P15056 (BRAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase B-raf
EC=2.7.11.1

Alternative name(s):
Proto-oncogene B-Raf
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	Monomer. Homodimer. Heterodimerizes with RAF1, and the heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers. Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer by phosphorylating BRAF at Thr-753. Found in a complex with at least BRAF, HRAS1, MAP2K1, MAPK3 and RGS14. Interacts with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with RAF1, a ternary complex inhibited by GNAI1 By similarity. Interacts with DGKH. Ref.21
Subcellular location	Nucleus By similarity. Cytoplasm. Cell membrane By similarity. Note: Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes By similarity.
Tissue specificity	Brain and testis.
Post-translational modification	Phosphorylation at Ser-365 by SGK1 inhibits its activity.
Involvement in disease	Note=Defects in BRAF are found in a wide range of cancers. Ref.10 Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:114500]. Ref.10 Defects in BRAF are involved in lung cancer (LNCR) [MIM:211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Ref.10 Ref.25 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.10 Ref.28 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. Ref.10 Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:613706]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits. Ref.10 Ref.35 Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:613707]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. Ref.10 Ref.35 Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation. Ref.10
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. The sequence CAQ43111.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAQ43112.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAQ43113.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAQ43114.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAQ43115.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAQ43116.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Cardiomyopathy Deafness Disease mutation Proto-oncogene
Domain	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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of MAPKK activity Traceable author statement. Source: Reactome anti-apoptosis Traceable author statement. Source: ProtInc nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome organ morphogenesis Traceable author statement. Source: ProtInc positive regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA plasma membrane Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAF1	P04049	19	EBI-365980,EBI-365996

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 766

765

Serine/threonine-protein kinase B-raf

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

Site

380 – 381

2

Breakpoint for translocation to form KIAA1549-BRAF fusion protein

Site

438 – 439

2

Breakpoint for translocation to form KIAA1549-BRAF fusion protein

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

151

1

Phosphoserine Ref.16

Modified residue

365

1

Phosphoserine; by SGK1 Ref.8 Ref.12 Ref.16

Modified residue

373

1

Phosphothreonine; by autocatalysis Ref.1 Ref.17

Modified residue

396

1

Phosphothreonine Ref.8

Modified residue

399

1

Phosphoserine Ref.8

Modified residue

401

1

Phosphothreonine Ref.8 Ref.13 Ref.14 Ref.16 Ref.19 Ref.20

Modified residue

418

1

N6-acetyllysine Ref.24

Modified residue

419

1

Phosphoserine Ref.15 Ref.16 Ref.22

Modified residue

446

1

Phosphoserine Ref.16 Ref.19

Modified residue

447

1

Phosphoserine Ref.19

Modified residue

465

1

Phosphoserine Ref.23

Modified residue

614

1

Phosphoserine Ref.23

Modified residue

729

1

Phosphoserine Ref.8 Ref.13 Ref.16 Ref.18 Ref.19 Ref.20

Modified residue

750

1

Phosphoserine Ref.16

Modified residue

753

1

Phosphothreonine; by MAPK1 Ref.21

Natural variations

Natural variant

241

1

T → M in a patient with Noonan syndrome. Ref.35

VAR_058620

Natural variant

241

1

T → P in CFC syndrome and LEOPARD3. Ref.34 Ref.35

VAR_058621

Natural variant

241

1

T → R in a patient with Noonan syndrome. Ref.35

VAR_058622

Natural variant

244

1

T → P in CFC syndrome. Ref.34

VAR_065171

Natural variant

245

1

L → F in CFC syndrome. Ref.35

VAR_058623

Natural variant

246

1

A → P in CFC syndrome. Ref.30 Ref.34 Ref.35

VAR_026113

Natural variant

257

1

Q → R in CFC syndrome. Ref.30 Ref.32 Ref.34 Ref.35

VAR_026114

Natural variant

262

1

Q → K in CFC syndrome. Ref.34

VAR_065172

Natural variant

275

1

E → K in CFC syndrome. Ref.35

VAR_058624

Natural variant

301

1

P → S. Ref.33
Corresponds to variant rs34776339 [ dbSNP | Ensembl ].

VAR_040391

Natural variant

462

1

R → I in colorectal cancer. Ref.27

VAR_018613

Natural variant

463

1

I → S in colorectal cancer. Ref.27

VAR_018614

Natural variant

464

1

G → E in colorectal cancer. Ref.26 Ref.27

VAR_018615

Natural variant

464

1

G → V in a colorectal cancer cell line; elevated kinase activity; efficiently induces cell transformation. Ref.26

VAR_018616

Natural variant

466

1

G → A in melanoma. Ref.26

VAR_018617

Natural variant

466

1

G → E in melanoma. Ref.26

VAR_018618

Natural variant

466

1

G → V in LNCR. Ref.25 Ref.26

VAR_018512

Natural variant

467

1

S → A in CFC syndrome. Ref.32

VAR_035096

Natural variant

468

1

F → S in CFC syndrome. Ref.32 Ref.34

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.26 Ref.28 Ref.33

VAR_018620

Natural variant

469

1

G → E in CFC syndrome and colon cancer. Ref.26 Ref.30 Ref.32 Ref.34 Ref.35

VAR_018621

Natural variant

469

1

G → R in NHL. Ref.28

VAR_018622

Natural variant

469

1

G → V in a colorectal adenocarcinoma sample; somatic mutation. Ref.33

VAR_040392

Natural variant

485

1

L → F in CFC syndrome. Ref.30 Ref.32 Ref.35

VAR_026115

Natural variant

499

1

K → E in CFC syndrome. Ref.30 Ref.32 Ref.34

VAR_026116

Natural variant

499

1

K → N in CFC syndrome. Ref.34 Ref.35

VAR_058625

Natural variant

501

1

E → G in CFC syndrome. Ref.30 Ref.32

VAR_026117

Natural variant

501

1

E → K in CFC syndrome. Ref.30 Ref.32 Ref.35

VAR_026118

Natural variant

525

1

L → P in CFC syndrome. Ref.35

VAR_058626

Natural variant

531

1

W → C in NS7. Ref.35

VAR_058627

Natural variant

580

1

N → D in CFC syndrome. Ref.34

VAR_065173

Natural variant

581

1

N → D in CFC syndrome. Ref.30 Ref.32 Ref.34

VAR_026119

Natural variant

581

1

N → S in a colorectal adenocarcinoma sample; somatic mutation. Ref.33

VAR_040393

Natural variant

586

1

E → K in ovarian cancer. Ref.26

VAR_018623

Natural variant

594

1

D → G in NHL. Ref.28

VAR_018624

Natural variant

595

1

F → L in colon cancer and CFC syndrome. Ref.26 Ref.32 Ref.34 Ref.35

VAR_018625

Natural variant

596

1

G → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.26 Ref.33

VAR_018626

Natural variant

596

1

G → V in CFC syndrome. Ref.32

VAR_035098

Natural variant

597

1

L → R in LNCR; also found in an ovarian serous carcinoma sample; somatic mutation. Ref.25 Ref.26 Ref.33

VAR_018513

Natural variant

597

1

L → V in NS7; also in a lung adenocarcinoma sample; somatic mutation; elevated kinase activity; efficiently induces cell transformation. Ref.26 Ref.33 Ref.35

VAR_018627

Natural variant

599

1

T → R in CFC syndrome. Ref.35

VAR_058628

Natural variant

600

1

V → D in a melanoma cell line; requires 2 nucleotide substitutions. Ref.26

VAR_018628

Natural variant

600

1

V → E in sarcoma, colorectal adenocarcinoma, metastatic melanoma, ovarian serous carcinoma, pilocytic astrocytoma; somatic mutation; most common mutation; constitutive and elevated kinase activity; efficiently induces cell transformation; suppression of mutation in melanoma causes growth arrest and promotes apoptosis. Ref.26 Ref.27 Ref.29 Ref.31 Ref.33

VAR_018629

Natural variant

601

1

K → E in colorectal cancer. Ref.27

VAR_018630

Natural variant

601

1

K → Q in CFC syndrome. Ref.35

VAR_058629

Natural variant

638

1

D → E in CFC syndrome. Ref.35

VAR_058630

Natural variant

709

1

Q → R in CFC syndrome. Ref.35

VAR_058631

Experimental info

Sequence conflict

766

1

H → D in AAA96495. Ref.11

Secondary structure

1

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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 [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]	NIEHS SNPs program Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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].
[6]	"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.
[7]	"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.
[8]	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.
[9]	"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.
[10]	"Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas." Jones D.T.W., Kocialkowski S., Liu L., Pearson D.M., Backlund L.M., Ichimura K., Collins V.P. Cancer Res. 68:8673-8677(2008) [PubMed: 18974108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 381-766, DISEASE, CHROMOSOMAL REARRANGEMENT. Tissue: Brain.
[11]	"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.
[12]	"Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf." Zhang B.H., Tang E.D., Zhu T., Greenberg M.E., Vojtek A.B., Guan K.L. J. Biol. Chem. 276:31620-31626(2001) [PubMed: 11410590] [Abstract] Cited for: PHOSPHORYLATION AT SER-365 BY SGK1.
[13]	"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: Cervix carcinoma.
[14]	"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: Cervix carcinoma.
[15]	"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: Cervix carcinoma.
[16]	"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. Tissue: Leukemic T-cell.
[17]	"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. Tissue: Cervix carcinoma.
[18]	"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. Tissue: Cervix carcinoma.
[19]	"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. Tissue: Cervix carcinoma.
[20]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401 AND SER-729, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[21]	"Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization." Yasuda S., Kai M., Imai S., Takeishi K., Taketomi A., Toyota M., Kanoh H., Sakane F. J. Biol. Chem. 284:29559-29570(2009) [PubMed: 19710016] [Abstract] Cited for: SUBUNIT, INTERACTION WITH DGKH, PHOSPHORYLATION AT THR-753 BY MAPK1.
[22]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, MASS SPECTROMETRY.
[23]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465 AND SER-614, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[24]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-418, MASS SPECTROMETRY.
[25]	"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 LNCR VAL-466 AND ARG-597.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome." Schulz A.L., Albrecht B., Arici C., van der Burgt I., Buske A., Gillessen-Kaesbach G., Heller R., Horn D., Hubner C.A., Korenke G.C., Konig R., Kress W., Kruger G., Meinecke P., Mucke J., Plecko B., Rossier E., Schinzel A. , Schulze A., Seemanova E., Seidel H., Spranger S., Tuysuz B., Uhrig S., Wieczorek D., Kutsche K., Zenker M. Clin. Genet. 73:62-70(2008) [PubMed: 18042262] [Abstract] Cited for: VARIANTS CFC SYNDROME PRO-241; PRO-244; PRO-246; ARG-257; LYS-262; SER-468; GLU-469; GLU-499; ASN-499; ASP-580; ASP-581 AND LEU-595.
[35]	"Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum." Sarkozy A., Carta C., Moretti S., Zampino G., Digilio M.C., Pantaleoni F., Scioletti A.P., Esposito G., Cordeddu V., Lepri F., Petrangeli V., Dentici M.L., Mancini G.M., Selicorni A., Rossi C., Mazzanti L., Marino B., Ferrero G.B. , Silengo M.C., Memo L., Stanzial F., Faravelli F., Stuppia L., Puxeddu E., Gelb B.D., Dallapiccola B., Tartaglia M. Hum. Mutat. 30:695-702(2009) [PubMed: 19206169] [Abstract] Cited for: VARIANT LEOPARD3 PRO-241, VARIANTS NS7 CYS-531 AND VAL-597, VARIANTS CFC SYNDROME PHE-245; PRO-246; ARG-257; LYS-275; GLU-469; PHE-485; ASN-499; LYS-501; PRO-525; LEU-595; ARG-599; GLN-601; GLU-638 AND ARG-709, VARIANTS ARG-241 AND MET-241.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M95712 mRNA. Translation: AAA35609.2.
AC006344 Genomic DNA. Translation: AAD43193.1. Sequence problems.
EU600171 Genomic DNA. Translation: ACD11489.1.
AC006347 Genomic DNA. Translation: AAD15551.1.
CH236950 Genomic DNA. Translation: EAL24023.1.
BC101757 mRNA. Translation: AAI01758.1.
BC112079 mRNA. Translation: AAI12080.1.
X65187 Genomic DNA. Translation: CAA46301.1.
M21001 mRNA. Translation: AAA96495.1.
AM989472 mRNA. Translation: CAQ43111.1. Different initiation.
AM989473 mRNA. Translation: CAQ43112.1. Different initiation.
AM989474 mRNA. Translation: CAQ43113.1. Different initiation.
AM989475 mRNA. Translation: CAQ43114.1. Different initiation.
AM989476 mRNA. Translation: CAQ43115.1. Different initiation.
AM989477 mRNA. Translation: CAQ43116.1. Different initiation.

IPI

IPI00303797.

PIR

TVHUBF. A57977.

RefSeq

NP_004324.2. NM_004333.4.

UniGene

Hs.550061.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2L05	NMR	-	A	149-232	[»]
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	[»]
3IDP	X-ray	2.70	A/B	434-727	[»]
3II5	X-ray	2.79	A/B	432-726	[»]
3NY5	X-ray	1.99	A/B/C/D	153-237	[»]
3OG7	X-ray	2.45	A/B	449-766	[»]
3PPJ	X-ray	3.70	A/B	432-726	[»]
3PPK	X-ray	3.00	A/B	432-726	[»]
3PRF	X-ray	2.90	A/B	432-726	[»]
3PRI	X-ray	3.50	A/B	432-726	[»]
3PSB	X-ray	3.40	A/B	433-726	[»]
3PSD	X-ray	3.60	A/B	432-726	[»]
3Q4C	X-ray	3.20	A/B	432-726	[»]
3Q96	X-ray	3.10	A/B	446-727	[»]
3SKC	X-ray	3.20	A/B	432-726	[»]
3TV4	X-ray	3.40	A/B	432-726	[»]
3TV6	X-ray	3.30	A/B	432-726	[»]

ProteinModelPortal

P15056.

SMR

P15056. Positions 149-283, 448-723.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1045N.

IntAct

P15056. 23 interactions.

MINT

MINT-1574728.

STRING

P15056.

PTM databases

PhosphoSite

P15056.

Polymorphism databases

DMDM

50403720.

Proteomic databases

PRIDE

P15056.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000288602; ENSP00000288602; ENSG00000157764.

GeneID

673.

KEGG

hsa:673.

UCSC

uc003vwc.2. human.

Organism-specific databases

CTD

673.

GeneCards

GC07M140424.

H-InvDB

HIX0007148.

HGNC

HGNC:1097. BRAF.

HPA

CAB004552.
HPA001328.

MIM

114500. phenotype.
115150. phenotype.
164757. gene.
211980. phenotype.
605027. phenotype.
613706. phenotype.
613707. phenotype.

neXtProt

NX_P15056.

Orphanet

1340. Cardiofaciocutaneous syndrome.
500. LEOPARD syndrome.
648. Noonan syndrome.

PharmGKB

PA25408.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG506535.

HOVERGEN

HBG001886.

InParanoid

P15056.

OMA

MKRLMAD.

OrthoDB

EOG41G33M.

PhylomeDB

P15056.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

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_111102. Signal Transduction.
REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P15056.

Bgee

P15056.

CleanEx

HS_BRAF.

Genevestigator

P15056.

GermOnline

ENSG00000157764. Homo sapiens.

Family and domain databases

InterPro

IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras-bd.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K04365.

Pfam

PF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]

PRINTS

PR00008. DAGPEDOMAIN.

SMART

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

SUPFAM

SSF56112. Kinase_like. 1 hit.

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

DrugBank

DB00398. Sorafenib.

NextBio

2776.

PMAP-CutDB

P15056.

SOURCE

Search...

Entry information

Entry name

BRAF_HUMAN

Accession

Primary (citable) accession number: P15056
Secondary accession number(s): A4D1T4 , B6HY61, B6HY62, B6HY63, B6HY64, B6HY65, B6HY66, Q13878, Q3MIN6, Q9UDP8, Q9Y6T3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	July 19, 2004
Last modified:	January 25, 2012
This is version 155 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.