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Gfra2 glial cell line derived neurotrophic factor family receptor alpha 2 [ Mus musculus (house mouse) ]

Gene ID: 14586, updated on 21-Apr-2024

Summary

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Official Symbol
Gfra2provided by MGI
Official Full Name
glial cell line derived neurotrophic factor family receptor alpha 2provided by MGI
Primary source
MGI:MGI:1195462
See related
Ensembl:ENSMUSG00000022103 AllianceGenome:MGI:1195462
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary
The protein encoded by this gene is part of the receptor complex that transduces glial cell-derived neurotrophic factor and neurturin signals by mediating autophosphorylation and activation of the RET receptor. Mice lacking this protein are viable and fertile but display growth retardation attributed to impaired salivary and pancreatic secretion and innervation deficits in the intestinal tract. In addition, knockout mice display neural defects including a failure to initiate outgrowth of dorsal ganglion root neurons, demonstrating a requirement in neuronal differentiation of these cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
Expression
Broad expression in testis adult (RPKM 14.5), cortex adult (RPKM 10.9) and 22 other tissues See more
Orthologs
human all
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Genomic context

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Location:
14 D2; 14 36.79 cM
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 14 NC_000080.7 (71127547..71217280)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 14 NC_000080.6 (70890107..70979840)

Chromosome 14 - NC_000080.7Genomic Context describing neighboring genes Neighboring gene RIKEN cDNA 2410012E07 gene Neighboring gene predicted gene, 34500 Neighboring gene STARR-seq mESC enhancer starr_37094 Neighboring gene predicted gene, 34588 Neighboring gene CapStarr-seq enhancer MGSCv37_chr14:71363450-71363603 Neighboring gene CapStarr-seq enhancer MGSCv37_chr14:71394528-71394637 Neighboring gene STARR-seq mESC enhancer starr_37095 Neighboring gene predicted gene, 34703 Neighboring gene STARR-seq mESC enhancer starr_37097 Neighboring gene CapStarr-seq enhancer MGSCv37_chr14:71475540-71475723 Neighboring gene STARR-seq mESC enhancer starr_37098 Neighboring gene STARR-seq mESC enhancer starr_37099 Neighboring gene predicted gene, 34757

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Lack of cholinergic innervation in gastric mucosa does not affect gastrin secretion or basal acid output in neurturin receptor GFRα2 deficient mice. Kupari J, et al. J Physiol, 2013 Apr 15. PMID 23339174, Free PMC Article
  2. Deficient nonpeptidergic epidermis innervation and reduced inflammatory pain in glial cell line-derived neurotrophic factor family receptor alpha2 knock-out mice. Lindfors PH, et al. J Neurosci, 2006 Feb 15. PMID 16481427, Free PMC Article
  3. Parasympathetic innervation and function of endocrine pancreas requires the glial cell line-derived factor family receptor alpha2 (GFRalpha2). Rossi J, et al. Diabetes, 2005 May. PMID 15855316
  4. Impaired behavioural flexibility and memory in mice lacking GDNF family receptor alpha2. Võikar V, et al. Eur J Neurosci, 2004 Jul. PMID 15245503
  5. Sympathetic cholinergic target innervation requires GDNF family receptor GFR alpha 2. Hiltunen PH, et al. Mol Cell Neurosci, 2004 Jul. PMID 15234349

See all (105) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase.
    Title: GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway.
  2. Ret and Gfra2 null mice display comparable early central projection deficits, but Gfra2 null rapidly adapting mechanoreceptors recover later.
    Title: Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors.
  3. neurons switch their GFRalpha signaling pathways during postnatal development
    Title: Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.
  4. 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.
  5. Cholinergic innervation of gastric mucosa depends on neurturin-GFRalpha2 signalling but is dispensable for gastrin secretion and for basal and maximal acid output
    Title: Lack of cholinergic innervation in gastric mucosa does not affect gastrin secretion or basal acid output in neurturin receptor GFRα2 deficient mice.
  6. our data demonstrate that RET/GFRalpha signals are dispensable for thymic T cell development in vivo
    Title: RET/GFRα signals are dispensable for thymic T cell development in vivo.
  7. Increased apoptosis of parasympathetic but not enteric neurons in the developing pancreas of mice lacking GFRalpha2.
    Title: Increased apoptosis of parasympathetic but not enteric neurons in mice lacking GFRalpha2.
  8. Demonstrate a role for GFRalpha2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.
    Title: Role of glial cell-line derived neurotropic factor family receptor alpha2 in the actions of the glucagon-like peptides on the murine intestine.
  9. The knockout mice of GFRalpha2 displayed significant impairment in contextual fear conditioning and conditioned taste aversion tests of memory.
    Title: Impaired behavioural flexibility and memory in mice lacking GDNF family receptor alpha2.
  10. Transduction-function role for GFR alpha2/neurturin signalling in a specific class of sensory neurons.
    Title: GFR alpha2/neurturin signalling regulates noxious heat transduction in isolectin B4-binding mouse sensory neurons.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (2)  1 citation
  • Endonuclease-mediated (3) 

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables glial cell-derived neurotrophic factor receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glial cell-derived neurotrophic factor receptor activity ISO
Inferred from Sequence Orthology
more info
  
enables heparan sulfate binding ISO
Inferred from Sequence Orthology
more info
  
enables signaling receptor activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within cell surface receptor protein tyrosine kinase signaling pathway IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in glial cell-derived neurotrophic factor receptor signaling pathway ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of protein autophosphorylation ISO
Inferred from Sequence Orthology
more info
  
involved_in nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within nervous system development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
part_of receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in side of membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
GDNF family receptor alpha-2
Names
GDNF receptor beta
GDNFR-alpha-2
GDNFR-beta
GFR alpha 2
NRTNR-alpha
NTNR-alpha
TGF-beta-related neurotrophic factor receptor 2
neurturin receptor alpha

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)

  1. NM_001302094.1 → NP_001289023.1  GDNF family receptor alpha-2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region. This results in a shorter protein (isoform 2) compared to isoform 1.
    Source sequence(s)
    AC124202, AI462772, AK138512, AK149349, BY257515
    UniProtKB/Swiss-Prot
    O08842
    UniProtKB/TrEMBL
    Q3UET6
    Conserved Domains (1) summary
    pfam02351
    Location:146 → 242
    GDNF; GDNF/GAS1 domain

  2. NM_001302095.1 → NP_001289024.1  GDNF family receptor alpha-2 isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two consecutive in-frame exons in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 3) compared to isoform 1. This isoform (3) may undergo proteolytic processing similar to isoform 1.
    Source sequence(s)
    AC124202, AI462772, AK138512, AK149349, BY257515, CN539269
    Consensus CDS
    CCDS88711.1
    UniProtKB/Swiss-Prot
    O08842
    UniProtKB/TrEMBL
    Q3UET6
    Related
    ENSMUSP00000154391.2, ENSMUST00000227697.2
    Conserved Domains (1) summary
    pfam02351
    Location:118 → 214
    GDNF; GDNF/GAS1 domain

  3. NM_008115.3 → NP_032141.2  GDNF family receptor alpha-2 isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_032141.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC124202, AI462772, AK138512, AK149349, BY257515
    Consensus CDS
    CCDS27263.1
    UniProtKB/Swiss-Prot
    O08842, Q3UUD8, Q920Y3, Q9Z2A2, Q9Z2A3
    Related
    ENSMUSP00000022699.9, ENSMUST00000022699.10
    Conserved Domains (2) summary
    smart00907
    Location:40 → 113
    GDNF; GDNF/GAS1 domain
    pfam02351
    Location:251 → 347
    GDNF; GDNF/GAS1 domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000080.7 Reference GRCm39 C57BL/6J

    Range
    71127547..71217280
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O08842.2 GenPept UniProtKB/Swiss-Prot:O08842

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