P20783 (NTF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurotrophin-3
Short name=NT-3

Alternative name(s):
HDNF
Nerve growth factor 2
Short name=NGF-2
Neurotrophic factor

Gene names

Name:

NTF3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	257 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	Seems to promote the survival of visceral and proprioceptive sensory neurons.
Subcellular location	Secreted.
Tissue specificity	Brain and peripheral tissues.
Polymorphism	Variant Glu-76 (frequently reported as Glu-63) was thought to be associated with severe forms of schizophrenia. This does not seem to be the case.
Sequence similarities	Belongs to the NGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
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	activation of MAPK activity Inferred from direct assay PubMed 23027130. Source: BHF-UCL activation of Ras GTPase activity Inferred from direct assay PubMed 23027130. Source: BHF-UCL activation of protein kinase B activity Inferred from direct assay PubMed 23027130. Source: BHF-UCL axon guidance Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement Ref.3. Source: ProtInc enteric nervous system development Inferred from electronic annotation. Source: Compara epidermis development Inferred from electronic annotation. Source: Compara glial cell fate determination Inferred from electronic annotation. Source: Compara induction of positive chemotaxis Inferred from direct assay PubMed 23027130. Source: BHF-UCL mechanoreceptor differentiation Inferred from electronic annotation. Source: Compara myelination Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 23027130. Source: BHF-UCL nerve development Inferred from electronic annotation. Source: Compara nervous system development Traceable author statement PubMed 1542658. Source: ProtInc neuromuscular synaptic transmission Inferred from electronic annotation. Source: Compara peripheral nervous system development Inferred from electronic annotation. Source: Compara positive regulation of actin cytoskeleton reorganization Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of cell migration Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of cell proliferation Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of glial cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of receptor internalization Inferred from direct assay PubMed 23027130. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of synaptic transmission Inferred from electronic annotation. Source: Compara smooth muscle cell differentiation Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase signaling pathway Inferred from direct assay PubMed 23027130. Source: BHF-UCL
Cellular_component	cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	chemoattractant activity Inferred from direct assay PubMed 23027130. Source: BHF-UCL growth factor activity Inferred from direct assay PubMed 23027130. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BDNF	P23560	1	EBI-1025994,EBI-1026003

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P20783-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P20783-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MVTFATILQVNKVM

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Propeptide

19 – 138

120

PRO_0000019659

Chain

139 – 257

119

Neurotrophin-3

PRO_0000019660

Amino acid modifications

Glycosylation

131

1

N-linked (GlcNAc...) Potential

Disulfide bond

152 ↔ 217

Disulfide bond

195 ↔ 246

Disulfide bond

205 ↔ 248

Natural variations

Alternative sequence

1

1

M → MVTFATILQVNKVM in isoform 2.

VSP_043353

Natural variant

76

1

G → E. Ref.11 Ref.12
Corresponds to variant rs1805149 [ dbSNP | Ensembl ].

VAR_012084

Secondary structure

1

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257

Helix Strand Turn

Details...

Beta strand

148 – 152

5

Beta strand

154 – 159

6

Beta strand

164 – 167

4

Beta strand

172 – 175

4

Beta strand

177 – 179

3

Turn

181 – 183

3

Beta strand

190 – 195

6

Beta strand

200 – 205

6

Turn

210 – 212

3

Beta strand

216 – 233

18

Beta strand

236 – 249

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 39A5BB3B28E25E03	FASTA	257	29,355
	10 20 30 40 50 60 MSILFYVIFL AYLRGIQGNN MDQRSLPEDS LNSLIIKLIQ ADILKNKLSK QMVDVKENYQ 70 80 90 100 110 120 STLPKAEAPR EPERGGPAKS AFQPVIAMDT ELLRQQRRYN SPRVLLSDST PLEPPPLYLM 130 140 150 160 170 180 EDYVGSPVVA NRTSRRKRYA EHKSHRGEYS VCDSESLWVT DKSSAIDIRG HQVTVLGEIK 190 200 210 220 230 240 TGNSPVKQYF YETRCKEARP VKNGCRGIDD KHWNSQCKTS QTYVRALTSE NNKLVGWRWI 250 RIDTSCVCAL SRKIGRT
	Isoform 2 [UniParc]. Checksum: 43B3342B32424E97	FASTA	270	30,800
	10 20 30 40 50 60 MVTFATILQV NKVMSILFYV IFLAYLRGIQ GNNMDQRSLP EDSLNSLIIK LIQADILKNK 70 80 90 100 110 120 LSKQMVDVKE NYQSTLPKAE APREPERGGP AKSAFQPVIA MDTELLRQQR RYNSPRVLLS 130 140 150 160 170 180 DSTPLEPPPL YLMEDYVGSP VVANRTSRRK RYAEHKSHRG EYSVCDSESL WVTDKSSAID 190 200 210 220 230 240 IRGHQVTVLG EIKTGNSPVK QYFYETRCKE ARPVKNGCRG IDDKHWNSQC KTSQTYVRAL 250 260 270 TSENNKLVGW RWIRIDTSCV CALSRKIGRT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a cDNA encoding a novel human neurotrophic factor." Kaisho Y., Yoshimura K., Nakahama K. FEBS Lett. 266:187-191(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Primary structure and biological activity of a novel human neurotrophic factor." Rosenthal A., Goeddel D.V., Nguyen T., Lewis M., Shih A., Laramee G.R., Nikolics K., Winslow J.W. Neuron 4:767-773(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]	"Molecular cloning of a human gene that is a member of the nerve growth factor family." Jones K.R., Reichardt L.F. Proc. Natl. Acad. Sci. U.S.A. 87:8060-8064(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations." Maisonpierre P.C., le Beau M.M., Espinosa R. III, Ip N.Y., Belluscio L., de la Monte S.M., Squinto S., Furth M.E., Yancopoulos G.D. Genomics 10:558-568(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cerebellum.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]	"Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary." Hallboeoek F., Ibanez C.F., Persson H. Neuron 6:845-858(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 194-236. Tissue: Leukocyte.
[10]	"Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer." Robinson R.C., Radziejewski C., Stuart D.I., Jones E.Y. Biochemistry 34:4139-4146(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[11]	"Association of neurotrophin-3 gene variant with severe forms of schizophrenia." Hattori M., Nanko S. Biochem. Biophys. Res. Commun. 209:513-518(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLU-76.
[12]	"Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia." Arinami T., Takekoshi K., Itokawa M., Hamaguchi H., Toru M. Psychiatr. Genet. 6:13-15(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLU-76.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53655 mRNA. Translation: CAA37703.1.
M37763 Genomic DNA. Translation: AAA59953.1.
M61180 Genomic DNA. Translation: AAA63231.1.
AK293895 mRNA. Translation: BAH11621.1.
CR541906 mRNA. Translation: CAG46704.1.
CH471116 Genomic DNA. Translation: EAW88824.1.
CH471116 Genomic DNA. Translation: EAW88825.1.
BC069773 mRNA. Translation: AAH69773.1.
BC107075 mRNA. Translation: AAI07076.1.

IPI

IPI00025474.
IPI00793439.

PIR

C40304. A36208.

RefSeq

NP_001096124.1. NM_001102654.1.
NP_002518.1. NM_002527.4.

UniGene

Hs.99171.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B8K	X-ray	2.15	A	139-257	[»]
1BND	X-ray	2.30	B	139-257	[»]
1NT3	X-ray	2.40	A	139-257	[»]
3BUK	X-ray	2.60	A/B	139-257	[»]

ProteinModelPortal

P20783.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-346N.

IntAct

P20783. 1 interaction.

STRING

9606.ENSP00000397297.

PTM databases

PhosphoSite

P20783.

Polymorphism databases

DMDM

128581.

Proteomic databases

PaxDb

P20783.

PRIDE

P20783.

Protocols and materials databases

DNASU

4908.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331010; ENSP00000328738; ENSG00000185652.
ENST00000423158; ENSP00000397297; ENSG00000185652.

GeneID

4908.

KEGG

hsa:4908.

UCSC

uc001qnl.4. human.

Organism-specific databases

CTD

4908.

GeneCards

GC12P005541.

HGNC

HGNC:8023. NTF3.

HPA

HPA032000.

MIM

162660. gene.

neXtProt

NX_P20783.

PharmGKB

PA31806.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39844.

HOGENOM

HOG000231516.

HOVERGEN

HBG006494.

InParanoid

P20783.

KO

K04356.

OMA

YAEHKSH.

OrthoDB

EOG46HGBB.

PhylomeDB

P20783.

Enzyme and pathway databases

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Gene expression databases

Bgee

P20783.

CleanEx

HS_NTF3.

Genevestigator

P20783.

GermOnline

ENSG00000185652. Homo sapiens.

Family and domain databases

InterPro

IPR020408. Nerve_growth_factor-like.
IPR002072. Nerve_growth_factor-rel.
IPR019846. Nerve_growth_factor_CS.
IPR015578. Neurotrophin-3.
[Graphical view]

PANTHER

PTHR11589. PTHR11589. 1 hit.
PTHR11589:SF4. PTHR11589:SF4. 1 hit.

Pfam

PF00243. NGF. 1 hit.
[Graphical view]

PIRSF

PIRSF001789. NGF. 1 hit.

PRINTS

PR01914. NEUROTROPHN3.
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

EvolutionaryTrace

P20783.

GenomeRNAi

4908.

NextBio

18887.

PMAP-CutDB

P20783.

SOURCE

Search...

Entry information

Entry name

NTF3_HUMAN

Accession

Primary (citable) accession number: P20783
Secondary accession number(s): B7Z1T5, Q6FH50

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 138 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.