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B Raf サマリー & タンパク質情報

B Raf 背景

触媒活性: ATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:21441910}.
補因子: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; ; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
酵素調節: ENZYME REGULATION: Activity is increased by EGF and HGF.
サブユニット構造: 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, HRAS, 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. Interacts with KSR2. {ECO:0000250, ECO:0000269|PubMed:18287029, ECO:0000269|PubMed:19710016, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:21917714}.
細胞内位置: Nucleus {ECO:0000250}. Cytoplasm. Cell membrane {ECO:0000250}. Note=Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes. {ECO:0000250}.
組織特異性: Brain and testis.
翻訳後: Phosphorylation at Ser-365 by SGK1 inhibits its activity. {ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:19710016, ECO:0000269|Ref.8}.; Methylation at Arg-671 decreases stability and kinase activity. {ECO:0000269|PubMed:21917714}.; Ubiquitinated by RNF149; which leads to proteasomal degradation. Polyubiquitinated at Lys-578 in response to EGF. {ECO:0000269|PubMed:22628551, ECO:0000269|PubMed:23907581}.
疾患関連性: DISEASE: Note=Defects in BRAF are found in a wide range of cancers. {ECO:0000269|PubMed:18974108}.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12198537, ECO:0000269|PubMed:23263490, ECO:0000269|PubMed:24455489}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Lung cancer (LNCR) [MIM:211980]: 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. {ECO:0000269|PubMed:12460919}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: 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. {ECO:0000269|PubMed:14612909}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Cardiofaciocutaneous syndrome 1 (CFC1) [MIM:115150]: A multiple congenital anomaly disorder 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. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Noonan syndrome 7 (NS7) [MIM:613706]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. {ECO:0000269|PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: LEOPARD syndrome 3 (LPRD3) [MIM:613707]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.; 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. {ECO:0000269|PubMed:18974108}.
シーケンスの類似性: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. {ECO:0000305}.; Contains 1 phorbol-ester/DAG-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00226}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.; Contains 1 RBD (Ras-binding) domain. {ECO:0000255|PROSITE-ProRule:PRU00262}.
General information above from UniProt

BRAF gene encodes a protein belonging to the raf/mil family of serine/threonine protein kinases. BRAFprotein plays a role in regulating the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation, and secretion. Mutations in BRAF gene are associated with cardiofaciocutaneous syndrome, a disease characterized by heart defects, mental retardation and a distinctive facial appearance. Mutations in BRAF gene have also been associated with various cancers, including non-Hodgkin lymphoma, colorectal cancer, malignant melanoma, thyroid carcinoma, non-small cell lung carcinoma, and adenocarcinoma of lung. A pseudogene, which is located on chromosome X, has been identified for this gene.

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B Raf 代替名

NS7,BRAF1,RAFB1,B-RAF1, [homo-sapiens]
B-raf,Braf2,Braf-2,C87398,AA120551,AA387315,AA473386,C230098H17,D6Ertd631e,9930012E13Rik, [mus-musculus]

B Raf 関連研究

  • Weston-Bell NJ, Tapper W, Gibson J, et al. Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V(600)E Lesion. Richards KL, ed. PLoS ONE. 2016;11(2):e0149162. doi:10.1371/journal.pone.0149162.
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