Reviewed, UniProtKB/Swiss-Prot P01138 (NGF_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. It stimulates division and differentiation of sympathetic and embryonic sensory neurons.
Subunit structure	Homodimer.
Subcellular location	Secreted.
Involvement in disease	Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:608654]. Hereditary sensory and autonomic neuropathies are characterized by loss of pain sensation in combination with other 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.
Sequence similarities	Belongs to the NGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Growth factor
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome nerve growth factor processing Inferred from Experiment. Source: Reactome transmembrane receptor protein tyrosine kinase signaling pathway Inferred from Experiment. Source: Reactome
Cellular component	Golgi lumen Inferred from Experiment. Source: Reactome endosome Inferred from Experiment. Source: Reactome extracellular region Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW nerve growth factor receptor binding Inferred from physical interaction. Source: UniProtKB
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

Modified residue

84

1

Phosphoserine

Glycosylation

69

1

N-linked (GlcNAc...) Potential

Glycosylation

114

1

N-linked (GlcNAc...) Potential

Disulfide bond

136 ↔ 201

Disulfide bond

179 ↔ 229

Disulfide bond

189 ↔ 231

Natural variations

Natural variant

35

1

A → V: dbSNP rs6330.

VAR_013783

Natural variant

72

1

V → M: dbSNP rs11466110.

VAR_025553

Natural variant

80

1

R → Q: dbSNP rs11466111.

VAR_025554

Natural variant

221

1

R → W in HSAN5. dbSNP rs11466112.

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

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

.

.

.

.

.

241

Helix Strand Turn

Details...

Beta strand

133 – 136

4

Beta strand

138 – 143

6

Beta strand

148 – 151

4

Beta strand

156 – 159

4

Beta strand

161 – 167

7

Beta strand

169 – 171

3

Beta strand

174 – 179

6

Beta strand

190 – 192

3

Turn

194 – 196

3

Beta strand

197 – 212

16

Beta strand

215 – 217

3

Beta strand

219 – 235

17

Sequences

	Sequence		Length	Mass (Da)
	P01138-1 [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: 6688123] [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: 6327169] [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: 2374737] [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: 10322959] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Silver project." Kitano T., Kobayakawa H., Saitou N. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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], VARIANT VAL-35. Tissue: Eye.
[11]	"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: 2025430] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 178-219. Tissue: Leukocyte.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"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: 10490030] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 122-241, DISULFIDE BONDS.
[14]	"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: 10391209] [Abstract] Cited for: VARIANT VAL-35.
[15]	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)
[16]	"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: 14976160] [Abstract] Cited for: VARIANT HSAN5 TRP-221.
+	Additional computationally mapped references.

Web resources

Wikipedia

Nerve growth factor entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC032517 mRNA. Translation: AAH32517.2. Different initiation.
X52599 mRNA. Translation: CAA36832.1.

PIR

NGHUBM. A01399.

RefSeq

NP_002497.2.

UniGene

Hs.2561

3D structure databases

PDBMSD

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5712N.

Genome annotation databases

Ensembl

ENSG00000134259. Homo sapiens. [Contig view]

GeneID

4803.

KEGG

hsa:4803.

Organism-specific databases

H-InvDB

HIX0028607.

HGNC

HGNC:7808. NGF.

MIM

162030. gene.
608654. phenotype.

Orphanet

64752. Neuropathy, sensory and autonomic , hereditary, type 5.

PharmGKB

PA31614.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P01138.

HOVERGEN

P01138.

Enzyme and pathway databases

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

P01138.

CleanEx

HS_NGF.

GermOnline

ENSG00000134259. Homo sapiens.

Family and domain databases

InterPro

IPR002072. NGF.
[Graphical view]

PANTHER

PTHR11589. NGF. 1 hit.

Pfam

PF00243. NGF. 1 hit.
[Graphical view]

PIRSF

PIRSF001789. NGF. 1 hit.

PRINTS

PR00268. NGF.

ProDom

PD002052. NGF. 2 hits.
[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 Resources

DrugBank

DB01407. Clenbuterol.

LinkHub

P01138.

NextBio

18514.

SOURCE

Search...

Entry information

Entry name

NGF_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 21, 2006
Last modified:	November 25, 2008
This is version 103 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)