GFRA4_HUMAN
ID GFRA4_HUMAN Reviewed; 299 AA.
AC Q9GZZ7; Q5JT74; Q9H191; Q9H192;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=GDNF family receptor alpha-4;
DE Short=GDNF receptor alpha-4;
DE Short=GDNFR-alpha-4;
DE Short=GFR-alpha-4;
DE AltName: Full=Persephin receptor;
DE Flags: Precursor;
GN Name=GFRA4;
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 GFRALPHA4A; GFRALPHA4B AND
RP GFRALPHA4C), AND GPI-ANCHOR.
RC TISSUE=Thyroid;
RX PubMed=11116144; DOI=10.1074/jbc.m008279200;
RA Lindahl M., Poteryaev D., Yu L., Arumae U., Timmusk T., Bongarzone I.,
RA Aiello A., Pierotti M.A., Airaksinen M.S., Saarma M.;
RT "Human glial cell line-derived neurotrophic factor receptor alpha4 is the
RT receptor for persephin and is predominantly expressed in normal and
RT malignant thyroid medullary cells.";
RL J. Biol. Chem. 276:9344-9351(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM GFRALPHA4A).
RA Zhou B., Levinson B., Gitschier J.;
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 persephin. Mediates the GDNF-induced
CC autophosphorylation and activation of the RET receptor. May be
CC important in C-cell development and, in the postnatal development of
CC the adrenal medulla.
CC -!- SUBUNIT: Interacts with SORL1. {ECO:0000269|PubMed:23333276}.
CC -!- SUBCELLULAR LOCATION: [Isoform GFRalpha4a]: Cell membrane; Lipid-
CC anchor, GPI-anchor.
CC -!- SUBCELLULAR LOCATION: [Isoform GFRalpha4b]: Cell membrane; Lipid-
CC anchor, GPI-anchor.
CC -!- SUBCELLULAR LOCATION: [Isoform GFRalpha4c]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=GFRalpha4b;
CC IsoId=Q9GZZ7-1; Sequence=Displayed;
CC Name=GFRalpha4a;
CC IsoId=Q9GZZ7-2; Sequence=VSP_007223;
CC Name=GFRalpha4c;
CC IsoId=Q9GZZ7-3; Sequence=VSP_007224, VSP_007225;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the adult thyroid gland.
CC Low levels also found in fetal adrenal and thyroid glands.
CC -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR EMBL; AJ291673; CAC19690.1; -; mRNA.
DR EMBL; AJ291674; CAC19691.1; -; mRNA.
DR EMBL; AJ291675; CAC19692.1; -; mRNA.
DR EMBL; AF253318; AAG25925.1; -; mRNA.
DR EMBL; AL356755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS13055.1; -. [Q9GZZ7-2]
DR CCDS; CCDS13056.1; -. [Q9GZZ7-1]
DR RefSeq; NP_071422.1; NM_022139.3. [Q9GZZ7-2]
DR RefSeq; NP_665705.1; NM_145762.2. [Q9GZZ7-1]
DR RefSeq; XP_005260850.1; XM_005260793.2. [Q9GZZ7-3]
DR AlphaFoldDB; Q9GZZ7; -.
DR SMR; Q9GZZ7; -.
DR BioGRID; 122057; 1.
DR STRING; 9606.ENSP00000313423; -.
DR GlyGen; Q9GZZ7; 1 site.
DR BioMuta; GFRA4; -.
DR DMDM; 30173123; -.
DR PaxDb; Q9GZZ7; -.
DR PeptideAtlas; Q9GZZ7; -.
DR PRIDE; Q9GZZ7; -.
DR ABCD; Q9GZZ7; 3 sequenced antibodies.
DR Antibodypedia; 23585; 261 antibodies from 26 providers.
DR DNASU; 64096; -.
DR Ensembl; ENST00000290417.7; ENSP00000290417.2; ENSG00000125861.16. [Q9GZZ7-2]
DR Ensembl; ENST00000319242.8; ENSP00000313423.3; ENSG00000125861.16. [Q9GZZ7-1]
DR Ensembl; ENST00000477160.1; ENSP00000435801.1; ENSG00000125861.16. [Q9GZZ7-3]
DR GeneID; 64096; -.
DR KEGG; hsa:64096; -.
DR MANE-Select; ENST00000290417.7; ENSP00000290417.2; NM_022139.4; NP_071422.1. [Q9GZZ7-2]
DR UCSC; uc002win.3; human. [Q9GZZ7-1]
DR CTD; 64096; -.
DR DisGeNET; 64096; -.
DR GeneCards; GFRA4; -.
DR HGNC; HGNC:13821; GFRA4.
DR HPA; ENSG00000125861; Tissue enhanced (thyroid).
DR MIM; 618679; gene.
DR neXtProt; NX_Q9GZZ7; -.
DR OpenTargets; ENSG00000125861; -.
DR PharmGKB; PA28656; -.
DR VEuPathDB; HostDB:ENSG00000125861; -.
DR eggNOG; ENOG502QSGA; Eukaryota.
DR GeneTree; ENSGT00940000160491; -.
DR HOGENOM; CLU_040179_2_0_1; -.
DR InParanoid; Q9GZZ7; -.
DR OMA; AFDSGWP; -.
DR OrthoDB; 1007489at2759; -.
DR PhylomeDB; Q9GZZ7; -.
DR TreeFam; TF331647; -.
DR PathwayCommons; Q9GZZ7; -.
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; Q9GZZ7; -.
DR SIGNOR; Q9GZZ7; -.
DR BioGRID-ORCS; 64096; 14 hits in 1062 CRISPR screens.
DR GenomeRNAi; 64096; -.
DR Pharos; Q9GZZ7; Tbio.
DR PRO; PR:Q9GZZ7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9GZZ7; protein.
DR Bgee; ENSG00000125861; Expressed in periodontal ligament and 21 other tissues.
DR Genevisible; Q9GZZ7; 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:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR InterPro; IPR016017; GDNF/GAS1.
DR InterPro; IPR037193; GDNF_alpha.
DR InterPro; IPR003438; GDNF_rcpt.
DR PANTHER; PTHR10269; PTHR10269; 1.
DR Pfam; PF02351; GDNF; 2.
DR PRINTS; PR01316; GDNFRECEPTOR.
DR SMART; SM00907; GDNF; 2.
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; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..278
FT /note="GDNF family receptor alpha-4"
FT /id="PRO_0000010793"
FT PROPEP 279..299
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010794"
FT REGION 145..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 278
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 132..197
FT /note="CARAAAGPWRGWGRGLSPAHRPPAAQASPPGLSGLVHPSAQRPRRLPAGPGR
FT PLPARLRGPRGVPA -> PRLLAFQVSCTPAPSAPDGCLLDQGARCLRAYAGLV (in
FT isoform GFRalpha4a)"
FT /evidence="ECO:0000303|PubMed:11116144"
FT /id="VSP_007223"
FT VAR_SEQ 132..182
FT /note="CARAAAGPWRGWGRGLSPAHRPPAAQASPPGLSGLVHPSAQRPRRLPAGPG
FT -> PRLLAFQVSCTPAPSAPDGCLLDQGARCLRAYAGLVGSPQAPPSPLTTWTT (in
FT isoform GFRalpha4c)"
FT /evidence="ECO:0000303|PubMed:11116144"
FT /id="VSP_007224"
FT VAR_SEQ 183..299
FT /note="Missing (in isoform GFRalpha4c)"
FT /evidence="ECO:0000303|PubMed:11116144"
FT /id="VSP_007225"
SQ SEQUENCE 299 AA; 31670 MW; 8443B8342FF10801 CRC64;
MVRCLGPALL LLLLLGSASS VGGNRCVDAA EACTADARCQ RLRSEYVAQC LGRAAQGGCP
RARCRRALRR FFARGPPALT HALLFCPCAG PACAERRRQT FVPSCAFSGP GPAPPSCLEP
LNFCERSRVC RCARAAAGPW RGWGRGLSPA HRPPAAQASP PGLSGLVHPS AQRPRRLPAG
PGRPLPARLR GPRGVPAGTA VTPNYVDNVS ARVAPWCDCG ASGNRREDCE AFRGLFTRNR
CLDGAIQAFA SGWPPVLLDQ LNPQGDPEHS LLQVSSTGRA LERRSLLSIL PVLALPALL
