Dif Dorsal-related immunity factor [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Difprovided by FlyBase
Official Full Name: Dorsal-related immunity factorprovided by FlyBase
Primary source: FLYBASE:FBgn0011274
Locus tag: Dmel_CG6794
See related: AllianceGenome:FB:FBgn0011274
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: 6794; CG6794; dif; DIF; Dif2; Dmel\CG6794; NF-kappaB; NF-KB; NFkappaB
Summary: Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including Toll signaling pathway; defense response to other organism; and positive regulation of macromolecule metabolic process. Located in cytosol and nucleus. Is expressed in adult heart; embryonic/larval fat body; embryonic/larval posterior spiracle; and embryonic/larval salivary gland. Used to study bacterial infectious disease. Human ortholog(s) of this gene implicated in breast cancer; carcinoma (multiple); ductal carcinoma in situ; immunodeficiency 53; and lymphoma. Orthologous to several human genes including RELA (RELA proto-oncogene, NF-kB subunit) and RELB (RELB proto-oncogene, NF-kB subunit). [provided by Alliance of Genome Resources, Apr 2022]
Orthologs: all
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Genomic context

Location:: 36C7-36C8; 2-53 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2L	NT_033779.5 (17413248..17433161, complement)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2L	NT_033779.4 (17413248..17433161, complement)

Chromosome 2L - NT_033779.5 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Interaction of lncRNA-CR33942 with Dif/Dorsal Facilitates Antimicrobial Peptide Transcriptions and Enhances Drosophila Toll Immune Responses.
Title: Interaction of lncRNA-CR33942 with Dif/Dorsal Facilitates Antimicrobial Peptide Transcriptions and Enhances Drosophila Toll Immune Responses.
Bacterial recognition by PGRP-SA and downstream signalling by Toll/DIF sustain commensal gut bacteria in Drosophila.
Title: Bacterial recognition by PGRP-SA and downstream signalling by Toll/DIF sustain commensal gut bacteria in Drosophila.
Study shows that Drosophila miR-317 only targets Dif-Rc, but not Dif-Ra/b/d, implying that miRNAs can regulate different isoforms of an alternative splicing gene to fine tune immune responses and maintain homeostasis in post-transcriptional level. During Gram-positive bacterial infection, the overexpressed miR-317 flies have poor survival outcome suggesting that the miR-317 might play a key role in Drosophila survival.
Title: The miR-317 functions as a negative regulator of Toll immune response and influences Drosophila survival.
These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity.
Title: miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.
Fasting increases survival to cold in dif mutant Drosophila melanogaster.
Title: Fasting increases survival to cold in FOXO, DIF, autophagy mutants and in other genotypes of Drosophila melanogaster.
DIF factor seems to be involved in the response to fungal infection after a mild cold stress and in the resistance to heat. DIF seems to have no role in the increased longevity of non-infected flies and resistance to a severe cold shock.
Title: The NF-κB-like factor DIF could explain some positive effects of a mild stress on longevity, behavioral aging, and resistance to strong stresses in Drosophila melanogaster.
Data show that the DIF and Relish complex is detectable in whole animal extracts, suggesting that this heterodimer may function in vivo to increase the spectrum and level of antimicrobial peptide production in response to different infections.
Title: Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila.
Molecular modeling was used to compare the tertiary structure of Dif with two other Drosophila proteins.
Title: Functional conservation of Rel binding sites in drosophilid genomes.
Various fungi stimulated antimicrobial peptides through at least two different pathways requiring Relish and/or Dif.
Title: Differential activation of the NF-kappaB-like factors Relish and Dif in Drosophila melanogaster by fungi and Gram-positive bacteria.
Dif and Dorsal control crucial aspects of the cellular immune response
Title: Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Toll signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Toll signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in Toll signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-positive bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to fungus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in non-canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in peripheral nervous system neuron development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of antifungal peptide production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of antimicrobial peptide production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of hemocyte proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in response to cytokine	IBA Inferred from Biological aspect of Ancestor more info
involved_in salivary gland histolysis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: Dorsal-related immunity factor

Names: CG6794-PA; CG6794-PB; CG6794-PC; CG6794-PD; Dif-PA; Dif-PB; Dif-PC; Dif-PD; Dorsal-like immunity factor; Dorsal-related transcription factor; dorsal related immunity factor; dorsal-related immunity factor

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033779.5 Reference assembly

Range

17413248..17433161 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001169528.1 → NP_001162999.1 Dorsal-related immunity factor, isoform D [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001162999.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P98149, Q1LYZ5, Q8MT54, Q9VJE2

UniProtKB/TrEMBL

E1JHK1

Conserved Domains (2) summary

cd07887
Location:78 → 252

RHD-n_Dorsal_Dif; N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Dorsal

pfam16179
Location:256 → 358

RHD_dimer; Rel homology dimerization domain
NM_165216.3 → NP_724050.1 Dorsal-related immunity factor, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_724050.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P98149, Q1LYZ5, Q8MT54, Q9VJE2

UniProtKB/TrEMBL

E1JHK1

Related

FBpp0080562

Conserved Domains (2) summary

cd07887
Location:78 → 252

RHD-n_Dorsal_Dif; N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Dorsal

pfam16179
Location:256 → 358

RHD_dimer; Rel homology dimerization domain
NM_078865.4 → NP_523589.2 Dorsal-related immunity factor, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_523589.2

Status: REVIEWED

UniProtKB/Swiss-Prot

P98149, Q1LYZ5, Q8MT54, Q9VJE2

UniProtKB/TrEMBL

E1JHK1

Related

FBpp0080561

Conserved Domains (2) summary

cd07887
Location:78 → 252

RHD-n_Dorsal_Dif; N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Dorsal

pfam16179
Location:256 → 358

RHD_dimer; Rel homology dimerization domain
NM_001169527.2 → NP_001162998.1 Dorsal-related immunity factor, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001162998.1

Status: REVIEWED

UniProtKB/TrEMBL

E1JHK2

Conserved Domains (2) summary

cd07887
Location:78 → 252

RHD-n_Dorsal_Dif; N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Dorsal

pfam16179
Location:256 → 358

RHD_dimer; Rel homology dimerization domain