Human Gene GFRA2 (ENST00000517892.5) from GENCODE V44
  Description: Homo sapiens GDNF family receptor alpha 2 (GFRA2), transcript variant 2, mRNA. (from RefSeq NM_001165038)
RefSeq Summary (NM_001165038): Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009].
Gencode Transcript: ENST00000517892.5
Gencode Gene: ENSG00000168546.11
Transcript (Including UTRs)
   Position: hg38 chr8:21,693,182-21,788,159 Size: 94,978 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg38 chr8:21,693,278-21,788,159 Size: 94,882 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:21,693,182-21,788,159)mRNA (may differ from genome)Protein (359 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GFRA2_HUMAN
DESCRIPTION: RecName: Full=GDNF family receptor alpha-2; Short=GDNF receptor alpha-2; Short=GDNFR-alpha-2; Short=GFR-alpha-2; AltName: Full=GDNF receptor beta; Short=GDNFR-beta; AltName: Full=Neurturin receptor alpha; Short=NRTNR-alpha; Short=NTNR-alpha; AltName: Full=RET ligand 2; AltName: Full=TGF-beta-related neurotrophic factor receptor 2; Flags: Precursor;
FUNCTION: Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor (By similarity).
TISSUE SPECIFICITY: Isoform 1 is found in both brain and placenta.
SIMILARITY: Belongs to the GDNFR family.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: GFRA2
Diseases sorted by gene-association score: malignant granular cell myoblastoma (16), hirschsprung disease 1 (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.27 RPKM in Thyroid
Total median expression: 70.12 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -12.7096-0.132 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016017 - GDNF/GAS1
IPR003438 - GDNF_rcpt
IPR003504 - GDNF_rcpt_a2
IPR017372 - Glial_neurotroph_fac_rcpt_a1/2

Pfam Domains:
PF02351 - GDNF/GAS1 domain

ModBase Predicted Comparative 3D Structure on O00451
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0016167 glial cell-derived neurotrophic factor receptor activity
GO:0038023 signaling receptor activity

Biological Process:
GO:0000165 MAPK cascade
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0033141 positive regulation of peptidyl-serine phosphorylation of STAT protein
GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway

Cellular Component:
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0019898 extrinsic component of membrane
GO:0031225 anchored component of membrane


-  Descriptions from all associated GenBank mRNAs
  BC033096 - Homo sapiens GDNF family receptor alpha 2, mRNA (cDNA clone IMAGE:5460331).
BC041688 - Homo sapiens GDNF family receptor alpha 2, mRNA (cDNA clone MGC:48679 IMAGE:5729102), complete cds.
LF385010 - JP 2014500723-A/192513: Polycomb-Associated Non-Coding RNAs.
MA620587 - JP 2018138019-A/192513: Polycomb-Associated Non-Coding RNAs.
U97145 - Homo sapiens RET ligand 2 (RETL2) mRNA, complete cds.
AK299623 - Homo sapiens cDNA FLJ53091 complete cds, highly similar to GDNF family receptor alpha-2 precursor.
AF002700 - Homo sapiens GDNF family receptor alpha 2 (GFRalpha2) mRNA, complete cds.
AY326396 - Homo sapiens glial cell line-derived neurotrophic factor family receptor alpha2c mRNA, complete cds.
AY941828 - Homo sapiens glial cell line-derived neurotrophic factor family receptor alpha2b mRNA, complete cds.
U93703 - Human glial cell line-derived neurotrophic factor receptor beta (GDNFR-beta) mRNA, complete cds.
JF432396 - Synthetic construct Homo sapiens clone IMAGE:100073598 GDNF family receptor alpha 2 (GFRA2) gene, encodes complete protein.
KJ891237 - Synthetic construct Homo sapiens clone ccsbBroadEn_00631 GFRA2 gene, encodes complete protein.
AB529071 - Synthetic construct DNA, clone: pF1KB4017, Homo sapiens GFRA2 gene for GDNF family receptor alpha 2, without stop codon, in Flexi system.
CU692022 - Synthetic construct Homo sapiens gateway clone IMAGE:100021149 5' read GFRA2 mRNA.
JD193611 - Sequence 174635 from Patent EP1572962.
JD458638 - Sequence 439662 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O00451 (Reactome details) participates in the following event(s):

R-HSA-8871226 RET binds GFRA1,GFRA2
R-HSA-375149 Interaction of NCAM1 with GFRalpha-1
R-HSA-8853789 GDNF,NRTN bind RET:GFRA1,GFRA2
R-HSA-375144 Interaction of NCAM1:GFRalpha-1 with GDNF
R-HSA-8853762 RET dimerizes
R-HSA-8853737 2x p-5Y-RET:GDNF:GFRA complexes bind SHC1
R-HSA-8853753 2x p-5Y-RET:GDNF:GFRA complexes bind GRB7,10
R-HSA-8853755 2x p-5Y-RET:GDNF:GFRA complexes bind PLCgamma1
R-HSA-8854899 2x p-5Y-RET:GDNF:GFRA complexes bind GRB2-1:SOS1
R-HSA-8855564 2x p-5Y-RET:GDNF:GFRA complexes bind FRS2
R-HSA-8855617 2x p-5Y-RET:GDNF:GFRA complexes binds DOK1,DOK2,DOK4,DOK5,DOK6
R-HSA-8855747 2x p-5Y-RET:GDNF:GFRA complexes bind SRC1, RAP1GAP
R-HSA-8855915 2x p-5Y-RET:GDNF:GFRA complexes bind RET interactors
R-HSA-8853792 RET tyrosine phosphorylation
R-HSA-8854908 PKA phosphorylates RET:GDNF:GFRA dimer
R-HSA-8853734 2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-8855508 p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11
R-HSA-8853659 RET signaling
R-HSA-419037 NCAM1 interactions
R-HSA-422475 Axon guidance
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-1266738 Developmental Biology
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000517892.1, ENST00000517892.2, ENST00000517892.3, ENST00000517892.4, GDNFRB, GFRA2_HUMAN, NM_001165038, O00451, O15316, O15328, Q6GTR9, Q7Z5C2, RETL2, TRNR2, uc003wzv.1, uc003wzv.2
UCSC ID: ENST00000517892.5
RefSeq Accession: NM_001165038
Protein: O00451 (aka GFRA2_HUMAN or GFR2_HUMAN)
CCDS: CCDS55208.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.