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P28028 (BRAF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length804 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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, HRAS, 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.5

Ubiquitinated by RNF149; which leads to proteasomal degradation. Polyubiquitinated at Lys-615 in response to EGF 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 componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseProto-oncogene
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Isopeptide bond
Methylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCD4-positive, alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 23334952. Source: MGI

alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 23334952. Source: MGI

cell differentiation

Inferred from genetic interaction PubMed 10704835. Source: MGI

cellular response to calcium ion

Inferred from electronic annotation. Source: Ensembl

cellular response to drug

Inferred from direct assay PubMed 22628551. Source: MGI

long-term synaptic potentiation

Inferred from mutant phenotype PubMed 16342120. Source: MGI

myeloid progenitor cell differentiation

Inferred from mutant phenotype PubMed 15784729. Source: MGI

negative regulation of endothelial cell apoptotic process

Inferred from mutant phenotype PubMed 9207797. Source: MGI

negative regulation of fibroblast migration

Inferred from mutant phenotype PubMed 15199148. Source: MGI

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 16980614. Source: MGI

negative regulation of synaptic vesicle exocytosis

Inferred from mutant phenotype PubMed 23616533. Source: MGI

positive T cell selection

Inferred from mutant phenotype PubMed 23334952. Source: MGI

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 22892241. Source: MGI

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of stress fiber assembly

Inferred from mutant phenotype PubMed 15199148. Source: MGI

positive regulation of substrate adhesion-dependent cell spreading

Inferred from mutant phenotype PubMed 15199148. Source: MGI

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 17563371. Source: BHF-UCL

regulation of cell proliferation

Inferred from genetic interaction PubMed 22891351. Source: MGI

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to epidermal growth factor

Inferred from direct assay PubMed 17563371. Source: BHF-UCL

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

somatic stem cell maintenance

Inferred from genetic interaction PubMed 23022482. Source: MGI

visual learning

Inferred from mutant phenotype PubMed 16342120. Source: MGI

   Cellular_componentcell body

Inferred from direct assay PubMed 16980614. Source: MGI

cytoplasm

Inferred from direct assay PubMed 15736129. Source: MGI

mitochondrion

Inferred from direct assay PubMed 16116448. Source: MGI

neuron projection

Inferred from direct assay PubMed 16980614. Source: MGI

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 15736129. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase kinase kinase activity

Inferred from electronic annotation. Source: Ensembl

calcium ion binding

Inferred from electronic annotation. Source: Ensembl

protein kinase activity

Inferred from direct assay PubMed 17563371. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Raf1Q99N572EBI-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:
     2-474: Missing.
     799-804: EFAAFK → GFPVH
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 804803Serine/threonine-protein kinase B-raf
PRO_0000085666

Regions

Domain139 – 21173RBD
Domain494 – 754261Protein kinase
Nucleotide binding500 – 5089ATP By similarity
Compositional bias6 – 3025Poly-Gly
Compositional bias465 – 4695Poly-Ser

Sites

Active site6131Proton acceptor By similarity
Metal binding2191Zinc 1 By similarity
Metal binding2321Zinc 2 By similarity
Metal binding2351Zinc 2 By similarity
Metal binding2451Zinc 1 By similarity
Metal binding2481Zinc 1 By similarity
Metal binding2531Zinc 2 By similarity
Metal binding2561Zinc 2 By similarity
Metal binding2641Zinc 1 By similarity
Binding site5201ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue3481Phosphoserine; by SGK1 By similarity
Modified residue3561Phosphothreonine; by autocatalysis By similarity
Modified residue4311Phosphothreonine By similarity
Modified residue4341Phosphoserine By similarity
Modified residue4361Phosphothreonine By similarity
Modified residue4831Phosphoserine Ref.4
Modified residue4841Phosphoserine By similarity
Modified residue7081Omega-N-methylarginine; by PRMT5 By similarity
Modified residue7661Phosphoserine By similarity
Modified residue7901Phosphothreonine; by MAPK1 By similarity
Cross-link615Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence2 – 474473Missing in isoform 2.
VSP_022169
Alternative sequence799 – 8046EFAAFK → GFPVH in isoform 2.
VSP_022170

Experimental info

Sequence conflict10 – 112SS → RR in BAE24384. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 4C6CC16A2C660A17

FASTA80488,780
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 89D505AD29A47209
Show »

FASTA33037,249

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[5]"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.
PIRTVMSBF. A40951.
RefSeqNP_647455.3. NM_139294.5.
UniGeneMm.245513.
Mm.489691.

3D structure databases

ProteinModelPortalP28028.
SMRP28028. Positions 133-267, 485-760.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid225124. 2 interactions.
DIPDIP-57050N.
IntActP28028. 8 interactions.
MINTMINT-1518176.

Chemistry

ChEMBLCHEMBL2331061.

PTM databases

PhosphoSiteP28028.

Proteomic databases

PaxDbP28028.
PRIDEP28028.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000002487; ENSMUSP00000002487; ENSMUSG00000002413. [P28028-1]
GeneID109880.
KEGGmmu:109880.
UCSCuc009bme.2. mouse. [P28028-1]
uc009bmf.1. mouse. [P28028-2]

Organism-specific databases

CTD673.
MGIMGI:88190. Braf.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117324.
HOGENOMHOG000252972.
HOVERGENHBG001886.
InParanoidP28028.
KOK04365.
OMAHRTRTSS.
OrthoDBEOG7F5128.
TreeFamTF317006.

Gene expression databases

ArrayExpressP28028.
BgeeP28028.
CleanExMM_BRAF.
GenevestigatorP28028.

Family and domain databases

InterProIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_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]
PfamPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

ChiTaRSBRAF. mouse.
NextBio362941.
PROP28028.
SOURCESearch...

Entry information

Entry nameBRAF_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot