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 27-MAR-2024, entry version 259. DE RecName: Full=Serine/threonine-protein kinase B-raf {ECO:0000305}; 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 {ECO:0000312|HGNC:HGNC:1097}; 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.12.9.3733-3742.1992; 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.8.6.2651-2654.1988; 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 FUNCTION, AND SUBUNIT. RX PubMed=36402789; DOI=10.1038/s41467-022-34907-0; RA McGrail K., Granado-Martinez P., Esteve-Puig R., Garcia-Ortega S., Ding Y., RA Sanchez-Redondo S., Ferrer B., Hernandez-Losa J., Canals F., Manzano A., RA Navarro-Sabate A., Bartrons R., Yanes O., Perez-Alea M., Munoz-Couselo E., RA Garcia-Patos V., Recio J.A.; RT "BRAF activation by metabolic stress promotes glycolysis sensitizing RT NRASQ61-mutated melanomas to targeted therapy."; RL Nat. Commun. 13:7113-7113(2022). RN [30] 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 [31] {ECO:0007744|PDB:5VR3, ECO:0007744|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 [32] 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] RP VARIANT LPRD3 PRO-241, VARIANTS NS7 ARG-241; MET-241; CYS-531 AND VAL-597, RP AND VARIANTS CFC1 PHE-245; PRO-246; ARG-257; LYS-275; GLU-469; PHE-485; RP ASN-499; LYS-501; PRO-525; LEU-595; ARG-599; GLN-601; GLU-638 AND ARG-709. 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 [43] 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 [44] 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). Phosphorylates CC PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses CC of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, CC ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, CC ECO:0000269|PubMed:36402789, 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 (PubMed:19710016). Homodimer (PubMed:19710016, CC PubMed:36402789). Heterodimerizes with RAF1, and the heterodimer CC possesses a highly increased kinase activity compared to the respective CC homodimers or monomers (PubMed:19710016). Heterodimerization is CC mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 CC activation can induce a negative feedback that promotes the CC dissociation of the heterodimer by phosphorylating BRAF at Thr-753. CC Heterodimerizes (via N-terminus) with KSR1 (via N-terminus) or KSR2 CC (via N-terminus) in a MAP2K1-dependent manner (PubMed:29433126). CC Interacts with MAP2K1 and MAP2K2 (PubMed:29433126). Found in a complex CC with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIT1. CC Interacts (via N-terminus) with RGS14 (via RBD domains); the CC interaction mediates the formation of a ternary complex with RAF1, a CC ternary complex inhibited by GNAI1 (By similarity). Interacts with DGKH CC (PubMed:19710016). Interacts with PRMT5 (PubMed:21917714). Interacts CC with KSR2 (PubMed:21441910). Interacts with AKAP13, MAP2K1 and KSR1. CC Identified in a complex with AKAP13, MAP2K1 and KSR1 (PubMed:21102438). CC Interacts 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, ECO:0000269|PubMed:36402789}. CC -!- INTERACTION: CC P15056; P15056: BRAF; NbExp=13; IntAct=EBI-365980, EBI-365980; CC P15056; P01112: HRAS; NbExp=7; IntAct=EBI-365980, EBI-350145; CC P15056; P08238: HSP90AB1; NbExp=4; IntAct=EBI-365980, EBI-352572; CC P15056; P46940: IQGAP1; NbExp=4; IntAct=EBI-365980, EBI-297509; CC P15056; Q02750: MAP2K1; NbExp=62; IntAct=EBI-365980, EBI-492564; CC P15056; P36507: MAP2K2; NbExp=11; IntAct=EBI-365980, EBI-1056930; CC P15056; Q13233: MAP3K1; NbExp=2; IntAct=EBI-365980, EBI-49776; CC P15056; P01111: NRAS; NbExp=6; IntAct=EBI-365980, EBI-721993; CC P15056; Q02156: PRKCE; NbExp=3; IntAct=EBI-365980, EBI-706254; CC P15056; P04049: RAF1; NbExp=71; IntAct=EBI-365980, EBI-365996; CC P15056; Q15349: RPS6KA2; NbExp=2; IntAct=EBI-365980, EBI-1384149; CC P15056; P31947: SFN; NbExp=5; IntAct=EBI-365980, EBI-476295; CC P15056; Q13114: TRAF3; NbExp=2; IntAct=EBI-365980, EBI-357631; CC P15056; P31946: YWHAB; NbExp=8; IntAct=EBI-365980, EBI-359815; CC P15056; P62258: YWHAE; NbExp=9; IntAct=EBI-365980, EBI-356498; CC P15056; P63104: YWHAZ; NbExp=10; IntAct=EBI-365980, EBI-347088; CC P15056; Q61097: Ksr1; Xeno; NbExp=3; IntAct=EBI-365980, EBI-1536336; CC P15056; P29678: MAP2K1; Xeno; NbExp=2; IntAct=EBI-365980, EBI-1631983; CC P15056; Q99N57: Raf1; Xeno; NbExp=3; IntAct=EBI-365980, EBI-397757; CC P15056; Q8CGE9: Rgs12; Xeno; NbExp=2; IntAct=EBI-365980, EBI-7340552; 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 variants 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 intellectual disability. Heart CC defects include pulmonic stenosis, atrial septal defects and CC hypertrophic cardiomyopathy. Some affected individuals present with CC ectodermal abnormalities such as sparse, friable hair, hyperkeratotic CC skin lesions and a generalized ichthyosis-like condition. Typical CC facial features are similar to Noonan syndrome. They include high CC forehead with bitemporal constriction, hypoplastic supraorbital ridges, CC downslanting palpebral fissures, a depressed nasal bridge, and CC posteriorly angulated ears with prominent helices. CC {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:16474404, CC ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 variants 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 variants 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="https://atlasgeneticsoncology.org/gene/828/BRAF"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 6N0Q; X-ray; 2.04 A; A/B=445-723. DR PDB; 6NSQ; X-ray; 3.05 A; A/B=444-723. DR PDB; 6NYB; EM; 4.10 A; A=1-766. DR PDB; 6P3D; X-ray; 2.11 A; A=448-721. DR PDB; 6P7G; X-ray; 2.65 A; A/B/C/D=448-723. DR PDB; 6PP9; X-ray; 2.59 A; A=445-723. DR PDB; 6Q0J; EM; 4.90 A; A/B=1-766. DR PDB; 6Q0K; EM; 6.80 A; A/B=1-766. DR PDB; 6Q0T; EM; 5.70 A; A/B=1-766. 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 PDB; 6UUO; X-ray; 3.29 A; A/B=444-723. DR PDB; 6V2U; X-ray; 3.78 A; A/B=445-723. DR PDB; 6V2W; X-ray; 3.12 A; A=445-723. DR PDB; 6V34; X-ray; 3.15 A; A/B=448-721. DR PDB; 6XAG; X-ray; 3.30 A; C/D=447-735. DR PDB; 6XFP; X-ray; 2.00 A; A=442-721. DR PDB; 6XLO; X-ray; 2.49 A; A/B=442-721. DR PDB; 7K0V; X-ray; 1.93 A; A/B/C/D=444-723. DR PDB; 7M0T; X-ray; 3.19 A; A=445-723. DR PDB; 7M0U; X-ray; 3.09 A; A=445-723. DR PDB; 7M0V; X-ray; 3.16 A; A=445-723. DR PDB; 7M0W; X-ray; 3.09 A; A=445-723. DR PDB; 7M0X; X-ray; 2.47 A; A=445-723. DR PDB; 7M0Y; X-ray; 3.45 A; A=445-723. DR PDB; 7M0Z; X-ray; 3.12 A; A=445-723. DR PDB; 7MFD; EM; 3.66 A; A=1-766. DR PDB; 7MFE; EM; 4.07 A; A=1-766. DR PDB; 7MFF; EM; 3.89 A; A/B=1-766. DR PDB; 7P3V; X-ray; 2.37 A; A/B=448-719. DR PDB; 7SHV; X-ray; 2.88 A; A/B=432-726. DR PDB; 7ZR0; EM; 3.40 A; K=1-766. DR PDB; 7ZR5; EM; 3.90 A; K=1-766. DR PDB; 7ZR6; EM; 4.20 A; K=1-766. DR PDB; 8C7X; X-ray; 1.65 A; A/B=444-721. DR PDB; 8C7Y; X-ray; 1.65 A; A/B=444-721. DR PDB; 8DGS; EM; 4.30 A; A=1-766. DR PDB; 8DGT; EM; 3.90 A; A=1-766. DR PDB; 8F7O; X-ray; 3.54 A; A/B=441-723. DR PDB; 8F7P; X-ray; 2.74 A; A/B=441-723. 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; 6N0Q; -. DR PDBsum; 6NSQ; -. DR PDBsum; 6NYB; -. DR PDBsum; 6P3D; -. DR PDBsum; 6P7G; -. DR PDBsum; 6PP9; -. DR PDBsum; 6Q0J; -. DR PDBsum; 6Q0K; -. DR PDBsum; 6Q0T; -. DR PDBsum; 6U2G; -. DR PDBsum; 6U2H; -. DR PDBsum; 6UAN; -. DR PDBsum; 6UUO; -. DR PDBsum; 6V2U; -. DR PDBsum; 6V2W; -. DR PDBsum; 6V34; -. DR PDBsum; 6XAG; -. DR PDBsum; 6XFP; -. DR PDBsum; 6XLO; -. DR PDBsum; 7K0V; -. DR PDBsum; 7M0T; -. DR PDBsum; 7M0U; -. DR PDBsum; 7M0V; -. DR PDBsum; 7M0W; -. DR PDBsum; 7M0X; -. DR PDBsum; 7M0Y; -. DR PDBsum; 7M0Z; -. DR PDBsum; 7MFD; -. DR PDBsum; 7MFE; -. DR PDBsum; 7MFF; -. DR PDBsum; 7P3V; -. DR PDBsum; 7SHV; -. DR PDBsum; 7ZR0; -. DR PDBsum; 7ZR5; -. DR PDBsum; 7ZR6; -. DR PDBsum; 8C7X; -. DR PDBsum; 8C7Y; -. DR PDBsum; 8DGS; -. DR PDBsum; 8DGT; -. DR PDBsum; 8F7O; -. DR PDBsum; 8F7P; -. DR AlphaFoldDB; P15056; -. DR BMRB; P15056; -. DR EMDB; EMD-0541; -. DR EMDB; EMD-20550; -. DR EMDB; EMD-20551; -. DR EMDB; EMD-20552; -. DR EMDB; EMD-20708; -. DR EMDB; EMD-23813; -. DR EMDB; EMD-23814; -. DR EMDB; EMD-23815; -. DR EMDB; EMD-27428; -. DR EMDB; EMD-27429; -. DR SMR; P15056; -. DR BioGRID; 107141; 183. DR CORUM; P15056; -. DR DIP; DIP-1045N; -. DR IntAct; P15056; 91. DR MINT; P15056; -. DR STRING; 9606.ENSP00000419060; -. 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; PLX-4720. DR DrugBank; DB05984; RAF-265. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB05190; XL281. DR DrugCentral; P15056; -. DR GuidetoPHARMACOLOGY; 1943; -. DR TCDB; 8.A.23.1.48; the basigin (basigin) family. DR iPTMnet; P15056; -. DR PhosphoSitePlus; P15056; -. DR BioMuta; BRAF; -. DR DMDM; 50403720; -. DR CPTAC; CPTAC-3112; -. DR CPTAC; CPTAC-3113; -. DR CPTAC; CPTAC-5771; -. DR CPTAC; CPTAC-5817; -. DR CPTAC; CPTAC-5818; -. DR CPTAC; CPTAC-5819; -. DR CPTAC; CPTAC-5820; -. DR CPTAC; CPTAC-5821; -. DR CPTAC; CPTAC-5822; -. DR CPTAC; non-CPTAC-5352; -. DR CPTAC; non-CPTAC-5353; -. DR CPTAC; non-CPTAC-5354; -. DR CPTAC; non-CPTAC-5355; -. DR CPTAC; non-CPTAC-5356; -. DR CPTAC; non-CPTAC-5357; -. DR CPTAC; non-CPTAC-5727; -. DR CPTAC; non-CPTAC-5728; -. DR CPTAC; non-CPTAC-5729; -. DR EPD; P15056; -. DR jPOST; P15056; -. DR MassIVE; P15056; -. DR MaxQB; P15056; -. DR PaxDb; 9606-ENSP00000288602; -. DR PeptideAtlas; P15056; -. DR ProteomicsDB; 53102; -. DR Pumba; P15056; -. DR Antibodypedia; 751; 2663 antibodies from 51 providers. DR CPTC; P15056; 7 antibodies. DR DNASU; 673; -. DR Ensembl; ENST00000646891.2; ENSP00000493543.1; ENSG00000157764.14. DR GeneID; 673; -. DR KEGG; hsa:673; -. DR MANE-Select; ENST00000646891.2; ENSP00000493543.1; NM_004333.6; NP_004324.2. DR UCSC; uc003vwc.5; human. DR AGR; HGNC:1097; -. DR CTD; 673; -. DR DisGeNET; 673; -. DR GeneCards; BRAF; -. DR GeneReviews; BRAF; -. DR HGNC; HGNC:1097; BRAF. DR HPA; ENSG00000157764; Low tissue specificity. 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; 96253; Cushing disease. DR Orphanet; 146; Differentiated thyroid carcinoma. DR Orphanet; 389; Langerhans cell histiocytosis. DR Orphanet; 626; Large congenital melanocytic nevus. DR Orphanet; 411533; NON RARE IN EUROPE: Melanoma. DR Orphanet; 500; Noonan syndrome with multiple lentigines. DR Orphanet; 251615; Pilomyxoid astrocytoma. DR Orphanet; 840; Syringocystadenoma papilliferum. DR PharmGKB; PA25408; -. DR VEuPathDB; HostDB:ENSG00000157764; -. DR eggNOG; KOG0193; Eukaryota. DR GeneTree; ENSGT00940000156154; -. DR HOGENOM; CLU_023684_1_0_1; -. DR InParanoid; P15056; -. DR OrthoDB; 4560496at2759; -. DR PhylomeDB; P15056; -. DR TreeFam; TF317006; -. DR BRENDA; 2.7.10.2; 2681. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; P15056; -. 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 RAF1 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 Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR Reactome; R-HSA-9726840; SHOC2 M1731 mutant abolishes MRAS complex function. DR Reactome; R-HSA-9726842; Gain-of-function MRAS complexes activate RAF signaling. DR SignaLink; P15056; -. DR SIGNOR; P15056; -. DR BioGRID-ORCS; 673; 88 hits in 1213 CRISPR screens. 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 buccal mucosa cell and 183 other cell types or tissues. DR ExpressionAtlas; P15056; baseline and differential. DR GO; GO:0044297; C:cell body; IEA:Ensembl. 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:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098793; C:presynapse; IEA:GOC. 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:0004708; F:MAP kinase kinase activity; IMP:UniProtKB. DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IBA:GO_Central. DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IEA:Ensembl. DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc. DR GO; GO:0043369; P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; IEA:Ensembl. DR GO; GO:0043367; P:CD4-positive, alpha-beta T cell differentiation; IEA:Ensembl. DR GO; GO:0071277; P:cellular response to calcium ion; IDA:BHF-UCL. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0090150; P:establishment of protein localization to membrane; IDA:CACAO. DR GO; GO:0060324; P:face development; IEA:Ensembl. DR GO; GO:0060323; P:head morphogenesis; IEA:Ensembl. DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB. DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; IEA:Ensembl. DR GO; GO:0048680; P:positive regulation of axon regeneration; IEA:Ensembl. DR GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl. 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:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0045580; P:regulation of T cell differentiation; IEA:Ensembl. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0043149; P:stress fiber assembly; IEA:Ensembl. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl. DR GO; GO:0016079; P:synaptic vesicle exocytosis; IEA:Ensembl. DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl. DR GO; GO:0070413; P:trehalose metabolism in response to stress; IMP:SGD. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd20871; C1_B-Raf; 1. DR CDD; cd17134; RBD_BRAF; 1. DR CDD; cd14062; STKc_Raf; 1. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR046349; C1-like_sf. 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 PANTHER; PTHR23257:SF731; NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE; 1. DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 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; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 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. DR Genevisible; P15056; HS. 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 variant; Ectodermal dysplasia; KW Intellectual disability; Isopeptide bond; Kinase; Membrane; Metal-binding; KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW 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 REGION 1..38 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 308..454 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 308..337 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 392..426 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 427..451 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 576 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 235 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 248 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 251 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 261 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 264 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 269 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 272 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 280 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 463..471 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 483 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" 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:0007744|PubMed:23186163, FT ECO:0007744|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:0000269|PubMed:11410590, ECO:0000269|Ref.8, FT ECO:0007744|PubMed:23186163" 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:0000269|Ref.8, ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 446 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 447 FT /note="Phosphoserine" FT /evidence="ECO:0007744|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:0000269|Ref.8, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" 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 NS7; 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 NS7; 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 CFC1; also found in colon cancer; 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:0007829|PDB:5VYK" FT HELIX 76..103 FT /evidence="ECO:0007829|PDB:5VYK" FT STRAND 156..161 FT /evidence="ECO:0007829|PDB:3NY5" FT TURN 162..164 FT /evidence="ECO:0007829|PDB:3NY5" FT STRAND 165..170 FT /evidence="ECO:0007829|PDB:3NY5" FT HELIX 177..186 FT /evidence="ECO:0007829|PDB:3NY5" FT TURN 187..189 FT /evidence="ECO:0007829|PDB:3NY5" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:3NY5" FT STRAND 195..199 FT /evidence="ECO:0007829|PDB:3NY5" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:3NY5" FT HELIX 214..217 FT /evidence="ECO:0007829|PDB:3NY5" FT STRAND 221..226 FT /evidence="ECO:0007829|PDB:3NY5" FT HELIX 448..450 FT /evidence="ECO:0007829|PDB:6P3D" FT HELIX 454..456 FT /evidence="ECO:0007829|PDB:5JRQ" FT STRAND 458..466 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 469..484 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 487..489 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 492..505 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 516..520 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 522..524 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 526..530 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 534..536 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 537..542 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 543..545 FT /evidence="ECO:0007829|PDB:6P3D" FT HELIX 550..569 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 579..581 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 582..585 FT /evidence="ECO:0007829|PDB:8C7X" FT TURN 586..588 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 589..592 FT /evidence="ECO:0007829|PDB:8C7X" FT TURN 598..600 FT /evidence="ECO:0007829|PDB:6XFP" FT TURN 602..605 FT /evidence="ECO:0007829|PDB:4RZV" FT HELIX 609..612 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 614..619 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 622..626 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 629..631 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 635..651 FT /evidence="ECO:0007829|PDB:8C7X" FT TURN 655..658 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 662..671 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 678..680 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 683..685 FT /evidence="ECO:0007829|PDB:5JRQ" FT HELIX 687..696 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 701..703 FT /evidence="ECO:0007829|PDB:8C7X" FT HELIX 707..721 FT /evidence="ECO:0007829|PDB:8C7X" FT STRAND 723..726 FT /evidence="ECO:0007829|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 //