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Aliases for RAF1 Gene

Aliases for RAF1 Gene

  • Raf-1 Proto-Oncogene, Serine/Threonine Kinase 2 3 5
  • V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1 2 3
  • Proto-Oncogene C-RAF 3 4
  • EC 2.7.11.1 4 63
  • Raf-1 3 4
  • CRAF 3 4
  • V-Raf-1 Murine Leukemia Viral Oncogene-Like Protein 1 3
  • Raf Proto-Oncogene Serine/Threonine Protein Kinase 3
  • C-Raf Proto-Oncogene, Serine/Threonine Kinase 3
  • Serine/Threonine Kinase 2
  • C-Raf Proto-Oncogene 2
  • Oncogene RAF1 3
  • EC 2.7.11 63
  • CMD1NN 3
  • C-Raf 3
  • NS5 3
  • RAF 4

External Ids for RAF1 Gene

Previous GeneCards Identifiers for RAF1 Gene

  • GC03M012554
  • GC03M012600
  • GC03M012559
  • GC03M012625

Summaries for RAF1 Gene

Entrez Gene Summary for RAF1 Gene

  • This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]

GeneCards Summary for RAF1 Gene

RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with RAF1 include noonan syndrome 5 and leopard syndrome 2. Among its related pathways are Platelet activation, signaling and aggregation and Sertoli-Sertoli Cell Junction Dynamics. GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is KSR1.

UniProtKB/Swiss-Prot for RAF1 Gene

  • 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.

Tocris Summary for RAF1 Gene

  • Raf kinases, a family of three serine/threonine kinases, are part of the Ras-MAPK signaling cascade and phosphorylate MEK. Upon growth factor stimulation, Raf-1 (c-Raf) is activated by GTP-bound Ras and recruited to the cell membrane. This activation process is tightly regulated.

Gene Wiki entry for RAF1 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RAF1 Gene

Genomics for RAF1 Gene

Regulatory Elements for RAF1 Gene

Promoters for RAF1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RAF1 on UCSC Golden Path with GeneCards custom track

Genomic Location for RAF1 Gene

Chromosome:
3
Start:
12,583,601 bp from pter
End:
12,664,226 bp from pter
Size:
80,626 bases
Orientation:
Minus strand

Genomic View for RAF1 Gene

Genes around RAF1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAF1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAF1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAF1 Gene

Proteins for RAF1 Gene

  • Protein details for RAF1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04049-RAF1_HUMAN
    Recommended name:
    RAF proto-oncogene serine/threonine-protein kinase
    Protein Accession:
    P04049
    Secondary Accessions:
    • B0LPH8
    • B2R5N3
    • Q15278
    • Q9UC20

    Protein attributes for RAF1 Gene

    Size:
    648 amino acids
    Molecular mass:
    73052 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Monomer. Homodimer. Heterodimerizes with BRAF and this 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. Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with BRAF, a ternary complex inhibited by GNAI1 (By similarity). Interacts with STK3/MST2; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at Thr-232). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (By similarity). Interacts with MAP3K5/ASF1 (via N-terminus) and this interaction inhibits the proapoptotic function of MAP3K5/ASK1. Interacts with PAK1 (via kinase domain). The phosphorylated form interacts with PIN1. The Ser-338 and Ser-339 phosphorylated form (by PAK1) interacts with BCL2. Interacts with PEBP1/RKIP and this interaction is enhanced if RAF1 is phosphorylated on residues Ser-338, Ser-339, Tyr-340 and Tyr-341. Interacts with ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, ROCK2, PPP1R12A, PKB/AKT1, PPP2CA, PPP2R1B, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin. In its active form, interacts with PRMT5. Interacts with FAM83B; displaces 14-3-3 proteins from RAF1 and activates RAF1 (PubMed:22886302).

    Three dimensional structures from OCA and Proteopedia for RAF1 Gene

    Alternative splice isoforms for RAF1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RAF1 Gene

Proteomics data for RAF1 Gene at MOPED

Post-translational modifications for RAF1 Gene

  • Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation.
  • Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Phosphorylation at Ser-338 by PAK1 and PAK7/PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization. Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells. Treatment of cells with HGF in the presence of the methylation inhibitor 5-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C results in a activity decrease.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for RAF1 Gene

Domains & Families for RAF1 Gene

Graphical View of Domain Structure for InterPro Entry

P04049

UniProtKB/Swiss-Prot:

RAF1_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
  • Contains 1 phorbol-ester/DAG-type zinc finger.
Domain:
  • Contains 1 protein kinase domain.
  • Contains 1 RBD (Ras-binding) domain.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Similarity:
  • Contains 1 phorbol-ester/DAG-type zinc finger.
genes like me logo Genes that share domains with RAF1: view

Function for RAF1 Gene

Molecular function for RAF1 Gene

GENATLAS Biochemistry:
murine sarcoma viral (v-raf-1) oncogene homolog 1 (mitogenic factor) interacting with TC21 for activation and translocation to plasma membrane
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for RAF1 Gene

Phenotypes for RAF1 Gene

MGI mutant phenotypes for RAF1:
inferred from 12 alleles
GenomeRNAi human phenotypes for RAF1:
genes like me logo Genes that share phenotypes with RAF1: view

Human Phenotype Ontology for RAF1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RAF1 Gene

MGI Knock Outs for RAF1:

Animal Model Products

No data available for Gene Ontology (GO) - Molecular Function , Transcription Factor Targets and HOMER Transcription for RAF1 Gene

Localization for RAF1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAF1 Gene

Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its mitochondrial localization. Retinoic acid-induced Ser-621 phosphorylated form of RAF1 is predominantly localized at the nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RAF1 Gene COMPARTMENTS Subcellular localization image for RAF1 gene
Compartment Confidence
cytosol 5
golgi apparatus 5
mitochondrion 5
nucleus 5
plasma membrane 5
cytoskeleton 2
extracellular 2
endoplasmic reticulum 1
endosome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for RAF1 Gene

Pathways & Interactions for RAF1 Gene

SuperPathways for RAF1 Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 IL-2 Pathway
3 IL-7 Signaling Pathways
4 Translation Insulin regulation of translation
5 Development HGF signaling pathway
genes like me logo Genes that share pathways with RAF1: view

Pathways by source for RAF1 Gene

SIGNOR curated interactions for RAF1 Gene

Gene Ontology (GO) - Biological Process for RAF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000186 activation of MAPKK activity IDA,TAS 10644344
GO:0001666 response to hypoxia IEA --
GO:0001678 cellular glucose homeostasis IEA --
GO:0006468 protein phosphorylation IEA,TAS 8063729
GO:0006915 apoptotic process TAS 8929532
genes like me logo Genes that share ontologies with RAF1: view

Drugs & Compounds for RAF1 Gene

(99) Drugs for RAF1 Gene - From: Novoseek, DGIdb, HMDB, ApexBio, Tocris, DrugBank, FDA Approved Drugs, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sorafenib Approved, Investigational Pharma inhibitors, inhibitor, Target Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 671
regorafenib Approved Pharma inhibitor, Target Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Platinum 2540
Docetaxel Approved May 1996, Investigational Pharma Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes 1844
Paclitaxel Approved Pharma Tubulin and Bcl2 inhibitor, Taxanes 2621

(60) Additional Compounds for RAF1 Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ZM 336372
208260-29-1
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Diglycerides Group A
  • 1,2-Dimyristoyl-rac-glycerol
  • DAG(14:0/14:0)
  • DAG(28:0)
  • DG(14:0/14:0)
  • DG(28:0)
Diglycerides Group B
  • 1-Palmitoleoyl-2-arachidonyl-sn-glycerol
  • DAG(16:1/20:0)
  • DAG(16:1n7/20:0)
  • DAG(16:1w7/20:0)
  • DAG(36:1)
Diglycerides Group C
  • 1-Myristoyl-3-stearoyl-sn-glycerol
  • 1-Tetradecanoyl-3-octadecanoyl-sn-glycerol
  • DAG(14:0/0:0/18:0)
  • DAG(32:0)
  • DG(32:0)

(5) Tocris Compounds for RAF1 Gene

Compound Action Cas Number
GDC 0879 Potent B-Raf inhibitor 905281-76-7
GW 5074 Potent, selective c-Raf1 kinase inhibitor 220904-83-6
L-779,450 Potent Raf kinase inhibitor 303727-31-3
SB 590885 Potent B-Raf inhibitor 405554-55-4
ZM 336372 Potent, selective c-Raf inhibitor 208260-29-1

(10) ApexBio Compounds for RAF1 Gene

Compound Action Cas Number
AZ 628 Raf kinases,potent and ATP-competitive 878739-06-1
CEP-32496 BRAF(V600E)inhibitor,highly potent 1188910-76-0
GDC-0879 B-Raf inhibitor,potent and selective 905281-76-7
GW5074 C-Raf inhibitor,potent and selective 220904-83-6
LGX818 RAF inhibitor,potent and selective 1269440-17-6
RAF265 Multiple intracellular kinases inhibitor 927880-90-8
Sorafenib Raf kinases and tyrosine kinases inhibitor 284461-73-0
Sorafenib Tosylate Raf kinases and tyrosine kinases inhibitor 475207-59-1
TAK-632 Pan-RAF inhibitor,potent and selective 1228591-30-7
ZM336372 C-Raf inhibitor, potent and selective 208260-29-1
genes like me logo Genes that share compounds with RAF1: view

Drug Products

Transcripts for RAF1 Gene

Unigene Clusters for RAF1 Gene

V-raf-1 murine leukemia viral oncogene homolog 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RAF1 Gene

No ASD Table

Relevant External Links for RAF1 Gene

GeneLoc Exon Structure for
RAF1
ECgene alternative splicing isoforms for
RAF1

Expression for RAF1 Gene

mRNA expression in normal human tissues for RAF1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RAF1 Gene