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UniProtKB/Swiss-Prot entry P15056


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name BRAF1_HUMAN
Primary accession number P15056
Secondary accession numbers Q13878 Q3MIN6 Q9UDP8 Q9Y6T3
Integrated into Swiss-Prot on November 1, 1990
Sequence was last modified on July 19, 2004 (Sequence version 4)
Annotations were last modified on    June 10, 2008 (Entry version 110)
Name and origin of the protein
Protein name B-Raf proto-oncogene serine/threonine-protein kinase
Synonyms EC 2.7.11.1
p94
v-Raf murine sarcoma viral oncogene homolog B1
Gene name
Name: BRAF
Synonyms: BRAF1, RAFB1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT THR-373.
TISSUE=Testis;
PubMed=1508179 [NCBI, ExPASy, EBI, Israel, Japan]
Stephens R.M., Sithanandam G., Copeland T.D., Kaplan D.R., Rapp U.R., Morrison D.K.;
"95-kilodalton B-Raf serine/threonine kinase: identification of the protein and its major autophosphorylation site.";
Mol. Cell. Biol. 12:3733-3742(1992).
[2]
SEQUENCE REVISION TO 31-33.
Albert S., Wixler L., Rapp U.R.;
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature01782; PubMed=12853948 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Liver;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200.
TISSUE=Placenta;
PubMed=1630826 [NCBI, ExPASy, EBI, Israel, Japan]
Eychene A., Barnier J.V., Apiou F., Dutrillaux B., Calothy G.;
"Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene.";
Oncogene 7:1657-1660(1992).
[6]
PROTEIN SEQUENCE OF 2-51; 56-95; 151-158; 253-260; 294-354; 361-424; 444-507; 510-522; 559-570; 579-626; 663-680; 692-698; 702-719; 727-735 AND 753-766, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, PHOSPHORYLATION AT THR-401 AND SER-729, AND MASS SPECTROMETRY.
TISSUE=Hepatoma;
Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.;
Submitted (JUL-2007) to UniProtKB.
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 117-766.
TISSUE=Testis;
PubMed=2284096 [NCBI, ExPASy, EBI, Israel, Japan]
Sithanandam G., Kolch W., Duh F.-M., Rapp U.R.;
"Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies.";
Oncogene 5:1775-1780(1990).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 439-766.
PubMed=3043188 [NCBI, ExPASy, EBI, Israel, Japan]
Ikawa S., Fukui M., Ueyama Y., Tamaoki N., Yamamoto T., Toyoshima K.;
"B-raf, a new member of the raf family, is activated by DNA rearrangement.";
Mol. Cell. Biol. 8:2651-2654(1988).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-729, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1021/pr070152u; PubMed=17924679 [NCBI, ExPASy, EBI, Israel, Japan]
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.";
J. Proteome Res. 6:4150-4162(2007).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-365; THR-401; SER-419; SER-446; SER-729 AND SER-750, AND MASS SPECTROMETRY.
DOI=10.1074/mcp.T600062-MCP200; PubMed=17192257 [NCBI, ExPASy, EBI, Israel, Japan]
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H.;
"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.";
Mol. Cell. Proteomics 6:537-547(2007).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[14]
VARIANTS LUNG CANCER VAL-466 AND ARG-597.
PubMed=12460919 [NCBI, ExPASy, EBI, Israel, Japan]
Naoki K., Chen T.-H., Richards W.G., Sugarbaker D.J., Meyerson M.;
"Missense mutations of the BRAF gene in human lung adenocarcinoma.";
Cancer Res. 62:7001-7003(2002).
[15]
VARIANTS CANCER GLU-464; VAL-464; ALA-466; GLU-466; VAL-466; ALA-469; GLU-469; LYS-586; LEU-595; ARG-596; ARG-597; VAL-597; GLU-600 AND ASP-600, AND CHARACTERIZATION OF VARIANTS CANCER VAL-464; ALA-469; VAL-597 AND GLU-600.
DOI=10.1038/nature00766; PubMed=12068308 [NCBI, ExPASy, EBI, Israel, Japan]
Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S., Teague J., Woffendin H., Garnett M.J., Bottomley W., Davis N., Dicks E., Ewing R., Floyd Y., Gray K., Hall S., Hawes R., Hughes J., Kosmidou V., Menzies A., Mould C., Parker A., Stevens C., Watt S., Hooper S., Wilson R., Jayatilake H., Gusterson B.A., Cooper C., Shipley J., Hargrave D., Pritchard-Jones K., Maitland N., Chenevix-Trench G., Riggins G.J., Bigner D.D., Palmieri G., Cossu A., Flanagan A., Nicholson A., Ho J.W.C., Leung S.Y., Yuen S.T., Weber B.L., Seigler H.F., Darrow T.L., Paterson H., Marais R., Marshall C.J., Wooster R., Stratton M.R., Futreal P.A.;
"Mutations of the BRAF gene in human cancer.";
Nature 417:949-954(2002).
[16]
VARIANTS COLORECTAL CANCER ILE-462; SER-463; GLU-464; GLU-600 AND GLU-601.
DOI=10.1038/418934a; PubMed=12198537 [NCBI, ExPASy, EBI, Israel, Japan]
Rajagopalan H., Bardelli A., Lengauer C., Kinzler K.W., Vogelstein B., Velculescu V.E.;
"Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.";
Nature 418:934-934(2002).
[17]
VARIANTS NHL ALA-469; ARG-469 AND GLY-594.
DOI=10.1038/sj.bjc.6601371; PubMed=14612909 [NCBI, ExPASy, EBI, Israel, Japan]
Lee J.W., Yoo N.J., Soung Ark W.S., Kim S.Y., Lee J.H., Park J.Y., Cho Y.G., Kim C.J., Ko Y.H., Kim S.H., Nam S.W., Lee J.Y., Lee S.H.;
"BRAF mutations in non-Hodgkin's lymphoma.";
Br. J. Cancer 89:1958-1960(2003).
[18]
CHARACTERIZATION OF VARIANT MELANOMA GLU-600.
PubMed=14500344 [NCBI, ExPASy, EBI, Israel, Japan]
Hingorani S.R., Jacobetz M.A., Robertson G.P., Herlyn M., Tuveson D.A.;
"Suppression of BRAF(V599E) in human melanoma abrogates transformation.";
Cancer Res. 63:5198-5202(2003).
[19]
VARIANTS CFC SYNDROME PRO-246; ARG-257; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501 AND ASP-581.
DOI=10.1038/ng1749; PubMed=16474404 [NCBI, ExPASy, EBI, Israel, Japan]
Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N., Hennekam R.C.M., Gillessen-Kaesbach G., Wieczorek D., Kavamura M.I., Kurosawa K., Ohashi H., Wilson L., Heron D., Bonneau D., Corona G., Kaname T., Naritomi K., Baumann C., Matsumoto N., Kato K., Kure S., Matsubara Y.;
"Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.";
Nat. Genet. 38:294-296(2006).
[20]
VARIANT [LARGE SCALE ANALYSIS] GLU-600.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
[21]
VARIANTS CFC SYNDROME ARG-257; ALA-467; SER-468; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501; ASP-581; LEU-595 AND VAL-596.
DOI=10.1126/science.1124642; PubMed=16439621 [NCBI, ExPASy, EBI, Israel, Japan]
Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., Rauen K.A.;
"Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.";
Science 311:1287-1290(2006).
[22]
VARIANTS [LARGE SCALE ANALYSIS] SER-301; ALA-469; VAL-469; SER-581; ARG-596; ARG-597; VAL-597; GLU-600; GLU-600 AND GLU-600.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M95712; AAA35609.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC006344; AAD43193.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC006347; AAD15551.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC101757; AAI01758.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC112079; AAI12080.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X65187; CAA46301.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M21001; AAA96495.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A57977; TVHUBF.
RefSeq NP_004324.2; -.
UniGene Hs.550061
3D structure databases
PDB
1UWH; X-ray; 2.95 A; A/B=448-723.[ExPASy / RCSB / EBI]
1UWJ; X-ray; 3.50 A; A/B=448-723.[ExPASy / RCSB / EBI]
2FB8; X-ray; 2.90 A; A/B=445-723.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1UWH; -.
1UWJ; -.
2FB8; -.
SMR P15056; 232-283.
ModBase P15056.
Protein-protein interaction databases
DIP DIP:1045N; -.
IntAct P15056; -.
PTM databases
PhosphoSite P15056; -.
Organism-specific databases
H-InvDB HIX0007148; -.
HGNC HGNC:1097; BRAF.
GeneLynx BRAF; Homo sapiens.
GenAtlas BRAF.
HPA CAB004552; -.
HPA001328; -.
MIM 114500; phenotype. [NCBI / EBI]
115150; phenotype. [NCBI / EBI]
164757; gene. [NCBI / EBI]
211980; phenotype. [NCBI / EBI]
605027; phenotype. [NCBI / EBI]
Orphanet 1340; Cardiofaciocutaneous syndrome.
PharmGKB PA25408; -.
GeneCards P15056.
Gene expression databases
ArrayExpress P15056; -.
CleanEx HS_BRAF; -.
GermOnline ENSG00000157764; Homo sapiens.
Ontologies
GO
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004672; Molecular function: protein kinase activity (traceable author statement from ProtInc).
GO:0006916; Biological process: anti-apoptosis (traceable author statement from ProtInc).
GO:0009887; Biological process: organ morphogenesis (traceable author statement from ProtInc).
GO:0006468; Biological process: protein amino acid phosphorylation (traceable author statement from ProtInc).
GO:0007264; Biological process: small GTPase mediated signal transduction (inferred from experiment from Reactome).
QuickGo view.
Family and domain databases
InterPro IPR002219; DAG_PE_bd.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR003116; Raf_like_ras_bd.
IPR008271; Ser_thr_pkin_AS.
Graphical view of domain structure.
Pfam PF00130; C1_1; 1.
PF02196; RBD; 1.
Pfam graphical view of domain structure.
PRINTS PR00008; DAGPEDOMAIN.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00109; C1; 1.
SM00455; RBD; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PS50898; RBD; 1.
PS00479; ZF_DAG_PE_1; 1.
PS50081; ZF_DAG_PE_2; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P15056.
Genome annotation databases
Ensembl ENSG00000157764; Homo sapiens. [Contig view]
GeneID 673; -.
KEGG hsa:673; -.
Phylogenomic databases
HOGENOM P15056; -.
HOVERGEN P15056; -.
Other
DrugBank DB00398; Sorafenib.
LinkHub P15056; -.
SOURCE BRAF; Homo sapiens.
ProtoNet P15056.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; ATP-binding; Cardiomyopathy; Cytoplasm; Direct protein sequencing; Disease mutation; Kinase; Metal-binding; Nucleotide-binding; Phorbol-ester binding; Phosphoprotein; Polymorphism; Proto-oncogene; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   766  765     B-Raf proto-oncogene serine/threonine-protein kinase. PRO_0000085665
DOMAIN   155   227  73     RBD. 
DOMAIN   457   717  261     Protein kinase. 
ZN_FING   234   280  47     Phorbol-ester/DAG-type. 
NP_BIND   463   471  9     ATP (By similarity). 
COMPBIAS   6    11  6     Poly-Gly. 
COMPBIAS   122   129  8     Poly-Ser. 
COMPBIAS   428   432  5     Poly-Ser. 
ACT_SITE   576   576        Proton acceptor (By similarity). 
METAL   235   235        Zinc 1 (By similarity). 
METAL   248   248        Zinc 2 (By similarity). 
METAL   251   251        Zinc 2 (By similarity). 
METAL   261   261        Zinc 1 (By similarity). 
METAL   264   264        Zinc 1 (By similarity). 
METAL   269   269        Zinc 2 (By similarity). 
METAL   272   272        Zinc 2 (By similarity). 
METAL   280   280        Zinc 1 (By similarity). 
BINDING   483   483        ATP (By similarity). 
MOD_RES   2     2        N-acetylalanine. 
MOD_RES   151   151        Phosphoserine. 
MOD_RES   365   365        Phosphoserine. 
MOD_RES   373   373        Phosphothreonine; by autocatalysis. 
MOD_RES   401   401        Phosphothreonine. 
MOD_RES   419   419        Phosphoserine. 
MOD_RES   446   446        Phosphoserine. 
MOD_RES   729   729        Phosphoserine. 
MOD_RES   750   750        Phosphoserine. 
VARIANT   246   246  1     A -> P (in CFC syndrome). VAR_026113 
VARIANT   257   257  1     Q -> R (in CFC syndrome). VAR_026114 
VARIANT   301   301  1     P -> S. VAR_040391 
VARIANT   462   462  1     R -> I (in colorectal cancer). VAR_018613 
VARIANT   463   463  1     I -> S (in colorectal cancer). VAR_018614 
VARIANT   464   464  1     G -> E (in colorectal cancer). VAR_018615 
VARIANT   464   464  1     G -> V (in a colorectal cancer cell line; elevated kinase activity; efficiently induces cell transformation). VAR_018616 
VARIANT   466   466  1     G -> A (in melanoma). VAR_018617 
VARIANT   466   466  1     G -> E (in melanoma). VAR_018618 
VARIANT   466   466  1     G -> V (in lung cancer). VAR_018512 
VARIANT   467   467  1     S -> A (in CFC syndrome). VAR_035096 
VARIANT   468   468  1     F -> S (in CFC syndrome). VAR_035097