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 10-FEB-2021, entry version 177. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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 ProteomicsDB; 78456; -. DR Antibodypedia; 11762; 461 antibodies. DR Ensembl; ENST00000303212; ENSP00000302648; ENSG00000171119. DR GeneID; 4902; -. DR KEGG; hsa:4902; -. DR UCSC; uc002mde.4; human. DR CTD; 4902; -. DR DisGeNET; 4902; -. DR GeneCards; NRTN; -. DR GeneReviews; 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:ENSG00000171119.2; -. DR eggNOG; ENOG502QWH4; Eukaryota. DR GeneTree; ENSGT00950000182993; -. DR HOGENOM; CLU_102221_1_1_1; -. DR InParanoid; Q99748; -. DR OMA; WKFAAIA; -. 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 SIGNOR; Q99748; -. DR BioGRID-ORCS; 4902; 3 hits in 870 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 right atrium auricular region and 106 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:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. 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 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:0000244|PDB:5NMZ" FT HELIX 112..115 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 117..119 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 124..133 FT /evidence="ECO:0000244|PDB:5NMZ" FT HELIX 140..150 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 165..170 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 172..177 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 183..188 FT /evidence="ECO:0000244|PDB:5NMZ" FT STRAND 190..196 FT /evidence="ECO:0000244|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 //