BRAF
Serine/threonine-protein kinase B-raf
Also known as: BRAF_HUMAN, BRAF-1, BRAF1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P15056
- Gene
- BRAF
- Ensembl
- ENSG00000157764
- Chromosome
- 7
- Canonical length
- 766 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Transporters
- Subcellular location
- Vesicles,Plasma membrane,Primary cilium,Centriolar satellite,Basal body,Cytosol,Mid piece,Principal piece,End piece
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
Canonical amino-acid sequenceUniProt
766 residues, UniProt reviewed canonical sequence.
>P15056|BRAF
1 MAALSGGGGG GAEPGQALFN GDMEPEAGAG AGAAASSAAD PAIPEEVWNI KQMIKLTQEH
61 IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESLGNGTDFS VSSSASMDTV
121 TSSSSSSLSV LPSSLSVFQN PTDVARSNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS
181 LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK
241 TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI
301 PQEEASLAET ALTSGSSPSA PASDSIGPQI LTSPSPSKSI PIPQPFRPAD EDHRNQFGQR
361 DRSSSAPNVH INTIEPVNID DLIRDQGFRG DGGSTTGLSA TPPASLPGSL TNVKALQKSP
421 GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV
481 AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH
541 LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV
601 KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN
661 NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS
721 LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GAFPVHLocalizationUniProt · AlphaFold · HPA
Whether an antibody against BRAF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 16 nTPM
Expression across tissuesHPA
Tissue
- retina: 16 nTPM
- bone marrow: 15 nTPM
- cerebellum: 13 nTPM
- testis: 13 nTPM
- parathyroid gland: 11 nTPM
- ovary: 11 nTPM
Single-cell type
- neutrophils: 2,034 nCPM
- syncytiotrophoblasts: 959 nCPM
- neutrophil progenitors: 890 nCPM
- somatotrophs: 677 nCPM
- lactotrophs: 631 nCPM
- mast cells: 584 nCPM
Immune cell
- eosinophil: 4.1 nTPM
- NK-cell: 3.5 nTPM
- naive CD4 T-cell: 2.6 nTPM
- neutrophil: 2.1 nTPM
- basophil: 1.9 nTPM
- gdT-cell: 1.5 nTPM
Brain region
- cerebellum: 42 nTPM
- cerebral cortex: 34 nTPM
- basal ganglia: 32 nTPM
- hypothalamus: 31 nTPM
- hippocampal formation: 30 nTPM
- white matter: 30 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about BRAF.
Disease | AllUniProt
Conditions BRAF is implicated in, by any mechanism.
- Colorectal cancer (CRC) MIM:114500
- Lung cancer (LNCR) MIM:211980
- Familial non-Hodgkin lymphoma (NHL) MIM:605027
- Cardiofaciocutaneous syndrome 1 (CFC1) MIM:115150
- Noonan syndrome 7 (NS7) MIM:613706
- LEOPARD syndrome 3 (LPRD3) MIM:613707
Disease | GeneticClinVar
129 pathogenic / likely-pathogenic of 1,560 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- RASopathy
- Cardio-facio-cutaneous syndrome
- Cardiofaciocutaneous syndrome 1
- Noonan syndrome 7
- Noonan syndrome
Disease | ImmuneIEDB
Conditions an epitope on BRAF was assayed in.
- papillary thyroid carcinoma T cell
- poorly differentiated thyroid carcinoma T cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against BRAF are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for BRAF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
7 publications
- Multiple biomarker approach for the diagnosis and therapy of rheumatoid arthritis.
2021 · Crit Rev Clin Lab Sci · RCR 2.6 · 35 citations - Autoantibodies to PAD4 and BRAF in rheumatoid arthritis.
2012 · Autoimmun Rev · RCR 1.2 · 37 citations - Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis.
2010 · Arthritis Res Ther · RCR 0.4 · 17 citations - Newly Identified BRAF Mutation in Rheumatoid Arthritis.
2016 · Arthritis Rheumatol · RCR 0.2 · 4 citations - Autoantibodies against the catalytic domain of BRAF are not specific serum markers for rheumatoid arthritis.
2011 · PLoS One · RCR 0.1 · 5 citations
Show 2 more
- [Significance of the detection of anti-v-raf murine sarcoma viral oncogene homologue B1 antibodies in the diagnostic practice of rheumatoid arthritis].
2012 · Beijing Da Xue Xue Bao Yi Xue Ban · RCR 0 · 1 citations - [Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis].
2023 · Beijing Da Xue Xue Bao Yi Xue Ban
Reference: T cellIEDB
2 publications
- BRAFV600E and BRAF-WT Specific Antitumor Immunity in Papillary Thyroid Cancer.
2022 · Horm Metab Res · RCR 0.2 · 2 citations - Tumor-infiltrating T Lymphocytes Recognize Thyroid-specific Proteins and Neo-antigens in Follicular Cell-derived Thyroid Cancers.
2026 · J Clin Endocrinol Metab · 3 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.21
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.72
- DepMap mean gene effect
- -0.11
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- animal organ morphogenesis
- CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
- CD4-positive, alpha-beta T cell differentiation
- cellular response to calcium ion
- cellular response to xenobiotic stimulus
- endothelial cell apoptotic process
- epidermal growth factor receptor signaling pathway
- ERK1 and ERK2 cascade
- establishment of protein localization to membrane
- face development
- head morphogenesis
- long-term synaptic potentiation
- MAPK cascade
- myeloid progenitor cell differentiation
- negative regulation of apoptotic process
- negative regulation of endothelial cell apoptotic process
- negative regulation of fibroblast migration
- negative regulation of neuron apoptotic process
- negative regulation of synaptic vesicle exocytosis
- positive regulation of axon regeneration
- positive regulation of axonogenesis
- positive regulation of D-glucose transmembrane transport
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of gene expression
- positive regulation of peptidyl-serine phosphorylation
- positive regulation of stress fiber assembly
- positive regulation of substrate adhesion-dependent cell spreading
- postsynaptic modulation of chemical synaptic transmission
- protein phosphorylation
- regulation of cell population proliferation
- regulation of T cell differentiation
- somatic stem cell population maintenance
- stress fiber assembly
- substrate adhesion-dependent cell spreading
- synaptic vesicle exocytosis
- T cell differentiation in thymus
- T cell receptor signaling pathway
- thymus development
- thyroid gland development
- visual learning
Molecular functions
- ATP binding
- calcium ion binding
- identical protein binding
- MAP kinase kinase activity
- MAP kinase kinase kinase activity
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- scaffold protein binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
- Raf-like Ras-binding
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Protein kinase, ATP binding site
- Diacylglycerol/phorbol-ester binding
- Ubiquitin-like domain superfamily
- C1-like domain superfamily
- Serine/Threonine Kinases and Pseudokinases
- Phorbol esters/diacylglycerol binding domain (C1 domain)
- Raf-like Ras-binding domain
- Protein tyrosine and serine/threonine kinase
KeywordsUniProt
- Acetylation
- Allosteric enzyme
- ATP-binding
- Cardiomyopathy
- Cell membrane
- Chromosomal rearrangement
- Cytoplasm
- Deafness
- Ectodermal dysplasia
- Intellectual disability
- Isopeptide bond
- Kinase
- Membrane
- Metal-binding
- Methylation
- Nucleotide-binding
- Nucleus
- Phosphoprotein
- Proto-oncogene
- Serine/threonine-protein kinase
- Transferase
- Ubl conjugation
- Zinc
- Zinc-finger
InteractionsUniProt · HPA
Protein binding partners of BRAF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads BRAF as an antibody target. Whether an autoantibody or antibody against BRAF could matter depends on whether native BRAF is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
BRAF is annotated at the cell surface, where native BRAF is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label BRAF as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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