RAF proto-oncogene serine/threonine-protein kinase

Details

Name
RAF proto-oncogene serine/threonine-protein kinase
Synonyms
  • 2.7.11.1
  • cRaf
  • Proto-oncogene c-RAF
  • RAF
  • Raf-1
Gene Name
RAF1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000072|RAF proto-oncogene serine/threonine-protein kinase
MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRV
FLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAAS
LIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKV
PTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTF
NTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNL
SPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSF
GTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIV
TQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGL
TVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYE
LMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFP
QILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF
Number of residues
648
Molecular Weight
73051.025
Theoretical pI
9.62
GO Classification
Functions
ATP binding / identical protein binding / MAP kinase kinase kinase activity / metal ion binding / protein kinase activity / protein serine/threonine kinase activity
Processes
activation of adenylate cyclase activity / activation of MAPKK activity / apoptotic process / axon guidance / blood coagulation / cell proliferation / death-inducing signaling complex assembly / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / heart development / innate immune response / insulin receptor signaling pathway / insulin secretion involved in cellular response to glucose stimulus / intermediate filament cytoskeleton organization / ion transmembrane transport / MAPK cascade / negative regulation of apoptotic process / negative regulation of cell proliferation / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of protein complex assembly / neurotrophin TRK receptor signaling pathway / platelet activation / positive regulation of peptidyl-serine phosphorylation / positive regulation of transcription from RNA polymerase II promoter / protein phosphorylation / Ras protein signal transduction / regulation of apoptotic process / regulation of cell differentiation / regulation of cell motility / regulation of Rho protein signal transduction / response to hypoxia / response to muscle stretch / signal transduction / small GTPase mediated signal transduction / somatic stem cell population maintenance / stimulatory C-type lectin receptor signaling pathway / synaptic transmission / transmembrane transport / vascular endothelial growth factor receptor signaling pathway / wound healing
Components
cytoplasm / cytosol / Golgi apparatus / mitochondrial outer membrane / nucleus / plasma membrane / pseudopodium
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0009890|RAF proto-oncogene serine/threonine-protein kinase (RAF1)
ATGGAGCACATACAGGGAGCTTGGAAGACGATCAGCAATGGTTTTGGATTCAAAGATGCC
GTGTTTGATGGCTCCAGCTGCATCTCTCCTACAATAGTTCAGCAGTTTGGCTATCAGCGC
CGGGCATCAGATGATGGCAAACTCACAGATCCTTCTAAGACAAGCAACACTATCCGTGTT
TTCTTGCCGAACAAGCAAAGAACAGTGGTCAATGTGCGAAATGGAATGAGCTTGCATGAC
TGCCTTATGAAAGCACTCAAGGTGAGGGGCCTGCAACCAGAGTGCTGTGCAGTGTTCAGA
CTTCTCCACGAACACAAAGGTAAAAAAGCACGCTTAGATTGGAATACTGATGCTGCGTCT
TTGATTGGAGAAGAACTTCAAGTAGATTTCCTGGATCATGTTCCCCTCACAACACACAAC
TTTGCTCGGAAGACGTTCCTGAAGCTTGCCTTCTGTGACATCTGTCAGAAATTCCTGCTC
AATGGATTTCGATGTCAGACTTGTGGCTACAAATTTCATGAGCACTGTAGCACCAAAGTA
CCTACTATGTGTGTGGACTGGAGTAACATCAGACAACTCTTATTGTTTCCAAATTCCACT
ATTGGTGATAGTGGAGTCCCAGCACTACCTTCTTTGACTATGCGTCGTATGCGAGAGTCT
GTTTCCAGGATGCCTGTTAGTTCTCAGCACAGATATTCTACACCTCACGCCTTCACCTTT
AACACCTCCAGTCCCTCATCTGAAGGTTCCCTCTCCCAGAGGCAGAGGTCGACATCCACA
CCTAATGTCCACATGGTCAGCACCACCCTGCCTGTGGACAGCAGGATGATTGAGGATGCA
ATTCGAAGTCACAGCGAATCAGCCTCACCTTCAGCCCTGTCCAGTAGCCCCAACAATCTG
AGCCCAACAGGCTGGTCACAGCCGAAAACCCCCGTGCCAGCACAAAGAGAGCGGGCACCA
GTATCTGGGACCCAGGAGAAAAACAAAATTAGGCCTCGTGGACAGAGAGATTCAAGCTAT
TATTGGGAAATAGAAGCCAGTGAAGTGATGCTGTCCACTCGGATTGGGTCAGGCTCTTTT
GGAACTGTTTATAAGGGTAAATGGCACGGAGATGTTGCAGTAAAGATCCTAAAGGTTGTC
GACCCAACCCCAGAGCAATTCCAGGCCTTCAGGAATGAGGTGGCTGTTCTGCGCAAAACA
CGGCATGTGAACATTCTGCTTTTCATGGGGTACATGACAAAGGACAACCTGGCAATTGTG
ACCCAGTGGTGCGAGGGCAGCAGCCTCTACAAACACCTGCATGTCCAGGAGACCAAGTTT
CAGATGTTCCAGCTAATTGACATTGCCCGGCAGACGGCTCAGGGAATGGACTATTTGCAT
GCAAAGAACATCATCCATAGAGACATGAAATCCAACAATATATTTCTCCATGAAGGCTTA
ACAGTGAAAATTGGAGATTTTGGTTTGGCAACAGTAAAGTCACGCTGGAGTGGTTCTCAG
CAGGTTGAACAACCTACTGGCTCTGTCCTCTGGATGGCCCCAGAGGTGATCCGAATGCAG
GATAACAACCCATTCAGTTTCCAGTCGGATGTCTACTCCTATGGCATCGTATTGTATGAA
CTGATGACGGGGGAGCTTCCTTATTCTCACATCAACAACCGAGATCAGATCATCTTCATG
GTGGGCCGAGGATATGCCTCCCCAGATCTTAGTAAGCTATATAAGAACTGCCCCAAAGCA
ATGAAGAGGCTGGTAGCTGACTGTGTGAAGAAAGTAAAGGAAGAGAGGCCTCTTTTTCCC
CAGATCCTGTCTTCCATTGAGCTGCTCCAACACTCTCTACCGAAGATCAACCGGAGCGCT
TCCGAGCCATCCTTGCATCGGGCAGCCCACACTGAGGATATCAATGCTTGCACGCTGACC
ACGTCCCCGAGGCTGCCTGTCTTCTAG
Chromosome Location
3
Locus
3p25
External Identifiers
ResourceLink
UniProtKB IDP04049
UniProtKB Entry NameRAF1_HUMAN
GenBank Protein ID35842
GenBank Gene IDX03484
GenAtlas IDRAF1
HGNC IDHGNC:9829
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalyesinhibitorDetails
DB04973LErafAONinvestigationalunknownDetails
DB05268iCo-007investigationalunknownDetails
DB05190XL281investigationalunknownDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB08912Dabrafenibapproved, investigationalyesantagonistinhibitorDetails
DB08862Cholecystokininapproved, investigationalunknownagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails