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GFRA4_MOUSE
ID   GFRA4_MOUSE             Reviewed;         260 AA.
AC   Q9JJT2; A2AP44; A2AP46; A2AP47; A2AP49; Q9JJT3; Q9JJT4; Q9JJT6; Q9JJT7;
AC   Q9JJT8;
DT   23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-APR-2003, sequence version 2.
DT   03-AUG-2022, entry version 129.
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   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 A1; A2; A3; B1; B2 AND B3).
RC   TISSUE=Thyroid;
RX   PubMed=10860579; DOI=10.1006/mcne.2000.0845;
RA   Lindahl M., Timmusk T., Rossi J., Saarma M., Airaksinen M.S.;
RT   "Expression and alternative splicing of mouse Gfra4 suggest roles in
RT   endocrine cell development.";
RL   Mol. Cell. Neurosci. 15:522-533(2000).
RN   [2]
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).
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:0000250|UniProtKB:Q9GZZ7}.
CC   -!- SUBCELLULAR LOCATION: [Isoform a1]: Cell membrane; Lipid-anchor, GPI-
CC       anchor.
CC   -!- SUBCELLULAR LOCATION: [Isoform b1]: Cell membrane; Lipid-anchor, GPI-
CC       anchor.
CC   -!- SUBCELLULAR LOCATION: [Isoform a3]: Secreted {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Isoform b3]: Secreted {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC         Comment=Additional isoforms seem to exist. Tissue-specific and,
CC         developmentally regulated splicing.;
CC       Name=a1;
CC         IsoId=Q9JJT2-1; Sequence=Displayed;
CC       Name=a2;
CC         IsoId=Q9JJT2-2; Sequence=VSP_007227;
CC       Name=a3;
CC         IsoId=Q9JJT2-3; Sequence=VSP_007228, VSP_007229;
CC       Name=b1;
CC         IsoId=Q9JJT2-4; Sequence=VSP_007226;
CC       Name=b2;
CC         IsoId=Q9JJT2-5; Sequence=VSP_007226, VSP_007227;
CC       Name=b3;
CC         IsoId=Q9JJT2-6; Sequence=VSP_007226, VSP_007228, VSP_007229;
CC   -!- TISSUE SPECIFICITY: Expressed in many tissues including adrenal
CC       medulla, brain neurons, with highest levels in the cerebral cortex and
CC       hippocampus. Moderate levels found in the gut circular muscle and
CC       myenteric ganglia as well as in other peripheral ganglia, including the
CC       sensory dorsal root and trigeminal as well as superior cervical and
CC       sympathetic chain ganglia. Isoform a1, isoform a2, isoform b1 and
CC       isoform b2 are exclusively found in the thyroid, parthyroid and
CC       pituitary glands.
CC   -!- DEVELOPMENTAL STAGE: Expressed in several tissues at different
CC       embryonic and postnatal stages such as the condensing mesenchyme of
CC       developing bones and developing nervous system. Expressed in the
CC       developing pituitary gland from 16 dpc and in developing thyroid C-
CC       cells from 14 dpc. In the ventral spinal cord, levels decline before
CC       birth. In the parathyroid, levels first detected in 3- to 6-week-old
CC       mice with high expression. In the adrenal medulla, expressed only in
CC       newborn, postnatal (P08) and adult mice. Isoform a1 and isoform b1 are
CC       prefentially expressed in 3-week-old thyroid, isoform a2 and isoform b2
CC       in newborn and 6-week-old thyroid glands as well as in postnatal
CC       adrenal and pituitary glands.
CC   -!- MISCELLANEOUS: [Isoform b1]: Alternative N-terminal. Probably non-
CC       functional. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform b2]: Alternative N-terminal. Probably non-
CC       functional. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform b3]: Alternative N-terminal. Probably non-
CC       functional. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the GDNFR family. {ECO:0000305}.
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DR   EMBL; AJ276870; CAB89690.1; -; mRNA.
DR   EMBL; AJ276871; CAB89691.1; -; mRNA.
DR   EMBL; AJ276872; CAB89692.1; -; mRNA.
DR   EMBL; AJ276514; CAB89687.1; -; mRNA.
DR   EMBL; AJ276515; CAB89688.1; -; mRNA.
DR   EMBL; AJ276516; CAB89689.1; -; mRNA.
DR   EMBL; AL833771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS16752.1; -. [Q9JJT2-5]
DR   CCDS; CCDS50715.1; -. [Q9JJT2-2]
DR   CCDS; CCDS59637.1; -. [Q9JJT2-4]
DR   CCDS; CCDS59638.1; -. [Q9JJT2-1]
DR   RefSeq; NP_001129535.1; NM_001136063.2. [Q9JJT2-2]
DR   RefSeq; NP_001257930.1; NM_001271001.1. [Q9JJT2-1]
DR   RefSeq; NP_001257931.1; NM_001271002.1. [Q9JJT2-4]
DR   RefSeq; NP_064398.1; NM_020014.2. [Q9JJT2-5]
DR   AlphaFoldDB; Q9JJT2; -.
DR   SMR; Q9JJT2; -.
DR   STRING; 10090.ENSMUSP00000028787; -.
DR   GlyGen; Q9JJT2; 1 site.
DR   PaxDb; Q9JJT2; -.
DR   PRIDE; Q9JJT2; -.
DR   Antibodypedia; 23585; 261 antibodies from 26 providers.
DR   DNASU; 14588; -.
DR   Ensembl; ENSMUST00000028787; ENSMUSP00000028787; ENSMUSG00000027316. [Q9JJT2-5]
DR   Ensembl; ENSMUST00000066958; ENSMUSP00000068357; ENSMUSG00000027316. [Q9JJT2-1]
DR   Ensembl; ENSMUST00000110234; ENSMUSP00000105863; ENSMUSG00000027316. [Q9JJT2-6]
DR   Ensembl; ENSMUST00000110235; ENSMUSP00000105864; ENSMUSG00000027316. [Q9JJT2-3]
DR   Ensembl; ENSMUST00000110239; ENSMUSP00000105868; ENSMUSG00000027316. [Q9JJT2-4]
DR   Ensembl; ENSMUST00000110240; ENSMUSP00000105869; ENSMUSG00000027316. [Q9JJT2-2]
DR   GeneID; 14588; -.
DR   KEGG; mmu:14588; -.
DR   UCSC; uc008mkd.2; mouse. [Q9JJT2-2]
DR   UCSC; uc008mkg.2; mouse. [Q9JJT2-4]
DR   UCSC; uc008mkh.2; mouse. [Q9JJT2-1]
DR   UCSC; uc008mki.1; mouse. [Q9JJT2-6]
DR   UCSC; uc008mkj.1; mouse. [Q9JJT2-3]
DR   CTD; 64096; -.
DR   MGI; MGI:1341873; Gfra4.
DR   VEuPathDB; HostDB:ENSMUSG00000027316; -.
DR   eggNOG; ENOG502QSGA; Eukaryota.
DR   GeneTree; ENSGT00940000160491; -.
DR   HOGENOM; CLU_040179_2_0_1; -.
DR   InParanoid; Q9JJT2; -.
DR   OMA; AFDSGWP; -.
DR   PhylomeDB; Q9JJT2; -.
DR   TreeFam; TF331647; -.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-8853659; RET signaling.
DR   BioGRID-ORCS; 14588; 2 hits in 73 CRISPR screens.
DR   PRO; PR:Q9JJT2; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9JJT2; protein.
DR   Bgee; ENSMUSG00000027316; Expressed in urinary bladder and 96 other tissues.
DR   ExpressionAtlas; Q9JJT2; baseline and differential.
DR   Genevisible; Q9JJT2; 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:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0015026; F:coreceptor activity; TAS:MGI.
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:0030279; P:negative regulation of ossification; IMP:MGI.
DR   GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR   GO; GO:0001503; P:ossification; IMP: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   PANTHER; PTHR10269; PTHR10269; 1.
DR   Pfam; PF02351; GDNF; 2.
DR   PRINTS; PR01316; GDNFRECEPTOR.
DR   SMART; SM00907; GDNF; 2.
DR   SUPFAM; SSF110035; SSF110035; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Glycoprotein; GPI-anchor; Lipoprotein;
KW   Membrane; Receptor; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..237
FT                   /note="GDNF family receptor alpha-4"
FT                   /id="PRO_0000010795"
FT   PROPEP          238..260
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000010796"
FT   LIPID           237
FT                   /note="GPI-anchor amidated threonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..17
FT                   /note="MAHCMESALLLLLLLGS -> MLRRAHLMDERPGQAIFLGLGSQRGS (in
FT                   isoform b1, isoform b2 and isoform b3)"
FT                   /evidence="ECO:0000303|PubMed:10860579"
FT                   /id="VSP_007226"
FT   VAR_SEQ         138..190
FT                   /note="PRLLAFQASCAPAPGSRDRCPEEGGPRCLRVYAGLIGTVVTPNYLDNVSARV
FT                   A -> CVRAGRAGPLTRVRARAGPVSLPSRPHALPRPAPATAARRRGARVVCASTQAS
FT                   (in isoform a3 and isoform b3)"
FT                   /evidence="ECO:0000303|PubMed:10860579"
FT                   /id="VSP_007228"
FT   VAR_SEQ         191..260
FT                   /note="Missing (in isoform a3 and isoform b3)"
FT                   /evidence="ECO:0000303|PubMed:10860579"
FT                   /id="VSP_007229"
FT   VAR_SEQ         245..260
FT                   /note="VSWLYALTALALQALL -> ARHEWPEKSWRQKQSLFCPNAQGVLAVCTHCP
FT                   GSPGPALIRNMNRGRHS (in isoform a2 and isoform b2)"
FT                   /evidence="ECO:0000303|PubMed:10860579"
FT                   /id="VSP_007227"
SQ   SEQUENCE   260 AA;  27990 MW;  2679BBC789E38075 CRC64;
     MAHCMESALL LLLLLGSASF TDGNRCVDAA EACTADERCQ QLRSEYVARC LGRAAPGGRP
     GPGGCVRSRC RRALRRFFAR GPPALTHALL FCGCEGSACA ERRRQTFAPA CAFSGPGLVP
     PSCLEPLERC ERSRLCRPRL LAFQASCAPA PGSRDRCPEE GGPRCLRVYA GLIGTVVTPN
     YLDNVSARVA PWCGCAASGN RREECEAFRK LFTRNPCLDG AIQAFDSLQP SVLQDQTAGC
     CFPRVSWLYA LTALALQALL
 
 
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