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Protein Page:
RAF1 (human)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
RAF1 a proto-oncogenic TKL kinase of the RAF family. Functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate and activate MEK1/2, which in turn phosphorylate and activate ERK1/2. Acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MEK1/2) and the extracellular signal-regulated kinases (ERK1/2). RAF1, subsequent to phosphorylation by PAK1, phosphorylates BAD (Bcl2-antagonist of cell death) at S75. Phosphorylates adenylyl cyclases ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2 (cardiac muscle troponin T). Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (ASK1 and MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.1; Kinase, protein; Protein kinase, TKL; Protein kinase, Ser/Thr (non-receptor); TKL group; RAF family
Cellular Component: Golgi apparatus; mitochondrial outer membrane; cytoplasm; plasma membrane; pseudopodium; nucleus; cytosol
Molecular Function: small GTPase binding; identical protein binding; protein serine/threonine kinase activity; protein binding; MAP kinase kinase kinase activity; protein heterodimerization activity; mitogen-activated protein kinase kinase binding; metal ion binding; ATP binding; protein kinase activity
Biological Process: axon guidance; nerve growth factor receptor signaling pathway; wound healing; activation of MAPKK activity; apoptosis; heart development; intermediate filament cytoskeleton organization and biogenesis; negative regulation of caspase activity; signal transduction; protein amino acid phosphorylation; regulation of apoptosis; synaptic transmission; negative regulation of cell proliferation; small GTPase mediated signal transduction; regulation of cell differentiation; transmembrane transport; epidermal growth factor receptor signaling pathway; platelet activation; fibroblast growth factor receptor signaling pathway; adenylate cyclase activation; MAPKKK cascade; positive regulation of peptidyl-serine phosphorylation; cell proliferation; Ras protein signal transduction; insulin receptor signaling pathway; regulation of Rho protein signal transduction; response to hypoxia; innate immune response; blood coagulation; negative regulation of protein complex assembly; negative regulation of apoptosis
Reference #:  P04049 (UniProtKB)
Alt. Names/Synonyms: c-Raf; cRaf; NS5; Oncogene RAF1; Proto-oncogene c-RAF; RAF; raf proto-oncogene serine/threonine protein kinase; RAF proto-oncogene serine/threonine-protein kinase; Raf-1; RAF1; v-raf-1 murine leukemia viral oncogene homolog 1
Gene Symbols: RAF1
Molecular weight: 73,052 Da
Basal Isoelectric point: 9.33  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  IL6 Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  T Cell Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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RAF1

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
carcinogenesis, induced: S338‑p
cell cycle regulation: S338‑p
cell growth, altered: S259‑p, S621‑p
enzymatic activity, induced: T269‑p, S289‑p, S296‑p, S301‑p, S338‑p, S339‑p, Y340‑p, Y341‑p, S471‑p, T481‑p, T491‑p, S494‑p, S497‑p, S499‑p, S619‑p, S621‑p
enzymatic activity, inhibited: S29‑p, S43‑p, S259‑p, S289‑p, S296‑p, S301‑p, Y340‑p, Y341‑p, S621‑p, S642‑p
intracellular localization: S29‑p, S43‑p, S259‑p, S289‑p, S296‑p, S301‑p, S338‑p, S339‑p, Y341‑p, S642‑p
molecular association, regulation: S29‑p, S43‑p, S233‑p, S259‑p, S289‑p, S296‑p, S301‑p, S338‑p, S339‑p, Y340‑p, S471‑p, S621‑p, S642‑p
phosphorylation: S259‑p, Y340‑p, Y341‑p, S499‑p, S621‑p
protein conformation: S338‑p, S621‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
2 6 S29-p FDGSSCIsPtIVQQF
0 1 T31-p GSSCIsPtIVQQFGy
0 2 Y38-p tIVQQFGyQRRAsDD
17 13 S43-p FGyQRRAsDDGKLTD
0 4 S211-p SGVPALPsLtMRRMR
0 5 T213-p VPALPsLtMRRMREs
0 1 S220-p tMRRMREsVSRMPVS
0 1 Y232-p PVSSQHRystPHAFt
2 3 S233-p VSSQHRystPHAFtF
0 5 T234-p SSQHRystPHAFtFN
0 1 T239-p ystPHAFtFNTSsPS
0 4 S244-p AFtFNTSsPSSEGSL
0 12 S252-p PSSEGSLsQRQRsts
1 28 S257-p SLsQRQRststPNVH
0 21 T258-p LsQRQRststPNVHM
45 140 S259-p sQRQRststPNVHMV
1 26 T260-p QRQRststPNVHMVS
4 0 T269-p NVHMVSTtLPVDSRM
0 2 S283-p MIEDAIRsHsEsAsP
0 5 S285-p EDAIRsHsEsAsPsA
0 3 S287-p AIRsHsEsAsPsALs
3 54 S289-p RsHsEsAsPsALsss
0 16 S291-p HsEsAsPsALsssPN
0 3 S294-p sAsPsALsssPNNLs
0 10 S295-p AsPsALsssPNNLsP
4 57 S296-p sPsALsssPNNLsPt
4 74 S301-p sssPNNLsPtGWsQP
0 17 T303-p sPNNLsPtGWsQPKt
0 1 S306-p NLsPtGWsQPKtPVP
0 3 T310-p tGWsQPKtPVPAQRE
0 2 T324-p ERAPVSGtQEKNKIR
73 8 S338-p RPRGQRDssyyWEIE
8 2 S339-p PRGQRDssyyWEIEA
23 2 Y340-p RGQRDssyyWEIEAS
28 2 Y341-p GQRDssyyWEIEASE
1 7 S357-p MLSTRIGsGsFGTVY
1 0 S359-p STRIGsGsFGTVYKG
0 2 K378-u DVAVKILkVVDPTPE
2 2 S471-p IIHRDMKsNNIFLHE
1 2 T481-p IFLHEGLtVKIGDFG
5 0 T491-p IGDFGLAtVksRWsG
0 2 K493-u DFGLAtVksRWsGsQ
5 0 S494-p FGLAtVksRWsGsQQ
2 0 S497-p AtVksRWsGsQQVEQ
2 0 S499-p VksRWsGsQQVEQPT
0 1 S612-p SIELLQHsLPKINRs
1 3 S619-p sLPKINRsAsEPSLH
22 41 S621-p PKINRsAsEPSLHRA
0 1 T638-p TEDINACtLtTsPRL
0 1 T640-p DINACtLtTsPRLPV
1 26 S642-p NACtLtTsPRLPVF_
9421 : Phospho-c-Raf (Ser259) Antibody
9392 : Phospho-c-Raf (Ser289) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9423 : Phospho-c-Raf (Ser296) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9427 : Phospho-c-Raf (Ser338) (56A6) Rabbit mAb
  mouse

 
S29 FDGSSCISPtIVQQF
T31-p GSSCISPtIVQQFGY
Y38 tIVQQFGYQRRAsDD
S43-p FGYQRRAsDDGKLTD
S211 SGVPAPPSFPMRRMR
P213 VPAPPSFPMRRMRES
S220 PMRRMRESVSRMPAS
Y232 PASSQHRYstPHAFt
S233-p ASSQHRYstPHAFtF
T234-p SSQHRYstPHAFtFN
T239-p YstPHAFtFNTSsPS
S244-p AFtFNTSsPSSEGSL
S252 PSSEGSLSQRQRSts
S257 SLSQRQRStsTPNVH
T258-p LSQRQRStsTPNVHM
S259-p SQRQRStsTPNVHMV
T260 QRQRStsTPNVHMVS
T269 NVHMVSTTLHVDSRM
S283 MIEDAIRSHSESAsP
S285 EDAIRSHSESAsPsA
S287 AIRSHSESAsPsALs
S289-p RSHSESAsPsALsss
S291-p HSESAsPsALsssPN
S294-p SAsPsALsssPNNLs
S295-p AsPsALsssPNNLsP
S296-p sPsALsssPNNLsPt
S301-p sssPNNLsPtGWsQP
T303-p sPNNLsPtGWsQPKT
S306-p NLsPtGWsQPKTPVP
T310 tGWsQPKTPVPAQRE
T324 ERAPGSGTQEKNKIR
S338-p RPRGQRDssyyWEIE
S339-p PRGQRDssyyWEIEA
Y340-p RGQRDssyyWEIEAS
Y341-p GQRDssyyWEIEASE
S357 MLSTRIGSGSFGTVY
S359 STRIGSGSFGTVYKG
K378 DVAVKILKVVDPTPE
S471 IIHRDMKSNNIFLHE
T481 IFLHEGLTVKIGDFG
T491-p IGDFGLAtVKsRWSG
K493 DFGLAtVKsRWSGSQ
S494-p FGLAtVKsRWSGSQQ
S497 AtVKsRWSGSQQVEQ
S499 VKsRWSGSQQVEQPT
S612 SIELLQHSLPKINRs
S619-p SLPKINRsAsEPSLH
S621-p PKINRsAsEPSLHRA
T638 TEDINACTLTTsPRL
T640 DINACTLTTsPRLPV
S642-p NACTLTTsPRLPVF_
9421 : Phospho-c-Raf (Ser259) Antibody
9392 : Phospho-c-Raf (Ser289) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9423 : Phospho-c-Raf (Ser296) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9431 : Phospho-c-Raf (Ser289/296/301) Antibody
9427 : Phospho-c-Raf (Ser338) (56A6) Rabbit mAb
  rat

 
S29 FDGSSCISPTIVQQF
T31 GSSCISPTIVQQFGY
Y38 TIVQQFGYQRRAsDD
S43-p FGYQRRAsDDGKLTD
S211 SGVPAPPSFTMRRMR
T213 VPAPPSFTMRRMRES
S220 TMRRMRESVSRMPAS
Y232 PASSQHRYSTPHAFT
S233 ASSQHRYSTPHAFTF
T234 SSQHRYSTPHAFTFN
T239 YSTPHAFTFNTSSPS
S244 AFTFNTSSPSSEGSL
S252 PSSEGSLSQRQRSTs
S257 SLSQRQRSTsTPNVH
T258 LSQRQRSTsTPNVHM
S259-p SQRQRSTsTPNVHMV
T260 QRQRSTsTPNVHMVS
T269 NVHMVSTTLPVDSRM
S283 MIEDAIRSHSESASP
S285 EDAIRSHSESASPSA
S287 AIRSHSESASPSALS
S289 RSHSESASPSALSSs
S291 HSESASPSALSSsPN
S294 SASPSALSSsPNNLs
S295 ASPSALSSsPNNLsP
S296-p SPSALSSsPNNLsPT
S301-p SSsPNNLsPTGWSQP
T303 sPNNLsPTGWSQPKT
S306 NLsPTGWSQPKTPVP
T310 TGWSQPKTPVPAQRE
T324 ERAPGSGTQEKNKIR
S338-p RPRGQRDsSyyWEIE
S339 PRGQRDsSyyWEIEA
Y340-p RGQRDsSyyWEIEAS
Y341-p GQRDsSyyWEIEASE
S357 MLSTRIGSGSFGTVY
S359 STRIGSGSFGTVYKG
K378 DVAVKILKVVDPTPE
S471 IIHRDMKSNNIFLHE
T481 IFLHEGLTVKIGDFG
T491 IGDFGLATVKSRWSG
K493 DFGLATVKSRWSGSQ
S494 FGLATVKSRWSGSQQ
S497 ATVKSRWSGSQQVEQ
S499 VKSRWSGSQQVEQPT
S612 SIELLQHSLPKINRS
S619 SLPKINRSAsEPSLH
S621-p PKINRSAsEPSLHRA
T638 TEDINACTLTTSPRL
T640 DINACTLTTSPRLPV
S642 NACTLTTSPRLPVF_
9421 : Phospho-c-Raf (Ser259) Antibody
9392 : Phospho-c-Raf (Ser289) Antibody
9423 : Phospho-c-Raf (Ser296) Antibody
9427 : Phospho-c-Raf (Ser338) (56A6) Rabbit mAb
  chicken

 
S29 FDGPNCISPTIVQQF
T31 GPNCISPTIVQQFGY
Y38 TIVQQFGYQRRASDD
S43 FGYQRRASDDGKISD
P211 SGVPALPPLTMRRMR
T213 VPALPPLTMRRMRES
S220 TMRRMRESVSRIPVS
Y232 PVSSQHRYSTPHVFT
S233 VSSQHRYSTPHVFTF
T234 SSQHRYSTPHVFTFN
T239 YSTPHVFTFNTSNPS
N244 VFTFNTSNPSSEGTL
S252 PSSEGTLSQRQRSTS
S257 TLSQRQRSTSTPNVH
T258 LSQRQRSTSTPNVHM
S259 SQRQRSTSTPNVHMV
T260 QRQRSTSTPNVHMVS
T269 NVHMVSTTMPVDSRI
N283 IIEDAIRNHSESASP
S285 EDAIRNHSESASPSA
S287 AIRNHSESASPSALS
S289 RNHSESASPSALSGS
S291 HSESASPSALSGSPN
S294 SASPSALSGSPNNMS
G295 ASPSALSGSPNNMSP
S296 SPSALSGSPNNMSPT
S301 SGSPNNMSPTGWSQP
T303 SPNNMSPTGWSQPKT
S306 NMSPTGWSQPKTPVP
T310 TGWSQPKTPVPAQRE
T324 ERAPGTNTQEKNKIR
S338-p RPRGQRDssyyWEIE
S339-p PRGQRDssyyWEIEA
Y340-p RGQRDssyyWEIEAS
Y341-p GQRDssyyWEIEASE
S357 MLSTRIGSGSFGTVY
S359 STRIGSGSFGTVYKG
K378 DVAVKILKVVDPTPE
S471 IIHRDMKSNNIFLHE
T481 IFLHEGLTVKIGDFG
T491 IGDFGLATVKSRWSG
K493 DFGLATVKSRWSGSQ
S494 FGLATVKSRWSGSQQ
S497 ATVKSRWSGSQQVEQ
S499 VKSRWSGSQQVEQPT
S612 SIELLQHSLPKINRS
S619 SLPKINRSASEPSLH
S621 PKINRSASEPSLHRA
T638 TEDINSCTLTSTRLP
T640 DINSCTLTSTRLPVF
T642 NSCTLTSTRLPVF__
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