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GFRA2 (gene)

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(Redirected fromGFRα2)

Protein-coding gene in the species Homo sapiens

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;OMA:GFRA2 - orthologs

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8p21.3	Start	21,690,398bp^[1]
Band	8p21.3	End	21,812,357bp^[1]

Gene location (Mouse)

Chr.	Chromosome 14 (mouse)^[2]

Band	14\|14 D2	Start	71,127,560bp^[2]
Band	14\|14 D2	End	71,217,278bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

secondary oocyte

Brodmann area 10

left lobe of thyroid gland

right lobe of thyroid gland

right frontal lobe

Brodmann area 9

primary visual cortex

cingulate gyrus

anterior cingulate cortex

testicle

Top expressed in

left lung lobe

median eminence

lumbar spinal ganglion

ascending aorta

aortic valve

lateral septal nucleus

genital tubercle

Gonadal ridge

molar

arcuate nucleus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	glial cell-derived neurotrophic factor receptor activity signaling receptor activity
Cellular component	anchored component of membrane membrane extrinsic component of membrane plasma membrane intracellular anatomical structure 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: 71.13 – 71.22 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

GDNF family receptor alpha-2 (GFRα2), also known as theneurturin receptor, is aprotein that in humans is encoded by theGFRA2gene.^[5]^[6]

Function

[edit]

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 theRET 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

[edit]

GFRA2 (gene) has been shown tointeract withGDNF.^[7]^[8]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000168546 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000022103 –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.
^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.
^^a ^b"Entrez Gene: GFRA2 GDNF family receptor alpha 2".
^Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM (December 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.
^Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE (September 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.

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.
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 (December 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.
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.S2CID 7677951.
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.PMC 6672776.PMID 17522305.

Growth factor receptor modulators

Angiopoietin

Agonists:Angiopoietin 1
Angiopoietin 4

Antagonists:Angiopoietin 2
Angiopoietin 3

Kinase inhibitors:Altiratinib
CE-245677
Rebastinib

Antibodies:Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists:Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors:Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies:Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists:Unknown/none Antibodies:Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors:Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists:Neuregulins (heregulins) (1,2,6 (neuroglycan C)) Antibodies:Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists:Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1,2,3,4,5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,8,10 (KGF2),20) Repifermin Selpercatinib Trafermin Velafermin
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 Antibodies:Aprutumab Aprutumab ixadotin Kinase inhibitors:Infigratinib
FGFR3	Agonists:Ersofermin FGF (1,2 (bFGF),4,8,9,18,23) Selpercatinib Sprifermin Trafermin Antibodies:Burosumab (against FGF23)
FGFR4	Agonists:Ersofermin FGF (1,2 (bFGF),4,6,8,9,19) Trafermin
Unsorted	Agonists:FGF15/19

HGF (c-Met)

Agonists:Fosgonimeton
Hepatocyte growth factor

Potentiators:Dihexa (PNB-0408)

IGF

IGF-1	Agonists:des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors:BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies:AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists:Insulin-like growth factor-2 (somatomedin A) Antibodies:Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins:IGFBP (1,2,3,4,5,6,7) Cleavage products/derivatives with unknown target:Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies:Against NGF:ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers:Against NGF:RBM-004

Decoy receptors:LEVI-04 (p75^NTR-Fc)

PDGF

Agonists:Becaplermin
Platelet-derived growth factor (A,B,C,D)

RET (GFL)

GFRα1	Agonists:Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors:Vandetanib
GFRα2	Agonists:Neurturin (NRTN) Kinase inhibitors:Vandetanib
GFRα3	Agonists:Artemin (ARTN) Kinase inhibitors:Vandetanib
GFRα4	Agonists:Persephin (PSPN) Kinase inhibitors:Vandetanib
Unsorted	Kinase inhibitors:Agerafenib

SCF (c-Kit)

Agonists:Ancestim
Stem cell factor

TGFβ

Seehere instead.

Trk

TrkA	Agonists:Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists:ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators:VM-902A Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies:Against TrkA:GBR-900;Against NGF:ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers:Against NGF:RBM-004 Decoy receptors:ReN-1820 (TrkAd5)
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 Antagonists:ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands:DHEA Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists:BNN-20 DHEA NT-3 Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486