FlyBase Gene Report: Dmel\Nf1

General Information

Symbol

Dmel\Nf1

Species

D. melanogaster

Name

Neurofibromin 1

Annotation Symbol

CG8318

Feature Type

protein_coding_gene

FlyBase ID

FBgn0015269

Gene Model Status

Current

Stock Availability

9 publicly available

Gene Snapshot

Neurofibromin 1 (Nf1) encodes a protein that functions as a GTPase activating protein for the products of Ras85D and Ras64B in the larval and adult nervous system. Loss of Nf1 results in excess Ras-Raf-ERK signaling and to a non-cell-autonomous cAMP/PKA signaling defect. The product of Nf1 contributes to postembryonic growth, learning/memory, and circadian rhythm. [Date last reviewed: 2019-03-14]

Other Summaries

Alliance
Auto summary
Gene Group
Interactive Fly

Also Known As

neurofibromin, Neurofibromatosis-1, neurofibromatosis type 1, dNf1, NF-1

Key Links

Genomic Location

Cytogenetic map

96F9-96F9

Sequence location

3R:25,983,013..25,995,737 [+]

Recombination map

3-89

RefSeq locus

NT_033777 REGION:25983013..25995737

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse GBrowse

Help me choose

Other Genome Views

The following external sites may use different assemblies or annotations than FlyBase.

Function

GO Summary Ribbons

Gene Ontology (GO) Annotations (19 terms)

Molecular Function (1 term)

Terms Based on Experimental Evidence (1 term)

CV Term

Evidence

References

enables GTPase activator activity

inferred from direct assay

(The et al., 1997)

Terms Based on Predictions or Assertions (0 terms)

Biological Process (18 terms)

Terms Based on Experimental Evidence (17 terms)

CV Term

Evidence

References

involved_in adult locomotory behavior

inferred from mutant phenotype

(van der Voet et al., 2016)

involved_in cAMP-mediated signaling

inferred from mutant phenotype

(The et al., 1997)

involved_in determination of adult lifespan

inferred from mutant phenotype

(Tong et al., 2007)

involved_in locomotor rhythm

inferred from mutant phenotype

(Williams et al., 2001)

involved_in long-term memory

inferred from mutant phenotype

(Buchanan and Davis, 2010)

involved_in negative regulation of synaptic growth at neuromuscular junction

inferred from mutant phenotype

(Tsai et al., 2012)

involved_in olfactory learning

inferred from mutant phenotype

(Buchanan and Davis, 2010, Guo et al., 2000)

involved_in perineurial glial growth

inferred from genetic interaction with FLYBASE:poe; FB:FBgn0011230

(Yager et al., 2001)

inferred from genetic interaction with FLYBASE:ine; FB:FBgn0011603

(Yager et al., 2001)

involved_in positive regulation of adenylate cyclase activity

inferred from mutant phenotype

(Guo et al., 1997)

involved_in positive regulation of multicellular organism growth

inferred from mutant phenotype

(Walker et al., 2006)

involved_in Ras protein signal transduction

inferred from genetic interaction with FLYBASE:Sos; FB:FBgn0001965

(Williams et al., 2001)

inferred from genetic interaction with FLYBASE:Ras85D; FB:FBgn0003205

(Williams et al., 2001)

involved_in regulation of circadian rhythm

inferred from mutant phenotype

(Bai et al., 2018)

inferred from genetic interaction with FLYBASE:Pdfr; FB:FBgn0260753

(Bai et al., 2018)

involved_in regulation of multicellular organism growth

inferred from mutant phenotype

(The et al., 1997)

involved_in regulation of Ras protein signal transduction

inferred from mutant phenotype

(Walker et al., 2006)

involved_in response to heat

inferred from mutant phenotype

(Tong et al., 2007)

involved_in response to oxidative stress

inferred from mutant phenotype

(Tong et al., 2007)

involved_in short-term memory

inferred from mutant phenotype

(Buchanan and Davis, 2010, Guo et al., 2000)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

involved_in regulation of GTPase activity

inferred from electronic annotation with InterPro:IPR001936

(assigned by InterPro )

(FlyBase Curators et al., 2004-)

Cellular Component (0 terms)

Terms Based on Experimental Evidence (0 terms)

Terms Based on Predictions or Assertions (0 terms)

Gene Group (FlyBase)

RAS-LIKE GTPASE ACTIVATING PROTEINS

Protein Family (UniProt)

Protein Signatures (InterPro)

Summaries

Gene Group (FlyBase)

RAS-LIKE GTPASE ACTIVATING PROTEINS -: Ras-like GTPase activating proteins are an evolutionary-related group of Ras GAPs that promote GTP hydrolysis by the Ras subfamily of the Ras GTPases. (Adapted from FBrf0229300).

Summary (Interactive Fly)

GAP-related domain protein functioning in the PKA pathway - critical to the biochemical processes underlying olfactory learning

Interactive Fly

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\Nf1 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_with_stop_codon_read_through ; SO:0000697

Stop-codon suppression (UGA) postulated; FBrf0216884.

Gene model reviewed during 5.44

Gene model reviewed during 5.47

Sequence Ontology: Class of Gene

gene_with_stop_codon_read_through

(Jungreis et al., 2011)

nuclear_gene

protein_coding_gene

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

Nf1-RB

FBtr0084952

NM_170253

8893

2802

Nf1-RC

FBtr0084953

NM_170252

8892

2746

Nf1-RD

FBtr0100113

NM_001014668

9737

2764

Nf1-RE

FBtr0330182

NM_001276049

9737

2793

Nf1-RF

FBtr0330183

NM_001276050

9647

2734

Additional Transcript Data and Comments

Reported size (kB)

9.750, 8.843 (compiled cDNA)

(The et al., 1997)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

RefSeq ID

GenBank

Nf1-PB

FBpp0084326

317.2

2802

6.86

NP_733132

AAF56543

Nf1-PC

FBpp0084327

311.1

2746

6.74

NP_733131

AAN14067

Nf1-PD

FBpp0100151

313.0

2764

6.80

NP_001014668

AAX52994

Nf1-PE

FBpp0303215

316.3

2793

6.96

NP_001262978

AGB96358

Nf1-PF

FBpp0303216

309.6

2734

6.76

NP_001262979

AGB96359

Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments

Reported size (kDa)

2802, 2764 (aa); 280 (kD observed)

(The et al., 1997)

Comments

External Data

Crossreferences

InterPro - A database of protein families, domains and functional sites

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Nf1 using the Feature Mapper tool.

External Data

Crossreferences

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Nf1_1

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

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

(The et al., 1997)

(The et al., 1997)

(Buchanan and Davis, 2010)

adult brain cell body rind

(Buchanan and Davis, 2010)

Additional Descriptive Data

Nf1 is expressed in most, if not all, cell body regions of the adult central brain. Expression is apparent in cell body regions surrounding the antennal lobes, protocerebrum, lateral horn and the mushroom body calyces.

(Buchanan and Davis, 2010)

Nf1 transcripts are widely expressed in low amounts.

(The et al., 1997)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

immunolocalization

Stage

Tissue/Position (including subcellular localization)

Reference

(The et al., 1997)

(The et al., 1997)

adult brain | restricted

(Gouzi et al., 2011)

calyx of adult mushroom body

(Gouzi et al., 2011)

cell body rind of adult mushroom body

(Gouzi et al., 2011)

protocerebral bridge

(Gouzi et al., 2011)

antennal lobe | faint | restricted

(Gouzi et al., 2011)

subesophageal ganglion

(Gouzi et al., 2011)

adult median bundle

(Gouzi et al., 2011)

third instar larval stage

embryonic/larval brain | restricted

(Gouzi et al., 2011)

ventral nerve cord

(Gouzi et al., 2011)

mushroom body calyx

(Gouzi et al., 2011)

embryonic/larval optic lobe

(Gouzi et al., 2011)

first instar larval stage -- third instar larval stage

neuron of embryonic/larval central nervous system

Comment: post-mitotic neurons

(Walker et al., 2006)

mass spectroscopy

Stage

Tissue/Position (including subcellular localization)

Reference

adult stage

adult head

• membrane

(Aradska et al., 2015)

Additional Descriptive Data

Nf1 protein is expressed throughout the third instar larval and adult brain. In the adult, labelling is stronger in the mushroom body calyx and cortex (dendrites and cell bodies of Kenyon cells, respectively), protocerebral bridge, subesophageal ganglion and median bundle. Expression of Nf1 protein in the protocerebral bridge and mushroom body calyx colocalises with that of Alk protein.

(Gouzi et al., 2011)

Nf1 protein is expressed in all post-mitotic neurons in the larval central nervous system, at all larval stages.

(Walker et al., 2006)

Nf1 protein is widely expressed in low amounts.

(The et al., 1997)

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\Nf1 in GBrowse 2

RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region

View exonic expression by developmental stage for Dmel\Nf1

View exonic expression by tissue for Dmel\Nf1

Bulk Downloads

RNA-Seq RPKM values for all genes

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

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0015269

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG8318-RB;CG8318-RB

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG8318

Flygut - An atlas of the Drosophila adult midgut

FBgn0015269

Images

FlyBase Wiki

Image Based Resources

Alleles, Insertions, and Transgenic Constructs

Classical and Insertion Alleles ( 12 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 34 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of Nf1

Transgenic constructs containing regulatory region of Nf1

Deletions and Duplications ( 2 )

Disrupted in

Df(3R)Espl3

(Williams et al., 2001)

Df(3R)Nf1^P1

(Cooper and Bray, 1999, Guo et al., 1997, The et al., 1997)

Phenotypes

For more details about a specific phenotype click on the relevant allele symbol.

Lethality

Allele

viable

viable, with Dcr-2^UAS.cDa, Scer\GAL4^elav.PLu

Nf1^GD13892

viable, with Scer\GAL4^Mef2.PR

Nf1^GD13892

viable, with Scer\GAL4^pnr-MD237

Nf1^GD13892

viable, with Scer\GAL4^tin.CΔ4

Nf1^GD13892

Sterility

Allele

fertile

Other Phenotypes

Allele

behavior defective

circadian rhythm defective | adult stage (with Nf1^P1)

Nf1^P2

circadian rhythm defective | adult stage (with Nf1^P2)

Nf1^P1

circadian rhythm defective | adult stage | RU486 conditional, with Scer\GAL4^GS.nSyb.PB

decreased cell size | adult stage

Nf1^E2

decreased fecundity, with Nf1^P1, Scer\GAL4^c305a

Nf1^UAS.cBa

decreased fecundity, with Nf1^UAS.cBa, Scer\GAL4^c305a

Nf1^P1

grooming behavior defective | adult stage

Nf1^P1

heat stress response defective

heat stress response defective (with Nf1^P1)

Nf1^P2

heat stress response defective (with Nf1^P2)

Nf1^P1

hyperactive, with Scer\GAL4^elav.PU

Nf1^KK101909

hyperactive (with Nf1^P1)

Nf1^P2

hyperactive (with Nf1^P2)

Nf1^P1

hyperactive | adult stage

Nf1^P1

hyperactive | adult stage, with Scer\GAL4^nSyb.PU

Nf1^KK101909

increased fecundity

Nf1^hs.PT

learning defective

learning defective | adult stage (with Nf1^E1)

Nf1^E2

learning defective | adult stage (with Nf1^E2)

Nf1^E1

learning defective | adult stage | dominant

Nf1^E2

locomotor rhythm defective

locomotor rhythm defective, with Scer\GAL4^elav.PU

Nf1^KK101909

locomotor rhythm defective (with Df(3R)Espl3)

locomotor rhythm defective (with Nf1^P1)

Nf1^P2

locomotor rhythm defective (with Nf1^P2)

Nf1^P1

locomotor rhythm defective | heat sensitive

locomotor rhythm defective | heat sensitive (with Nf1^P1)

Nf1^P2

locomotor rhythm defective | heat sensitive (with Nf1^P2)

Nf1^P1

long lived, with Scer\GAL4^arm.PS

Nf1^UAS.cTa

long lived, with Scer\GAL4^elav-C155

Nf1^UAS.cTa

long lived | heat sensitive

Nf1^hs.PT

memory defective

neuroanatomy defective | larval stage

Nf1^E2

neuroanatomy defective | larval stage, with Scer\GAL4^elav.PU

Nf1^A.UAS

neuroanatomy defective | larval stage (with Nf1^E1)

Nf1^E2

neuroanatomy defective | larval stage (with Nf1^E2)

Nf1^E1

neuroanatomy defective | third instar larval stage

Nf1^E2

neurophysiology defective | larval stage

Nf1^E2

neurophysiology defective | larval stage (with Nf1^E1)

Nf1^E2

neurophysiology defective | larval stage (with Nf1^E2)

Nf1^E1

oxidative stress response defective | heat sensitive

oxidative stress response defective | heat sensitive (with Nf1^P1)

Nf1^P2

oxidative stress response defective | heat sensitive (with Nf1^P2)

Nf1^P1

short lived

short lived (with Nf1^P1)

Nf1^P2

short lived (with Nf1^P2)

Nf1^P1

size defective

Nf1^unspecified

size defective | dominant | pupal stage

Nf1^E2

size defective | pupal stage (with Nf1^E1)

Nf1^E2

size defective | pupal stage (with Nf1^E2)

Nf1^E1

sleep defective, with Scer\GAL4^elav.PU

Nf1^KK101909

sleep defective (with Nf1^c00617)

Nf1^P2

sleep defective (with Nf1^P1)

Nf1^P2

sleep defective (with Nf1^P2)

sleep defective | adult stage

Nf1^P1

sleep defective | adult stage, with Scer\GAL4^nSyb.PU

Nf1^KK101909

small body

small body | larval stage

Nf1^E2

small body | male limited

Nf1^c00617

small body | pupal stage

small body | pupal stage (with Nf1^E1)

Nf1^P2

small body | pupal stage (with Nf1^E2)

Nf1^P2

small body | pupal stage (with Nf1^E3)

Nf1^P2

small body | pupal stage (with Nf1^E4)

Nf1^P2

small body | pupal stage (with Nf1^P1)

Nf1^P2

small body | pupal stage (with Nf1^P2)

small body | pupal stage | heat sensitive

Nf1^E4

wild-type

Nf1^hs.PT

Phenotype manifest in

Allele

CNS surface associated glial cell

Nf1^P2

eye photoreceptor cell

neuromuscular junction | larval stage

NMJ bouton | larval stage | supernumerary

Nf1^E2

NMJ bouton | larval stage | supernumerary, with Scer\GAL4^elav.PU

Nf1^A.UAS

NMJ bouton | larval stage | supernumerary (with Nf1^E1)

Nf1^E2

NMJ bouton | larval stage | supernumerary (with Nf1^E2)

Nf1^E1

NMJ bouton | supernumerary | third instar larval stage

Nf1^E2

pupa

pupa (with Nf1^E1)

Nf1^P2

pupa (with Nf1^E2)

Nf1^P2

pupa (with Nf1^E4)

Nf1^P2

pupa (with Nf1^P2)

wing

wing disc

Nf1^E1

Orthologs

Downloads

Download All DIOPT Orthologs

Download All OrthoDB Orthologs

Human Orthologs (via DIOPT v8.0)

Homo sapiens (Human) (5)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Hsap\NF1

13 of 15

Yes

Hsap\IQGAP2

1 of 15

Yes

Hsap\NEK2

1 of 15

Hsap\RASA2

1 of 15

Hsap\RASA3

1 of 15

Model Organism Orthologs (via DIOPT v8.0)

Mus musculus (laboratory mouse) (5)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Mmus\Nf1

12 of 15

Yes

Mmus\Iqgap2

1 of 15

Yes

Mmus\Nek2

1 of 15

Mmus\Rasa2

1 of 15

Mmus\Rasa3

1 of 15

Rattus norvegicus (Norway rat) (2)

Rnor\Nf1

10 of 13

Yes

Rnor\Nek2

1 of 13

Xenopus tropicalis (Western clawed frog) (3)

Xtro\nf1

8 of 12

Yes

Xtro\nek2

1 of 12

Xtro\rasa2

1 of 12

Danio rerio (Zebrafish) (6)

Drer\nf1b

14 of 15

Yes

Drer\nf1a

9 of 15

Yes

Drer\iqgap2

1 of 15

Yes

Drer\nek2

1 of 15

Drer\rasa2

1 of 15

Drer\rasa3

1 of 15

Caenorhabditis elegans (Nematode, roundworm) (1)

Cele\gap-1

1 of 15

Yes

Arabidopsis thaliana (thale-cress) (0)

No records found.

Saccharomyces cerevisiae (Brewer's yeast) (3)

Scer\IRA1

7 of 15

Yes

Scer\IRA2

6 of 15

Yes

Scer\BUD2

2 of 15

Schizosaccharomyces pombe (Fission yeast) (2)

Spom\gap1

2 of 12

Yes

Spom\rng2

1 of 12

Yes

Ortholog(s) in Drosophila Species (via OrthoDB v9.1) ( EOG0919003D )

Organism

Common Name

Gene

AAA Syntenic Ortholog

Multiple Dmel Genes in this Orthologous Group

Drosophila suzukii

Spotted wing Drosophila

Drosophila simulans

Drosophila sechellia

Drosophila sechellia

Drosophila erecta

Drosophila yakuba

Drosophila ananassae

Drosophila pseudoobscura pseudoobscura

Dpse\GA26413

Drosophila persimilis

Dper\GL21812

Drosophila willistoni

Dwil\GK12879

Drosophila virilis

Dvir\GJ23901

Drosophila mojavensis

Dmoj\GI24684

Drosophila grimshawi

Dgri\GH19449

Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG0915002A )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Musca domestica

House fly

Mdoa\17012072

Glossina morsitans

Tsetse fly

Gmor\GMOY006395

Lucilia cuprina

Australian sheep blowfly

Lcup\FF38_13015

Mayetiola destructor

Hessian fly

Mdes\Mdes005590

Aedes aegypti

Yellow fever mosquito

Aaeg\AAEL008371

Anopheles darlingi

American malaria mosquito

Adar\ADAC006000

Anopheles gambiae

Malaria mosquito

Agam\AGAP003140

Culex quinquefasciatus

Southern house mosquito

Cqui\CPIJ011774

Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W001O )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Bombyx mori

Silkmoth

Bmor\BGIBMGA011404

Bombyx mori

Silkmoth

Bmor\BGIBMGA011405

Danaus plexippus

Monarch butterfly

Dple\DPOGS200453-PA

Heliconius melpomene

Postman butterfly

Hmel\HMEL013071

Apis florea

Little honeybee

Aflo\2845884196

Apis mellifera

Western honey bee

Amel\GB46321

Bombus impatiens

Common eastern bumble bee

Bimp\BIMP24289

Bombus terrestris

Buff-tailed bumblebee

Bter\15208448

Linepithema humile

Argentine ant

Lhum\LH26233

Megachile rotundata

Alfalfa leafcutting bee

Mrot\MROTU:002674

Nasonia vitripennis

Parasitic wasp

Nvit\Nasvi2EG011800

Dendroctonus ponderosae

Mountain pine beetle

Dpod\YQE_02454

Dendroctonus ponderosae

Mountain pine beetle

Dpod\YQE_02453

Tribolium castaneum

Red flour beetle

Tcas\TC031561

Pediculus humanus

Human body louse

Phum\PHUM364110

Cimex lectularius

Bed bug

Clec\CLEC006242

Zootermopsis nevadensis

Nevada dampwood termite

Znev\Znev_07727

Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X001M )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Strigamia maritima

European centipede

Smar\SMAR009214

Stegodyphus mimosarum

African social velvet spider

Smim\KFM78370.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM60222.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM60221.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM78369.1

Tetranychus urticae

Two-spotted spider mite

Turt\tetur02g01260

Daphnia pulex

Water flea

Dpux\DAPPUDRAFT_307021

Daphnia pulex

Water flea

Dpux\DAPPUDRAFT_2283

Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G03FI )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Strongylocentrotus purpuratus

Purple sea urchin

Spur\SPU_013864gn

Strongylocentrotus purpuratus

Purple sea urchin

Spur\SPU_018040gn

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Nf1-2

Strongylocentrotus purpuratus

Purple sea urchin

Spur\SPU_014523gn

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Nf1

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000018975

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000017469

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000003511

Gallus gallus

Domestic chicken

Ggal\NF1

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v8.0)

Drosophila melanogaster (Fruit fly) (3)

Gene Symbol

Score

Source

Alignment

3 of 10

2 of 10

vap

2 of 10

Human Disease Associations

FlyBase Human Disease Model Reports

neurofibromatosis, type 1

Disease Model Summary Ribbon

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 7 )

Allele

Disease

Evidence

References

Nf1^JF01767

model of sleep disorder

CEA

(Bai et al., 2018)

Nf1^E1

model of neurofibromatosis

CEA

(Walker et al., 2006)

CEA with Nf1^E2

(Walker et al., 2006)

Nf1^E2

model of neurofibromatosis

CEA

(Walker et al., 2006)

CEA with Nf1^E1

(Walker et al., 2006)

Nf1^P1

model of sleep disorder

CEA with Nf1^P2

(Bai et al., 2018)

model of neurofibromatosis 1

CEA

(Guo et al., 2000, Guo et al., 1997)

Nf1^P2

model of sleep disorder

CEA with Nf1^P1

(Bai et al., 2018)

model of neurofibromatosis 1

CEA

(Guo et al., 2000, Guo et al., 1997)

Nf1^JF01866

model of sleep disorder

CEA

(Bai et al., 2018)

Nf1^KK101909

model of attention deficit hyperactivity disorder

CEA

(King et al., 2016, van der Voet et al., 2016)

model of sleep disorder

CEA

(King et al., 2016)

Potential Models Based on Orthology ( 3 )

Human Ortholog

Disease

Evidence

References

NF1; neurofibromin 1

model of neurofibromatosis-Noonan syndrome

IEA

(FlyBase, 2019-)

model of juvenile myelomonocytic leukemia

IEA

(FlyBase, 2019-)

model of neurofibromatosis 1

IEA

(FlyBase, 2019-)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Nf1^E2

model of neurofibromatosis

is ameliorated by Raf¹²

(Walker et al., 2006)

is ameliorated by rl¹

(Walker et al., 2006)

is ameliorated by Ras85D^unspecified

(Walker et al., 2006)

is ameliorated by vap^UAS.Tag:MYC

(Walker et al., 2006)

is ameliorated by jeb^weli

(Walker et al., 2013)

is ameliorated by car¹

(Walker et al., 2013)

is ameliorated by elav¹

(Walker et al., 2013)

is ameliorated by cnk^XE-385

(Walker et al., 2013)

is ameliorated by amx^f06362

(Walker et al., 2013)

is ameliorated by Rab9^{S26N.UASp.YFP}

(Walker et al., 2013)

is exacerbated by nAChRα6^DAS2

(Walker et al., 2013)

is ameliorated by dnc^KK108541

(Walker et al., 2013)

is ameliorated by car^Δ146

(Walker et al., 2013)

is ameliorated by Rab9^KK109041

(Walker et al., 2013)

is ameliorated by jeb^KK111857

(Walker et al., 2013)

is exacerbated by Cul3^gft2

(Walker et al., 2013)

is ameliorated by Dap160^Δ1

(Walker et al., 2013)

is ameliorated by Dap160^KK102297

(Walker et al., 2013)

is exacerbated by nAChRα6^KG05852

(Walker et al., 2013)

is exacerbated by Pka-C1^B3

(Walker et al., 2013)

is ameliorated by cnk^E-2083

(Walker et al., 2013)

is ameliorated by Dap160^Δ2

(Walker et al., 2013)

is NOT ameliorated by Ret^K805A.UAS

(Walker et al., 2013)

is ameliorated by dnc^ML

(Walker et al., 2013)

is ameliorated by NAAT1^KK112890

(Walker et al., 2013)

is exacerbated by Pka-C1^BG02142

(Walker et al., 2013)

is ameliorated by Mmus\Prkaca^act.2xUAS

(Walker et al., 2013)

is exacerbated by nAChRα6^DAS1

(Walker et al., 2013)

is ameliorated by Alk⁸

(Walker et al., 2013)

is ameliorated by dor⁸

(Walker et al., 2013)

is ameliorated by Dsor1^LH110

(Walker et al., 2013)

is ameliorated by amx^GD1168

(Walker et al., 2013)

is ameliorated by elav^G0031

(Walker et al., 2013)

is exacerbated by Pka-C1⁰⁶³⁵³

(Walker et al., 2013)

is ameliorated by HERC2^KK100181

(Walker et al., 2013)

is ameliorated by Mmus\Prkaca^act.3xUAS

(Walker et al., 2013)

is ameliorated by dnc¹

(Walker et al., 2013)

is ameliorated by CCKLR-17D1^KK108482

(Walker et al., 2013)

is ameliorated by dnc^M14

(Walker et al., 2013)

is ameliorated by Mmus\Prkaca^mC.UAS

(Walker et al., 2013)

is ameliorated by cnk^KK109209

(Walker et al., 2013)

is ameliorated by Mmus\Prkaca^act.4xUAS

(Walker et al., 2013)

is ameliorated by Alk⁹

(Walker et al., 2013, Gouzi et al., 2011)

is ameliorated by Dsor1^KK102276

(Walker et al., 2013)

is ameliorated by Alk^KK102942

(Walker et al., 2013)

is ameliorated by Hs3st-B^KK108793

(Walker et al., 2013)

is ameliorated by Dsor1^GD9123

(Walker et al., 2013)

is ameliorated by Alk¹

(Gouzi et al., 2011)

is ameliorated by Alk^{EC.UAS.Tag:MYC}

(Gouzi et al., 2011)

is ameliorated by Alk^GD42

(Gouzi et al., 2011)

Nf1^P1

model of neurofibromatosis 1

is ameliorated by Mmus\Prkaca^hs.PJ

(Guo et al., 2000)

Nf1^P2

model of neurofibromatosis 1

is ameliorated by Mmus\Prkaca^hs.PJ

(Guo et al., 2000)

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.

Homo sapiens (Human)

Gene name

Score

OMIM

OMIM Phenotype

DO term

Complementation?

Transgene?

NF1; neurofibromin 1

13 of 15

613113

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.

Interactions

Summary of Physical Interactions

esyN Network Diagram

Interactions Browser

View in Interactions Browser

Please see the Physical Interaction reports below for full details

protein-protein

Physical Interaction

Assay

References

Nf1 - Fak

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down

(Tsai et al., 2012)

Nf1 - Ras64B

gtpase assay, autoradiography

(Walker et al., 2006)

Nf1 - Ras85D

gtpase assay, autoradiography

(Walker et al., 2006)

RNA-protein

Physical Interaction

Assay

References

Nf1 - stau

anti bait coimmunoprecipitation, partial DNA sequence identification by hybridization

(Laver et al., 2013)

Summary of Genetic Interactions

esyN Network Diagram

esyN Network Key:

Suppression

Enhancement

View in Interactions Browser

Please look at the allele data for full details of the genetic interactions

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Nf1

suppressible

Alk

(Walker et al., 2013, Gouzi et al., 2011)

Nf1

suppressible

amx

(Walker et al., 2013)

Nf1

suppressible

car

(Walker et al., 2013)

Nf1

suppressible

CCKLR-17D1

(Walker et al., 2013)

Nf1

suppressible

cnk

(Walker et al., 2013)

Nf1

enhanceable

Cul3

(Walker et al., 2013)

Nf1

suppressible

Dap160

(Walker et al., 2013)

Nf1

suppressible

Dcr-2|NAAT1

(Walker et al., 2013)

Nf1

suppressible

dnc

(Walker et al., 2013, Williams et al., 2001)

Nf1

suppressible

dor

(Walker et al., 2013)

Nf1

suppressible

Dsor1

(Walker et al., 2013)

Nf1

enhanceable

eag

(Yager et al., 2001)

Nf1

suppressible

elav

(Walker et al., 2013)

Nf1

suppressible

HERC2

(Walker et al., 2013)

Nf1

suppressible

Hs3st-B

(Walker et al., 2013)

Nf1

enhanceable

ine

(Yager et al., 2001)

Nf1

suppressible

jeb

(Walker et al., 2013)

Nf1

enhanceable

jeb

(Gouzi et al., 2011)

Nf1

suppressible

NAAT1

(Walker et al., 2013)

Nf1

enhanceable

nAChRα6

(Walker et al., 2013)

Nf1

enhanceable

Pka-C1

(Walker et al., 2013)

Nf1

enhanceable

poe

(Yager et al., 2001)

Nf1

suppressible

Rab9

(Walker et al., 2013)

Nf1

suppressible

Raf|rl

(Walker et al., 2006)

Nf1

suppressible

Ras85D

(Williams et al., 2001)

Nf1

suppressible

Ras85D|Raf

(Walker et al., 2006)

Nf1

suppressible

(Williams et al., 2001)

Nf1

suppressible

Sos

(Williams et al., 2001)

Nf1

suppressible

vap

(Walker et al., 2006)

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Alk

suppressible

Nf1

(Bai and Sehgal, 2015)

Fak

suppressible

Nf1

(Tsai et al., 2012)

ine

enhanceable

Nf1

(Yager et al., 2001)

suppressible

(Bai et al., 2018)

enhanceable

(Yager et al., 2001)

enhanceable

(Bai et al., 2018)

suppressible

(Bourouis et al., 2019)

External Data

Linkouts

BioGRID - A database of protein and genetic interactions.

68049

DroID - A comprehensive database of gene and protein interactions.

FBgn0015269

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

43149

MIST (genetic) - An integrated Molecular Interaction Database

MIST (protein-protein) - An integrated Molecular Interaction Database

Pathways

Signaling Pathways (FlyBase)

Metabolic Pathways

External Data

Linkouts

Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.

Regulation of RAS by GAPs

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

3-89

Cytogenetic map

96F9-96F9

Sequence location

3R:25,983,013..25,995,737 [+]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

96F9-96F9

Limits computationally determined from genome sequence between P{PZ}l(3)rQ197^rQ197 and P{lacW}scrib^j7B3

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

96F-96F

(Bernards, 1997.4.8)

96F-96F

(determined by in situ hybridisation)

(The et al., 1997)

Experimentally Determined Recombination Data

Location

3-89

(FlyBase, 2016)

3-87.4

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (9)

Bloomington

10201

w¹¹¹⁸; PBac{PB}Nf1^c00617

25845

y¹ v¹; P{TRiP.JF01866}attP2

31466

y¹ v¹; P{TRiP.JF01767}attP2

53322

y¹ v¹; P{TRiP.HMC03551}attP40

78681

y¹ sc^* v¹ sev²¹; P{TOE.GS02013}attP40

80739

y¹ sc^* v¹ sev²¹; P{TKO.GS01796}attP40

34427

y¹ w^*; Mi{MIC}Nf1^MI01388/TM3, Sb¹ Ser¹

VDRC

v109637

P{KK101909}VIE-260B

v35877

w¹¹¹⁸; P{GD13892}v35877/TM3

Genomic Clones (19)

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (34)

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.

FBgn0015269

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0015269

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

43149

Antibody Information

Laboratory Generated Antibodies

monoclonal

(The et al., 1997)

Commercially Available Antibodies

Other Information

Relationship to Other Genes

Source for database identify of

Source for database merge of

Additional comments

Other Comments

Nf1 mutant flies are defective in memory acquisition but not memory stability.

(Buchanan and Davis, 2010)

The reduced life span seen in Nf1 mutants is the product of the impairment of adenylyl cyclase/cAMP/PKA signalling.

(Tong et al., 2007)

Inactivation of Nf1 increases oxidative stress, mediated by downregulation of adenylyl cyclase/cAMP/PKA.

(Tong et al., 2007)

One of 42 Drosophila genes identified as being most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to human Mental Retardation disorders.

(Inlow and Restifo, 2004)

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

(Kiger et al., 2003)

Nf1 has a role in circadian output via the Ras/MAPK signaling pathway.

(Williams et al., 2001)

Nf1 affects learning and short-term memory independently of its developmental effects.

(Guo et al., 2000)

Nf1 functions either upstream of adenylyl cyclase or in a parallel pathway.

(Bernards, 1998.11.6)

Nf1 deficient phenotypes (reduced size, absence of a PACAP-induced rectifying potassium current at the larval neuromuscular junction) are not modified by manipulating Ras85D or Ras64B gene dosage, but rather are rescued by increasing signaling through the cAMP - PKA pathway.

(Bernards, 1998.11.6)

Activation of rut protein through heterotrimeric guanine nucleotide-binding protein-coupled receptor is regulated by Nf1.

(Guo et al., 1997)

Nf1 and Pka-C1 interact in a pathway that controls the overall growth of flies.

(The et al., 1997)

Nf1 is a crucial component for activation of the cAMP pathway.

(Zhong, 1997)

Origin and Etymology

Discoverer

Etymology

Identification

External Crossreferences and Linkouts ( 72 )

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.

43149

GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.

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/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information

Other crossreferences

Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones

FBgn0015269

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

Nf1_1

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG8318

Flygut - An atlas of the Drosophila adult midgut

FBgn0015269

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

43149

iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)

TC031561

InterPro - A database of protein families, domains and functional sites

KEGG Genes - Molecular building blocks of life in the genomic space.

Dmel_CG8318

modMine - A data warehouse for the modENCODE project

FBgn0015269

Linkouts

BioGRID - A database of protein and genetic interactions.

68049

DroID - A comprehensive database of gene and protein interactions.

FBgn0015269

DRSC - Results frm RNAi screens

FBgn0015269

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0015269

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG8318-RB;CG8318-RB

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0015269

FlyMine - An integrated database for Drosophila genomics

FBgn0015269

Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution

Interactive Fly

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

43149

MIST (genetic) - An integrated Molecular Interaction Database

MIST (protein-protein) - An integrated Molecular Interaction Database

Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.

Regulation of RAS by GAPs

Synonyms and Secondary IDs (18)

Reported As

Symbol Synonym

CG8318

(Çiçek et al., 2016, Ni et al., 2010.12.1, Keleman et al., 2009.8.5, Perkins et al., 2009.1.15, Ni et al., 2008, Kim et al., 2004)

FBpp0084326

(van Dam et al., 2011)

NF-1

(Hendricks, 2003, Mittnach, 2000)

Nf-1

(Stanewsky, 2003)

Nf1

(Maurer et al., 2020, Berlandi et al., 2019, Fenckova et al., 2019, Hegazi et al., 2019, Zahoor et al., 2019, Greenblatt and Spradling, 2018, Tomita et al., 2017, Transgenic RNAi Project members, 2017-, Zhu et al., 2017, Schwartz et al., 2016, van der Voet et al., 2016, Bai and Sehgal, 2015, Davis, 2015, Jindal et al., 2015, Liu and Secombe, 2015, Ma et al., 2015, Wurmbach and Preiss, 2014, Lee et al., 2013, Li et al., 2013, Neckameyer and Argue, 2013, Houot et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Pezzulo et al., 2012, Diez et al., 2011, Gouzi et al., 2011, Jungreis et al., 2011, Gilchrist et al., 2008, Bakal et al., 2007, Ho et al., 2007, Kankel et al., 2007, Lavery and Stern, 2007, Maines et al., 2007, Hannan et al., 2006, Jordan et al., 2005, Mertens et al., 2005, Stanewsky, 2003, Stanewsky, 2002, Tong et al., 2002, Sokolowski, 2001, Williams et al., 2001, Pickeral et al., 2000, The et al., 1997)

dNF1

(Tong et al., 2007, Holmes and Sheeba, 2005)

dNf1

(Okray and Hassan, 2013, Walker et al., 2013)

nf1

(King et al., 2016, Buchanan and Davis, 2010)

Name Synonyms

Neurofibromatosis 1

(Liu et al., 2009)

Neurofibromatosis Factor 1

(Mertens et al., 2005)

Neurofibromatosis-1

(Stanewsky, 2003, Stanewsky, 2002, Williams et al., 2001)

Neurofibromin

(Tong et al., 2002)

Neurofibromin 1

(Tomita et al., 2017, Laver et al., 2013, Mummery-Widmer et al., 2009, Yager et al., 2000)

neurofibramatosis-1

(Tong et al., 2007)

neurofibromatosis 1

(Walker et al., 2006)

neurofibromatosis type 1

(Burrell and Sahley, 2001, Stocker and Hafen, 2000, Zars, 2000)

neurofibromin

(Davis, 2015, Hangartner et al., 2015, Buchanan and Davis, 2010)

Secondary FlyBase IDs

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

References (140)

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