P28028 (BRAF_MOUSE) 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

Gene names

Name:	Braf
Synonyms:	B-raf

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	804 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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 2 zinc ions per subunit Potential.
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-790. 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 By similarity. Interacts with PRMT5 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cell membrane By similarity. Note: Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes By similarity.
Post-translational modification	Phosphorylation at Ser-348 by SGK1 inhibits its activity By similarity. Methylation by PRMT5 decreases stability and kinase activity. Ref.6 Ubiquitinated by RNF149; which leads to proteasomal degradation By similarity.
Involvement in disease	Participates in a chromosomal translocation that produces a Tif1a-BRAF (T18) oncogene originally isolated from a furfural-induced hepatoma.
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 AAA37320.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAA37320.1 differs from that shown. Reason: Chimeric cDNA.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to calcium ion Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara response to epidermal growth factor stimulus Inferred from direct assay PubMed 17563371. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from direct assay PubMed 15736129. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay PubMed 15736129. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: Compara protein kinase activity Inferred from direct assay PubMed 17563371. Source: BHF-UCL protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Raf1	Q99N57	2	EBI-2584830,EBI-397757

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P28028-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P28028-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-474: Missing.
     799-804: EFAAFK → GFPVH

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 804	803	Serine/threonine-protein kinase B-raf		PRO_0000085666
Regions
	Domain	139 – 211	73	RBD
	Domain	494 – 754	261	Protein kinase
	Nucleotide binding	500 – 508	9	ATP By similarity
	Compositional bias	6 – 30	25	Poly-Gly
	Compositional bias	465 – 469	5	Poly-Ser
Sites
	Active site	613	1	Proton acceptor By similarity
	Metal binding	219	1	Zinc 1 By similarity
	Metal binding	232	1	Zinc 2 By similarity
	Metal binding	235	1	Zinc 2 By similarity
	Metal binding	245	1	Zinc 1 By similarity
	Metal binding	248	1	Zinc 1 By similarity
	Metal binding	253	1	Zinc 2 By similarity
	Metal binding	256	1	Zinc 2 By similarity
	Metal binding	264	1	Zinc 1 By similarity
	Binding site	520	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	348	1	Phosphoserine; by SGK1 By similarity
	Modified residue	356	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	431	1	Phosphothreonine By similarity
	Modified residue	434	1	Phosphoserine By similarity
	Modified residue	436	1	Phosphothreonine By similarity
	Modified residue	483	1	Phosphoserine Ref.4 Ref.5
	Modified residue	484	1	Phosphoserine By similarity
	Modified residue	708	1	Omega-N-methylarginine; by PRMT5 By similarity
	Modified residue	766	1	Phosphoserine By similarity
	Modified residue	790	1	Phosphothreonine; by MAPK1 By similarity
Natural variations
	Alternative sequence	1 – 474	474	Missing in isoform 2.		VSP_022169
	Alternative sequence	799 – 804	6	EFAAFK → GFPVH in isoform 2.		VSP_022170
Experimental info
	Sequence conflict	10 – 11	2	SS → RR in BAE24384. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 4C6CC16A2C660A17	FASTA	804	88,780
	10 20 30 40 50 60 MAALSGGGGS SSGGGGGGGG GGGGGDGGGG AEQGQALFNG DMEPEAGAGA AASSAADPAI 70 80 90 100 110 120 PEEVWNIKQM IKLTQEHIEA LLDKFGGEHN PPSIYLEAYE EYTSKLDALQ QREQQLLESL 130 140 150 160 170 180 VFQTPTDASR NNPKSPQKPI VRVFLPNKQR TVVPARCGVT VRDSLKKALM MRGLIPECCA 190 200 210 220 230 240 VYRIQDGEKK PIGWDTDISW LTGEELHVEV LENVPLTTHN FVRKTFFTLA FCDFCRKLLF 250 260 270 280 290 300 QGFRCQTCGY KFHQRCSTEV PLMCVNYDQL DLLFVSKFFE HHPVPQEEAS FPETALPSGS 310 320 330 340 350 360 SSAPPSDSTG PQILTSPSPS KSIPIPQPFR PADEDHRNQF GQRDRSSSAP NVHINTIEPV 370 380 390 400 410 420 NIDEKFPEVE LQDQRDLIRD QGFRGDGAPL NQLMRCLRKY QSRTPSPLLH SVPSEIVFDF 430 440 450 460 470 480 EPGPVFRGST TGLSATPPAS LPGSLTNVKA LQKSPGPQRE RKSSSSSSSE DRSRMKTLGR 490 500 510 520 530 540 RDSSDDWEIP DGQITVGQRI GSGSFGTVYK GKWHGDVAVK MLNVTAPTPQ QLQAFKNEVG 550 560 570 580 590 600 VLRKTRHVNI LLFMGYSTKP QLAIVTQWCE GSSLYHHLHI IETKFEMIKL IDIARQTAQG 610 620 630 640 650 660 MDYLHAKSII HRDLKSNNIF LHEDLTVKIG DFGLATVKSR WSGSHQFEQL SGSILWMAPE 670 680 690 700 710 720 VIRMQDKNPY SFQSDVYAFG IVLYELMTGQ LPYSNINNRD QIIFMVGRGY LSPDLSKVRS 730 740 750 760 770 780 NCPKAMKRLM AECLKKKRDE RPLFPQILAS IELLARSLPK IHRSASEPSL NRAGFQTEDF 790 800 SLYACASPKT PIQAGGYGEF AAFK
	Isoform 2 [UniParc]. Checksum: 93913670A27EAB2C	FASTA	329	37,118
	10 20 30 40 50 60 MKTLGRRDSS DDWEIPDGQI TVGQRIGSGS FGTVYKGKWH GDVAVKMLNV TAPTPQQLQA 70 80 90 100 110 120 FKNEVGVLRK TRHVNILLFM GYSTKPQLAI VTQWCEGSSL YHHLHIIETK FEMIKLIDIA 130 140 150 160 170 180 RQTAQGMDYL HAKSIIHRDL KSNNIFLHED LTVKIGDFGL ATVKSRWSGS HQFEQLSGSI 190 200 210 220 230 240 LWMAPEVIRM QDKNPYSFQS DVYAFGIVLY ELMTGQLPYS NINNRDQIIF MVGRGYLSPD 250 260 270 280 290 300 LSKVRSNCPK AMKRLMAECL KKKRDERPLF PQILASIELL ARSLPKIHRS ASEPSLNRAG 310 320 FQTEDFSLYA CASPKTPIQA GGYGGFPVH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Medulla oblongata.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Development of a highly efficient expression cDNA cloning system: application to oncogene isolation." Miki T., Fleming T.P., Crescenzi M., Molloy C.J., Blam S.B., Reynolds S.H., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 88:5167-5171(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 476-804 (ISOFORM 2).
[4]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483, MASS SPECTROMETRY. Tissue: Liver.
[5]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483, MASS SPECTROMETRY. Tissue: Melanoma.
[6]	"Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF." Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G., Avila M.A., Recio J.A. Sci. Signal. 4:RA58-RA58(2011) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK140431 mRNA. Translation: BAE24384.1. AC122345 Genomic DNA. No translation available. AC163109 Genomic DNA. No translation available. M64429 mRNA. Translation: AAA37320.1. Sequence problems.
IPI	IPI00230719. IPI00816967.
PIR	TVMSBF. A40951.
RefSeq	NP_647455.3. NM_139294.5.
UniGene	Mm.245513. Mm.489691.
3D structure databases
ProteinModelPortal	P28028.
SMR	P28028. Positions 133-267, 485-760.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-57050N.
IntAct	P28028. 2 interactions.
PTM databases
PhosphoSite	P28028.
Proteomic databases
PaxDb	P28028.
PRIDE	P28028.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002487; ENSMUSP00000002487; ENSMUSG00000002413.
GeneID	109880.
KEGG	mmu:109880.
UCSC	uc009bme.1. mouse. uc009bmf.1. mouse.
Organism-specific databases
CTD	673.
MGI	MGI:88190. Braf.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099647.
HOGENOM	HOG000252972.
HOVERGEN	HBG001886.
InParanoid	P28028.
KO	K04365.
OMA	DWEIPEG.
OrthoDB	EOG41G33M.
Gene expression databases
ArrayExpress	P28028.
Bgee	P28028.
CleanEx	MM_BRAF.
Genevestigator	P28028.
GermOnline	ENSMUSG00000002413. Mus musculus.
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_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
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
ChiTaRS	BRAF. mouse.
NextBio	362941.
SOURCE	Search...

Entry information

Entry name

BRAF_MOUSE

Accession

Primary (citable) accession number: P28028
Secondary accession number(s): E9QNG9, Q3USE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 130 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program