FlyBase Gene Report: Dmel\Dif

General Information

Symbol

Dmel\Dif

Species

D. melanogaster

Name

Dorsal-related immunity factor

Annotation Symbol

CG6794

Feature Type

protein_coding_gene

FlyBase ID

FBgn0011274

Gene Model Status

Current

Stock Availability

30 publicly available

Gene Summary

Dorsal-related immunity factor (Dif) encodes a transcription factor that contributes to zygotic function of the Toll pathway, notably the regulation of antimicrobial peptides, but it is not involved in dorsoventral patterning of the embryo. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)

All Summaries

Gene Snapshot
Alliance
Auto summary
Pathway
Gene Group
UniProtKB
Interactive Fly

Also Known As

NF-κB

Key Links

Genomic Location

Cytogenetic map

36C7-36C8

Sequence location

2L:17,413,248..17,433,161 [-]

Recombination map

2-53

RefSeq locus

NT_033779 REGION:17413248..17433161

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse

Other Genome Views

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

Function

Gene Ontology (GO) Annotations (28 terms)

Molecular Function (7 terms)

Terms Based on Experimental Evidence (5 terms)

CV Term

Evidence

References

enables DNA-binding transcription activator activity, RNA polymerase II-specific

inferred from direct assay

(Junell et al., 2007, Ip et al., 1993)

enables DNA-binding transcription factor activity, RNA polymerase II-specific

inferred from direct assay

(Lehming et al., 1995)

enables DNA-binding transcription factor activity

inferred from direct assay

(Petersen et al., 1995)

enables protein binding

inferred from physical interaction with FLYBASE:cact; FB:FBgn0000250

(Lehming et al., 1995)

inferred from physical interaction with FLYBASE:MED17; FB:FBgn0038578

(Park et al., 2003)

enables RNA polymerase II transcription regulatory region sequence-specific DNA binding

inferred from direct assay

(Copley et al., 2007, Lehming et al., 1995, Ip et al., 1993)

Terms Based on Predictions or Assertions (4 terms)

CV Term

Evidence

References

enables DNA binding

inferred from electronic annotation with InterPro:IPR011539, InterPro:IPR037059

(InterPro Project Members, 2004-)

enables DNA-binding transcription factor activity, RNA polymerase II-specific

inferred from biological aspect of ancestor with PANTHER:PTN000652442

(GO Reference Genome Project, 2011-)

enables DNA-binding transcription factor activity

inferred from electronic annotation with InterPro:IPR000451, InterPro:IPR008967, InterPro:IPR011363, InterPro:IPR011539, InterPro:IPR037059

(InterPro Project Members, 2004-)

inferred from electronic annotation with InterPro:IPR000451, InterPro:IPR008967, InterPro:IPR011539, InterPro:IPR037059

(InterPro Project Members, 2004-)

enables RNA polymerase II cis-regulatory region sequence-specific DNA binding

inferred from biological aspect of ancestor with PANTHER:PTN000652442

(GO Reference Genome Project, 2011-)

Biological Process (18 terms)

Terms Based on Experimental Evidence (13 terms)

CV Term

Evidence

References

involved_in canonical NF-kappaB signal transduction

inferred from direct assay

(Lehming et al., 1995)

involved_in defense response to fungus

inferred from mutant phenotype

(Gobert et al., 2003, Rutschmann et al., 2000)

involved_in defense response to Gram-positive bacterium

inferred from mutant phenotype

(Brown et al., 2009, Gobert et al., 2003, Rutschmann et al., 2002, Rutschmann et al., 2000)

involved_in immune response

inferred from mutant phenotype

(Xylourgidis et al., 2006)

inferred from mutant phenotype

(Christofi and Apidianakis, 2013)

involved_in innate immune response

inferred from mutant phenotype

(Meng et al., 1999)

involved_in peripheral nervous system neuron development

inferred from mutant phenotype

(Ayyar et al., 2007)

involved_in positive regulation of antifungal peptide production

inferred from mutant phenotype

(Rutschmann et al., 2000)

involved_in positive regulation of antimicrobial peptide production

inferred from mutant phenotype

(Manfruelli et al., 1999)

involved_in positive regulation of gene expression

inferred from genetic interaction with FLYBASE:Rel; FB:FBgn0014018

(Brown et al., 2009)

involved_in positive regulation of transcription by RNA polymerase II

inferred from direct assay

(Zhou et al., 2021, Park et al., 2003, Roxstrom-Lindquist et al., 2002, Lehming et al., 1995)

involved_in regulation of hemocyte proliferation

inferred from direct assay

(Matova and Anderson, 2006)

involved_in salivary gland histolysis

inferred from mutant phenotype

(Lehmann et al., 2002)

involved_in Toll signaling pathway

inferred from mutant phenotype

(Manfruelli et al., 1999, Meng et al., 1999)

inferred from direct assay

(Zhou et al., 2022, Zhou et al., 2021)

inferred from genetic interaction with FLYBASE:Tl; FB:FBgn0262473

(Koltun et al., 2017, Rutschmann et al., 2000, Ip et al., 1993)

Terms Based on Predictions or Assertions (8 terms)

CV Term

Evidence

References

involved_in canonical NF-kappaB signal transduction

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

involved_in inflammatory response

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

involved_in innate immune response

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

involved_in non-canonical NF-kappaB signal transduction

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

involved_in positive regulation of transcription by RNA polymerase II

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

involved_in regulation of DNA-templated transcription

inferred from electronic annotation with InterPro:IPR000451, InterPro:IPR008967, InterPro:IPR011539, InterPro:IPR037059

(InterPro Project Members, 2004-)

involved_in regulation of transcription by RNA polymerase II

inferred from electronic annotation with InterPro:IPR011363

(InterPro Project Members, 2004-)

involved_in response to cytokine

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

Cellular Component (3 terms)

Terms Based on Experimental Evidence (3 terms)

CV Term

Evidence

References

located_in cytoplasm

inferred from direct assay

(Xylourgidis et al., 2006)

inferred from direct assay

(Bhattacharya and Steward, 2002, Wu and Anderson, 1998)

located_in cytosol

inferred from direct assay

(Cha et al., 2003, Ip et al., 1993)

located_in nucleus

inferred from direct assay

(Cha et al., 2003, Park et al., 2003, Bhattacharya and Steward, 2002, Wu and Anderson, 1998, Ip et al., 1993)

inferred from direct assay

(Xylourgidis et al., 2006)

Terms Based on Predictions or Assertions (2 terms)

CV Term

Evidence

References

is_active_in cytoplasm

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

located_in cytoplasm

inferred from electronic annotation with InterPro:IPR000451, InterPro:IPR011363

(InterPro Project Members, 2004-)

is_active_in nucleus

inferred from biological aspect of ancestor with PANTHER:PTN000652441

(GO Reference Genome Project, 2011-)

located_in nucleus

inferred from electronic annotation with InterPro:IPR011363

(InterPro Project Members, 2004-)

Gene Group (FlyBase)

NUCLEAR FACTOR - KAPPA B

Pathway (FlyBase)

TOLL-NF-kappaB SIGNALING PATHWAY CORE COMPONENTS

Protein Family (UniProt)

Protein Signatures (InterPro)

Summaries

Gene Snapshot

Gene Group (FlyBase)

NUCLEAR FACTOR - KAPPA B -: The NF-κB transcription factor family share an N-terminal Rel homology domain. NF-κB transcription factors play a major role in development and immunity. (Adapted from FBrf0155649 and FBrf0210750).

Pathway (FlyBase)

TOLL-NF-kappaB SIGNALING PATHWAY CORE COMPONENTS -: In Drosophila, the canonical Toll signaling pathway is initiated by the binding of a spatzle ligand to Toll (Tl) or a Toll-like receptor leading to the nuclear localization of the NF-κB (dl or Dif) transcription factor. (Adapted from FBrf0091014 and FBrf0223077).

Protein Function (UniProtKB)

Mediates an immune response in larvae (PubMed:8242747). DIF binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of the immunity gene CECA1 (PubMed:8242747). Involved in the melanization immune response to bacterial challenge, possibly by acting in a Toll signaling pathway that down-regulates Spn27A in response to infection (PubMed:12456640). Part of a signaling pathway involving NF-kappa-B (rel) and Toll-related receptors, that functions in the apoptosis of unfit cells during cell competition (PubMed:25477468). May be part of a NF-kappa-B and Tollo signaling cascade that regulates development of the peripheral nervous system (PubMed:18000549).

(UniProt, P98149)

Summary (Interactive Fly)

NFkappaB/rel homolog - a regulator of the immune response - Dorsal and DIF act downstream of the Toll pathway in the immune response

Interactive Fly

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\Dif 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

Structure

Protein 3D structure (Predicted by AlphaFold) (AlphaFold entry P98149)

If you don't see a structure in the viewer, refresh your browser.

Model Confidence:

Very high (pLDDT > 90)
Confident (90 > pLDDT > 70)
Low (70 > pLDDT > 50)
Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures

Crossreferences

Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.50

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

Dif-RA

FBtr0081008

NM_078865

2835

667

Dif-RB

FBtr0081009

NM_165216

2483

667

Dif-RC

FBtr0301577

NM_001169527

4306

987

Dif-RD

FBtr0301578

NM_001169528

2595

667

Additional Transcript Data and Comments

Reported size (kB)

2.8 (northern blot)

(Ip et al., 1993)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

UniProt

RefSeq ID

GenBank

Dif-PA

FBpp0080561

73.9

667

5.77

FBpp0080562

73.9

667

5.77

FBpp0290792

107.9

987

4.78

FBpp0290793

73.9

667

5.77

P98149

NP_001162999

ACZ94285

Polypeptides with Identical Sequences

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

667 aa isoforms: Dif-PA, Dif-PB, Dif-PD

Additional Polypeptide Data and Comments

Reported size (kDa)

667 (aa)

(Ip et al., 1993)

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\Dif using the Feature Mapper tool.

External Data

Crossreferences

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

Dif_1
Dif_2

Linkouts

Expression Data

Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-1.33

Transcript Expression

No Assay Recorded

Stage

Tissue/Position (including subcellular localization)

Reference

pupal stage

(Ip et al., 1993)

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 13 -- 16

embryonic/larval fat body

(Fisher et al., 2012)

embryonic/larval posterior spiracle

(Fisher et al., 2012)

northern blot

Stage

Tissue/Position (including subcellular localization)

Reference

larval stage

(Ip et al., 1993)

prepupal stage P4(ii)

embryonic/larval salivary gland

Comment: 12 hr APF

(Lehmann et al., 2002)

adult stage

(Ip et al., 1993)

Additional Descriptive Data

Dif transcript is expressed in salivary glands at the end of the prepupal ecdyosne pulse.

(Lehmann et al., 2002)

dif is expressed at high levels in third instar larvae, pupae, and adults.

(Ip et al., 1993)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

immunolocalization

Stage

Tissue/Position (including subcellular localization)

Reference

larval stage

embryonic/larval fat body

(Ip et al., 1993)

mass spectroscopy

Stage

Tissue/Position (including subcellular localization)

Reference

day 7 of adulthood -- day 49 of adulthood

adult heart

(Cammarato et al., 2011)

Additional Descriptive Data

Dif protein is expressed in the larval fat body.

(Ip et al., 1993)

Marker for

Subcellular Localization

CV Term

Evidence

References

located_in cytoplasm

inferred from direct assay

(Xylourgidis et al., 2006)

inferred from direct assay

(Bhattacharya and Steward, 2002, Wu and Anderson, 1998)

located_in cytosol

inferred from direct assay

(Cha et al., 2003, Ip et al., 1993)

located_in nucleus

inferred from direct assay

(Cha et al., 2003, Park et al., 2003, Bhattacharya and Steward, 2002, Wu and Anderson, 1998, Ip et al., 1993)

inferred from direct assay

(Xylourgidis et al., 2006)

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Dif in JBrowse

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

View exonic expression by developmental stage for Dmel\Dif

View exonic expression by tissue for Dmel\Dif

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

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0011274

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

35045/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0011274

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0011274

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0011274

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

CG6794

Images

FlyExpress - Embryonic expression images (BDGP data)

Show all FlyExpress processed images for Dmel\Dif

Stages(s) 13-16

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 15 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 31 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of Dif

Transgenic constructs containing regulatory region of Dif

Aberrations (Deficiencies and Duplications) ( 5 )

Inferred from experimentation ( 5 )

Gene disrupted in

Df(2L)Exel7068

(Ryder, 2004.4.26)

Df(2L)Exel8036

(Ryder, 2004.4.26)

Df(2L)J4b

(Rutschmann et al., 2000)

Df(2L)J4

(Matova and Anderson, 2006, Chiu et al., 2005, Huang et al., 2005)

Df(2L)TW119

(Matova and Anderson, 2006, Chiu et al., 2005, Huang et al., 2005, Rutschmann et al., 2000)

Inferred from location ( 11 )

Variants

Variant Molecular Consequences

Alleles Representing Disease-Implicated Variants

Phenotypes

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

Lethality

Allele

lethal

lethal, with Scer\GAL4^Bx-MS1096

Dif^{UAS.ORF.GW.Tag:HA}

lethal, with Scer\GAL4^hs.PB

Dif^UAS.cIa

lethal | cold sensitive, with Scer\GAL4^Bx-MS1096

Dif^{UAS.ORF.GW.Tag:HA}

partially lethal, with Scer\GAL4^arm.PS

Dif^UAS.ECFP

viable

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

Dif^GD4442

viable, with Scer\GAL4^Cg.PA

Dif^UAS.ECFP

viable, with Scer\GAL4^Mef2.PR

Dif^GD4442

viable, with Scer\GAL4^pnr-MD237

Dif^GD4442

Sterility

Allele

fertile

Dif^LA00958

Other Phenotypes

Allele

abnormal chemosensory behavior | adult stage

abnormal immune response

abnormal immune response, with Scer\GAL4^da.G32

Dif^RNAi.UAS.cKa

abnormal immune response (with Df(2L)J4b)

Dif¹

abnormal immune response | adult stage

abnormal immune response | adult stage, with Scer\GAL4^c564

Dif^RNAi.UAS.cKa

abnormal immune response | adult stage | recessive

Dif¹

abnormal size | adult stage, with Scer\GAL4^r4

Dif^UAS.cYa

abnormal sleep | adult stage

Dif¹

abnormal sleep | adult stage, with Scer\GAL4^0407-G4

Dif^GD4442

abnormal sleep | adult stage, with Scer\GAL4^VT008975

Dif^GD4442

abnormal sleep | adult stage (with Df(2L)J4)

Dif¹

abnormal sleep | adult stage (with Dif¹)

Dif^0407-G4

abnormal sleep | adult stage (with Dif^0407-G4)

Dif¹

abnormal sleep | adult stage | female, with Scer\GAL4^Ilp2.PU

Dif^GD4442

abnormal stress response

Dif¹

decreased rate of feeding behavior | adult stage | female

Dif^ΔB

decreased sleep | adult stage

Dif¹

decreased sleep | adult stage, with Scer\GAL4^0407-G4

Dif^GD4442

decreased sleep | adult stage, with Scer\GAL4^Gbp3.PW

Dif^GD4442

decreased sleep | adult stage, with Scer\GAL4^Ilp2.PU

Dif^GD4442

decreased sleep | adult stage, with Scer\GAL4^VT008975

Dif^GD4442

decreased sleep | adult stage, with Scer\GAL4^VT056377

Dif^GD4442

decreased sleep | adult stage (with Df(2L)J4)

Dif¹

decreased sleep | adult stage (with Dif¹)

Dif^0407-G4

decreased sleep | adult stage (with Dif^0407-G4)

Dif¹

decreased sleep | adult stage | female, with Scer\GAL4^c767

Dif^GD4442

decreased sleep | adult stage | female, with Scer\GAL4^GMR21A07

Dif^GD4442

decreased sleep | adult stage | female, with Scer\GAL4^VT003282

Dif^GD4442

decreased sleep | adult stage | male, with Scer\GAL4^VT018146

Dif^GD4442

decreased sleep | adult stage | RU486 conditional, with Scer\GAL4^{elav.Switch.PO}

decreased sleep | female

Dif^0407-G4

increased mortality | adult stage | conditional

Dif^ΔA

increased mortality | conditional

Dif^nmc

short lived | conditional

Dif¹

visible, with Scer\GAL4^sca-537.4

Dif^LA00958

visible | adult stage, with Scer\GAL4^r4

Dif^UAS.cYa

visible | cold sensitive

Dif¹

visible | dominant

Dif¹

Phenotype manifest in

Allele

dorsocentral bristle

Dif¹

embryonic/larval hemocyte | increased number, with Scer\GAL4^Cg.PA

Dif^UAS.cIa

embryonic/larval plasmatocyte | increased number, with Scer\GAL4^Cg.PA

Dif^UAS.cIa

lamellocyte | increased number, with Scer\GAL4^Cg.PA

Dif^UAS.cIa

macrochaeta, with Scer\GAL4^sca-537.4

Dif^LA00958

macrochaeta | ectopic | cold sensitive

Dif¹

mesonotum, with Scer\GAL4^sca-537.4

Dif^LA00958

mesonotum | ectopic | cold sensitive

Dif¹

salivary gland | heat sensitive

Dif^RD.hs

salivary gland | heat sensitive, with Scer\GAL4^hs.PB

Dif^UAS.cLa

wing, with Scer\GAL4^r4

Dif^UAS.cYa

Orthologs

Downloads

Download All DIOPT Orthologs

Human Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Homo sapiens (Human) (26)

Hsap\RELA

7 of 14

Yes

3920

Hsap\REL

7 of 14

Yes

Hsap\RELB

6 of 14

Yes

5 of 14

5 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Model Organism Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Rattus norvegicus (Norway rat) (17)

Rnor\Rela

8 of 14

Yes

Rnor\Rel

8 of 14

Yes

Rnor\Nfkb2

5 of 14

Rnor\Relb

5 of 14

Yes

3 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Mus musculus (laboratory mouse) (19)

Mmus\Rel

8 of 14

Yes

Mmus\Rela

7 of 14

Mmus\Relb

6 of 14

Yes

5 of 14

4 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Xenopus tropicalis (Western clawed frog) (12)

Xtro\rela

6 of 13

Yes

Xtro\relb

5 of 13

Yes

5 of 13

4 of 13

4 of 13

2 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Danio rerio (Zebrafish) (25)

Drer\rel

9 of 14

Yes

8 of 14

5 of 14

4 of 14

4 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Yes

Drer\ankrd28b

1 of 14

Drer\ankrd44

1 of 14

Drer\ankrd67

1 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Caenorhabditis elegans (Nematode, roundworm) (2)

Cele\M60.7

1 of 14

Yes

Cele\trp-4

1 of 14

Yes

Anopheles gambiae (African malaria mosquito) (6)

Agam\REL1

6 of 12

Yes

2 of 12

1 of 12

1 of 12

1 of 12

1 of 12

Arabidopsis thaliana (thale-cress) (0)

Saccharomyces cerevisiae (Brewer's yeast) (0)

Schizosaccharomyces pombe (Fission yeast) (0)

Escherichia coli (enterobacterium) (0)

Other Organism Orthologs (via OrthoDB)

Data provided directly from OrthoDB:Dif. Refer to their site for version information.

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v9.1)

Gene Symbol

Score

Source

Alignment

Drosophila melanogaster (Fruit fly) (5)

8 of 13

Rel

4 of 13

Arms

1 of 13

NFAT

1 of 13

nompC

1 of 13

Human Disease Associations

FlyBase Human Disease Model Reports

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Dif¹

model of bacterial infectious disease

CEA

(Christofi and Apidianakis, 2013)

Potential Models Based on Orthology ( 2 )

Human Ortholog

Disease

Evidence

References

REL; REL proto-oncogene, NF-kB subunit

model of immunodeficiency 92

IEA

(FlyBase, 2019-)

RELB; RELB proto-oncogene, NF-kB subunit

model of immunodeficiency 53

IEA

(FlyBase, 2019-)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Dif^LA00958

exacerbates carcinoma

modeled by scrib¹

(Katsukawa et al., 2018)

Dif^HM05257

ameliorates epilepsy

modeled by pk^sple-1

(Nukala et al., 2023)

Dif^RNAi.UAS.cUa

ameliorates neurodegenerative disease

modeled by Zzzz\CAG^{127Q.UAS.Tag:HA}

(Dubey and Tapadia, 2018)

Disease Associations of Human Orthologs (via DIOPT v9.1 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?

RELA; RELA proto-oncogene, NF-kB subunit

7 of 14

164014

AUTOINFLAMMATORY DISEASE, FAMILIAL, BEHCET-LIKE 3; AIFBL3

REL; REL proto-oncogene, NF-kB subunit

7 of 14

164910

IMMUNODEFICIENCY 92; IMD92

immunodeficiency 92

RELB; RELB proto-oncogene, NF-kB subunit

6 of 14

604758

IMMUNODEFICIENCY 53; IMD53

immunodeficiency 53

NFKB1; nuclear factor kappa B subunit 1

5 of 14

164011

IMMUNODEFICIENCY, COMMON VARIABLE, 12, WITH AUTOIMMUNITY; CVID12

common variable immunodeficiency 12

NFKB2; nuclear factor kappa B subunit 2

5 of 14

164012

IMMUNODEFICIENCY, COMMON VARIABLE, 10; CVID10

common variable immunodeficiency 10

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

Interaction Browsers

View in FlyBase Interactions Browser View in MIST tool (external link)

Please see the Physical Interaction reports below for full details

protein-protein

Physical Interaction

Assay

References

Dif - Cdk8

pull down, western blot

(Park et al., 2003)

Dif - Dcp-1

anti tag coimmunoprecipitation, anti tag western blot

(Wu et al., 2022)

Dif - Drice

anti tag coimmunoprecipitation, anti tag western blot, enzymatic study

(Wu et al., 2022)

Dif - MED16

pull down, autoradiography

(Kim et al., 2004)

Dif - MED17

pull down, autoradiography, western blot

(Kim et al., 2004, Park et al., 2003)

Dif - MED21

pull down, western blot

(Park et al., 2003)

Dif - MED23

pull down, autoradiography

(Kim et al., 2004)

Dif - MED25

pull down, autoradiography

(Kim et al., 2004)

Dif - MED31

pull down, western blot

(Park et al., 2003)

Dif - Poxm

two hybrid array

(Shokri et al., 2019)

Dif - Ptx1

two hybrid array

(Shokri et al., 2019)

Dif - Rel

surface plasmon resonance, anti tag coimmunoprecipitation, anti tag western blot

(Chowdhury et al., 2019, Bitra et al., 2012)

Dif - cact

pull down, autoradiography, surface plasmon resonance, two hybrid, anti tag western blot

(Bitra et al., 2012, Minakhina et al., 2003, Lehming et al., 1995, Tatei and Levine, 1995)

Dif - tin

two hybrid array

(Shokri et al., 2019)

RNA-protein

Physical Interaction

Assay

References

Dif - asRNA:CR11538

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Zhou et al., 2021)

Dif - asRNA:CR46018

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Zhou et al., 2021)

Dif - lncRNA:CR33942

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Zhou et al., 2022)

RNA-RNA

Physical Interaction

Assay

References

Dif - mir-958

luminiscence technology, necessary binding region, western blot

(Li et al., 2017)

Summary of Genetic Interactions

Interaction Browsers

View in FlyBase Interactions Browser View in MIST tool (external link)

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

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

Dif

suppressible

(Matova and Anderson, 2006)

Dif

enhanceable

(Matova and Anderson, 2006)

Dif

suppressible

nur

(O'Hara et al., 2024)

Dif

enhanceable

Rel

(O'Hara et al., 2024)

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

asp

suppressible

Rel|Dif

(Mannino et al., 2023)

asp

suppressible

Dif

(Mannino et al., 2023)

cact

suppressible

Dif

(Zang et al., 2015)

suppressible

Dif

(Matova and Anderson, 2006, Stein et al., 1998)

krz

suppressible

Dif

(Anjum et al., 2013)

lwr

suppressible

Dif

(Chiu et al., 2005, Huang et al., 2005)

nur

suppressible

Dif

(O'Hara et al., 2024)

suppressible

Dif

(Suzawa et al., 2019, Roth et al., 2018, Zang et al., 2015)

External Data

Linkouts

BioGRID - A database of protein and genetic interactions.

61041

DroID - A comprehensive database of gene and protein interactions.

FBgn0011274

MIST (genetic) - An integrated Molecular Interaction Database

35045

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

35045

Pathways

Signaling Pathways (FlyBase)

TOLL-NF-kappaB SIGNALING PATHWAY CORE COMPONENTS

Metabolic Pathways

FlyBase

External Links

External Data

Linkouts

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

Toll and Imd signaling pathway

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

Class of Gene

nuclear_gene

protein_coding_gene

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

2-53

Cytogenetic map

36C7-36C8

Sequence location

2L:17,413,248..17,433,161 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

36C7-36C8

Limits computationally determined from genome sequence between P{lacW}Mhc^k10423&P{lacW}Cas^k03902 and P{lacW}Aac11^k06710

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

36C2-36C2

(Ip, 1994.2.18)

36C-36C

(determined by in situ hybridisation)

(Ip et al., 1993)

Experimentally Determined Recombination Data

Location

2-53

(FlyBase, 2016)

2-52.7

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (30)

Genomic Clones (20)

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

cDNA Clones (155)

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 JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced

BDGP DGC clones

RE18723

Other clones

FI01004

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.

FBgn0011274

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0011274

Antibody Information

Laboratory Generated Antibodies

polyclonal

(Li et al., 2019, Li et al., 2017, Zhou et al., 2015, Ip et al., 1993)

Commercially Available Antibodies

Cell Line Information

Publicly Available Cell Lines

Other Stable Cell Lines

Other Comments

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)

Dif does not show high cooperative DNA binding with Dsp1 protein. dl can activate transcription from zen and twi promoters, and additional Dsp1 inhibits the zen activation and increases the twi activation.

(Brickman et al., 1999)

Dif and dl are functionally redundant in their ability to control Drs gene expression in larvae.

(Manfruelli et al., 1999)

A linear activation cascade spz-Tl-cact-dl/Dif leads to the induction of the Drs gene in larval fat body cells.

(Manfruelli et al., 1999)

Dif protein is capable of substituting, to a significant degree, for dl protein in its role in defining the dorsal-ventral axis of the embryo.

(Stein et al., 1998)

Tl pathway is required for the nuclear import of dl in the immune response, but not required for the nuclear import of Dif. Cytoplasmic retention of both dl and Dif depends on cact protein. The two signalling pathways that target cact for degradation must discriminate between cact-dl and cact-Dif complexes.

(Wu and Anderson, 1998)

The molecular evolution of the Rel/NF-κB and IκB proteins is studied in parallel. Phylogenetic analysis allows the structure of the putative ancestor genes to be defined and proposes and evolutionary model that clusters both families in a unique Rel/NF-κB/IκB superfamily.

(Huguet et al., 1997)

Deletion analysis reveals the GATA site is necessary for CecA1 expression. Cotransfection analysis demonstrates Dif required an intact GATA site for maximal transactivation of the CecA1 gene.

(Kadalayil et al., 1997)

Antibacterial genes are not induced in L.boulardi resistant strains of Drosophila suggesting they cannot be involved directly in the antiparasitoid response.

(Coustau et al., 1996)

dl and Dif have distinct DNA-binding characteristics and the proteins can heterodimerise in vitro. Mutants carrying no copies of dl and a single copy of Dif retain their full capacity to express the Dpt and CecA1 genes in response to bacterial challenge.

(Gross et al., 1996)

Dif is a rel family protein that is thought to function in the humoral immune response.

(Liu and Steward, 1995)

Injury or bacterial infection leads to rapid translocation of dl and Dif gene products from the cytoplasm to the nucleus, this translocation is regulated in part by Tl signalling pathway. In direction of increasing cytology: Dif? dl?

(Liu and Steward, 1995)

The Dif gene product is a sequence specific transcription factor which trans-activates the CecA1 gene in cotransfection assays. Transactivation requires a 40bp upstream element including an insect κΒ-like motif. dl can also activate the CecA1 promoter, but to a lesser extent and in a less sequence-specific manner than Dif. The dl product exerts a dominant negative effect on Dif transactivation of CecA1.

(Petersen et al., 1995)

18w is involved in the translocation of Dif product into the nuclei of the larval fat body upon infection.

(Williams et al., 1995)

Dif mediates an immune response in Drosophila larvae. Otherwise cytoplasmic, Dif accumulates in the nucleus upon bacterial infection or injury.

(Ip et al., 1993)

Once in the nucleus Dif binds to κB-like sequence motifs present in promoter regions of the immunity gene, CecA1.

(Ip et al., 1993)

Relationship to Other Genes

Source for database merge of

Additional comments

Nomenclature History

Source for database identify of

Source for identity of: Dif CG6794

(Zhong, 1999.11)

Nomenclature comments

Etymology

Synonyms and Secondary IDs (14)

Reported As

Symbol Synonym

6794

(Ravi et al., 2009)

CG6794

(National Institute of Genetics Fly Stocks, 2022-, Cammarato et al., 2011, Keleman et al., 2009.8.5, Perkins et al., 2009, Hernandez-Romano et al., 2008, Muse et al., 2007, Lee et al., 2003, De Gregorio et al., 2001)

Dif

(Krejčová et al., 2025, Qin et al., 2025, Xiu et al., 2025, Balakireva et al., 2024, Hachfi et al., 2024, Li et al., 2024, Lu et al., 2024, Luo et al., 2024, Meyer et al., 2024, Mpamhanga and Kounatidis, 2024, Nagata and Igaki, 2024, Nigg et al., 2024, Tang et al., 2024, Zhou et al., 2024, Zhou et al., 2024, Bastin and Eleftherianos, 2023, Bland, 2023, Chen et al., 2023, He et al., 2023, Keith, 2023, Kietz and Meinander, 2023, Li et al., 2023, Mannino et al., 2023, Stączek et al., 2023, Tafesh-Edwards and Eleftherianos, 2023, Wang et al., 2023, Williams et al., 2023, Benoit et al., 2022, Cheung et al., 2022, D'Souza et al., 2022, Evans et al., 2022, Kong et al., 2022, Lu and Chtarbanova, 2022, Marshall and Dionne, 2022, National Institute of Genetics Fly Stocks, 2022-, Nüsslein-Volhard, 2022, Valanne et al., 2022, Weiss and O'Neill, 2022, Yu et al., 2022, Zhou et al., 2022, Beňová-Liszeková et al., 2021, Buhlman et al., 2021, Cattenoz et al., 2021, Fabian et al., 2021, Gautam et al., 2021, Ge et al., 2021, Harnish et al., 2021, Kanoh et al., 2021, Mishra et al., 2021, Ozakman and Eleftherianos, 2021, Parra-Peralbo et al., 2021, Rosendo Machado et al., 2021, Salem Wehbe et al., 2021, Schneider and Imler, 2021, Sciambra and Chtarbanova, 2021, Sharma et al., 2021, Sinenko et al., 2021, Tang et al., 2021, Ullastres et al., 2021, Yu et al., 2021, Zhou et al., 2021, Zhou et al., 2021, Blount et al., 2020, Cho et al., 2020, Deng et al., 2020, Hegde et al., 2020, Jeon et al., 2020, Karageorgiou et al., 2020, Khor and Cai, 2020, Krautz et al., 2020, Li et al., 2020, Makhnovskii et al., 2020, Martínez et al., 2020, Tafesh-Edwards and Eleftherianos, 2020, Younes et al., 2020, Zhang et al., 2020, Asri et al., 2019, Banerjee et al., 2019, Fahey-Lozano et al., 2019, Lang et al., 2019, Meltzer, 2019-, Meltzer et al., 2019, Palmer et al., 2019, Shokri et al., 2019, Tang and Engström, 2019, Baillon et al., 2018, Garschall and Flatt, 2018, Gene Disruption Project members, 2018-, Green et al., 2018, Hao et al., 2018, Katsukawa et al., 2018, Lee et al., 2018, Min and Tatar, 2018, Steele et al., 2018, Troha et al., 2018, Wei et al., 2018, Yu et al., 2018, Christesen et al., 2017, Foldi et al., 2017, Kenmoku et al., 2017, Lee et al., 2017, Li et al., 2017, Louradour et al., 2017, Mohr et al., 2017, Park et al., 2017, Transgenic RNAi Project members, 2017-, Chatterjee et al., 2016, Clandinin and Owens, 2016-, Di Gregorio et al., 2016, Gao et al., 2016, Kumar et al., 2016, Lamiable et al., 2016, Okuda et al., 2016, Sarov et al., 2016, Troutwine et al., 2016, Yadav et al., 2016, Bandarra et al., 2015, Gene Disruption Project members, 2015-, Kanoh et al., 2015, Li and Dijkers, 2015, Liu et al., 2015, Schertel et al., 2015, Ward et al., 2015, Wu et al., 2015, Xia et al., 2015, Yamamoto-Hino et al., 2015, Zang et al., 2015, Zhan et al., 2015, Zhou et al., 2015, Carvalho et al., 2014, Chtarbanova et al., 2014, Ferreira et al., 2014, Imler, 2014, Keebaugh and Schlenke, 2014, Kuo and Williams, 2014, Lindsay and Wasserman, 2014, McClure et al., 2014, Wang et al., 2014, Xu and Cherry, 2014, Anjum et al., 2013, Bangi, 2013, Christofi and Apidianakis, 2013, Clark et al., 2013, Gueguen et al., 2013, McIlroy et al., 2013, Morin-Poulard et al., 2013, Nelson et al., 2013, Petersen et al., 2013, Quintin et al., 2013, Shravage et al., 2013, Telonis-Scott et al., 2013, Turner et al., 2013, Bier and Guichard, 2012, Bitra et al., 2012, Eleftherianos and Castillo, 2012, Hamilos et al., 2012, Igboin et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Jones et al., 2012, Kounatidis and Ligoxygakis, 2012, Nakamoto et al., 2012, Pilátová and Dionne, 2012, Rynes et al., 2012, Spokony, 2012.12.12, Abruzzi et al., 2011, Akhouayri et al., 2011, Bou Aoun et al., 2011, Chtarbanova and Imler, 2011, Clark et al., 2011, Fullaondo et al., 2011, Glittenberg et al., 2011, Nehme et al., 2011, Ragab et al., 2011, Valanne et al., 2011, van Uden et al., 2011, Aymeric et al., 2010, Goto et al., 2010, Hill-Burns and Clark, 2010, Kuttenkeuler et al., 2010, Matova and Anderson, 2010, Matskevich et al., 2010, Moule et al., 2010, Nedelsky et al., 2010, Paddibhatla et al., 2010, Sabin et al., 2010, Tanji et al., 2010, Brody, 2009.3.30, Brown et al., 2009, Buchon et al., 2009, Diangelo et al., 2009, Ha et al., 2009, Jin et al., 2009, Obbard et al., 2009, Towb et al., 2009, Boltz and Carney, 2008, Jones et al., 2008, Kalamarz et al., 2008, Leone et al., 2008, Pal et al., 2008, Ratnaparkhi and Courey, 2008, Ratnaparkhi et al., 2008, Reed et al., 2008, Tan et al., 2008, Wang et al., 2008, Yano et al., 2008, Ayyar et al., 2007, Busse et al., 2007, Copley et al., 2007, Hallem et al., 2007, Junell et al., 2007, Kuranaga and Miura, 2007, Lesch et al., 2007, Matova and Anderson, 2007, Minidorff et al., 2007, Muse et al., 2007, Muse et al., 2007, Nehme et al., 2007, Tanji et al., 2007, Tsichritzis et al., 2007, Waterhouse et al., 2007, Williams et al., 2007, Wu and Silverman, 2007, Wu et al., 2007, Zeitouni et al., 2007, Bergmann, 2006, Chen, 2006, Chen et al., 2006, Gottar et al., 2006, Kambris et al., 2006, Leclerc et al., 2006, Matova and Anderson, 2006, Minakhina and Steward, 2006, Ryu et al., 2006, Senger et al., 2006, Tang et al., 2006, Xylourgidis et al., 2006, Beramendi et al., 2005, Kim and Lis, 2005, Mace et al., 2005, Thoetkiattikul et al., 2005, Bettencourt et al., 2004, Bischoff et al., 2004, Han et al., 2004, Gobert et al., 2003, Goto et al., 2003, Lau et al., 2003, Minakhina et al., 2003, Park et al., 2003, Uvell and Engstrom, 2003, Avila et al., 2002, Bhattacharya and Steward, 2002, Cornwell et al., 2002, Lehmann et al., 2002, Ligoxygakis et al., 2002, Roxstrom-Lindquist et al., 2002, Rutschmann et al., 2002, Chen et al., 2000, Rutschmann et al., 2000, Lehming et al., 1995)

Dif2

(Yu et al., 2018)

NF-KB

(Ma et al., 2021)

NF-κB

(Quigley and Amdam, 2021, Gohel et al., 2020)

NFκB

(Luo et al., 2020)

Name Synonyms

Dif

(Blount et al., 2020, Anthoney et al., 2018)

Dorsal related immunity factor

(Wang et al., 2014, Ayyar et al., 2007)

Dorsal-like immunity factor

(Ratnaparkhi and Courey, 2008)

Dorsal-related immunity factor

(Gao et al., 2016, Cammarato et al., 2011, Matova and Anderson, 2010, Hernandez-Romano et al., 2008, Zeitouni et al., 2007, Yajima et al., 2003, Rutschmann et al., 2000)

Dorsal-related transcription factor

(Li and Dijkers, 2015)

dorsal-related immunity factor

(Garschall and Flatt, 2018, Zhan et al., 2015, Marcu et al., 2011, Rutschmann et al., 2002)

Secondary FlyBase IDs

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

Study result (0)

Result

Result Type

Title

External Crossreferences and Linkouts ( 73 )

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.

35045

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/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.

P98149

UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information

P98149

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

Other crossreferences

AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.

P98149

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0011274

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

35045/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0011274

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0011274

FlyMine - An integrated database for Drosophila genomics

FBgn0011274

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

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

dme:Dmel_CG6794

MARRVEL_MODEL - MARRVEL (model organism gene)

35045

Linkouts

BioGRID - A database of protein and genetic interactions.

61041

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

FBgn0011274

DroID - A comprehensive database of gene and protein interactions.

FBgn0011274

DRSC - Results frm RNAi screens

FBgn0011274

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

Dif_1
Dif_2

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0011274

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0011274

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

CG6794

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

Interactive Fly

KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.

Toll and Imd signaling pathway

MIST (genetic) - An integrated Molecular Interaction Database

35045

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

35045

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

References (550)

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

-1.33

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