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Protein-coding gene in the species Homo sapiens
GDNF family receptor alpha-1 (GFRα1 ), also known as the GDNF receptor , is a protein that in humans is encoded by the GFRA1 gene .[ 5] [ 6]
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 gene is a candidate gene for Hirschsprung disease . Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.[ 7]
GDNF family receptor alpha 1 has been shown to interact with GDNF[ 8] [ 9] [ 9] [ 10]
^ a b c GRCh38: Ensembl release 89: ENSG00000151892 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025089 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Gorodinsky A, Zimonjic DB, Popescu NC, Milbrandt J (March 1998). "Assignment of the GDNF family receptor alpha-1 (GFRA1) to human chromosome band 10q26 by in situ hybridization". Cytogenetics and Cell Genetics . 78 (3–4): 289–90. doi :10.1159/000134674 . PMID 9465905 . ^ Angrist M, Jing S, Bolk S, Bentley K, Nallasamy S, Halushka M, Fox GM, Chakravarti A (Mar 1998). "Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility". Genomics . 48 (3): 354–62. doi :10.1006/geno.1997.5191 . PMID 9545641 . ^ "Entrez Gene: GFRA1 GDNF family receptor alpha 1" .^ 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 . ^ a b 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 . ^ 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. Bibcode :1997Natur.387..717K . doi :10.1038/42722 PMID 9192898 . S2CID 4360246 .
Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A (Jul 1996). "Characterization of a multicomponent receptor for GDNF". Nature . 382 (6586): 80–3. Bibcode :1996Natur.382...80T . doi :10.1038/382080a0 . PMID 8657309 . S2CID 4253979 . Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM (Jun 1996). "GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF" . Cell . 85 (7): 1113–24. doi :10.1016/S0092-8674(00)81311-2 PMID 8674117 . S2CID 1724567 . Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery" . Genome Research . 6 (9): 791–806. doi :10.1101/gr.6.9.791 PMID 8889548 . Gattei V, Celetti A, Cerrato A, Degan M, De Iuliis A, Rossi FM, Chiappetta G, Consales C, Improta S, Zagonel V, Aldinucci D, Agosti V, Santoro M, Vecchio G, Pinto A, Grieco M (Apr 1997). "Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment". Blood . 89 (8): 2925–37. PMID 9108413 . 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. Bibcode :1997PNAS...94.6238S . doi :10.1073/pnas.94.12.6238 PMC 21033 PMID 9177201 . 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. Bibcode :1997Natur.387..717K . doi :10.1038/42722 PMID 9192898 . S2CID 4360246 . 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 . Eng C, Myers SM, Kogon MD, Sanicola M, Hession C, Cate RL, Mulligan LM (Feb 1998). "Genomic structure and chromosomal localization of the human GDNFR-alpha gene". Oncogene . 16 (5): 597–601. doi :10.1038/sj.onc.1201573 . PMID 9482105 . S2CID 735754 . Shefelbine SE, Khorana S, Schultz PN, Huang E, Thobe N, Hu ZJ, Fox GM, Jing S, Cote GJ, Gagel RF (Apr 1998). "Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux". Human Genetics . 102 (4): 474–8. doi :10.1007/s004390050724 . PMID 9600247 . S2CID 5631327 . Cacalano G, Fariñas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A (Jul 1998). "GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney" . Neuron . 21 (1): 53–62. doi :10.1016/S0896-6273(00)80514-0 . PMC 2710137 PMID 9697851 . Enokido Y, de Sauvage F, Hongo JA, Ninkina N, Rosenthal A, Buchman VL, Davies AM (Sep 1998). "GFR alpha-4 and the tyrosine kinase Ret form a functional receptor complex for persephin" . Current Biology . 8 (18): 1019–22. Bibcode :1998CBio....8.1019E . doi :10.1016/S0960-9822(07)00422-8 PMID 9740802 . 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 . Hase A, Suzuki H, Arahata K, Akazawa C (Jul 1999). "Expression of human GFR alpha-1 (GDNF receptor) at the neuromuscular junction and myelinated nerves". Neuroscience Letters . 269 (1): 55–7. doi :10.1016/S0304-3940(99)00419-X . hdl :10271/1630 PMID 10821644 . S2CID 54274004 . 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 . Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibáñez CF (Jan 2001). "Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts" (PDF) . Neuron . 29 (1): 171–84. doi :10.1016/S0896-6273(01)00188-X . PMID 11182089 . S2CID 14757558 . Gimm O, Dziema H, Brown J, Hoang-Vu C, Hinze R, Dralle H, Mulligan LM, Eng C (Apr 2001). "Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma" . Oncogene . 20 (17): 2161–70. doi :10.1038/sj.onc.1204289 PMID 11360200 . Japón MA, Urbano AG, Sáez C, Segura DI, Cerro AL, Diéguez C, Alvarez CV (Apr 2002). "Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors" . The Journal of Clinical Endocrinology and Metabolism . 87 (4): 1879–84. doi :10.1210/jcem.87.4.8383 PMID 11932334 .
Overview of all the structural information available in the PDB for UniProt : P56159 PDBe-KB .
Angiopoietin CNTF EGF (ErbB)
FGF
FGFR1 FGFR2
Agonists: Ersofermin FGF (1 , 2 (bFGF) , 3 , 4 , 5 , 6 , 7 (KGF ), 8 , 9 , 10 (KGF2) , 17 , 18 , 22 )Palifermin Repifermin Selpercatinib Sprifermin Trafermin FGFR3 FGFR4 Unsorted
HGF (c-Met) IGF
LNGF (p75NTR ) PDGF RET (GFL)
SCF (c-Kit) TGFβ Trk
TrkA
Negative allosteric modulators: VM-902A TrkB
Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 TrkC
VEGF Others
Additional growth factors: Adrenomedullin Colony-stimulating factors (see here instead)Connective tissue growth factor (CTGF) Ephrins (A1 , A2 , A3 , A4 , A5 , B1 , B2 , B3 )Erythropoietin (see here instead)Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins /T-cell growth factors (see here instead)Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (see here instead)Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
