Serine/threonine-protein kinase B-raf
Also known as: BRAF, BRAF1, RAFB1
Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway. Phosphorylates PFKFB2. May play a role in the postsynaptic responses of hippocampal neurons.
Classification
- Family (Pfam)
- PF00130 C1_1, PF07714 PK_Tyr_Ser-Thr, PF02196 RBD
- InterPro
- C1-like_sf, DAG/PE-bd, Kinase-like_dom_sf, PKC_DAG/PE, Prot_kinase_dom, Protein_kinase_ATP_BS, RBD_dom, Ser-Thr/Tyr_kinase_cat_dom, Ser/Thr_kinase_AS, Ser/Thr_Kinases-Pseudokinases, Ubiquitin-like_domsf
- Functional cluster
- RNA Polymerase II Transcription Factors
Experimental structures · PDB · 131
- 1UWH X-ray 2.95A
- 1UWJ X-ray 3.50A
- 2FB8 X-ray 2.90A
- 2L05 NMR
- 3C4C X-ray 2.57A
- 3D4Q X-ray 2.80A
- 3IDP X-ray 2.70A
- 3II5 X-ray 2.79A
- 3NY5 X-ray 1.99A
- 3OG7 X-ray 2.45A
- 3PPJ X-ray 3.70A
- 3PPK X-ray 3.00A
- … and 119 more
A predicted model is available from AlphaFold.
Gene Ontology · 31
- GO:0044297 cell body
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0098978 glutamatergic synapse
- GO:0005739 mitochondrion
- GO:0043005 neuron projection
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0005524 ATP binding
- GO:0005509 calcium ion binding
- GO:0042802 identical protein binding
- GO:0004708 MAP kinase kinase activity
- GO:0004709 MAP kinase kinase kinase activity
- GO:0004672 protein kinase activity
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0097110 scaffold protein binding
- GO:0008270 zinc ion binding
- GO:0009887 animal organ morphogenesis
- GO:0071277 cellular response to calcium ion
- GO:0007173 epidermal growth factor receptor signaling pathway
- GO:0090150 establishment of protein localization to membrane
- GO:0000165 MAPK cascade
- GO:0043066 negative regulation of apoptotic process
- GO:0010828 positive regulation of D-glucose transmembrane transport
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0010628 positive regulation of gene expression
- GO:0033138 positive regulation of peptidyl-serine phosphorylation
- GO:0099170 postsynaptic modulation of chemical synaptic transmission
- GO:0006468 protein phosphorylation
Disease associations
- colorectal cancer MONDO:0005575
- cardiofaciocutaneous syndrome 1 MONDO:0007265
- lung cancer MONDO:0008903
- lymphoma, non-Hodgkin, familial MONDO:0011508
- Noonan syndrome 7 MONDO:0013379
- LEOPARD syndrome 3 MONDO:0013380
Drugs targeting this protein · 15
- SORAFENIB TOSYLATE inhibitor
- VEMURAFENIB inhibitor
- REGORAFENIB inhibitor
- CEP-32496 inhibitor
- DABRAFENIB MESYLATE inhibitor
- ENCORAFENIB inhibitor
- TOVORAFENIB inhibitor
- XL-281 inhibitor
- LY-3009120 inhibitor
- BELVARAFENIB inhibitor
- LIFIRAFENIB inhibitor
- PLIXORAFENIB inhibitor
- NAPORAFENIB inhibitor
- ARQ-736 inhibitor
- RAF-265 inhibitor
Related proteins · sequence + function similarity
- Serine/threonine-protein kinase B-raf 0.99
- Serine/threonine-protein kinase B-raf 0.98
- Serine/threonine-protein kinase B-raf 0.98
- RAF proto-oncogene serine/threonine-protein kinase 0.89
- Serine/threonine-protein kinase A-Raf 0.89
- RAF proto-oncogene serine/threonine-protein kinase 0.89
- RAF proto-oncogene serine/threonine-protein kinase 0.89
- Serine/threonine-protein kinase A-Raf 0.88
- RAF proto-oncogene serine/threonine-protein kinase 0.88
- RAF proto-oncogene serine/threonine-protein kinase 0.88
- RAF proto-oncogene serine/threonine-protein kinase 0.88
- Serine/threonine-protein kinase A-Raf 0.87
Co-cited proteins · studied together in the literature
- E3 ubiquitin-protein ligase RNF149 1 shared papers
- UPF0606 protein KIAA1549 1 shared papers
- Dual specificity mitogen-activated protein kinase kinase 1 1 shared papers
- Kinase suppressor of Ras 2 2 shared papers
- Dual specificity mitogen-activated protein kinase kinase 2 3 shared papers
- Diacylglycerol kinase eta 1 shared papers
- Serine/threonine-protein kinase B-raf 2 shared papers
- GTPase KRas 3 shared papers
- Glutamate receptor ionotropic, NMDA 2A 1 shared papers
- Dual specificity mitogen-activated protein kinase kinase 1 3 shared papers
- RAF proto-oncogene serine/threonine-protein kinase 5 shared papers
- Serine/threonine-protein kinase A-Raf 2 shared papers
Literature · 43 cited papers
- BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy. Nat. Commun. · 2022
- Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature · 2022
- Structural basis for SHOC2 modulation of RAS signalling. Nature · 2022
- A YWHAZ variant associated with cardiofaciocutaneous syndrome activates the RAF-ERK pathway. Front. Physiol. · 2019
- MEK drives BRAF activation through allosteric control of KSR proteins. Nature · 2018
- The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat. Commun. · 2016
- Evidence that GRIN2A mutations in melanoma correlate with decreased survival. Front. Oncol. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Lys63-linked polyubiquitination of BRAF at lysine 578 is required for BRAF-mediated signaling. Sci. Rep. · 2013
- Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). J. Biol. Chem. · 2012
- … and 31 more in the literature graph
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