InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BRAF

Summary

InnateDB Protein

IDBP-44353.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BRAF

Protein Name

v-raf murine sarcoma viral oncogene homolog B1

Synonyms

B-RAF1; BRAF1; NS7; RAFB1;

Species

Homo sapiens

Ensembl Protein

ENSP00000288602

InnateDB Gene

IDBG-44351 (BRAF)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:21441910}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasm. Cell membrane {ECO:0000250}. Note=Colocalizes with RGS14 and RAF1 in both the cytoplasm and membranes. {ECO:0000250}.

Disease Associations

Note=Defects in BRAF are found in a wide range of cancers. {ECO:0000269PubMed:18974108}.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:0000269PubMed:12198537, ECO:0000269PubMed:23263490}. Note=The disease may be caused by mutations affecting the gene represented in this entry.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:0000269PubMed:12460919}. Note=The gene represented in this entry is involved in disease pathogenesis.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:0000269PubMed:14612909}. Note=The gene represented in this entry is involved in disease pathogenesis.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:0000269PubMed:16439621, ECO:0000269PubMed:16474404, ECO:0000269PubMed:18042262, ECO:0000269PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.LEOPARD syndrome 3 (LEOPARD3) [MIM:613707]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269PubMed:19206169}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:18974108}.

Tissue Specificity

Brain and testis.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 70 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	70 [view]
Protein-Protein	69 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005057	receptor signaling protein activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031434	mitogen-activated protein kinase kinase binding
GO:0042802	identical protein binding
GO:0046982	protein heterodimerization activity

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0002318	myeloid progenitor cell differentiation
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007264	small GTPase mediated signal transduction
GO:0007268	synaptic transmission
GO:0008542	visual learning
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009887	organ morphogenesis
GO:0010628	positive regulation of gene expression
GO:0010764	negative regulation of fibroblast migration
GO:0030154	cell differentiation
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0035019	somatic stem cell maintenance
GO:0035556	intracellular signal transduction
GO:0035690	cellular response to drug
GO:0042127	regulation of cell proliferation
GO:0043066	negative regulation of apoptotic process
GO:0043367	CD4-positive, alpha-beta T cell differentiation
GO:0043368	positive T cell selection
GO:0043434	response to peptide hormone
GO:0043524	negative regulation of neuron apoptotic process
GO:0046632	alpha-beta T cell differentiation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051291	protein heterooligomerization
GO:0051496	positive regulation of stress fiber assembly
GO:0051591	response to cAMP
GO:0060291	long-term synaptic potentiation
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070849	response to epidermal growth factor
GO:0071277	cellular response to calcium ion
GO:1900026	positive regulation of substrate adhesion-dependent cell spreading
GO:2000301	negative regulation of synaptic vesicle exocytosis
GO:2000352	negative regulation of endothelial cell apoptotic process

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0043005	neuron projection
GO:0044297	cell body

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003116 Raf-like Ras-binding
IPR011009 Protein kinase-like domain
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714
PF00130
PF02196

PRINTS

PR00109
PR00008

PIRSF

SMART

SM00109
SM00220
SM00455
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt