======= RAF1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RAF1
  * **<color #00a2e8>Official Name</color>**: Raf-1 proto-oncogene, serine/threonine kinase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5894|5894]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P04049|P04049]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RAF1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RAF1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/164760|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|C1 1|
|Pkinase Tyr|
|Pkinase|
|RBD|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|adenylate cyclase activator activity|
|insulin secretion involved in cellular response to glucose stimulus|
|death-inducing signaling complex assembly|
|mitogen-activated protein kinase kinase binding|
|adenylate cyclase binding|
|pseudopodium|
|response to muscle stretch|
|MAP kinase kinase kinase activity|
|neurotrophin TRK receptor signaling pathway|
|thyroid gland development|
|small GTPase binding|
|neurotrophin signaling pathway|
|negative regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|insulin secretion|
|activation of adenylate cyclase activity|
|thymus development|
|face development|
|intermediate filament cytoskeleton organization|
|intermediate filament-based process|
|activation of MAPKK activity|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|peptide hormone secretion|
|somatic stem cell population maintenance|
|cellular response to glucose stimulus|
|cellular response to hexose stimulus|
|hormone secretion|
|cellular response to monosaccharide stimulus|
|cellular response to carbohydrate stimulus|
|hormone transport|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|cellular glucose homeostasis|
|negative regulation of cysteine-type endopeptidase activity|
|extrinsic apoptotic signaling pathway|
|negative regulation of extrinsic apoptotic signaling pathway|
|positive regulation of peptidyl-serine phosphorylation|
|stimulatory C-type lectin receptor signaling pathway|
|innate immune response activating cell surface receptor signaling pathway|
|endocrine system development|
|negative regulation of protein complex assembly|
|stem cell population maintenance|
|regulation of peptidyl-serine phosphorylation|
|maintenance of cell number|
|response to glucose|
|platelet activation|
|regulation of Rho protein signal transduction|
|response to hexose|
|response to monosaccharide|
|regulation of extrinsic apoptotic signaling pathway|
|protein secretion|
|establishment of protein localization to extracellular region|
|mitochondrial outer membrane|
|protein localization to extracellular region|
|signal release|
|response to carbohydrate|
|peptide secretion|
|glucose homeostasis|
|carbohydrate homeostasis|
|response to mechanical stimulus|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|negative regulation of apoptotic signaling pathway|
|innate immune response-activating signal transduction|
|protein kinase activity|
|regulation of cysteine-type endopeptidase activity|
|regulation of Ras protein signal transduction|
|negative regulation of endopeptidase activity|
|negative regulation of peptidase activity|
|activation of innate immune response|
|positive regulation of MAP kinase activity|
|apoptotic signaling pathway|
|blood coagulation|
|coagulation|
|hemostasis|
|activation of protein kinase activity|
|positive regulation of protein serine/threonine kinase activity|
|positive regulation of innate immune response|
|regulation of MAP kinase activity|
|response to hypoxia|
|regulation of small GTPase mediated signal transduction|
|enzyme binding|
|negative regulation of proteolysis|
|response to decreased oxygen levels|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|MAPK cascade|
|response to oxygen levels|
|signal transduction by protein phosphorylation|
|regulation of apoptotic signaling pathway|
|nuclear speck|
|gland development|
|regulation of endopeptidase activity|
|regulation of peptidase activity|
|immune response-activating cell surface receptor signaling pathway|
|regulation of protein complex assembly|
|regulation of innate immune response|
|negative regulation of hydrolase activity|
|positive regulation of defense response|
|wound healing|
|immune response-regulating cell surface receptor signaling pathway|
|protein heterodimerization activity|
|regulation of body fluid levels|
|cellular response to growth factor stimulus|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|regulation of response to biotic stimulus|
|heart development|
|response to growth factor|
|regulation of hormone levels|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|immune response-activating signal transduction|
|response to wounding|
|positive regulation of kinase activity|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|hematopoietic or lymphoid organ development|
|activation of immune response|
|immune system development|
|positive regulation of transferase activity|
|negative regulation of cell population proliferation|
|negative regulation of cellular component organization|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|cellular chemical homeostasis|
|regulation of MAPK cascade|
|regulation of defense response|
|regulation of multi-organism process|
|head development|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|positive regulation of immune response|
|circulatory system development|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|regulation of cell motility|
|apoptotic process|
|ion transmembrane transport|
|regulation of cellular component biogenesis|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|Golgi apparatus|
|regulation of cellular component movement|
|negative regulation of cell death|
|secretion by cell|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|cell activation|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|chemical homeostasis|
|cell-cell signaling|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|response to abiotic stimulus|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|transmembrane transport|
|phosphorylation|
|negative regulation of cell communication|
|negative regulation of signaling|
|ion transport|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|protein transport|
|peptide transport|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|amide transport|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|nitrogen compound transport|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|-2.85|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-2.57|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-2.54|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-2.47|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.26|
|[[:results:exp443|SNS-032 15μM R08 exp443]]|-1.97|
|[[:results:exp149|SB203580 25μM R03 exp149]]|-1.87|
|[[:results:exp340|BN82002 4μM R07 exp340]]|-1.81|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|-1.8|
|[[:results:exp360|Genistein 15μM R07 exp360]]|-1.79|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|-1.78|
|[[:results:exp432|YM155 0.001μM R08 exp432]]|1.85|
|[[:results:exp248|UM0131023 0.05μM R05 exp248]]|1.95|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|2.1|
|[[:results:exp538|ZLN024 50μM R08 exp538]]|2.39|
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|2.43|
|[[:results:exp447|Amiloride 100μM R08 exp447]]|2.93|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|5.73|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:n:nras|NRAS]]|0.594|
|[[:human genes:s:shoc2|SHOC2]]|0.517|
|[[:human genes:m:mapk1|MAPK1]]|0.461|
|[[:human genes:b:braf|BRAF]]|0.434|
|[[:human genes:s:scrib|SCRIB]]|0.405|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 7/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|1/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|1/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 5725
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.6 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RAF1 Expression in NALM6 Cells: 7.6'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>