Human Gene BRAF (ENST00000646891.2) from GENCODE V43
Description: Homo sapiens B-Raf proto-oncogene, serine/threonine kinase (BRAF), transcript variant 1, mRNA. (from RefSeq NM_004333) RefSeq Summary (NM_004333): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000646891.2 Gencode Gene: ENSG00000157764.14 Transcript (Including UTRs) Position: hg38 chr7:140,730,665-140,924,929 Size: 194,265 Total Exon Count: 18 Strand: - Coding Region Position: hg38 chr7:140,734,597-140,924,703 Size: 190,107 Coding Exon Count: 18
ID:BRAF_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase B-raf; EC=2.7.11.1; AltName: Full=Proto-oncogene B-Raf; AltName: Full=p94; AltName: Full=v-Raf murine sarcoma viral oncogene homolog B1; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 2 zinc ions per subunit (By similarity). ENZYME REGULATION: Activity is increased by EGF and HGF. SUBUNIT: 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- 753. 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. Interacts with PRMT5. INTERACTION: P04049:RAF1; NbExp=30; IntAct=EBI-365980, EBI-365996; SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm. Cell membrane (By similarity). Note=Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes (By similarity). TISSUE SPECIFICITY: Brain and testis. PTM: Phosphorylation at Ser-365 by SGK1 inhibits its activity. PTM: Methylation at Arg-671 decreases stability and kinase activity. PTM: Ubiquitinated by RNF149; which leads to proteasomal degradation. DISEASE: Note=Defects in BRAF are found in a wide range of cancers. DISEASE: Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:114500]. DISEASE: Defects in BRAF are involved in lung cancer (LNCR) [MIM:211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. DISEASE: Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. DISEASE: Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. DISEASE: Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:613706]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits. DISEASE: Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:613707]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. DISEASE: Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 RBD (Ras-binding) domain. SEQUENCE CAUTION: Sequence=AAD43193.1; Type=Erroneous gene model prediction; Sequence=CAQ43111.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAQ43112.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAQ43113.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAQ43114.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAQ43115.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAQ43116.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BRAFID828.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/BRAF";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P15056
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0000186 activation of MAPKK activity GO:0006468 protein phosphorylation GO:0007165 signal transduction GO:0009887 animal organ morphogenesis GO:0009968 negative regulation of signal transduction GO:0010628 positive regulation of gene expression GO:0010828 positive regulation of glucose transport GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0035556 intracellular signal transduction GO:0043066 negative regulation of apoptotic process GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0070413 trehalose metabolism in response to stress GO:0071277 cellular response to calcium ion GO:0090150 establishment of protein localization to membrane
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