GDNF_HUMAN
ID GDNF_HUMAN Reviewed; 211 AA.
AC P39905; B7WPK7; O95448; O95449; O95986; Q6FH33; Q96L44; Q9UD32; Q9UD33;
AC Q9UMV2; Q9UP67; Q9UP97;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 213.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 and
RT 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., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 (ISOFORMS 3
RP AND 4).
RC TISSUE=Brain, and Kidney;
RA Suter-Crazzolara C., Baecker P.A., Lee W.H., Johnson R.M., 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., Schindelhauer D.,
RA 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, HOMODIMERIZATION,
RP 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 the
RT intermolecular disulfide linkage and characterization of its disulfide
RT structure.";
RL Biochemistry 35:16799-16805(1996).
RN [12]
RP POSSIBLE INVOLVEMENT IN PCC, AND VARIANT 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 genes
RT GDNF, RET and VHL.";
RL Hum. Mol. Genet. 6:1051-1056(1997).
RN [13]
RP INTERACTION WITH SORL1.
RX PubMed=15364913; DOI=10.1074/jbc.m408873200;
RA Westergaard U.B., Soerensen E.S., Hermey G., Nielsen M.S., Nykjaer A.,
RA Kirkegaard K., Jacobsen C., Gliemann J., Madsen P., Petersen C.M.;
RT "Functional organization of the sortilin Vps10p domain.";
RL J. Biol. Chem. 279:50221-50229(2004).
RN [14]
RP INTERACTION WITH SORL1 AND RET, AND SUBCELLULAR LOCATION.
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 [15]
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 and
RT their regulation in human middle temporal gyrus of Alzheimer disease.";
RL J. Biol. Chem. 286:45093-45102(2011).
RN [16]
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 the
RT phenotype.";
RL Eur. J. Hum. Genet. 5:180-185(1997).
RN [17]
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).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 78-211, GLYCOSYLATION AT ASN-126,
RP 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 bend
RT angle to RET signalling.";
RL Acta Crystallogr. F 65:551-558(2009).
RN [19]
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 complex,
RT in Hirschsprung disease.";
RL Hum. Mol. Genet. 5:2023-2026(1996).
RN [20]
RP VARIANT 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 (GDNF)
RT and RET in a Hirschsprung disease patient.";
RL Nat. Genet. 14:341-344(1996).
RN [21]
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., Sarnacki S.,
RA Goulet O., Ricour C., Nihoul-Fekete C., Munnich A., 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 [22]
RP VARIANT 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 [23]
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 morphological
CC differentiation of dopaminergic neurons and increases their high-
CC affinity dopamine uptake. {ECO:0000269|PubMed:8493557}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8493557, PubMed:8988018,
CC PubMed:19478429). Interacts with RET (PubMed:21994944). Interacts (via
CC propeptide) with SORL1 (via N-terminal ectodomain); this interaction
CC affects GDNF-regulated, but not constitutive secretion
CC (PubMed:15364913, PubMed:21994944, PubMed:23333276). Also interacts
CC with SORL1 in complex with GFRA1; this interaction leads to GDNF
CC endocytosis and lysosomal degradation (PubMed:23333276).
CC {ECO:0000269|PubMed:15364913, ECO:0000269|PubMed:19478429,
CC ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276,
CC ECO:0000269|PubMed:8493557, ECO:0000269|PubMed:8988018}.
CC -!- INTERACTION:
CC P39905; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-10207709, EBI-741181;
CC P39905-3; P15941-11: MUC1; NbExp=3; IntAct=EBI-12702062, EBI-17263240;
CC P39905-3; Q8TAC9: SCAMP5; NbExp=3; IntAct=EBI-12702062, EBI-2695784;
CC P39905-3; P08247: SYP; NbExp=3; IntAct=EBI-12702062, EBI-9071725;
CC PRO_0000034005; Q92673: SORL1; NbExp=6; IntAct=EBI-25397146, EBI-1171329;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21994944,
CC 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, GDNF delta 78
CC {ECO:0000303|PubMed:21994944}, 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 -!- TISSUE SPECIFICITY: In the brain, predominantly expressed in the
CC striatum with highest levels in the caudate and lowest in the putamen.
CC Isoform 2 is absent from most tissues except for low levels in
CC intestine and kidney. Highest expression of isoform 3 is found in
CC pancreatic islets. Isoform 5 is expressed at very low levels in
CC putamen, nucleus accumbens, prefrontal cortex, amygdala, hypothalamus
CC and intestine. Isoform 3 is up-regulated in the middle temporal gyrus
CC of Alzheimer disease patients while isoform 2 shows no change.
CC {ECO:0000269|PubMed:22081608, 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 of
CC neural crest development characterized by absence of enteric ganglia
CC along a variable length of the intestine. It is the most common cause
CC of congenital intestinal obstruction. Early symptoms range from
CC complete acute neonatal obstruction, characterized by vomiting,
CC abdominal distention and failure to pass stool, to chronic constipation
CC in the older child. {ECO:0000269|PubMed:10917288,
CC ECO:0000269|PubMed:8896568, ECO:0000269|PubMed:8896569,
CC ECO:0000269|PubMed:8968758}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing
CC tumor of chromaffin tissue of the adrenal medulla or sympathetic
CC paraganglia. The cardinal symptom, reflecting the increased secretion
CC of epinephrine and norepinephrine, is hypertension, which may be
CC persistent or intermittent. {ECO:0000269|PubMed:9215674}. Note=The gene
CC represented in this entry may act as a disease modifier.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000305}.
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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 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 PDB; 6Q2N; EM; 4.40 A; A/B=78-211.
DR PDBsum; 2V5E; -.
DR PDBsum; 3FUB; -.
DR PDBsum; 4UX8; -.
DR PDBsum; 6Q2N; -.
DR AlphaFoldDB; P39905; -.
DR SMR; P39905; -.
DR BioGRID; 108936; 35.
DR DIP; DIP-59051N; -.
DR IntAct; P39905; 13.
DR STRING; 9606.ENSP00000409007; -.
DR DrugBank; DB09301; Chondroitin sulfate.
DR GlyGen; P39905; 2 sites.
DR iPTMnet; P39905; -.
DR PhosphoSitePlus; P39905; -.
DR BioMuta; GDNF; -.
DR DMDM; 729567; -.
DR jPOST; P39905; -.
DR PaxDb; P39905; -.
DR PRIDE; P39905; -.
DR TopDownProteomics; P39905-3; -. [P39905-3]
DR Antibodypedia; 3924; 564 antibodies from 41 providers.
DR DNASU; 2668; -.
DR Ensembl; ENST00000326524.7; ENSP00000317145.2; ENSG00000168621.15. [P39905-1]
DR Ensembl; ENST00000344622.8; ENSP00000339703.4; ENSG00000168621.15. [P39905-2]
DR Ensembl; ENST00000381826.8; ENSP00000371248.4; ENSG00000168621.15. [P39905-4]
DR Ensembl; ENST00000427982.5; ENSP00000409007.1; ENSG00000168621.15. [P39905-3]
DR Ensembl; ENST00000515058.5; ENSP00000425928.1; ENSG00000168621.15. [P39905-2]
DR Ensembl; ENST00000620847.1; ENSP00000478722.1; ENSG00000168621.15. [P39905-5]
DR GeneID; 2668; -.
DR KEGG; hsa:2668; -.
DR MANE-Select; ENST00000326524.7; ENSP00000317145.2; NM_000514.4; NP_000505.1.
DR UCSC; uc011cpd.2; human. [P39905-1]
DR CTD; 2668; -.
DR DisGeNET; 2668; -.
DR GeneCards; GDNF; -.
DR HGNC; HGNC:4232; GDNF.
DR HPA; ENSG00000168621; Tissue enhanced (skeletal).
DR MalaCards; GDNF; -.
DR MIM; 171300; phenotype.
DR MIM; 600837; gene.
DR MIM; 613711; phenotype.
DR neXtProt; NX_P39905; -.
DR OpenTargets; ENSG00000168621; -.
DR Orphanet; 661; Congenital central hypoventilation syndrome.
DR Orphanet; 388; Hirschsprung disease.
DR PharmGKB; PA28644; -.
DR VEuPathDB; HostDB:ENSG00000168621; -.
DR eggNOG; ENOG502QWCH; Eukaryota.
DR GeneTree; ENSGT00950000182993; -.
DR HOGENOM; CLU_102221_1_0_1; -.
DR InParanoid; P39905; -.
DR OrthoDB; 1373773at2759; -.
DR PhylomeDB; P39905; -.
DR TreeFam; TF332366; -.
DR PathwayCommons; P39905; -.
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 BioGRID-ORCS; 2668; 15 hits in 1068 CRISPR screens.
DR ChiTaRS; GDNF; human.
DR EvolutionaryTrace; P39905; -.
DR GeneWiki; Glial_cell_line-derived_neurotrophic_factor; -.
DR GenomeRNAi; 2668; -.
DR Pharos; P39905; Tbio.
DR PRO; PR:P39905; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P39905; protein.
DR Bgee; ENSG00000168621; Expressed in hindlimb stylopod muscle and 112 other tissues.
DR ExpressionAtlas; P39905; baseline and differential.
DR Genevisible; P39905; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:1902379; F:chemoattractant activity involved in axon guidance; TAS:ARUK-UCL.
DR GO; GO:0030116; F:glial cell-derived neurotrophic factor receptor binding; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0008344; P:adult locomotory behavior; TAS:BHF-UCL.
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: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:0007422; P:peripheral nervous system development; IBA:GO_Central.
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 population 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 DisProt; DP02574; -.
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 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Growth factor; Hirschsprung disease; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..75
FT /evidence="ECO:0000250"
FT /id="PRO_0000034004"
FT CHAIN 78..211
FT /note="Glial cell line-derived neurotrophic factor"
FT /id="PRO_0000034005"
FT REGION 21..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19478429"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 118..179
FT /evidence="ECO:0000269|PubMed:8988018"
FT DISULFID 145..208
FT /evidence="ECO:0000269|PubMed:8988018"
FT DISULFID 149..210
FT /evidence="ECO:0000269|PubMed:8988018"
FT DISULFID 178
FT /note="Interchain"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_042298"
FT VAR_SEQ 1
FT /note="M -> MQSLPNSNGAAAGRDFKM (in isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_026368"
FT VAR_SEQ 25..51
FT /note="GKRPPEAPAEDRSLGRRRAPFALSSDS -> A (in isoform 2 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:7867768, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.9"
FT /id="VSP_006420"
FT VARIANT 21
FT /note="P -> S (in HSCR3; unknown pathological significance;
FT dbSNP:rs777451569)"
FT /evidence="ECO:0000269|PubMed:8896569"
FT /id="VAR_009494"
FT VARIANT 93
FT /note="R -> W (may be a risk factor for Hirschsprung
FT disease; dbSNP:rs36119840)"
FT /evidence="ECO:0000269|PubMed:8896568,
FT ECO:0000269|PubMed:9215674, ECO:0000269|PubMed:9497256"
FT /id="VAR_009495"
FT VARIANT 150
FT /note="D -> N (risk factor for Hirschsprung disease;
FT dbSNP:rs76466003)"
FT /evidence="ECO:0000269|PubMed:8896569"
FT /id="VAR_009496"
FT VARIANT 154
FT /note="T -> S (in HSCR3; sporadic form; dbSNP:rs104893891)"
FT /evidence="ECO:0000269|PubMed:8968758"
FT /id="VAR_009497"
FT VARIANT 211
FT /note="I -> M (in HSCR3; dbSNP:rs121918536)"
FT /evidence="ECO:0000269|PubMed:10917288"
FT /id="VAR_018152"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 127..130
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:2V5E"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 197..200
FT /evidence="ECO:0007829|PDB:2V5E"
FT STRAND 204..211
FT /evidence="ECO:0007829|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
