Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

BRAF (P15056) - Overview - Molecular Target Synopsis

Protein


BRAF, Serine/threonine-protein kinase B-raf
Enzyme Classification 2.7.11.1
UniProt P15056

Also Known as BRAF_HUMAN, BRAF, BRAF1, RAFB1

Protein kinase 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. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway. 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 (PubMed:19710016). Interacts with PRMT5 (PubMed:21917714). Interacts with KSR2 (PubMed:21441910). Interacts with AKAP13, MAP2K1 and KSR1. Identified in a complex with AKAP13, MAP2K1 and KSR1 (PubMed:21102438). Interacts with FNIP1 and FNIP2 (PubMed:27353360).

1UWH
THE COMPLEX OF WILD TYPE B-RAF AND BAY439006.
RCSB/PDB
Inspect Structure
See all 3D Structures for BRAF

Isoforms / Transcripts (Protein Coding)


Drugs


BRAF is targeted by Approved Drugs Sorafenib, Dabrafenib, Vemurafenib. (see details)
Sorafenib
Dabrafenib
Vemurafenib

Sub-cellular localization


UniProt: BRAF is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus.
GO terms: BRAF is active in the following subcellular-locations: cell body, cytosol, intracellular membrane-bounded organelle, mitochondrion, neuron projection, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BRAF has gain in 4 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_5, SR, NCI_H522

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK23, L-363, MDA-MB-134-VI

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, SK-N-SH_RA, AG445

(see details)

RNA Interference


BRAF was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, OVAS. (see details)

3D Structures


For BRAF there are:
69 structures (143 chains) solved
63 are solved in complex with at least one small molecule ligand
8 are solved with an approved drug

BRAF is solved in complex with the approved drug(s):

P06/DABRAFENIB (4XV2_A, 4XV2_B, 5CSW_A, 5CSW_B, 5HIE_A, 5HIE_B, 5HIE_C, 5HIE_D),
032/VEMURAFENIB (3OG7_A, 4RZV_A, 4RZV_B),
BAX/SORAFENIB (1UWH_A, 1UWH_B, 1UWJ_A, 1UWJ_B, 5HI2_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BRAF has been screened with 2412 compounds (4512 bioactivities), 1164 compounds have bioactivities that show binding affinity of <= 500nM (1482 bioactivities). (see details)