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Protein

Neurotrophin-4

Gene

NTF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Target-derived survival factor for peripheral sensory sympathetic neurons.

GO - Molecular functioni

  1. growth factor activity Source: ProtInc
  2. neurotrophin p75 receptor binding Source: GO_Central

GO - Biological processi

  1. adult locomotory behavior Source: UniProtKB
  2. cell-cell signaling Source: GO_Central
  3. epidermis development Source: UniProtKB
  4. ganglion mother cell fate determination Source: UniProtKB
  5. innervation Source: Ensembl
  6. long-term memory Source: UniProtKB
  7. mechanoreceptor differentiation Source: Ensembl
  8. negative regulation of neuron apoptotic process Source: GO_Central
  9. neuron projection morphogenesis Source: GO_Central
  10. regulation of neuron differentiation Source: GO_Central
  11. sensory organ boundary specification Source: UniProtKB
  12. taste bud development Source: Ensembl
  13. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
Recommended name:
Neurotrophin-4
Short name:
NT-4
Alternative name(s):
Neurotrophin-5
Short name:
NT-5
Neutrophic factor 4
Gene namesi
Name:NTF4
Synonyms:NTF5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:8024. NTF4.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasmic membrane-bounded vesicle Source: GO_Central
  2. endoplasmic reticulum lumen Source: UniProtKB
  3. extracellular region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Glaucoma 1, open angle, O (GLC1O)

Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Disease descriptionA 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. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.

See also OMIM:613100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71C → Y in GLC1O; unknown pathological significance. 1 Publication
VAR_063196
Natural varianti84 – 841E → K in GLC1O; unknown pathological significance. 1 Publication
VAR_063197
Natural varianti90 – 901R → H in GLC1O; unknown pathological significance. 1 Publication
VAR_063201
Natural varianti206 – 2061R → Q in GLC1O; unknown pathological significance. 1 Publication
VAR_063205
Natural varianti206 – 2061R → W in GLC1O; also found in patients with normal pressure glaucoma; unknown pathological significance; impaired ligand-mediated TRKB signaling and reduced neurite outgrowth. 2 Publications
VAR_063206
Natural varianti209 – 2091R → G in GLC1O; unknown pathological significance. 1 Publication
VAR_063209

Keywords - Diseasei

Glaucoma

Organism-specific databases

MIMi613100. phenotype.
Orphaneti353225. Primary adult open-angle glaucoma.
PharmGKBiPA162398206.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Propeptidei25 – 8056PRO_0000019669Add
BLAST
Chaini81 – 210130Neurotrophin-4PRO_0000019670Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi76 – 761N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi97 ↔ 170
Disulfide bondi141 ↔ 199
Disulfide bondi158 ↔ 201

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP34130.
PRIDEiP34130.

Expressioni

Tissue specificityi

Highest levels in prostate, lower levels in thymus, placenta, and skeletal muscle. Expressed in embryonic and adult tissues.

Gene expression databases

BgeeiP34130.
CleanExiHS_NTF4.
ExpressionAtlasiP34130. baseline and differential.
GenevestigatoriP34130.

Interactioni

Protein-protein interaction databases

BioGridi110964. 4 interactions.
IntActiP34130. 3 interactions.
MINTiMINT-1508589.
STRINGi9606.ENSP00000301411.

Structurei

Secondary structure

1
210
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi83 – 853Combined sources
Helixi88 – 903Combined sources
Beta strandi94 – 974Combined sources
Beta strandi99 – 1046Combined sources
Beta strandi109 – 1124Combined sources
Beta strandi117 – 1204Combined sources
Beta strandi122 – 1254Combined sources
Beta strandi127 – 1337Combined sources
Beta strandi136 – 1416Combined sources
Turni146 – 1483Combined sources
Beta strandi153 – 1564Combined sources
Turni163 – 1653Combined sources
Beta strandi166 – 18217Combined sources
Beta strandi188 – 20518Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1B8MX-ray2.75B81-210[»]
1B98X-ray2.75A/M81-210[»]
1HCFX-ray2.70A/B81-210[»]
ProteinModelPortaliP34130.
SMRiP34130. Positions 85-208.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34130.

Family & Domainsi

Sequence similaritiesi

Belongs to the NGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42623.
GeneTreeiENSGT00390000007725.
HOGENOMiHOG000231516.
HOVERGENiHBG006494.
InParanoidiP34130.
KOiK12457.
OMAiSVPMEPH.
PhylomeDBiP34130.
TreeFamiTF106463.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR020408. Nerve_growth_factor-like.
IPR002072. Nerve_growth_factor-rel.
IPR019846. Nerve_growth_factor_CS.
IPR020432. Neurotrophin-4.
[Graphical view]
PANTHERiPTHR11589. PTHR11589. 1 hit.
PfamiPF00243. NGF. 1 hit.
[Graphical view]
PIRSFiPIRSF001789. NGF. 1 hit.
PRINTSiPR01915. NEUROTROPHN4.
PR00268. NGF.
ProDomiPD002052. Nerve_growth_factor-rel. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00140. NGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00248. NGF_1. 1 hit.
PS50270. NGF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P34130-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPLPSCSLP ILLLFLLPSV PIESQPPPST LPPFLAPEWD LLSPRVVLSR
60 70 80 90 100
GAPAGPPLLF LLEAGAFRES AGAPANRSRR GVSETAPASR RGELAVCDAV
110 120 130 140 150
SGWVTDRRTA VDLRGREVEV LGEVPAAGGS PLRQYFFETR CKADNAEEGG
160 170 180 190 200
PGAGGGGCRG VDRRHWVSEC KAKQSYVRAL TADAQGRVGW RWIRIDTACV
210
CTLLSRTGRA
Length:210
Mass (Da):22,427
Last modified:February 1, 1994 - v1
Checksum:iDBC6A30195E139AD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71C → Y in GLC1O; unknown pathological significance. 1 Publication
VAR_063196
Natural varianti84 – 841E → K in GLC1O; unknown pathological significance. 1 Publication
VAR_063197
Natural varianti88 – 881A → V.2 Publications
VAR_063198
Natural varianti89 – 891S → N.1 Publication
VAR_063199
Natural varianti90 – 901R → C.1 Publication
VAR_063200
Natural varianti90 – 901R → H in GLC1O; unknown pathological significance. 1 Publication
VAR_063201
Natural varianti114 – 1141R → G.1 Publication
VAR_063202
Natural varianti133 – 1331R → H.1 Publication
VAR_063203
Natural varianti140 – 1401R → C.1 Publication
VAR_063204
Natural varianti206 – 2061R → Q in GLC1O; unknown pathological significance. 1 Publication
VAR_063205
Natural varianti206 – 2061R → W in GLC1O; also found in patients with normal pressure glaucoma; unknown pathological significance; impaired ligand-mediated TRKB signaling and reduced neurite outgrowth. 2 Publications
VAR_063206
Natural varianti207 – 2071T → I.1 Publication
VAR_063207
Natural varianti207 – 2071T → S.1 Publication
VAR_063208
Natural varianti209 – 2091R → G in GLC1O; unknown pathological significance. 1 Publication
VAR_063209

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12754.1.
PIRiA42687.
RefSeqiNP_006170.1. NM_006179.4.
XP_005259019.1. XM_005258962.1.
XP_006723295.1. XM_006723232.1.
UniGeneiHs.266902.
Hs.743915.

Genome annotation databases

EnsembliENST00000593537; ENSP00000469455; ENSG00000225950.
GeneIDi4909.
KEGGihsa:4909.
UCSCiuc002pmf.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12754.1.
PIRiA42687.
RefSeqiNP_006170.1. NM_006179.4.
XP_005259019.1. XM_005258962.1.
XP_006723295.1. XM_006723232.1.
UniGeneiHs.266902.
Hs.743915.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1B8MX-ray2.75B81-210[»]
1B98X-ray2.75A/M81-210[»]
1HCFX-ray2.70A/B81-210[»]
ProteinModelPortaliP34130.
SMRiP34130. Positions 85-208.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110964. 4 interactions.
IntActiP34130. 3 interactions.
MINTiMINT-1508589.
STRINGi9606.ENSP00000301411.

Proteomic databases

PaxDbiP34130.
PRIDEiP34130.

Protocols and materials databases

DNASUi4909.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000593537; ENSP00000469455; ENSG00000225950.
GeneIDi4909.
KEGGihsa:4909.
UCSCiuc002pmf.4. human.

Organism-specific databases

CTDi4909.
GeneCardsiGC19M049565.
HGNCiHGNC:8024. NTF4.
MIMi162662. gene.
613100. phenotype.
neXtProtiNX_P34130.
Orphaneti353225. Primary adult open-angle glaucoma.
PharmGKBiPA162398206.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42623.
GeneTreeiENSGT00390000007725.
HOGENOMiHOG000231516.
HOVERGENiHBG006494.
InParanoidiP34130.
KOiK12457.
OMAiSVPMEPH.
PhylomeDBiP34130.
TreeFamiTF106463.

Miscellaneous databases

EvolutionaryTraceiP34130.
GenomeRNAii4909.
NextBioi18893.
PROiP34130.
SOURCEiSearch...

Gene expression databases

BgeeiP34130.
CleanExiHS_NTF4.
ExpressionAtlasiP34130. baseline and differential.
GenevestigatoriP34130.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR020408. Nerve_growth_factor-like.
IPR002072. Nerve_growth_factor-rel.
IPR019846. Nerve_growth_factor_CS.
IPR020432. Neurotrophin-4.
[Graphical view]
PANTHERiPTHR11589. PTHR11589. 1 hit.
PfamiPF00243. NGF. 1 hit.
[Graphical view]
PIRSFiPIRSF001789. NGF. 1 hit.
PRINTSiPR01915. NEUROTROPHN4.
PR00268. NGF.
ProDomiPD002052. Nerve_growth_factor-rel. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00140. NGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00248. NGF_1. 1 hit.
PS50270. NGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1990) [PubMed] [Europe PMC] [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(1991) [PubMed] [Europe PMC] [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 (APR-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 (MAY-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(2003) [PubMed] [Europe PMC] [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(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS).
  7. Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO GLAUCOMA, VARIANTS GLC1O TYR-7; LYS-84; HIS-90; TRP-206; GLN-206 AND GLY-209, VARIANTS VAL-88 AND SER-207, CHARACTERIZATION OF VARIANT GLC1O TRP-206.
  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(2009) [PubMed] [Europe PMC] [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.

Entry informationi

Entry nameiNTF4_HUMAN
AccessioniPrimary (citable) accession number: P34130
Secondary accession number(s): Q6FH56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 1, 2015
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.