Reviewed, UniProtKB/Swiss-Prot Q99748 (NRTN_HUMAN)

Names and origin

Protein names

Recommended name:
    Neurturin

Gene names

Name:

NRTN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	197 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Supports the survival of sympathetic neurons in culture. May regulate the development and maintenance of the CNS. Might control the size of non-neuronal cell population such as haemopoietic cells.
Subunit structure	Homodimer; disulfide-linked.
Subcellular location	Secreted.
Involvement in disease	Defects in NRTN are a cause of Hirschsprung disease (HSCR) [MIM:142623]. In association with mutations of RET gene, and possibly with other loci, defects in NRTN are 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. Ref.3
Sequence similarities	Belongs to the TGF-beta family. GDNF subfamily.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hirschsprung disease
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond
Gene Ontology (GO)
Biological process	MAPKKK cascade Ref.1 Traceable author statement. Source: ProtInc neural crest cell migration Inferred from direct assay. Source: MGI neuron projection development Inferred from direct assay. Source: MGI transmembrane receptor protein tyrosine kinase signaling pathway Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Propeptide	20 – 95	76	By similarity		PRO_0000034010
	Chain	96 – 197	102	Neurturin		PRO_0000034011
Amino acid modifications
	Disulfide bond	103 ↔ 165		By similarity
	Disulfide bond	130 ↔ 194		By similarity
	Disulfide bond	134 ↔ 196		By similarity
	Disulfide bond	164		Interchain By similarity
Natural variations
	Natural variant	96	1	A → S in HSCR; associated to a RET mutation; incomplete penetrance. dbSNP rs1801281. Ref.3		VAR_009498

Sequences

	Sequence		Length	Mass (Da)
	Q99748-1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 91AFAC8C3F8971FD	FASTA	197	22,405
	10 20 30 40 50 60 MQRWKAAALA SVLCSSVLSI WMCREGLLLS HRLGPALVPL HRLPRTLDAR IARLAQYRAL 70 80 90 100 110 120 LQGAPDAMEL RELTPWAGRP PGPRRRAGPR RRRARARLGA RPCGLRELEV RVSELGLGYA 130 140 150 160 170 180 SDETVLFRYC AGACEAAARV YDLGLRRLRQ RRRLRRERVR AQPCCRPTAY EDEVSFLDAH 190 SRYHTVHELS ARECACV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neurturin, a relative of glial-cell-line-derived neurotrophic factor." Kotzbauer P.T., Lampe P.A., Heuckeroth R.O., Golden J.P., Creedon D.J., Johnson E.M. Jr., Milbrandt J. Nature 384:467-470(1996) [PubMed: 8945474] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Melanoma.
[3]	"Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease." Doray B., Salomon R., Amiel J., Pelet A., Touraine R., Billaud M., Attie T., Bachy B., Munnich A., Lyonnet S. Hum. Mol. Genet. 7:1449-1452(1998) [PubMed: 9700200] [Abstract] Cited for: VARIANT HSCR SER-96. Tissue: Peripheral blood lymphocyte.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U78110 mRNA. Translation: AAC50898.1. AL161995 mRNA. Translation: CAB82327.1.
IPI	IPI00017787.
PIR	T47159.
RefSeq	NP_004549.1.
UniGene	Hs.234775
3D structure databases
HSSP	HSSP built from PDB template 1AGQ based on UniProtKB Q07731.
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000171119. Homo sapiens. [Contig view]
GeneID	4902.
KEGG	hsa:4902.
Organism-specific databases
GeneCards	GC19P005774.
H-InvDB	HIX0014687.
HGNC	HGNC:8007. NRTN.
MIM	142623. phenotype. 602018. gene.
Orphanet	388. Hirschsprung disease.
PharmGKB	PA31785.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q99748.
HOVERGEN	Q99748.
OMA	Q99748. MCREGLL.
Gene expression databases
ArrayExpress	Q99748.
Bgee	Q99748.
CleanEx	HS_NRTN.
GermOnline	ENSG00000171119. Homo sapiens.
Family and domain databases
InterPro	IPR001839. TGFb. IPR017948. TGFb_CS. [Graphical view]
Pfam	PF00019. TGF_beta. 1 hit. [Graphical view]
ProDom	PD000357. TGFb. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. False negative. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	18867.
SOURCE	Search...

Entry information

Entry name

NRTN_HUMAN

Accession

Primary (citable) accession number: Q99748

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 1, 1997
Last modified:	June 16, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)