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IID00292
UniprotP04049
ProteinRAF proto-oncogene serine/threonine-protein kinase
GeneRAF1
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
648
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 51-131 Hetero dimer : P01112
 Evidence X-RAY 3kud B Reference
       Region 3kud B 51-55 disorder
       Region 3kud B 56-131 order
 Evidence X-RAY 4g3x B Reference
       Region 4g3x B 55-131 order
 Evidence X-RAY 4g0n B Reference
       Region 4g0n B 54-131 order
Seq 51-131 Hetero dimer : P62834
 Evidence X-RAY 3kuc B Reference
       Region 3kuc B 51-55 disorder
       Region 3kuc B 56-131 order
 Evidence X-RAY 1gua B Reference
       Region 1gua B 51-55 disorder
       Region 1gua B 56-131 order
 Evidence X-RAY 1c1y B Reference
       Region 1c1y B 55-131 order
Seq 55-132 Monomer :
 Evidence NMR 1rfa A Reference
       Region 1rfa A 55-132 order
Seq 136-187 Monomer :
 Evidence NMR 1far A Reference
       Region 1far A 136-187 order
 Evidence NMR 1faq A Reference
       Region 1faq A 136-187 order
       Region 1faq A 136-137 high_rmsd
       Region 1faq A 185-187 high_rmsd
Seq 229-264 Hetero trimer : IID00061Complex
 Evidence X-RAY 4ihl P Reference
       Region 4ihl P 229-229 disorder
       Region 4ihl P 230-237 order
       Region 4ihl P 238-254 disorder
       Region 4ihl P 255-263 order
       Region 4ihl P 264-264 disorder
 Evidence X-RAY 4fj3 P Reference
       Region 4fj3 P 229-229 disorder
       Region 4fj3 P 230-235 order
       Region 4fj3 P 236-255 disorder
       Region 4fj3 P 256-263 order
       Region 4fj3 P 264-264 disorder
Seq 255-264 Hetero tetramer : IID00301Complex
 Evidence X-RAY 3o8i B Reference
       Region 3o8i B 255-255 disorder
       Region 3o8i B 256-263 order
       Region 3o8i B 264-264 disorder
 Evidence X-RAY 3iqv P Reference
       Region 3iqv P 255-260 order
 Evidence X-RAY 3iqu P Reference
       Region 3iqu P 255-260 order
 Evidence X-RAY 3iqj P Reference
       Region 3iqj P 255-262 order
       Region 3iqj P 263-264 disorder
Seq 255-264 Hetero tetramer : IID00061Complex
 Evidence X-RAY 3nkx Q Reference
       Region 3nkx Q 255-255 disorder
       Region 3nkx Q 256-263 order
       Region 3nkx Q 264-264 disorder
 Evidence X-RAY 3nkx P Reference
       Region 3nkx P 255-255 disorder
       Region 3nkx P 256-264 order
 Evidence X-RAY 3cu8 Q Reference
       Region 3cu8 Q 256-263 order
       Region 3cu8 Q 264-264 disorder
 Evidence X-RAY 3cu8 P Reference
       Region 3cu8 P 256-264 order
Seq 323-618 Homo dimer :
 Evidence X-RAY 3omv B Reference
       Region 3omv B 323-339 disorder
       Region 3omv B 340-492 order
       Region 3omv B 493-504 disorder
       Region 3omv B 505-615 order
       Region 3omv B 616-618 disorder
 Evidence X-RAY 3omv A Reference
       Region 3omv A 323-339 disorder
       Region 3omv A 340-492 order
       Region 3omv A 493-504 disorder
       Region 3omv A 505-615 order
       Region 3omv A 616-618 disorder
Seq 618-625 Hetero tetramer : IID00301Complex
 Evidence X-RAY 4iea P Reference
       Region 4iea P 618-625 order
Seqphosphorylation
    642-642 Phosphoserine; by MAPK1
    621-621 Phosphoserine
    499-499 Phosphoserine; by PKC
    494-494 Phosphoserine
    491-491 Phosphothreonine
    471-471 Phosphoserine
    341-341 Phosphotyrosine; by SRC
    340-340 Phosphotyrosine; by SRC
    339-339 Phosphoserine; by PAK1
    338-338 Phosphoserine; by PAK1
    301-301 Phosphoserine; by MAPK1
    296-296 Phosphoserine
    289-289 Phosphoserine; by MAPK1
    269-269 Phosphothreonine; by PKA
    268-268 Phosphothreonine; by autocatalysis
    259-259 Phosphoserine; by PKA
    252-252 Phosphoserine
    43-43 Phosphoserine; by PKA and MAPK1
    29-29 Phosphoserine; by MAPK1
 
Prediction
NeProc
Disorder 1-14,22-54,194-332,614-648
Order 15-21,55-104,111-193,333-613
ProS 1-14,22-36,194-210,221-225,237-242,258-283,304-319,325-332,614-648
AlphaFold
Disorder 1-55,64-64,90-90,103-108,132-137,183-183,185-256,263-337,339-339,359-359,488-507,614-648
Order 56-63,65-89,91-102,109-131,138-182,184-184,257-262,338-338,340-358,360-487,508-613
Pfam Hmmer
PF02196 56-131 1.8e-40
PF00130 139-187 3.5e-18
PF00069 349-606 9.5e-85
SEG 283-301
Function
Function in SwissProt
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.
Biological Process
Diagram with PDB data
RAF1/YWHAZHuman 14-3-3 isoform zeta in complex with a diphoyphorylated C-RAF peptide and Cotylenin A