GDNF_DANRE
ID GDNF_DANRE Reviewed; 235 AA.
AC Q98TU0;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Glial cell line-derived neurotrophic factor;
DE Short=zGDNF;
DE Flags: Precursor;
GN Name=gdnf {ECO:0000312|EMBL:AAK11259.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAK11259.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Glial cell {ECO:0000269|PubMed:11237470};
RX PubMed=11237470; DOI=10.1006/dbio.2000.0145;
RA Shepherd I.T., Beattie C.E., Raible D.W.;
RT "Functional analysis of zebrafish GDNF.";
RL Dev. Biol. 231:420-435(2001).
CC -!- FUNCTION: Neurotrophic factor that enhances survival and morphological
CC differentiation of dopaminergic neurons and increases their high-
CC affinity dopamine uptake (By similarity). Essential for the development
CC of the enteric nervous system, but appears dispensable for the
CC development of the kidney and primary motor neuron. {ECO:0000250,
CC ECO:0000269|PubMed:11237470}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:Q07731}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: First expressed at 14 hours post-fertilization
CC (hpf) in the ventral half of anterior somites and in intermediate
CC mesoderm. Ventral somitic expression persists and extends more
CC posteriorly over the next 12 hours. Expressed throughout the ventral
CC trunk mesoderm and endoderm at 24 hpf. By 30 hpf, somitic expression
CC ceases and by 36 hpf, expression becomes restricted to the endodermal
CC cells forming the gut, with expression along the whole length of the
CC developing gut tube at 72 hpf. {ECO:0000269|PubMed:11237470}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000255}.
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DR EMBL; AF329853; AAK11259.1; -; mRNA.
DR PDB; 7AB8; X-ray; 2.20 A; B=138-235.
DR PDB; 7AML; EM; 3.50 A; C/F=135-235.
DR PDBsum; 7AB8; -.
DR PDBsum; 7AML; -.
DR AlphaFoldDB; Q98TU0; -.
DR SMR; Q98TU0; -.
DR STRING; 7955.ENSDARP00000124666; -.
DR PaxDb; Q98TU0; -.
DR ZFIN; ZDB-GENE-010226-1; gdnfa.
DR eggNOG; ENOG502QWCH; Eukaryota.
DR InParanoid; Q98TU0; -.
DR PhylomeDB; Q98TU0; -.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-8853659; RET signaling.
DR PRO; PR:Q98TU0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030116; F:glial cell-derived neurotrophic factor receptor binding; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:ZFIN.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:InterPro.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0048484; P:enteric nervous system development; IMP:ZFIN.
DR GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
DR GO; GO:0048255; P:mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0030432; P:peristalsis; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0032770; P:positive regulation of monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0072107; P:positive regulation of ureteric bud formation; ISS:UniProtKB.
DR GO; GO:0021784; P:postganglionic parasympathetic fiber development; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IPI:ZFIN.
DR GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; ISS:UniProtKB.
DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; ISS:UniProtKB.
DR GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR016649; GDNF.
DR InterPro; IPR043401; GDNF_fam.
DR InterPro; IPR001839; TGF-b_C.
DR PANTHER; PTHR12173; PTHR12173; 1.
DR PANTHER; PTHR12173:SF1; PTHR12173:SF1; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR PIRSF; PIRSF016238; GDNF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..87
FT /evidence="ECO:0000250|UniProtKB:Q07731"
FT /id="PRO_0000292932"
FT CHAIN 90..235
FT /note="Glial cell line-derived neurotrophic factor"
FT /evidence="ECO:0000255"
FT /id="PRO_0000292933"
FT REGION 34..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..107
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 142..203
FT /evidence="ECO:0000250|UniProtKB:Q07731"
FT DISULFID 169..232
FT /evidence="ECO:0000250|UniProtKB:Q07731"
FT DISULFID 173..234
FT /evidence="ECO:0000250|UniProtKB:Q07731"
FT DISULFID 202
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q07731"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:7AB8"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:7AB8"
FT STRAND 163..171
FT /evidence="ECO:0007829|PDB:7AB8"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:7AB8"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:7AB8"
FT TURN 191..195
FT /evidence="ECO:0007829|PDB:7AB8"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:7AB8"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:7AB8"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:7AB8"
FT STRAND 228..234
FT /evidence="ECO:0007829|PDB:7AB8"
SQ SEQUENCE 235 AA; 26829 MW; EB711B38D755F329 CRC64;
MKLWDILATC LLLLSSVSTR PLFHKLQPSK RAVVRSESPA LDPIIDSQPE TSNPKQASME
EQYDLTGLYP EQFEDVMDFI EATLGRLRRS SDVEPQMKRD RVRQKAAANT EKSGGRGRGE
RKRSRGRARS RDDRVKGQGR GCLLKEIHLN VTDLDLGYRT KEELIFRYCS GPCHDAETNY
DKILNNLTHN KKLDKDTPSR TCCRPIAFDD DISFLDDSLE YHTLKKHSAK KCACV