UniProt:P15056 BRAF

chain
  • initiator methionine:1
  • chain:2-766
checksum 0798C2AAB487E813
comment
  • 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 (PubMed:21441910, PubMed:29433126). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179).ACTIVITY REGULATION In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains. Following mitogen-mediated cell activation, binds via its RGB domain to active HRAS (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains. This allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which activates BRAF.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. Heterodimerizes (via N-terminus) with KSR1 (via N-terminus) or KSR2 (via N-terminus) in a MAP2K1-dependent manner (PubMed:29433126). Interacts with MAP2K1 and MAP2K2 (PubMed:29433126). 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).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.PTM Ubiquitinated by RNF149; which leads to proteasomal degradation. Polyubiquitinated at Lys-578 in response to EGF.DISEASE Defects in BRAF are found in a wide range of cancers.DISEASE 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.
crossReference
databaseName UniProt
dbId 58251
description
  • recommendedName: fullName evidence="33"Serine/threonine-protein kinase B-raf ecNumber evidence="24 31"2.7.11.1/ecNumber alternativeName: Proto-oncogene B-Raf alternativeName: p94 alternativeName: v-Raf murine sarcoma viral oncogene homolog B1
displayName UniProt:P15056 BRAF
geneName
  • BRAF
  • BRAF1
  • RAFB1
identifier P15056
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Allosteric enzyme
  • ATP-binding
  • Cardiomyopathy
  • Cell membrane
  • Chromosomal rearrangement
  • Cytoplasm
  • Deafness
  • Direct protein sequencing
  • Disease variant
  • Ectodermal dysplasia
  • Isopeptide bond
  • Kinase
  • Membrane
  • Mental retardation
  • Metal-binding
  • Methylation
  • Nucleotide-binding
  • Nucleus
  • Phosphoprotein
  • Proto-oncogene
  • Reference proteome
  • Serine/threonine-protein kinase
  • Transferase
  • Ubl conjugation
  • Zinc
  • Zinc-finger
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • BRAF
otherIdentifier
  • 11732491_s_at
  • 1654_at
  • 17063631
  • 206044_s_at
  • 3076364
  • 3076365
  • 3076366
  • 3076367
  • 3076368
  • 3076370
  • 3076372
  • 3076374
  • 3076375
  • 3076380
  • 3076381
  • 3076382
  • 3076383
  • 3076384
  • 3076386
  • 3076388
  • 3076392
  • 3076393
  • 3076396
  • 3076399
  • 3076414
  • 3076416
  • 3076439
  • 3076440
  • 3076441
  • 3076442
  • 3982166
  • 3982173
  • 40306_at
  • 673
  • 8143417
  • 86199_r_at
  • A_23_P42935
  • GE58163
  • GE766137
  • GO:0000165
  • GO:0000166
  • GO:0000186
  • GO:0003674
  • GO:0003824
  • GO:0004672
  • GO:0004674
  • GO:0005509
  • GO:0005515
  • GO:0005524
  • GO:0005575
  • GO:0005622
  • GO:0005634
  • GO:0005737
  • GO:0005829
  • GO:0005886
  • GO:0005975
  • GO:0006464
  • GO:0006468
  • GO:0006810
  • GO:0006950
  • GO:0007165
  • GO:0007173
  • GO:0008150
  • GO:0008152
  • GO:0008219
  • GO:0009887
  • GO:0010628
  • GO:0010828
  • GO:0016020
  • GO:0016301
  • GO:0016310
  • GO:0016740
  • GO:0033138
  • GO:0035556
  • GO:0042802
  • GO:0043066
  • GO:0043167
  • GO:0043226
  • GO:0043231
  • GO:0046872
  • GO:0048856
  • GO:0055085
  • GO:0070374
  • GO:0070413
  • GO:0071277
  • GO:0090150
  • GO:0097110
  • GO:0106310
  • GO:0106311
  • HMNXSV003020754
  • ILMN_1652472
  • M95712_at
  • PH_hs_0027912
  • TC07001927.hg
  • g4757867_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • BRAF_HUMAN
  • A4D1T4
  • B6HY61
  • B6HY62
  • B6HY63
  • B6HY64
  • B6HY65
  • B6HY66
  • Q13878
  • Q3MIN6
  • Q9UDP8
  • Q9Y6T3
sequenceLength 766
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P15056

Referrals

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