HCSGD entry for BRAF
1. General information
| Official gene symbol | BRAF |
|---|---|
| Entrez ID | 673 |
| Gene full name | v-raf murine sarcoma viral oncogene homolog B1 |
| Other gene symbols | B-RAF1 BRAF1 NS7 RAFB1 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000186 | Activation of MAPKK activity | TAS | biological_process |
| GO:0004672 | Protein kinase activity | IDA IEA | molecular_function |
| GO:0004674 | Protein serine/threonine kinase activity | IDA IEA | molecular_function |
| GO:0004709 | MAP kinase kinase kinase activity | IEA | molecular_function |
| GO:0005057 | Receptor signaling protein activity | IEA | molecular_function |
| GO:0005509 | Calcium ion binding | IDA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IEA | molecular_function |
| GO:0005634 | Nucleus | IEA | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0005886 | Plasma membrane | TAS | cellular_component |
| GO:0006468 | Protein phosphorylation | IDA | biological_process |
| GO:0007264 | Small GTPase mediated signal transduction | TAS | biological_process |
| GO:0007268 | Synaptic transmission | TAS | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0009887 | Organ morphogenesis | TAS | biological_process |
| GO:0010628 | Positive regulation of gene expression | IMP | biological_process |
| GO:0031434 | Mitogen-activated protein kinase kinase binding | IEA | molecular_function |
| GO:0033138 | Positive regulation of peptidyl-serine phosphorylation | IDA | biological_process |
| GO:0042802 | Identical protein binding | IPI | molecular_function |
| GO:0043005 | Neuron projection | IEA | cellular_component |
| GO:0043066 | Negative regulation of apoptotic process | IDA | biological_process |
| GO:0043434 | Response to peptide hormone | IEA | biological_process |
| GO:0043524 | Negative regulation of neuron apoptotic process | IEA | biological_process |
| GO:0046982 | Protein heterodimerization activity | IEA | molecular_function |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0051291 | Protein heterooligomerization | IEA | biological_process |
| GO:0051591 | Response to cAMP | IEA | biological_process |
| GO:0070374 | Positive regulation of ERK1 and ERK2 cascade | IDA | biological_process |
| GO:0070849 | Response to epidermal growth factor | IDA | biological_process |
| GO:0071277 | Cellular response to calcium ion | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.3696459481 | 0.5350982599 | 0.9999902473 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.0931919295 |
| GSE13712_SHEAR | Down | -0.1908150088 |
| GSE13712_STATIC | Up | 0.0095805849 |
| GSE19018 | Up | 0.0777953926 |
| GSE19899_A1 | Down | -0.1496135941 |
| GSE19899_A2 | Up | 0.4678619205 |
| PubMed_21979375_A1 | Down | -0.3207618261 |
| PubMed_21979375_A2 | Up | 0.5313142360 |
| GSE35957 | Down | -0.3551524681 |
| GSE36640 | Up | 0.6069378526 |
| GSE54402 | Up | 0.2042068351 |
| GSE9593 | Down | -0.0598177930 |
| GSE43922 | - | - |
| GSE24585 | - | - |
| GSE37065 | - | - |
| GSE28863_A1 | Up | 0.3341915783 |
| GSE28863_A2 | Up | 0.3694672134 |
| GSE28863_A3 | Down | -0.5136301420 |
| GSE28863_A4 | Down | -0.2980234481 |
| GSE48662 | Up | 0.0021353273 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Sorafenib | DB00398 | APRD01304 | DB07438 |
| XL281 | DB05190 | - |
| PLX4032 | DB05238 | - |
| N-{3-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide | DB06999 | - |
| N-{2,4-difluoro-3-[(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)carbonyl]phenyl}ethanesulfonamide | DB07000 | - |
| (1E)-5-(1-piperidin-4-yl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime | DB08553 | - |
| Vemurafenib | DB08881 | - |
| Regorafenib | DB08896 | - |
| Dabrafenib | DB08912 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-744-5p | MIMAT0004945 | MIRT037574 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-378a-5p | MIMAT0000731 | MIRT043975 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-191-5p | MIMAT0000440 | MIRT045803 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 29 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27141064 | In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations |
| 27141064 | 5%, while Braf mutations range from 23% to 48% |
| 27141064 | In contrast, Braf mutations in OLGSCa range from 0% to 33% |
| 27141064 | Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa |
| 27141064 | OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes |
| 27141064 | In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations |
| 27052162 | IFN signaling-deficient melanocytes expressing activated Braf do not exhibit senescence and develop aggressive melanomas |
| 26824319 | This is neither dependent on p65/NF-kappaB signaling nor RAF/MEK/ERK pathway activity as inhibition of MEK by GSK1120212 (trametinib) and induction of ERK1/2 activity by parthenolide itself do not interfere with parthenolide-triggered depletion of MITF-M in both wild-type BRAF and BRAF(V600E) melanoma populations |
| 26586345 | Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells |
| 26586345 | Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials |
| 26586345 | Notably, combining LGX818 with autophagy modulators has anti-proliferative effect in LGX818-resistant BRAF mutant melanoma cells |
| 26152738 | When death receptors were activated in senescent tumor cells, both intrinsic and extrinsic apoptotic pathways were induced independent of BRAF, NRAS, or p53 mutation status |
| 25188864 | BRAF mutation is associated with a specific cell type with features suggestive of senescence in ovarian serous borderline (atypical proliferative) tumors |
| 25188864 | In this study, we correlated the morphologic and immunohistochemical phenotypes of 71 APSTs and 18 LGSCs with the mutational status of KRAS and BRAF, the most common molecular genetic changes in these neoplasms |
| 25188864 | A subset of cells characterized by abundant eosinophilic cytoplasm (EC), discrete cell borders, and bland nuclei was identified in all (100%) 25 BRAF-mutated APSTs but in only 5 (10%) of 46 APSTs without BRAF mutations (P<0 |
| 25188864 | Among the 18 LGSCs, EC cells were found in only 2, and both contained BRAF mutations |
| 25188864 | In conclusion, this study sheds light on the pathogenesis of this unique group of ovarian tumors by showing that BRAF mutation is associated with cellular senescence and the presence of a specific cell type characterized by abundant EC |
| 24961811 | Despite the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called oncogene-induced senescence |
| 24961811 | Among the regulated phosphorylation sites we encountered components of the interleukin, BRAF/MAPK, and CDK-retinoblastoma pathways and several other factors |
| 24815188 | We also found that phosphorylation of these sites in pRb is increased in the presence of the B-Raf V600E oncogenic mutation |
| 24471909 | The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH) |
| 24471909 | In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1) |
| 24471909 | We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16(INK4a) and p21(CIP1/WAF1) were expressed, irrespective of BRAF mutation status |
| 24089445 | The recent clinical success of targeted therapies in melanoma directed at the oncogene BRAF validates the concept of targeting oncogenes |
| 23904845 | No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed |
| 23685455 | Finally, depletion of PDK1 eradicated melanoma subpopulations resistant to targeted BRAF inhibition, and caused regression of established melanomas |
| 23535008 | Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies "initial" and "final" passage sarcoma cells |
| 23535008 | Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations |
| 23296668 | The B-RAF kinase is a downstream effector of the RAS family of proto-oncogenes and is constitutively activated in the majority of human melanomas |
| 23174937 | Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively |
| 22996177 | Identification of the V600D mutation in Exon 15 of the BRAF oncogene in congenital, benign langerhans cell histiocytosis |
| 22996177 | Although BRAF V600E mutations were recently identified as a recurrent genetic alteration in LCH cases, the clinical significance of this mutation within the heterogeneous spectrum of LCH is also currently unknown |
| 22996177 | Sequencing analysis of Exon 15 of the BRAF gene revealed the V600D mutation, with an allelic abundance of 25-30%, corresponding to the LCH cells being hemizygous for the mutant allele |
| 22996177 | BRAF V600E-specific polymerase chain reaction was negative |
| 22996177 | Our report is the first to identify the rare, variant BRAF V600D mutation in LCH, and provides support for constitutively activated BRAF oncogene-induced cell senescence as a mechanism of regression in congenital, benign LCH |
| 22996177 | Additional clinicopathologic studies in larger numbers of LCH patients may be valuable to ascertain the pathophysiologic role of BRAF mutations in LCH |
| 22836754 | B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer |
| 22611400 | Recent high-throughput-sequencing of the cancer genome has identified oncogenic mutations in BRaf genetic locus as one of the critical events in melanomagenesis |
| 22611400 | In normal cells, the activity of BRaf is tightly regulated |
| 22611400 | The activating mutation of BRaf will also induce the cells to senesce |
| 22611400 | However, the mechanism by which the oncogenic BRaf induces the senescent barrier remains poorly defined |
| 22611400 | Here we show that expression of several microRNAs is altered when the oncogenic version of BRaf is introduced in cultured primary melanocytes and these cells undergo premature cellular senescence |
| 22611400 | Taken together, our results suggest that the change in microRNA expression rates may play a vital role in senescence induced by the oncogenic BRaf |
| 21636552 | BRAF activation induces transformation and then senescence in human neural stem cells: a pilocytic astrocytoma model |
| 21636552 | PURPOSE: BRAF is frequently activated by gene fusion or point mutation in pilocytic astrocytoma, the most common pediatric brain tumor |
| 21636552 | We investigated the functional effect of constitutive BRAF activation in normal human neural stem and progenitor cells to determine its role in tumor induction in the brain |
| 21636552 | CONCLUSIONS: BRAF activation in human neural stem and progenitor cells initially promotes clonogenic growth in soft agarose, suggesting partial cellular transformation, but oncogene-induced senescence subsequently limits proliferation |
| 21636552 | Induction of senescence by BRAF may help explain the low-grade pathobiology of pilocytic astrocytoma, whereas worse clinical outcomes associated with tumors lacking p16(INK4a) expression could reflect failure to induce senescence or an escape from oncogene-induced senescence |
| 21514450 | A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence |
| 20959475 | Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence |
| 20227040 | Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR) |
| 20151845 | Integral components of this pathway such as Ras and B-Raf are also activated by mutation |
| 20027224 | Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling |
| 20027224 | Recent studies have shown that an activating mutation of BRAF (BRAF(V600E)) is tightly associated with CIMP, raising the question of whether BRAF(V600E) plays a causal role in the development of CIMP or whether CIMP provides a favorable environment for the acquisition of BRAF(V600E) |
| 20027224 | We first examined whether expression of BRAF(V600E) causes DNA hypermethylation by stably expressing BRAF(V600E) in the CIMP-negative, BRAF wild-type COLO 320DM colorectal cancer cell line |
| 19723919 | Cox proportional hazard models computed hazard ratio (HR) for death, adjusted for potential confounders, including p53, cyclin D1, KRAS, BRAF, PIK3CA, LINE-1 hypomethylation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) |
| 19696787 | To identify microRNAs (miRNAs) involved in oncogene-induced senescence, we examined the expression of miRNAs in primary human TIG3 fibroblasts after constitutive activation of B-RAF |
| 18353141 | Loci with established importance in melanoma, like CDKN2A, BRAF and PTEN, have been joined by some less familiar genes including transcription factor sequences TBX2 and STK11 (LKB) |
| 17724477 | Of the RAF family of protein kinases, BRAF is the only member to be frequently activated by mutation in cancer |
| 17724477 | A single amino acid substitution (V600E) accounts for the vast majority and results in constitutive activation of BRAF kinase function |
| 16880792 | Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi |
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