GFRA2_HUMAN
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 03-AUG-2022, entry version 175.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Milbrandt J.;
RT "TrnR2, a novel receptor that mediates neurturin and GDNF signaling through
RT 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., Saarma M.;
RT "Cloning, mRNA distribution and chromosomal localisation of the gene for
RT glial cell line-derived neurotrophic factor receptor beta, a homologue to
RT 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 can
RT 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., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., 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., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH SORL1.
RX PubMed=23333276; DOI=10.1016/j.celrep.2012.12.011;
RA Glerup S., Lume M., Olsen D., Nyengaard J.R., Vaegter C.B., Gustafsen C.,
RA Christensen E.I., Kjolby M., Hay-Schmidt A., Bender D., Madsen P.,
RA Saarma M., Nykjaer A., Petersen C.M.;
RT "SorLA controls neurotrophic activity by sorting of GDNF and its receptors
RT GFRalpha1 and RET.";
RL Cell Rep. 3:186-199(2013).
CC -!- FUNCTION: Receptor for neurturin. Mediates the NRTN-induced
CC autophosphorylation and activation of the RET receptor. Also able to
CC mediate GDNF signaling through the RET tyrosine kinase receptor.
CC -!- FUNCTION: [Isoform 2]: Participates in NRTN-induced 'Ser-727'
CC phosphorylation of STAT3. {ECO:0000250|UniProtKB:O08842}.
CC -!- SUBUNIT: Interacts with SORL1. {ECO:0000269|PubMed:23333276}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC 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 -!- TISSUE SPECIFICITY: Isoform 1 is found in both brain and placenta.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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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 PDB; 5MR4; X-ray; 2.40 A; C/D=1-458.
DR PDB; 5MR5; X-ray; 2.00 A; C/D=147-362.
DR PDB; 6GL7; EM; 6.30 A; C/D=22-441.
DR PDB; 6Q2O; EM; 3.65 A; C/D=24-362.
DR PDB; 6Q2R; EM; 4.30 A; C/D/W/X=24-362.
DR PDBsum; 5MR4; -.
DR PDBsum; 5MR5; -.
DR PDBsum; 6GL7; -.
DR PDBsum; 6Q2O; -.
DR PDBsum; 6Q2R; -.
DR AlphaFoldDB; O00451; -.
DR SMR; O00451; -.
DR BioGRID; 108943; 3.
DR STRING; 9606.ENSP00000428518; -.
DR GlyGen; O00451; 5 sites, 3 O-linked glycans (2 sites).
DR iPTMnet; O00451; -.
DR PhosphoSitePlus; O00451; -.
DR BioMuta; GFRA2; -.
DR MassIVE; O00451; -.
DR PaxDb; O00451; -.
DR PeptideAtlas; O00451; -.
DR PRIDE; O00451; -.
DR ProteomicsDB; 19584; -.
DR ProteomicsDB; 47897; -. [O00451-1]
DR ProteomicsDB; 47898; -. [O00451-2]
DR Antibodypedia; 5212; 409 antibodies from 35 providers.
DR DNASU; 2675; -.
DR Ensembl; ENST00000517328.5; ENSP00000429445.1; ENSG00000168546.11. [O00451-1]
DR Ensembl; ENST00000517892.5; ENSP00000429979.1; ENSG00000168546.11. [O00451-3]
DR Ensembl; ENST00000518077.5; ENSP00000429206.1; ENSG00000168546.11. [O00451-2]
DR Ensembl; ENST00000524240.6; ENSP00000428518.1; ENSG00000168546.11. [O00451-1]
DR GeneID; 2675; -.
DR KEGG; hsa:2675; -.
DR MANE-Select; ENST00000524240.6; ENSP00000428518.1; NM_001495.5; NP_001486.4.
DR UCSC; uc003wzu.2; human. [O00451-1]
DR CTD; 2675; -.
DR DisGeNET; 2675; -.
DR GeneCards; GFRA2; -.
DR HGNC; HGNC:4244; GFRA2.
DR HPA; ENSG00000168546; Tissue enhanced (testis, thyroid gland).
DR MIM; 601956; gene.
DR neXtProt; NX_O00451; -.
DR OpenTargets; ENSG00000168546; -.
DR PharmGKB; PA28654; -.
DR VEuPathDB; HostDB:ENSG00000168546; -.
DR eggNOG; ENOG502QS3P; Eukaryota.
DR GeneTree; ENSGT00940000156168; -.
DR HOGENOM; CLU_040179_1_1_1; -.
DR InParanoid; O00451; -.
DR OMA; DTGKPCN; -.
DR OrthoDB; 482696at2759; -.
DR PhylomeDB; O00451; -.
DR TreeFam; TF331647; -.
DR PathwayCommons; O00451; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; O00451; -.
DR SIGNOR; O00451; -.
DR BioGRID-ORCS; 2675; 14 hits in 1066 CRISPR screens.
DR ChiTaRS; GFRA2; human.
DR GeneWiki; GFRA2_(gene); -.
DR GenomeRNAi; 2675; -.
DR Pharos; O00451; Tbio.
DR PRO; PR:O00451; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O00451; protein.
DR Bgee; ENSG00000168546; Expressed in secondary oocyte and 126 other tissues.
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:0038023; F:signaling receptor activity; IBA:GO_Central.
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; Glycoprotein;
KW GPI-anchor; Lipoprotein; Membrane; Receptor; Reference proteome; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..444
FT /note="GDNF family receptor alpha-2"
FT /id="PRO_0000010785"
FT PROPEP 445..464
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010786"
FT REGION 363..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 444
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 14..146
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9182803, ECO:0000303|Ref.4"
FT /id="VSP_001661"
FT VAR_SEQ 14..118
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_046112"
FT VARIANT 462
FT /note="L -> Q (in dbSNP:rs1128397)"
FT /evidence="ECO:0000269|PubMed:9182803,
FT ECO:0000269|PubMed:9259272, ECO:0000269|Ref.4"
FT /id="VAR_059976"
FT CONFLICT 6
FT /note="V -> A (in Ref. 2; AAB61922)"
FT /evidence="ECO:0000305"
FT HELIX 40..48
FT /evidence="ECO:0007829|PDB:5MR4"
FT HELIX 51..64
FT /evidence="ECO:0007829|PDB:5MR4"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:5MR4"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:5MR4"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:5MR4"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 172..186
FT /evidence="ECO:0007829|PDB:5MR5"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5MR4"
FT HELIX 197..210
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 213..220
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 227..235
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 239..242
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:5MR5"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 290..298
FT /evidence="ECO:0007829|PDB:5MR5"
FT TURN 299..302
FT /evidence="ECO:0007829|PDB:5MR5"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:5MR5"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:5MR5"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 332..343
FT /evidence="ECO:0007829|PDB:5MR5"
FT HELIX 346..355
FT /evidence="ECO:0007829|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
