P01138 (NGF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-nerve growth factor
Short name=Beta-NGF

Gene names

Name:	NGF
Synonyms:	NGFB

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	241 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	Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival.
Subunit structure	Homodimer.
Subcellular location	Secreted.
Involvement in disease	Hereditary sensory and autonomic neuropathy 5 (HSAN5) [MIM:608654]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.18 Ref.19
Sequence similarities	Belongs to the NGF-beta family.
Sequence caution	The sequence AAH32517.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neuropathy
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	Ras protein signal transduction Traceable author statement. Source: Reactome activation of MAPKK activity Traceable author statement. Source: Reactome activation of phospholipase C activity Traceable author statement. Source: Reactome adult locomotory behavior Inferred from electronic annotation. Source: Compara apoptotic signaling pathway Traceable author statement. Source: Reactome inflammatory response Inferred from electronic annotation. Source: Compara memory Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Traceable author statement. Source: Reactome negative regulation of cell cycle Traceable author statement. Source: Reactome negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara nerve growth factor processing Traceable author statement. Source: Reactome neuron projection development Inferred from electronic annotation. Source: Compara neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome peripheral nervous system development Inferred from electronic annotation. Source: Compara phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome positive regulation of axon extension Inferred from electronic annotation. Source: Compara positive regulation of axonogenesis Traceable author statement. Source: Reactome positive regulation of gene expression Inferred from mutant phenotype PubMed 16153003. Source: UniProtKB positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of neurotrophin TRK receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of protein autophosphorylation Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of stem cell proliferation Inferred from electronic annotation. Source: Compara regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to electrical stimulus Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to ozone Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara response to radiation Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome endosome Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	receptor signaling protein activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Propeptide

19 – 121

103

PRO_0000019599

Chain

122 – 241

120

Beta-nerve growth factor

PRO_0000019600

Amino acid modifications

Glycosylation

69

1

N-linked (GlcNAc...) Potential

Glycosylation

114

1

N-linked (GlcNAc...) Potential

Disulfide bond

136 ↔ 201

Ref.14

Disulfide bond

179 ↔ 229

Ref.14

Disulfide bond

189 ↔ 231

Ref.14

Natural variations

Natural variant

35

1

A → V. Ref.1 Ref.2 Ref.3 Ref.5 Ref.10 Ref.11 Ref.15
Corresponds to variant rs6330 [ dbSNP | Ensembl ].

VAR_013783

Natural variant

72

1

V → M.
Corresponds to variant rs11466110 [ dbSNP | Ensembl ].

VAR_025553

Natural variant

80

1

R → Q.
Corresponds to variant rs11466111 [ dbSNP | Ensembl ].

VAR_025554

Natural variant

162

1

E → EGE in HSAN5; uncertain pathological significance.

VAR_068478

Natural variant

187

1

S → N Found in a patient with congenital insensitivity to pain; uncertain pathological significance. Ref.19

VAR_068479

Natural variant

221

1

R → W in HSAN5; the mutant protein is unable to activate the NTRK1 receptor; may act as a hypomorphic allele. Ref.17 Ref.18
Corresponds to variant rs11466112 [ dbSNP | Ensembl ].

VAR_030659

Experimental info

Sequence conflict

164

1

N → S in AAL05874. Ref.6

Sequence conflict

230

1

V → M in AAL05874. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

241

Helix Strand Turn

Details...

Helix

127 – 130

4

Beta strand

133 – 136

4

Beta strand

138 – 143

6

Beta strand

148 – 151

4

Beta strand

156 – 159

4

Beta strand

161 – 171

11

Beta strand

174 – 179

6

Beta strand

190 – 192

3

Turn

194 – 196

3

Beta strand

197 – 213

17

Beta strand

215 – 235

21

Sequences

	Sequence		Length	Mass (Da)
	P01138 [UniParc]. Last modified March 21, 2006. Version 3. Checksum: 619DFC65EB3BD671	FASTA	241	26,959
	10 20 30 40 50 60 MSMLFYTLIT AFLIGIQAEP HSESNVPAGH TIPQAHWTKL QHSLDTALRR ARSAPAAAIA 70 80 90 100 110 120 ARVAGQTRNI TVDPRLFKKR RLRSPRVLFS TQPPREAADT QDLDFEVGGA APFNRTHRSK 130 140 150 160 170 180 RSSSHPIFHR GEFSVCDSVS VWVGDKTTAT DIKGKEVMVL GEVNINNSVF KQYFFETKCR 190 200 210 220 230 240 DPNPVDSGCR GIDSKHWNSY CTTTHTFVKA LTMDGKQAAW RFIRIDTACV CVLSRKAVRR A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human beta-nerve growth factor gene sequence highly homologous to that of mouse." Ullrich A., Gray A., Berman C., Dull T.J. Nature 303:821-825(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-35.
[2]	"Sequence homology of human and mouse beta-NGF subunit genes." Ullrich A., Gray A., Berman C., Coussens L., Dull T.J. Cold Spring Harb. Symp. Quant. Biol. 48:435-442(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-35.
[3]	"cDNA sequence of human beta-NGF." Borsani G., Pizzuti A., Rugarli E.I., Falini A., Silani V., Sidoli A., Scarlato G., Barelle F.E. Nucleic Acids Res. 18:4020-4020(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-35. Tissue: Brain.
[4]	"Cloning and sequencing of the gene for premature beta nerve growth factor." Tong Y., Wang H., Chen W. Zhongguo Ying Yong Sheng Li Xue Za Zhi 13:316-318(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Human-specific amino acid changes found in 103 protein-coding genes." Kitano T., Liu Y.-H., Ueda S., Saitou N. Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-35.
[6]	Zhang Y., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"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].
[8]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-35.
[11]	"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], VARIANT VAL-35. Tissue: Eye.
[12]	"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 [MRNA] OF 178-219. Tissue: Leukocyte.
[13]	"The trk proto-oncogene encodes a receptor for nerve growth factor." Klein R., Jing S., Nanduri V., O'Rourke E., Barbacid M. Cell 65:189-197(1991) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF NTRK1 AS THE HIGH AFFINITY NGF RECEPTOR.
[14]	"Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor." Wiesmann C., Ultsch M.H., Bass S.H., de Vos A.M. Nature 401:184-188(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 122-241, DISULFIDE BONDS.
[15]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VAL-35.
[16]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[17]	"A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception." Einarsdottir E., Carlsson A., Minde J., Toolanen G., Svensson O., Solders G., Holmgren G., Holmberg D., Holmberg M. Hum. Mol. Genet. 13:799-805(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HSAN5 TRP-221.
[18]	"A novel NGF mutation clarifies the molecular mechanism and extends the phenotypic spectrum of the HSAN5 neuropathy." Carvalho O.P., Thornton G.K., Hertecant J., Houlden H., Nicholas A.K., Cox J.J., Rielly M., Al-Gazali L., Woods C.G. J. Med. Genet. 48:131-135(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT HSAN5 TRP-221.
[19]	"Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort." Davidson G.L., Murphy S.M., Polke J.M., Laura M., Salih M.A., Muntoni F., Blake J., Brandner S., Davies N., Horvath R., Price S., Donaghy M., Roberts M., Foulds N., Ramdharry G., Soler D., Lunn M.P., Manji H. , Davis M.B., Houlden H., Reilly M.M. J. Neurol. 259:1673-1685(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HSAN5 GLY-GLU-162 INS, VARIANT ASN-187.
+	Additional computationally mapped references.

Web resources

Wikipedia

Nerve growth factor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01511 Genomic DNA. Translation: CAA24755.1.
M21062 Genomic DNA. Translation: AAA59931.1.
AF150960 Genomic DNA. Translation: AAD55975.1.
AB037517 Genomic DNA. Translation: BAA90437.1.
AF411526 mRNA. Translation: AAL05874.1.
CR541855 mRNA. Translation: CAG46653.1.
BT019733 mRNA. Translation: AAV38538.1.
AL049825 Genomic DNA. Translation: CAB75625.1.
CH471122 Genomic DNA. Translation: EAW56629.1.
BC032517 mRNA. Translation: AAH32517.2. Different initiation.
BC126148 mRNA. Translation: AAI26149.1.
BC126150 mRNA. Translation: AAI26151.1.
X52599 mRNA. Translation: CAA36832.1.

IPI

IPI00000076.

PIR

NGHUBM. A01399.

RefSeq

NP_002497.2. NM_002506.2.

UniGene

Hs.2561.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SG1	X-ray	2.40	A/B	122-241	[»]
1WWW	X-ray	2.20	V/W	122-241	[»]
2IFG	X-ray	3.40	E/F	122-241	[»]

ProteinModelPortal

P01138.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5712N.

IntAct

P01138. 2 interactions.

MINT

MINT-122414.

STRING

9606.ENSP00000358525.

PTM databases

PhosphoSite

P01138.

Polymorphism databases

DMDM

90110037.

Proteomic databases

PaxDb

P01138.

PRIDE

P01138.

Protocols and materials databases

DNASU

4803.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369512; ENSP00000358525; ENSG00000134259.

GeneID

4803.

KEGG

hsa:4803.

UCSC

uc001efu.1. human.

Organism-specific databases

CTD

4803.

GeneCards

GC01M115828.

HGNC

HGNC:7808. NGF.

MIM

162030. gene.
608654. phenotype.

neXtProt

NX_P01138.

Orphanet

64752. Hereditary sensory and autonomic neuropathy type 5.

PharmGKB

PA162397475.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44820.

HOGENOM

HOG000231516.

HOVERGEN

HBG006494.

InParanoid

P01138.

KO

K02582.

OMA

IFHRGEF.

OrthoDB

EOG4BRWMZ.

PhylomeDB

P01138.

Enzyme and pathway databases

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
p75ntrpathway. p75(NTR)-mediated signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_111102. Signal Transduction.

SignaLink

P01138.

Gene expression databases

Bgee

P01138.

CleanEx

HS_NGF.

Genevestigator

P01138.

GermOnline

ENSG00000134259. Homo sapiens.

Family and domain databases

InterPro

IPR020408. Nerve_growth_factor-like.
IPR002072. Nerve_growth_factor-rel.
IPR020425. Nerve_growth_factor_bsu.
IPR020437. Nerve_growth_factor_bsu_mml.
IPR019846. Nerve_growth_factor_CS.
[Graphical view]

PANTHER

PTHR11589. PTHR11589. 1 hit.

Pfam

PF00243. NGF. 1 hit.
[Graphical view]

PIRSF

PIRSF001789. NGF. 1 hit.

PRINTS

PR01925. MAMLNGFBETA.
PR00268. NGF.
PR01913. NGFBETA.

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

ChEMBL

CHEMBL1649058.

DrugBank

DB01407. Clenbuterol.

EvolutionaryTrace

P01138.

GenomeRNAi

4803.

NextBio

18514.

PMAP-CutDB

P01138.

SOURCE

Search...

Entry information

Entry name

NGF_HUMAN

Accession

Primary (citable) accession number: P01138
Secondary accession number(s): A1A4E5 , Q6FHA0, Q96P60, Q9P2Q8, Q9UKL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 21, 2006
Last modified:	May 29, 2013
This is version 150 of the entry and version 3 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.