P34130 (NTF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurotrophin-4
Short name=NT-4

Alternative name(s):
Neurotrophin-5
Short name=NT-5
Neutrophic factor 4

Gene names

Name:	NTF4
Synonyms:	NTF5

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	210 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	Target-derived survival factor for peripheral sensory sympathetic neurons.
Subcellular location	Secreted.
Tissue specificity	Highest levels in prostate, lower levels in thymus, placenta, and skeletal muscle. Expressed in embryonic and adult tissues.
Involvement in disease	Defects in NTF4 may be associated with susceptibility to primary open angle glaucoma type 1O (GLC1O) [MIM:613100]. A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
Sequence similarities	Belongs to the NGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Glaucoma
Domain	Signal
Molecular function	Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adult locomotory behavior Inferred from sequence or structural similarity. Source: UniProtKB epidermis development Inferred from sequence or structural similarity. Source: UniProtKB ganglion mother cell fate determination Inferred from sequence or structural similarity. Source: UniProtKB long-term memory Inferred from sequence or structural similarity. Source: UniProtKB sensory organ boundary specification Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	endoplasmic reticulum lumen Inferred from sequence or structural similarity. Source: UniProtKB extracellular region Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	growth factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Propeptide

25 – 80

56

PRO_0000019669

Chain

81 – 210

130

Neurotrophin-4

PRO_0000019670

Amino acid modifications

Glycosylation

76

1

N-linked (GlcNAc...) Potential

Disulfide bond

97 ↔ 170

Disulfide bond

141 ↔ 199

Disulfide bond

158 ↔ 201

Natural variations

Natural variant

7

1

C → Y in a patient with primary open-angle glaucoma; uncertain pathological significance. Ref.7

VAR_063196

Natural variant

84

1

E → K in a patient with primary open-angle glaucoma; uncertain pathological significance. Ref.7

VAR_063197

Natural variant

88

1

A → V. Ref.7 Ref.8

VAR_063198

Natural variant

89

1

S → N. Ref.8

VAR_063199

Natural variant

90

1

R → C. Ref.8

VAR_063200

Natural variant

90

1

R → H in a patient with primary open-angle glaucoma; uncertain pathological significance. Ref.7

VAR_063201

Natural variant

114

1

R → G. Ref.8

VAR_063202

Natural variant

133

1

R → H. Ref.8

VAR_063203

Natural variant

140

1

R → C. Ref.8

VAR_063204

Natural variant

206

1

R → Q in a patient with primary open-angle glaucoma; uncertain pathological significance. Ref.7

VAR_063205

Natural variant

206

1

R → W in patients with primary open-angle glaucoma and normal pressure glaucoma; uncertain pathological significance; impaired ligand-mediated TRKB signaling and reduced neurite outgrowth. Ref.7 Ref.8

VAR_063206

Natural variant

207

1

T → I. Ref.8

VAR_063207

Natural variant

207

1

T → S. Ref.7

VAR_063208

Natural variant

209

1

R → G in a patient with primary open-angle glaucoma; uncertain pathological significance. Ref.7

VAR_063209

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

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.

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.

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210

Helix Strand Turn

Details...

Beta strand

83 – 85

3

Helix

88 – 90

3

Beta strand

95 – 97

3

Beta strand

99 – 104

6

Beta strand

109 – 112

4

Beta strand

117 – 120

4

Beta strand

136 – 141

6

Turn

146 – 148

3

Beta strand

150 – 153

4

Turn

163 – 165

3

Beta strand

168 – 182

15

Beta strand

184 – 186

3

Beta strand

189 – 203

15

Sequences

	Sequence		Length	Mass (Da)
	P34130 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: DBC6A30195E139AD	FASTA	210	22,427
	10 20 30 40 50 60 MLPLPSCSLP ILLLFLLPSV PIESQPPPST LPPFLAPEWD LLSPRVVLSR GAPAGPPLLF 70 80 90 100 110 120 LLEAGAFRES AGAPANRSRR GVSETAPASR RGELAVCDAV SGWVTDRRTA VDLRGREVEV 130 140 150 160 170 180 LGEVPAAGGS PLRQYFFETR CKADNAEEGG PGAGGGGCRG VDRRHWVSEC KAKQSYVRAL 190 200 210 TADAQGRVGW RWIRIDTACV CTLLSRTGRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB." Berkemeier L.R., Winslow J.W., Kaplan D.R., Nikolics K., Goeddel D.V., Rosenthal A. Neuron 7:857-866(1991) [PubMed: 1742028] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity." Ip N.Y., Ibanez C.F., Nye S.H., McClain J., Jones P.F., Gies D.R., Belluscio L., le Beau M.M., Espinosa R. III, Squinto S.P., Persson H., Yancopoulos G.D. Proc. Natl. Acad. Sci. U.S.A. 89:3060-3064(1992) [PubMed: 1313578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Prostate.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[6]	"The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site." Robinson R.C., Radziejewski C., Spraggon G., Greenwald J., Kostura M.R., Burtnick L.D., Stuart D.I., Choe S., Jones E.Y. Protein Sci. 8:2589-2597(1999) [PubMed: 10631974] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS).
[7]	"Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma." Pasutto F., Matsumoto T., Mardin C.Y., Sticht H., Brandstatter J.H., Michels-Rautenstrauss K., Weisschuh N., Gramer E., Ramdas W.D., van Koolwijk L.M., Klaver C.C., Vingerling J.R., Weber B.H., Kruse F.E., Rautenstrauss B., Barde Y.A., Reis A. Am. J. Hum. Genet. 85:447-456(2009) [PubMed: 19765683] [Abstract] Cited for: VARIANTS TYR-7; LYS-84; VAL-88; HIS-90; TRP-206; GLN-206; SER-207 AND GLY-209, CHARACTERIZATION OF VARIANT TRP-206, INVOLVEMENT IN SUSCEPTIBILITY TO GLAUCOMA.
[8]	"No evidence of association of heterozygous NTF4 mutations in patients with primary open-angle glaucoma." Liu Y., Liu W., Crooks K., Schmidt S., Allingham R.R., Hauser M.A. Am. J. Hum. Genet. 86:498-499(2010) [PubMed: 20215012] [Abstract] Cited for: VARIANTS VAL-88; ASN-89; CYS-90; GLY-114; HIS-133; CYS-140; TRP-206 AND ILE-207, DISCUSSION OF ASSOCIATION WITH GLAUCOMA.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M86528 Genomic DNA. Translation: AAA60154.1.
BT019368 mRNA. Translation: AAV38175.1.
BT019369 mRNA. Translation: AAV38176.1.
CR541900 mRNA. Translation: CAG46698.1.
BC012421 mRNA. Translation: AAH12421.1.

IPI

IPI00030097.

PIR

A42687.

RefSeq

NP_006170.1. NM_006179.4.

UniGene

Hs.266902.
Hs.730176.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B8M	X-ray	2.75	B	81-210	[»]
1B98	X-ray	2.75	A/M	81-210	[»]
1HCF	X-ray	2.70	A/B	81-210	[»]

ProteinModelPortal

P34130.

SMR

P34130. Positions 85-208.

ModBase

Search...

Protein-protein interaction databases

IntAct

P34130. 1 interaction.

STRING

P34130.

Polymorphism databases

DMDM

462741.

Proteomic databases

PRIDE

P34130.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301411; ENSP00000301411; ENSG00000167744.

GeneID

4909.

KEGG

hsa:4909.

UCSC

uc002pmf.2. human.

Organism-specific databases

CTD

4909.

GeneCards

GC19M049564.

HGNC

HGNC:8024. NTF4.

HPA

CAB010167.

MIM

162662. gene.
613100. phenotype.

neXtProt

NX_P34130.

PharmGKB

PA162398206.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16489.

GeneTree

ENSGT00390000007725.

HOGENOM

HBG713304.

HOVERGEN

HBG006494.

InParanoid

P34130.

OMA

PSVPMEP.

OrthoDB

EOG4VHK7R.

PhylomeDB

P34130.

Enzyme and pathway databases

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.

Gene expression databases

ArrayExpress

P34130.

Bgee

P34130.

CleanEx

HS_NTF4.

Genevestigator

P34130.

GermOnline

ENSG00000167744. Homo sapiens.

Family and domain databases

InterPro

IPR020408. Nerve_growth_factor-like.
IPR002072. Nerve_growth_factor-rel.
IPR019846. Nerve_growth_factor_CS.
IPR020432. Neurotrophin-4.
[Graphical view]

KO

K12457.

PANTHER

PTHR11589. NGF. 1 hit.

Pfam

PF00243. NGF. 1 hit.
[Graphical view]

PIRSF

PIRSF001789. NGF. 1 hit.

PRINTS

PR01915. NEUROTROPHN4.
PR00268. NGF.

ProDom

PD002052. Nerve_growth_factor-rel. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00140. NGF. 1 hit.
[Graphical view]

PROSITE

PS00248. NGF_1. 1 hit.
PS50270. NGF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

18893.

SOURCE

Search...

Entry information

Entry name

NTF4_HUMAN

Accession

Primary (citable) accession number: P34130
Secondary accession number(s): Q6FH56

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	January 25, 2012
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.