GDNF_RAT
ID GDNF_RAT Reviewed; 211 AA.
AC Q07731; Q63214; Q64062; Q64063; Q8R485; Q9QX94; Q9QX95; Q9QXJ7; Q9QXJ8;
AC Q9QXJ9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 25-MAY-2022, entry version 162.
DE RecName: Full=Glial cell line-derived neurotrophic factor;
DE AltName: Full=Astrocyte-derived trophic factor;
DE Short=ATF;
DE Flags: Precursor;
GN Name=Gdnf;
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] (ISOFORM 1), HOMODIMERIZATION, DISULFIDE BONDS,
RP GLYCOSYLATION, AND PROTEIN SEQUENCE OF 78-102.
RC TISSUE=Glial tumor;
RX PubMed=8493557; DOI=10.1126/science.8493557;
RA Lin L.-F.H., Doherty D.H., Lile J.D., Bektesh S., Collins F.;
RT "GDNF: a glial cell line-derived neurotrophic factor for midbrain
RT dopaminergic neurons.";
RL Science 260:1130-1132(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=7895811; DOI=10.1016/0014-4886(95)90006-3;
RA Springer J.E., Seeburger J.L., He J., Gabrea A., Blankenhorn E.P.,
RA Bergman L.W.;
RT "cDNA sequence and differential mRNA regulation of two forms of glial cell
RT line-derived neurotrophic factor in Schwann cells and rat skeletal
RT muscle.";
RL Exp. Neurol. 131:47-52(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-125 (ISOFORMS 1; 2 AND 3), FUNCTION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=10828539; DOI=10.1016/s0306-4522(00)00079-8;
RA Russell F.D., Koishi K., Jiang Y., McLennan I.S.;
RT "Anterograde axonal transport of glial cell line-derived neurotrophic
RT factor and its receptors in rat hypoglossal nerve.";
RL Neuroscience 97:575-580(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-76 (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Kidney;
RX PubMed=7696586; DOI=10.1097/00001756-199412000-00020;
RA Suter-Crazzolara C., Unsicker K.;
RT "GDNF is expressed in two forms in many tissues outside the CNS.";
RL NeuroReport 5:2486-2488(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
RA Schmidt C., Suter-Crazzolara C.;
RT "The Rat GDNF gene.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-207 (ISOFORM 1), AND INDUCTION.
RC TISSUE=Glial tumor;
RX PubMed=11930164; DOI=10.1097/00001756-200203250-00023;
RA Armstrong K.J., Niles L.P.;
RT "Induction of GDNF mRNA expression by melatonin in rat C6 glioma cells.";
RL NeuroReport 13:473-475(2002).
RN [7]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=7867768; DOI=10.1006/exnr.1994.1218;
RA Schaar D.G., Sieber B.-A., Sherwood A.C., Dean D., Mendoza G.,
RA Ramakrishnan L., Dreyfus C.F., Black I.B.;
RT "Multiple astrocyte transcripts encode nigral trophic factors in rat and
RT human.";
RL Exp. Neurol. 130:387-393(1994).
RN [8]
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=9187648; DOI=10.1038/nsb0697-435;
RA Eigenbrot C., Gerber C.;
RT "X-ray structure of glial cell-derived neurotrophic factor at 1.9-A
RT resolution and implications for receptor binding.";
RL Nat. Struct. Biol. 4:435-438(1997).
CC -!- FUNCTION: Neurotrophic factor that enhances survival and morphological
CC differentiation of dopaminergic neurons and increases their high-
CC affinity dopamine uptake. May also modulate local neuronal effects in
CC distal regions of the motor neuron. {ECO:0000269|PubMed:10828539}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8493557). 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, ECO:0000269|PubMed:8493557}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P39905}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=GDNF633;
CC IsoId=Q07731-1; Sequence=Displayed;
CC Name=2; Synonyms=ATF-1, GDNF555, sGDNF, Smaller GDNF;
CC IsoId=Q07731-2; Sequence=VSP_006422;
CC Name=3;
CC IsoId=Q07731-3; Sequence=VSP_026365;
CC Name=4;
CC IsoId=Q07731-4; Sequence=VSP_026366;
CC -!- TISSUE SPECIFICITY: Expressed in both the central nervous system (CNS)
CC and in non-CNS tissues, including the kidney, lung, bone, heart, liver,
CC spleen, sciatic nerve and blood (PubMed:7696586). Expressed in brain
CC (at protein level) (PubMed:21994944). Localizes at the proximal
CC ligature of the hypoglossal nerve (PubMed:10828539).
CC {ECO:0000269|PubMed:10828539, ECO:0000269|PubMed:21994944,
CC ECO:0000269|PubMed:7696586}.
CC -!- INDUCTION: By melatonin. {ECO:0000269|PubMed:11930164}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB64357.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB64358.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; L15305; AAA67909.1; -; mRNA.
DR EMBL; S75583; AAB33891.1; -; mRNA.
DR EMBL; S75585; AAB33892.1; -; mRNA.
DR EMBL; AF205713; AAF23767.1; -; mRNA.
DR EMBL; AF205714; AAF23768.1; -; mRNA.
DR EMBL; AF205715; AAF23769.1; -; mRNA.
DR EMBL; X92495; CAA63237.1; -; mRNA.
DR EMBL; AJ011432; CAB64357.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AJ011432; CAB64358.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF497634; AAM18096.1; -; mRNA.
DR PIR; A37499; A37499.
DR RefSeq; NP_062012.1; NM_019139.1. [Q07731-1]
DR PDB; 1AGQ; X-ray; 1.90 A; A/B/C/D=78-211.
DR PDBsum; 1AGQ; -.
DR AlphaFoldDB; Q07731; -.
DR SMR; Q07731; -.
DR BioGRID; 247487; 2.
DR STRING; 10116.ENSRNOP00000044012; -.
DR GlyGen; Q07731; 2 sites.
DR PaxDb; Q07731; -.
DR GeneID; 25453; -.
DR KEGG; rno:25453; -.
DR CTD; 2668; -.
DR RGD; 2677; Gdnf.
DR eggNOG; ENOG502QWCH; Eukaryota.
DR InParanoid; Q07731; -.
DR OrthoDB; 1373773at2759; -.
DR PhylomeDB; Q07731; -.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-8853659; RET signaling.
DR EvolutionaryTrace; Q07731; -.
DR PRO; PR:Q07731; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0043235; C:receptor complex; IDA:RGD.
DR GO; GO:0030116; F:glial cell-derived neurotrophic factor receptor binding; IPI:CAFA.
DR GO; GO:0008083; F:growth factor activity; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0048018; F:receptor ligand activity; IMP:CAFA.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:CAFA.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IDA:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:UniProtKB.
DR GO; GO:0071679; P:commissural neuron axon guidance; ISO:RGD.
DR GO; GO:0021516; P:dorsal spinal cord development; ISO:RGD.
DR GO; GO:0048568; P:embryonic organ development; ISO:RGD.
DR GO; GO:0048484; P:enteric nervous system development; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; IDA:UniProtKB.
DR GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
DR GO; GO:0030901; P:midbrain development; IEP:RGD.
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:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IDA:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0001759; P:organ induction; ISO:RGD.
DR GO; GO:0007422; P:peripheral nervous system development; ISO:RGD.
DR GO; GO:0030432; P:peristalsis; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IDA:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0072108; P:positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; ISO:RGD.
DR GO; GO:0032770; P:positive regulation of monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:CAFA.
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; ISS:UniProtKB.
DR GO; GO:0001941; P:postsynaptic membrane organization; ISO:RGD.
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:RGD.
DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; ISS:UniProtKB.
DR GO; GO:2001260; P:regulation of semaphorin-plexin signaling pathway; ISO:RGD.
DR GO; GO:0072106; P:regulation of ureteric bud formation; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IDA:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
DR GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR GO; GO:0060676; P:ureteric bud formation; ISO:RGD.
DR DisProt; DP00029; -.
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 SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..75
FT /id="PRO_0000034008"
FT CHAIN 78..211
FT /note="Glial cell line-derived neurotrophic factor"
FT /id="PRO_0000034009"
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:0000269|PubMed:8493557"
FT DISULFID 145..208
FT /evidence="ECO:0000269|PubMed:8493557"
FT DISULFID 149..210
FT /evidence="ECO:0000269|PubMed:8493557"
FT DISULFID 178
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:8493557"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10828539"
FT /id="VSP_026365"
FT VAR_SEQ 1..20
FT /note="MKLWDVVAVCLVLLHTASAF -> MGFGPLGVNVQLGVYGDRIR (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_026366"
FT VAR_SEQ 25..51
FT /note="GKRLLEAPAEDHSLGHRRVPFALTSDS -> A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10828539,
FT ECO:0000303|PubMed:7696586, ECO:0000303|PubMed:7895811"
FT /id="VSP_006422"
FT CONFLICT 77
FT /note="R -> S (in Ref. 2; AAB33891/AAB33892)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="E -> K (in Ref. 2; AAB33891/AAB33892)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="Q -> L (in Ref. 3; AAF23767)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="E -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:1AGQ"
FT HELIX 127..130
FT /evidence="ECO:0007829|PDB:1AGQ"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:1AGQ"
FT HELIX 155..166
FT /evidence="ECO:0007829|PDB:1AGQ"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:1AGQ"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1AGQ"
FT STRAND 197..200
FT /evidence="ECO:0007829|PDB:1AGQ"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:1AGQ"
SQ SEQUENCE 211 AA; 23619 MW; AE06C646682895A5 CRC64;
MKLWDVVAVC LVLLHTASAF PLPAGKRLLE APAEDHSLGH RRVPFALTSD SNMPEDYPDQ
FDDVMDFIQA TIKRLKRSPD KQAAALPRRE RNRQAAAASP ENSRGKGRRG QRGKNRGCVL
TAIHLNVTDL GLGYETKEEL IFRYCSGSCE AAETMYDKIL KNLSRSRRLT SDKVGQACCR
PVAFDDDLSF LDDSLVYHIL RKHSAKRCGC I
