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Database: UniProt
Entry: P15056
LinkDB: P15056
Original site: P15056 
ID   BRAF_HUMAN              Reviewed;         766 AA.
AC   P15056; A4D1T4; B6HY61; B6HY62; B6HY63; B6HY64; B6HY65; B6HY66; Q13878;
AC   Q3MIN6; Q9UDP8; Q9Y6T3;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 4.
DT   11-DEC-2019, entry version 237.
DE   RecName: Full=Serine/threonine-protein kinase B-raf;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126};
DE   AltName: Full=Proto-oncogene B-Raf;
DE   AltName: Full=p94;
DE   AltName: Full=v-Raf murine sarcoma viral oncogene homolog B1;
GN   Name=BRAF; Synonyms=BRAF1, RAFB1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP   PHOSPHORYLATION AT THR-373.
RC   TISSUE=Testis;
RX   PubMed=1508179; DOI=10.1128/mcb.12.9.3733;
RA   Stephens R.M., Sithanandam G., Copeland T.D., Kaplan D.R., Rapp U.R.,
RA   Morrison D.K.;
RT   "95-kilodalton B-Raf serine/threonine kinase: identification of the protein
RT   and its major autophosphorylation site.";
RL   Mol. Cell. Biol. 12:3733-3742(1992).
RN   [2]
RP   SEQUENCE REVISION TO 31-33.
RA   Albert S., Wixler L., Rapp U.R.;
RL   Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NIEHS SNPs program;
RL   Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200.
RC   TISSUE=Placenta;
RX   PubMed=1630826;
RA   Eychene A., Barnier J.V., Apiou F., Dutrillaux B., Calothy G.;
RT   "Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-
RT   raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene.";
RL   Oncogene 7:1657-1660(1992).
RN   [8]
RP   PROTEIN SEQUENCE OF 2-51; 56-95; 151-158; 189-199; 253-260; 294-354;
RP   361-424; 444-507; 510-522; 559-570; 579-626; 663-680; 692-698; 702-719;
RP   727-735 AND 753-766, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP   ALA-2, PHOSPHORYLATION AT SER-365; THR-396; SER-399; THR-401 AND SER-729,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Colon carcinoma, and Hepatoma;
RA   Bienvenut W.V., Boldt K., von Kriegsheim A.F., Zebisch A., Kolch W.;
RL   Submitted (DEC-2008) to UniProtKB.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 117-766.
RC   TISSUE=Testis;
RX   PubMed=2284096;
RA   Sithanandam G., Kolch W., Duh F.-M., Rapp U.R.;
RT   "Complete coding sequence of a human B-raf cDNA and detection of B-raf
RT   protein kinase with isozyme specific antibodies.";
RL   Oncogene 5:1775-1780(1990).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 381-766, DISEASE, AND CHROMOSOMAL
RP   REARRANGEMENT.
RC   TISSUE=Brain;
RX   PubMed=18974108; DOI=10.1158/0008-5472.can-08-2097;
RA   Jones D.T.W., Kocialkowski S., Liu L., Pearson D.M., Backlund L.M.,
RA   Ichimura K., Collins V.P.;
RT   "Tandem duplication producing a novel oncogenic BRAF fusion gene defines
RT   the majority of pilocytic astrocytomas.";
RL   Cancer Res. 68:8673-8677(2008).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 439-766.
RX   PubMed=3043188; DOI=10.1128/mcb.8.6.2651;
RA   Ikawa S., Fukui M., Ueyama Y., Tamaoki N., Yamamoto T., Toyoshima K.;
RT   "B-raf, a new member of the raf family, is activated by DNA
RT   rearrangement.";
RL   Mol. Cell. Biol. 8:2651-2654(1988).
RN   [12]
RP   PHOSPHORYLATION AT SER-365 BY SGK1.
RX   PubMed=11410590; DOI=10.1074/jbc.m102808200;
RA   Zhang B.H., Tang E.D., Zhu T., Greenberg M.E., Vojtek A.B., Guan K.L.;
RT   "Serum- and glucocorticoid-inducible kinase SGK phosphorylates and
RT   negatively regulates B-Raf.";
RL   J. Biol. Chem. 276:31620-31626(2001).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-446; SER-447 AND
RP   SER-729, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [16]
RP   SUBUNIT, INTERACTION WITH DGKH, SUBCELLULAR LOCATION, AND PHOSPHORYLATION
RP   AT THR-753 BY MAPK1.
RX   PubMed=19710016; DOI=10.1074/jbc.m109.043604;
RA   Yasuda S., Kai M., Imai S., Takeishi K., Taketomi A., Toyota M., Kanoh H.,
RA   Sakane F.;
RT   "Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf
RT   heterodimerization.";
RL   J. Biol. Chem. 284:29559-29570(2009).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [18]
RP   INTERACTION WITH AKAP13; MAP2K1 AND KSR1.
RX   PubMed=21102438; DOI=10.1038/ncb2130;
RA   Smith F.D., Langeberg L.K., Cellurale C., Pawson T., Morrison D.K.,
RA   Davis R.J., Scott J.D.;
RT   "AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade.";
RL   Nat. Cell Biol. 12:1242-1249(2010).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [20]
RP   INTERACTION WITH KSR2, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, AND
RP   MUTAGENESIS OF LYS-483.
RX   PubMed=21441910; DOI=10.1038/nature09860;
RA   Brennan D.F., Dar A.C., Hertz N.T., Chao W.C., Burlingame A.L.,
RA   Shokat K.M., Barford D.;
RT   "A Raf-induced allosteric transition of KSR stimulates phosphorylation of
RT   MEK.";
RL   Nature 472:366-369(2011).
RN   [21]
RP   INTERACTION WITH PRMT5, METHYLATION AT ARG-671, CHARACTERIZATION OF VARIANT
RP   CRC GLU-600, AND MUTAGENESIS OF ARG-671.
RX   PubMed=21917714; DOI=10.1126/scisignal.2001936;
RA   Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M.,
RA   Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G.,
RA   Avila M.A., Recio J.A.;
RT   "Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction
RT   amplitude and cell fate through CRAF.";
RL   Sci. Signal. 4:RA58-RA58(2011).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [23]
RP   UBIQUITINATION BY RNF149.
RX   PubMed=22628551; DOI=10.1074/jbc.m111.319822;
RA   Hong S.W., Jin D.H., Shin J.S., Moon J.H., Na Y.S., Jung K.A., Kim S.M.,
RA   Kim J.C., Kim K.P., Hong Y.S., Lee J.L., Choi E.K., Lee J.S., Kim T.W.;
RT   "Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-
RT   Raf murine sarcoma viral oncogene homolog B1 (BRAF).";
RL   J. Biol. Chem. 287:24017-24025(2012).
RN   [24]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-365; THR-401;
RP   SER-446 AND SER-729, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [25]
RP   UBIQUITINATION AT LYS-578, AND MUTAGENESIS OF LYS-578.
RX   PubMed=23907581; DOI=10.1038/srep02344;
RA   An L., Jia W., Yu Y., Zou N., Liang L., Zhao Y., Fan Y., Cheng J., Shi Z.,
RA   Xu G., Li G., Yang J., Zhang H.;
RT   "Lys63-linked polyubiquitination of BRAF at lysine 578 is required for
RT   BRAF-mediated signaling.";
RL   Sci. Rep. 3:2344-2344(2013).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [27]
RP   INTERACTION WITH FNIP1 AND FNIP2.
RX   PubMed=27353360; DOI=10.1038/ncomms12037;
RA   Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D.,
RA   Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W.,
RA   Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W.,
RA   Bratslavsky G., Mollapour M.;
RT   "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance
RT   drug binding.";
RL   Nat. Commun. 7:12037-12037(2016).
RN   [28]
RP   INTERACTION WITH YWHAZ.
RX   PubMed=31024343; DOI=10.3389/fphys.2019.00388;
RA   Popov I.K., Hiatt S.M., Whalen S., Keren B., Ruivenkamp C.,
RA   van Haeringen A., Chen M.J., Cooper G.M., Korf B.R., Chang C.;
RT   "A YWHAZ variant associated with cardiofaciocutaneous syndrome activates
RT   the RAF-ERK pathway.";
RL   Front. Physiol. 10:388-388(2019).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.57 ANGSTROMS) OF 444-719 IN COMPLEX WITH
RP   INHIBITOR.
RX   PubMed=18287029; DOI=10.1073/pnas.0711741105;
RA   Tsai J., Lee J.T., Wang W., Zhang J., Cho H., Mamo S., Bremer R.,
RA   Gillette S., Kong J., Haass N.K., Sproesser K., Li L., Smalley K.S.,
RA   Fong D., Zhu Y.L., Marimuthu A., Nguyen H., Lam B., Liu J., Cheung I.,
RA   Rice J., Suzuki Y., Luu C., Settachatgul C., Shellooe R., Cantwell J.,
RA   Kim S.H., Schlessinger J., Zhang K.Y., West B.L., Powell B., Habets G.,
RA   Zhang C., Ibrahim P.N., Hirth P., Artis D.R., Herlyn M., Bollag G.;
RT   "Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent
RT   antimelanoma activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:3041-3046(2008).
RN   [30] {ECO:0000244|PDB:5VR3, ECO:0000244|PDB:5VYK}
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 36-110, FUNCTION, CATALYTIC
RP   ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH KSR1; KSR2; MAP2K1 AND
RP   MAP2K2, AND MUTAGENESIS OF MET-53; LYS-88; ARG-509 AND ILE-666.
RX   PubMed=29433126; DOI=10.1038/nature25478;
RA   Lavoie H., Sahmi M., Maisonneuve P., Marullo S.A., Thevakumaran N., Jin T.,
RA   Kurinov I., Sicheri F., Therrien M.;
RT   "MEK drives BRAF activation through allosteric control of KSR proteins.";
RL   Nature 554:549-553(2018).
RN   [31]
RP   VARIANTS LNCR VAL-466 AND ARG-597.
RX   PubMed=12460919;
RA   Naoki K., Chen T.-H., Richards W.G., Sugarbaker D.J., Meyerson M.;
RT   "Missense mutations of the BRAF gene in human lung adenocarcinoma.";
RL   Cancer Res. 62:7001-7003(2002).
RN   [32]
RP   VARIANTS CANCER GLU-464; VAL-464; ALA-466; GLU-466; VAL-466; ALA-469;
RP   GLU-469; LYS-586; LEU-595; ARG-596; ARG-597; VAL-597; GLU-600 AND ASP-600,
RP   AND CHARACTERIZATION OF VARIANTS CANCER VAL-464; ALA-469; VAL-597 AND
RP   GLU-600.
RX   PubMed=12068308; DOI=10.1038/nature00766;
RA   Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S.,
RA   Teague J., Woffendin H., Garnett M.J., Bottomley W., Davis N., Dicks E.,
RA   Ewing R., Floyd Y., Gray K., Hall S., Hawes R., Hughes J., Kosmidou V.,
RA   Menzies A., Mould C., Parker A., Stevens C., Watt S., Hooper S., Wilson R.,
RA   Jayatilake H., Gusterson B.A., Cooper C., Shipley J., Hargrave D.,
RA   Pritchard-Jones K., Maitland N., Chenevix-Trench G., Riggins G.J.,
RA   Bigner D.D., Palmieri G., Cossu A., Flanagan A., Nicholson A., Ho J.W.C.,
RA   Leung S.Y., Yuen S.T., Weber B.L., Seigler H.F., Darrow T.L., Paterson H.,
RA   Marais R., Marshall C.J., Wooster R., Stratton M.R., Futreal P.A.;
RT   "Mutations of the BRAF gene in human cancer.";
RL   Nature 417:949-954(2002).
RN   [33]
RP   VARIANTS CRC ILE-462; SER-463; GLU-464; GLU-600 AND GLU-601.
RX   PubMed=12198537; DOI=10.1038/418934a;
RA   Rajagopalan H., Bardelli A., Lengauer C., Kinzler K.W., Vogelstein B.,
RA   Velculescu V.E.;
RT   "Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.";
RL   Nature 418:934-934(2002).
RN   [34]
RP   VARIANTS NHL ALA-469; ARG-469 AND GLY-594.
RX   PubMed=14612909; DOI=10.1038/sj.bjc.6601371;
RA   Lee J.W., Yoo N.J., Soung Ark W.S., Kim S.Y., Lee J.H., Park J.Y.,
RA   Cho Y.G., Kim C.J., Ko Y.H., Kim S.H., Nam S.W., Lee J.Y., Lee S.H.;
RT   "BRAF mutations in non-Hodgkin's lymphoma.";
RL   Br. J. Cancer 89:1958-1960(2003).
RN   [35]
RP   CHARACTERIZATION OF VARIANT MELANOMA GLU-600.
RX   PubMed=14500344;
RA   Hingorani S.R., Jacobetz M.A., Robertson G.P., Herlyn M., Tuveson D.A.;
RT   "Suppression of BRAF(V599E) in human melanoma abrogates transformation.";
RL   Cancer Res. 63:5198-5202(2003).
RN   [36]
RP   VARIANTS CFC1 PRO-246; ARG-257; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501
RP   AND ASP-581.
RX   PubMed=16474404; DOI=10.1038/ng1749;
RA   Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N.,
RA   Hennekam R.C.M., Gillessen-Kaesbach G., Wieczorek D., Kavamura M.I.,
RA   Kurosawa K., Ohashi H., Wilson L., Heron D., Bonneau D., Corona G.,
RA   Kaname T., Naritomi K., Baumann C., Matsumoto N., Kato K., Kure S.,
RA   Matsubara Y.;
RT   "Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.";
RL   Nat. Genet. 38:294-296(2006).
RN   [37]
RP   VARIANT [LARGE SCALE ANALYSIS] GLU-600.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [38]
RP   VARIANTS CFC1 ARG-257; ALA-467; SER-468; GLU-469; PHE-485; GLU-499;
RP   LYS-501; GLY-501; ASP-581; LEU-595 AND VAL-596.
RX   PubMed=16439621; DOI=10.1126/science.1124642;
RA   Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A.,
RA   Cruz M.S., McCormick F., Rauen K.A.;
RT   "Germline mutations in genes within the MAPK pathway cause cardio-facio-
RT   cutaneous syndrome.";
RL   Science 311:1287-1290(2006).
RN   [39]
RP   VARIANTS [LARGE SCALE ANALYSIS] SER-301; ALA-469; VAL-469; SER-581;
RP   ARG-596; ARG-597; VAL-597 AND GLU-600.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [40]
RP   VARIANTS CFC1 PRO-241; PRO-244; PRO-246; ARG-257; LYS-262; SER-468;
RP   GLU-469; GLU-499; ASN-499; ASP-580; ASP-581 AND LEU-595.
RX   PubMed=18042262; DOI=10.1111/j.1399-0004.2007.00931.x;
RA   Schulz A.L., Albrecht B., Arici C., van der Burgt I., Buske A.,
RA   Gillessen-Kaesbach G., Heller R., Horn D., Hubner C.A., Korenke G.C.,
RA   Konig R., Kress W., Kruger G., Meinecke P., Mucke J., Plecko B.,
RA   Rossier E., Schinzel A., Schulze A., Seemanova E., Seidel H., Spranger S.,
RA   Tuysuz B., Uhrig S., Wieczorek D., Kutsche K., Zenker M.;
RT   "Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous
RT   and Costello syndrome.";
RL   Clin. Genet. 73:62-70(2008).
RN   [41]
RP   VARIANT LPRD3 PRO-241, VARIANTS NS7 CYS-531 AND VAL-597, VARIANTS CFC1
RP   PHE-245; PRO-246; ARG-257; LYS-275; GLU-469; PHE-485; ASN-499; LYS-501;
RP   PRO-525; LEU-595; ARG-599; GLN-601; GLU-638 AND ARG-709, AND VARIANTS
RP   ARG-241 AND MET-241.
RX   PubMed=19206169; DOI=10.1002/humu.20955;
RA   Sarkozy A., Carta C., Moretti S., Zampino G., Digilio M.C., Pantaleoni F.,
RA   Scioletti A.P., Esposito G., Cordeddu V., Lepri F., Petrangeli V.,
RA   Dentici M.L., Mancini G.M., Selicorni A., Rossi C., Mazzanti L., Marino B.,
RA   Ferrero G.B., Silengo M.C., Memo L., Stanzial F., Faravelli F., Stuppia L.,
RA   Puxeddu E., Gelb B.D., Dallapiccola B., Tartaglia M.;
RT   "Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous
RT   syndromes: molecular diversity and associated phenotypic spectrum.";
RL   Hum. Mutat. 30:695-702(2009).
RN   [42]
RP   VARIANT CRC GLU-600.
RX   PubMed=23263490; DOI=10.1038/ng.2503;
RG   CORGI Consortium;
RG   WGS500 Consortium;
RA   Palles C., Cazier J.B., Howarth K.M., Domingo E., Jones A.M., Broderick P.,
RA   Kemp Z., Spain S.L., Guarino Almeida E., Salguero I., Sherborne A.,
RA   Chubb D., Carvajal-Carmona L.G., Ma Y., Kaur K., Dobbins S., Barclay E.,
RA   Gorman M., Martin L., Kovac M.B., Humphray S., Lucassen A., Holmes C.C.,
RA   Bentley D., Donnelly P., Taylor J., Petridis C., Roylance R., Sawyer E.J.,
RA   Kerr D.J., Clark S., Grimes J., Kearsey S.E., Thomas H.J., McVean G.,
RA   Houlston R.S., Tomlinson I.;
RT   "Germline mutations affecting the proofreading domains of POLE and POLD1
RT   predispose to colorectal adenomas and carcinomas.";
RL   Nat. Genet. 45:136-144(2013).
RN   [43]
RP   VARIANT CRC GLU-600.
RX   PubMed=24455489; DOI=10.3389/fonc.2013.00333;
RA   D'mello S.A., Flanagan J.U., Green T.N., Leung E.Y., Askarian-Amiri M.E.,
RA   Joseph W.R., McCrystal M.R., Isaacs R.J., Shaw J.H., Furneaux C.E.,
RA   During M.J., Finlay G.J., Baguley B.C., Kalev-Zylinska M.L.;
RT   "Evidence that GRIN2A mutations in melanoma correlate with decreased
RT   survival.";
RL   Front. Oncol. 3:333-333(2014).
CC   -!- FUNCTION: Protein kinase involved in the transduction of mitogenic
CC       signals from the cell membrane to the nucleus (Probable).
CC       Phosphorylates MAP2K1, and thereby activates the MAP kinase signal
CC       transduction pathway (PubMed:21441910, PubMed:29433126). May play a
CC       role in the postsynaptic responses of hippocampal neurons
CC       (PubMed:1508179). {ECO:0000269|PubMed:1508179,
CC       ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000305}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21441910};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: In quiescent cells, maintained in an inactive
CC       state via an intramolecular interaction between the protein kinase and
CC       N-terminal domains. Following mitogen-mediated cell activation, binds
CC       via its RGB domain to active HRAS (GTP-bound) which releases the
CC       inhibitory intramolecular interaction between the two domains. This
CC       allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which
CC       activates BRAF. {ECO:0000269|PubMed:29433126}.
CC   -!- SUBUNIT: Monomer. Homodimer. Heterodimerizes with RAF1, and the
CC       heterodimer possesses a highly increased kinase activity compared to
CC       the respective homodimers or monomers. Heterodimerization is mitogen-
CC       regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can
CC       induce a negative feedback that promotes the dissociation of the
CC       heterodimer by phosphorylating BRAF at Thr-753. Heterodimerizes (via N-
CC       terminus) with KSR1 (via N-terminus) or KSR2 (via N-terminus) in a
CC       MAP2K1-dependent manner (PubMed:29433126). Interacts with MAP2K1 and
CC       MAP2K2 (PubMed:29433126). Found in a complex with at least BRAF, HRAS,
CC       MAP2K1, MAPK3 and RGS14. Interacts with RIT1. Interacts (via N-
CC       terminus) with RGS14 (via RBD domains); the interaction mediates the
CC       formation of a ternary complex with RAF1, a ternary complex inhibited
CC       by GNAI1 (By similarity). Interacts with DGKH (PubMed:19710016).
CC       Interacts with PRMT5 (PubMed:21917714). Interacts with KSR2
CC       (PubMed:21441910). Interacts with AKAP13, MAP2K1 and KSR1. Identified
CC       in a complex with AKAP13, MAP2K1 and KSR1 (PubMed:21102438). Interacts
CC       with FNIP1 and FNIP2 (PubMed:27353360). {ECO:0000250,
CC       ECO:0000269|PubMed:18287029, ECO:0000269|PubMed:19710016,
CC       ECO:0000269|PubMed:21102438, ECO:0000269|PubMed:21441910,
CC       ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:27353360,
CC       ECO:0000269|PubMed:29433126}.
CC   -!- INTERACTION:
CC       Self; NbExp=13; IntAct=EBI-365980, EBI-365980;
CC       P10398:ARAF; NbExp=4; IntAct=EBI-365980, EBI-365961;
CC       P01112:HRAS; NbExp=5; IntAct=EBI-365980, EBI-350145;
CC       P08238:HSP90AB1; NbExp=2; IntAct=EBI-365980, EBI-352572;
CC       P46940:IQGAP1; NbExp=4; IntAct=EBI-365980, EBI-297509;
CC       Q61097:Ksr1 (xeno); NbExp=3; IntAct=EBI-365980, EBI-1536336;
CC       P29678:MAP2K1 (xeno); NbExp=2; IntAct=EBI-365980, EBI-1631983;
CC       Q02750:MAP2K1; NbExp=58; IntAct=EBI-365980, EBI-492564;
CC       P36507:MAP2K2; NbExp=7; IntAct=EBI-365980, EBI-1056930;
CC       Q13233:MAP3K1; NbExp=2; IntAct=EBI-365980, EBI-49776;
CC       P01111:NRAS; NbExp=3; IntAct=EBI-365980, EBI-721993;
CC       P04049:RAF1; NbExp=55; IntAct=EBI-365980, EBI-365996;
CC       Q99N57:Raf1 (xeno); NbExp=3; IntAct=EBI-365980, EBI-397757;
CC       Q8CGE9:Rgs12 (xeno); NbExp=2; IntAct=EBI-365980, EBI-7340552;
CC       Q15349:RPS6KA2; NbExp=2; IntAct=EBI-365980, EBI-1384149;
CC       Q13114:TRAF3; NbExp=2; IntAct=EBI-365980, EBI-357631;
CC       P31946:YWHAB; NbExp=3; IntAct=EBI-365980, EBI-359815;
CC       P63104:YWHAZ; NbExp=6; IntAct=EBI-365980, EBI-347088;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm
CC       {ECO:0000269|PubMed:19710016}. Cell membrane
CC       {ECO:0000269|PubMed:19710016}. Note=Colocalizes with RGS14 and RAF1 in
CC       both the cytoplasm and membranes. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Brain and testis.
CC   -!- PTM: Phosphorylation at Ser-365 by SGK1 inhibits its activity.
CC       {ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:1508179,
CC       ECO:0000269|PubMed:19710016, ECO:0000269|Ref.8}.
CC   -!- PTM: Methylation at Arg-671 decreases stability and kinase activity.
CC       {ECO:0000269|PubMed:21917714}.
CC   -!- PTM: Ubiquitinated by RNF149; which leads to proteasomal degradation.
CC       Polyubiquitinated at Lys-578 in response to EGF.
CC       {ECO:0000269|PubMed:22628551, ECO:0000269|PubMed:23907581}.
CC   -!- DISEASE: Note=Defects in BRAF are found in a wide range of cancers.
CC       {ECO:0000269|PubMed:18974108}.
CC   -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC       characterized by malignant lesions arising from the inner wall of the
CC       large intestine (the colon) and the rectum. Genetic alterations are
CC       often associated with progression from premalignant lesion (adenoma) to
CC       invasive adenocarcinoma. Risk factors for cancer of the colon and
CC       rectum include colon polyps, long-standing ulcerative colitis, and
CC       genetic family history. {ECO:0000269|PubMed:12198537,
CC       ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:23263490,
CC       ECO:0000269|PubMed:24455489}. Note=The disease may be caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting
CC       tissues of the lung. The most common form of lung cancer is non-small
CC       cell lung cancer (NSCLC) that can be divided into 3 major histologic
CC       subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung
CC       cancer. NSCLC is often diagnosed at an advanced stage and has a poor
CC       prognosis. {ECO:0000269|PubMed:12460919}. Note=The gene represented in
CC       this entry is involved in disease pathogenesis.
CC   -!- DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that
CC       starts in cells of the lymph system, which is part of the body's immune
CC       system. NHLs can occur at any age and are often marked by enlarged
CC       lymph nodes, fever and weight loss. {ECO:0000269|PubMed:14612909}.
CC       Note=The gene represented in this entry is involved in disease
CC       pathogenesis.
CC   -!- DISEASE: Cardiofaciocutaneous syndrome 1 (CFC1) [MIM:115150]: A
CC       multiple congenital anomaly disorder characterized by a distinctive
CC       facial appearance, heart defects and mental retardation. Heart defects
CC       include pulmonic stenosis, atrial septal defects and hypertrophic
CC       cardiomyopathy. Some affected individuals present with ectodermal
CC       abnormalities such as sparse, friable hair, hyperkeratotic skin lesions
CC       and a generalized ichthyosis-like condition. Typical facial features
CC       are similar to Noonan syndrome. They include high forehead with
CC       bitemporal constriction, hypoplastic supraorbital ridges, downslanting
CC       palpebral fissures, a depressed nasal bridge, and posteriorly angulated
CC       ears with prominent helices. {ECO:0000269|PubMed:16439621,
CC       ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262,
CC       ECO:0000269|PubMed:19206169}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Noonan syndrome 7 (NS7) [MIM:613706]: A form of Noonan
CC       syndrome, a disease characterized by short stature, facial dysmorphic
CC       features such as hypertelorism, a downward eyeslant and low-set
CC       posteriorly rotated ears, and a high incidence of congenital heart
CC       defects and hypertrophic cardiomyopathy. Other features can include a
CC       short neck with webbing or redundancy of skin, deafness, motor delay,
CC       variable intellectual deficits, multiple skeletal defects,
CC       cryptorchidism, and bleeding diathesis. Individuals with Noonan
CC       syndrome are at risk of juvenile myelomonocytic leukemia, a
CC       myeloproliferative disorder characterized by excessive production of
CC       myelomonocytic cells. {ECO:0000269|PubMed:19206169}. Note=The disease
CC       is caused by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: LEOPARD syndrome 3 (LPRD3) [MIM:613707]: A disorder
CC       characterized by lentigines, electrocardiographic conduction
CC       abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities
CC       of genitalia, retardation of growth, and sensorineural deafness.
CC       {ECO:0000269|PubMed:19206169}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Note=A chromosomal aberration involving BRAF is found in
CC       pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to
CC       the expression of a KIAA1549-BRAF fusion protein with a constitutive
CC       kinase activity and inducing cell transformation.
CC       {ECO:0000269|PubMed:18974108}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC       protein kinase family. RAF subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD43193.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAQ43111.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAQ43112.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAQ43113.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAQ43114.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAQ43115.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAQ43116.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/BRAFID828.html";
DR   EMBL; M95712; AAA35609.2; -; mRNA.
DR   EMBL; AC006344; AAD43193.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; EU600171; ACD11489.1; -; Genomic_DNA.
DR   EMBL; AC006347; AAD15551.1; -; Genomic_DNA.
DR   EMBL; CH236950; EAL24023.1; -; Genomic_DNA.
DR   EMBL; BC101757; AAI01758.1; -; mRNA.
DR   EMBL; BC112079; AAI12080.1; -; mRNA.
DR   EMBL; X65187; CAA46301.1; -; Genomic_DNA.
DR   EMBL; M21001; AAA96495.1; -; mRNA.
DR   EMBL; AM989472; CAQ43111.1; ALT_INIT; mRNA.
DR   EMBL; AM989473; CAQ43112.1; ALT_INIT; mRNA.
DR   EMBL; AM989474; CAQ43113.1; ALT_INIT; mRNA.
DR   EMBL; AM989475; CAQ43114.1; ALT_INIT; mRNA.
DR   EMBL; AM989476; CAQ43115.1; ALT_INIT; mRNA.
DR   EMBL; AM989477; CAQ43116.1; ALT_INIT; mRNA.
DR   CCDS; CCDS5863.1; -.
DR   PIR; A57977; TVHUBF.
DR   RefSeq; NP_004324.2; NM_004333.4.
DR   PDB; 1UWH; X-ray; 2.95 A; A/B=448-723.
DR   PDB; 1UWJ; X-ray; 3.50 A; A/B=448-723.
DR   PDB; 2FB8; X-ray; 2.90 A; A/B=445-723.
DR   PDB; 2L05; NMR; -; A=149-232.
DR   PDB; 3C4C; X-ray; 2.57 A; A/B=444-721.
DR   PDB; 3D4Q; X-ray; 2.80 A; A/B=433-726.
DR   PDB; 3IDP; X-ray; 2.70 A; A/B=434-727.
DR   PDB; 3II5; X-ray; 2.79 A; A/B=432-726.
DR   PDB; 3NY5; X-ray; 1.99 A; A/B/C/D=153-237.
DR   PDB; 3OG7; X-ray; 2.45 A; A/B=448-720.
DR   PDB; 3PPJ; X-ray; 3.70 A; A/B=432-726.
DR   PDB; 3PPK; X-ray; 3.00 A; A/B=432-726.
DR   PDB; 3PRF; X-ray; 2.90 A; A/B=432-726.
DR   PDB; 3PRI; X-ray; 3.50 A; A/B=432-726.
DR   PDB; 3PSB; X-ray; 3.40 A; A/B=433-726.
DR   PDB; 3PSD; X-ray; 3.60 A; A/B=433-726.
DR   PDB; 3Q4C; X-ray; 3.20 A; A/B=432-726.
DR   PDB; 3Q96; X-ray; 3.10 A; A/B=446-727.
DR   PDB; 3SKC; X-ray; 3.20 A; A/B=432-726.
DR   PDB; 3TV4; X-ray; 3.40 A; A/B=432-726.
DR   PDB; 3TV6; X-ray; 3.30 A; A/B=432-726.
DR   PDB; 4CQE; X-ray; 2.30 A; A/B=448-723.
DR   PDB; 4DBN; X-ray; 3.15 A; A/B=445-726.
DR   PDB; 4E26; X-ray; 2.55 A; A/B=432-726.
DR   PDB; 4E4X; X-ray; 3.60 A; A/B=432-726.
DR   PDB; 4EHE; X-ray; 3.30 A; A/B=432-726.
DR   PDB; 4EHG; X-ray; 3.50 A; A/B=432-726.
DR   PDB; 4FC0; X-ray; 2.95 A; A/B=445-726.
DR   PDB; 4FK3; X-ray; 2.65 A; A/B=444-723.
DR   PDB; 4G9C; X-ray; 3.50 A; A/B=432-726.
DR   PDB; 4G9R; X-ray; 3.20 A; A/B=432-726.
DR   PDB; 4H58; X-ray; 3.10 A; A/B/C=448-722.
DR   PDB; 4JVG; X-ray; 3.09 A; A/B/C/D=444-723.
DR   PDB; 4KSP; X-ray; 2.93 A; A/B=445-726.
DR   PDB; 4KSQ; X-ray; 3.30 A; A/B=445-726.
DR   PDB; 4MBJ; X-ray; 3.60 A; A/B=432-723.
DR   PDB; 4MNE; X-ray; 2.85 A; B/C/F/G=432-726.
DR   PDB; 4MNF; X-ray; 2.80 A; A/B=432-736.
DR   PDB; 4PP7; X-ray; 3.40 A; A/B=432-726.
DR   PDB; 4R5Y; X-ray; 3.50 A; A/B=444-723.
DR   PDB; 4RZV; X-ray; 2.99 A; A/B=443-723.
DR   PDB; 4RZW; X-ray; 3.49 A; A/B=443-723.
DR   PDB; 4WO5; X-ray; 2.83 A; A/B=444-723.
DR   PDB; 4XV1; X-ray; 2.47 A; A/B=444-705.
DR   PDB; 4XV2; X-ray; 2.50 A; A/B=444-705.
DR   PDB; 4XV3; X-ray; 2.80 A; A/B=444-705.
DR   PDB; 4XV9; X-ray; 2.00 A; A=442-705.
DR   PDB; 4YHT; X-ray; 3.05 A; A/B=449-720.
DR   PDB; 5C9C; X-ray; 2.70 A; A/B=432-726.
DR   PDB; 5CSW; X-ray; 2.66 A; A/B=442-721.
DR   PDB; 5CSX; X-ray; 2.51 A; A=442-721.
DR   PDB; 5CT7; X-ray; 3.17 A; A/B=445-723.
DR   PDB; 5FD2; X-ray; 2.89 A; A/B=433-726.
DR   PDB; 5HI2; X-ray; 2.51 A; A=444-737.
DR   PDB; 5HID; X-ray; 2.50 A; A/B=444-737.
DR   PDB; 5HIE; X-ray; 3.00 A; A/B/C/D=432-726.
DR   PDB; 5ITA; X-ray; 1.95 A; A/B=448-723.
DR   PDB; 5J17; NMR; -; A=151-232.
DR   PDB; 5J18; NMR; -; A=151-232.
DR   PDB; 5J2R; NMR; -; A=151-232.
DR   PDB; 5JRQ; X-ray; 2.29 A; A/B=448-723.
DR   PDB; 5JSM; X-ray; 2.19 A; A/B/C/D=448-723.
DR   PDB; 5JT2; X-ray; 2.70 A; A/B/C/D=448-723.
DR   PDB; 5VAL; X-ray; 2.26 A; A/B=445-723.
DR   PDB; 5VAM; X-ray; 2.10 A; A/B=445-723.
DR   PDB; 5VR3; X-ray; 2.10 A; A=36-114.
DR   PDB; 5VYK; X-ray; 1.75 A; A/C=36-110.
DR   PDB; 6B8U; X-ray; 2.68 A; A/B=445-723.
DR   PDB; 6CAD; X-ray; 2.55 A; A/B=444-723.
DR   PDB; 6N0P; X-ray; 2.37 A; A/B=449-721.
DR   PDB; 6NSQ; X-ray; 3.05 A; A/B=444-723.
DR   PDB; 6U2G; X-ray; 2.89 A; B=432-726.
DR   PDB; 6U2H; X-ray; 2.50 A; C/D=447-735.
DR   PDB; 6UAN; EM; 3.90 A; B/C=1-766.
DR   PDBsum; 1UWH; -.
DR   PDBsum; 1UWJ; -.
DR   PDBsum; 2FB8; -.
DR   PDBsum; 2L05; -.
DR   PDBsum; 3C4C; -.
DR   PDBsum; 3D4Q; -.
DR   PDBsum; 3IDP; -.
DR   PDBsum; 3II5; -.
DR   PDBsum; 3NY5; -.
DR   PDBsum; 3OG7; -.
DR   PDBsum; 3PPJ; -.
DR   PDBsum; 3PPK; -.
DR   PDBsum; 3PRF; -.
DR   PDBsum; 3PRI; -.
DR   PDBsum; 3PSB; -.
DR   PDBsum; 3PSD; -.
DR   PDBsum; 3Q4C; -.
DR   PDBsum; 3Q96; -.
DR   PDBsum; 3SKC; -.
DR   PDBsum; 3TV4; -.
DR   PDBsum; 3TV6; -.
DR   PDBsum; 4CQE; -.
DR   PDBsum; 4DBN; -.
DR   PDBsum; 4E26; -.
DR   PDBsum; 4E4X; -.
DR   PDBsum; 4EHE; -.
DR   PDBsum; 4EHG; -.
DR   PDBsum; 4FC0; -.
DR   PDBsum; 4FK3; -.
DR   PDBsum; 4G9C; -.
DR   PDBsum; 4G9R; -.
DR   PDBsum; 4H58; -.
DR   PDBsum; 4JVG; -.
DR   PDBsum; 4KSP; -.
DR   PDBsum; 4KSQ; -.
DR   PDBsum; 4MBJ; -.
DR   PDBsum; 4MNE; -.
DR   PDBsum; 4MNF; -.
DR   PDBsum; 4PP7; -.
DR   PDBsum; 4R5Y; -.
DR   PDBsum; 4RZV; -.
DR   PDBsum; 4RZW; -.
DR   PDBsum; 4WO5; -.
DR   PDBsum; 4XV1; -.
DR   PDBsum; 4XV2; -.
DR   PDBsum; 4XV3; -.
DR   PDBsum; 4XV9; -.
DR   PDBsum; 4YHT; -.
DR   PDBsum; 5C9C; -.
DR   PDBsum; 5CSW; -.
DR   PDBsum; 5CSX; -.
DR   PDBsum; 5CT7; -.
DR   PDBsum; 5FD2; -.
DR   PDBsum; 5HI2; -.
DR   PDBsum; 5HID; -.
DR   PDBsum; 5HIE; -.
DR   PDBsum; 5ITA; -.
DR   PDBsum; 5J17; -.
DR   PDBsum; 5J18; -.
DR   PDBsum; 5J2R; -.
DR   PDBsum; 5JRQ; -.
DR   PDBsum; 5JSM; -.
DR   PDBsum; 5JT2; -.
DR   PDBsum; 5VAL; -.
DR   PDBsum; 5VAM; -.
DR   PDBsum; 5VR3; -.
DR   PDBsum; 5VYK; -.
DR   PDBsum; 6B8U; -.
DR   PDBsum; 6CAD; -.
DR   PDBsum; 6N0P; -.
DR   PDBsum; 6NSQ; -.
DR   PDBsum; 6U2G; -.
DR   PDBsum; 6U2H; -.
DR   PDBsum; 6UAN; -.
DR   SMR; P15056; -.
DR   BioGrid; 107141; 123.
DR   CORUM; P15056; -.
DR   DIP; DIP-1045N; -.
DR   IntAct; P15056; 57.
DR   MINT; P15056; -.
DR   STRING; 9606.ENSP00000288602; -.
DR   BindingDB; P15056; -.
DR   ChEMBL; CHEMBL5145; -.
DR   DrugBank; DB08553; (1E)-5-(1-piperidin-4-yl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime.
DR   DrugBank; DB08912; Dabrafenib.
DR   DrugBank; DB11718; Encorafenib.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB07000; N-{2,4-difluoro-3-[(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]phenyl}ethanesulfonamide.
DR   DrugBank; DB06999; N-{3-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide.
DR   DrugBank; DB05984; RAF-265.
DR   DrugBank; DB08896; Regorafenib.
DR   DrugBank; DB00398; Sorafenib.
DR   DrugBank; DB08881; Vemurafenib.
DR   DrugBank; DB05190; XL281.
DR   DrugCentral; P15056; -.
DR   GuidetoPHARMACOLOGY; 1943; -.
DR   iPTMnet; P15056; -.
DR   PhosphoSitePlus; P15056; -.
DR   BioMuta; BRAF; -.
DR   DMDM; 50403720; -.
DR   EPD; P15056; -.
DR   jPOST; P15056; -.
DR   MassIVE; P15056; -.
DR   MaxQB; P15056; -.
DR   PaxDb; P15056; -.
DR   PeptideAtlas; P15056; -.
DR   PRIDE; P15056; -.
DR   ProteomicsDB; 53102; -.
DR   DNASU; 673; -.
DR   Ensembl; ENST00000646891; ENSP00000493543; ENSG00000157764.
DR   GeneID; 673; -.
DR   KEGG; hsa:673; -.
DR   UCSC; uc003vwc.5; human.
DR   CTD; 673; -.
DR   DisGeNET; 673; -.
DR   EuPathDB; HostDB:ENSG00000157764.12; -.
DR   GeneCards; BRAF; -.
DR   GeneReviews; BRAF; -.
DR   HGNC; HGNC:1097; BRAF.
DR   HPA; CAB004552; -.
DR   HPA; HPA001328; -.
DR   HPA; HPA071048; -.
DR   MalaCards; BRAF; -.
DR   MIM; 114500; phenotype.
DR   MIM; 115150; phenotype.
DR   MIM; 164757; gene.
DR   MIM; 211980; phenotype.
DR   MIM; 605027; phenotype.
DR   MIM; 613706; phenotype.
DR   MIM; 613707; phenotype.
DR   neXtProt; NX_P15056; -.
DR   OpenTargets; ENSG00000157764; -.
DR   Orphanet; 1340; Cardiofaciocutaneous syndrome.
DR   Orphanet; 58017; Classic hairy cell leukemia.
DR   Orphanet; 54595; Craniopharyngioma.
DR   Orphanet; 146; Differentiated thyroid carcinoma.
DR   Orphanet; 99872; Hashimoto-Pritzker syndrome.
DR   Orphanet; 411533; NON RARE IN EUROPE: Melanoma.
DR   Orphanet; 648; Noonan syndrome.
DR   Orphanet; 500; Noonan syndrome with multiple lentigines.
DR   Orphanet; 251615; Pilomyxoid astrocytoma.
DR   Orphanet; 357194; Selection of therapeutic option in colorectal cancer.
DR   Orphanet; 544260; Selection of therapeutic option in melanoma.
DR   Orphanet; 357191; Selection of therapeutic option in non-small cell lung carcinoma.
DR   PharmGKB; PA25408; -.
DR   eggNOG; KOG0193; Eukaryota.
DR   eggNOG; ENOG410Y4UP; LUCA.
DR   GeneTree; ENSGT00940000156154; -.
DR   InParanoid; P15056; -.
DR   KO; K04365; -.
DR   OMA; NDIVFDF; -.
DR   OrthoDB; 1586678at2759; -.
DR   PhylomeDB; P15056; -.
DR   TreeFam; TF317006; -.
DR   BRENDA; 2.7.10.2; 2681.
DR   Reactome; R-HSA-1295596; Spry regulation of FGF signaling.
DR   Reactome; R-HSA-170968; Frs2-mediated activation.
DR   Reactome; R-HSA-170984; ARMS-mediated activation.
DR   Reactome; R-HSA-187706; Signalling to p38 via RIT and RIN.
DR   Reactome; R-HSA-5673000; RAF activation.
DR   Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR   Reactome; R-HSA-5674499; Negative feedback regulation of MAPK pathway.
DR   Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR   Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR   Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR   Reactome; R-HSA-6802952; Signaling by BRAF and RAF fusions.
DR   Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR   Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR   SignaLink; P15056; -.
DR   SIGNOR; P15056; -.
DR   ChiTaRS; BRAF; human.
DR   EvolutionaryTrace; P15056; -.
DR   GeneWiki; BRAF_(gene); -.
DR   GenomeRNAi; 673; -.
DR   Pharos; P15056; Tclin.
DR   PRO; PR:P15056; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P15056; protein.
DR   Bgee; ENSG00000157764; Expressed in 203 organ(s), highest expression level in buccal mucosa cell.
DR   ExpressionAtlas; P15056; baseline and differential.
DR   Genevisible; P15056; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046982; F:protein heterodimerization activity; IMP:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0000186; P:activation of MAPKK activity; IDA:UniProtKB.
DR   GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR   GO; GO:0071277; P:cellular response to calcium ion; IDA:BHF-UCL.
DR   GO; GO:0090150; P:establishment of protein localization to membrane; IDA:CACAO.
DR   GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR   GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IDA:CACAO.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0070413; P:trehalose metabolism in response to stress; IMP:SGD.
DR   CDD; cd00029; C1; 1.
DR   InterPro; IPR020454; DAG/PE-bd.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR002219; PE/DAG-bd.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR003116; RBD_dom.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   Pfam; PF00130; C1_1; 1.
DR   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF02196; RBD; 1.
DR   PRINTS; PR00008; DAGPEDOMAIN.
DR   SMART; SM00109; C1; 1.
DR   SMART; SM00455; RBD; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50898; RBD; 1.
DR   PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR   PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Cardiomyopathy;
KW   Cell membrane; Chromosomal rearrangement; Cytoplasm; Deafness;
KW   Direct protein sequencing; Disease mutation; Ectodermal dysplasia;
KW   Isopeptide bond; Kinase; Membrane; Mental retardation; Metal-binding;
KW   Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW   Proto-oncogene; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.8"
FT   CHAIN           2..766
FT                   /note="Serine/threonine-protein kinase B-raf"
FT                   /id="PRO_0000085665"
FT   DOMAIN          155..227
FT                   /note="RBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT   DOMAIN          457..717
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ZN_FING         234..280
FT                   /note="Phorbol-ester/DAG-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT   NP_BIND         463..471
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   COMPBIAS        6..11
FT                   /note="Poly-Gly"
FT   COMPBIAS        122..129
FT                   /note="Poly-Ser"
FT   COMPBIAS        428..432
FT                   /note="Poly-Ser"
FT   ACT_SITE        576
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   METAL           235
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250"
FT   METAL           248
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250"
FT   METAL           251
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250"
FT   METAL           261
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250"
FT   METAL           264
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250"
FT   METAL           269
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250"
FT   METAL           272
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000250"
FT   METAL           280
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000250"
FT   BINDING         483
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   SITE            380..381
FT                   /note="Breakpoint for translocation to form KIAA1549-BRAF
FT                   fusion protein"
FT   SITE            438..439
FT                   /note="Breakpoint for translocation to form KIAA1549-BRAF
FT                   fusion protein"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|Ref.8"
FT   MOD_RES         151
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569"
FT   MOD_RES         333
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P28028"
FT   MOD_RES         365
FT                   /note="Phosphoserine; by SGK1"
FT                   /evidence="ECO:0000244|PubMed:23186163,
FT                   ECO:0000269|PubMed:11410590, ECO:0000269|Ref.8"
FT   MOD_RES         373
FT                   /note="Phosphothreonine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:1508179"
FT   MOD_RES         396
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|Ref.8"
FT   MOD_RES         399
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|Ref.8"
FT   MOD_RES         401
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:16964243,
FT                   ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:23186163,
FT                   ECO:0000269|Ref.8"
FT   MOD_RES         446
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         447
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         671
FT                   /note="Omega-N-methylarginine; by PRMT5"
FT                   /evidence="ECO:0000269|PubMed:21917714"
FT   MOD_RES         729
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163,
FT                   ECO:0000269|Ref.8"
FT   MOD_RES         750
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P28028"
FT   MOD_RES         753
FT                   /note="Phosphothreonine; by MAPK1"
FT                   /evidence="ECO:0000269|PubMed:19710016"
FT   CROSSLNK        578
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000269|PubMed:23907581"
FT   VARIANT         241
FT                   /note="T -> M (in a patient with Noonan syndrome;
FT                   dbSNP:rs387906660)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058620"
FT   VARIANT         241
FT                   /note="T -> P (in CFC1 and LPRD3; dbSNP:rs387906661)"
FT                   /evidence="ECO:0000269|PubMed:18042262,
FT                   ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058621"
FT   VARIANT         241
FT                   /note="T -> R (in a patient with Noonan syndrome;
FT                   dbSNP:rs387906660)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058622"
FT   VARIANT         244
FT                   /note="T -> P (in CFC1; dbSNP:rs397507465)"
FT                   /evidence="ECO:0000269|PubMed:18042262"
FT                   /id="VAR_065171"
FT   VARIANT         245
FT                   /note="L -> F (in CFC1; dbSNP:rs397507466)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058623"
FT   VARIANT         246
FT                   /note="A -> P (in CFC1; dbSNP:rs180177034)"
FT                   /evidence="ECO:0000269|PubMed:16474404,
FT                   ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169"
FT                   /id="VAR_026113"
FT   VARIANT         257
FT                   /note="Q -> R (in CFC1; dbSNP:rs180177035)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262,
FT                   ECO:0000269|PubMed:19206169"
FT                   /id="VAR_026114"
FT   VARIANT         262
FT                   /note="Q -> K (in CFC1; dbSNP:rs397507470)"
FT                   /evidence="ECO:0000269|PubMed:18042262"
FT                   /id="VAR_065172"
FT   VARIANT         275
FT                   /note="E -> K (in CFC1)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058624"
FT   VARIANT         301
FT                   /note="P -> S (in dbSNP:rs34776339)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040391"
FT   VARIANT         462
FT                   /note="R -> I (in CRC; dbSNP:rs180177032)"
FT                   /evidence="ECO:0000269|PubMed:12198537"
FT                   /id="VAR_018613"
FT   VARIANT         463
FT                   /note="I -> S (in CRC; dbSNP:rs180177033)"
FT                   /evidence="ECO:0000269|PubMed:12198537"
FT                   /id="VAR_018614"
FT   VARIANT         464
FT                   /note="G -> E (in CRC; dbSNP:rs121913348)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:12198537"
FT                   /id="VAR_018615"
FT   VARIANT         464
FT                   /note="G -> V (in a colorectal cancer cell line; elevated
FT                   kinase activity; efficiently induces cell transformation;
FT                   dbSNP:rs121913348)"
FT                   /evidence="ECO:0000269|PubMed:12068308"
FT                   /id="VAR_018616"
FT   VARIANT         466
FT                   /note="G -> A (in melanoma; dbSNP:rs121913351)"
FT                   /evidence="ECO:0000269|PubMed:12068308"
FT                   /id="VAR_018617"
FT   VARIANT         466
FT                   /note="G -> E (in melanoma; dbSNP:rs121913351)"
FT                   /evidence="ECO:0000269|PubMed:12068308"
FT                   /id="VAR_018618"
FT   VARIANT         466
FT                   /note="G -> V (in LNCR; dbSNP:rs121913351)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:12460919"
FT                   /id="VAR_018512"
FT   VARIANT         467
FT                   /note="S -> A (in CFC1; dbSNP:rs869025606)"
FT                   /evidence="ECO:0000269|PubMed:16439621"
FT                   /id="VAR_035096"
FT   VARIANT         468
FT                   /note="F -> S (in CFC1; dbSNP:rs397507473)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:18042262"
FT                   /id="VAR_035097"
FT   VARIANT         469
FT                   /note="G -> A (in NHL; also in a lung adenocarcinoma
FT                   sample; somatic mutation; elevated kinase activity;
FT                   efficiently induces cell transformation;
FT                   dbSNP:rs121913355)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:14612909, ECO:0000269|PubMed:17344846"
FT                   /id="VAR_018620"
FT   VARIANT         469
FT                   /note="G -> E (in CFC1 and colon cancer;
FT                   dbSNP:rs121913355)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:16474404,
FT                   ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169"
FT                   /id="VAR_018621"
FT   VARIANT         469
FT                   /note="G -> R (in NHL; dbSNP:rs121913357)"
FT                   /evidence="ECO:0000269|PubMed:14612909"
FT                   /id="VAR_018622"
FT   VARIANT         469
FT                   /note="G -> V (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs121913355)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040392"
FT   VARIANT         485
FT                   /note="L -> F (in CFC1; dbSNP:rs180177036)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:19206169"
FT                   /id="VAR_026115"
FT   VARIANT         499
FT                   /note="K -> E (in CFC1; dbSNP:rs180177037)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262"
FT                   /id="VAR_026116"
FT   VARIANT         499
FT                   /note="K -> N (in CFC1; dbSNP:rs397507476)"
FT                   /evidence="ECO:0000269|PubMed:18042262,
FT                   ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058625"
FT   VARIANT         501
FT                   /note="E -> G (in CFC1; dbSNP:rs180177039)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404"
FT                   /id="VAR_026117"
FT   VARIANT         501
FT                   /note="E -> K (in CFC1; dbSNP:rs180177038)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:19206169"
FT                   /id="VAR_026118"
FT   VARIANT         525
FT                   /note="L -> P (in CFC1; dbSNP:rs869025340)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058626"
FT   VARIANT         531
FT                   /note="W -> C (in NS7; dbSNP:rs606231228)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058627"
FT   VARIANT         580
FT                   /note="N -> D (in CFC1)"
FT                   /evidence="ECO:0000269|PubMed:18042262"
FT                   /id="VAR_065173"
FT   VARIANT         581
FT                   /note="N -> D (in CFC1; dbSNP:rs180177040)"
FT                   /evidence="ECO:0000269|PubMed:16439621,
FT                   ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262"
FT                   /id="VAR_026119"
FT   VARIANT         581
FT                   /note="N -> S (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs121913370)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040393"
FT   VARIANT         586
FT                   /note="E -> K (in ovarian cancer; dbSNP:rs121913340)"
FT                   /evidence="ECO:0000269|PubMed:12068308"
FT                   /id="VAR_018623"
FT   VARIANT         594
FT                   /note="D -> G (in NHL; dbSNP:rs121913338)"
FT                   /evidence="ECO:0000269|PubMed:14612909"
FT                   /id="VAR_018624"
FT   VARIANT         595
FT                   /note="F -> L (in colon cancer and CFC1;
FT                   dbSNP:rs121913341)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262,
FT                   ECO:0000269|PubMed:19206169"
FT                   /id="VAR_018625"
FT   VARIANT         596
FT                   /note="G -> R (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs121913361)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_018626"
FT   VARIANT         596
FT                   /note="G -> V (in CFC1; dbSNP:rs397507483)"
FT                   /evidence="ECO:0000269|PubMed:16439621"
FT                   /id="VAR_035098"
FT   VARIANT         597
FT                   /note="L -> R (in LNCR; also found in an ovarian serous
FT                   carcinoma sample; somatic mutation; dbSNP:rs121913366)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:12460919, ECO:0000269|PubMed:17344846"
FT                   /id="VAR_018513"
FT   VARIANT         597
FT                   /note="L -> V (in NS7; also in a lung adenocarcinoma
FT                   sample; somatic mutation; elevated kinase activity;
FT                   efficiently induces cell transformation;
FT                   dbSNP:rs121913369)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:19206169"
FT                   /id="VAR_018627"
FT   VARIANT         599
FT                   /note="T -> R (in CFC1; dbSNP:rs121913375)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058628"
FT   VARIANT         600
FT                   /note="V -> D (in a melanoma cell line; requires 2
FT                   nucleotide substitutions; dbSNP:rs121913377)"
FT                   /evidence="ECO:0000269|PubMed:12068308"
FT                   /id="VAR_018628"
FT   VARIANT         600
FT                   /note="V -> E (in CRC; also found in sarcoma, metastatic
FT                   melanoma, ovarian serous carcinoma, pilocytic astrocytoma;
FT                   somatic mutation; most common mutation; constitutive and
FT                   elevated kinase activity; efficiently induces cell
FT                   transformation; suppression of mutation in melanoma causes
FT                   growth arrest and promotes apoptosis; loss of regulation by
FT                   PMRT5; dbSNP:rs113488022)"
FT                   /evidence="ECO:0000269|PubMed:12068308,
FT                   ECO:0000269|PubMed:12198537, ECO:0000269|PubMed:14500344,
FT                   ECO:0000269|PubMed:16959974, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:23263490,
FT                   ECO:0000269|PubMed:24455489"
FT                   /id="VAR_018629"
FT   VARIANT         601
FT                   /note="K -> E (in CRC; dbSNP:rs121913364)"
FT                   /evidence="ECO:0000269|PubMed:12198537"
FT                   /id="VAR_018630"
FT   VARIANT         601
FT                   /note="K -> Q (in CFC1; dbSNP:rs121913364)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058629"
FT   VARIANT         638
FT                   /note="D -> E (in CFC1; dbSNP:rs180177042)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058630"
FT   VARIANT         709
FT                   /note="Q -> R (in CFC1; dbSNP:rs397507486)"
FT                   /evidence="ECO:0000269|PubMed:19206169"
FT                   /id="VAR_058631"
FT   MUTAGEN         53
FT                   /note="M->D: Reduces interaction with KSR1 and MAP2K1 and
FT                   thus phosphorylation of MAP2K1."
FT                   /evidence="ECO:0000269|PubMed:29433126"
FT   MUTAGEN         88
FT                   /note="K->E: Reduces interaction with KSR1 and MAP2K1 and
FT                   thus phosphorylation of MAP2K1."
FT                   /evidence="ECO:0000269|PubMed:29433126"
FT   MUTAGEN         483
FT                   /note="K->S: Reduces kinase activity with MAP2K1."
FT                   /evidence="ECO:0000269|PubMed:21441910"
FT   MUTAGEN         509
FT                   /note="R->H: Loss of MAP2K1-mediated-BRAF-KSR1
FT                   dimerization."
FT                   /evidence="ECO:0000269|PubMed:29433126"
FT   MUTAGEN         578
FT                   /note="K->R: Blocks EGF-induced ubiquitination and ERK
FT                   activation."
FT                   /evidence="ECO:0000269|PubMed:23907581"
FT   MUTAGEN         666
FT                   /note="I->R: No effect on MAP2K1-mediated-BRAF-KSR1
FT                   dimerization, however loss of BRAF-mediated phosphorylation
FT                   of MAP2K1."
FT                   /evidence="ECO:0000269|PubMed:29433126"
FT   MUTAGEN         671
FT                   /note="R->K: Increased kinase activity and stability in
FT                   response to EGF treatment."
FT                   /evidence="ECO:0000269|PubMed:21917714"
FT   CONFLICT        766
FT                   /note="H -> D (in Ref. 11; AAA96495)"
FT                   /evidence="ECO:0000305"
FT   HELIX           43..68
FT                   /evidence="ECO:0000244|PDB:5VYK"
FT   HELIX           76..103
FT                   /evidence="ECO:0000244|PDB:5VYK"
FT   STRAND          156..161
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   TURN            162..164
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   STRAND          165..170
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   HELIX           177..186
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   TURN            187..189
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   HELIX           192..194
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   STRAND          195..199
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   STRAND          206..208
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   HELIX           214..217
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   STRAND          221..226
FT                   /evidence="ECO:0000244|PDB:3NY5"
FT   HELIX           448..450
FT                   /evidence="ECO:0000244|PDB:5JRQ"
FT   HELIX           454..456
FT                   /evidence="ECO:0000244|PDB:5JRQ"
FT   STRAND          458..466
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          469..486
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          487..489
FT                   /evidence="ECO:0000244|PDB:6N0P"
FT   HELIX           492..506
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          516..520
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          522..524
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          526..530
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          534..536
FT                   /evidence="ECO:0000244|PDB:5VAM"
FT   HELIX           537..542
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          543..545
FT                   /evidence="ECO:0000244|PDB:4RZW"
FT   HELIX           550..569
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           579..581
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          582..585
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   TURN            586..588
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          589..592
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   TURN            598..600
FT                   /evidence="ECO:0000244|PDB:5JSM"
FT   TURN            602..605
FT                   /evidence="ECO:0000244|PDB:4RZV"
FT   HELIX           611..613
FT                   /evidence="ECO:0000244|PDB:4WO5"
FT   TURN            614..616
FT                   /evidence="ECO:0000244|PDB:5HID"
FT   HELIX           617..619
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           622..625
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          629..631
FT                   /evidence="ECO:0000244|PDB:5VAM"
FT   HELIX           635..651
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   TURN            655..659
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           662..670
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           678..680
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   STRAND          683..685
FT                   /evidence="ECO:0000244|PDB:5JRQ"
FT   HELIX           687..696
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           701..703
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   HELIX           707..717
FT                   /evidence="ECO:0000244|PDB:5ITA"
FT   TURN            718..720
FT                   /evidence="ECO:0000244|PDB:4RZV"
FT   STRAND          723..726
FT                   /evidence="ECO:0000244|PDB:6U2H"
SQ   SEQUENCE   766 AA;  84437 MW;  0798C2AAB487E813 CRC64;
     MAALSGGGGG GAEPGQALFN GDMEPEAGAG AGAAASSAAD PAIPEEVWNI KQMIKLTQEH
     IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESLGNGTDFS VSSSASMDTV
     TSSSSSSLSV LPSSLSVFQN PTDVARSNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS
     LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK
     TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI
     PQEEASLAET ALTSGSSPSA PASDSIGPQI LTSPSPSKSI PIPQPFRPAD EDHRNQFGQR
     DRSSSAPNVH INTIEPVNID DLIRDQGFRG DGGSTTGLSA TPPASLPGSL TNVKALQKSP
     GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV
     AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH
     LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV
     KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN
     NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS
     LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GAFPVH
//
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