GDNF_MOUSE
ID GDNF_MOUSE Reviewed; 211 AA.
AC P48540; O09058; P70446; P97919; P97920; Q6LEL9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Glial cell line-derived neurotrophic factor;
DE Short=mGDNF;
DE AltName: Full=Astrocyte-derived trophic factor;
DE Short=ATF;
DE Flags: Precursor;
GN Name=Gdnf;
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] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Spinal ganglion;
RX PubMed=7650763; DOI=10.1002/jnr.490410215;
RA Watabe K., Fukuda T., Tanaka J., Honda H., Toyohara K., Sakai O.;
RT "Spontaneously immortalized adult mouse Schwann cells secrete autocrine and
RT paracrine growth-promoting activities.";
RL J. Neurosci. Res. 41:279-290(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=129/SvJ; TISSUE=Glial cell;
RX PubMed=8808409; DOI=10.1016/0925-4773(95)00464-5;
RA Hellmich H.L., Kos L., Cho E.S., Mahon K.A., Zimmer A.;
RT "Embryonic expression of glial cell-line derived neurotrophic factor (GDNF)
RT suggests multiple developmental roles in neural differentiation and
RT epithelial-mesenchymal interactions.";
RL Mech. Dev. 54:95-105(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [GENOMIC DNA],
RP AND INDUCTION.
RC TISSUE=Neonatal brain;
RX PubMed=9426245; DOI=10.1016/s0378-1119(97)00506-4;
RA Matsushita N., Fujita Y., Tanaka M., Nagatsu T., Kiuchi K.;
RT "Cloning and structural organization of the gene encoding the mouse glial
RT cell line-derived neurotrophic factor, GDNF.";
RL Gene 203:149-157(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL NUCLEOTIDE SEQUENCE
RP [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1-103 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC STRAIN=BALB/cJ, and C57BL/10J; TISSUE=Brain, and Glial cell;
RX PubMed=12168040;
RA Wang F.-J., Zhao J., Too H.P.;
RT "Cloning and characterization of mouse glial cell line-derived neurotrophic
RT growth factor (GDNF).";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 30:375-381(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [6]
RP INTERACTION WITH SORL1.
RX PubMed=21994944; DOI=10.1074/jbc.m111.246413;
RA Geng Z., Xu F.Y., Huang S.H., Chen Z.Y.;
RT "Sorting protein-related receptor SorLA controls regulated secretion of
RT glial cell line-derived neurotrophic factor.";
RL J. Biol. Chem. 286:41871-41882(2011).
CC -!- FUNCTION: Neurotrophic factor that enhances survival and morphological
CC differentiation of dopaminergic neurons and increases their high-
CC affinity dopamine uptake.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC RET (By similarity). Interacts (via propeptide) with SORL1 (via N-
CC terminal ectodomain), either alone or in complex with GFRA1;
CC interaction with SORL1 affects GDNF-regulated, but not constitutive
CC secretion (PubMed:21994944). Also interacts with SORL1 in complex with
CC GFRA1; this interaction leads to GDNF endocytosis and lysosomal
CC degradation (By similarity). {ECO:0000250|UniProtKB:P39905,
CC ECO:0000269|PubMed:21994944}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P39905}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=GDNF-alpha;
CC IsoId=P48540-1; Sequence=Displayed;
CC Name=2; Synonyms=GDNF-beta;
CC IsoId=P48540-2; Sequence=VSP_026367, VSP_006421;
CC Name=3;
CC IsoId=P48540-3; Sequence=VSP_026367;
CC -!- TISSUE SPECIFICITY: Expressed in both the central nervous system (CNS)
CC and in non-CNS tissues. Expressed in a highly dynamic pattern in the
CC anterior neuroectoderm during the early stages of neurogenesis between
CC 7.5 dpc and 10.5 dpc. Beginning at 10.5 dpc, expression begins in
CC mesenchymal tissues of several organs including the digestive tract,
CC kidney, testis, frontonasal mass, tooth primordium, tongue, mandible,
CC whisker follicles, ear, eye, limb bud and in distinct regions of the
CC brain. Also expressed in the heart, ileum, liver and muscle.
CC {ECO:0000269|PubMed:12168040, ECO:0000269|PubMed:8808409}.
CC -!- DEVELOPMENTAL STAGE: First detected at 7.5 dpc, reaches its peak around
CC 9.5 dpc and declines considerably after 10.5 dpc.
CC {ECO:0000269|PubMed:8808409}.
CC -!- INDUCTION: Expression in C6 glioma cells was transiently induced by
CC treatment with phorbol myristate acetate (PMA), but not by forskolin.
CC {ECO:0000269|PubMed:9426245}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000305}.
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DR EMBL; D49921; BAA08660.1; -; mRNA.
DR EMBL; U36449; AAB52953.1; -; Genomic_DNA.
DR EMBL; D88264; BAA13566.1; -; mRNA.
DR EMBL; D88352; BAB12221.1; -; Genomic_DNA.
DR EMBL; D88352; BAA13591.1; -; Genomic_DNA.
DR EMBL; U37459; AAB18672.1; -; mRNA.
DR EMBL; U66195; AAB07463.1; -; Genomic_DNA.
DR EMBL; U75532; AAB18343.1; -; mRNA.
DR EMBL; BC119031; AAI19032.1; -; mRNA.
DR CCDS; CCDS27371.1; -. [P48540-3]
DR PIR; I49686; I49686.
DR RefSeq; NP_001288261.1; NM_001301332.1. [P48540-2]
DR RefSeq; NP_001288286.1; NM_001301357.1. [P48540-1]
DR RefSeq; NP_034405.1; NM_010275.3. [P48540-3]
DR AlphaFoldDB; P48540; -.
DR SMR; P48540; -.
DR CORUM; P48540; -.
DR STRING; 10090.ENSMUSP00000022744; -.
DR GlyGen; P48540; 2 sites.
DR iPTMnet; P48540; -.
DR PhosphoSitePlus; P48540; -.
DR PaxDb; P48540; -.
DR PRIDE; P48540; -.
DR Antibodypedia; 3924; 564 antibodies from 41 providers.
DR DNASU; 14573; -.
DR Ensembl; ENSMUST00000022744; ENSMUSP00000022744; ENSMUSG00000022144. [P48540-3]
DR GeneID; 14573; -.
DR KEGG; mmu:14573; -.
DR UCSC; uc007vee.2; mouse. [P48540-3]
DR UCSC; uc007vef.2; mouse. [P48540-2]
DR UCSC; uc056yyf.1; mouse. [P48540-1]
DR CTD; 2668; -.
DR MGI; MGI:107430; Gdnf.
DR VEuPathDB; HostDB:ENSMUSG00000022144; -.
DR eggNOG; ENOG502QWCH; Eukaryota.
DR GeneTree; ENSGT00950000182993; -.
DR HOGENOM; CLU_102221_1_0_1; -.
DR InParanoid; P48540; -.
DR OMA; AKRCGCV; -.
DR OrthoDB; 1373773at2759; -.
DR PhylomeDB; P48540; -.
DR TreeFam; TF332366; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 14573; 3 hits in 76 CRISPR screens.
DR PRO; PR:P48540; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P48540; protein.
DR Bgee; ENSMUSG00000022144; Expressed in metanephric mesenchyme and 124 other tissues.
DR Genevisible; P48540; MM.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0030116; F:glial cell-derived neurotrophic factor receptor binding; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; TAS:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IDA:MGI.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:MGI.
DR GO; GO:0071679; P:commissural neuron axon guidance; IGI:ARUK-UCL.
DR GO; GO:0021516; P:dorsal spinal cord development; IMP:ARUK-UCL.
DR GO; GO:0048568; P:embryonic organ development; IMP:ARUK-UCL.
DR GO; GO:0048484; P:enteric nervous system development; IDA:UniProtKB.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; IEP:UniProtKB.
DR GO; GO:0001656; P:metanephros development; IMP:UniProtKB.
DR GO; GO:0048255; P:mRNA stabilization; ISS:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
DR GO; GO:1901166; P:neural crest cell migration involved in autonomic nervous system development; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0001759; P:organ induction; IGI:MGI.
DR GO; GO:0007422; P:peripheral nervous system development; IMP:MGI.
DR GO; GO:0030432; P:peristalsis; IMP:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0072108; P:positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; IMP:UniProtKB.
DR GO; GO:0032770; P:positive regulation of monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0072107; P:positive regulation of ureteric bud formation; ISS:UniProtKB.
DR GO; GO:0021784; P:postganglionic parasympathetic fiber development; IMP:UniProtKB.
DR GO; GO:0001941; P:postsynaptic membrane organization; IDA:MGI.
DR GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; IDA:MGI.
DR GO; GO:2001260; P:regulation of semaphorin-plexin signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0072106; P:regulation of ureteric bud formation; ISO:MGI.
DR GO; GO:0009611; P:response to wounding; ISO:MGI.
DR GO; GO:0048485; P:sympathetic nervous system development; IMP:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:MGI.
DR GO; GO:0001657; P:ureteric bud development; IDA:MGI.
DR GO; GO:0060676; P:ureteric bud formation; IMP:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR016649; GDNF.
DR InterPro; IPR043401; GDNF_fam.
DR InterPro; IPR001839; TGF-b_C.
DR PANTHER; PTHR12173; PTHR12173; 1.
DR PANTHER; PTHR12173:SF1; PTHR12173:SF1; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR PIRSF; PIRSF016238; GDNF; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..75
FT /evidence="ECO:0000250"
FT /id="PRO_0000034006"
FT CHAIN 78..211
FT /note="Glial cell line-derived neurotrophic factor"
FT /id="PRO_0000034007"
FT REGION 76..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 118..179
FT /evidence="ECO:0000250"
FT DISULFID 145..208
FT /evidence="ECO:0000250"
FT DISULFID 149..210
FT /evidence="ECO:0000250"
FT DISULFID 178
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MGFGPLGVNVQLGVYGDRIRGAAAGRDSKM (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12168040,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9426245"
FT /id="VSP_026367"
FT VAR_SEQ 25..51
FT /note="GKRLLEAPAEDHSLGHRRVPFALTSDS -> A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12168040"
FT /id="VSP_006421"
SQ SEQUENCE 211 AA; 23662 MW; B6731C767A3A95B7 CRC64;
MKLWDVVAVC LVLLHTASAF PLPAGKRLLE APAEDHSLGH RRVPFALTSD SNMPEDYPDQ
FDDVMDFIQA TIKRLKRSPD KQAAALPRRE RNRQAAAASP ENSRGKGRRG QRGKNRGCVL
TAIHLNVTDL GLGYETKEEL IFRYCSGSCE SAETMYDKIL KNLSRSRRLT SDKVGQACCR
PVAFDDDLSF LDDNLVYHIL RKHSAKRCGC I
