GFRA2 (gene)

GDNF family receptor alpha-2 (GFRα2), also known as the neurturin receptor, is a protein that in humans is encoded by the GFRA2 gene.[5][6]

GFRA2
Identifiers
Aliases	GFRA2, GDNFRB, NRTNR-ALPHA, NTNRA, RETL2, TRNR2, GDNF family receptor alpha 2
External IDs	OMIM: 601956 MGI: 1195462 HomoloGene: 1145 GeneCards: GFRA2
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p21.3 Start 21,690,398 bp[1] End 21,812,357 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 D2 Start 70,890,120 bp[2] End 70,979,838 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • Ras guanyl-nucleotide exchange factor activity • glial cell-derived neurotrophic factor receptor activity • signaling receptor activity Cellular component • anchored component of membrane • membrane • extrinsic component of membrane • cell membrane • intracellular • external side of plasma membrane • receptor complex Biological process • glial cell-derived neurotrophic factor receptor signaling pathway • nervous system development • transmembrane receptor protein tyrosine kinase signaling pathway • MAPK cascade • axon guidance • positive regulation of peptidyl-serine phosphorylation of STAT protein • negative regulation of protein autophosphorylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2675	14586
Ensembl	ENSG00000168546	ENSMUSG00000022103
UniProt	O00451	O08842
RefSeq (mRNA)	NM_001165038 NM_001165039 NM_001495	NM_008115 NM_001302094 NM_001302095
RefSeq (protein)	NP_001158510 NP_001158511 NP_001486	NP_001289023 NP_001289024 NP_032141
Location (UCSC)	Chr 8: 21.69 – 21.81 Mb	Chr 14: 70.89 – 70.98 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Interactions

GFRA2 (gene) has been shown to interact with GDNF.[7][8]

See also

• GFRα

References

1. GRCh38: Ensembl release 89: ENSG00000168546 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022103 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: GFRA2 GDNF family receptor alpha 2".
7. 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.
8. 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.