Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  RAF proto-oncogene serine/threonine-protein kinase  

UniProtKB / Swiss-Prot ID :  RAF1_HUMAN

Gene Name (Synonyms) : 
RAF1, RAF  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphoryl 

Protein Function :  Serine/threonine-protein kinase that 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 (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2- antagonist of cell death at 'Ser-75'. 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 (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. 

Protein Sequence MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRVFLPNKQRTVV...
Predicted Secondary Structure CCCHHHHHHHHHCCCCCHHHHCCCCCCCCHHHHHHCCCCCCCCCCCCCCCCCCCCCEEEEECCCCCEEEE...
Protein Variant
LocationDescription
256R -> S (in NS5). VAR_037807
257S -> L (in NS5 and LEOPARD2; shows invitro greater kinase activity and
259S -> A (in an ovarian serous carcinomasample; somatic mutation; increased ERK
259S -> F (in NS5). VAR_037809
260T -> I (in hypertrophic cardiomyopathy). VAR_037810
260T -> R (in NS5). VAR_037811
261P -> A (in NS5; shows in vitro greaterkinase activity and enhanced MAPK1
261P -> L (in NS5; shows greater kinaseactivity and enhanced MAPK1 activation
261P -> S (in NS5; shows in vitro greaterkinase activity and enhanced MAPK1
263V -> A (in NS5; shows in vitro greaterkinase activity and enhanced MAPK1
308P -> L (in dbSNP:rs5746220). VAR_018840
335Q -> H (in a lung adenocarcinoma sample;somatic mutation).
486D -> G (in NS5). VAR_037816
486D -> N (in NS5; has reduced or absentkinase activity).
491T -> I (in NS5; has reduced or absentkinase activity).
491T -> R (in NS5). VAR_037819
612S -> T (in NS5). VAR_037820
613L -> V (in NS5 and LEOPARD2; shows invitro greater kinase activity and
- top -

Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
- top -

Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
29PhosphoserineSSCISPTIV
CCCCCHHHH
21.96PhosphoELM
Link-
29PhosphoserineSSCISPTIV
CCCCCHHHH
21.96Phosphositeplus
Link-
29Phosphoserine (MAPK1)SSCISPTIV
CCCCCHHHH
21.96HPRD
Link-
43PhosphoserineQRRASDDGK
CCCCCCCCC
34.13Phosphositeplus
Link-
43PhosphoserineQRRASDDGK
CCCCCCCCC
34.13SysPTM
Link-
43Phosphoserine (PKA_group)QRRASDDGK
CCCCCCCCC
34.13PhosphoELM
Link-
43Phosphoserine (PRKACA)QRRASDDGK
CCCCCCCCC
34.13HPRD
Link-
43Phosphoserine; by PKA and MAPK1.QRRASDDGK
CCCCCCCCC
34.13UniProtKB
Link-
232PhosphotyrosineSQHRYSTPH
CCCCCCCCC
18.12Phosphositeplus
Link-
233PhosphoserineQHRYSTPHA
CCCCCCCCC
35.10PhosphoELM
Link-
233PhosphoserineQHRYSTPHA
CCCCCCCCC
35.10Phosphositeplus
Link-
233Phosphoserine (PRKACA)QHRYSTPHA
CCCCCCCCC
35.10HPRD
Link-
233Phosphoserine; by PKA.QHRYSTPHA
CCCCCCCCC
35.10UniProtKB
Link-
234PhosphothreonineHRYSTPHAF
CCCCCCCCC
15.34Phosphositeplus
Link-
239PhosphothreoninePHAFTFNTS
CCCCCCCCC
19.43Phosphositeplus
Link-
244PhosphoserineFNTSSPSSE
CCCCCCCCC
27.11HPRD
Link-
244PhosphoserineFNTSSPSSE
CCCCCCCCC
27.11Phosphositeplus
Link-
244PhosphoserineFNTSSPSSE
CCCCCCCCC
27.11SysPTM
Link-
244Phosphoserine.FNTSSPSSE
CCCCCCCCC
27.11UniProtKB
Link-
252PhosphoserineEGSLSQRQR
CCCCCCCCC
25.64HPRD
Link-
252PhosphoserineEGSLSQRQR
CCCCCCCCC
25.64PhosphoELM
Link-
252PhosphoserineEGSLSQRQR
CCCCCCCCC
25.64Phosphositeplus
Link-
252Phosphoserine.EGSLSQRQR
CCCCCCCCC
25.64UniProtKB
Link-
257PhosphoserineQRQRSTSTP
CCCCCCCCC
20.55HPRD
Link-
257PhosphoserineQRQRSTSTP
CCCCCCCCC
20.55PhosphoELM
Link-
257PhosphoserineQRQRSTSTP
CCCCCCCCC
20.55Phosphositeplus
Link-
257Phosphoserine.QRQRSTSTP
CCCCCCCCC
20.55UniProtKB
Link-
258PhosphothreonineRQRSTSTPN
CCCCCCCCC
38.52HPRD
Link-
258PhosphothreonineRQRSTSTPN
CCCCCCCCC
38.52PhosphoELM
Link-
258PhosphothreonineRQRSTSTPN
CCCCCCCCC
38.52Phosphositeplus
Link-
258Phosphothreonine.RQRSTSTPN
CCCCCCCCC
38.52UniProtKB
Link-
259PhosphoserineQRSTSTPNV
CCCCCCCCC
43.01HPRD
Link-
259PhosphoserineQRSTSTPNV
CCCCCCCCC
43.01Phosphositeplus
Link-
259PhosphoserineQRSTSTPNV
CCCCCCCCC
43.01SysPTM
Link-
259Phosphoserine (AKT1)QRSTSTPNV
CCCCCCCCC
43.01HPRD
Link-
259Phosphoserine (PKA_group;PKB_group)QRSTSTPNV
CCCCCCCCC
43.01PhosphoELM
Link-
259Phosphoserine (PRKACA)QRSTSTPNV
CCCCCCCCC
43.01HPRD
Link-
259Phosphoserine; by PKA, PKC and PKB/AKT1.QRSTSTPNV
CCCCCCCCC
43.01UniProtKB
Link-
260PhosphothreonineRSTSTPNVH
CCCCCCCCC
20.97HPRD
Link-
260PhosphothreonineRSTSTPNVH
CCCCCCCCC
20.97PhosphoELM
Link-
260PhosphothreonineRSTSTPNVH
CCCCCCCCC
20.97Phosphositeplus
Link-
268Phosphothreonine (RAF1)HMVSTTLPV
CCCCCCCCC
22.42HPRD
Link-
268Phosphothreonine; by autocatalysis.HMVSTTLPV
CCCCCCCCC
22.42UniProtKB
Link-
269PhosphothreonineMVSTTLPVD
CCCCCCCCC
22.89HPRD
Link-
269PhosphothreonineMVSTTLPVD
CCCCCCCCC
22.89Phosphositeplus
Link-
269Phosphothreonine (KSR1;KSR1)MVSTTLPVD
CCCCCCCCC
22.89PhosphoELM
Link-
269Phosphothreonine; by PKA.MVSTTLPVD
CCCCCCCCC
22.89UniProtKB
Link-
289PhosphoserineSESASPSAL
CCCCCCCCC
28.77PhosphoELM
Link-
289PhosphoserineSESASPSAL
CCCCCCCCC
28.77Phosphositeplus
Link-
289Phosphoserine (MAPK1)SESASPSAL
CCCCCCCCC
28.77HPRD
Link-
289Phosphoserine; by MAPK1.SESASPSAL
CCCCCCCCC
28.77UniProtKB
Link-
291PhosphoserineSASPSALSS
CCCCCCCCC
39.07HPRD
Link-
294PhosphoserinePSALSSSPN
CCCCCCCCC
28.61HPRD
Link-
294PhosphoserinePSALSSSPN
CCCCCCCCC
28.61PhosphoELM
Link-
294PhosphoserinePSALSSSPN
CCCCCCCCC
28.61SysPTM
Link-
294Phosphoserine.PSALSSSPN
CCCCCCCCC
28.61UniProtKB
Link-
295PhosphoserineSALSSSPNN
CCCCCCCCC
51.14HPRD
Link-
296PhosphoserineALSSSPNNL
CCCCCCCCC
28.42PhosphoELM
Link-
296PhosphoserineALSSSPNNL
CCCCCCCCC
28.42Phosphositeplus
Link-
296Phosphoserine (MAPK1)ALSSSPNNL
CCCCCCCCC
28.42HPRD
Link-
301PhosphoserinePNNLSPTGW
CCCCCCCCC
23.65PhosphoELM
Link-
301PhosphoserinePNNLSPTGW
CCCCCCCCC
23.65Phosphositeplus
Link-
301PhosphoserinePNNLSPTGW
CCCCCCCCC
23.65SysPTM
Link-
301Phosphoserine (MAPK1)PNNLSPTGW
CCCCCCCCC
23.65HPRD
Link-
301Phosphoserine; by MAPK1.PNNLSPTGW
CCCCCCCCC
23.65UniProtKB
Link-
303PhosphothreonineNLSPTGWSQ
CCCCCCCCC
48.16HPRD
Link-
338PhosphoserineGQRDSSYYW
CCCCCCCCC
23.56Phosphositeplus
Link-
338Phosphoserine (PAK1)GQRDSSYYW
CCCCCCCCC
23.56HPRD
Link-
338Phosphoserine (PAK3)GQRDSSYYW
CCCCCCCCC
23.56HPRD
Link-
338Phosphoserine (PAK_group;PAK_group;PAK3;PAK1;PAK1)GQRDSSYYW
CCCCCCCCC
23.56PhosphoELM
Link-
338Phosphoserine (RHEB)GQRDSSYYW
CCCCCCCCC
23.56HPRD
Link-
338Phosphoserine (SRC)GQRDSSYYW
CCCCCCCCC
23.56HPRD
Link-
338Phosphoserine; by PAK1, PAK2, PAK3 andPAK7/PAK5.GQRDSSYYW
CCCCCCCCC
23.56UniProtKB
Link-
339PhosphoserineQRDSSYYWE
CCCCCCCCC
26.91HPRD
Link-
339PhosphoserineQRDSSYYWE
CCCCCCCCC
26.91Phosphositeplus
Link-
339Phosphoserine (PAK1)QRDSSYYWE
CCCCCCCCC
26.91PhosphoELM
Link-
339Phosphoserine (SRC)QRDSSYYWE
CCCCCCCCC
26.91HPRD
Link-
339Phosphoserine; by PAK1, PAK2 and PAK3.QRDSSYYWE
CCCCCCCCC
26.91UniProtKB
Link-
340DePhosphotyrosineRDSSYYWEI
CCCCCCCCC
19.29HPRD
Link-
340PhosphotyrosineRDSSYYWEI
CCCCCCCCC
19.29PhosphoELM
Link-
340PhosphotyrosineRDSSYYWEI
CCCCCCCCC
19.29Phosphositeplus
Link-
340Phosphotyrosine (JAK2)RDSSYYWEI
CCCCCCCCC
19.29HPRD
Link-
340Phosphotyrosine (SRC)RDSSYYWEI
CCCCCCCCC
19.29HPRD
Link-
340Phosphotyrosine; by SRC.RDSSYYWEI
CCCCCCCCC
19.29UniProtKB
Link-
341PhosphotyrosineDSSYYWEIE
CCCCCCCCC
9.86Phosphositeplus
Link-
341Phosphotyrosine (JAK2)DSSYYWEIE
CCCCCCCCC
9.86HPRD
Link-
341Phosphotyrosine (SRC)DSSYYWEIE
CCCCCCCCC
9.86HPRD
Link-
341Phosphotyrosine (SRC)DSSYYWEIE
CCCCCCCCC
9.86PhosphoELM
Link-
341Phosphotyrosine; by SRC.DSSYYWEIE
CCCCCCCCC
9.86UniProtKB
Link-
357PhosphoserineTRIGSGSFG
EEEECCCCE
28.97Phosphositeplus
Link-
471PhosphoserineRDMKSNNIF
EEECCCCEE
28.59PhosphoELM
Link-
471PhosphoserineRDMKSNNIF
EEECCCCEE
28.59Phosphositeplus
Link-
471Phosphoserine.RDMKSNNIF
EEECCCCEE
28.59UniProtKB
Link-
481PhosphothreonineHEGLTVKIG
CCCCEEEEE
30.52Phosphositeplus
Link-
491PhosphothreonineFGLATVKSR
CCEEEECCC
33.24HPRD
Link-
491PhosphothreonineFGLATVKSR
CCEEEECCC
33.24PhosphoELM
Link-
491PhosphothreonineFGLATVKSR
CCEEEECCC
33.24Phosphositeplus
Link-
491Phosphothreonine.FGLATVKSR
CCEEEECCC
33.24UniProtKB
Link-
494PhosphoserineATVKSRWSG
EEECCCCCC
34.35HPRD
Link-
494PhosphoserineATVKSRWSG
EEECCCCCC
34.35PhosphoELM
Link-
494PhosphoserineATVKSRWSG
EEECCCCCC
34.35Phosphositeplus
Link-
494Phosphoserine.ATVKSRWSG
EEECCCCCC
34.35UniProtKB
Link-
497PhosphoserineKSRWSGSQQ
CCCCCCCCC
27.70Phosphositeplus
Link-
497Phosphoserine; by PKC.KSRWSGSQQ
CCCCCCCCC
27.70UniProtKB
Link-
499PhosphoserineRWSGSQQVE
CCCCCCCCC
16.36Phosphositeplus
Link-
499Phosphoserine (PKC_group)RWSGSQQVE
CCCCCCCCC
16.36PhosphoELM
Link-
499Phosphoserine (PRKCA)RWSGSQQVE
CCCCCCCCC
16.36HPRD
Link-
499Phosphoserine; by PKC.RWSGSQQVE
CCCCCCCCC
16.36UniProtKB
Link-
563Symmetric dimethylarginine; by PRMT5.FMVGRGYAS
HHHHCCCCC
24.44UniProtKB
Link-
612PhosphoserineLLQHSLPKI
HHHHCCCCC
33.15Phosphositeplus
Link-
612Phosphoserine.LLQHSLPKI
HHHHCCCCC
33.15UniProtKB
Link-
619PhosphoserineKINRSASEP
CCCCCCCCC
31.49HPRD
Link-
619PhosphoserineKINRSASEP
CCCCCCCCC
31.49Phosphositeplus
Link-
621PhosphoserineNRSASEPSL
CCCCCCCCC
51.81Phosphositeplus
Link-
621Phosphoserine (PKA_group)NRSASEPSL
CCCCCCCCC
51.81PhosphoELM
Link-
621Phosphoserine (PRKAA1)NRSASEPSL
CCCCCCCCC
51.81HPRD
Link-
621Phosphoserine (PRKACA)NRSASEPSL
CCCCCCCCC
51.81HPRD
Link-
621Phosphoserine (RAF1)NRSASEPSL
CCCCCCCCC
51.81HPRD
Link-
621Phosphoserine.NRSASEPSL
CCCCCCCCC
51.81UniProtKB
Link-
624PhosphoserineASEPSLHRA
CCCCCCCCC
32.53HPRD
Link-
641PhosphothreonineCTLTTSPRL
CCCCCCCCC
39.59HPRD
Link-
642PhosphoserineTLTTSPRLP
CCCCCCCCC
11.64PhosphoELM
Link-
642PhosphoserineTLTTSPRLP
CCCCCCCCC
11.64Phosphositeplus
Link-
642PhosphoserineTLTTSPRLP
CCCCCCCCC
11.64SysPTM
Link-
642Phosphoserine (MAPK1)TLTTSPRLP
CCCCCCCCC
11.64HPRD
Link-
642Phosphoserine; by MAPK1.TLTTSPRLP
CCCCCCCCC
11.64UniProtKB
Link-
- top -

Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
RASH_HUMANphysical interactionMINT-17119MINT8332187
RASH_HUMANphysical interactionMINT-17120MINT8332187
K1C19_HUMANphysical interactionMINT-51050MINT15314064
MPIP1_HUMANphysical interactionMINT-16191MINT7744247
MPIP1_HUMANphysical interactionMINT-16192MINT7744247
1433B_HUMANphysical interactionMINT-14321MINT7644510
1433B_HUMANphysical interactionMINT-14322MINT7644510
TCPG_HUMANphysical interactionMINT-19325MINT12620389
1433Z_HUMANphysical interactionMINT-45799MINT9153224
PAK1_HUMANphosphorylation reactionMINT-3389399MINT17097642
GRB10_HUMANphysical interactionMINT-14422MINT9553107
GRB10_HUMANphysical interactionMINT-14421MINT9553107
RHEB_HUMANphysical interactionMINT-16188MINT9001246
RHEB_HUMANphysical interactionMINT-19210MINT9001246
RHEB_HUMANphysical interactionMINT-19211MINT9001246
SHOC2_HUMANphysical interactionMINT-15017MINT10783161
RASN_HUMANphysical interactionDIP:602EDIP8876196
1433Z_HUMANphysical interactionDIP:478EDIP7935795
BCL2_HUMANphysical interactionDIP:2EDIP9194558
MP2K1_HUMANphysical interactionDIP:1115EDIP1326789
RAP1A_HUMANphysical interactionDIP:10995EDIP7791872
1433Z_HUMANdirect interaction
physical interaction
EBI-1181878
EBI-445314
intact16306228
10887173
PAK2_HUMANdirect interaction
phosphorylation
EBI-1182700
EBI-1187075
intact16837009
16837009
1433B_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
physical interaction
EBI-537314
EBI-537419
EBI-537
intact12620389
12620389
12620389
12620389
12620389
OIP5_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-537335
EBI-537412
EBI-537
intact12620389
12620389
12620389
12620389
TCPG_HUMANphysical interaction
physical interaction
physical interaction
EBI-537328
EBI-537377
EBI-537
intact12620389
12620389
12620389
INT10_HUMANphysical interaction
physical interaction
EBI-537321
EBI-537244
intact12620389
12620389
CPSM_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-537307
EBI-537405
EBI-537
intact12620389
12620389
12620389
12620389
RRAS2_HUMANphysical interactionEBI-537300
intact12620389
TOPK_HUMANphysical interactionEBI-537293
intact12620389
CSN3_HUMANphysical interaction
physical interaction
EBI-537286
EBI-537384
intact12620389
12620389
NUD14_HUMANphysical interactionEBI-537279
intact12620389
TIM50_HUMANphysical interaction
physical interaction
physical interaction
EBI-537272
EBI-537391
EBI-537
intact12620389
12620389
12620389
RASH_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
physical interaction
physical interaction
EBI-537265
EBI-537342
EBI-537
intact12620389
12620389
12620389
8670882
9144171
10545207
KPYM_HUMANphysical interaction
physical interaction
physical interaction
EBI-537258
EBI-537356
EBI-537
intact12620389
12620389
12620389
FBLN3_HUMANphysical interactionEBI-537251
intact12620389
HS90B_HUMANphysical interactionEBI-974419
intact16330544
RAP1A_HUMANdirect interaction
direct interaction
EBI-1026035
EBI-1026154
intact7791872
8756332
1433F_HUMANin vivoHPRD:01265HPRD8702721
FYN_HUMANin vitro
in vivo
HPRD:01265HPRD7517401
GCR_HUMANin vivoHPRD:01265HPRD11005817
HS90A_HUMANin vivoHPRD:01265HPRD8408024
16093354
INSR_HUMANin vivoHPRD:01265HPRD11409918
JAK1_HUMANin vivoHPRD:01265HPRD9446616
BRAF1_HUMANin vivoHPRD:01265HPRD11325826
RAF1_HUMANin vitro
in vivo
HPRD:01265HPRD11971957
9710607
9091312
8349614
16093354
MP2K1_HUMANin vitro
in vivo
HPRD:01265HPRD11604401
8157000
8621729
8394352
7731720
16093354
BCL2_HUMANin vitro
in vivo
HPRD:01265HPRD8929532
8910675
LCK_HUMANin vivoHPRD:01265HPRD8939988
RASK_HUMANin vitroHPRD:01265HPRD9446616
ARRB2_HUMANin vitroHPRD:01265HPRD11226259
STK3_HUMANin vitro
in vivo
HPRD:01265HPRD15618521
KPCD_HUMANin vitroHPRD:01265HPRD11171046
MP2K2_HUMANin vitro
in vivo
HPRD:01265HPRD9671314
8393135
8157000
SPY2_HUMANin vitroHPRD:01265HPRD12717443
BAD_HUMANin vitroHPRD:01265HPRD8929531
8929532
TA2R_HUMANin vitroHPRD:01265HPRD16413928
HSP7C_HUMANin vitro
in vivo
HPRD:01265HPRD16093354
HSP74_HUMANin vitro
in vivo
HPRD:01265HPRD16093354
MK01_HUMANENSP00000251849STRING
PP2AB_HUMANENSP00000251849STRING
CDC37_HUMANENSP00000251849STRING
BAG1_HUMANENSP00000251849STRING
PAXI_HUMANENSP00000251849STRING
CDN1A_HUMANENSP00000251849STRING
RAP2A_HUMANENSP00000251849STRING
RAP2A_HUMANENSP00000251849STRING
PIN1_HUMANENSP00000251849STRING
PIN1_HUMANENSP00000251849STRING
1433F_HUMANENSP00000251849STRING
RASK_HUMANENSP00000251849STRING
RRAS2_HUMANENSP00000251849STRING
PEBP1_HUMANENSP00000251849STRING
RHEB_HUMANENSP00000251849STRING
PAK3_HUMANENSP00000251849STRING
MP2K2_HUMANENSP00000251849STRING
MK03_HUMANENSP00000251849STRING
1433E_HUMANENSP00000251849STRING
1433E_HUMANENSP00000251849STRING
EGF_HUMANENSP00000251849STRING
VDAC1_HUMANENSP00000251849STRING
RB_HUMANENSP00000251849STRING
P53_HUMANENSP00000251849STRING
AKT1_HUMANENSP00000251849STRING
AGTR1_HUMANENSP00000251849STRING
RASA1_HUMANENSP00000251849STRING
KPCA_HUMANENSP00000251849STRING
BRAF1_HUMANENSP00000251849STRING
RASM_HUMANENSP00000251849STRING
VAV_HUMANENSP00000251849STRING
MP2K1_HUMANENSP00000251849STRING
HSP74_HUMANENSP00000251849STRING
MPIP1_HUMANENSP00000251849STRING
1433G_HUMANENSP00000251849STRING
BAD_HUMANENSP00000251849STRING
RASH_HUMANENSP00000251849STRING
RIN1_HUMANENSP00000251849STRING
PAK2_HUMANENSP00000251849STRING
CDC42_HUMANENSP00000251849STRING
2AAA_HUMANENSP00000251849STRING
2ABA_HUMANENSP00000251849STRING
CSF1_HUMANENSP00000251849STRING
KPCD_HUMANENSP00000251849STRING
HS90A_HUMANENSP00000251849STRING
HS90A_HUMANENSP00000251849STRING
HS90A_HUMANENSP00000251849STRING
STK3_HUMANENSP00000251849STRING
M3K5_HUMANENSP00000251849STRING
MK08_HUMANENSP00000251849STRING
- top -

Disease Reference
Kegg disease
OMIM disease
611553Noonan syndrome 5 (NS5)
611554LEOPARD syndrome 2 (LPRD2)
615916Cardiomyopathy, dilated 1NN (CMD1NN)
Drug Reference
DrugBank
DB08912Dabrafenib
DB08896Regorafenib
DB00398Sorafenib
- top -
Related Literatures of Post-Translational Modification
Methylation
ReferencePubMed
"Protein arginine methyltransferase 5 regulates ERK1/2 signaltransduction amplitude and cell fate through CRAF.";
Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C.,Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R.,Canals F., Merlino G., Avila M.A., Recio J.A.;
Sci. Signal. 4:RA58-RA58(2011).
Cited for: PROTEIN SEQUENCE OF 42-53; 60-65; 310-316 AND 564-572, INTERACTIONWITH PRMT5, METHYLATION AT ARG-563, PHOSPHORYLATION AT SER-289;SER-296; SER-301; SER-338 AND SER-621, AND MUTAGENESIS OF ARG-563.
Phosphorylation
ReferencePubMed
"Identification of the major phosphorylation sites of the Raf-1kinase.";
Morrison D.K., Heidecker G., Rapp U.R., Copeland T.D.;
J. Biol. Chem. 268:17309-17316(1993).
Cited for: PHOSPHORYLATION AT SER-43; SER-259; THR-268; SER-499 AND SER-621.
"Phosphorylation and regulation of Raf by Akt (protein kinase B).";
Zimmermann S., Moelling K.;
Science 286:1741-1744(1999).
Cited for: PHOSPHORYLATION AT SER-259 BY PKB/AKT1, ENZYME REGULATION, ANDINTERACTION WITH PKB/AKT1.
"Raf-1-associated protein phosphatase 2A as a positive regulator ofkinase activation.";
Abraham D., Podar K., Pacher M., Kubicek M., Welzel N., Hemmings B.A.,Dilworth S.M., Mischak H., Kolch W., Baccarini M.;
J. Biol. Chem. 275:22300-22304(2000).
Cited for: PHOSPHORYLATION AT SER-259 AND SER-621, DEPHOSPHORYLATION AT SER-43;SER-259 AND SER-621, ENZYME REGULATION, AND INTERACTION WITH PPP2CAAND PPP2R1B.
"Interaction between active Pak1 and Raf-1 is necessary forphosphorylation and activation of Raf-1.";
Zang M., Hayne C., Luo Z.;
J. Biol. Chem. 277:4395-4405(2002).
Cited for: PHOSPHORYLATION AT SER-338 BY PAK1, ENZYME REGULATION, AND INTERACTIONWITH PAK1.
"Dephosphorylation of Ser-259 regulates Raf-1 membrane association.";
Kubicek M., Pacher M., Abraham D., Podar K., Eulitz M., Baccarini M.;
J. Biol. Chem. 277:7913-7919(2002).
Cited for: PHOSPHORYLATION AT SER-259, DEPHOSPHORYLATION AT SER-259, ANDSUBCELLULAR LOCATION.
"LGI1, a putative tumor metastasis suppressor gene, controls in vitroinvasiveness and expression of matrix metalloproteinases in gliomacells through the ERK1/2 pathway.";
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
J. Biol. Chem. 279:23151-23157(2004).
Cited for: PHOSPHORYLATION AT SER-259.
"p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1regulates its mitochondrial localization, phosphorylation of BAD, andBcl-2 association.";
Jin S., Zhuo Y., Guo W., Field J.;
J. Biol. Chem. 280:24698-24705(2005).
Cited for: FUNCTION IN THE PHOSPHORYLATION OF BAD, PHOSPHORYLATION AT SER-338 ANDSER-339 BY PAK1, SUBCELLULAR LOCATION, AND INTERACTION WITH BCL2.
"Identification of Raf-1 S471 as a novel phosphorylation site criticalfor Raf-1 and B-Raf kinase activities and for MEK binding.";
Zhu J., Balan V., Bronisz A., Balan K., Sun H., Leicht D.T., Luo Z.,Qin J., Avruch J., Tzivion G.;
Mol. Biol. Cell 16:4733-4744(2005).
Cited for: PHOSPHORYLATION AT SER-471.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-301, ANDMASS SPECTROMETRY.
"A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalyticsubunit of PP1 functions as an M-Ras effector to modulate Rafactivity.";
Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M.,McCormick F.;
Mol. Cell 22:217-230(2006).
Cited for: IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; SHOC2 ANDMRAS, PHOSPHORYLATION AT SER-259, AND CHARACTERIZATION OF VARIANTALA-259.
"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage.";
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
Science 316:1160-1166(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND MASSSPECTROMETRY.
"Evaluation of the low-specificity protease elastase for large-scalephosphoproteome analysis.";
Wang B., Malik R., Nigg E.A., Korner R.;
Anal. Chem. 80:9526-9533(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, AND MASSSPECTROMETRY.
"p21 activated kinase 5 activates Raf-1 and targets it tomitochondria.";
Wu X., Carr H.S., Dan I., Ruvolo P.P., Frost J.A.;
J. Cell. Biochem. 105:167-175(2008).
Cited for: PHOSPHORYLATION AT SER-338 BY PAK5.
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis.";
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III;
J. Proteome Res. 7:1346-1351(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257 AND THR-258, ANDMASS SPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43; SER-244 AND SER-259,AND MASS SPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, AND MASSSPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289; SER-301 ANDSER-612, AND MASS SPECTROMETRY.
"Protein arginine methyltransferase 5 regulates ERK1/2 signaltransduction amplitude and cell fate through CRAF.";
Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C.,Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R.,Canals F., Merlino G., Avila M.A., Recio J.A.;
Sci. Signal. 4:RA58-RA58(2011).
Cited for: PROTEIN SEQUENCE OF 42-53; 60-65; 310-316 AND 564-572, INTERACTIONWITH PRMT5, METHYLATION AT ARG-563, PHOSPHORYLATION AT SER-289;SER-296; SER-301; SER-338 AND SER-621, AND MUTAGENESIS OF ARG-563.
"Phosphorylation of Raf by ceramide-activated protein kinase.";
Yao B., Zhang Y., Delikat S., Mathias S., Basu S., Kolesnick R.;
Nature 378:307-310(1995).
Cited for: PROTEIN SEQUENCE OF 254-278, AND PHOSPHORYLATION AT THR-269.
- top -
Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures