upd3 unpaired 3 [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: upd3provided by FlyBase
Official Full Name: unpaired 3provided by FlyBase
Primary source: FLYBASE:FBgn0053542
Locus tag: Dmel_CG33542
See related: AllianceGenome:FB:FBgn0053542
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: cg15062; CG15062; CG15062/CG5963; CG33542; cg5963; CG5963; Dmel\CG33542; od; odsy; os; sy; Unpaireds; upd; Upd; upd 3; upd-3; Upd-3; Upd-like; Upd3; UPD3
Summary: Enables cytokine activity. Involved in several processes, including intestinal epithelial structure maintenance; intestinal stem cell homeostasis; and lamellocyte differentiation. Located in extracellular space. Is expressed in several structures, including adult anal pad; cortical zone of lymph gland primary lobe; cuboidal/columnar epithelium; dorsal mesothoracic pleura primordium; and gut section. Used to study cancer. [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 17A4-17A4; 1-60 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	X	NC_004354.4 (18277233..18284596)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	X	NC_004354.3 (18171266..18178629)

Chromosome X - NC_004354.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Coordination of tumor growth and host wasting by tumor-derived Upd3.
Title: Coordination of tumor growth and host wasting by tumor-derived Upd3.
we show that loss of PGANT4 disrupts the mucosal barrier, resulting in epithelial expression of the IL-6-like cytokine Upd3, leading to activation of JAK/STAT signaling, differentiation of cells that form the progenitor cell niche, and abnormal proliferation of progenitor cells. This niche disruption could be recapitulated by overexpressing upd3 and rescued by deleting upd3, highlighting a crucial role for this cytokine.
Title: Loss of the mucosal barrier alters the progenitor cell niche via Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling.
Infection-induced upd3 expression in enterocytes requires the indirect functions of snail and its transcriptional co-repressors, as well as homeodomain transcription factors and epigenetic regulators. Upd3 transcription is regulated by a combination of microbe-responsive, cell-specific and region-specific enhancers.
Title: Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.
Our study shows that haemocytes express the three upd genes and that injury markedly induces the expression of upd3 by the JNK pathway in haemocytes, which in turn activates the JAK/STAT pathway in the fat body and the gut. Surprisingly, release of Upd3 from haemocytes upon injury can remotely stimulate stem cell proliferation and the expression of Drosomycin-like genes in the intestine.
Title: Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila.
controls glucose metabolism and reduces lifespan on a lipid-rich diet via activation of the JAK-STAT pathway
Title: Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet.
unpaired 3 is essential for a subset of JAK-mediated developmental functions.
Title: Pleiotropy of the Drosophila JAK pathway cytokine Unpaired 3 in development and aging.
Drosophila protein Upd3 is related to vertebrate IL-6 and has a role as a monomeric-alpha helical cytokine, an ancestor of the four-helix bundle cytokines
Title: Upd3--an ancestor of the four-helix bundle cytokines.
The production of the UPD3 cytokine in stem cell progeny stimulates intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment.
Title: The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment.
Data suggest that the Imd pathway is not fundamental in regulating the levels of unpaired-3, whereas it controls the expression of the putative cytokine Drosophila helical factor.
Title: unpaired (upd)-3 expression and other immune-related functions are stimulated by interleukin-8 in Drosophila melanogaster SL2 cell line.

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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 cytokine activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in antimicrobial humoral response	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway via JAK-STAT	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic development via the syncytial blastoderm	IEA Inferred from Electronic Annotation more info
involved_in intestinal epithelial structure maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intestinal stem cell homeostasis	IEP Inferred from Expression Pattern more info	PubMed
involved_in intestinal stem cell homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lamellocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in oogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in paracrine signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in wound healing	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	ISM Inferred from Sequence Model more info	PubMed

General protein information

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Preferred Names: unpaired 3

Names: CG33542-PB; Unpaired3; Upd3; outstretched; outstretched-smalleye; small-eye; unpaired; unpaired 3beta; unpaired-3; unpaired-3.3; unpaired-like protein 3; upd homolog; upd3-PB