GFRA1_MOUSE
ID GFRA1_MOUSE Reviewed; 468 AA.
AC P97785; O35246; O35252;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=GDNF family receptor alpha-1;
DE Short=GDNF receptor alpha-1;
DE Short=GDNFR-alpha-1;
DE Short=GFR-alpha-1;
DE AltName: Full=TGF-beta-related neurotrophic factor receptor 1;
DE Flags: Precursor;
GN Name=Gfra1; Synonyms=Gdnfra, Trnr1;
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), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=9592044; DOI=10.1097/00001756-199801050-00008;
RA Dey B.K., Wong Y.W., Too H.P.;
RT "Cloning of a novel murine isoform of the glial cell line-derived
RT neurotrophic factor receptor.";
RL NeuroReport 9:37-42(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Spinal ganglion;
RA Watabe K.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Olfactory epithelium;
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 [5]
RP TISSUE SPECIFICITY.
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 GDNF. Mediates the GDNF-induced
CC autophosphorylation and activation of the RET receptor (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: 2 molecules of GDNFR-alpha are thought to form a complex with
CC the disulfide-linked GDNF dimer and with 2 molecules of RET (By
CC similarity). Interacts with RET (By similarity). Interacts with SORL1,
CC either alone or in complex with GDNF. Interaction between SORL1 and
CC GFRA1 leads to GFRA1 internalization, but not degradation (By
CC similarity). {ECO:0000250|UniProtKB:P56159,
CC ECO:0000250|UniProtKB:Q62997}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q62997};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q62997}. Golgi
CC apparatus, trans-Golgi network {ECO:0000250|UniProtKB:Q62997}. Endosome
CC {ECO:0000250|UniProtKB:Q62997}. Endosome, multivesicular body
CC {ECO:0000250|UniProtKB:Q62997}. Note=Localizes mainly to the plasma
CC membrane. In the presence of SORL1, shifts to vesicular structures,
CC including trans-Golgi network, endosomes and multivesicular bodies.
CC {ECO:0000250|UniProtKB:Q62997}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=GDNFR-alpha;
CC IsoId=P97785-1; Sequence=Displayed;
CC Name=2; Synonyms=GDNFR-beta;
CC IsoId=P97785-2; Sequence=VSP_041630;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, in hippocampal neurons (at
CC protein level) (PubMed:23333276). Isoform 1 and isoform 2 are expressed
CC in heart, brain, lung, liver, kidney and testis.
CC {ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:9592044}.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR EMBL; AF014117; AAB86599.1; -; mRNA.
DR EMBL; AF015172; AAB86600.1; -; mRNA.
DR EMBL; AB000800; BAA19185.1; -; mRNA.
DR EMBL; CH466585; EDL01795.1; -; Genomic_DNA.
DR EMBL; CH466585; EDL01796.1; -; Genomic_DNA.
DR EMBL; BC054378; AAH54378.1; -; mRNA.
DR CCDS; CCDS38028.1; -. [P97785-1]
DR CCDS; CCDS70967.1; -. [P97785-2]
DR RefSeq; NP_001272386.1; NM_001285457.2. [P97785-2]
DR RefSeq; NP_034409.1; NM_010279.3. [P97785-1]
DR RefSeq; XP_006526744.1; XM_006526681.1. [P97785-1]
DR RefSeq; XP_006526745.1; XM_006526682.1. [P97785-1]
DR RefSeq; XP_006526746.1; XM_006526683.3. [P97785-1]
DR RefSeq; XP_006526747.1; XM_006526684.1. [P97785-1]
DR AlphaFoldDB; P97785; -.
DR SMR; P97785; -.
DR BioGRID; 199904; 4.
DR CORUM; P97785; -.
DR IntAct; P97785; 1.
DR STRING; 10090.ENSMUSP00000026076; -.
DR GlyGen; P97785; 3 sites.
DR iPTMnet; P97785; -.
DR PhosphoSitePlus; P97785; -.
DR MaxQB; P97785; -.
DR PaxDb; P97785; -.
DR PeptideAtlas; P97785; -.
DR PRIDE; P97785; -.
DR ProteomicsDB; 268866; -. [P97785-1]
DR ProteomicsDB; 268867; -. [P97785-2]
DR Antibodypedia; 18697; 470 antibodies from 40 providers.
DR DNASU; 14585; -.
DR Ensembl; ENSMUST00000026076; ENSMUSP00000026076; ENSMUSG00000025089. [P97785-1]
DR Ensembl; ENSMUST00000129100; ENSMUSP00000117196; ENSMUSG00000025089. [P97785-2]
DR Ensembl; ENSMUST00000152507; ENSMUSP00000120333; ENSMUSG00000025089. [P97785-1]
DR Ensembl; ENSMUST00000169850; ENSMUSP00000130128; ENSMUSG00000025089. [P97785-1]
DR GeneID; 14585; -.
DR KEGG; mmu:14585; -.
DR UCSC; uc008ial.2; mouse. [P97785-2]
DR UCSC; uc008ian.2; mouse. [P97785-1]
DR CTD; 2674; -.
DR MGI; MGI:1100842; Gfra1.
DR VEuPathDB; HostDB:ENSMUSG00000025089; -.
DR eggNOG; ENOG502QQA2; Eukaryota.
DR GeneTree; ENSGT00940000155560; -.
DR InParanoid; P97785; -.
DR OMA; CKKFLNF; -.
DR OrthoDB; 482696at2759; -.
DR PhylomeDB; P97785; -.
DR TreeFam; TF331647; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 14585; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Gfra1; mouse.
DR PRO; PR:P97785; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P97785; protein.
DR Bgee; ENSMUSG00000025089; Expressed in vestibular membrane of cochlear duct and 211 other tissues.
DR ExpressionAtlas; P97785; baseline and differential.
DR Genevisible; P97785; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0019898; C:extrinsic component of membrane; TAS:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0098797; C:plasma membrane protein complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0005030; F:neurotrophin receptor activity; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:MGI.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:MGI.
DR InterPro; IPR016017; GDNF/GAS1.
DR InterPro; IPR037193; GDNF_alpha.
DR InterPro; IPR003438; GDNF_rcpt.
DR InterPro; IPR003503; GDNF_rcpt_A1.
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; PR01317; GDNFRALPHA1.
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; Disulfide bond; Endosome;
KW Glycoprotein; Golgi apparatus; GPI-anchor; Lipoprotein; Membrane; Receptor;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..430
FT /note="GDNF family receptor alpha-1"
FT /id="PRO_0000010779"
FT PROPEP 431..468
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010780"
FT REPEAT 25..113
FT /note="1"
FT REPEAT 150..238
FT /note="2"
FT REPEAT 239..342
FT /note="3"
FT LIPID 430
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..87
FT /evidence="ECO:0000250"
FT DISULFID 36..42
FT /evidence="ECO:0000250"
FT DISULFID 52..72
FT /evidence="ECO:0000250"
FT DISULFID 89..99
FT /evidence="ECO:0000250"
FT DISULFID 154..214
FT /evidence="ECO:0000250"
FT DISULFID 161..167
FT /evidence="ECO:0000250"
FT DISULFID 178..192
FT /evidence="ECO:0000250"
FT DISULFID 187..233
FT /evidence="ECO:0000250"
FT DISULFID 216..221
FT /evidence="ECO:0000250"
FT DISULFID 243..313
FT /evidence="ECO:0000250"
FT DISULFID 250..256
FT /evidence="ECO:0000250"
FT DISULFID 267..285
FT /evidence="ECO:0000250"
FT DISULFID 277..337
FT /evidence="ECO:0000250"
FT DISULFID 315..325
FT /evidence="ECO:0000250"
FT VAR_SEQ 140..144
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9592044"
FT /id="VSP_041630"
FT CONFLICT 366
FT /note="T -> M (in Ref. 2; BAA19185)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 51752 MW; 997105C2A6DD6446 CRC64;
MFLATLYFVL PLLDLLMSAE VSGGDRLDCV KASDQCLKEQ SCSTKYRTLR QCVAGKETNF
SLTSGLEAKD ECRSAMEALK QKSLYNCRCK RGMKKEKNCL RIYWSMYQSL QGNDLLEDSP
YEPVNSRLSD IFRAVPFISD VFQQVEHISK GNNCLDAAKA CNLDDTCKKY RSAYITPCTT
SMSNEVCNRR KCHKALRQFF DKVPAKHSYG MLFCSCRDVA CTERRRQTIV PVCSYEERER
PNCLNLQDSC KTNYICRSRL ADFFTNCQPE SRSVSNCLKE NYADCLLAYS GLIGTVMTPN
YIDSSSLSVA PWCDCSNSGN DLEDCLKFLN FFKDNTCLKN AIQAFGNGSD VTMWQPAPPV
QTTTATTTTA FRIKNKPLGP AGSENEIPTH VLPPCANLQA QKLKSNVSGS THLCLSDNDY
GKDGLAGASS HITTKSMAAP PSCGLSSLPV MVFTALAALL SVSLAETS
