GFRA2_MOUSE
ID GFRA2_MOUSE Reviewed; 464 AA.
AC O08842; Q3UUD8; Q920Y3; Q9Z2A2; Q9Z2A3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 2.
DT 03-AUG-2022, entry version 158.
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=TGF-beta-related neurotrophic factor receptor 2;
DE Flags: Precursor;
GN Name=Gfra2 {ECO:0000312|EMBL:AAC82464.1, ECO:0000312|MGI:MGI:1195462};
GN Synonyms=Gdnfrb, Trnr2 {ECO:0000303|PubMed:9182803};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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] (ISOFORMS 2 AND 3), AND TISSUE SPECIFICITY.
RC TISSUE=Brain {ECO:0000303|PubMed:9875703};
RX PubMed=9875703; DOI=10.1097/00001756-199812010-00002;
RA Wong Y.W., Too H.P.;
RT "Identification of mammalian GFRalpha-2 splice isoforms.";
RL NeuroReport 9:3767-3773(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAK97483.1};
RX PubMed=12829325; DOI=10.1016/s0169-328x(03)00169-4;
RA Too H.P.;
RT "Real time PCR quantification of GFRalpha-2 alternatively spliced isoforms
RT in murine brain and peripheral tissues.";
RL Brain Res. Mol. Brain Res. 114:146-153(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION (ISOFORM 2).
RX PubMed=23872421; DOI=10.1016/j.bbamcr.2013.07.004;
RA Zhou L., Too H.P.;
RT "GDNF family ligand dependent STAT3 activation is mediated by specific
RT alternatively spliced isoforms of GFRalpha2 and RET.";
RL Biochim. Biophys. Acta 1833:2789-2802(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 {ECO:0000269|PubMed:9182803}.
CC -!- FUNCTION: [Isoform 2]: Participates in NRTN-induced 'Ser-727'
CC phosphorylation of STAT3. {ECO:0000269|PubMed:23872421}.
CC -!- SUBUNIT: Interacts with SORL1. {ECO:0000250|UniProtKB:O00451}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:9182803};
CC Lipid-anchor, GPI-anchor {ECO:0000305|PubMed:9182803}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.
CC {ECO:0000305|PubMed:12829325};
CC Name=1; Synonyms=Long, 2a {ECO:0000303|PubMed:12829325,
CC ECO:0000303|PubMed:9875703};
CC IsoId=O08842-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, 2c {ECO:0000303|PubMed:12829325,
CC ECO:0000303|PubMed:9875703};
CC IsoId=O08842-2; Sequence=VSP_001662;
CC Name=3; Synonyms=2b {ECO:0000303|PubMed:12829325,
CC ECO:0000303|PubMed:9875703};
CC IsoId=O08842-3; Sequence=VSP_057520;
CC -!- TISSUE SPECIFICITY: Neurons of the superior cervical and dorsal root
CC ganglia, and adult brain and testis. Low level in the substantia nigra,
CC spleen and adrenal gland (PubMed:9182803). Isoform 1, isoform 2 and
CC isoform 3 are all expressed in brain, liver, ileum, spleen, heart and
CC kidney (PubMed:9875703). In brain, isoform 1 is most abundant, isoform
CC 2 slightly less and isoform 3 is lowest. No significant levels of
CC isoform 1, isoform 2 or isoform 3 expression in testis
CC (PubMed:12829325). {ECO:0000269|PubMed:12829325,
CC ECO:0000269|PubMed:9182803, ECO:0000269|PubMed:9875703}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low level in the ventral
CC mesencephalon at 14 dpc. Highly expressed in the developing dorsal root
CC ganglia (PubMed:9182803). Isoform 1, isoform 2 and isoform 3 are all
CC highly expressed in the late embryonic development (15 dpc and 17 dpc)
CC (PubMed:12829325). {ECO:0000269|PubMed:12829325,
CC ECO:0000269|PubMed:9182803}.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC53548.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC82464.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC82465.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK97483.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF002701; AAC53548.1; ALT_SEQ; mRNA.
DR EMBL; AF079107; AAC82464.1; ALT_SEQ; mRNA.
DR EMBL; AF079108; AAC82465.1; ALT_SEQ; mRNA.
DR EMBL; AF398416; AAK97483.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF398411; AAK97483.1; JOINED; Genomic_DNA.
DR EMBL; AF398412; AAK97483.1; JOINED; Genomic_DNA.
DR EMBL; AF398413; AAK97483.1; JOINED; Genomic_DNA.
DR EMBL; AF398414; AAK97483.1; JOINED; Genomic_DNA.
DR EMBL; AF398415; AAK97483.1; JOINED; Genomic_DNA.
DR EMBL; AK138512; BAE23689.1; -; mRNA.
DR EMBL; AC124202; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466535; EDL35876.1; -; Genomic_DNA.
DR EMBL; BC138561; AAI38562.1; -; mRNA.
DR CCDS; CCDS27263.1; -. [O08842-1]
DR CCDS; CCDS88711.1; -. [O08842-2]
DR RefSeq; NP_001289023.1; NM_001302094.1. [O08842-3]
DR RefSeq; NP_001289024.1; NM_001302095.1. [O08842-2]
DR RefSeq; NP_032141.2; NM_008115.3. [O08842-1]
DR AlphaFoldDB; O08842; -.
DR SMR; O08842; -.
DR BioGRID; 199905; 1.
DR IntAct; O08842; 1.
DR MINT; O08842; -.
DR STRING; 10090.ENSMUSP00000022699; -.
DR GlyGen; O08842; 3 sites.
DR iPTMnet; O08842; -.
DR PhosphoSitePlus; O08842; -.
DR MaxQB; O08842; -.
DR PaxDb; O08842; -.
DR PeptideAtlas; O08842; -.
DR PRIDE; O08842; -.
DR ProteomicsDB; 268868; -. [O08842-1]
DR ProteomicsDB; 268869; -. [O08842-2]
DR ProteomicsDB; 268870; -. [O08842-3]
DR Antibodypedia; 5212; 409 antibodies from 35 providers.
DR DNASU; 14586; -.
DR Ensembl; ENSMUST00000022699; ENSMUSP00000022699; ENSMUSG00000022103. [O08842-1]
DR Ensembl; ENSMUST00000227697; ENSMUSP00000154391; ENSMUSG00000022103. [O08842-2]
DR GeneID; 14586; -.
DR KEGG; mmu:14586; -.
DR UCSC; uc007uoz.2; mouse. [O08842-1]
DR UCSC; uc007upb.2; mouse. [O08842-2]
DR CTD; 2675; -.
DR MGI; MGI:1195462; Gfra2.
DR VEuPathDB; HostDB:ENSMUSG00000022103; -.
DR eggNOG; ENOG502QS3P; Eukaryota.
DR GeneTree; ENSGT00940000156168; -.
DR HOGENOM; CLU_040179_1_1_1; -.
DR InParanoid; O08842; -.
DR OMA; DTGKPCN; -.
DR PhylomeDB; O08842; -.
DR TreeFam; TF331647; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 14586; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Gfra2; mouse.
DR PRO; PR:O08842; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; O08842; protein.
DR Bgee; ENSMUSG00000022103; Expressed in left lung lobe and 213 other tissues.
DR ExpressionAtlas; O08842; baseline and differential.
DR Genevisible; O08842; MM.
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:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0016167; F:glial cell-derived neurotrophic factor receptor activity; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IGI:MGI.
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 Alternative splicing; Cell membrane; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Receptor; Reference proteome; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..443
FT /note="GDNF family receptor alpha-2"
FT /id="PRO_0000010787"
FT PROPEP 444..464
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010788"
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 443
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:12829325,
FT ECO:0000303|PubMed:9182803"
FT /id="VSP_001662"
FT VAR_SEQ 14..118
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12829325"
FT /id="VSP_057520"
FT CONFLICT 157
FT /note="K -> E (in Ref. 2; AAC82464/AAC82465)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="D -> E (in Ref. 3; AAK97483)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="L -> I (in Ref. 3; AAK97483)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="S -> G (in Ref. 3; AAK97483)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 51727 MW; 3A7FB495FA58C61F CRC64;
MILANAFCLF FFLDETLRSL ASPSSPQGSE LHGWRPQVDC VRANELCAAE SNCSSRYRTL
RQCLAGRDRN TMLANKECQA ALEVLQESPL YDCRCKRGMK KELQCLQIYW SIHLGLTEGE
EFYEASPYEP VTSRLSDIFR LASIFSGTGA DPVVSAKSNH CLDAAKACNL NDNCKKLRSS
YISICNREIS PTERCNRRKC HKALRQFFDR VPSEYTYRML FCSCQDQACA ERRRQTILPS
CSYEDKEKPN CLDLRSLCRT DHLCRSRLAD FHANCRASYR TITSCPADNY QACLGSYAGM
IGFDMTPNYV DSNPTGIVVS PWCNCRGSGN MEEECEKFLK DFTENPCLRN AIQAFGNGTD
VNMSPKGPTF SATQAPRVEK TPSLPDDLSD STSLGTSVIT TCTSIQEQGL KANNSKELSM
CFTELTTNIS PGSKKVIKLY SGSCRARLST ALTALPLLMV TLAQ
