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   16-JAN-2019, entry version 162.
DE   RecName: Full=Neurturin;
DE   Flags: Precursor;
GN   Name=NRTN;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Creedon D.J., Johnson E.M. Jr., Milbrandt J.;
RT   "Neurturin, a relative of glial-cell-line-derived neurotrophic
RT   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.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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
RT   inheritance in Hirschsprung disease.";
RL   Hum. Mol. Genet. 7:1449-1452(1998).
CC   -!- FUNCTION: Supports the survival of sympathetic neurons in culture.
CC       May regulate the development and maintenance of the CNS. Might
CC       control the size of non-neuronal cell population such as
CC       haemopoietic cells.
CC   -!- SUBUNIT: Homodimer; disulfide-linked.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- DISEASE: Note=Genetic variations in NRTN may contribute to
CC       Hirschsprung disease, in association with mutations of RET gene,
CC       and possibly mutations in other loci. Hirschsprung disease is a
CC       disorder of neural crest development is characterized by the
CC       absence of intramural ganglion cells in the hindgut, often
CC       resulting in intestinal 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   UniGene; Hs.234775; -.
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   PDBsum; 5MR4; -.
DR   PDBsum; 5MR5; -.
DR   PDBsum; 5MR9; -.
DR   PDBsum; 5NMZ; -.
DR   ProteinModelPortal; 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   ProteomicsDB; 78456; -.
DR   Ensembl; ENST00000303212; ENSP00000302648; ENSG00000171119.
DR   GeneID; 4902; -.
DR   KEGG; hsa:4902; -.
DR   UCSC; uc002mde.4; human.
DR   CTD; 4902; -.
DR   DisGeNET; 4902; -.
DR   EuPathDB; HostDB:ENSG00000171119.2; -.
DR   GeneCards; NRTN; -.
DR   GeneReviews; NRTN; -.
DR   HGNC; HGNC:8007; NRTN.
DR   MalaCards; NRTN; -.
DR   MIM; 602018; gene.
DR   neXtProt; NX_Q99748; -.
DR   OpenTargets; ENSG00000171119; -.
DR   Orphanet; 388; Hirschsprung disease.
DR   PharmGKB; PA31785; -.
DR   eggNOG; ENOG410IWH0; Eukaryota.
DR   eggNOG; ENOG410YM89; LUCA.
DR   GeneTree; ENSGT00940000154202; -.
DR   HOGENOM; HOG000220877; -.
DR   HOVERGEN; HBG003694; -.
DR   InParanoid; Q99748; -.
DR   OMA; WKGATFA; -.
DR   OrthoDB; 1166960at2759; -.
DR   PhylomeDB; Q99748; -.
DR   TreeFam; TF332366; -.
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   GenomeRNAi; 4902; -.
DR   PRO; PR:Q99748; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000171119; Expressed in 91 organ(s), highest expression level in right atrium auricular region.
DR   CleanEx; HS_NRTN; -.
DR   Genevisible; Q99748; HS.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
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; IPR001839; TGF-b_C.
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; Complete proteome; Disease mutation; Disulfide bond;
KW   Growth factor; Hirschsprung disease; Polymorphism; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   PROPEP       20     95       {ECO:0000250}.
FT                                /FTId=PRO_0000034010.
FT   CHAIN        96    197       Neurturin.
FT                                /FTId=PRO_0000034011.
FT   DISULFID    103    165       {ECO:0000250}.
FT   DISULFID    130    194       {ECO:0000250}.
FT   DISULFID    134    196       {ECO:0000250}.
FT   DISULFID    164    164       Interchain. {ECO:0000250}.
FT   VARIANT      96     96       A -> S (may contribute to Hirschsprung
FT                                disease in patients carrying a RET
FT                                mutation; dbSNP:rs575363266).
FT                                {ECO:0000269|PubMed:9700200}.
FT                                /FTId=VAR_009498.
FT   STRAND      102    111       {ECO:0000244|PDB:5NMZ}.
FT   HELIX       112    115       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      117    119       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      124    133       {ECO:0000244|PDB:5NMZ}.
FT   HELIX       140    150       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      165    170       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      172    177       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      183    188       {ECO:0000244|PDB:5NMZ}.
FT   STRAND      190    196       {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
//