NRTN_HUMAN
ID NRTN_HUMAN Reviewed; 197 AA.
AC Q99748; B2RPE8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Neurturin;
DE Flags: Precursor;
GN Name=NRTN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8945474; DOI=10.1038/384467a0;
RA Kotzbauer P.T., Lampe P.A., Heuckeroth R.O., Golden J.P., Creedon D.J.,
RA Johnson E.M. Jr., Milbrandt J.;
RT "Neurturin, a relative of glial-cell-line-derived neurotrophic factor.";
RL Nature 384:467-470(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP VARIANT SER-96, AND POSSIBLE INVOLVEMENT IN HIRSCHSPRUNG DISEASE.
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=9700200; DOI=10.1093/hmg/7.9.1449;
RA Doray B., Salomon R., Amiel J., Pelet A., Touraine R., Billaud M.,
RA Attie T., Bachy B., Munnich A., Lyonnet S.;
RT "Mutation of the RET ligand, neurturin, supports multigenic inheritance in
RT Hirschsprung disease.";
RL Hum. Mol. Genet. 7:1449-1452(1998).
CC -!- FUNCTION: Supports the survival of sympathetic neurons in culture. May
CC regulate the development and maintenance of the CNS. Might control the
CC size of non-neuronal cell population such as haemopoietic cells.
CC -!- SUBUNIT: Homodimer; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISEASE: Note=Genetic variations in NRTN may contribute to Hirschsprung
CC disease, in association with mutations of RET gene, and possibly
CC mutations in other loci. Hirschsprung disease is a disorder of neural
CC crest development is characterized by the absence of intramural
CC ganglion cells in the hindgut, often resulting in intestinal
CC obstruction. {ECO:0000269|PubMed:9700200}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000305}.
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DR EMBL; U78110; AAC50898.1; -; mRNA.
DR EMBL; AL161995; CAB82327.1; -; mRNA.
DR EMBL; CH471139; EAW69140.1; -; Genomic_DNA.
DR EMBL; BC137399; AAI37400.1; -; mRNA.
DR EMBL; BC137400; AAI37401.1; -; mRNA.
DR CCDS; CCDS12151.1; -.
DR PIR; T47159; T47159.
DR RefSeq; NP_004549.1; NM_004558.4.
DR RefSeq; XP_011526343.1; XM_011528041.2.
DR PDB; 5MR4; X-ray; 2.40 A; A/B=96-197.
DR PDB; 5MR5; X-ray; 2.00 A; A/B=96-197.
DR PDB; 5MR9; X-ray; 2.40 A; A/B=96-197.
DR PDB; 5NMZ; X-ray; 1.60 A; A/B/C/D=97-197.
DR PDB; 6GL7; EM; 6.30 A; A/B=96-197.
DR PDB; 6Q2O; EM; 3.65 A; A/B=96-197.
DR PDB; 6Q2R; EM; 4.30 A; A/B/U/V=96-197.
DR PDBsum; 5MR4; -.
DR PDBsum; 5MR5; -.
DR PDBsum; 5MR9; -.
DR PDBsum; 5NMZ; -.
DR PDBsum; 6GL7; -.
DR PDBsum; 6Q2O; -.
DR PDBsum; 6Q2R; -.
DR AlphaFoldDB; Q99748; -.
DR SMR; Q99748; -.
DR BioGRID; 110958; 3.
DR STRING; 9606.ENSP00000302648; -.
DR PhosphoSitePlus; Q99748; -.
DR BioMuta; NRTN; -.
DR DMDM; 2501180; -.
DR PaxDb; Q99748; -.
DR PRIDE; Q99748; -.
DR Antibodypedia; 11762; 471 antibodies from 41 providers.
DR DNASU; 4902; -.
DR Ensembl; ENST00000303212.3; ENSP00000302648.1; ENSG00000171119.3.
DR GeneID; 4902; -.
DR KEGG; hsa:4902; -.
DR MANE-Select; ENST00000303212.3; ENSP00000302648.1; NM_004558.5; NP_004549.1.
DR UCSC; uc002mde.4; human.
DR CTD; 4902; -.
DR DisGeNET; 4902; -.
DR GeneCards; NRTN; -.
DR HGNC; HGNC:8007; NRTN.
DR HPA; ENSG00000171119; Tissue enhanced (heart muscle, pancreas).
DR MalaCards; NRTN; -.
DR MIM; 602018; gene.
DR neXtProt; NX_Q99748; -.
DR OpenTargets; ENSG00000171119; -.
DR Orphanet; 388; Hirschsprung disease.
DR PharmGKB; PA31785; -.
DR VEuPathDB; HostDB:ENSG00000171119; -.
DR eggNOG; ENOG502QWH4; Eukaryota.
DR GeneTree; ENSGT00950000182993; -.
DR HOGENOM; CLU_102221_1_1_1; -.
DR InParanoid; Q99748; -.
DR OMA; TFAFMLC; -.
DR OrthoDB; 1373819at2759; -.
DR PhylomeDB; Q99748; -.
DR TreeFam; TF332366; -.
DR PathwayCommons; Q99748; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q99748; -.
DR SIGNOR; Q99748; -.
DR BioGRID-ORCS; 4902; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; NRTN; human.
DR GenomeRNAi; 4902; -.
DR Pharos; Q99748; Tbio.
DR PRO; PR:Q99748; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q99748; protein.
DR Bgee; ENSG00000171119; Expressed in apex of heart and 87 other tissues.
DR Genevisible; Q99748; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0030971; F:receptor tyrosine kinase binding; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0000165; P:MAPK cascade; TAS:ProtInc.
DR GO; GO:0021675; P:nerve development; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0001755; P:neural crest cell migration; IDA:MGI.
DR GO; GO:0031175; P:neuron projection development; IDA:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; TAS:ProtInc.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR043401; GDNF_fam.
DR InterPro; IPR001839; TGF-b_C.
DR PANTHER; PTHR12173; PTHR12173; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Disulfide bond; Growth factor;
KW Hirschsprung disease; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..95
FT /evidence="ECO:0000250"
FT /id="PRO_0000034010"
FT CHAIN 96..197
FT /note="Neurturin"
FT /id="PRO_0000034011"
FT REGION 74..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 103..165
FT /evidence="ECO:0000250"
FT DISULFID 130..194
FT /evidence="ECO:0000250"
FT DISULFID 134..196
FT /evidence="ECO:0000250"
FT DISULFID 164
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VARIANT 96
FT /note="A -> S (may contribute to Hirschsprung disease in
FT patients carrying a RET mutation; dbSNP:rs575363266)"
FT /evidence="ECO:0000269|PubMed:9700200"
FT /id="VAR_009498"
FT STRAND 102..111
FT /evidence="ECO:0007829|PDB:5NMZ"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 124..133
FT /evidence="ECO:0007829|PDB:5NMZ"
FT HELIX 140..150
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:5NMZ"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:5NMZ"
SQ SEQUENCE 197 AA; 22405 MW; 91AFAC8C3F8971FD CRC64;
MQRWKAAALA SVLCSSVLSI WMCREGLLLS HRLGPALVPL HRLPRTLDAR IARLAQYRAL
LQGAPDAMEL RELTPWAGRP PGPRRRAGPR RRRARARLGA RPCGLRELEV RVSELGLGYA
SDETVLFRYC AGACEAAARV YDLGLRRLRQ RRRLRRERVR AQPCCRPTAY EDEVSFLDAH
SRYHTVHELS ARECACV
