ID   GFRA2_HUMAN             Reviewed;         464 AA.
AC   O00451; E9PD47; O15316; O15328; Q58J92; Q6GTR9; Q7Z5C2;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 2.
DT   13-FEB-2019, entry version 157.
DE   RecName: Full=GDNF family receptor alpha-2;
DE            Short=GDNF receptor alpha-2;
DE            Short=GDNFR-alpha-2;
DE            Short=GFR-alpha-2;
DE   AltName: Full=GDNF receptor beta;
DE            Short=GDNFR-beta;
DE   AltName: Full=Neurturin receptor alpha;
DE            Short=NRTNR-alpha;
DE            Short=NTNR-alpha;
DE   AltName: Full=RET ligand 2;
DE   AltName: Full=TGF-beta-related neurotrophic factor receptor 2;
DE   Flags: Precursor;
GN   Name=GFRA2; Synonyms=GDNFRB, RETL2, TRNR2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT GLN-462.
RX   PubMed=9182803; DOI=10.1016/S0896-6273(00)80318-9;
RA   Baloh R.H., Tansey M.G., Golden J.P., Creedon D.J., Heuckeroth R.O.,
RA   Keck C.L., Zimonjic D.B., Popescu N.C., Johnson E.M. Jr.,
RA   Milbrandt J.;
RT   "TrnR2, a novel receptor that mediates neurturin and GDNF signaling
RT   through Ret.";
RL   Neuron 18:793-802(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-462.
RC   TISSUE=Fetal brain;
RX   PubMed=9259272; DOI=10.1093/hmg/6.8.1267;
RA   Suvanto P., Wartiovaara K., Lindahl M., Arumae U., Moshnyakov M.,
RA   Horelli-Kuitunen N., Airaksinen M.S., Palotie A., Sariola H.,
RA   Saarma M.;
RT   "Cloning, mRNA distribution and chromosomal localisation of the gene
RT   for glial cell line-derived neurotrophic factor receptor beta, a
RT   homologue to GDNFR-alpha.";
RL   Hum. Mol. Genet. 6:1267-1273(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=9177201; DOI=10.1073/pnas.94.12.6238;
RA   Sanicola M., Hession C.A., Worley D.S., Carmillo P., Ehrenfels C.,
RA   Walus L., Robinson S., Jaworski G., Wei H., Tizard R., Whitty A.,
RA   Pepinsky R.B., Cate R.L.;
RT   "Glial cell line-derived neurotrophic factor-dependent RET activation
RT   can be mediated by two different cell-surface accessory proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:6238-6243(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANT GLN-462.
RA   Yoong L.F., Too H.P.;
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA   Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA   Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA   Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA   DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA   Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA   Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA   O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA   Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA   Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA   Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA   Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA   Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Receptor for neurturin. Mediates the NRTN-induced
CC       autophosphorylation and activation of the RET receptor. Also able
CC       to mediate GDNF signaling through the RET tyrosine kinase
CC       receptor.
CC   -!- FUNCTION: Isoform 2: participates in NRTN-induced 'Ser-727'
CC       phosphorylation of STAT3. {ECO:0000250|UniProtKB:O08842}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor,
CC       GPI-anchor {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Long;
CC         IsoId=O00451-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short;
CC         IsoId=O00451-2; Sequence=VSP_001661;
CC       Name=3;
CC         IsoId=O00451-3; Sequence=VSP_046112;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is found in both brain and placenta.
CC   -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   -----------------------------------------------------------------------
DR   EMBL; AF002700; AAC52036.1; -; mRNA.
DR   EMBL; U93703; AAB61922.1; -; mRNA.
DR   EMBL; U97145; AAC51647.1; -; mRNA.
DR   EMBL; AY326396; AAP88378.1; -; mRNA.
DR   EMBL; AY941828; AAX46325.1; -; mRNA.
DR   EMBL; AC105186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC129925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP008236; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC041688; AAH41688.1; -; mRNA.
DR   CCDS; CCDS47816.1; -. [O00451-1]
DR   CCDS; CCDS55207.1; -. [O00451-2]
DR   CCDS; CCDS55208.1; -. [O00451-3]
DR   RefSeq; NP_001158510.1; NM_001165038.1. [O00451-3]
DR   RefSeq; NP_001158511.1; NM_001165039.1. [O00451-2]
DR   RefSeq; NP_001486.4; NM_001495.4. [O00451-1]
DR   RefSeq; XP_006716390.1; XM_006716327.3. [O00451-1]
DR   RefSeq; XP_011542786.1; XM_011544484.2. [O00451-1]
DR   UniGene; Hs.441202; -.
DR   PDB; 5MR4; X-ray; 2.40 A; C/D=1-458.
DR   PDB; 5MR5; X-ray; 2.00 A; C/D=147-362.
DR   PDBsum; 5MR4; -.
DR   PDBsum; 5MR5; -.
DR   ProteinModelPortal; O00451; -.
DR   SMR; O00451; -.
DR   BioGrid; 108943; 3.
DR   STRING; 9606.ENSP00000428518; -.
DR   iPTMnet; O00451; -.
DR   PhosphoSitePlus; O00451; -.
DR   BioMuta; GFRA2; -.
DR   PaxDb; O00451; -.
DR   PeptideAtlas; O00451; -.
DR   PRIDE; O00451; -.
DR   ProteomicsDB; 47897; -.
DR   ProteomicsDB; 47898; -. [O00451-2]
DR   DNASU; 2675; -.
DR   Ensembl; ENST00000517328; ENSP00000429445; ENSG00000168546. [O00451-1]
DR   Ensembl; ENST00000517892; ENSP00000429979; ENSG00000168546. [O00451-3]
DR   Ensembl; ENST00000518077; ENSP00000429206; ENSG00000168546. [O00451-2]
DR   Ensembl; ENST00000524240; ENSP00000428518; ENSG00000168546. [O00451-1]
DR   GeneID; 2675; -.
DR   KEGG; hsa:2675; -.
DR   UCSC; uc003wzu.2; human. [O00451-1]
DR   CTD; 2675; -.
DR   DisGeNET; 2675; -.
DR   EuPathDB; HostDB:ENSG00000168546.10; -.
DR   GeneCards; GFRA2; -.
DR   HGNC; HGNC:4244; GFRA2.
DR   HPA; CAB032791; -.
DR   HPA; HPA024704; -.
DR   MIM; 601956; gene.
DR   neXtProt; NX_O00451; -.
DR   OpenTargets; ENSG00000168546; -.
DR   PharmGKB; PA28654; -.
DR   eggNOG; ENOG410IU4F; Eukaryota.
DR   eggNOG; ENOG410XPTA; LUCA.
DR   GeneTree; ENSGT00940000156168; -.
DR   HOGENOM; HOG000008695; -.
DR   HOVERGEN; HBG051725; -.
DR   InParanoid; O00451; -.
DR   OMA; NSGPCRA; -.
DR   OrthoDB; 482696at2759; -.
DR   PhylomeDB; O00451; -.
DR   TreeFam; TF331647; -.
DR   Reactome; R-HSA-419037; NCAM1 interactions.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-8853659; RET signaling.
DR   SIGNOR; O00451; -.
DR   GeneWiki; GFRA2_(gene); -.
DR   GenomeRNAi; 2675; -.
DR   PRO; PR:O00451; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000168546; Expressed in 145 organ(s), highest expression level in anterior cingulate cortex.
DR   ExpressionAtlas; O00451; baseline and differential.
DR   Genevisible; O00451; HS.
DR   GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0019898; C:extrinsic component of membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0016167; F:glial cell-derived neurotrophic factor receptor activity; IBA:GO_Central.
DR   GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR   GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR   GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR   GO; GO:0031953; P:negative regulation of protein autophosphorylation; IEA:Ensembl.
DR   GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:ProtInc.
DR   InterPro; IPR016017; GDNF/GAS1.
DR   InterPro; IPR037193; GDNF_alpha.
DR   InterPro; IPR003438; GDNF_rcpt.
DR   InterPro; IPR003504; GDNF_rcpt_a2.
DR   InterPro; IPR017372; Glial_neurotroph_fac_rcpt_a1/2.
DR   PANTHER; PTHR10269; PTHR10269; 1.
DR   Pfam; PF02351; GDNF; 3.
DR   PIRSF; PIRSF038071; GDNF_family_receptor_alpha; 1.
DR   PRINTS; PR01318; GDNFRALPHA2.
DR   PRINTS; PR01316; GDNFRECEPTOR.
DR   SMART; SM00907; GDNF; 3.
DR   SUPFAM; SSF110035; SSF110035; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW   Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Polymorphism;
KW   Receptor; Reference proteome; Signal.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   CHAIN        22    444       GDNF family receptor alpha-2.
FT                                /FTId=PRO_0000010785.
FT   PROPEP      445    464       Removed in mature form. {ECO:0000255}.
FT                                /FTId=PRO_0000010786.
FT   LIPID       444    444       GPI-anchor amidated serine.
FT                                {ECO:0000255}.
FT   CARBOHYD     52     52       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    357    357       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    413    413       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VAR_SEQ      14    146       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:9182803,
FT                                ECO:0000303|Ref.4}.
FT                                /FTId=VSP_001661.
FT   VAR_SEQ      14    118       Missing (in isoform 3).
FT                                {ECO:0000303|Ref.4}.
FT                                /FTId=VSP_046112.
FT   VARIANT     462    462       L -> Q (in dbSNP:rs1128397).
FT                                {ECO:0000269|PubMed:9182803,
FT                                ECO:0000269|PubMed:9259272,
FT                                ECO:0000269|Ref.4}.
FT                                /FTId=VAR_059976.
FT   CONFLICT      6      6       V -> A (in Ref. 2; AAB61922).
FT                                {ECO:0000305}.
FT   HELIX        40     48       {ECO:0000244|PDB:5MR4}.
FT   HELIX        51     64       {ECO:0000244|PDB:5MR4}.
FT   HELIX        76     86       {ECO:0000244|PDB:5MR4}.
FT   TURN         89     92       {ECO:0000244|PDB:5MR4}.
FT   HELIX       102    111       {ECO:0000244|PDB:5MR4}.
FT   HELIX       160    169       {ECO:0000244|PDB:5MR5}.
FT   HELIX       172    186       {ECO:0000244|PDB:5MR5}.
FT   STRAND      193    195       {ECO:0000244|PDB:5MR4}.
FT   HELIX       197    210       {ECO:0000244|PDB:5MR5}.
FT   HELIX       213    220       {ECO:0000244|PDB:5MR5}.
FT   HELIX       227    235       {ECO:0000244|PDB:5MR5}.
FT   HELIX       239    242       {ECO:0000244|PDB:5MR5}.
FT   HELIX       251    260       {ECO:0000244|PDB:5MR5}.
FT   HELIX       262    275       {ECO:0000244|PDB:5MR5}.
FT   STRAND      279    281       {ECO:0000244|PDB:5MR5}.
FT   HELIX       286    288       {ECO:0000244|PDB:5MR5}.
FT   HELIX       290    298       {ECO:0000244|PDB:5MR5}.
FT   TURN        299    302       {ECO:0000244|PDB:5MR5}.
FT   STRAND      307    309       {ECO:0000244|PDB:5MR5}.
FT   STRAND      314    316       {ECO:0000244|PDB:5MR5}.
FT   STRAND      319    322       {ECO:0000244|PDB:5MR5}.
FT   HELIX       329    331       {ECO:0000244|PDB:5MR5}.
FT   HELIX       332    343       {ECO:0000244|PDB:5MR5}.
FT   HELIX       346    355       {ECO:0000244|PDB:5MR5}.
SQ   SEQUENCE   464 AA;  51544 MW;  8BC61529530FF21F CRC64;
     MILANVFCLF FFLDETLRSL ASPSSLQGPE LHGWRPPVDC VRANELCAAE SNCSSRYRTL
     RQCLAGRDRN TMLANKECQA ALEVLQESPL YDCRCKRGMK KELQCLQIYW SIHLGLTEGE
     EFYEASPYEP VTSRLSDIFR LASIFSGTGA DPVVSAKSNH CLDAAKACNL NDNCKKLRSS
     YISICNREIS PTERCNRRKC HKALRQFFDR VPSEYTYRML FCSCQDQACA ERRRQTILPS
     CSYEDKEKPN CLDLRGVCRT DHLCRSRLAD FHANCRASYQ TVTSCPADNY QACLGSYAGM
     IGFDMTPNYV DSSPTGIVVS PWCSCRGSGN MEEECEKFLR DFTENPCLRN AIQAFGNGTD
     VNVSPKGPSF QATQAPRVEK TPSLPDDLSD STSLGTSVIT TCTSVQEQGL KANNSKELSM
     CFTELTTNII PGSNKVIKPN SGPSRARPSA ALTVLSVLML KLAL
//