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FLASH GENE
Symbol BRAF contributors: mct - updated : 21-06-2017
HGNC name v-raf murine sarcoma viral oncogene homolog B1
HGNC id 1097
Corresponding disease
CFC2 cardio-facio-cutaneous syndrome 2
Location 7q34      Physical location : 140.433.814 - 140.624.564
Synonym name
  • B-Raf proto-oncogene serine/threonine-protein kinase (p94)
  • 94 kDa B-raf protein
    • Synonym symbol(s) RAFB1, BRAF1, B-RAF, FLJ95109, MGC126806, MGC138284, p94, NS7
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 190.75 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 2949 85 766 - 1992 1508179
    13 - - 61 554 - -
  • lacks exons 4–8
  • enhanced dimerization in cells with low levels of RAS activation, as compared to full-length
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    Urinarykidneynephronrenal capsuleglomerulus 
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Urinarypodocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text coexpressed and colocalize in developing and mature glomerular podocytes
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • RAF-like, RAS binding domain
  • tyrosine kinase catalytic domain
  • one zinc dependent phorbol-ester and DAG binding domain
  • autophosphorylation site at threonine 372 in the conserved region 2 domain, present at similar positions in all three mammalian Raf family members and may represent a regulatory site for these proteins
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine sarcoma 3611 viral (v-raf) oncogene B1 (Rmil)
    ortholog to rattus Braf
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • RAF subfamily
    • CATEGORY enzyme , protooncogene , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text primarily localized in the cytosol
    basic FUNCTION
  • serine/threonine kinase involved in transduction of mitogenic signals from the cell membrane to the nucleus
  • may be playing a role in the postsynaptic responses of hippocampal neuron
  • participating to the RAS-RAF-MEK-ERK- pathway in promoting tumorigenesis
  • plays a critical role in regulating MITF expression to ensure that its protein levels are compatible with proliferation and survival of melanoma cells
  • induces senescence in melanocytes and fibroblasts, irrespective of the presence of IGFBP7
  • elevates SLC9A1 activity and elevates pHi in the tumoral cells
  • is the most effective RAF kinase in terms of induction of MEK/ERK activity
  • is implicated in sustained Erk signaling after TCR stimulation
    • CELLULAR PROCESS cell life, antiapoptosis
    protein, post translation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text organ morphogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    key regulator of the RAS-RAF-MEK-ERK pathway
    a component
  • KSR1, BRAF, and MEK form a ternary complex
  • molecular complex composed of NDE1, PAFAH1B1, and BRAP regulates the dynamic MAPK signaling threshold in a spatially dependent fashion
    • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • binding two zinc Zn2+ per subunit
  • ATP binding
    • protein
  • interacts with MEK1
  • interacts with PLCepsilon1 (PLCE1)
  • BRAF associates with and stimulates SLC9A1 activity and BRAF(V600E) also increases SLC9A1 activity that raises intracellular pH
  • association of BRAF with RAF1 induces the activation of RAF1
  • bound to the cytosolic regulatory tail of SLC9A1 (can directly bind to the C-terminal 182 AAs of SLC9A1 protein)
  • bound directly to the C-terminal kinase-containing domain of BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein
  • BRAF enhanced the Na+-coupled glucose transporter SLC5A1 protein abundance in the cell membrane
  • NF1 cooperates with BRAF mutations in melanoma
  • target of BRAF, the melanocyte lineage factor MITF, directly regulates the expression of PPARGC1A
  • MITF is a target of BRAF, directly regulating the expression of PPARGC1A
  • regulatory role for BRAF in the MAPK pathway independent of its kinase activity but dependent on interaction with MAP2K1
  • RHEB interaction with BRAF is crucial for inhibiting RAF/MEK/ERK signaling
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CFC2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with TIF1A to form the oncoprotein T18
    tumoral somatic mutation      
    in malignant melanoma of the skin UV-exposed and in naevus, rarely in colorectal cancer with mismatch repair deficiency and in lung adenocarcinoma
    tumoral somatic mutation      
    a missense transversion T1796A in lung, head and neck cancers
    tumoral somatic mutation      
    V599E mutation in adult sporadic papillary thyroid carcinomas, with poorer clinicopathological outcomes
    constitutional germinal mutation      
    de novo missense mutation in CFC, at the interface of the ATP binding cleft and altering the catalytic activity of kinase domain
    tumoral     --low  
    by aberrant DNA methylation in colorectal cancer
    tumoral       gain of function
    in melanomas, mutation gain de function V600E (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage
    tumoral fusion      
    tandem duplication at 7q34 leading to a fusion between KIAA1549 and BRAF occurs in the majority of Pilocytic astrocytomas
    tumoral   amplification    
    duplication was the most frequent genomic aberration in constitutes a mechanism of MAPK pathway activation in low-grade astrocytoma
    tumoral fusion      
    KIAA1549-BRAF fusion gene in cells forming microvascular proliferations in pilocytic astrocytoma
    Susceptibility
  • to melanoma
  • to chronic lymphocytic leukaemia and prolymphocytic leukaemia.
    • Variant & Polymorphism SNP
  • SNP found to be weakly associated with melanoma status but not with development of nevi or freckles
  • BRAF V600E mutation associated with chronic lymphocytic leukaemia and prolymphocytic leukaemia
    • Candidate gene
  • useful molecular marker to assist in risk stratification for patients with papillary thyroid cancer
  • useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma (BRAF V600E mutation was associated with tumour recurrence in 21p100 with mutation vs 7p100 without mutation)
    • Marker
  • BRAF V600E is an important marker, especially, for classic variant of papillary thyroid carcinoma
    • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting oncogenic serine/threonine-protein kinase BRAF in cancer cells inhibits angiogenesis
    ANIMAL & CELL MODELS
    mice with a targeted disruption in the Braf gene die of vascular defects during midgestation