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This proto-oncogene belongs to the RAF subfamily of the Ser/Thr protein kinase family, and maybe involved in cell growth and development. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2012]
ARAF has recently become increasingly considered for its oncogenic potential. Its potential as a target for informing clinical action was demonstrated by a single case of advanced lung adenocarcinoma harboring an S214C mutation that, when treated with sorafenib, acheived near-complete clinical remission. This finding has brought new focus on ARAF as a marker that should be assayed for in cancer treatment.
ARAF (A-Raf Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with ARAF include Pallister-Killian Syndrome and Mycobacterium Marinum. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Negative regulation of MAPK pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is RAF1.
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.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA,TAS | 3029685 |
GO:0004674 | protein serine/threonine kinase activity | IEA,IDA | 19667065 |
GO:0004709 | MAP kinase kinase kinase activity | IEA | -- |
GO:0005515 | protein binding | IPI | 11909642 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005575 | cellular_component | ND | -- |
GO:0005739 | mitochondrion | IEA,IBA | 21873635 |
GO:0005829 | cytosol | IEA,TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways | ||
3 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
ErbB2-ErbB3 Heterodimers
.49
|
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
IL-4 Pathway
.34
|
4 | Endometrial cancer |
.32
|
|
5 | Glioma |
.49
.46
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | IEA,TAS | -- |
GO:0000186 | activation of MAPKK activity | IEA | -- |
GO:0006464 | cellular protein modification process | TAS | 3029685 |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0007165 | signal transduction | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
regorafenib | Approved | Pharma | inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Sorafenib | Approved, Investigational | Pharma | inhibitors, inhibitor | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 779 | |
alpha-D-Fucopyranose | Experimental | Pharma | Target | 0 | ||
Alpha-L-Arabinose | Experimental | Pharma | Target | 0 | ||
beta-D-fucose | Experimental | Pharma | Target | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 | |||
Diglycerides Group A |
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Diglycerides Group B |
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Diglycerides Group C |
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Diglycerides Group D |
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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 |
LGX818 | RAF inhibitor,potent and selective | 1269440-17-6 |
TAK-632 | Pan-RAF inhibitor,potent and selective | 1228591-30-7 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2a | · | 2b | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6a | · | 6b | ^ | 7a | · | 7b | · | 7c | ^ | 8a | · | 8b | ^ | 9a | · | 9b | · | 9c | · | 9d | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - |
ExUns: | 15 | ^ | 16 | ^ | 17 | ^ | 18 |
---|---|---|---|---|---|---|---|
SP1: | |||||||
SP2: | |||||||
SP3: | |||||||
SP4: | |||||||
SP5: | |||||||
SP6: | |||||||
SP7: | |||||||
SP8: | |||||||
SP9: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ARAF 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | ARAF 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | ARAF 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Araf 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Araf 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | ARAF 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | ARAF 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | ARAF 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | araf 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | phl 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | lin-45 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.10630 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 0X pos | Variation | AA Info | Type |
---|---|---|---|---|---|
713393 | Benign: not provided | 47,569,651(+) | G/A | SYNONYMOUS_VARIANT | |
747628 | Benign: not provided | 47,571,370(+) | G/C | MISSENSE_VARIANT | |
789251 | Benign: not provided | 47,567,358(+) | C/T | SYNONYMOUS_VARIANT | |
rs1057519786 | Likely Pathogenic: Lung adenocarcinoma; Non-small cell lung cancer; Papillary renal cell carcinoma, sporadic; Malignant melanoma of skin. Likely Pathogenic: Lung adenocarcinoma; Papillary renal cell carcinoma, sporadic; Malignant melanoma of skin | 47,566,722(+) | C/GC/T | MISSENSE_VARIANT | |
rs1057519876 | Likely Pathogenic: Lung adenocarcinoma; Papillary renal cell carcinoma, sporadic; Malignant melanoma of skin | 47,566,721(+) | T/G | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
pallister-killian syndrome |
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mycobacterium marinum |
|
|
adenocarcinoma |
|
|
langerhans cell histiocytosis |
|
|
histiocytosis |
|
|