Reviewed, UniProtKB/Swiss-Prot P15056 (BRAF1_HUMAN)

Names and origin

Protein names

Recommended name:
    B-Raf proto-oncogene serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    p94
    v-Raf murine sarcoma viral oncogene homolog B1

Gene names

Name:	BRAF
Synonyms:	BRAF1, RAFB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	766 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 2 zinc ions per subunit By similarity.
Subunit structure	Interacts with RIT1 By similarity.
Subcellular location	Cytoplasm.
Tissue specificity	Brain and testis.
Involvement in disease	Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Defects in BRAF are involved in a wide range of cancers. Defects in BRAF are involved in lung cancer [MIM:211980]. Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. Ref.19 Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:114500].
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. Contains 1 RBD (Ras-binding) domain.
Sequence caution	The sequence AAD43193.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Cardiomyopathy Disease mutation Proto-oncogene
Domain	Phorbol-ester binding Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc organ morphogenesis Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.7 Traceable author statement. Source: ProtInc small GTPase mediated signal transduction Inferred from Experiment. Source: Reactome
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAB	P31946	1	EBI-365980,EBI-359815
YWHAG	P61981	1	EBI-365980,EBI-359832
YWHAQ	P27348	1	EBI-365980,EBI-359854
YWHAZ	P63104	1	EBI-365980,EBI-347088

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 766

765

B-Raf proto-oncogene serine/threonine-protein kinase

PRO_0000085665

Regions

Domain

155 – 227

73

RBD

Domain

457 – 717

261

Protein kinase

Zinc finger

234 – 280

47

Phorbol-ester/DAG-type

Nucleotide binding

463 – 471

9

ATP By similarity

Compositional bias

6 – 11

6

Poly-Gly

Compositional bias

122 – 129

8

Poly-Ser

Compositional bias

428 – 432

5

Poly-Ser

Sites

Active site

576

1

Proton acceptor By similarity

Metal binding

235

1

Zinc 1 By similarity

Metal binding

248

1

Zinc 2 By similarity

Metal binding

251

1

Zinc 2 By similarity

Metal binding

261

1

Zinc 1 By similarity

Metal binding

264

1

Zinc 1 By similarity

Metal binding

269

1

Zinc 2 By similarity

Metal binding

272

1

Zinc 2 By similarity

Metal binding

280

1

Zinc 1 By similarity

Binding site

483

1

ATP By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

151

1

Phosphoserine Ref.12

Modified residue

365

1

Phosphoserine Ref.6 Ref.12

Modified residue

373

1

Phosphothreonine; by autocatalysis Ref.1 Ref.13

Modified residue

396

1

Phosphothreonine Ref.6

Modified residue

399

1

Phosphoserine Ref.6

Modified residue

401

1

Phosphothreonine Ref.6 Ref.12 Ref.9 Ref.10 Ref.15

Modified residue

419

1

Phosphoserine Ref.12 Ref.11

Modified residue

446

1

Phosphoserine Ref.12 Ref.15

Modified residue

447

1

Phosphoserine Ref.15

Modified residue

729

1

Phosphoserine Ref.6 Ref.12 Ref.9 Ref.15 Ref.14

Modified residue

750

1

Phosphoserine Ref.12

Natural variations

Natural variant

246

1

A → P in CFC syndrome.

VAR_026113

Natural variant

257

1

Q → R in CFC syndrome.

VAR_026114

Natural variant

301

1

P → S Ref.24

VAR_040391

Natural variant

462

1

R → I in colorectal cancer. Ref.18

VAR_018613

Natural variant

463

1

I → S in colorectal cancer. Ref.18

VAR_018614

Natural variant

464

1

G → E in colorectal cancer. Ref.18 Ref.17

VAR_018615

Natural variant

464

1

G → V in a colorectal cancer cell line; elevated kinase activity; efficiently induces cell transformation. Ref.18 Ref.17

VAR_018616

Natural variant

466

1

G → A in melanoma. Ref.17 Ref.16

VAR_018617

Natural variant

466

1

G → E in melanoma. Ref.17 Ref.16

VAR_018618

Natural variant

466

1

G → V in lung cancer. Ref.17 Ref.16

VAR_018512

Natural variant

467

1

S → A in CFC syndrome.

VAR_035096

Natural variant

468

1

F → S in CFC syndrome.

VAR_035097

Natural variant

469

1

G → A in NHL; also in a lung adenocarcinoma sample; somatic mutation; elevated kinase activity; efficiently induces cell transformation. Ref.19

VAR_018620

Natural variant

469

1

G → E in CFC syndrome and colon cancer.

VAR_018621

Natural variant

469

1

G → R in NHL. Ref.19

VAR_018622

Natural variant

469

1

G → V in a colorectal adenocarcinoma sample; somatic mutation. Ref.19 Ref.24 Ref.17 Ref.21 Ref.23

VAR_040392

Natural variant

485

1

L → F in CFC syndrome.

VAR_026115

Natural variant

499

1

K → E in CFC syndrome.

VAR_026116

Natural variant

501

1

E → G in CFC syndrome.

VAR_026117

Natural variant

501

1

E → K in CFC syndrome.

VAR_026118

Natural variant

581

1

N → D in CFC syndrome.

VAR_026119

Natural variant

581

1

N → S in a colorectal adenocarcinoma sample; somatic mutation. Ref.24 Ref.21 Ref.23

VAR_040393

Natural variant

586

1

E → K in ovarian cancer. Ref.17

VAR_018623

Natural variant

594

1

D → G in NHL. Ref.19

VAR_018624

Natural variant

595

1

F → L in colon cancer. Ref.17 Ref.23

VAR_018625

Natural variant

596

1

G → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.24 Ref.17 Ref.23

VAR_018626

Natural variant

596

1

G → V in CFC syndrome.

VAR_035098

Natural variant

597

1

L → R in lung cancer and ovarian cancer; ovarian serous carcinoma sample; somatic mutation. Ref.24 Ref.17 Ref.16

VAR_018513

Natural variant

597

1

L → V in a lung adenocarcinoma sample; somatic mutation; elevated kinase activity; efficiently induces cell transformation. Ref.24 Ref.17 Ref.16

VAR_018627

Natural variant

600

1

V → D in a melanoma cell line; requires 2 nucleotide substitutions. Ref.24 Ref.18 Ref.17 Ref.20 Ref.22

VAR_018628

Natural variant

600

1

V → E in sarcoma, colorectal adenocarcinoma, metastatic melanoma, ovarian serous carcinoma; somatic mutation; most common mutation; elevated kinase activity; efficiently induces cell transformation; suppression of mutation in melanoma causes growth arrest and promotes apoptosis. Ref.24 Ref.18 Ref.17 Ref.20 Ref.22

VAR_018629

Natural variant

601

1

K → E in colorectal cancer. Ref.18

VAR_018630

Experimental info

Sequence conflict

766

1

H → D in AAA96495. Ref.8

Secondary structure

1

.

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.

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.

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.

.

.

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.

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.

.

.

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.

.

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.

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.

766

Helix Strand Turn

Details...

Beta strand

461 – 465

5

Beta strand

470 – 484

15

Helix

494 – 505

12

Beta strand

516 – 520

5

Beta strand

522 – 524

3

Beta strand

526 – 530

5

Beta strand

534 – 536

3

Helix

537 – 542

6

Helix

550 – 569

20

Helix

579 – 581

3

Beta strand

582 – 585

4

Beta strand

588 – 592

5

Helix

617 – 619

3

Helix

622 – 625

4

Helix

635 – 651

17

Turn

655 – 658

4

Helix

662 – 670

9

Helix

678 – 680

3

Helix

687 – 696

10

Helix

701 – 703

3

Helix

707 – 719

13

Sequences

	Sequence		Length	Mass (Da)
	P15056-1 [UniParc]. Last modified July 19, 2004. Version 4. Checksum: 0798C2AAB487E813	FASTA	766	84,437
	10 20 30 40 50 60 MAALSGGGGG GAEPGQALFN GDMEPEAGAG AGAAASSAAD PAIPEEVWNI KQMIKLTQEH 70 80 90 100 110 120 IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESLGNGTDFS VSSSASMDTV 130 140 150 160 170 180 TSSSSSSLSV LPSSLSVFQN PTDVARSNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS 190 200 210 220 230 240 LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK 250 260 270 280 290 300 TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI 310 320 330 340 350 360 PQEEASLAET ALTSGSSPSA PASDSIGPQI LTSPSPSKSI PIPQPFRPAD EDHRNQFGQR 370 380 390 400 410 420 DRSSSAPNVH INTIEPVNID DLIRDQGFRG DGGSTTGLSA TPPASLPGSL TNVKALQKSP 430 440 450 460 470 480 GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV 490 500 510 520 530 540 AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH 550 560 570 580 590 600 LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV 610 620 630 640 650 660 KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN 670 680 690 700 710 720 NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS 730 740 750 760 LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GAFPVH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"95-kilodalton B-Raf serine/threonine kinase: identification of the protein and its major autophosphorylation site." Stephens R.M., Sithanandam G., Copeland T.D., Kaplan D.R., Rapp U.R., Morrison D.K. Mol. Cell. Biol. 12:3733-3742(1992) [PubMed: 1508179] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT THR-373. Tissue: Testis.
[2]	Albert S., Wixler L., Rapp U.R. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 31-33.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	"Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene." Eychene A., Barnier J.V., Apiou F., Dutrillaux B., Calothy G. Oncogene 7:1657-1660(1992) [PubMed: 1630826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200. Tissue: Placenta.
[6]	Bienvenut W.V., Boldt K., von Kriegsheim A.F., Zebisch A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-51; 56-95; 151-158; 189-199; 253-260; 294-354; 361-424; 444-507; 510-522; 559-570; 579-626; 663-680; 692-698; 702-719; 727-735 AND 753-766, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-365; THR-396; SER-399; THR-401 AND SER-729, MASS SPECTROMETRY. Tissue: Colon carcinoma and Hepatoma.
[7]	"Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies." Sithanandam G., Kolch W., Duh F.-M., Rapp U.R. Oncogene 5:1775-1780(1990) [PubMed: 2284096] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 117-766. Tissue: Testis.
[8]	"B-raf, a new member of the raf family, is activated by DNA rearrangement." Ikawa S., Fukui M., Ueyama Y., Tamaoki N., Yamamoto T., Toyoshima K. Mol. Cell. Biol. 8:2651-2654(1988) [PubMed: 3043188] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 439-766.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-729, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-365; THR-401; SER-419; SER-446; SER-729 AND SER-750, MASS SPECTROMETRY.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, MASS SPECTROMETRY.
[14]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729, MASS SPECTROMETRY.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-446; SER-447 AND SER-729, MASS SPECTROMETRY.
[16]	"Missense mutations of the BRAF gene in human lung adenocarcinoma." Naoki K., Chen T.-H., Richards W.G., Sugarbaker D.J., Meyerson M. Cancer Res. 62:7001-7003(2002) [PubMed: 12460919] [Abstract] Cited for: VARIANTS LUNG CANCER VAL-466 AND ARG-597.
[17]	"Mutations of the BRAF gene in human cancer." Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S., Teague J., Woffendin H., Garnett M.J., Bottomley W., Davis N., Dicks E., Ewing R., Floyd Y., Gray K., Hall S., Hawes R., Hughes J. , Kosmidou V., Menzies A., Mould C., Parker A., Stevens C., Watt S., Hooper S., Wilson R., Jayatilake H., Gusterson B.A., Cooper C., Shipley J., Hargrave D., Pritchard-Jones K., Maitland N., Chenevix-Trench G., Riggins G.J., Bigner D.D., Palmieri G., Cossu A., Flanagan A., Nicholson A., Ho J.W.C., Leung S.Y., Yuen S.T., Weber B.L., Seigler H.F., Darrow T.L., Paterson H., Marais R., Marshall C.J., Wooster R., Stratton M.R., Futreal P.A. Nature 417:949-954(2002) [PubMed: 12068308] [Abstract] Cited for: VARIANTS CANCER GLU-464; VAL-464; ALA-466; GLU-466; VAL-466; ALA-469; GLU-469; LYS-586; LEU-595; ARG-596; ARG-597; VAL-597; GLU-600 AND ASP-600, CHARACTERIZATION OF VARIANTS CANCER VAL-464; ALA-469; VAL-597 AND GLU-600.
[18]	"Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status." Rajagopalan H., Bardelli A., Lengauer C., Kinzler K.W., Vogelstein B., Velculescu V.E. Nature 418:934-934(2002) [PubMed: 12198537] [Abstract] Cited for: VARIANTS COLORECTAL CANCER ILE-462; SER-463; GLU-464; GLU-600 AND GLU-601.
[19]	"BRAF mutations in non-Hodgkin's lymphoma." Lee J.W., Yoo N.J., Soung Ark W.S., Kim S.Y., Lee J.H., Park J.Y., Cho Y.G., Kim C.J., Ko Y.H., Kim S.H., Nam S.W., Lee J.Y., Lee S.H. Br. J. Cancer 89:1958-1960(2003) [PubMed: 14612909] [Abstract] Cited for: VARIANTS NHL ALA-469; ARG-469 AND GLY-594.
[20]	"Suppression of BRAF(V599E) in human melanoma abrogates transformation." Hingorani S.R., Jacobetz M.A., Robertson G.P., Herlyn M., Tuveson D.A. Cancer Res. 63:5198-5202(2003) [PubMed: 14500344] [Abstract] Cited for: CHARACTERIZATION OF VARIANT MELANOMA GLU-600.
[21]	"Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome." Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N., Hennekam R.C.M., Gillessen-Kaesbach G., Wieczorek D., Kavamura M.I., Kurosawa K., Ohashi H., Wilson L., Heron D., Bonneau D., Corona G., Kaname T. , Naritomi K., Baumann C., Matsumoto N., Kato K., Kure S., Matsubara Y. Nat. Genet. 38:294-296(2006) [PubMed: 16474404] [Abstract] Cited for: VARIANTS CFC SYNDROME PRO-246; ARG-257; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501 AND ASP-581.
[22]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-600.
[23]	"Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome." Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., Rauen K.A. Science 311:1287-1290(2006) [PubMed: 16439621] [Abstract] Cited for: VARIANTS CFC SYNDROME ARG-257; ALA-467; SER-468; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501; ASP-581; LEU-595 AND VAL-596.
[24]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-301; ALA-469; VAL-469; SER-581; ARG-596; ARG-597; VAL-597; GLU-600; GLU-600 AND GLU-600.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M95712 mRNA. Translation: AAA35609.2.
AC006344 Genomic DNA. Translation: AAD43193.1. Sequence problems.
AC006347 Genomic DNA. Translation: AAD15551.1.
BC101757 mRNA. Translation: AAI01758.1.
BC112079 mRNA. Translation: AAI12080.1.
X65187 Genomic DNA. Translation: CAA46301.1.
M21001 mRNA. Translation: AAA96495.1.

IPI

IPI00303797.

PIR

TVHUBF. A57977.

RefSeq

NP_004324.2.

UniGene

Hs.550061

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UWH	X-ray	2.95	A/B	448-723	[»]
1UWJ	X-ray	3.50	A/B	448-723	[»]
2FB8	X-ray	2.90	A/B	445-723	[»]
3C4C	X-ray	2.57	A/B	444-719	[»]
3C4D	X-ray	2.65	A/B	444-719	[»]
3D4Q	X-ray	2.80	A/B	433-726	[»]

SMR

P15056. Positions 232-283.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1045N.

IntAct

P15056. 23 interactions.

PTM databases

PhosphoSite

P15056.

Proteomic databases

PRIDE

P15056.

Genome annotation databases

Ensembl

ENSG00000157764. Homo sapiens. [Contig view]

GeneID

673.

KEGG

hsa:673.

Organism-specific databases

GeneCards

GC07M140080.

H-InvDB

HIX0007148.

HGNC

HGNC:1097. BRAF.

HPA

CAB004552.
HPA001328.

MIM

114500. phenotype.
115150. phenotype.
164757. gene.
211980. phenotype.
605027. phenotype.

Orphanet

1340. Cardiofaciocutaneous syndrome.

PharmGKB

PA25408.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15056.

HOVERGEN

P15056.

OMA

P15056. IVFDFEP.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.
2.7.11.1. 247.

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

P15056.

Bgee

P15056.

CleanEx

HS_BRAF.

GermOnline

ENSG00000157764. Homo sapiens.

Family and domain databases

InterPro

IPR002219. DAG_PE_bd.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras_bd.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF00069. Pkinase. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50898. RBD. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00398. Sorafenib.

NextBio

2776.

PMAP-CutDB

P15056.

SOURCE

Search...

Entry information

Entry name

BRAF1_HUMAN

Accession

Primary (citable) accession number: P15056
Secondary accession number(s): Q13878 , Q3MIN6, Q9UDP8, Q9Y6T3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	July 19, 2004
Last modified:	June 16, 2009
This is version 122 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)