Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Serine/threonine-protein kinase B-raf  

UniProtKB / Swiss-Prot ID :  BRAF_HUMAN

Gene Name (Synonyms) : 
BRAF, BRAF1, RAFB1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Nucleus (By similarity). Cytoplasm. Cell membrane (By similarity). Note=Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes (By similarity). 

Protein Function :  Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. 

Protein Sequence MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGG...
Predicted Secondary Structure  -
Protein Variant
LocationDescription
241T -> M (in a patient with Noonansyndrome).
241T -> P (in CFC syndrome and LEOPARD3). VAR_058621
241T -> R (in a patient with Noonansyndrome).
244T -> P (in CFC syndrome). VAR_065171
245L -> F (in CFC syndrome). VAR_058623
246A -> P (in CFC syndrome). VAR_026113
257Q -> R (in CFC syndrome). VAR_026114
262Q -> K (in CFC syndrome). VAR_065172
275E -> K (in CFC syndrome). VAR_058624
301P -> S (in dbSNP:rs34776339). VAR_040391
462R -> I (in colorectal cancer). VAR_018613
463I -> S (in colorectal cancer). VAR_018614
464G -> E (in colorectal cancer). VAR_018615
464G -> V (in a colorectal cancer cell line;elevated kinase activity; efficiently
466G -> A (in melanoma). VAR_018617
466G -> E (in melanoma). VAR_018618
466G -> V (in LNCR). VAR_018512
467S -> A (in CFC syndrome). VAR_035096
468F -> S (in CFC syndrome). VAR_035097
469G -> A (in NHL; also in a lungadenocarcinoma sample; somatic mutation;
469G -> E (in CFC syndrome and coloncancer).
469G -> R (in NHL). VAR_018622
469G -> V (in a colorectal adenocarcinomasample; somatic mutation).
485L -> F (in CFC syndrome). VAR_026115
499K -> E (in CFC syndrome). VAR_026116
499K -> N (in CFC syndrome). VAR_058625
501E -> G (in CFC syndrome). VAR_026117
501E -> K (in CFC syndrome). VAR_026118
525L -> P (in CFC syndrome). VAR_058626
531W -> C (in NS7). VAR_058627
580N -> D (in CFC syndrome). VAR_065173
581N -> D (in CFC syndrome). VAR_026119
581N -> S (in a colorectal adenocarcinomasample; somatic mutation).
586E -> K (in ovarian cancer). VAR_018623
594D -> G (in NHL). VAR_018624
595F -> L (in colon cancer and CFCsyndrome).
596G -> R (in a colorectal adenocarcinomasample; somatic mutation).
596G -> V (in CFC syndrome). VAR_035098
597L -> R (in LNCR; also found in an ovarianserous carcinoma sample; somatic
597L -> V (in NS7; also in a lungadenocarcinoma sample; somatic mutation;
599T -> R (in CFC syndrome). VAR_058628
600V -> D (in a melanoma cell line; requires2 nucleotide substitutions).
600V -> E (in sarcoma, colorectaladenocarcinoma, metastatic melanoma,
601K -> E (in colorectal cancer). VAR_018630
601K -> Q (in CFC syndrome). VAR_058629
638D -> E (in CFC syndrome). VAR_058630
709Q -> R (in CFC syndrome). VAR_058631
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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
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-acetylalanine.---MAALSG
---
19.67UniProtKB
Link-
119PhosphothreonineASMDTVTSS
19.62HPRD
Link-
119PhosphothreonineASMDTVTSS
19.62Phosphositeplus
Link-
147PhosphoserineDVARSNPKS
47.98Phosphositeplus
Link-
147Phosphoserine (BRAF)DVARSNPKS
47.98HPRD
Link-
151PhosphoserineSNPKSPQKP
33.54PhosphoELM
Link-
151PhosphoserineSNPKSPQKP
33.54Phosphositeplus
Link-
151Phosphoserine (BRAF)SNPKSPQKP
33.54HPRD
Link-
151Phosphoserine.SNPKSPQKP
33.54UniProtKB
Link-
319PhosphoserineGSSPSAPAS
49.16HPRD
Link-
319PhosphoserineGSSPSAPAS
49.16PhosphoELM
Link-
333PhosphoserineQILTSPSPS
21.67HPRD
Link-
333PhosphoserineQILTSPSPS
21.67PhosphoELM
Link-
333PhosphoserineQILTSPSPS
21.67Phosphositeplus
Link-
335PhosphoserineLTSPSPSKS
41.39HPRD
Link-
335PhosphoserineLTSPSPSKS
41.39PhosphoELM
Link-
363PhosphoserineQRDRSSSAP
32.69HPRD
Link-
363PhosphoserineQRDRSSSAP
32.69Phosphositeplus
Link-
364PhosphoserineRDRSSSAPN
31.26HPRD
Link-
364PhosphoserineRDRSSSAPN
31.26PhosphoELM
Link-
364PhosphoserineRDRSSSAPN
31.26Phosphositeplus
Link-
365PhosphoserineDRSSSAPNV
49.33Phosphositeplus
Link-
365Phosphoserine (AKT1)DRSSSAPNV
49.33HPRD
Link-
365Phosphoserine (PKB_group;PKB_group;SGK_group)DRSSSAPNV
49.33PhosphoELM
Link-
365Phosphoserine (SGK1)DRSSSAPNV
49.33HPRD
Link-
365Phosphoserine; by SGK1.DRSSSAPNV
49.33UniProtKB
Link-
373PhosphothreonineVHINTIEPV
26.56PhosphoELM
Link-
373PhosphothreonineVHINTIEPV
26.56Phosphositeplus
Link-
373Phosphothreonine (BRAF)VHINTIEPV
26.56HPRD
Link-
373Phosphothreonine; by autocatalysis.VHINTIEPV
26.56UniProtKB
Link-
396Phosphothreonine.GGSTTGLSA
37.51UniProtKB
Link-
399PhosphoserineTTGLSATPP
31.29PhosphoELM
Link-
399Phosphoserine.TTGLSATPP
31.29UniProtKB
Link-
401PhosphothreonineGLSATPPAS
26.82HPRD
Link-
401PhosphothreonineGLSATPPAS
26.82PhosphoELM
Link-
401PhosphothreonineGLSATPPAS
26.82Phosphositeplus
Link-
401PhosphothreonineGLSATPPAS
26.82SysPTM
Link-
401Phosphothreonine.GLSATPPAS
26.82UniProtKB
Link-
418N6-acetyllysineKALQKSPGP
60.51HPRD
Link-
418N6-acetyllysineKALQKSPGP
60.51Phosphositeplus
Link-
418N6-acetyllysine.KALQKSPGP
60.51UniProtKB
Link-
419PhosphoserineALQKSPGPQ
23.33PhosphoELM
Link-
419PhosphoserineALQKSPGPQ
23.33Phosphositeplus
Link-
419Phosphoserine (BRAF)ALQKSPGPQ
23.33HPRD
Link-
419Phosphoserine.ALQKSPGPQ
23.33UniProtKB
Link-
429PhosphoserineERKSSSSSE
36.96Phosphositeplus
Link-
429Phosphoserine (AKT1)ERKSSSSSE
36.96HPRD
Link-
429Phosphoserine (PKA_group;PKB_group)ERKSSSSSE
36.96PhosphoELM
Link-
430Phosphoserine (PRKACA)RKSSSSSED
45.00HPRD
Link-
440PhosphothreonineNRMKTLGRR
25.71HPRD
Link-
440PhosphothreonineNRMKTLGRR
25.71PhosphoELM
Link-
440PhosphothreonineNRMKTLGRR
25.71Phosphositeplus
Link-
446PhosphoserineGRRDSSDDW
33.58HPRD
Link
446PhosphoserineGRRDSSDDW
33.58Phosphositeplus
Link
446PhosphoserineGRRDSSDDW
33.58SysPTM
Link
446Phosphoserine (PAK1)GRRDSSDDW
33.58PhosphoELM
Link
446Phosphoserine (RHEB)GRRDSSDDW
33.58HPRD
Link
446Phosphoserine.GRRDSSDDW
33.58UniProtKB
Link
447PhosphoserineRRDSSDDWE
43.83HPRD
Link
447PhosphoserineRRDSSDDWE
43.83PhosphoELM
Link
447PhosphoserineRRDSSDDWE
43.83Phosphositeplus
Link
447PhosphoserineRRDSSDDWE
43.83SysPTM
Link
447Phosphoserine.RRDSSDDWE
43.83UniProtKB
Link
465PhosphoserineQRIGSGSFG
28.97Phosphositeplus
Link
465Phosphoserine.QRIGSGSFG
28.97UniProtKB
Link
579PhosphoserineRDLKSNNIF
42.26PhosphoELM
Link
579PhosphoserineRDLKSNNIF
42.26Phosphositeplus
Link
599PhosphothreonineFGLATVKSR
33.24HPRD
Link-
599PhosphothreonineFGLATVKSR
33.24PhosphoELM
Link-
599PhosphothreonineFGLATVKSR
33.24Phosphositeplus
Link-
602PhosphoserineATVKSRWSG
34.35HPRD
Link-
602PhosphoserineATVKSRWSG
34.35PhosphoELM
Link-
602PhosphoserineATVKSRWSG
34.35Phosphositeplus
Link-
605PhosphoserineKSRWSGSHQ
29.34Phosphositeplus
Link-
614PhosphoserineFEQLSGSIL
30.13Phosphositeplus
Link
614Phosphoserine.FEQLSGSIL
30.13UniProtKB
Link
671Omega-N-methylarginine; by PRMT5.FMVGRGYLS
21.12UniProtKB
Link
727PhosphoserineKIHRSASEP
23.22PhosphoELM
Link-
729PhosphoserineHRSASEPSL
51.81HPRD
Link-
729PhosphoserineHRSASEPSL
51.81PhosphoELM
Link-
729PhosphoserineHRSASEPSL
51.81Phosphositeplus
Link-
729PhosphoserineHRSASEPSL
51.81SysPTM
Link-
729Phosphoserine.HRSASEPSL
51.81UniProtKB
Link-
746PhosphotyrosineDFSLYACAS
9.84Phosphositeplus
Link-
750PhosphoserineYACASPKTP
27.15PhosphoELM
Link-
750PhosphoserineYACASPKTP
27.15Phosphositeplus
Link-
750Phosphoserine (BRAF)YACASPKTP
27.15HPRD
Link-
750Phosphoserine.YACASPKTP
27.15UniProtKB
Link-
753PhosphothreonineASPKTPIQA
29.07Phosphositeplus
Link-
753Phosphothreonine; by MAPK1.ASPKTPIQA
29.07UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
There are no Protein-Protein Interactions.
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Disease Reference
Kegg disease
H00032 Thyroid cancer
H00038 Malignant melanoma
H00523 Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noona
OMIM disease
0000269|PubMedNote=Defects in BRAF are found in a wide range of cancers. {ECO
114500
211980Lung cancer (LNCR)
605027Familial non-Hodgkin lymphoma (NHL)
115150Cardiofaciocutaneous syndrome 1 (CFC1)
613706Noonan syndrome 7 (NS7)
613707LEOPARD syndrome 3 (LPRD3)
Drug Reference
Kegg drug
D06272 Sorafenib tosilate (JAN); Sorafenib tosylate (USAN); Nexavar (TN)
D08524 Sorafenib (USAN/INN)
D09996 Vemurafenib (USAN/INN); Zelboraf (TN)
D10064 Dabrafenib (USAN)
D10104 Dabrafenib mesylate (USAN); Tafinlar (TN)
DrugBank
DB08912Dabrafenib
DB08896Regorafenib
DB00398Sorafenib
DB08881Vemurafenib
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-418, AND MASS SPECTROMETRY.
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: INTERACTION WITH PRMT5, METHYLATION AT ARG-671, CHARACTERIZATION OFVARIANT GLU-600, AND MUTAGENESIS OF ARG-671.
Phosphorylation
ReferencePubMed
"Serum- and glucocorticoid-inducible kinase SGK phosphorylates andnegatively regulates B-Raf.";
Zhang B.H., Tang E.D., Zhu T., Greenberg M.E., Vojtek A.B., Guan K.L.;
J. Biol. Chem. 276:31620-31626(2001).
Cited for: PHOSPHORYLATION AT SER-365 BY SGK1.
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-729, ANDMASS SPECTROMETRY.
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization.";
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
Nat. Biotechnol. 24:1285-1292(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, AND MASSSPECTROMETRY.
"Improved titanium dioxide enrichment of phosphopeptides from HeLacells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.";
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
J. Proteome Res. 6:4150-4162(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, AND MASSSPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-365; THR-401;SER-419; SER-446; SER-729 AND SER-750, AND MASS SPECTROMETRY.
"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 THR-373, AND MASSSPECTROMETRY.
"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-729, AND MASSSPECTROMETRY.
"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 THR-401; SER-446; SER-447AND SER-729, AND MASS SPECTROMETRY.
"95-kilodalton B-Raf serine/threonine kinase: identification of theprotein and its major autophosphorylation site.";
Stephens R.M., Sithanandam G., Copeland T.D., Kaplan D.R., Rapp U.R.,Morrison D.K.;
Mol. Cell. Biol. 12:3733-3742(1992).
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, ANDPHOSPHORYLATION AT THR-373.
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-729, ANDMASS SPECTROMETRY.
"Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Rafheterodimerization.";
Yasuda S., Kai M., Imai S., Takeishi K., Taketomi A., Toyota M.,Kanoh H., Sakane F.;
J. Biol. Chem. 284:29559-29570(2009).
Cited for: SUBUNIT, INTERACTION WITH DGKH, AND PHOSPHORYLATION AT THR-753 BYMAPK1.
"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-419, 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-465 AND SER-614, ANDMASS SPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures