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UniProtKB - P39905 (GDNF_HUMAN)

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Protein

Glial cell line-derived neurotrophic factor

Gene

GDNF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.1 Publication

GO - Molecular functioni

  • chemoattractant activity involved in axon guidance Source: ARUK-UCL
  • growth factor activity Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • signaling receptor binding Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • adult locomotory behavior Source: BHF-UCL
  • axon guidance Source: Reactome
  • 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
  • MAPK cascade Source: Reactome
  • 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
  • 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 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
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGrowth factor

Enzyme and pathway databases

ReactomeiR-HSA-419037 NCAM1 interactions
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-8853659 RET signaling
SignaLinkiP39905
SIGNORiP39905

Names & Taxonomyi

Protein namesi
Recommended name:
Glial cell line-derived neurotrophic factor
Short name:
hGDNF
Alternative name(s):
Astrocyte-derived trophic factor
Short name:
ATF
Gene namesi
Name:GDNF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000168621.14
HGNCiHGNC:4232 GDNF
MIMi600837 gene
neXtProtiNX_P39905

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hirschsprung disease 3 (HSCR3)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
See also OMIM:613711
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00949421P → S in HSCR3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777451569EnsemblClinVar.1
Natural variantiVAR_00949593R → W in HSCR3, CCHS and PCC; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs36119840EnsemblClinVar.1
Natural variantiVAR_009497154T → S in HSCR3; sporadic form. 1 PublicationCorresponds to variant dbSNP:rs104893891EnsemblClinVar.1
Natural variantiVAR_018152211I → M in HSCR3. 1 PublicationCorresponds to variant dbSNP:rs121918536EnsemblClinVar.1
Congenital central hypoventilation syndrome (CCHS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
See also OMIM:209880
Pheochromocytoma (PCC)1 Publication
The gene represented in this entry may act as a disease modifier.
Disease descriptionA catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
See also OMIM:171300

Keywords - Diseasei

Disease mutation, Hirschsprung disease

Organism-specific databases

DisGeNETi2668
GeneReviewsiGDNF
MalaCardsiGDNF
MIMi171300 phenotype
209880 phenotype
613711 phenotype
OpenTargetsiENSG00000168621
Orphaneti388 Hirschsprung disease
PharmGKBiPA28644

Chemistry databases

DrugBankiDB05066 AV411

Polymorphism and mutation databases

BioMutaiGDNF
DMDMi729567

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000003400420 – 75By similarityAdd BLAST56
ChainiPRO_000003400578 – 211Glial cell line-derived neurotrophic factorAdd BLAST134

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi118 ↔ 1791 Publication
Glycosylationi126N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi145 ↔ 2081 Publication
Disulfide bondi149 ↔ 2101 Publication
Glycosylationi162N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi178Interchain

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP39905
PRIDEiP39905
ProteomicsDBi55328
55329 [P39905-2]
55330 [P39905-3]
55331 [P39905-4]
55332 [P39905-5]
TopDownProteomicsiP39905-3 [P39905-3]

PTM databases

iPTMnetiP39905
PhosphoSitePlusiP39905

Expressioni

Tissue specificityi

In the brain, predominantly expressed in the striatum with highest levels in the caudate and lowest in the putamen. Isoform 2 is absent from most tissues except for low levels in intestine and kidney. Highest expression of isoform 3 is found in pancreatic islets. Isoform 5 is expressed at very low levels in putamen, nucleus accumbens, prefrontal cortex, amygdala, hypothalamus and intestine. Isoform 3 is up-regulated in the middle temporal gyrus of Alzheimer disease patients while isoform 2 shows no change.2 Publications

Inductioni

By cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA) and FGF2.1 Publication

Gene expression databases

BgeeiENSG00000168621
ExpressionAtlasiP39905 baseline and differential
GenevisibleiP39905 HS

Organism-specific databases

HPAiCAB005210
HPA070283

Interactioni

Subunit structurei

Homodimer; disulfide-linked.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTRAPQ6RW133EBI-10207709,EBI-741181

GO - Molecular functioni

  • chemoattractant activity involved in axon guidance Source: ARUK-UCL
  • growth factor activity Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • signaling receptor binding Source: ProtInc
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108936, 13 interactors
DIPiDIP-59051N
IntActiP39905, 7 interactors
STRINGi9606.ENSP00000409007

Structurei

Secondary structure

1211
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni114 – 117Combined sources4
Beta strandi119 – 126Combined sources8
Helixi127 – 130Combined sources4
Beta strandi139 – 147Combined sources9
Helixi155 – 165Combined sources11
Beta strandi168 – 173Combined sources6
Beta strandi178 – 184Combined sources7
Beta strandi188 – 191Combined sources4
Beta strandi197 – 200Combined sources4
Beta strandi204 – 211Combined sources8

3D structure databases

ProteinModelPortaliP39905
SMRiP39905
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP39905

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family. GDNF subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGT5 Eukaryota
ENOG4111I3D LUCA
GeneTreeiENSGT00520000055559
HOVERGENiHBG106680
InParanoidiP39905
KOiK05452
OMAiAETMYDK
OrthoDBiEOG091G0P1K
PhylomeDBiP39905
TreeFamiTF332366

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR016649 GDNF
IPR001839 TGF-b_C
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PIRSFiPIRSF016238 GDNF, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS51362 TGF_BETA_2, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P39905-1) [UniParc]FASTAAdd to basket
Also known as: Ex1_4L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:211
Mass (Da):23,720
Last modified:February 1, 1995 - v1
Checksum:iA0D1EBF77FC82691
GO
Isoform 2 (identifier: P39905-2) [UniParc]FASTAAdd to basket
Also known as: ATF-1, Ex1_4S, Ex3_4S, HFK2-GDNF

The sequence of this isoform differs from the canonical sequence as follows:
     25-51: GKRPPEAPAEDRSLGRRRAPFALSSDS → A

Show »
Length:185
Mass (Da):20,885
Checksum:i1988C50DA5EA1B10
GO
Isoform 3 (identifier: P39905-3) [UniParc]FASTAAdd to basket
Also known as: Ex2_4L, HFK3-GDNF

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQSLPNSNGAAAGRDFKM

Show »
Length:228
Mass (Da):25,466
Checksum:i5BAAAC69FEDDBA4C
GO
Isoform 4 (identifier: P39905-4) [UniParc]FASTAAdd to basket
Also known as: HFK4-GDNF

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQSLPNSNGAAAGRDFKM
     25-51: GKRPPEAPAEDRSLGRRRAPFALSSDS → A

Show »
Length:202
Mass (Da):22,631
Checksum:i2CAFBC675D40CF2F
GO
Isoform 5 (identifier: P39905-5) [UniParc]FASTAAdd to basket
Also known as: Ex4S_5

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.

Note: No experimental confirmation available.
Show »
Length:159
Mass (Da):18,123
Checksum:i97CFDCE97459E34B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00949421P → S in HSCR3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777451569EnsemblClinVar.1
Natural variantiVAR_00949593R → W in HSCR3, CCHS and PCC; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs36119840EnsemblClinVar.1
Natural variantiVAR_009496150D → N Polymorphism; risk factor for Hirschsprung disease. 1 PublicationCorresponds to variant dbSNP:rs76466003Ensembl.1
Natural variantiVAR_009497154T → S in HSCR3; sporadic form. 1 PublicationCorresponds to variant dbSNP:rs104893891EnsemblClinVar.1
Natural variantiVAR_018152211I → M in HSCR3. 1 PublicationCorresponds to variant dbSNP:rs121918536EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0422981 – 52Missing in isoform 5. CuratedAdd BLAST52
Alternative sequenceiVSP_0263681M → MQSLPNSNGAAAGRDFKM in isoform 3 and isoform 4. 1 Publication1
Alternative sequenceiVSP_00642025 – 51GKRPP…LSSDS → A in isoform 2 and isoform 4. 3 PublicationsAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19063, L19062 Genomic DNA Translation: AAA67910.1
AY052832 mRNA Translation: AAL11017.1
CR541923 mRNA Translation: CAG46721.1
AC008869 Genomic DNA No translation available.
CH471119 Genomic DNA Translation: EAW55963.1
BC069119 mRNA Translation: AAH69119.1
BC069369 mRNA Translation: AAH69369.1
BC128108 mRNA Translation: AAI28109.1
BC128109 mRNA Translation: AAI28110.1
AF053748 mRNA Translation: AAD43139.1
AJ001896 Genomic DNA Translation: CAA05074.1
AJ001897 mRNA Translation: CAA05075.1
AJ001898 mRNA Translation: CAA05076.1
AJ001899 mRNA Translation: CAA05077.1
AJ001900 mRNA Translation: CAA05078.1
AF063586 Genomic DNA Translation: AAC98782.1
CCDSiCCDS3922.1 [P39905-1]
CCDS3923.1 [P39905-2]
CCDS54845.1 [P39905-3]
CCDS54846.1 [P39905-4]
CCDS75237.1 [P39905-5]
PIRiB37499
RefSeqiNP_000505.1, NM_000514.3 [P39905-1]
NP_001177397.1, NM_001190468.1 [P39905-3]
NP_001177398.1, NM_001190469.1 [P39905-4]
NP_001265027.1, NM_001278098.1 [P39905-5]
NP_954701.1, NM_199231.2 [P39905-2]
XP_011512332.1, XM_011514030.2 [P39905-5]
XP_016864826.1, XM_017009337.1 [P39905-2]
UniGeneiHs.248114

Genome annotation databases

EnsembliENST00000326524; ENSP00000317145; ENSG00000168621 [P39905-1]
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]
GeneIDi2668
KEGGihsa:2668
UCSCiuc011cpd.2 human [P39905-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGDNF_HUMAN
AccessioniPrimary (citable) accession number: P39905
Secondary accession number(s): B7WPK7
, O95448, O95449, O95986, Q6FH33, Q96L44, Q9UD32, Q9UD33, Q9UMV2, Q9UP67, Q9UP97
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 18, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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