GFRA2 (gene)

GDNF family receptor alpha 2
Identifiers
Symbols	GFRA2 ; GDNFRB; NRTNR-ALPHA; NTNRA; RETL2; TRNR2
External IDs	OMIM: 601956 MGI: 1195462 HomoloGene: 1145 IUPHAR: 1744 GeneCards: GFRA2 Gene
Gene ontology Molecular function • glial cell-derived neurotrophic factor receptor activity Cellular component • plasma membrane • extrinsic component of membrane • anchored component of membrane Biological process • transmembrane receptor protein tyrosine kinase signaling pathway • nervous system development • negative regulation of protein autophosphorylation • glial cell-derived neurotrophic factor receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2675	14586
Ensembl	ENSG00000168546	ENSMUSG00000022103
UniProt	O00451	O08842
RefSeq (mRNA)	NM_001165038	NM_001302094
RefSeq (protein)	NP_001158510	NP_001289023
Location (UCSC)	Chr 8: 21.69 – 21.81 Mb	Chr 14: 70.89 – 70.98 Mb
PubMed search

GDNF family receptor alpha-2 (GFRα2), also known as the neurturin receptor, is a protein that in humans is encoded by the GFRA2 gene.^[1][2]

Function

The GFRA2 protein is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor. It is part of the GDNF receptor family. 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. They both bind the GFRA2 receptor. The receptor 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.^[2]

Interactions

GFRA2 (gene) has been shown to interact with GDNF.^[3][4]

See also

• GFRα

References

1. Sanicola M, Hession C, Worley D, Carmillo P, Ehrenfels C, Walus L, Robinson S, Jaworski G, Wei H, Tizard R, Whitty A, Pepinsky RB, Cate RL (Jun 1997). "Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins". Proceedings of the National Academy of Sciences of the United States of America 94 (12): 6238–43. doi:10.1073/pnas.94.12.6238. PMC 21033. PMID 9177201.
2. "Entrez Gene: GFRA2 GDNF family receptor alpha 2".
3. Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM (Dec 1997). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family". The Journal of Biological Chemistry 272 (52): 33111–7. doi:10.1074/jbc.272.52.33111. PMID 9407096.
4. Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE (Sep 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". The Journal of Biological Chemistry 275 (36): 27505–12. doi:10.1074/jbc.M000306200. PMID 10829012.

Further reading

• Baloh RH, Tansey MG, Golden JP, Creedon DJ, Heuckeroth RO, Keck CL, Zimonjic DB, Popescu NC, Johnson EM, Milbrandt J (May 1997). "TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret". Neuron 18 (5): 793–802. doi:10.1016/S0896-6273(00)80318-9. PMID 9182803.
• Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A (Jun 1997). "A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor". Nature 387 (6634): 717–21. doi:10.1038/42722. PMID 9192898.
• Suvanto P, Wartiovaara K, Lindahl M, Arumae U, Moshnyakov M, Horelli-Kuitunen N, Airaksinen MS, Palotie A, Sariola H, Saarma M (Aug 1997). "Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha". Human Molecular Genetics 6 (8): 1267–73. doi:10.1093/hmg/6.8.1267. PMID 9259272.
• Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM (Dec 1997). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family". The Journal of Biological Chemistry 272 (52): 33111–7. doi:10.1074/jbc.272.52.33111. PMID 9407096. Check date values in: |year= / |date= mismatch (help)
• Tansey MG, Baloh RH, Milbrandt J, Johnson EM (Mar 2000). "GFRalpha-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival". Neuron 25 (3): 611–23. doi:10.1016/S0896-6273(00)81064-8. PMID 10774729.
• Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE (Sep 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". The Journal of Biological Chemistry 275 (36): 27505–12. doi:10.1074/jbc.M000306200. PMID 10829012.
• Vanhorne JB, Gimm O, Myers SM, Kaushik A, von Deimling A, Eng C, Mulligan LM (May 2001). "Cloning and characterization of the human GFRA2 locus and investigation of the gene in Hirschsprung disease". Human Genetics 108 (5): 409–15. doi:10.1007/s004390100506. PMID 11409869.
• Yoong LF, Too HP (May 2007). "Glial cell line-derived neurotrophic factor and neurturin inhibit neurite outgrowth and activate RhoA through GFR alpha 2b, an alternatively spliced isoform of GFR alpha 2". The Journal of Neuroscience 27 (21): 5603–14. doi:10.1523/JNEUROSCI.4552-06.2007. PMID 17522305.