Ret Ret oncogene [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Retprovided by FlyBase
Official Full Name: Ret oncogeneprovided by FlyBase
Primary source: FLYBASE:FBgn0011829
Locus tag: Dmel_CG14396
See related: AllianceGenome:FB:FBgn0011829
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: CG1061; CG14396; D-ret; Dmel\CG14396; DmHD-59; DmRet; dret; dRet; dRET; Dret; DRet; DRET; HD-59; MEN2; ret; RET; Reto
Summary: Enables integrin binding activity and kinase activity. Involved in several processes, including dendrite development; positive regulation of cell-matrix adhesion; and regulation of dendrite development. Located in cell surface; dendrite; and plasma membrane. Is expressed in several structures, including embryonic/larval head sense organ; ganglia; germline cell; gut section; and somatic precursor cell. Used to study Hirschsprung's disease; cancer; familial medullary thyroid carcinoma; multiple endocrine neoplasia type 2A; and multiple endocrine neoplasia type 2B. Human ortholog(s) of this gene implicated in several diseases, including Hirschsprung's disease; familial medullary thyroid carcinoma; multiple endocrine neoplasia type 2A; multiple endocrine neoplasia type 2B; and pheochromocytoma. Orthologous to human RET (ret proto-oncogene). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 39B1-39B1; 2-54 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2L	NT_033779.5 (21182446..21198762, complement)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2L	NT_033779.4 (21182446..21198762, complement)

Chromosome 2L - NT_033779.5 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?

Gfrl shares the same enteric nervous system (ENS) and feeding defects with Ret, suggesting that Ret and Gfrl might function together via a common ligand. We identified the TGFbeta family member Maverick (Mav) as a ligand for Gfrl and a Mav chromosomal deficiency displayed similar embryonic ENS defects. Results suggest that the Ret and Gfrl families co-evolved before the separation of invertebrate and vertebrate lineages.
Title: The Drosophila Ret gene functions in the stomatogastric nervous system with the Maverick TGFβ ligand and the Gfrl co-receptor.
We demonstrate that this phospho-S909 arises from an intrinsic RET dual-specificity kinase activity and show that an equivalent serine is required for RET signaling in Drosophila. Our findings reveal dual-specificity and allosteric components for the mechanism of RET activation and signaling with direct implications for drug discovery
Title: RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements.
Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases.
Title: Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.
Ret as a regulator in dendrite patterning and adhesion distinct from its role in axon guidance, is proposed.
Title: The Ret receptor regulates sensory neuron dendrite growth and integrin mediated adhesion.
A signaling active version of Ret (Ret(MENB) rescues muscle degeneration, disintegration of mitochondria and ATP content of Pink1 mutants.
Title: Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants.
Significant conservation between the biological effects elicited by the human and Drosophila RET kinases was shown which suggests functions for dRET in neuronal differentiation in the fly.
Title: Drosophila RET contains an active tyrosine kinase and elicits neurotrophic activities in mammalian cells.
strong propensity to self-association in the RET-transmembrane underlies - and may be required for - dimer formation and oncogenic activation of juxtamembrane cysteine mutants of RET
Title: Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutations.

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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 ATP binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in actin filament organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell-matrix adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: Ret oncogene

Names: CG14396-PA; CG14396-PB; CG14396-PC; Ret-PA; Ret-PB; Ret-PC; dret

NP_477044.1

EC 2.7.10.1

NP_724315.1

EC 2.7.10.1

NP_724316.1

EC 2.7.10.1

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

21182446..21198762 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_057696.4 → NP_477044.1 Ret oncogene, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_477044.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KA88, Q7KT06

Related

FBpp0081023

Conserved Domains (2) summary

smart00219
Location:771 → 1042

TyrKc; Tyrosine kinase, catalytic domain

cl21453
Location:770 → 1049

PKc_like; Protein Kinases, catalytic domain
NM_165358.2 → NP_724315.1 Ret oncogene, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_724315.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KA88, Q7KT06

Related

FBpp0081022

Conserved Domains (2) summary

smart00219
Location:771 → 1042

TyrKc; Tyrosine kinase, catalytic domain

cl21453
Location:770 → 1049

PKc_like; Protein Kinases, catalytic domain
NM_165359.2 → NP_724316.1 Ret oncogene, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_724316.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KA88, Q7KT06

Related

FBpp0081021

Conserved Domains (2) summary

smart00219
Location:771 → 1042

TyrKc; Tyrosine kinase, catalytic domain

cl21453
Location:770 → 1049

PKc_like; Protein Kinases, catalytic domain

Nucleotide		Protein
Heading	Accession and Version	Protein

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q7JQD5		Q7JQD5
Q7KA88		Q7KA88
Q7KA90		Q7KA90
Q7KAN0		Q7KAN0
Q7KT06		Q7KT06
Q95RP6		Q95RP6
Q9BHA9		Q9BHA9
Q9GP67		Q9GP67
Q9GP68		Q9GP68
Q9VIE4		Q9VIE4