GFRA1_RAT
ID GFRA1_RAT Reviewed; 468 AA.
AC Q62997;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 138.
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=RET ligand 1;
DE AltName: Full=TGF-beta-related neurotrophic factor receptor 1;
DE Flags: Precursor;
GN Name=Gfra1; Synonyms=Gdnfra, Retl1, Trnr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Retina;
RX PubMed=8674117; DOI=10.1016/s0092-8674(00)81311-2;
RA Jing S., Wen D., Yu Y., Holst P.L., Luo Y., Fang M., Tamir R., Antonio L.,
RA Hu Z., Cupples R., Louis J.-C., Hu S., Altrock B.W., Fox G.M.;
RT "GDNF-induced activation of the ret protein tyrosine kinase is mediated by
RT GDNFR-alpha, a novel receptor for GDNF.";
RL Cell 85:1113-1124(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8657309; DOI=10.1038/382080a0;
RA Treanor J.J.S., Googman L., de Sauvage F., Stone D.M., Poulsen K.T.,
RA Beck C.D., Gray C., Armanini M.P., Pollock R.A., Hefti F., Phillips H.S.,
RA Goddard A., Moore M.W., Buj-Bello A., Davies A.M., Asai N., Takahashi M.,
RA Vandlen R., Henderson C.E., Rosenthal A.;
RT "Characterization of a multicomponent receptor for GDNF.";
RL Nature 382:80-83(1996).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10719212; DOI=10.1016/s0169-328x(99)00328-9;
RA Stoever T., Gong T.-W.L., Cho Y., Altschuler R.A., Lomax M.I.;
RT "Expression of the GDNF family members and their receptors in the mature
RT rat cochlea.";
RL Brain Res. Mol. Brain Res. 76:25-35(2000).
RN [5]
RP INTERACTION WITH RET AND SORL1, AND SUBCELLULAR LOCATION.
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).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 239-346, AND DISULFIDE BONDS.
RX PubMed=15044950; DOI=10.1038/sj.emboj.7600174;
RA Leppanen V.M., Bespalov M.M., Runeberg-Roos P., Puurand U., Merits A.,
RA Saarma M., Goldman A.;
RT "The structure of GFRalpha1 domain 3 reveals new insights into GDNF binding
RT and RET activation.";
RL EMBO J. 23:1452-1462(2004).
CC -!- FUNCTION: Receptor for GDNF. Mediates the GDNF-induced
CC autophosphorylation and activation of the RET receptor.
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
CC (PubMed:15044950). Interacts with RET (By similarity). Interacts with
CC SORL1, either alone or in complex with GDNF. Interaction between SORL1
CC and GFRA1 leads to GFRA1 internalization, but not degradation (By
CC similarity). {ECO:0000250|UniProtKB:P56159,
CC ECO:0000269|PubMed:15044950}.
CC -!- INTERACTION:
CC Q62997; Q92673: SORL1; Xeno; NbExp=5; IntAct=EBI-25397991, EBI-1171329;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23333276};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:8674117}. Golgi apparatus,
CC trans-Golgi network {ECO:0000269|PubMed:23333276}. Endosome
CC {ECO:0000269|PubMed:23333276}. Endosome, multivesicular body
CC {ECO:0000269|PubMed:23333276}. 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:0000269|PubMed:23333276}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, brain, kidney and cochlea.
CC {ECO:0000269|PubMed:10719212}.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR EMBL; U59486; AAC52663.1; -; mRNA.
DR EMBL; U97142; AAC53300.1; -; mRNA.
DR RefSeq; NP_037091.1; NM_012959.1.
DR RefSeq; XP_008758734.1; XM_008760512.2.
DR PDB; 1Q8D; X-ray; 1.80 A; A=239-346.
DR PDB; 2V5E; X-ray; 2.35 A; A=150-349.
DR PDB; 3FUB; X-ray; 2.35 A; A/C=145-425.
DR PDB; 4UX8; EM; 24.00 A; C/E=1-468.
DR PDBsum; 1Q8D; -.
DR PDBsum; 2V5E; -.
DR PDBsum; 3FUB; -.
DR PDBsum; 4UX8; -.
DR AlphaFoldDB; Q62997; -.
DR SMR; Q62997; -.
DR BioGRID; 247488; 2.
DR IntAct; Q62997; 3.
DR STRING; 10116.ENSRNOP00000023667; -.
DR GlyGen; Q62997; 3 sites.
DR PhosphoSitePlus; Q62997; -.
DR PaxDb; Q62997; -.
DR Ensembl; ENSRNOT00000119102; ENSRNOP00000091664; ENSRNOG00000017438.
DR GeneID; 25454; -.
DR KEGG; rno:25454; -.
DR CTD; 2674; -.
DR RGD; 2681; Gfra1.
DR eggNOG; ENOG502QQA2; Eukaryota.
DR GeneTree; ENSGT00940000155560; -.
DR InParanoid; Q62997; -.
DR OrthoDB; 482696at2759; -.
DR PhylomeDB; Q62997; -.
DR TreeFam; TF331647; -.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-8853659; RET signaling.
DR EvolutionaryTrace; Q62997; -.
DR PRO; PR:Q62997; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098797; C:plasma membrane protein complex; IDA:CAFA.
DR GO; GO:0043235; C:receptor complex; IDA:RGD.
DR GO; GO:0005178; F:integrin binding; IPI:RGD.
DR GO; GO:0005030; F:neurotrophin receptor activity; IDA:RGD.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0016477; P:cell migration; IMP:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IMP:RGD.
DR GO; GO:0031175; P:neuron projection development; IDA:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:CAFA.
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 3D-structure; Cell membrane; Disulfide bond; Endosome; Glycoprotein;
KW 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_0000010781"
FT PROPEP 431..468
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010782"
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:0000269|PubMed:15044950"
FT DISULFID 250..256
FT /evidence="ECO:0000269|PubMed:15044950"
FT DISULFID 267..285
FT /evidence="ECO:0000269|PubMed:15044950"
FT DISULFID 277..337
FT /evidence="ECO:0000269|PubMed:15044950"
FT DISULFID 315..325
FT /evidence="ECO:0000269|PubMed:15044950"
FT HELIX 153..162
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 165..179
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 189..202
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 205..213
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:2V5E"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 243..251
FT /evidence="ECO:0007829|PDB:1Q8D"
FT HELIX 254..266
FT /evidence="ECO:0007829|PDB:1Q8D"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:1Q8D"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:1Q8D"
FT HELIX 282..290
FT /evidence="ECO:0007829|PDB:1Q8D"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:1Q8D"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:3FUB"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:1Q8D"
FT HELIX 322..333
FT /evidence="ECO:0007829|PDB:1Q8D"
FT HELIX 336..345
FT /evidence="ECO:0007829|PDB:1Q8D"
SQ SEQUENCE 468 AA; 51650 MW; B2EE5906F5025E0F CRC64;
MFLATLYFAL PLLDLLMSAE VSGGDRLDCV KASDQCLKEQ SCSTKYRTLR QCVAGKETNF
SLTSGLEAKD ECRSAMEALK QKSLYNCRCK RGMKKEKNCL RIYWSMYQSL QGNDLLEDSP
YEPVNSRLSD IFRAVPFISD VFQQVEHISK GNNCLDAAKA CNLDDTCKKY RSAYITPCTT
SMSNEVCNRR KCHKALRQFF DKVPAKHSYG MLFCSCRDIA CTERRRQTIV PVCSYEERER
PNCLSLQDSC KTNYICRSRL ADFFTNCQPE SRSVSNCLKE NYADCLLAYS GLIGTVMTPN
YVDSSSLSVA PWCDCSNSGN DLEDCLKFLN FFKDNTCLKN AIQAFGNGSD VTMWQPAPPV
QTTTATTTTA FRVKNKPLGP AGSENEIPTH VLPPCANLQA QKLKSNVSGS THLCLSDSDF
GKDGLAGASS HITTKSMAAP PSCSLSSLPV LMLTALAALL SVSLAETS
