GenomeNet

Database: UniProt
Entry: P39905
LinkDB: P39905
Original site: P39905 
ID   GDNF_HUMAN              Reviewed;         211 AA.
AC   P39905; B7WPK7; O95448; O95449; O95986; Q6FH33; Q96L44; Q9UD32;
AC   Q9UD33; Q9UMV2; Q9UP67; Q9UP97;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   07-NOV-2018, entry version 189.
DE   RecName: Full=Glial cell line-derived neurotrophic factor;
DE            Short=hGDNF;
DE   AltName: Full=Astrocyte-derived trophic factor;
DE            Short=ATF;
DE   Flags: Precursor;
GN   Name=GDNF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, HOMODIMERIZATION, AND
RP   DISULFIDE BONDS.
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), 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
RT   and human.";
RL   Exp. Neurol. 130:387-393(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Zhang B., Feng Z., Zhou Y., Peng X., Yuan J., Qiang B.;
RL   Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-187 (ISOFORM 1).
RC   TISSUE=Fetal kidney;
RX   PubMed=10366742; DOI=10.1016/S0169-328X(99)00106-0;
RA   Baecker P.A., Lee W.H., Verity A.N., Eglen R.M., Johnson R.M.;
RT   "Characterization of a promoter for the human glial cell line-derived
RT   neurotrophic factor gene.";
RL   Brain Res. Mol. Brain Res. 69:209-222(1999).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-88 (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP   [GENOMIC DNA] OF 1-77, AND NUCLEOTIDE SEQUENCE [MRNA] OF 1-59
RP   (ISOFORMS 3 AND 4).
RC   TISSUE=Brain, and Kidney;
RA   Suter-Crazzolara C., Baecker P.A., Lee W.H., Johnson R.M.,
RA   Unsicker K.;
RT   "The human GDNF gene promoter.";
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50, SUBCELLULAR LOCATION, AND
RP   INDUCTION.
RX   PubMed=9811930; DOI=10.1093/hmg/7.12.1873;
RA   Grimm L., Holinski-Feder E., Teodoridis J., Scheffer B.,
RA   Schindelhauer D., Meitinger T., Ueffing M.;
RT   "Analysis of the human GDNF gene reveals an inducible promoter, three
RT   exons, a triplet repeat within the 3'-UTR and alternative splice
RT   products.";
RL   Hum. Mol. Genet. 7:1873-1886(1998).
RN   [11]
RP   PROTEIN SEQUENCE OF 87-122; 141-153; 173-184 AND 196-211,
RP   HOMODIMERIZATION, AND DISULFIDE BONDS.
RX   PubMed=8988018; DOI=10.1021/bi9605550;
RA   Haniu M., Hui J., Young Y., Le J., Katta V., Lee R., Shimamoto G.,
RA   Rohde M.F.;
RT   "Glial cell line-derived neurotrophic factor: selective reduction of
RT   the intermolecular disulfide linkage and characterization of its
RT   disulfide structure.";
RL   Biochemistry 35:16799-16805(1996).
RN   [12]
RP   POSSIBLE INVOLVEMENT IN PCC, AND VARIANT PCC TRP-93.
RX   PubMed=9215674; DOI=10.1093/hmg/6.7.1051;
RA   Woodward E.R., Eng C., McMahon R., Voutilainen R., Affara N.A.,
RA   Ponder B.A., Maher E.R.;
RT   "Genetic predisposition to phaeochromocytoma: analysis of candidate
RT   genes GDNF, RET and VHL.";
RL   Hum. Mol. Genet. 6:1051-1056(1997).
RN   [13]
RP   ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 5), AND TISSUE SPECIFICITY.
RX   PubMed=22081608; DOI=10.1074/jbc.M111.310250;
RA   Airavaara M., Pletnikova O., Doyle M.E., Zhang Y.E., Troncoso J.C.,
RA   Liu Q.R.;
RT   "Identification of novel GDNF isoforms and cis-antisense GDNFOS gene
RT   and their regulation in human middle temporal gyrus of Alzheimer
RT   disease.";
RL   J. Biol. Chem. 286:45093-45102(2011).
RN   [14]
RP   REVIEW ON VARIANTS.
RX   PubMed=9359036;
RA   Hofstra R.M.W., Osinga J., Buys C.H.C.M.;
RT   "Mutations in Hirschsprung disease: when does a mutation contribute to
RT   the phenotype.";
RL   Eur. J. Hum. Genet. 5:180-185(1997).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 78-211, GLYCOSYLATION AT
RP   ASN-126, AND DISULFIDE BONDS.
RX   PubMed=19478429; DOI=10.1107/S1744309109017722;
RA   Parkash V., Goldman A.;
RT   "Comparison of GFL-GFRalpha complexes: further evidence relating GFL
RT   bend angle to RET signalling.";
RL   Acta Crystallogr. F 65:551-558(2009).
RN   [16]
RP   VARIANT HSCR3 SER-154.
RX   PubMed=8968758; DOI=10.1093/hmg/5.12.2023;
RA   Ivanchuk S.M., Myers S.M., Eng C., Mulligan L.M.;
RT   "De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor
RT   complex, in Hirschsprung disease.";
RL   Hum. Mol. Genet. 5:2023-2026(1996).
RN   [17]
RP   VARIANT HSCR3 TRP-93.
RX   PubMed=8896568; DOI=10.1038/ng1196-341;
RA   Angrist M., Bolk S., Halushka M., Lapchak P.A., Chakravarti A.;
RT   "Germline mutations in glial cell line-derived neurotrophic factor
RT   (GDNF) and RET in a Hirschsprung disease patient.";
RL   Nat. Genet. 14:341-344(1996).
RN   [18]
RP   VARIANT HSCR3 SER-21, AND VARIANT ASN-150.
RX   PubMed=8896569; DOI=10.1038/ng1196-345;
RA   Salomon R., Attie T., Pelet A., Bidaud C., Eng C., Amiel J.,
RA   Sarnacki S., Goulet O., Ricour C., Nihoul-Fekete C., Munnich A.,
RA   Lyonnet S.;
RT   "Germline mutations of the RET ligand GDNF are not sufficient to cause
RT   Hirschsprung disease.";
RL   Nat. Genet. 14:345-347(1996).
RN   [19]
RP   VARIANT CCHS TRP-93.
RX   PubMed=9497256; DOI=10.1086/301759;
RA   Amiel J., Salomon R., Attie T., Pelet A., Trang H., Mokhtari M.,
RA   Gaultier C., Munnich A., Lyonnet S.;
RT   "Mutations of the RET-GDNF signaling pathway in Ondine's curse.";
RL   Am. J. Hum. Genet. 62:715-717(1998).
RN   [20]
RP   VARIANT HSCR3 MET-211.
RX   PubMed=10917288; DOI=10.1053/jpsu.2000.7763;
RA   Martucciello G., Ceccherini I., Lerone M., Jasonni V.;
RT   "Pathogenesis of Hirschsprung's disease.";
RL   J. Pediatr. Surg. 35:1017-1025(2000).
CC   -!- FUNCTION: Neurotrophic factor that enhances survival and
CC       morphological differentiation of dopaminergic neurons and
CC       increases their high-affinity dopamine uptake.
CC       {ECO:0000269|PubMed:8493557}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked.
CC       {ECO:0000269|PubMed:19478429, ECO:0000269|PubMed:8493557,
CC       ECO:0000269|PubMed:8988018}.
CC   -!- INTERACTION:
CC       Q6RW13:AGTRAP; NbExp=3; IntAct=EBI-10207709, EBI-741181;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9811930}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1; Synonyms=Ex1_4L;
CC         IsoId=P39905-1; Sequence=Displayed;
CC       Name=2; Synonyms=ATF-1, Ex1_4S, Ex3_4S, HFK2-GDNF;
CC         IsoId=P39905-2; Sequence=VSP_006420;
CC       Name=3; Synonyms=Ex2_4L, HFK3-GDNF;
CC         IsoId=P39905-3; Sequence=VSP_026368;
CC       Name=4; Synonyms=HFK4-GDNF;
CC         IsoId=P39905-4; Sequence=VSP_026368, VSP_006420;
CC       Name=5; Synonyms=Ex4S_5;
CC         IsoId=P39905-5; Sequence=VSP_042298;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: In the brain, predominantly expressed in the
CC       striatum with highest levels in the caudate and lowest in the
CC       putamen. Isoform 2 is absent from most tissues except for low
CC       levels in intestine and kidney. Highest expression of isoform 3 is
CC       found in pancreatic islets. Isoform 5 is expressed at very low
CC       levels in putamen, nucleus accumbens, prefrontal cortex, amygdala,
CC       hypothalamus and intestine. Isoform 3 is up-regulated in the
CC       middle temporal gyrus of Alzheimer disease patients while isoform
CC       2 shows no change. {ECO:0000269|PubMed:22081608,
CC       ECO:0000269|PubMed:7867768}.
CC   -!- INDUCTION: By cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA) and
CC       FGF2. {ECO:0000269|PubMed:9811930}.
CC   -!- DISEASE: Hirschsprung disease 3 (HSCR3) [MIM:613711]: A disorder
CC       of neural crest development characterized by absence of enteric
CC       ganglia along a variable length of the intestine. It is the most
CC       common cause of congenital intestinal obstruction. Early symptoms
CC       range from complete acute neonatal obstruction, characterized by
CC       vomiting, abdominal distention and failure to pass stool, to
CC       chronic constipation in the older child.
CC       {ECO:0000269|PubMed:10917288, ECO:0000269|PubMed:8896568,
CC       ECO:0000269|PubMed:8896569, ECO:0000269|PubMed:8968758}.
CC       Note=Disease susceptibility is associated with variations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Congenital central hypoventilation syndrome (CCHS)
CC       [MIM:209880]: Rare disorder characterized by abnormal control of
CC       respiration in the absence of neuromuscular or lung disease, or an
CC       identifiable brain stem lesion. A deficiency in autonomic control
CC       of respiration results in inadequate or negligible ventilatory and
CC       arousal responses to hypercapnia and hypoxemia.
CC       {ECO:0000269|PubMed:9497256}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-
CC       producing tumor of chromaffin tissue of the adrenal medulla or
CC       sympathetic paraganglia. The cardinal symptom, reflecting the
CC       increased secretion of epinephrine and norepinephrine, is
CC       hypertension, which may be persistent or intermittent.
CC       {ECO:0000269|PubMed:9215674}. Note=The gene represented in this
CC       entry may act as a disease modifier.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC       {ECO:0000305}.
DR   EMBL; L19063; AAA67910.1; -; Genomic_DNA.
DR   EMBL; L19062; AAA67910.1; JOINED; Genomic_DNA.
DR   EMBL; AY052832; AAL11017.1; -; mRNA.
DR   EMBL; CR541923; CAG46721.1; -; mRNA.
DR   EMBL; AC008869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471119; EAW55963.1; -; Genomic_DNA.
DR   EMBL; BC069119; AAH69119.1; -; mRNA.
DR   EMBL; BC069369; AAH69369.1; -; mRNA.
DR   EMBL; BC128108; AAI28109.1; -; mRNA.
DR   EMBL; BC128109; AAI28110.1; -; mRNA.
DR   EMBL; AF053748; AAD43139.1; -; mRNA.
DR   EMBL; AJ001896; CAA05074.1; -; Genomic_DNA.
DR   EMBL; AJ001897; CAA05075.1; -; mRNA.
DR   EMBL; AJ001898; CAA05076.1; -; mRNA.
DR   EMBL; AJ001899; CAA05077.1; -; mRNA.
DR   EMBL; AJ001900; CAA05078.1; -; mRNA.
DR   EMBL; AF063586; AAC98782.1; -; Genomic_DNA.
DR   CCDS; CCDS3922.1; -. [P39905-1]
DR   CCDS; CCDS3923.1; -. [P39905-2]
DR   CCDS; CCDS54845.1; -. [P39905-3]
DR   CCDS; CCDS54846.1; -. [P39905-4]
DR   CCDS; CCDS75237.1; -. [P39905-5]
DR   PIR; B37499; B37499.
DR   RefSeq; NP_000505.1; NM_000514.3. [P39905-1]
DR   RefSeq; NP_001177397.1; NM_001190468.1. [P39905-3]
DR   RefSeq; NP_001177398.1; NM_001190469.1. [P39905-4]
DR   RefSeq; NP_001265027.1; NM_001278098.1. [P39905-5]
DR   RefSeq; NP_954701.1; NM_199231.2. [P39905-2]
DR   RefSeq; XP_011512332.1; XM_011514030.2. [P39905-5]
DR   RefSeq; XP_016864826.1; XM_017009337.1. [P39905-2]
DR   UniGene; Hs.248114; -.
DR   PDB; 2V5E; X-ray; 2.35 A; B=111-211.
DR   PDB; 3FUB; X-ray; 2.35 A; B/D=78-211.
DR   PDB; 4UX8; EM; 24.00 A; D/F=78-211.
DR   PDBsum; 2V5E; -.
DR   PDBsum; 3FUB; -.
DR   PDBsum; 4UX8; -.
DR   ProteinModelPortal; P39905; -.
DR   SMR; P39905; -.
DR   BioGrid; 108936; 13.
DR   DIP; DIP-59051N; -.
DR   IntAct; P39905; 7.
DR   STRING; 9606.ENSP00000409007; -.
DR   DrugBank; DB05066; AV411.
DR   iPTMnet; P39905; -.
DR   PhosphoSitePlus; P39905; -.
DR   BioMuta; GDNF; -.
DR   DMDM; 729567; -.
DR   PaxDb; P39905; -.
DR   PRIDE; P39905; -.
DR   ProteomicsDB; 55328; -.
DR   ProteomicsDB; 55329; -. [P39905-2]
DR   ProteomicsDB; 55330; -. [P39905-3]
DR   ProteomicsDB; 55331; -. [P39905-4]
DR   ProteomicsDB; 55332; -. [P39905-5]
DR   TopDownProteomics; P39905-3; -. [P39905-3]
DR   DNASU; 2668; -.
DR   Ensembl; ENST00000326524; ENSP00000317145; ENSG00000168621. [P39905-1]
DR   Ensembl; ENST00000344622; ENSP00000339703; ENSG00000168621. [P39905-2]
DR   Ensembl; ENST00000381826; ENSP00000371248; ENSG00000168621. [P39905-4]
DR   Ensembl; ENST00000427982; ENSP00000409007; ENSG00000168621. [P39905-3]
DR   Ensembl; ENST00000515058; ENSP00000425928; ENSG00000168621. [P39905-2]
DR   Ensembl; ENST00000620847; ENSP00000478722; ENSG00000168621. [P39905-5]
DR   GeneID; 2668; -.
DR   KEGG; hsa:2668; -.
DR   UCSC; uc011cpd.2; human. [P39905-1]
DR   CTD; 2668; -.
DR   DisGeNET; 2668; -.
DR   EuPathDB; HostDB:ENSG00000168621.14; -.
DR   GeneCards; GDNF; -.
DR   GeneReviews; GDNF; -.
DR   HGNC; HGNC:4232; GDNF.
DR   HPA; CAB005210; -.
DR   HPA; HPA070283; -.
DR   MalaCards; GDNF; -.
DR   MIM; 171300; phenotype.
DR   MIM; 209880; phenotype.
DR   MIM; 600837; gene.
DR   MIM; 613711; phenotype.
DR   neXtProt; NX_P39905; -.
DR   OpenTargets; ENSG00000168621; -.
DR   Orphanet; 388; Hirschsprung disease.
DR   Orphanet; 661; Ondine syndrome.
DR   PharmGKB; PA28644; -.
DR   eggNOG; ENOG410IGT5; Eukaryota.
DR   eggNOG; ENOG4111I3D; LUCA.
DR   GeneTree; ENSGT00520000055559; -.
DR   HOVERGEN; HBG106680; -.
DR   InParanoid; P39905; -.
DR   KO; K05452; -.
DR   OMA; AETMYDK; -.
DR   OrthoDB; EOG091G0P1K; -.
DR   PhylomeDB; P39905; -.
DR   TreeFam; TF332366; -.
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; P39905; -.
DR   SIGNOR; P39905; -.
DR   ChiTaRS; GDNF; human.
DR   EvolutionaryTrace; P39905; -.
DR   GeneWiki; Glial_cell_line-derived_neurotrophic_factor; -.
DR   GenomeRNAi; 2668; -.
DR   PRO; PR:P39905; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000168621; Expressed in 91 organ(s), highest expression level in quadriceps femoris.
DR   ExpressionAtlas; P39905; baseline and differential.
DR   Genevisible; P39905; HS.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005622; C:intracellular; IEA:GOC.
DR   GO; GO:1902379; F:chemoattractant activity involved in axon guidance; TAS:ARUK-UCL.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR   GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR   GO; GO:0008344; P:adult locomotory behavior; TAS:BHF-UCL.
DR   GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR   GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR   GO; GO:0071679; P:commissural neuron axon guidance; ISS:ARUK-UCL.
DR   GO; GO:0021516; P:dorsal spinal cord development; ISS:ARUK-UCL.
DR   GO; GO:0048568; P:embryonic organ development; ISS:ARUK-UCL.
DR   GO; GO:0048484; P:enteric nervous system development; ISS:UniProtKB.
DR   GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR   GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; IEA:Ensembl.
DR   GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
DR   GO; GO:0048255; P:mRNA stabilization; IDA:BHF-UCL.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:UniProtKB.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR   GO; GO:0007399; P:nervous system development; TAS:ARUK-UCL.
DR   GO; GO:0001755; P:neural crest cell migration; IDA:MGI.
DR   GO; GO:0031175; P:neuron projection development; IDA:MGI.
DR   GO; GO:0001759; P:organ induction; IEA:Ensembl.
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; IGI:MGI.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IDA:MGI.
DR   GO; GO:0033603; P:positive regulation of dopamine secretion; TAS:BHF-UCL.
DR   GO; GO:0072108; P:positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; IEA:Ensembl.
DR   GO; GO:0032770; P:positive regulation of monooxygenase activity; IDA:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0072107; P:positive regulation of ureteric bud formation; IDA:UniProtKB.
DR   GO; GO:0021784; P:postganglionic parasympathetic fiber development; ISS:UniProtKB.
DR   GO; GO:0001941; P:postsynaptic membrane organization; IEA:Ensembl.
DR   GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; IDA:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
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; ISS:ARUK-UCL.
DR   GO; GO:2000736; P:regulation of stem cell differentiation; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB.
DR   GO; GO:0060676; P:ureteric bud formation; IEA:Ensembl.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR016649; GDNF.
DR   InterPro; IPR001839; TGF-b_C.
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   3D-structure; Alternative splicing;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Disease mutation; Disulfide bond;
KW   Glycoprotein; Growth factor; Hirschsprung disease; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   PROPEP       20     75       {ECO:0000250}.
FT                                /FTId=PRO_0000034004.
FT   CHAIN        78    211       Glial cell line-derived neurotrophic
FT                                factor.
FT                                /FTId=PRO_0000034005.
FT   CARBOHYD    126    126       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:19478429}.
FT   CARBOHYD    162    162       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    118    179       {ECO:0000269|PubMed:8988018}.
FT   DISULFID    145    208       {ECO:0000269|PubMed:8988018}.
FT   DISULFID    149    210       {ECO:0000269|PubMed:8988018}.
FT   DISULFID    178    178       Interchain.
FT   VAR_SEQ       1     52       Missing (in isoform 5). {ECO:0000305}.
FT                                /FTId=VSP_042298.
FT   VAR_SEQ       1      1       M -> MQSLPNSNGAAAGRDFKM (in isoform 3 and
FT                                isoform 4). {ECO:0000303|Ref.9}.
FT                                /FTId=VSP_026368.
FT   VAR_SEQ      25     51       GKRPPEAPAEDRSLGRRRAPFALSSDS -> A (in
FT                                isoform 2 and isoform 4).
FT                                {ECO:0000303|PubMed:7867768,
FT                                ECO:0000303|Ref.3, ECO:0000303|Ref.9}.
FT                                /FTId=VSP_006420.
FT   VARIANT      21     21       P -> S (in HSCR3; unknown pathological
FT                                significance; dbSNP:rs777451569).
FT                                {ECO:0000269|PubMed:8896569}.
FT                                /FTId=VAR_009494.
FT   VARIANT      93     93       R -> W (in HSCR3, CCHS and PCC; unknown
FT                                pathological significance;
FT                                dbSNP:rs36119840).
FT                                {ECO:0000269|PubMed:8896568,
FT                                ECO:0000269|PubMed:9215674,
FT                                ECO:0000269|PubMed:9497256}.
FT                                /FTId=VAR_009495.
FT   VARIANT     150    150       D -> N (polymorphism; risk factor for
FT                                Hirschsprung disease; dbSNP:rs76466003).
FT                                {ECO:0000269|PubMed:8896569}.
FT                                /FTId=VAR_009496.
FT   VARIANT     154    154       T -> S (in HSCR3; sporadic form;
FT                                dbSNP:rs104893891).
FT                                {ECO:0000269|PubMed:8968758}.
FT                                /FTId=VAR_009497.
FT   VARIANT     211    211       I -> M (in HSCR3; dbSNP:rs121918536).
FT                                {ECO:0000269|PubMed:10917288}.
FT                                /FTId=VAR_018152.
FT   TURN        114    117       {ECO:0000244|PDB:2V5E}.
FT   STRAND      119    126       {ECO:0000244|PDB:2V5E}.
FT   HELIX       127    130       {ECO:0000244|PDB:2V5E}.
FT   STRAND      139    147       {ECO:0000244|PDB:2V5E}.
FT   HELIX       155    165       {ECO:0000244|PDB:2V5E}.
FT   STRAND      168    173       {ECO:0000244|PDB:2V5E}.
FT   STRAND      178    184       {ECO:0000244|PDB:2V5E}.
FT   STRAND      188    191       {ECO:0000244|PDB:2V5E}.
FT   STRAND      197    200       {ECO:0000244|PDB:2V5E}.
FT   STRAND      204    211       {ECO:0000244|PDB:2V5E}.
SQ   SEQUENCE   211 AA;  23720 MW;  A0D1EBF77FC82691 CRC64;
     MKLWDVVAVC LVLLHTASAF PLPAGKRPPE APAEDRSLGR RRAPFALSSD SNMPEDYPDQ
     FDDVMDFIQA TIKRLKRSPD KQMAVLPRRE RNRQAAAANP ENSRGKGRRG QRGKNRGCVL
     TAIHLNVTDL GLGYETKEEL IFRYCSGSCD AAETTYDKIL KNLSRNRRLV SDKVGQACCR
     PIAFDDDLSF LDDNLVYHIL RKHSAKRCGC I
//
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