UniProtKB - P39905 (GDNF_HUMAN)
Glial cell line-derived neurotrophic factor
GDNF
Functioni
Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
1 PublicationGO - Molecular functioni
- chemoattractant activity involved in axon guidance Source: ARUK-UCL
- glial cell-derived neurotrophic factor receptor binding Source: InterPro
- growth factor activity Source: GO_Central
- protein homodimerization activity Source: UniProtKB
- receptor tyrosine kinase binding Source: InterPro
- signaling receptor binding Source: ProtInc
GO - Biological processi
- adult locomotory behavior Source: BHF-UCL
- branching involved in ureteric bud morphogenesis Source: UniProtKB
- commissural neuron axon guidance Source: ARUK-UCL
- dorsal spinal cord development Source: ARUK-UCL
- embryonic organ development Source: ARUK-UCL
- enteric nervous system development Source: UniProtKB
- mesenchymal to epithelial transition involved in metanephros morphogenesis Source: Ensembl
- metanephros development Source: UniProtKB
- mRNA stabilization Source: BHF-UCL
- negative regulation of apoptotic process Source: ProtInc
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
- negative regulation of neuron apoptotic process Source: UniProtKB
- nervous system development Source: ARUK-UCL
- neural crest cell migration Source: MGI
- neuron projection development Source: MGI
- organ induction Source: Ensembl
- peripheral nervous system development Source: GO_Central
- peristalsis Source: UniProtKB
- positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
- positive regulation of cell differentiation Source: MGI
- positive regulation of cell population proliferation Source: MGI
- positive regulation of dopamine secretion Source: BHF-UCL
- positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Source: Ensembl
- positive regulation of monooxygenase activity Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of ureteric bud formation Source: UniProtKB
- postganglionic parasympathetic fiber development Source: UniProtKB
- postsynaptic membrane organization Source: Ensembl
- regulation of dopamine uptake involved in synaptic transmission Source: UniProtKB
- regulation of gene expression Source: MGI
- regulation of morphogenesis of a branching structure Source: UniProtKB
- regulation of semaphorin-plexin signaling pathway Source: ARUK-UCL
- regulation of stem cell differentiation Source: ParkinsonsUK-UCL
- signal transduction Source: ProtInc
- sympathetic nervous system development Source: UniProtKB
- ureteric bud formation Source: Ensembl
Keywordsi
Molecular function | Growth factor |
Enzyme and pathway databases
PathwayCommonsi | P39905 |
Reactomei | R-HSA-419037, NCAM1 interactions R-HSA-5673001, RAF/MAP kinase cascade R-HSA-8853659, RET signaling |
SignaLinki | P39905 |
SIGNORi | P39905 |
Names & Taxonomyi
Protein namesi | Recommended name: Glial cell line-derived neurotrophic factorShort name: hGDNF Alternative name(s): Astrocyte-derived trophic factor Short name: ATF |
Gene namesi | Name:GDNF |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4232, GDNF |
MIMi | 600837, gene |
neXtProti | NX_P39905 |
VEuPathDBi | HostDB:ENSG00000168621 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: GO_Central
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Hirschsprung disease 3 (HSCR3)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009494 | 21 | P → S in HSCR3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777451569EnsemblClinVar. | 1 | |
Natural variantiVAR_009495 | 93 | R → W in HSCR3, CCHS and PCC; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs36119840EnsemblClinVar. | 1 | |
Natural variantiVAR_009497 | 154 | T → S in HSCR3; sporadic form. 1 PublicationCorresponds to variant dbSNP:rs104893891EnsemblClinVar. | 1 | |
Natural variantiVAR_018152 | 211 | I → M in HSCR3. 1 PublicationCorresponds to variant dbSNP:rs121918536EnsemblClinVar. | 1 |
Congenital central hypoventilation syndrome (CCHS)1 Publication
Pheochromocytoma (PCC)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009495 | 93 | R → W in HSCR3, CCHS and PCC; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs36119840EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Hirschsprung diseaseOrganism-specific databases
DisGeNETi | 2668 |
MalaCardsi | GDNF |
MIMi | 171300, phenotype 209880, phenotype 613711, phenotype |
OpenTargetsi | ENSG00000168621 |
Orphaneti | 388, Hirschsprung disease 661, Ondine syndrome |
PharmGKBi | PA28644 |
Miscellaneous databases
Pharosi | P39905, Tbio |
Chemistry databases
DrugBanki | DB09301, Chondroitin sulfate |
Genetic variation databases
BioMutai | GDNF |
DMDMi | 729567 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
PropeptideiPRO_0000034004 | 20 – 75 | By similarityAdd BLAST | 56 | |
ChainiPRO_0000034005 | 78 – 211 | Glial cell line-derived neurotrophic factorAdd BLAST | 134 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 118 ↔ 179 | 1 Publication | ||
Glycosylationi | 126 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 145 ↔ 208 | 1 Publication | ||
Disulfide bondi | 149 ↔ 210 | 1 Publication | ||
Glycosylationi | 162 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 178 | Interchain |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, GlycoproteinProteomic databases
jPOSTi | P39905 |
PaxDbi | P39905 |
PRIDEi | P39905 |
TopDownProteomicsi | P39905-3 [P39905-3] |
PTM databases
GlyGeni | P39905, 2 sites |
iPTMneti | P39905 |
PhosphoSitePlusi | P39905 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000168621, Expressed in quadriceps femoris and 108 other tissues |
ExpressionAtlasi | P39905, baseline and differential |
Genevisiblei | P39905, HS |
Organism-specific databases
HPAi | ENSG00000168621, Tissue enhanced (skeletal) |
Interactioni
Subunit structurei
Homodimer; disulfide-linked (PubMed:8493557, PubMed:8988018, PubMed:19478429).
Interacts with RET (PubMed:21994944).
Interacts (via propeptide) with SORL1 (via N-terminal ectodomain); this interaction affects GDNF-regulated, but not constitutive secretion (PubMed:15364913, PubMed:21994944, PubMed:23333276).
Also interacts with SORL1 in complex with GFRA1; this interaction leads to GDNF endocytosis and lysosomal degradation (PubMed:23333276).
6 PublicationsBinary interactionsi
P39905
With | #Exp. | IntAct |
---|---|---|
AGTRAP [Q6RW13] | 3 | EBI-10207709,EBI-741181 |
Isoform 3 [P39905-3]
With | #Exp. | IntAct |
---|---|---|
MUC1 - isoform Y-LSP [P15941-11] | 3 | EBI-12702062,EBI-17263240 |
SCAMP5 [Q8TAC9] | 3 | EBI-12702062,EBI-2695784 |
SYP [P08247] | 3 | EBI-12702062,EBI-9071725 |
Glial cell line-derived neurotrophic factor (PRO_0000034005)
With | #Exp. | IntAct |
---|---|---|
SORL1 [Q92673] | 6 | EBI-25397146,EBI-1171329 |
GO - Molecular functioni
- chemoattractant activity involved in axon guidance Source: ARUK-UCL
- glial cell-derived neurotrophic factor receptor binding Source: InterPro
- growth factor activity Source: GO_Central
- protein homodimerization activity Source: UniProtKB
- receptor tyrosine kinase binding Source: InterPro
- signaling receptor binding Source: ProtInc
Protein-protein interaction databases
BioGRIDi | 108936, 25 interactors |
DIPi | DIP-59051N |
IntActi | P39905, 13 interactors |
STRINGi | 9606.ENSP00000409007 |
Miscellaneous databases
RNActi | P39905, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P39905 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P39905 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 21 – 56 | DisorderedSequence analysisAdd BLAST | 36 | |
Regioni | 78 – 113 | DisorderedSequence analysisAdd BLAST | 36 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QWCH, Eukaryota |
GeneTreei | ENSGT00950000182993 |
HOGENOMi | CLU_102221_1_0_1 |
InParanoidi | P39905 |
OrthoDBi | 1373773at2759 |
PhylomeDBi | P39905 |
TreeFami | TF332366 |
Family and domain databases
DisProti | DP02574 |
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR029034, Cystine-knot_cytokine IPR016649, GDNF IPR043401, GDNF_fam IPR001839, TGF-b_C |
PANTHERi | PTHR12173, PTHR12173, 1 hit PTHR12173:SF1, PTHR12173:SF1, 1 hit |
Pfami | View protein in Pfam PF00019, TGF_beta, 1 hit |
PIRSFi | PIRSF016238, GDNF, 1 hit |
SMARTi | View protein in SMART SM00204, TGFB, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS51362, TGF_BETA_2, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKLWDVVAVC LVLLHTASAF PLPAGKRPPE APAEDRSLGR RRAPFALSSD
60 70 80 90 100
SNMPEDYPDQ FDDVMDFIQA TIKRLKRSPD KQMAVLPRRE RNRQAAAANP
110 120 130 140 150
ENSRGKGRRG QRGKNRGCVL TAIHLNVTDL GLGYETKEEL IFRYCSGSCD
160 170 180 190 200
AAETTYDKIL KNLSRNRRLV SDKVGQACCR PIAFDDDLSF LDDNLVYHIL
210
RKHSAKRCGC I
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0C4DGC2 | A0A0C4DGC2_HUMAN | Glial cell line-derived neurotrophi... | GDNF | 61 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009494 | 21 | P → S in HSCR3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777451569EnsemblClinVar. | 1 | |
Natural variantiVAR_009495 | 93 | R → W in HSCR3, CCHS and PCC; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs36119840EnsemblClinVar. | 1 | |
Natural variantiVAR_009496 | 150 | D → N Risk factor for Hirschsprung disease. 1 PublicationCorresponds to variant dbSNP:rs76466003EnsemblClinVar. | 1 | |
Natural variantiVAR_009497 | 154 | T → S in HSCR3; sporadic form. 1 PublicationCorresponds to variant dbSNP:rs104893891EnsemblClinVar. | 1 | |
Natural variantiVAR_018152 | 211 | I → M in HSCR3. 1 PublicationCorresponds to variant dbSNP:rs121918536EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042298 | 1 – 52 | Missing in isoform 5. CuratedAdd BLAST | 52 | |
Alternative sequenceiVSP_026368 | 1 | M → MQSLPNSNGAAAGRDFKM in isoform 3 and isoform 4. 1 Publication | 1 | |
Alternative sequenceiVSP_006420 | 25 – 51 | GKRPP…LSSDS → A in isoform 2 and isoform 4. 3 PublicationsAdd BLAST | 27 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000326524; ENSP00000317145; ENSG00000168621 ENST00000344622; ENSP00000339703; ENSG00000168621 [P39905-2] ENST00000381826; ENSP00000371248; ENSG00000168621 [P39905-4] ENST00000427982; ENSP00000409007; ENSG00000168621 [P39905-3] ENST00000515058; ENSP00000425928; ENSG00000168621 [P39905-2] ENST00000620847; ENSP00000478722; ENSG00000168621 [P39905-5] |
GeneIDi | 2668 |
KEGGi | hsa:2668 |
MANE-Selecti | ENST00000326524.7; ENSP00000317145.2; NM_000514.4; NP_000505.1 |
UCSCi | uc011cpd.2, human [P39905-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2V5E | X-ray | 2.35 | B | 111-211 | [»] | |
3FUB | X-ray | 2.35 | B/D | 78-211 | [»] | |
4UX8 | electron microscopy | 24.00 | D/F | 78-211 | [»] | |
6Q2N | electron microscopy | 4.40 | A/B | 78-211 | [»] | |
SMRi | P39905 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108936, 25 interactors |
DIPi | DIP-59051N |
IntActi | P39905, 13 interactors |
STRINGi | 9606.ENSP00000409007 |
Chemistry databases
DrugBanki | DB09301, Chondroitin sulfate |
PTM databases
GlyGeni | P39905, 2 sites |
iPTMneti | P39905 |
PhosphoSitePlusi | P39905 |
Genetic variation databases
BioMutai | GDNF |
DMDMi | 729567 |
Proteomic databases
jPOSTi | P39905 |
PaxDbi | P39905 |
PRIDEi | P39905 |
TopDownProteomicsi | P39905-3 [P39905-3] |
Protocols and materials databases
Antibodypediai | 3924, 569 antibodies from 41 providers |
DNASUi | 2668 |
Genome annotation databases
Ensembli | ENST00000326524; ENSP00000317145; ENSG00000168621 ENST00000344622; ENSP00000339703; ENSG00000168621 [P39905-2] ENST00000381826; ENSP00000371248; ENSG00000168621 [P39905-4] ENST00000427982; ENSP00000409007; ENSG00000168621 [P39905-3] ENST00000515058; ENSP00000425928; ENSG00000168621 [P39905-2] ENST00000620847; ENSP00000478722; ENSG00000168621 [P39905-5] |
GeneIDi | 2668 |
KEGGi | hsa:2668 |
MANE-Selecti | ENST00000326524.7; ENSP00000317145.2; NM_000514.4; NP_000505.1 |
UCSCi | uc011cpd.2, human [P39905-1] |
Organism-specific databases
CTDi | 2668 |
DisGeNETi | 2668 |
GeneCardsi | GDNF |
HGNCi | HGNC:4232, GDNF |
HPAi | ENSG00000168621, Tissue enhanced (skeletal) |
MalaCardsi | GDNF |
MIMi | 171300, phenotype 209880, phenotype 600837, gene 613711, phenotype |
neXtProti | NX_P39905 |
OpenTargetsi | ENSG00000168621 |
Orphaneti | 388, Hirschsprung disease 661, Ondine syndrome |
PharmGKBi | PA28644 |
VEuPathDBi | HostDB:ENSG00000168621 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QWCH, Eukaryota |
GeneTreei | ENSGT00950000182993 |
HOGENOMi | CLU_102221_1_0_1 |
InParanoidi | P39905 |
OrthoDBi | 1373773at2759 |
PhylomeDBi | P39905 |
TreeFami | TF332366 |
Enzyme and pathway databases
PathwayCommonsi | P39905 |
Reactomei | R-HSA-419037, NCAM1 interactions R-HSA-5673001, RAF/MAP kinase cascade R-HSA-8853659, RET signaling |
SignaLinki | P39905 |
SIGNORi | P39905 |
Miscellaneous databases
BioGRID-ORCSi | 2668, 5 hits in 1034 CRISPR screens |
ChiTaRSi | GDNF, human |
EvolutionaryTracei | P39905 |
GeneWikii | Glial_cell_line-derived_neurotrophic_factor |
GenomeRNAii | 2668 |
Pharosi | P39905, Tbio |
PROi | PR:P39905 |
RNActi | P39905, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000168621, Expressed in quadriceps femoris and 108 other tissues |
ExpressionAtlasi | P39905, baseline and differential |
Genevisiblei | P39905, HS |
Family and domain databases
DisProti | DP02574 |
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR029034, Cystine-knot_cytokine IPR016649, GDNF IPR043401, GDNF_fam IPR001839, TGF-b_C |
PANTHERi | PTHR12173, PTHR12173, 1 hit PTHR12173:SF1, PTHR12173:SF1, 1 hit |
Pfami | View protein in Pfam PF00019, TGF_beta, 1 hit |
PIRSFi | PIRSF016238, GDNF, 1 hit |
SMARTi | View protein in SMART SM00204, TGFB, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS51362, TGF_BETA_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GDNF_HUMAN | |
Accessioni | P39905Primary (citable) accession number: P39905 Secondary accession number(s): B7WPK7 Q9UP97 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | February 23, 2022 | |
This is version 211 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families