GDNF

Protein identityUniProt · HPA

UniProt accession

P39905

Gene

GDNF

Ensembl

ENSG00000168621

Chromosome

5

Canonical length

211 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm,Vesicles

Secretome location

Secreted in other tissues

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

Canonical amino-acid sequenceUniProt

211 residues, UniProt reviewed canonical sequence.

>P39905|GDNF
     1  MKLWDVVAVC LVLLHTASAF PLPAGKRPPE APAEDRSLGR RRAPFALSSD SNMPEDYPDQ
    61  FDDVMDFIQA TIKRLKRSPD KQMAVLPRRE RNRQAAAANP ENSRGKGRRG QRGKNRGCVL
   121  TAIHLNVTDL GLGYETKEEL IFRYCSGSCD AAETTYDKIL KNLSRNRRLV SDKVGQACCR
   181  PIAFDDDLSF LDDNLVYHIL RKHSAKRCGC I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GDNF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.54

Highest tissue expression

9.7 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GDNF.

Disease | AllUniProt

Conditions GDNF is implicated in, by any mechanism.

• Hirschsprung disease 3 (HSCR3) MIM:613711
• Pheochromocytoma (PCC) MIM:171300

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.92

gnomAD pLI

0.2

gnomAD missense Z

1.1

DepMap mean gene effect

0.15

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult locomotory behavior
• branching involved in ureteric bud morphogenesis
• commissural neuron axon guidance
• dorsal spinal cord development
• embryonic organ development
• enteric nervous system development
• glial cell-derived neurotrophic factor receptor signaling pathway
• mesenchymal to epithelial transition involved in metanephros morphogenesis
• metanephros development
• mRNA stabilization
• negative regulation of apoptotic process
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• negative regulation of neuron apoptotic process
• nervous system development
• neural crest cell migration
• neural crest cell migration involved in autonomic nervous system development
• neuron projection development
• organ induction
• peripheral nervous system development
• peristalsis
• positive regulation of branching involved in ureteric bud morphogenesis
• positive regulation of cell differentiation
• positive regulation of cell population proliferation
• positive regulation of dopamine secretion
• positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
• positive regulation of transcription by RNA polymerase II
• positive regulation of ureteric bud formation
• postganglionic parasympathetic fiber development
• postsynaptic membrane organization
• regulation of dopamine uptake involved in synaptic transmission
• regulation of gene expression
• regulation of morphogenesis of a branching structure
• regulation of semaphorin-plexin signaling pathway
• regulation of stem cell differentiation
• signal transduction
• sympathetic nervous system development
• ureteric bud formation

Molecular functions

• chemoattractant activity involved in axon guidance
• glial cell-derived neurotrophic factor receptor binding
• growth factor activity
• protein homodimerization activity
• receptor tyrosine kinase binding
• signaling receptor binding

Cellular components

• extracellular region
• extracellular space
• Golgi apparatus

Protein domainsUniProt · Pfam · InterPro

• Transforming growth factor-beta, C-terminal
• Cystine-knot cytokine
• Glial cell line-derived neurotrophic factor family
• Transforming growth factor beta like domain
• Glial cell line-derived neurotrophic factor
• Glial cell line-derived neurotrophic factor, TGF-beta-like domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• Glycoprotein
• Growth factor
• Hirschsprung disease
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of GDNF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GFRA1
• SORL1