Ret ret proto-oncogene [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Retprovided by RGD
Official Full Name: ret proto-oncogeneprovided by RGD
Primary source: RGD:3556
See related: EnsemblRapid:ENSRNOG00000014751 AllianceGenome:RGD:3556
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Predicted to enable calcium ion binding activity and transmembrane receptor protein tyrosine kinase activity. Involved in several processes, including innervation; positive regulation of neuron maturation; and retina development in camera-type eye. Located in several cellular components, including dendrite; early endosome; and neuronal cell body. Biomarker of Parkinsonism; brain ischemia; and pheochromocytoma. 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, Nov 2024]
Expression: Biased expression in Brain (RPKM 34.7), Lung (RPKM 33.7) and 7 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 4q42

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	4	NC_086022.1 (152998344..153040556, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	4	NC_051339.1 (151325969..151368176, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	4	NC_005103.4 (150202170..150249196, complement)

Chromosome 4 - NC_086022.1 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

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential expression of RET and GDNF family receptor, GFR-alpha1, between striatum and substantia nigra following nigrostriatal lesion: A case for diminished GDNF-signaling.
Title: Differential expression of RET and GDNF family receptor, GFR-α1, between striatum and substantia nigra following nigrostriatal lesion: A case for diminished GDNF-signaling.
GDNF requires HIF-1alpha and RET activation for suppression of programmed cell death of enteric neurons by metabolic challenge.
Title: GDNF requires HIF-1α and RET activation for suppression of programmed cell death of enteric neurons by metabolic challenge.
The findings demonstrate that elevated GDNF levels can reduce the retinal injury, whereby down-regulated miR-216a aggravates the YAG laser-induced retinal injury by targeting the GDNF level through the GDNF/GFRa1/RET signaling pathway.
Title: Down-regulation of microRNA-216a confers protection against yttrium aluminium garnet laser-induced retinal injury via the GDNF-mediated GDNF/GFRα1/RET signalling pathway.
the inverse relationship between GFRalpha1 and C-Ret, as knocking down C-Ret led to increases in GFRalpha1 expression.
Title: Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons.
activation of the MAPK and PI3K-AKT pathways primarily regulated Ser-727 phosphorylation, whereas a physical interaction between RET/PTC3 and STAT1, followed by a direct tyrosine phosphorylation event, was necessary for STAT1 Tyr-701 phosphorylation. These data provide the first evidence of a direct link between IDO1 expression and the oncogenic activation of RET in thyroid carcinoma
Title: Signal Transducer and Activator of Transcription 1 Plays a Pivotal Role in RET/PTC3 Oncogene-induced Expression of Indoleamine 2,3-Dioxygenase 1.
These data provide the first evidence for a physiologic role of these isoforms in RET pathway function.
Title: Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction.
STAT3 phosphorylation by neurturin was found to be mediated specifically by GFRalpha2c and RET9 isoforms.
Title: GDNF family ligand dependent STAT3 activation is mediated by specific alternatively spliced isoforms of GFRα2 and RET.
Ret receptor is one of the IB4-reactive glycoconjugate accounting for the IB4 stain in microglia under physiological and ischemic conditions.
Title: The isolectin IB4 binds RET receptor tyrosine kinase in microglia.
Identification of a key motif that determines the differential surface levels of RET and TrkB tyrosine kinase receptors and controls depolarization enhanced RET surface insertion.
Title: Identification of a key motif that determines the differential surface levels of RET and TrkB tyrosine kinase receptors and controls depolarization enhanced RET surface insertion.
Tyr981 in the intracellular domain of RET was crucial for the interaction with Rap1GAP.
Title: Rap1GAP interacts with RET and suppresses GDNF-induced neurite outgrowth.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Ret (e-PCR), detects polymorphism
- UniSTS:144346

AA859878 (e-PCR)
- UniSTS:243948

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
enables transmembrane receptor protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in GDF15-GFRAL signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in Peyer's patch morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cell surface receptor protein tyrosine kinase signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cellular response to retinoic acid	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within embryonic epithelial tube formation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within enteric nervous system development	ISO Inferred from Sequence Orthology more info
involved_in glial cell-derived neurotrophic factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in glial cell-derived neurotrophic factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in homophilic cell adhesion via plasma membrane adhesion molecules	IEA Inferred from Electronic Annotation more info
involved_in innervation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein proteolysis	ISO Inferred from Sequence Orthology more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within nervous system development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neural crest cell migration	ISO Inferred from Sequence Orthology more info
involved_in neuron cell-cell adhesion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron maturation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell adhesion mediated by integrin	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cell size	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of metanephric glomerulus development	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of peptidyl-serine phosphorylation of STAT protein	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of axonogenesis	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in response to pain	ISO Inferred from Sequence Orthology more info
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in retina development in camera-type eye	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within ureter maturation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within ureteric bud development	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of plasma membrane protein complex	ISO Inferred from Sequence Orthology more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: proto-oncogene tyrosine-protein kinase receptor Ret

Names: Ret gene for receptor tyrosin; Ret proto-oncogene (multiple endocrine neoplasia MEN2A MEN2B and medullary thyroid carcinoma 1 Hirschsprung disease); receptor tyrosine kinase

NP_001103569.1

EC 2.7.10.1

NP_036775.2

EC 2.7.10.1

XP_063141631.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001110099.1 → NP_001103569.1 proto-oncogene tyrosine-protein kinase receptor Ret isoform b precursor

See identical proteins and their annotated locations for NP_001103569.1

Status: PROVISIONAL

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (b) has a shorter and unique C-terminus compared to isoform a.

Source sequence(s)

JAXUCZ010000004

UniProtKB/TrEMBL

A6IL58

Conserved Domains (3) summary

cd05045
Location:724 → 1013

PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein

pfam00028
Location:173 → 248

Cadherin; Cadherin domain

pfam07714
Location:725 → 1006

Pkinase_Tyr; Protein tyrosine kinase
NM_012643.2 → NP_036775.2 proto-oncogene tyrosine-protein kinase receptor Ret isoform a precursor

See identical proteins and their annotated locations for NP_036775.2

Status: PROVISIONAL

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

JAXUCZ010000004

UniProtKB/Swiss-Prot

G3V9H8, Q9EPA1, Q9EPC3

Related

ENSRNOP00000047793.3, ENSRNOT00000047685.6

Conserved Domains (3) summary

cd05045
Location:724 → 1013

PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein

pfam00028
Location:173 → 248

Cadherin; Cadherin domain

pfam07714
Location:725 → 1006

Pkinase_Tyr; Protein tyrosine kinase