P15056

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. 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. 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"; GENE SYNONYMS:BRAF BRAF1 RAFB1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 766 AA; 84437 MW; 0798C2AAB487E813 CRC64;

BRAF_HUMAN

urn:biopax:ModificationFeature:BRAF_HUMAN_1, urn:biopax:ModificationFeature:BRAF_HUMAN_10, urn:biopax:ModificationFeature:BRAF_HUMAN_11, urn:biopax:ModificationFeature:BRAF_HUMAN_12, urn:biopax:ModificationFeature:BRAF_HUMAN_13, urn:biopax:ModificationFeature:BRAF_HUMAN_14, urn:biopax:ModificationFeature:BRAF_HUMAN_15, urn:biopax:ModificationFeature:BRAF_HUMAN_16, urn:biopax:ModificationFeature:BRAF_HUMAN_17, urn:biopax:ModificationFeature:BRAF_HUMAN_2, urn:biopax:ModificationFeature:BRAF_HUMAN_3, urn:biopax:ModificationFeature:BRAF_HUMAN_4, urn:biopax:ModificationFeature:BRAF_HUMAN_5, urn:biopax:ModificationFeature:BRAF_HUMAN_6, urn:biopax:ModificationFeature:BRAF_HUMAN_7, urn:biopax:ModificationFeature:BRAF_HUMAN_8, urn:biopax:ModificationFeature:BRAF_HUMAN_9

MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTVTSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDSLKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRKTFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPIPQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQRDRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARSLPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH