP1; NbExp=1; IntAct=EBI-401755, EBI-298336; Q96T58:SPEN; NbExp=1; IntAct=EBI-401755, EBI-765739; P78524:ST5; NbExp=1; IntAct=EBI-401755, EBI-962633; Q9UJT2:STK22S1; NbExp=1; IntAct=EBI-401755, EBI-852101; Q9H5I1:SUV39H2; NbExp=1; IntAct=EBI-401755, EBI-723127; O15056:SYNJ2; NbExp=1; IntAct=EBI-401755, EBI-310513; O43493:TGOLN2; NbExp=1; IntAct=EBI-401755, EBI-1752146; P42167:TMPO; NbExp=1; IntAct=EBI-401755, EBI-455283; Q92956:TNFRSF14; NbExp=1; IntAct=EBI-401755, EBI-1056653; Q92973:TNPO1; NbExp=1; IntAct=EBI-401755, EBI-286693; Q9ULW0:TPX2; NbExp=1; IntAct=EBI-401755, EBI-1037322; Q9BWF2:TRAIP; NbExp=1; IntAct=EBI-401755, EBI-1756205; Q9HCM9:TRIM39; NbExp=1; IntAct=EBI-401755, EBI-739510; O00294:TULP1; NbExp=1; IntAct=EBI-401755, EBI-1756778; Q16851:UGP2; NbExp=1; IntAct=EBI-401755, EBI-743729; P15498:VAV1; NbExp=1; IntAct=EBI-401755, EBI-625518; Q96RL7:VPS13A; NbExp=1; IntAct=EBI-401755, EBI-1752583; O00401:WASL; NbExp=1; IntAct=EBI-401755, EBI-957615; Q9UMN6:WBP7; NbExp=1; IntAct=EBI-401755, EBI-765774; Q92970:zf30; NbExp=1; IntAct=EBI-401755, EBI-1760698; Q92967:ZF6; NbExp=1; IntAct=EBI-401755, EBI-1760656; Q9BRR0:ZKSCAN3; NbExp=1; IntAct=EBI-401755, EBI-1965777; Q96GC6:ZNF274; NbExp=1; IntAct=EBI-401755, EBI-1965735; Q5JNZ3:ZNF311; NbExp=1; IntAct=EBI-401755, EBI-1965761; P17041:ZNF32; NbExp=1; IntAct=EBI-401755, EBI-1965483; SUBCELLULAR LOCATION: Golgi apparatus (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist; Name=1; Synonyms=Ash-L; IsoId=P62993-1, P29354-1; Sequence=Displayed; Name=GRB3-3; IsoId=P62993-2, P29354-2; Sequence=VSP_001839; DOMAIN: The SH3 domains mediate interaction with RALGPS1 and SHB. SIMILARITY: Belongs to the GRB2/sem-5/DRK family. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 2 SH3 domains. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html"; Reactome http://www.reactome.org Homo sapiens NCBI_taxonomy 9606 UniProt P62993 Reactome DB_ID: 64847 1 UniProt:Q07889 RecName: Full=Son of sevenless homolog 1; Short=SOS-1; GN Name=SOS1; OS Homo sapiens (Human) SOS1 FUNCTION: Promotes the exchange of Ras-bound GDP by GTP. SUBUNIT: Interacts with GRB2. Forms a complex with phosphorylated MUC1 and GRB2 (via its SH3 domains). Interacts with phosphorylated LAT2. INTERACTION: Q9Y5K6:CD2AP; NbExp=1; IntAct=EBI-297487, EBI-298152; P46108:CRK; NbExp=1; IntAct=EBI-297487, EBI-886; P06241:FYN; NbExp=1; IntAct=EBI-297487, EBI-515315; P62993:GRB2; NbExp=3; IntAct=EBI-297487, EBI-401755; P08631:HCK; NbExp=1; IntAct=EBI-297487, EBI-346340; P01112:HRAS; NbExp=1; IntAct=EBI-297487, EBI-350145; P16333:NCK1; NbExp=2; IntAct=EBI-297487, EBI-389883; Q9UKS6:PACSIN3; NbExp=2; IntAct=EBI-297487, EBI-77926; P27986:PIK3R1; NbExp=1; IntAct=EBI-297487, EBI-79464; P19174:PLCG1; NbExp=1; IntAct=EBI-297487, EBI-79387; Q96RF0:SNX18; NbExp=1; IntAct=EBI-297487, EBI-298169; Q9Y5X1:SNX9; NbExp=2; IntAct=EBI-297487, EBI-77848; P12931:SRC; NbExp=1; IntAct=EBI-297487, EBI-621482; TISSUE SPECIFICITY: Expressed in gingival tissues. DISEASE: Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:135300]; also designated GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common. DISEASE: Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common. SIMILARITY: Contains 1 DH (DBL-homology) domain. SIMILARITY: Contains 1 N-terminal Ras-GEF domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 Ras-GEF domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SOS1"; WEB RESOURCE: Name=Wikipedia; Note=Son of sevenless entry; URL="http://en.wikipedia.org/wiki/Son_of_Sevenless"; UniProt Q07889 Reactome DB_ID: 109797 1 GRB2:SOS [cytosol] GRB2:SOS Reactome DB_ID: 74686 1 Reactome DB_ID: 64847 1 Reactome 109797 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109797 Reactome REACT_4435 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4435.1 Reactome 109813 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109813 Reactome REACT_2257 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2257.3 8479541 Pubmed 1993 Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Li, N Batzer, A Daly, R Yajnik, V Skolnik, E Margolis, B Schlessinger, J Nature 363:85-8 Sos:Grb2 complex binds to EGF:EGFR complex Sos:Grb2 complex binds to EGF:EGFR complex Cytoplasmic target proteins containing the SH2 domain can bind to activated EGFR. One such protein, growth factor receptor-bound protein 2 (GRB2), can bind activated EGFR with its SH2 domain whilst in complex with SOS through its SH3 domain. GRB2 can bind at either Y1068 and/or Y1086 tyrosine autophosphorylation sites on the receptor. Authored: Castagnoli, L, 2006-10-10 13:09:34 Reviewed: Heldin, CH, 2008-02-12 09:44:02 Reactome DB_ID: 109797 1 Reactome DB_ID: 179882 1 plasma membrane GO 0005886 EGF:Phospho-EGFR (Y992, Y1068, Y1086, Y1148, Y1173) dimer [plasma membrane] EGF:Phospho-EGFR (Y992, Y1068, Y1086, Y1148, Y1173) dimer Reactome DB_ID: 179860 2 EGF:Phospho-EGFR [plasma membrane] EGF:Phospho-EGFR Reactome DB_ID: 179863 1 extracellular region GO 0005576 UniProt:P01133 RecName: Full=Pro-epidermal growth factor; Short=EGF; Contains: RecName: Full=Epidermal growth factor; AltName: Full=Urogastrone; Flags: Precursor; GN Name=EGF; OS Homo sapiens (Human) EGF FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. INTERACTION: P00533:EGFR; NbExp=2; IntAct=EBI-640857, EBI-297353; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Expressed in kidney, salivary gland, cerebrum and prostate. DISEASE: Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4) [MIM:611718]; also known as renal hypomagnesemia normocalciuric. HOMG4 is a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to mederate psychomotor retardation, and brisk tendon reflexes. SIMILARITY: Contains 9 EGF-like domains. SIMILARITY: Contains 9 LDL-receptor class B repeats. WEB RESOURCE: Name=Wikipedia; Note=Epidermal growth factor entry; URL="http://en.wikipedia.org/wiki/Epidermal_growth_factor"; UniProt P01133 Chain Coordinates 971 EQUAL 1023 EQUAL Reactome DB_ID: 179803 1 UniProt:P00533-1 RecName: Full=Epidermal growth factor receptor; EC=2.7.10.1; AltName: Full=Receptor tyrosine-protein kinase ErbB-1; Flags: Precursor; GN Name=EGFR; Synonyms=ERBB1; OS Homo sapiens (Human) EGFR ERBB1 FUNCTION: Receptor for EGF, but also for other members of the EGF family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor. Is involved in the control of cell growth and differentiation. Phosphorylates MUC1 in breast cancer cells and increases the interaction of MUC1 with C-SRC and CTNNB1/beta-catenin. FUNCTION: Isoform 2/truncated isoform may act as an antagonist. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: Binds RIPK1. CBL interacts with the autophosphorylated C- terminal tail of the EGF receptor. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. The autophosphorylated form interacts with PIK3C2B, maybe indirectly. Interacts with PELP1. Binds MUC1. INTERACTION: Self; NbExp=1; IntAct=EBI-297353, EBI-297353; Q29376:- (xeno); NbExp=1; IntAct=EBI-297353, EBI-1256881; P62157:CALM (xeno); NbExp=1; IntAct=EBI-297353, EBI-397403; P62158:CALM1; NbExp=1; IntAct=EBI-297353, EBI-397435; P62161:Calm1 (xeno); NbExp=2; IntAct=EBI-297353, EBI-397530; P62204:Calm1 (xeno); NbExp=1; IntAct=EBI-297353, EBI-397460; P22681:CBL; NbExp=1; IntAct=EBI-297353, EBI-518228; P22682:Cbl (xeno); NbExp=1; IntAct=EBI-297353, EBI-640919; P13987:CD59; NbExp=1; IntAct=EBI-297353, EBI-297972; P01133:EGF; NbExp=2; IntAct=EBI-297353, EBI-640857; P04626:ERBB2; NbExp=2; IntAct=EBI-297353, EBI-641062; P21860:ERBB3; NbExp=2; IntAct=EBI-297353, EBI-720706; Q15303:ERBB4; NbExp=2; IntAct=EBI-297353, EBI-80371; P62993:GRB2; NbExp=2; IntAct=EBI-297353, EBI-401755; O00750:PIK3C2B; NbExp=4; IntAct=EBI-297353, EBI-641107; Q9UJ41:RABGEF1; NbExp=2; IntAct=EBI-297353, EBI-913954; P98083:Shc1 (xeno); NbExp=1; IntAct=EBI-297353, EBI-300201; P13866:SLC5A1; NbExp=3; IntAct=EBI-297353, EBI-1772443; P63104:YWHAZ; NbExp=1; IntAct=EBI-297353, EBI-347088; SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 2: Secreted. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=p170; IsoId=P00533-1; Sequence=Displayed; Name=2; Synonyms=p60, Truncated, TEGFR; IsoId=P00533-2; Sequence=VSP_002887, VSP_002888; Name=3; Synonyms=p110; IsoId=P00533-3; Sequence=VSP_002889, VSP_002890; Name=4; IsoId=P00533-4; Sequence=VSP_002891, VSP_002892; TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. PTM: Phosphorylation of Ser-695 is partial and occurs only if Thr- 693 is phosphorylated. PTM: Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur. DISEASE: Defects in EGFR are associated with lung cancer [MIM:211980]. MISCELLANEOUS: Binding of EGF to the receptor leads to dimerization, internalization of the EGF-receptor complex, induction of the tyrosine kinase activity, stimulation of cell DNA synthesis, and cell proliferation. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=EGFR"; WEB RESOURCE: Name=Wikipedia; Note=EGFR entry; URL="http://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor"; UniProt P00533 phosphate group on L-Tyrosine [ChEBI:6313] 1068 of UniProt:P00533-1 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor protein-tyrosine kinase ErbB-1) residue: L-Tyrosine [ChEBI:17895] 1068 EQUAL phosphate group ChEBI 35780 phosphate group on L-Tyrosine [ChEBI:6313] 1148 of UniProt:P00533-1 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor protein-tyrosine kinase ErbB-1) residue: L-Tyrosine [ChEBI:17895] 1148 EQUAL phosphate group on L-Tyrosine [ChEBI:6313] 1173 of UniProt:P00533-1 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor protein-tyrosine kinase ErbB-1) residue: L-Tyrosine [ChEBI:17895] 1173 EQUAL phosphate group on L-Tyrosine [ChEBI:6313] 1086 of UniProt:P00533-1 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor protein-tyrosine kinase ErbB-1) residue: L-Tyrosine [ChEBI:17895] 1086 EQUAL phosphate group on L-Tyrosine [ChEBI:6313] 992 of UniProt:P00533-1 Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor protein-tyrosine kinase ErbB-1) residue: L-Tyrosine [ChEBI:17895] 992 EQUAL 25 EQUAL 1210 EQUAL Reactome 179860 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179860 Reactome REACT_9712 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_9712.1 Reactome 179882 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179882 Reactome REACT_9673 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_9673.1 Reactome DB_ID: 179820 1 GRB2:SOS-EGF-Phospho-EGFR dimer [plasma membrane] GRB2:SOS-EGF-Phospho-EGFR dimer Reactome DB_ID: 109797 1 Reactome DB_ID: 179882 1 Reactome 179820 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179820 Reactome REACT_12657 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_12657.1 Reactome 177943 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177943 Reactome REACT_12392 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_12392.1 7527043 Pubmed 1994 Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells Okutani, T Okabayashi, Y Kido, Y Sugimoto, Y Sakaguchi, K Matuoka, K Takenawa, T Kasuga, M J Biol Chem 269:31310-4 7518560 Pubmed 1994 Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor Batzer, AG Rotin, D Urena, JM Skolnik, EY Schlessinger, J Mol Cell Biol 14:5192-201 Sos-mediated nucleotide exchange of Ras (EGF:EGFR-Sos:Grb2) Sos-mediated nucleotide exchange of Ras (EGF:EGFR-Sos:Grb2) The guanine nucleotide exchange factor SOS interacts with EGFR through the adaptor protein, GRB2. Upon formation of this complex, SOS activates Ras by promoting GDP release and GTP binding. Authored: Castagnoli, L, 2006-10-10 13:09:34 Reviewed: Heldin, CH, 2008-02-12 09:44:02 Reactome DB_ID: 109796 1 p21 RAS:GDP [plasma membrane] p21 RAS:GDP Converted from EntitySet in Reactome Reactome DB_ID: 109782 1 p21 RAS [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity p21A (K-Ras 2A) [plasma membrane] p21/N-Ras [plasma membrane] p21/H-RAS-1 [plasma membrane] UniProt P01116 UniProt P01111 UniProt P01112 Reactome DB_ID: 29420 1 GDP [ChEBI:17552] GDP Guanosine 5'-diphosphate Guanosine diphosphate ChEBI 17552 Reactome 109796 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109796 Reactome REACT_2657 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2657.1 Reactome DB_ID: 29438 1 GTP [ChEBI:15996] GTP Guanosine 5'-triphosphate ChEBI 15996 Reactome DB_ID: 109783 1 p21 RAS:GTP [plasma membrane] p21 RAS:GTP Converted from EntitySet in Reactome Reactome DB_ID: 109782 1 Reactome DB_ID: 29438 1 Reactome 109783 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109783 Reactome REACT_4782 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4782.1 Reactome DB_ID: 29420 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 179820 GO 0005088 GO molecular function Reactome 177932 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177932 Reactome 177938 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177938 Reactome REACT_12386 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_12386.1 8493579 Pubmed 1993 Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 Chardin, P Camonis, JH Gale, NW Van Aelst, L Schlessinger, J Wigler, MH Bar-Sagi, D Science 260:1338-43 RAF activation RAF activation Phosphorylated RAF is activated by Ras binding and stabilised in its active form by transient disassociation and reassociation of 14-3-3, as well as further phosphorylation. Authored: Charalambous, M, 2004-04-29 09:21:24 Reviewed: Greene, LA, 2007-11-08 15:39:37 Transient dissociation of 14-3-3 upon Ras binding Transient dissociation of 14-3-3 upon Ras binding Activated p21ras (the GTP-bound form) is associated with the plasma membrane. Inactive Raf-1 is associated in the cytoplasm with 14-3-3. 14-3-3 binds to Raf-1 via the Ser259 phosphorylation site (S1). This interaction stabilises the inactive conformation of Raf-1 in which the Ras-binding Cysteine-rich domain (CRD) is obscured. The Raf-1 molecule contains an additional p21ras-binding domain (RBD), a second serine phosphorylation site at S621 (S2) and two tyrosine phosphorylation sites (at 340, Y1 and 341, Y2).<br>Raf-1 binds activated p21ras via the RBD. This displaces 14-3-3 from Ser259 and unmasks the CRD. Authored: Charalambous, M, 2005-01-07 11:17:43 Reviewed: Heldin, CH, 2008-02-12 09:44:02 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109783 1 Reactome DB_ID: 109787 1 phospho-RAF:14-3-3 [cytosol] phospho-RAF:14-3-3 Reactome DB_ID: 48888 1 UniProt:P31946-1 RecName: Full=14-3-3 protein beta/alpha; AltName: Full=Protein kinase C inhibitor protein 1; Short=KCIP-1; AltName: Full=Protein 1054; GN Name=YWHAB; OS Homo sapiens (Human) YWHAB FUNCTION: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathway. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. SUBUNIT: Homodimer. Interacts with SSH1 and TORC2/CRTC2. INTERACTION: Q9P0K1-1:ADAM22; NbExp=2; IntAct=EBI-359815, EBI-1567258; Q9P0K1-3:ADAM22; NbExp=1; IntAct=EBI-359815, EBI-1567267; Q12802:AKAP13; NbExp=1; IntAct=EBI-359815, EBI-1373806; O43521:BCL2L11; NbExp=1; IntAct=EBI-359815, EBI-526406; P15056:BRAF; NbExp=1; IntAct=EBI-359815, EBI-365980; P46527:CDKN1B; NbExp=1; IntAct=EBI-359815, EBI-519280; Q9P2M7:CGN; NbExp=1; IntAct=EBI-359815, EBI-79537; P68400:CSNK2A1; NbExp=1; IntAct=EBI-359815, EBI-347804; Q7Z401:DENND4A; NbExp=1; IntAct=EBI-359815, EBI-1046479; Q13627-2:DYRK1A; NbExp=3; IntAct=EBI-359815, EBI-1053621; Q96F86:EDC3; NbExp=1; IntAct=EBI-359815, EBI-997311; Q9Y2J2:EPB41L3; NbExp=1; IntAct=EBI-359815, EBI-310986; Q96TC7:FAM82A2; NbExp=1; IntAct=EBI-359815, EBI-1056589; Q9Y4H2:IRS2; NbExp=1; IntAct=EBI-359815, EBI-1049582; Q02241:KIF23; NbExp=1; IntAct=EBI-359815, EBI-306852; P33176:KIF5B; NbExp=1; IntAct=EBI-359815, EBI-355878; Q07866:KLC1; NbExp=1; IntAct=EBI-359815, EBI-721019; Q6PKG0:LARP1; NbExp=1; IntAct=EBI-359815, EBI-1052114; P27448:MARK3; NbExp=1; IntAct=EBI-359815, EBI-707595; Q6WCQ1:MPRIP; NbExp=1; IntAct=EBI-359815, EBI-1022605; Q9Y2A7:NCKAP1; NbExp=1; IntAct=EBI-359815, EBI-389845; Q9H4L5:OSBPL3; NbExp=1; IntAct=EBI-359815, EBI-1051317; Q8TEW0:PARD3; NbExp=1; IntAct=EBI-359815, EBI-81968; O94921:PFTK1; NbExp=5; IntAct=EBI-359815, EBI-1043945; Q9UBF8:PI4KB; NbExp=1; IntAct=EBI-359815, EBI-1053214; Q9UJ41:RABGEF1; NbExp=1; IntAct=EBI-359815, EBI-913954; Q9H0H5:RACGAP1; NbExp=1; IntAct=EBI-359815, EBI-717233; P04049:RAF1; NbExp=4; IntAct=EBI-359815, EBI-365996; Q9P0K7:RAI14; NbExp=1; IntAct=EBI-359815, EBI-1023749; Q5PRF9:SAMD4B; NbExp=1; IntAct=EBI-359815, EBI-1047489; Q9Y6M7:SLC4A7; NbExp=1; IntAct=EBI-359815, EBI-1044546; Q9UQ35:SRRM2; NbExp=1; IntAct=EBI-359815, EBI-1050142; Q9UDY2:TJP2; NbExp=1; IntAct=EBI-359815, EBI-1042602; P40818:USP8; NbExp=1; IntAct=EBI-359815, EBI-1050865; SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. ALTERNATIVE PRODUCTS: Event=Alternative initiation; Named isoforms=2; Name=Long; IsoId=P31946-1; Sequence=Displayed; Name=Short; IsoId=P31946-2; Sequence=VSP_018632; Note=Contains a N-acetylmethionine at position 1 (By similarity); PTM: Isoform alpha differs from isoform beta in being phosphorylated (By similarity). PTM: Isoform Short contains a N-acetylmethionine at position 1 (By similarity). SIMILARITY: Belongs to the 14-3-3 family. UniProt P31946 Reactome DB_ID: 109786 1 UniProt:P04049-1 RecName: Full=RAF proto-oncogene serine/threonine-protein kinase; EC=2.7.11.1; AltName: Full=C-RAF; Short=cRaf; AltName: Full=Raf-1; GN Name=RAF1; Synonyms=RAF; OS Homo sapiens (Human) RAF1 RAF FUNCTION: Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 2 zinc ions per subunit. SUBUNIT: Interacts with Ras proteins. The interaction with Ras is antagonized by RIN1. Weakly interacts with RIT1 (By similarity). Interacts with STK3, which inhibits its pro-apoptotic activity. INTERACTION: P49368:CCT3; NbExp=3; IntAct=EBI-365996, EBI-356673; Q9UNS2:COPS3; NbExp=2; IntAct=EBI-365996, EBI-350590; P31327:CPS1; NbExp=2; IntAct=EBI-365996, EBI-536811; P01112:HRAS; NbExp=5; IntAct=EBI-365996, EBI-350145; P08238:HSP90AB1; NbExp=1; IntAct=EBI-365996, EBI-352572; P11021:HSPA5; NbExp=3; IntAct=EBI-365996, EBI-354921; Q9NVR2:INTS10; NbExp=2; IntAct=EBI-365996, EBI-536703; Q02750:MAP2K1; NbExp=1; IntAct=EBI-365996, EBI-492564; O43482:OIP5; NbExp=3; IntAct=EBI-365996, EBI-536879; Q13177:PAK2; NbExp=2; IntAct=EBI-365996, EBI-1045887; P14618:PKM2; NbExp=3; IntAct=EBI-365996, EBI-353408; P62834:RAP1A; NbExp=2; IntAct=EBI-365996, EBI-491414; P53805-2:RCAN1; NbExp=3; IntAct=EBI-365996, EBI-1541912; Q3ZCQ8:TIMM50; NbExp=3; IntAct=EBI-365996, EBI-355175; P31946:YWHAB; NbExp=4; IntAct=EBI-365996, EBI-359815; P61981:YWHAG; NbExp=1; IntAct=EBI-365996, EBI-359832; Q04917:YWHAH; NbExp=1; IntAct=EBI-365996, EBI-306940; P27348:YWHAQ; NbExp=1; IntAct=EBI-365996, EBI-359854; P63104:YWHAZ; NbExp=2; IntAct=EBI-365996, EBI-347088; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=6C; IsoId=P04049-1; Sequence=Displayed; Name=2; Synonyms=1A; IsoId=P04049-2; Sequence=VSP_034649; TISSUE SPECIFICITY: In skeletal muscle, isoform 1 is more abundant than isoform 2. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity. DISEASE: Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. DISEASE: Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD syndrome-2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 RBD (Ras-binding) domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=RAF1"; WEB RESOURCE: Name=NIEHS SNPs; URL="http://egp.gs.washington.edu/data/raf1/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RAF1ID42032ch3p25.html"; UniProt P04049 phosphate group on L-Serine 259 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 259 EQUAL phosphate group on L-Serine 621 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 621 EQUAL Reactome 109787 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109787 Reactome REACT_4612 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4612.1 Reactome DB_ID: 48888 1 Reactome DB_ID: 109788 1 RAS:RAF [plasma membrane] RAS:RAF Reactome DB_ID: 109786 1 phosphate group on L-Serine 259 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 259 EQUAL phosphate group on L-Serine 621 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 621 EQUAL Reactome DB_ID: 109783 1 Reactome 109788 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109788 Reactome REACT_3036 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3036.1 Reactome 109803 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109803 Reactome REACT_359 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_359.4 9069260 Pubmed 1997 The complexity of Raf-1 regulation. Morrison, DK Cutler, RE Curr Opin Cell Biol 9:174-9 Stabilisation of RAS:RAF by 14-3-3 Stabilisation of RAS:RAF by 14-3-3 14-3-3 has been displaced from Ser259. 14-3-3 may now bind its higher affinity Ser621 (S2) site. This stabilises an 'open' Raf-1 conformation that is catalytically active, and bound to p21ras via both p21ras-binding domains, CRD and RBD. Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 48888 1 Reactome DB_ID: 109788 1 Reactome DB_ID: 109789 1 RAS:RAF:14-3-3 [plasma membrane] RAS:RAF:14-3-3 Reactome DB_ID: 48888 1 Reactome DB_ID: 109788 1 Reactome 109789 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109789 Reactome REACT_3642 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3642.1 Reactome 109802 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109802 Reactome REACT_996 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_996.3 2.7.10 Stabilisation of RAF by further phosphorylation Stabilisation of RAF by further phosphorylation Un as yet unidentified protein tyrosine kinase located in the plasma membrane phosphorylates Tyrosines 340 and 341 (Y1, Y2) of Raf-1. Tyrosine phosphorylation serves to further stabilise the active 'open' Raf-1 conformation. (While the kinase has not been definitively identified, the Src kinase is a plausible candidate.) Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 113592 2 ATP [ChEBI:15422] ATP Adenosine 5'-triphosphate ChEBI 15422 Reactome DB_ID: 109789 1 Reactome DB_ID: 109793 1 activated RAF complex [plasma membrane] activated RAF complex Reactome DB_ID: 48888 1 Reactome DB_ID: 109792 1 phosphate group on L-Serine 259 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 259 EQUAL phosphate group on L-Serine 621 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf-1) (C-RAF) (cRaf) residue: L-Serine [ChEBI:6301] 621 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 340 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf- 1) (C-RAF) (cRaf) residue: L-Tyrosine [ChEBI:17895] 340 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 341 of UniProt:P04049 RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.1.37) (Raf- 1) (C-RAF) (cRaf) residue: L-Tyrosine [ChEBI:17895] 341 EQUAL Reactome DB_ID: 109783 1 Reactome 109793 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109793 Reactome REACT_4906 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4906.1 Reactome DB_ID: 29370 2 ADP [ChEBI:16761] ADP Adenosine 5'-diphosphate ChEBI 16761 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 163338 unidentified protein tyrosine kinase [plasma membrane] unidentified protein tyrosine kinase GO 0004713 GO molecular function Reactome 112332 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112332 Reactome 109829 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109829 Reactome REACT_525 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_525.2 Reactome 110029 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110029 Reactome REACT_2077 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2077.4 MAP kinase cascade MAP kinase cascade The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus. Authored: Charalambous, M, 2004-04-29 09:21:24 Reviewed: Greene, LA, 2007-11-08 15:39:37 MEK activation MEK activation MEK is phosphorylated and activated by RAF. Authored: Charalambous, M, 2004-04-29 09:21:24 Reviewed: Greene, LA, 2007-11-08 15:39:37 Activated RAF complex binds MEK Activated RAF complex binds MEK MEK-1/2 have a proline rich domain (P) and critical Serine residues (MEK-1 S218/222, MEK-2 unknown, S) upon which the molecules may be phosphorylated. MEK1/2 are found in the cytoplasm of unstimulated cells.<br>MEK-1/2 bind to active Raf-1 via the proline-rich domain. Active Raf-1 is able to phosphorylate target Serine and Threonine residues in the presence of ATP. Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109793 1 Converted from EntitySet in Reactome Reactome DB_ID: 112398 1 MEK [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity MEK1 [cytosol] MEK2 [cytosol] UniProt Q02750 UniProt P36507 Reactome DB_ID: 112406 1 RAF:MEK [plasma membrane] RAF:MEK Reactome DB_ID: 109793 1 Converted from EntitySet in Reactome Reactome DB_ID: 112398 1 Reactome 112406 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112406 Reactome REACT_3953 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3953.1 Reactome 109830 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109830 Reactome REACT_143 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_143.3 RAF phosphorylates MEK RAF phosphorylates MEK Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active. Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 RAF phosphorylates MEK1 RAF phosphorylates MEK1 Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active. Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109794 1 RAF:MEK1 [plasma membrane] RAF:MEK1 Reactome DB_ID: 59502 1 UniProt:Q02750 RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1; Short=MAP kinase kinase 1; Short=MAPKK 1; EC=2.7.12.2; AltName: Full=ERK activator kinase 1; AltName: Full=MAPK/ERK kinase 1; Short=MEK1; GN Name=MAP2K1; Synonyms=MEK1, PRKMK1; OS Homo sapiens (Human) MAP2K1 PRKMK1 MEK1 FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates ERK1 and ERK2 MAP kinases. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activated by phosphorylation. SUBUNIT: Interacts with MORG1 (By similarity). Interacts with Yersinia yopJ. INTERACTION: Q9NR09:BIRC6; NbExp=1; IntAct=EBI-492564, EBI-1765160; P04049:RAF1; NbExp=1; IntAct=EBI-492564, EBI-365996; Q96RU8:TRIB1; NbExp=1; IntAct=EBI-492564, EBI-492555; Q96RU7:TRIB3; NbExp=1; IntAct=EBI-492564, EBI-492476; PTM: Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity. PTM: Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. DISEASE: Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=MAP2K1"; Reactome DB_ID: 109793 1 Reactome 109794 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109794 Reactome REACT_4256 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4256.1 Reactome DB_ID: 113592 2 Reactome DB_ID: 109837 1 phosphate group on L-Serine 218 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 218 EQUAL phosphate group on L-Serine 222 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 222 EQUAL Reactome DB_ID: 109793 1 Reactome DB_ID: 29370 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 109794 GO 0016301 GO molecular function Reactome 109834 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109834 Reactome 109841 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109841 Reactome REACT_545 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_545.2 2.7.11 RAF phosphorylates MEK2 RAF phosphorylates MEK2 Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active. Authored: Charalambous, M, 2005-01-07 11:17:43 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109795 1 RAF:MEK2 [plasma membrane] RAF:MEK2 Reactome DB_ID: 109793 1 Reactome DB_ID: 59504 1 UniProt:P36507 RecName: Full=Dual specificity mitogen-activated protein kinase kinase 2; Short=MAP kinase kinase 2; Short=MAPKK 2; EC=2.7.12.2; AltName: Full=ERK activator kinase 2; AltName: Full=MAPK/ERK kinase 2; Short=MEK2; GN Name=MAP2K2; Synonyms=MEK2, MKK2, PRKMK2; OS Homo sapiens (Human) MKK2 MAP2K2 PRKMK2 MEK2 FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Interacts with MORG1 (By similarity). INTERACTION: P10398:ARAF; NbExp=3; IntAct=EBI-1056930, EBI-365961; PTM: MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1). DISEASE: Defects in MAP2K2 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=MAP2K2"; Reactome 109795 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109795 Reactome REACT_4223 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4223.1 Reactome DB_ID: 113592 2 Reactome DB_ID: 109848 1 phosphate group on unknown ChEBI:6301 L-Serine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Serine [ChEBI:6301] phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Threonine [ChEBI:6308] Reactome DB_ID: 109793 1 Reactome DB_ID: 29370 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 109795 GO 0004674 GO molecular function Reactome 110045 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110045 Reactome 109852 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109852 Reactome REACT_1727 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1727.2 Reactome 112407 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112407 Reactome REACT_614 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_614.3 Reactome 110049 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110049 Reactome REACT_962 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_962.4 GO 0000186 GO biological process ERK activation ERK activation Activated MEK phosphorylates and activates ERK. Reviewed: Greene, LA, 2007-11-08 15:39:37 ERK1 activation ERK1 activation Activated MEK1 phosphorylates and activates ERK1. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 MEK1 binds ERK-1 MEK1 binds ERK-1 In the cytoplasm activated MEK1 (Serine phosphorylated) may encounter monomeric, inactive ERK1. ERK1 in its inactive form is not phosphorylated on a critical Threonine (T) and a critical Tyrosine (Y). Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109837 1 phosphate group on L-Serine 218 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 218 EQUAL phosphate group on L-Serine 222 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 222 EQUAL Reactome DB_ID: 59284 1 UniProt:P27361 RecName: Full=Mitogen-activated protein kinase 3; EC=2.7.11.24; AltName: Full=Extracellular signal-regulated kinase 1; Short=ERK-1; AltName: Full=Insulin-stimulated MAP2 kinase; AltName: Full=MAP kinase 1; Short=MAPK 1; AltName: Full=p44-ERK1; AltName: Full=ERT2; AltName: Full=p44-MAPK; AltName: Full=Microtubule-associated protein 2 kinase; GN Name=MAPK3; Synonyms=ERK1, PRKM3; OS Homo sapiens (Human) ERK1 MAPK3 PRKM3 FUNCTION: Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 (By similarity). Phosphorylates heat shock factor protein 4 (HSF4). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activated by tyrosine phosphorylation in response to insulin and NGF. SUBUNIT: Interacts with MORG1 (By similarity). Binds to HIV-1 Nef. This interaction inhibits its kinase activity. Interacts with HSF4 and NISCH. INTERACTION: P53355:DAPK1; NbExp=3; IntAct=EBI-73995, EBI-358616; P19419:ELK1; NbExp=1; IntAct=EBI-73995, EBI-726632; O75676:RPS6KA4; NbExp=1; IntAct=EBI-73995, EBI-73933; DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. UniProt P27361 Reactome DB_ID: 109838 1 MEK1:ERK-1 [cytosol] MEK1:ERK-1 Reactome DB_ID: 109837 1 phosphate group on L-Serine 218 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 218 EQUAL phosphate group on L-Serine 222 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 222 EQUAL Reactome DB_ID: 59284 1 Reactome 109838 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109838 Reactome REACT_5539 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5539.1 Reactome 109857 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109857 Reactome REACT_1780 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1780.3 8388392 Pubmed 1993 Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. Zheng, CF Guan, KL J Biol Chem 268:11435-9 2.7.11 MEK1 phosphorylates ERK-1 MEK1 phosphorylates ERK-1 MEK1 phosphorylates the critical Tyrosine and Threonine on ERK1, converting two ATP to ADP. Phosphorylation of ERK-1 activates its kinase activity. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109838 1 Reactome DB_ID: 113592 2 Reactome DB_ID: 109843 1 phospho-ERK-1:MEK1 [cytosol] phospho-ERK-1:MEK1 Reactome DB_ID: 109837 1 phosphate group on L-Serine 218 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 218 EQUAL phosphate group on L-Serine 222 of UniProt:Q02750 Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1) residue: L-Serine [ChEBI:6301] 222 EQUAL Reactome DB_ID: 109842 1 phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Threonine [ChEBI:6308] phosphate group on unknown ChEBI:6313 L-Tyrosine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Tyrosine [ChEBI:17895] Reactome 109843 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109843 Reactome REACT_2796 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2796.1 Reactome DB_ID: 29370 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 109838 Reactome 109859 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109859 Reactome 109860 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109860 Reactome REACT_136 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_136.3 Dimerisation of phospho-ERK-1 Dimerisation of phospho-ERK-1 Two phospho-ERK1 molecules dimerise and enter the nucleus, where they may phosphorylate downstream targets. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109842 2 phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Threonine [ChEBI:6308] phosphate group on unknown ChEBI:6313 L-Tyrosine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Tyrosine [ChEBI:17895] Reactome DB_ID: 109844 1 phospho-ERK-1 dimer [cytosol] phospho-ERK-1 dimer Reactome DB_ID: 109842 2 phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Threonine [ChEBI:6308] phosphate group on unknown ChEBI:6313 L-Tyrosine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Tyrosine [ChEBI:17895] Reactome 109844 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109844 Reactome REACT_3932 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3932.1 Reactome 109865 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109865 Reactome REACT_1289 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1289.3 Nuclear translocation of phospho-ERK-1 dimer Nuclear translocation of phospho-ERK-1 dimer In this reaction, 1 molecule of 'phospho-ERK-1 dimer' is translocated from cytosol to nucleoplasm.<br><br>This reaction takes place in the 'intracellular'.<br> Reviewed: Greene, LA, 2007-11-08 15:39:37 Reactome DB_ID: 109844 1 Reactome DB_ID: 109845 1 nucleoplasm GO 0005654 phospho-ERK-1 dimer [nucleoplasm] phospho-ERK-1 dimer Reactome DB_ID: 112359 2 phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Threonine [ChEBI:6308] phosphate group on unknown ChEBI:6313 L-Tyrosine of UniProt:P27361 Mitogen-activated protein kinase 3 (EC 2.7.1.37) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) residue: L-Tyrosine [ChEBI:17895] Reactome 109845 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109845 Reactome REACT_3152 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3152.1 Reactome 109867 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109867 Reactome REACT_1866 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1866.5 GO 0000189 GO biological process Reactome 110056 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110056 Reactome REACT_1391 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1391.3 ERK2 activation ERK2 activation Activated MEK2 phosphorylates and activates ERK2. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 MEK2 binds ERK-2 MEK2 binds ERK-2 In the cytoplasm activated MEK2 (Serine phosphorylated) may encounter monomeric, inactive ERK2. ERK2 in its inactive form is not phosphorylated on a critical Threonine (T183) and a critical Tyrosine (Y185). Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109848 1 phosphate group on unknown ChEBI:6301 L-Serine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Serine [ChEBI:6301] phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Threonine [ChEBI:6308] Reactome DB_ID: 59282 1 UniProt:P28482 RecName: Full=Mitogen-activated protein kinase 1; EC=2.7.11.24; AltName: Full=Extracellular signal-regulated kinase 2; Short=ERK-2; AltName: Full=Mitogen-activated protein kinase 2; Short=MAP kinase 2; Short=MAPK 2; AltName: Full=p42-MAPK; AltName: Full=ERT1; GN Name=MAPK1; Synonyms=ERK2, PRKM1, PRKM2; OS Homo sapiens (Human) MAPK1 ERK2 PRKM2 PRKM1 FUNCTION: Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 (By similarity). Phosphorylates heat shock factor protein 4 (HSF4) and ARHGEF2. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activated by phosphorylation on tyrosine and threonine in response to insulin and NGF. Both phosphorylations are required for activity (By similarity). SUBUNIT: Interacts with MORG1 (By similarity). Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine- kinase activity. Interacts with its substrates HSF4 and ARHGEF2. Interacts with NISCH. INTERACTION: P28562:DUSP1; NbExp=2; IntAct=EBI-959949, EBI-975493; P19419:ELK1; NbExp=1; IntAct=EBI-959949, EBI-726632; P02687:MBP (xeno); NbExp=1; IntAct=EBI-959949, EBI-908215; DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Wikipedia; Note=Extracellular signal-regulated kinase entry; URL="http://en.wikipedia.org/wiki/Extracellular_signal-regulated_kinase"; UniProt P28482 Reactome DB_ID: 109849 1 MEK2:ERK-2 [cytosol] MEK2:ERK-2 Reactome DB_ID: 109848 1 phosphate group on unknown ChEBI:6301 L-Serine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Serine [ChEBI:6301] phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Threonine [ChEBI:6308] Reactome DB_ID: 59282 1 Reactome 109849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109849 Reactome REACT_5435 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5435.1 Reactome 109858 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109858 Reactome REACT_495 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_495.3 2.7.11 MEK2 phosphorylates ERK-2 MEK2 phosphorylates ERK-2 MEK2 phosphorylates the critical Tyrosine and Threonine on ERK2, converting two ATP to ADP. Phosphorylation of ERK-2 activates its kinase activity. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 113592 2 Reactome DB_ID: 109849 1 Reactome DB_ID: 29370 2 Reactome DB_ID: 109854 1 phospho-ERK-2:MEK2 [cytosol] phospho-ERK-2:MEK2 Reactome DB_ID: 109853 1 phosphate group on ChEBI:6308 L-Threonine 183 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Threonine [ChEBI:6308] 183 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 185 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Tyrosine [ChEBI:17895] 185 EQUAL Reactome DB_ID: 109848 1 phosphate group on unknown ChEBI:6301 L-Serine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Serine [ChEBI:6301] phosphate group on unknown ChEBI:6308 L-Threonine of UniProt:P36507 Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2) residue: L-Threonine [ChEBI:6308] Reactome 109854 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109854 Reactome REACT_3199 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3199.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 109849 Reactome 109861 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109861 Reactome 109862 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109862 Reactome REACT_2247 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2247.3 Dimerisation of phospho-ERK-2 Dimerisation of phospho-ERK-2 Two phospho-ERK2 molecules dimerise and enter the nucleus, where they may phosphorylate downstream targets. Authored: Charalambous, M, 2005-02-04 06:50:22 Reviewed: Greene, LA, 2007-11-08 15:39:37 Edited: Schmidt, EE, 0000-00-00 00:00:00 Reactome DB_ID: 109853 2 phosphate group on ChEBI:6308 L-Threonine 183 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Threonine [ChEBI:6308] 183 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 185 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Tyrosine [ChEBI:17895] 185 EQUAL Reactome DB_ID: 109855 1 phospho-ERK-2 dimer [cytosol] phospho-ERK-2 dimer Reactome DB_ID: 109853 2 phosphate group on ChEBI:6308 L-Threonine 183 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Threonine [ChEBI:6308] 183 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 185 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Tyrosine [ChEBI:17895] 185 EQUAL Reactome 109855 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109855 Reactome REACT_3688 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3688.1 Reactome 109866 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109866 Reactome REACT_2196 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2196.3 Nuclear translocation of phospho-ERK-2 dimer Nuclear translocation of phospho-ERK-2 dimer In this reaction, 1 molecule of 'phospho-ERK-2 dimer' is translocated from cytosol to nucleoplasm.<br><br>This reaction takes place in the 'intracellular'.<br> Reviewed: Greene, LA, 2007-11-08 15:39:37 Reactome DB_ID: 109855 1 Reactome DB_ID: 109856 1 phospho-ERK-2 dimer [nucleoplasm] phospho-ERK-2 dimer Reactome DB_ID: 112354 2 phosphate group on ChEBI:6308 L-Threonine 183 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Threonine [ChEBI:6308] 183 EQUAL phosphate group on ChEBI:6313 L-Tyrosine 185 of UniProt:P28482 Mitogen-activated protein kinase 1 (EC 2.7.1.37) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) residue: L-Tyrosine [ChEBI:17895] 185 EQUAL Reactome 109856 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109856 Reactome REACT_5046 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5046.1 Reactome 109868 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109868 Reactome REACT_487 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_487.5 Reactome 112411 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112411 Reactome REACT_1183 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1183.3 Reactome 112409 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112409 Reactome REACT_1482 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1482.4 GO 0000187 GO biological process Reactome 109869 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109869 Reactome REACT_634 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_634.4 GO 0000165 GO biological process Reactome 179812 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179812 Reactome REACT_12606 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_12606.1 11706405 Pubmed 2001 GRB2: a pivotal protein in signal transduction Tari, AM Lopez-Berestein, G Semin Oncol 28:142-7 11498013 Pubmed 2001 Internalization of the epidermal growth factor receptor: role in signalling Sorkin, A Biochem Soc Trans 29:480-4