Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glial cell line-derived neurotrophic factor

Gene

Gdnf

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. May also modulate local neuronal effects in distal regions of the motor neuron.1 Publication

GO - Molecular functioni

  • glial cell-derived neurotrophic factor receptor binding Source: RGD
  • growth factor activity Source: RGD
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
Recommended name:
Glial cell line-derived neurotrophic factor
Alternative name(s):
Astrocyte-derived trophic factor
Short name:
ATF
Gene namesi
Name:Gdnf
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2677. Gdnf.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: RGD
  • receptor complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Propeptidei20 – 7556PRO_0000034008Add
BLAST
Chaini78 – 211134Glial cell line-derived neurotrophic factorPRO_0000034009Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi118 ↔ 1791 Publication
Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence analysis
Disulfide bondi145 ↔ 2081 Publication
Disulfide bondi149 ↔ 2101 Publication
Glycosylationi162 – 1621N-linked (GlcNAc...)Sequence analysis
Disulfide bondi178 – 178Interchain1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ07731.

Expressioni

Tissue specificityi

Expressed in both the central nervous system (CNS) and in non-CNS tissues, including the kidney, lung, bone, heart, liver, spleen, sciatic nerve and blood. In the brain, predominantly expressed in the striatum with highest levels in the caudate and lowest in the putamen. Localizes at the proximal ligature of the hypoglossal nerve.3 Publications

Inductioni

By melatonin.1 Publication

Interactioni

Subunit structurei

Homodimer; disulfide-linked.1 Publication

GO - Molecular functioni

  • glial cell-derived neurotrophic factor receptor binding Source: RGD
  • growth factor activity Source: RGD
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi247487. 1 interaction.
STRINGi10116.ENSRNOP00000044012.

Structurei

Secondary structure

1
211
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi118 – 1269Combined sources
Helixi127 – 1304Combined sources
Beta strandi139 – 1479Combined sources
Helixi155 – 16612Combined sources
Beta strandi178 – 1847Combined sources
Beta strandi188 – 1914Combined sources
Beta strandi197 – 2004Combined sources
Beta strandi204 – 2118Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AGQX-ray1.90A/B/C/D78-211[»]
DisProtiDP00029.
ProteinModelPortaliQ07731.
SMRiQ07731. Positions 117-211.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07731.

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGT5. Eukaryota.
ENOG4111I3D. LUCA.
HOVERGENiHBG106680.
InParanoidiQ07731.
KOiK05452.
PhylomeDBiQ07731.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR016649. GDNF.
IPR001839. TGF-b_C.
[Graphical view]
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
PIRSFiPIRSF016238. GDNF. 1 hit.
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q07731-1) [UniParc]FASTAAdd to basket

Also known as: GDNF633

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 PLPAGKRLLE APAEDHSLGH RRVPFALTSD
60 70 80 90 100
SNMPEDYPDQ FDDVMDFIQA TIKRLKRSPD KQAAALPRRE RNRQAAAASP
110 120 130 140 150
ENSRGKGRRG QRGKNRGCVL TAIHLNVTDL GLGYETKEEL IFRYCSGSCE
160 170 180 190 200
AAETMYDKIL KNLSRSRRLT SDKVGQACCR PVAFDDDLSF LDDSLVYHIL
210
RKHSAKRCGC I
Length:211
Mass (Da):23,619
Last modified:February 1, 1995 - v1
Checksum:iAE06C646682895A5
GO
Isoform 2 (identifier: Q07731-2) [UniParc]FASTAAdd to basket

Also known as: ATF-1, GDNF555, sGDNF, Smaller GDNF

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

Show »
Length:185
Mass (Da):20,748
Checksum:iDAF95B585293C0CE
GO
Isoform 3 (identifier: Q07731-3) [UniParc]FASTAAdd to basket

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

Show »
Length:159
Mass (Da):17,985
Checksum:i54BE42BC83203895
GO
Isoform 4 (identifier: Q07731-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MKLWDVVAVCLVLLHTASAF → MGFGPLGVNVQLGVYGDRIR

Show »
Length:211
Mass (Da):23,551
Checksum:i33D2F285680D2FED
GO

Sequence cautioni

The sequence CAB64357.1 differs from that shown. Reason: Erroneous gene model prediction. Curated
The sequence CAB64358.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti77 – 771R → S in AAB33891 (PubMed:7895811).Curated
Sequence conflicti77 – 771R → S in AAB33892 (PubMed:7895811).Curated
Sequence conflicti90 – 901E → K in AAB33891 (PubMed:7895811).Curated
Sequence conflicti90 – 901E → K in AAB33892 (PubMed:7895811).Curated
Sequence conflicti94 – 941Q → L in AAF23767 (PubMed:10828539).Curated
Sequence conflicti101 – 1011E → D AA sequence (PubMed:8493557).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5252Missing in isoform 3. 1 PublicationVSP_026365Add
BLAST
Alternative sequencei1 – 2020MKLWD…TASAF → MGFGPLGVNVQLGVYGDRIR in isoform 4. CuratedVSP_026366Add
BLAST
Alternative sequencei25 – 5127GKRLL…LTSDS → A in isoform 2. 3 PublicationsVSP_006422Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15305 mRNA. Translation: AAA67909.1.
S75583 mRNA. Translation: AAB33891.1.
S75585 mRNA. Translation: AAB33892.1.
AF205713 mRNA. Translation: AAF23767.1.
AF205714 mRNA. Translation: AAF23768.1.
AF205715 mRNA. Translation: AAF23769.1.
X92495 mRNA. Translation: CAA63237.1.
AJ011432 Genomic DNA. Translation: CAB64357.1. Sequence problems.
AJ011432 Genomic DNA. Translation: CAB64358.1. Sequence problems.
AF497634 mRNA. Translation: AAM18096.1.
PIRiA37499.
RefSeqiNP_062012.1. NM_019139.1. [Q07731-1]
UniGeneiRn.53970.

Genome annotation databases

GeneIDi25453.
KEGGirno:25453.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15305 mRNA. Translation: AAA67909.1.
S75583 mRNA. Translation: AAB33891.1.
S75585 mRNA. Translation: AAB33892.1.
AF205713 mRNA. Translation: AAF23767.1.
AF205714 mRNA. Translation: AAF23768.1.
AF205715 mRNA. Translation: AAF23769.1.
X92495 mRNA. Translation: CAA63237.1.
AJ011432 Genomic DNA. Translation: CAB64357.1. Sequence problems.
AJ011432 Genomic DNA. Translation: CAB64358.1. Sequence problems.
AF497634 mRNA. Translation: AAM18096.1.
PIRiA37499.
RefSeqiNP_062012.1. NM_019139.1. [Q07731-1]
UniGeneiRn.53970.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AGQX-ray1.90A/B/C/D78-211[»]
DisProtiDP00029.
ProteinModelPortaliQ07731.
SMRiQ07731. Positions 117-211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247487. 1 interaction.
STRINGi10116.ENSRNOP00000044012.

Proteomic databases

PaxDbiQ07731.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25453.
KEGGirno:25453.

Organism-specific databases

CTDi2668.
RGDi2677. Gdnf.

Phylogenomic databases

eggNOGiENOG410IGT5. Eukaryota.
ENOG4111I3D. LUCA.
HOVERGENiHBG106680.
InParanoidiQ07731.
KOiK05452.
PhylomeDBiQ07731.

Miscellaneous databases

EvolutionaryTraceiQ07731.
NextBioi606705.
PROiQ07731.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR016649. GDNF.
IPR001839. TGF-b_C.
[Graphical view]
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
PIRSFiPIRSF016238. GDNF. 1 hit.
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons."
    Lin L.-F.H., Doherty D.H., Lile J.D., Bektesh S., Collins F.
    Science 260:1130-1132(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), HOMODIMERIZATION, DISULFIDE BONDS, GLYCOSYLATION, PROTEIN SEQUENCE OF 78-102.
    Tissue: Glial tumor.
  2. "cDNA sequence and differential mRNA regulation of two forms of glial cell line-derived neurotrophic factor in Schwann cells and rat skeletal muscle."
    Springer J.E., Seeburger J.L., He J., Gabrea A., Blankenhorn E.P., Bergman L.W.
    Exp. Neurol. 131:47-52(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  3. "Anterograde axonal transport of glial cell line-derived neurotrophic factor and its receptors in rat hypoglossal nerve."
    Russell F.D., Koishi K., Jiang Y., McLennan I.S.
    Neuroscience 97:575-580(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-125 (ISOFORMS 1; 2 AND 3), FUNCTION, TISSUE SPECIFICITY.
    Strain: Wistar.
    Tissue: Brain.
  4. "GDNF is expressed in two forms in many tissues outside the CNS."
    Suter-Crazzolara C., Unsicker K.
    NeuroReport 5:2486-2488(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-76 (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    Strain: Wistar.
    Tissue: Kidney.
  5. "The Rat GDNF gene."
    Schmidt C., Suter-Crazzolara C.
    Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
  6. "Induction of GDNF mRNA expression by melatonin in rat C6 glioma cells."
    Armstrong K.J., Niles L.P.
    NeuroReport 13:473-475(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-207 (ISOFORM 1), INDUCTION.
    Tissue: Glial tumor.
  7. "Multiple astrocyte transcripts encode nigral trophic factors in rat and human."
    Schaar D.G., Sieber B.-A., Sherwood A.C., Dean D., Mendoza G., Ramakrishnan L., Dreyfus C.F., Black I.B.
    Exp. Neurol. 130:387-393(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
  8. "X-ray structure of glial cell-derived neurotrophic factor at 1.9-A resolution and implications for receptor binding."
    Eigenbrot C., Gerber C.
    Nat. Struct. Biol. 4:435-438(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).

Entry informationi

Entry nameiGDNF_RAT
AccessioniPrimary (citable) accession number: Q07731
Secondary accession number(s): Q63214
, Q64062, Q64063, Q8R485, Q9QX94, Q9QX95, Q9QXJ7, Q9QXJ8, Q9QXJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: May 11, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.