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Protein

Glial cell line-derived neurotrophic factor

Gene

Gdnf

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • transforming growth factor beta receptor binding Source: MGI

GO - Biological processi

  • branching involved in ureteric bud morphogenesis Source: UniProtKB
  • enteric nervous system development Source: UniProtKB
  • mesenchymal to epithelial transition involved in metanephros morphogenesis Source: UniProtKB
  • metanephros development Source: UniProtKB
  • mRNA stabilization Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • nervous system development Source: MGI
  • neural crest cell migration Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • organ induction Source: MGI
  • peripheral nervous system development Source: MGI
  • 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 mesenchymal to epithelial transition involved in metanephros morphogenesis Source: UniProtKB
  • positive regulation of monooxygenase activity Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of ureteric bud formation Source: UniProtKB
  • postganglionic parasympathetic fiber development Source: UniProtKB
  • postsynaptic membrane organization Source: MGI
  • regulation of dopamine uptake involved in synaptic transmission Source: UniProtKB
  • regulation of gene expression Source: MGI
  • regulation of morphogenesis of a branching structure Source: MGI
  • sympathetic nervous system development Source: UniProtKB
  • transforming growth factor beta receptor signaling pathway Source: MGI
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
  • ureteric bud development Source: MGI
  • ureteric bud formation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiR-MMU-5673001. RAF/MAP kinase cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Glial cell line-derived neurotrophic factor
Short name:
mGDNF
Alternative name(s):
Astrocyte-derived trophic factor
Short name:
ATF
Gene namesi
Name:Gdnf
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:107430. Gdnf.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Propeptidei20 – 7556By similarityPRO_0000034006Add
BLAST
Chaini78 – 211134Glial cell line-derived neurotrophic factorPRO_0000034007Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi118 ↔ 179By similarity
Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence analysis
Disulfide bondi145 ↔ 208By similarity
Disulfide bondi149 ↔ 210By similarity
Glycosylationi162 – 1621N-linked (GlcNAc...)Sequence analysis
Disulfide bondi178 – 178InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP48540.
PRIDEiP48540.

PTM databases

iPTMnetiP48540.

Expressioni

Tissue specificityi

Expressed in both the central nervous system (CNS) and in non-CNS tissues. Expressed in a highly dynamic pattern in the anterior neuroectoderm during the early stages of neurogenesis between E7.5 and E10.5. Beginning at E10.5, expression begins in mesenchymal tissues of several organs including the digestive tract, kidney, testis, frontonasal mass, tooth primordium, tongue, mandible, whisker follicles, ear, eye, limb bud and in distinct regions of the brain. Also expressed in the heart, ileum, liver and muscle.2 Publications

Developmental stagei

Expressed begins by E7.5, reaches its peak around E9.5 and declines considerably after E10.5.1 Publication

Inductioni

Expression in C6 glioma cells was transiently induced by treatment with phorbol myristate acetate (PMA), but not by forskolin.1 Publication

Gene expression databases

BgeeiP48540.
CleanExiMM_GDNF.
GenevisibleiP48540. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • transforming growth factor beta receptor binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000022744.

Structurei

3D structure databases

ProteinModelPortaliP48540.
SMRiP48540. Positions 117-211.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGT5. Eukaryota.
ENOG4111I3D. LUCA.
GeneTreeiENSGT00520000055559.
HOGENOMiHOG000220877.
HOVERGENiHBG106680.
InParanoidiP48540.
KOiK05452.
OMAiAKRCGCV.
OrthoDBiEOG7BS4BR.
PhylomeDBiP48540.
TreeFamiTF332366.

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.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48540-1) [UniParc]FASTAAdd to basket

Also known as: GDNF-alpha

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
SAETMYDKIL KNLSRSRRLT SDKVGQACCR PVAFDDDLSF LDDNLVYHIL
210
RKHSAKRCGC I
Length:211
Mass (Da):23,662
Last modified:February 1, 1996 - v1
Checksum:iB6731C767A3A95B7
GO
Isoform 2 (identifier: P48540-2) [UniParc]FASTAAdd to basket

Also known as: GDNF-beta

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

Show »
Length:214
Mass (Da):23,735
Checksum:iCCCB3D0D5526A02D
GO
Isoform 3 (identifier: P48540-3) [UniParc]FASTAAdd to basket

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

Show »
Length:240
Mass (Da):26,606
Checksum:i8F5C69E4C4F6CAD5
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MGFGPLGVNVQLGVYGDRIR GAAAGRDSKM in isoform 2 and isoform 3. 3 PublicationsVSP_026367
Alternative sequencei25 – 5127GKRLL…LTSDS → A in isoform 2. 1 PublicationVSP_006421Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49921 mRNA. Translation: BAA08660.1.
U36449 Genomic DNA. Translation: AAB52953.1.
D88264 mRNA. Translation: BAA13566.1.
D88352 Genomic DNA. Translation: BAB12221.1.
D88352 Genomic DNA. Translation: BAA13591.1.
U37459 mRNA. Translation: AAB18672.1.
U66195 Genomic DNA. Translation: AAB07463.1.
U75532 mRNA. Translation: AAB18343.1.
BC119031 mRNA. Translation: AAI19032.1.
CCDSiCCDS27371.1. [P48540-3]
PIRiI49686.
RefSeqiNP_001288261.1. NM_001301332.1. [P48540-2]
NP_001288286.1. NM_001301357.1. [P48540-1]
NP_034405.1. NM_010275.3. [P48540-3]
UniGeneiMm.4679.

Genome annotation databases

EnsembliENSMUST00000022744; ENSMUSP00000022744; ENSMUSG00000022144. [P48540-3]
GeneIDi14573.
KEGGimmu:14573.
UCSCiuc007vee.2. mouse. [P48540-3]
uc007vef.2. mouse. [P48540-2]
uc056yyf.1. mouse. [P48540-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49921 mRNA. Translation: BAA08660.1.
U36449 Genomic DNA. Translation: AAB52953.1.
D88264 mRNA. Translation: BAA13566.1.
D88352 Genomic DNA. Translation: BAB12221.1.
D88352 Genomic DNA. Translation: BAA13591.1.
U37459 mRNA. Translation: AAB18672.1.
U66195 Genomic DNA. Translation: AAB07463.1.
U75532 mRNA. Translation: AAB18343.1.
BC119031 mRNA. Translation: AAI19032.1.
CCDSiCCDS27371.1. [P48540-3]
PIRiI49686.
RefSeqiNP_001288261.1. NM_001301332.1. [P48540-2]
NP_001288286.1. NM_001301357.1. [P48540-1]
NP_034405.1. NM_010275.3. [P48540-3]
UniGeneiMm.4679.

3D structure databases

ProteinModelPortaliP48540.
SMRiP48540. Positions 117-211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000022744.

PTM databases

iPTMnetiP48540.

Proteomic databases

PaxDbiP48540.
PRIDEiP48540.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022744; ENSMUSP00000022744; ENSMUSG00000022144. [P48540-3]
GeneIDi14573.
KEGGimmu:14573.
UCSCiuc007vee.2. mouse. [P48540-3]
uc007vef.2. mouse. [P48540-2]
uc056yyf.1. mouse. [P48540-1]

Organism-specific databases

CTDi2668.
MGIiMGI:107430. Gdnf.

Phylogenomic databases

eggNOGiENOG410IGT5. Eukaryota.
ENOG4111I3D. LUCA.
GeneTreeiENSGT00520000055559.
HOGENOMiHOG000220877.
HOVERGENiHBG106680.
InParanoidiP48540.
KOiK05452.
OMAiAKRCGCV.
OrthoDBiEOG7BS4BR.
PhylomeDBiP48540.
TreeFamiTF332366.

Enzyme and pathway databases

ReactomeiR-MMU-5673001. RAF/MAP kinase cascade.

Miscellaneous databases

PROiP48540.
SOURCEiSearch...

Gene expression databases

BgeeiP48540.
CleanExiMM_GDNF.
GenevisibleiP48540. MM.

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.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Spontaneously immortalized adult mouse Schwann cells secrete autocrine and paracrine growth-promoting activities."
    Watabe K., Fukuda T., Tanaka J., Honda H., Toyohara K., Sakai O.
    J. Neurosci. Res. 41:279-290(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: ICR.
    Tissue: Spinal ganglion.
  2. "Embryonic expression of glial cell-line derived neurotrophic factor (GDNF) suggests multiple developmental roles in neural differentiation and epithelial-mesenchymal interactions."
    Hellmich H.L., Kos L., Cho E.S., Mahon K.A., Zimmer A.
    Mech. Dev. 54:95-105(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Strain: 129/SvJ.
    Tissue: Glial cell.
  3. "Cloning and structural organization of the gene encoding the mouse glial cell line-derived neurotrophic factor, GDNF."
    Matsushita N., Fujita Y., Tanaka M., Nagatsu T., Kiuchi K.
    Gene 203:149-157(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION.
    Tissue: Neonatal brain.
  4. "Cloning and characterization of mouse glial cell line-derived neurotrophic growth factor (GDNF)."
    Wang F.-J., Zhao J., Too H.P.
    Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 30:375-381(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1-103 (ISOFORM 2), TISSUE SPECIFICITY.
    Strain: BALB/cJ and C57BL/10J.
    Tissue: Brain and Glial cell.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Brain.

Entry informationi

Entry nameiGDNF_MOUSE
AccessioniPrimary (citable) accession number: P48540
Secondary accession number(s): O09058
, P70446, P97919, P97920, Q6LEL9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: June 8, 2016
This is version 141 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

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  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.