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General Information
Symbol
Dmel\Raf
Species
D. melanogaster
Name
Raf oncogene
Annotation Symbol
CG2845
Feature Type
FlyBase ID
FBgn0003079
Gene Model Status
Stock Availability
Enzyme Name (EC)
Mitogen-activated protein kinase kinase kinase (2.7.11.25)
Gene Snapshot
Raf oncogene (Raf) encodes a serine-threonine protein kinase that acts downstream of the product of ras. It activates the MEK/ERK pathway to regulate cell proliferation, differentiation and survival downstream of receptor tyrosine kinases such as those encoded by tor, Egfr, and sev. [Date last reviewed: 2019-03-14]
Also Known As

D-raf, Draf, phl, pole hole, l(1)ph

Key Links
Genomic Location
Cytogenetic map
Sequence location
X:2,295,466..2,343,870 [+]
Recombination map

1-0.9

RefSeq locus
NC_004354 REGION:2295466..2343870
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Ontology (GO) Annotations (45 terms)
Molecular Function (6 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR000719, InterPro:IPR017441
(assigned by InterPro )
inferred from biological aspect of ancestor with PANTHER:PTN001908418
(assigned by GO_Central )
Biological Process (37 terms)
Terms Based on Experimental Evidence (37 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:hop; FB:FBgn0004864
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with UniProtKB:P51023
(assigned by UniProt )
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:Ras85D; FB:FBgn0003205
inferred from genetic interaction with FLYBASE:csw; FB:FBgn0000382, FLYBASE:sev; FB:FBgn0003366
inferred from high throughput genetic interaction with FLYBASE:Ras85D; FB:FBgn0003205
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:Ras85D; FB:FBgn0003205
inferred from genetic interaction with FLYBASE:csw; FB:FBgn0000382, FLYBASE:sev; FB:FBgn0003366
inferred from mutant phenotype
Terms Based on Predictions or Assertions (0 terms)
Cellular Component (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from sequence or structural similarity with HGNC:9829
inferred from sequence or structural similarity with HGNC:9829
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. (P11346)
Catalytic Activity (EC)
Experimental Evidence
ATP + a protein = ADP + a phosphoprotein (2.7.11.25)
Predictions / Assertions
-
Summaries
Pathway (FlyBase)
Torso Signaling Pathway Core Components -
The formation of Drosophila embryonic termini is controlled by the localized activation of Torso (tor) receptor tyrosine kinase. The Torso signaling pathway acts via the canonical Ras/Raf/MAP kinase cascade. (Adapted from FBrf0157176.)
Sevenless Signaling Pathway Core Components -
The specification of the R7 photoreceptor cell in each ommatidium of the developing Drosophila eye is dependent on activation of Sevenless receptor tyrosine kinase, which acts via the canonical Ras/Raf/MAP kinase cascade to promote the expression of lz and pros. sev, expressed in presumptive R7 cells, is activated by binding to Bride of Sevenless (boss), a seven-transmembrane protein expressed in R8 cells. (Adapted from FBrf0127283 and FBrf0221727).
EGFR Signaling Pathway Core Components -
The Epidermal Growth Factor Receptor (EGFR) signaling pathway is used multiple times during development (FBrf0190321). It is activated by the binding of a secreted ligand to the receptor tyrosine kinase Egfr and acts via the canonical Ras/Raf/MAP kinase (ERK) cascade. (Adapted from FBrf0190321 and FBrf0221727).
FGFR Core Components -
Fibroblast Growth Factor Receptor (FGFR) signaling pathway is initiated by the binding of secreted FGFs - bnl or ths/pyr to receptor tyrosine kinases btl or htl, respectively, to initiate signaling primarily via the canonical Ras/Raf/MAP kinase (ERK) cascade. (Adapted from FBrf0221038).
Pvr Signaling Pathway Core Components -
PDGF/VEGF (Platelet-Derived Growth Factor/Vascular Endothelial Growth Factor)-receptor related (Pvr) encodes a receptor tyrosine kinase activated by the binding of PDGF- and VEGF-related factors (Pvf1,Pvf2 or Pvf3). Pvr has been shown to activate the canonical Ras/Raf/MAP kinase (ERK) cascade, the PI3K kinase pathway, TORC1 (FBrf0222697), Rho family small GTPases (FBrf0221764, FBrf0180198) and the JNK cascade (FBrf0180198), in a context-dependent manner. (Adapted from FBrf0222697 and FBrf0221727).
Gene Group (FlyBase)
NON-RECEPTOR TLK KINASES -
Non-receptor tyrosine kinase-like (TKL) kinases are a diverse group of intracellular serine-threonine protein kinases with sequence similarity to tyrosine kinases (TK) but lacking TK-specific motifs.
Protein Function (UniProtKB)
Serine/threonine kinase required in the early embryo for the formation of terminal structure (PubMed:3135183, PubMed:8423783). Also required during the proliferation of imaginal cells (PubMed:3135183). May act downstream of Ras85D in the tor signal transduction pathway (PubMed:8423783). During larval development, mediates Ptth/tor signaling leading to the production of ecdysone, a hormone required for the initiation of metamorphosis (PubMed:19965758).
(UniProt, P11346)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
phl: pole hole
The wild-type allele of phl seems to be involved in the setting up of positional values in embryos and also in the proliferation of diploid cells in imaginal disks (Ambrosio, Perrimon, and Mahowald, 1988). phl mutants are recessive early-pupal lethals, which display very small imaginal disks. Embryos derived from germ-line clones and lacking phl+ activity show the "torso" or "pole hole" phenotype; structures at the anterior and the posterior end (spiracles, anal tufts, and the entire eighth abdominal segment) fail to develop (Perrimon et al., 1984; Ambrosia, Mahowald, and Perrimon, 1988). The fate map of the blastoderm is shifted posteriorly and fewer segments with more cells result. A partial rescue of these mutants has been obtained with phl+ sperm (Ambrosio, Engstrom, and Mahowald); all structures posterior to abdominal segment seven are missing (Perrimon and Mahowald, 1986).
Summary (Interactive Fly)

serine/threonine-protein kinase - an effector of Ras - directs the RAF/MEK/ERK pathway to regulate cell proliferation, differentiation and survival downstream of receptor tyrosine kinases such as Torso, Epidermal growth factor receptor, and Sevenless.

Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\Raf for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model

Gene model reviewed during 5.51

Gene model reviewed during 5.46

Gene model reviewed during 5.53

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0070401
3247
739
FBtr0344007
4247
739
Additional Transcript Data and Comments
Reported size (kB)

3.2 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0070385
83.7
739
8.89
FBpp0310458
83.7
739
8.89
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

739 aa isoforms: Raf-PA, Raf-PE
Additional Polypeptide Data and Comments
Reported size (kDa)

782 (aa); 89 (kD predicted)

781 (aa); 90 (kD observed)

Comments
External Data
Subunit Structure (UniProtKB)

Interacts with Dsor1/MEK1 and ksr; Dsor1 binding to ksr probably promotes ksr and Raf dimerization and ksr-mediated Raf transactivation.

(UniProt, P11346)
Post Translational Modification

Extensively phosphorylated 1 to 2 hours after egg laying.

(UniProt, P11346)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Raf using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

phl transcripts are ubiquitously distributed throughout the oocyte and embryo and are not localized to the termini. phl transcripts are expressed throughout development.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

phl protein is detected in lysates from embryos. Levels are highest in 0-1 hr embryos and decrease thereafter. A shift in mobility of phl protein occurs at ~1-2 hrs which is due to phosphorylation of the protein.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Raf in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 1-3
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 11-12
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 58 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 44 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Raf
Transgenic constructs containing regulatory region of Raf
Deletions and Duplications ( 46 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
bract | ectopic & adult external prothorax, with Scer\GAL4hs.PB
bract | ectopic & arista, with Scer\GAL4hs.PB
bract | ectopic & costal vein, with Scer\GAL4hs.PB
bract | ectopic & gena, with Scer\GAL4hs.PB
bract | ectopic & haltere, with Scer\GAL4hs.PB
bract | ectopic & mesothoracic tergum, with Scer\GAL4hs.PB
bract | ectopic & wing | dorsal, with Scer\GAL4hs.PB
bract | ectopic & wing hinge | dorsal, with Scer\GAL4hs.PB
macrochaeta & mesothoracic tergum, with Scer\GAL4179b
mesothoracic tergum & macrochaeta | ectopic, with Scer\GAL4sca-C253
Orthologs
Human Orthologs (via DIOPT v8.0)
Homo sapiens (Human) (19)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
2  
12 of 15
No
Yes
11 of 15
No
Yes
 
5  
2 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Model Organism Orthologs (via DIOPT v8.0)
Mus musculus (laboratory mouse) (17)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
15 of 15
Yes
Yes
12 of 15
No
Yes
10 of 15
No
Yes
2 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Rattus norvegicus (Norway rat) (17)
11 of 13
Yes
Yes
9 of 13
No
Yes
9 of 13
No
Yes
2 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (12)
9 of 12
Yes
Yes
6 of 12
No
Yes
2 of 12
No
Yes
2 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
Yes
Danio rerio (Zebrafish) (22)
14 of 15
Yes
Yes
11 of 15
No
Yes
10 of 15
No
Yes
5 of 15
No
Yes
2 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (6)
9 of 15
Yes
Yes
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (30)
2 of 9
Yes
Yes
2 of 9
Yes
Yes
2 of 9
Yes
Yes
2 of 9
Yes
Yes
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
1 of 9
No
Yes
1 of 9
No
Yes
6  
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
1 of 9
No
No
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 15
Yes
No
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Ortholog(s) in Drosophila Species (via OrthoDB v9.1) ( EOG091903YM )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091501X3 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W0210 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X01YF )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Tetranychus urticae
Two-spotted spider mite
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G09SB )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v8.0)
Drosophila melanogaster (Fruit fly) (11)
2 of 10
2 of 10
2 of 10
2 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Model Summary Ribbon
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 3 )
Potential Models Based on Orthology ( 7 )
Modifiers Based on Experimental Evidence ( 4 )
Disease Associations of Human Orthologs (via DIOPT v8.0 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Dmel gene
Ortholog showing functional complementation
Supporting References
Interactions
Summary of Physical Interactions
esyN Network Diagram
Show neighbor-neighbor interactions:
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Interactions Browser

Please see the Physical Interaction reports below for full details
protein-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
suppressible
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
suppressible
suppressible
External Data
Subunit Structure (UniProtKB)
Interacts with Dsor1/MEK1 and ksr; Dsor1 binding to ksr probably promotes ksr and Raf dimerization and ksr-mediated Raf transactivation.
(UniProt, P11346 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Signaling Pathways (FlyBase)
Torso Signaling Pathway Core Components -
The formation of Drosophila embryonic termini is controlled by the localized activation of Torso (tor) receptor tyrosine kinase. The Torso signaling pathway acts via the canonical Ras/Raf/MAP kinase cascade. (Adapted from FBrf0157176.)
Sevenless Signaling Pathway Core Components -
The specification of the R7 photoreceptor cell in each ommatidium of the developing Drosophila eye is dependent on activation of Sevenless receptor tyrosine kinase, which acts via the canonical Ras/Raf/MAP kinase cascade to promote the expression of lz and pros. sev, expressed in presumptive R7 cells, is activated by binding to Bride of Sevenless (boss), a seven-transmembrane protein expressed in R8 cells. (Adapted from FBrf0127283 and FBrf0221727).
EGFR Signaling Pathway Core Components -
The Epidermal Growth Factor Receptor (EGFR) signaling pathway is used multiple times during development (FBrf0190321). It is activated by the binding of a secreted ligand to the receptor tyrosine kinase Egfr and acts via the canonical Ras/Raf/MAP kinase (ERK) cascade. (Adapted from FBrf0190321 and FBrf0221727).
FGFR Core Components -
Fibroblast Growth Factor Receptor (FGFR) signaling pathway is initiated by the binding of secreted FGFs - bnl or ths/pyr to receptor tyrosine kinases btl or htl, respectively, to initiate signaling primarily via the canonical Ras/Raf/MAP kinase (ERK) cascade. (Adapted from FBrf0221038).
Pvr Signaling Pathway Core Components -
PDGF/VEGF (Platelet-Derived Growth Factor/Vascular Endothelial Growth Factor)-receptor related (Pvr) encodes a receptor tyrosine kinase activated by the binding of PDGF- and VEGF-related factors (Pvf1,Pvf2 or Pvf3). Pvr has been shown to activate the canonical Ras/Raf/MAP kinase (ERK) cascade, the PI3K kinase pathway, TORC1 (FBrf0222697), Rho family small GTPases (FBrf0221764, FBrf0180198) and the JNK cascade (FBrf0180198), in a context-dependent manner. (Adapted from FBrf0222697 and FBrf0221727).
Metabolic Pathways
External Data
Genomic Location and Detailed Mapping Data
Chromosome (arm)
X
Recombination map

1-0.9

Cytogenetic map
Sequence location
X:2,295,466..2,343,870 [+]
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
3A1-3A1
Limits computationally determined from genome sequence between P{EP}EP1606 and P{EP}EP1605
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
3A-3A
(determined by in situ hybridisation)
2F6-2F6
(determined by in situ hybridisation)
2F6-3A1
(determined by in situ hybridisation)
2F5-2F6
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (37)
Genomic Clones (33)
cDNA Clones (54)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Laboratory Generated Antibodies
 

polyclonal

Commercially Available Antibodies
 
Other Information
Relationship to Other Genes
Source for database identify of

Source for identity of: phl CG2845

Source for identity of: Raf phl

Source for database merge of
Additional comments

Renamed from 'phl' to 'Raf' to reflect overwhelmingly preferred usage in the literature.

Other Comments

dsRNA made from templates generated with primers directed against this gene.

dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.

A basal level of phl activity is required for the accumulation of circulating blood cells, while high level activity of phl is required for the generation of differentiated lamellocytes in larvae. phl acts downstream of hop during differentiation of lamellocytes in larvae.

phl is required in somatic cells that surround germ cells.

The C-terminal portion of the cnk protein regulates phl, a component of rl (MAPK) signalling while the N-terminal portion of cnk is involved in a rl-independent pathway.

The MAPK cascade is required for Ras85D mitogenic response, loss of function mutations in phl, Dsor1, rl and ksr dominantly suppress hyperplastic growth, as do mutations in the Ras85D effector loop that disrupt the Ras85D-phl interaction.

In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.

The role of Ras85D in phl activation is not limited to the translocation of phl to the membrane through a Ras85D-phl association. Ras85D is essential for the activation of an additional factor which in turn activates phl.

Genetic studies suggest that 14-3-3ε functions in multiple receptor tyrosine kinase pathways, acting downstream or parallel to phl, but upstream of aop and phyl, two nuclear factors involved in Ras85D signalling.

Genetic studies indicate that 14-3-3ζ acts downstream of Ras85D and upstream of phl in the developing eye disc.

Shows no genetic interaction with sdk.

Endogenous mutant forms of phl may compete with wild-type phl for a positive factor required for its activation and/or membrane association or block access to it substrate(s) thereby affecting rescue of the tor pathway.

Two sequences homologous to DRE (DNA replication-related element) in the 5' flanking region of the phl gene are identified and transcriptional activity is confirmed through gel mobility shift assays, transient Ecol\CAT assays and spatial expression of Ecol\lacZ in transgenic larval tissues. phl is another target of zen protein in cultured cells.

Wild-type and mutant forms of Hsp83 bind to activated phl but the mutant Hsp83 protein causes a reduction in the kinase activity of phl. Results indicate Hsp83 is essential for phl function in vivo.

The csw SH2-containing tyrosine phosphatase is required during signalling by sev, Ras85D and phl.

In vitro studies reveal amino acid S743 is essential for phl function in embryos. Altered forms of phl have distinct activity profiles indicating that each structural modification differentially affects the regulation and/or propagation of the tor signal by the mutant phl proteins.

phl Ser/Thr kinase activity is essential for its role in tor signal transduction.

Studies of interaction between argos and members of the Ras/MAPK pathway demonstrate the argos gene product is a negative regulator of signal transduction that acts upstream of the Ras/MAPK cascade.

Immunoprecipitation experiments reveals the physical association between the phl and ksr products in Drosophila embryos.

mts positively regulates R7 differentiation induced by activated phl.

The membrane targetted phl kinase generates a signal that directs terminal development.

Genetic data suggest phyl acts downstream of Ras85D, phl and aop to promote neuronal differentiation in R1, R6 and R7.

phl can be activated by tor in the complete absence of Ras85D, phl can be activated by RPTK in a Ras-independent pathway.

phl can be activated by tor in the complete absence of Ras85D function.

A screen to identify mutations affecting the Ras85D signalling pathway identified alleles of phl, Dsor1, rl, aop, βggt-I, mts, ksr and phyl.

Synaptic current and modulation of K+ current triggered by Pacap38 are mediated by coactivation of the Ras/Raf (Ras85D/phl) and rut cyclase pathways.

An allele of Hsp83 was isolated in a screen for suppressors of the rough eye phenotype caused by an activated phl kinase.

Scer\GAL4-UAS system has been used to demonstrate that activating phl in the follicle cells is sufficient to dorsalise the egg suggesting that phl is required in the follicle cells, rather than in the oocyte, to specify dorsoventral polarity. Mutant combinations of phl and Egfr demonstrates that phl acts downstream of Egfr.

Hsap\RAF1 and phl are functionally similar in that either can induce ventral follicle cells to assume a dorsal fate.

Analysis of a temperature sensitive phl mutation demonstrates phl is needed during most of the developmental stages.

Dsor1 acts downstream of phl in the DER pathway.

phl gene product transduces the signal generated by the activation of the tor receptor.

Clonal analysis shows that mutations that alter conserved residues in the phl product known to be necessary for kinase activity are associated with a null phenotype, demonstrating that phl activity is necessary for its role in torso signalling. Weaker alleles show phenotype similar to corkscrew maternal effect phenotype. Two mutations affecting late phl functions imply a novel role for phl in cell fate establishment in the eye.

Germline clone analysis with an artificial bcd responder gene (three bcd consensus binding sites driving Ecol\lacZ) indicates that the bcd responder is not efficiently repressed in phl mutants, and that phl may be involved in the kinase pathway mediating inhibition of bcd-dependent activation.

Biochemical analysis of the signal transduction pathway determining terminal structure development.

Dsor1 and phl both play a role in the determination of the rate of proliferation.

The phl serine/threonine kinase plays a crucial role in the R7 pathway: the response to sev gene product activity is dependent on phl function, and a constitutively activated phl protein can induce R7 cell development in the absence of sev function. Genetic evidence suggests that phl acts downstream of Ras85D and upstream of sina in this signal transduction pathway.

csw and phl acts in concert to regulate tll expression.

The maternal terminal system is necessary to activate tll expression in the terminal caps.

Comparison of CpG distribution in the coding region of 121 genes from six species supports the mCpG mutational hotspot explanation of CpG suppression in methylated species at position II-III and III-I.

The maternal and embryonic requirements of phl have been analysed. phl is a member of the terminal gene class.

phl is zygotically expressed and encodes a potential Ser/Thr kinase. phl acts downstream of tor.

Mutant analysis suggests that phl is required for the normal rate of cell proliferation. Clonal analysis reveals that the maternal phl gene activity is necessary for embryonic development.

phl is essential for continued cell proliferation of diploid cells in the larva.

The wild-type allele of phl seems to be involved in the setting up of positional values in embryos and also in the proliferation of diploid cells in imaginal discs (Ambrosio, Mahowald and Perrimon, 1989a). phl mutants are recessive early-pupal lethals, which display very small imaginal discs. Embryos derived from germ-line clones and lacking phl+ activity show the 'torso' or 'pole hole' phenotype; structures at the anterior and the posterior end (spiracles, anal tufts and the entire eighth abdominal segment) fail to develop (Perrimon, Engstrom and Mahowald, 1984a; Perrimon, Engstrom and Mahowald, 1984b; Ambrosio, Mahowald and Perrimon, 1989a). The fate map of the blastoderm is shifted posteriorly and fewer segments with more cells result. A partial rescue of these mutants has been obtained with phl+ sperm (Ambrosio, Engstrom and Mahowald); all structures posterior to abdominal segment seven are missing (Perrimon and Mahowald, 1986).

Origin and Etymology
Discoverer
Etymology
Identification
External Crossreferences and Linkouts ( 115 )
Sequence Crossreferences
NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
Other crossreferences
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
KEGG Genes - Molecular building blocks of life in the genomic space.
modMine - A data warehouse for the modENCODE project
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Linkouts
BioGRID - A database of protein and genetic interactions.
DPiM - Drosophila Protein interaction map
DroID - A comprehensive database of gene and protein interactions.
DRSC - Results frm RNAi screens
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
FlyMine - An integrated database for Drosophila genomics
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Synonyms and Secondary IDs (44)
Reported As
Symbol Synonym
Raf
(Graves et al., 2020, Kushnir et al., 2020, Noyes et al., 2020, Vega-Cuesta et al., 2020, Xu et al., 2020, Chai et al., 2019, Fenckova et al., 2019, Khezri and Rusten, 2019, Meltzer et al., 2019, Moreno et al., 2019, Pfeifle et al., 2019, Singh et al., 2019, Song et al., 2019, Das and Cagan, 2018, Gene Disruption Project members, 2018-, Inoue et al., 2018, Lee et al., 2018, Sriskanthadevan-Pirahas et al., 2018, Sriskanthadevan-Pirahas et al., 2018, Houtz et al., 2017, Lusk et al., 2017, Skeath et al., 2017, Transgenic RNAi Project members, 2017-, Wolfstetter et al., 2017, Xiang et al., 2017, Young and Marcotte, 2017, Clandinin and Owens, 2016-, Ma et al., 2016, Malartre, 2016, Niwa and Niwa, 2016, Snee et al., 2016, Bieli et al., 2015, Grillo-Hill et al., 2015, Yu et al., 2015, Iordanou et al., 2014, Macagno et al., 2014, Salazar-Jaramillo et al., 2014, Khoo et al., 2013, Mbodj et al., 2013, Read et al., 2013, Sato et al., 2013, Sidor et al., 2013, Wang et al., 2013, Yu et al., 2013, Foronda et al., 2012, Yang and Terman, 2012, Zhai et al., 2012, Zoller and Schulz, 2012, Bangi et al., 2011, Friedman et al., 2011, Friedman et al., 2011, Galindo et al., 2011, Jiang et al., 2011, Salamanca et al., 2011, Zhang et al., 2011, Aron et al., 2010, Bhuin and Roy, 2010, Buchon et al., 2010, Freeman et al., 2010, Herr et al., 2010, Roignant and Treisman, 2010, Tipping et al., 2010, Yamashita et al., 2010, Yan et al., 2010, Zeng et al., 2010, Almudi et al., 2009, Jeon and Zinn, 2009, Jiang and Edgar, 2009, Moressis et al., 2009, Rajakulendran et al., 2009, Rewitz et al., 2009, Sims et al., 2009, Patel and Jacobs, 2008, Xia et al., 2008, Bianco et al., 2007, de Navascués and Modolell, 2007, Dominguez-Gimenez et al., 2007, Khoo et al., 2007, Lavery and Stern, 2007, Lavery et al., 2007, Letizia et al., 2007, Mogila et al., 2007, O'Keefe et al., 2007, Tong et al., 2007, Caldwell et al., 2006, Cela and Llimargas, 2006, Edgar, 2006, Guichard et al., 2006, Kim et al., 2006, Pallavi et al., 2006, Uhlirova and Bohmann, 2006, Walker et al., 2006, Caldwell et al., 2005, Caldwell et al., 2005, Hariharan, 2005, Shingleton, 2005, Sotillos and De Celis, 2005, Uhlirova et al., 2005, Wilson et al., 2005, Yamashita et al., 2005, Gallio et al., 2004, Kim et al., 2004, Meister, 2004, Patel et al., 2004, Benton and St. Johnston, 2003, Brumby and Richardson, 2003, Douziech et al., 2003, Ghabrial et al., 2003, Hipfner and Cohen, 2003, Pallavi and Shashidhara, 2003, Rawlins et al., 2003, Shilo, 2003, Uv et al., 2003, Amiri and Stein, 2002, Claeys et al., 2002, Gorski and Marra, 2002, Koh et al., 2002, Peri et al., 2002, Prober and Edgar, 2002, Richardson and Kumar, 2002, Roy and Therrien, 2002, Baker, 2001, Baker, 2001, Bilder, 2001, del Alamo and Diaz-Benjumea, 2001, Williams et al., 2001, Baonza et al., 2000, Dobens and Raftery, 2000, Gibson et al., 2000, Rebay et al., 2000, Sotillos and Campuzano, 2000, Therrien et al., 2000, Zhang and Lu, 2000, Casci et al., 1999, Chen et al., 1999, Hipfner and Cohen, 1999, Karim and Rubin, 1999, Li and Perrimon, 1999, Martin-Blanco et al., 1999, McNeill and Downward, 1999, Prokop, 1999, Reich et al., 1999, Ruden et al., 1999, Stronach and Perrimon, 1999, Therrien et al., 1999, Tran et al., 1999, Zhang et al., 1999, Perrimon and Duffy, 1998, Rommel and Hafen, 1998, Freeman, 1997, Stemerdink and Jacobs, 1997, Tang et al., 1997, Allard et al., 1996, Allard et al., 1996, Badenhorst et al., 1996, Karim et al., 1996, Ray and Schupbach, 1996, Downward, 1995, Lee and Montell, 1995, van der Straten et al., 1995, Brown and Hartley, 1994, Wilson, 1994, Cagan, 1993, Hafen et al., 1993, Mlodzik et al., 1993, Dickson et al., 1992)
l(1)polehole/draf
l(1)raf
raf
(Sheng and Du, 2020, Pascual et al., 2017, Selcho et al., 2017, Li et al., 2015, Ashton-Beaucage et al., 2014, Baril et al., 2014, Ukken et al., 2014, Kingsolver et al., 2013, Kim et al., 2012, Rodrigues et al., 2012, Zoller and Schulz, 2012, Jiang et al., 2011, Ashton-Beaucage et al., 2010, Liu et al., 2010, Rendina et al., 2010, Hou et al., 2008, Legent et al., 2008, Yoneda et al., 2007, Roignant et al., 2006, Uhlirova and Bohmann, 2006, Ayala et al., 2005, Jordan et al., 2005, Vidal et al., 2005, Xie et al., 2005, Zhu et al., 2005, Gilboa and Lehmann, 2004, Kim and Bar-Sagi, 2004, Lin et al., 2004, Bach et al., 2003, Escudero et al., 2003, Wallenfang and DiNardo, 2003, Yang and Baker, 2003, Bach and Perrimon, 2002, Benton et al., 2002, Cavodeassi et al., 2002, del Alamo et al., 2002, Lin, 2002, Terry et al., 2002, Zhao and Garbers, 2002, Zhu et al., 2002, Gupta and Schupbach, 2001, Kimbrell and Beutler, 2001, Spradling et al., 2001, Tang et al., 2001, Wilson et al., 2001, Wittwer et al., 2001, Yang and Baker, 2001, Bui et al., 2000, Fanto, 2000, Fanto et al., 2000, Johnson Hamlet and Perkins, 2000, Kumar and Moses, 2000, Tran et al., 2000, Bergmann et al., 1999, Brenner et al., 1999, Burden and Osheroff, 1999, Greenwood and Struhl, 1999, Staehling-Hampton et al., 1999, Superti-Furga, 1999, Bergmann et al., 1998, Bergmann et al., 1998, Hayashi et al., 1998, Sternberg and Alberola-Ila, 1998, Guo et al., 1997, Kockel et al., 1997, Luo and Dearolf, 1997, Matsuo et al., 1997, Nguyen et al., 1997, Nishida, 1997.11.7, Posey et al., 1997, Scholz et al., 1997, Scholz et al., 1997, Huang and Fischer-Vize, 1996, Klämbt et al., 1996, Peverali et al., 1996, Begemann et al., 1995, Chang et al., 1995, Dickson et al., 1995, Morisato and Anderson, 1995, Schnorr and Berg, 1995, Schweitzer et al., 1995, Zhong, 1995, Zhong, 1995, Brunner et al., 1994, Diaz-Benjumea and Hafen, 1994, Freeman, 1994, Marshall, 1994, Schupbach and Roth, 1994, Cohen, 1993, Dickson and Hafen, 1993, Hayashi et al., 1993, Melnick, 1993.6.15, Perkins et al., 1992, Schorderet and Gartler, 1992, Hartley and White, 1990)
Secondary FlyBase IDs
  • FBgn0040149
Datasets (1)
Study focus (1)
Experimental Role
Project
Project Type
Title
  • bait_protein
Interaction map generated by purification of receptor tyrosine kinase pathway factors, with identification of copurifying proteins by mass spectrometry.
References (646)