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Reviewed, UniProtKB/Swiss-Prot P39905 (GDNF_HUMAN)

Last modified November 25, 2008. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Glial cell line-derived neurotrophic factor
Alternative name(s):
    Astrocyte-derived trophic factor
      Short name=ATF
      Short name=hGDNF
Gene names
Name: GDNF
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length211 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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

Subunit structure

Homodimer; disulfide-linked.

Subcellular location

Secreted.

Tissue specificity

In the brain, predominantly expressed in the striatum with highest levels in the caudate and lowest in the putamen.

Induction

By cAMP, tetradecanoyl 12-phorbol acetate and fibroblast growth factor 2.

Involvement in disease

Defects in GDNF may be a cause of Hirschsprung disease (HSCR) [MIM:142623]. In association with mutations of RET gene, defects in GDNF may be involved in Hirschsprung disease. This genetic disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.

Defects in GDNF are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare 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.

Sequence similarities

Belongs to the TGF-beta family. GDNF subfamily.

Ontologies

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P39905-1)

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.
Isoform 2 (identifier: P39905-2)

Also known as: ATF-1; HFK2-GDNF;

The sequence of this isoform differs from the canonical sequence as follows:
     25-51: GKRPPEAPAEDRSLGRRRAPFALSSDS → A
Isoform 3 (identifier: P39905-3)

Also known as: HFK3-GDNF;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQSLPNSNGAAAGRDFKM
Isoform 4 (identifier: P39905-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 7556 By similarity
PRO_0000034004
Chain78 – 211134Glial cell line-derived neurotrophic factor
PRO_0000034005

Amino acid modifications

Glycosylation1261N-linked (GlcNAc...) Potential
Glycosylation1621N-linked (GlcNAc...) Potential
Disulfide bond118 ↔ 179
Disulfide bond145 ↔ 208
Disulfide bond149 ↔ 210
Disulfide bond178Interchain

Natural variations

Alternative sequence11M → MQSLPNSNGAAAGRDFKM in isoform 3 and isoform 4.
VSP_026368
Alternative sequence25 – 5127GKRPP…LSSDS → A in isoform 2 and isoform 4.
VSP_006420
Natural variant211P → S in HSCR; could be a polymorphism.
VAR_009494
Natural variant931R → W in HSCR and CCHS; associated to a RET mutation; could be an extremely rare polymorphism.
VAR_009495
Natural variant1501D → N in HSCR; could be a polymorphism.
VAR_009496
Natural variant1541T → S in HSCR; sporadic form.
VAR_009497
Natural variant2111I → M in HSCR.
VAR_018152

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: A0D1EBF77FC82691

FASTA21123,720
        10         20         30         40         50         60 
MKLWDVVAVC LVLLHTASAF PLPAGKRPPE APAEDRSLGR RRAPFALSSD SNMPEDYPDQ 

        70         80         90        100        110        120 
FDDVMDFIQA TIKRLKRSPD KQMAVLPRRE RNRQAAAANP ENSRGKGRRG QRGKNRGCVL 

       130        140        150        160        170        180 
TAIHLNVTDL GLGYETKEEL IFRYCSGSCD AAETTYDKIL KNLSRNRRLV SDKVGQACCR 

       190        200        210 
PIAFDDDLSF LDDNLVYHIL RKHSAKRCGC I 

« Hide

Isoform 2 (ATF-1) (HFK2-GDNF) [UniParc].

Checksum: 1988C50DA5EA1B10
Show »

18520,885
Isoform 3 (HFK3-GDNF) [UniParc].

Checksum: 5BAAAC69FEDDBA4C
Show »

22825,466
Isoform 4 (HFK4-GDNF) [UniParc].

Checksum: 2CAFBC675D40CF2F
Show »

20222,631

References

« Hide 'large scale' references
[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: 8493557] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, HOMODIMERIZATION, DISULFIDE BONDS.
[2]"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: 7867768] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[3]Zhang B., Feng Z., Zhou Y., Peng X., Yuan J., Qiang B.
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"Characterization of a promoter for the human glial cell line-derived neurotrophic factor gene."
Baecker P.A., Lee W.H., Verity A.N., Eglen R.M., Johnson R.M.
Brain Res. Mol. Brain Res. 69:209-222(1999) [PubMed: 10366742] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-187 (ISOFORM 1).
Tissue: Fetal kidney.
[7]"The Human GDNF Gene promoter."
Suter-Crazzolara C., Baecker P.A., Lee W.H., Johnson R.M., Unsicker K.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-88 (ISOFORM 2), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-77, NUCLEOTIDE SEQUENCE [MRNA] OF 1-59 (ISOFORMS 3 AND 4).
Tissue: Brain and Kidney.
[8]"Analysis of the human GDNF gene reveals an inducible promoter, three exons, a triplet repeat within the 3'-UTR and alternative splice products."
Grimm L., Holinski-Feder E., Teodoridis J., Scheffer B., Schindelhauer D., Meitinger T., Ueffing M.
Hum. Mol. Genet. 7:1873-1886(1998) [PubMed: 9811930] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50, SUBCELLULAR LOCATION, INDUCTION.
[9]"Glial cell line-derived neurotrophic factor: selective reduction of the intermolecular disulfide linkage and characterization of its disulfide structure."
Haniu M., Hui J., Young Y., Le J., Katta V., Lee R., Shimamoto G., Rohde M.F.
Biochemistry 35:16799-16805(1996) [PubMed: 8988018] [Abstract]
Cited for: PROTEIN SEQUENCE OF 87-122; 141-153; 173-184 AND 196-211, HOMODIMERIZATION, DISULFIDE BONDS.
[10]"Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype."
Hofstra R.M.W., Osinga J., Buys C.H.C.M.
Eur. J. Hum. Genet. 5:180-185(1997) [PubMed: 9359036] [Abstract]
Cited for: REVIEW ON VARIANTS.
[11]"De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease."
Ivanchuk S.M., Myers S.M., Eng C., Mulligan L.M.
Hum. Mol. Genet. 5:2023-2026(1996) [PubMed: 8968758] [Abstract]
Cited for: VARIANT HSCR SER-154.
[12]"Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient."
Angrist M., Bolk S., Halushka M., Lapchak P.A., Chakravarti A.
Nat. Genet. 14:341-344(1996) [PubMed: 8896568] [Abstract]
Cited for: VARIANT HSCR TRP-93.
[13]"Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease."
Salomon R., Attie T., Pelet A., Bidaud C., Eng C., Amiel J., Sarnacki S., Goulet O., Ricour C., Nihoul-Fekete C., Munnich A., Lyonnet S.
Nat. Genet. 14:345-347(1996) [PubMed: 8896569] [Abstract]
Cited for: VARIANTS HSCR SER-21 AND ASN-150.
[14]"Mutations of the RET-GDNF signaling pathway in Ondine's curse."
Amiel J., Salomon R., Attie T., Pelet A., Trang H., Mokhtari M., Gaultier C., Munnich A., Lyonnet S.
Am. J. Hum. Genet. 62:715-717(1998) [PubMed: 9497256] [Abstract]
Cited for: VARIANT CCHS TRP-93.
[15]"Pathogenesis of Hirschsprung's disease."
Martucciello G., Ceccherini I., Lerone M., Jasonni V.
J. Pediatr. Surg. 35:1017-1025(2000) [PubMed: 10917288] [Abstract]
Cited for: VARIANT HSCR MET-211.
+Additional computationally mapped references.

Cross-references

Sequence databases

L19063, L19062 Genomic DNA. Translation: AAA67910.1.
AY052832 mRNA. Translation: AAL11017.1.
CR541923 mRNA. Translation: CAG46721.1.
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.
PIRB37499.
RefSeqNP_000505.1.
NP_954701.1.
NP_954704.1.
UniGeneHs.248114

3D structure databases

HSSPHSSP built from PDB template 1AGQ based on UniProtKB Q07731.
SMRP39905. Positions 117-211.
ModBaseSearch...

PTM databases

PhosphoSiteP39905.

Genome annotation databases

EnsemblENSG00000168621. Homo sapiens. [Contig view]
GeneID2668.
KEGGhsa:2668.

Organism-specific databases

H-InvDBHIX0031958.
HGNCHGNC:4232. GDNF.
HPACAB005210.
MIM142623. phenotype.
209880. phenotype.
600837. gene.
Orphanet388. Hirschsprung disease.
661. Ondine syndrome.
PharmGKBPA28644.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP39905.
HOVERGENP39905.

Gene expression databases

ArrayExpressP39905.
GermOnlineENSG00000168621. Homo sapiens.

Family and domain databases

InterProIPR016649. GDNF.
IPR002400. GF_cysknot.
IPR001839. TGFb.
[Graphical view]
PfamPF00019. TGF_beta. 1 hit.
[Graphical view]
PIRSFPIRSF016238. GDNF. 1 hit.
PRINTSPR00438. GFCYSKNOT.
ProDomPD000357. TGFb. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. False negative.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio10524.
SOURCESearch...

Entry information

Entry nameGDNF_HUMAN
AccessionPrimary (citable) accession number: P39905
Secondary accession number(s): O95448 expand/collapse secondary AC list , O95449, O95986, Q6FH33, Q96L44, Q9UD32, Q9UD33, Q9UMV2, Q9UP67, Q9UP97
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 25, 2008
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents