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Protein

Beta-nerve growth factor

Gene

NGF

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

Functioni

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. Inhibits metalloproteinase dependent proteolysis of platelet glycoprotein VI (PubMed:20164177).1 Publication

GO - Molecular functioni

  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: ARUK-UCL
  • death receptor agonist activity Source: ARUK-UCL
  • growth factor activity Source: GO_Central
  • metalloendopeptidase inhibitor activity Source: UniProtKB
  • nerve growth factor receptor binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-167021 PLC-gamma1 signalling
R-HSA-167044 Signalling to RAS
R-HSA-167060 NGF processing
R-HSA-170968 Frs2-mediated activation
R-HSA-170984 ARMS-mediated activation
R-HSA-177504 Retrograde neurotrophin signalling
R-HSA-187042 TRKA activation by NGF
R-HSA-187706 Signalling to p38 via RIT and RIN
R-HSA-193648 NRAGE signals death through JNK
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1
R-HSA-193681 Ceramide signalling
R-HSA-198203 PI3K/AKT activation
R-HSA-198745 Signalling to STAT3
R-HSA-205017 NFG and proNGF binds to p75NTR
R-HSA-205025 NADE modulates death signalling
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-209543 p75NTR recruits signalling complexes
R-HSA-209560 NF-kB is activated and signals survival
R-HSA-209563 Axonal growth stimulation
SignaLinkiP01138
SIGNORiP01138

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-nerve growth factor
Short name:
Beta-NGF
Gene namesi
Name:NGF
Synonyms:NGFB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000134259.3
HGNCiHGNC:7808 NGF
MIMi162030 gene
neXtProtiNX_P01138

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Neuropathy, hereditary sensory and autonomic, 5 (HSAN5)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:608654
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068478162E → EGE in HSAN5; uncertain pathological significance. 1 Publication1
Natural variantiVAR_030659221R → W in HSAN5; the mutant protein is unable to activate the NTRK1 receptor. 2 PublicationsCorresponds to variant dbSNP:rs11466112EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi4803
MalaCardsiNGF
MIMi608654 phenotype
OpenTargetsiENSG00000134259
Orphaneti64752 Hereditary sensory and autonomic neuropathy type 5
PharmGKBiPA162397475

Chemistry databases

ChEMBLiCHEMBL1649058
DrugBankiDB01407 Clenbuterol
DB05892 RI 624

Polymorphism and mutation databases

BioMutaiNGF

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000001959919 – 121Add BLAST103
ChainiPRO_0000019600122 – 241Beta-nerve growth factorAdd BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi69N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi114N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi136 ↔ 2011 Publication
Disulfide bondi179 ↔ 2291 Publication
Disulfide bondi189 ↔ 2311 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP01138
PeptideAtlasiP01138
PRIDEiP01138
ProteomicsDBi51338

PTM databases

iPTMnetiP01138
PhosphoSitePlusiP01138

Miscellaneous databases

PMAP-CutDBiP01138

Expressioni

Gene expression databases

BgeeiENSG00000134259
CleanExiHS_NGF
GenevisibleiP01138 HS

Interactioni

Subunit structurei

Homodimer. Interacts with ADAM10 in a divalent cation-dependent manner.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • death receptor agonist activity Source: ARUK-UCL
  • growth factor activity Source: GO_Central
  • nerve growth factor receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110869, 6 interactors
CORUMiP01138
DIPiDIP-5712N
IntActiP01138, 6 interactors
MINTiP01138
STRINGi9606.ENSP00000358525

Structurei

Secondary structure

1241
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi127 – 130Combined sources4
Beta strandi133 – 136Combined sources4
Beta strandi138 – 143Combined sources6
Beta strandi148 – 151Combined sources4
Beta strandi156 – 159Combined sources4
Beta strandi161 – 171Combined sources11
Beta strandi174 – 179Combined sources6
Beta strandi190 – 192Combined sources3
Turni194 – 196Combined sources3
Beta strandi197 – 213Combined sources17
Beta strandi215 – 235Combined sources21

3D structure databases

ProteinModelPortaliP01138
SMRiP01138
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01138

Family & Domainsi

Sequence similaritiesi

Belongs to the NGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IIPQ Eukaryota
ENOG4111F87 LUCA
GeneTreeiENSGT00390000007725
HOGENOMiHOG000231516
HOVERGENiHBG006494
InParanoidiP01138
KOiK02582
OMAiNNVFKQY
OrthoDBiEOG091G0GHL
PhylomeDBiP01138
TreeFamiTF106463

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
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
PANTHERiPTHR11589 PTHR11589, 1 hit
PfamiView protein in Pfam
PF00243 NGF, 1 hit
PIRSFiPIRSF001789 NGF, 1 hit
PRINTSiPR01925 MAMLNGFBETA
PR00268 NGF
PR01913 NGFBETA
ProDomiView protein in ProDom or Entries sharing at least one domain
PD002052 Nerve_growth_factor-rel, 1 hit
SMARTiView protein in SMART
SM00140 NGF, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00248 NGF_1, 1 hit
PS50270 NGF_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

P01138-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSMLFYTLIT AFLIGIQAEP HSESNVPAGH TIPQAHWTKL QHSLDTALRR
60 70 80 90 100
ARSAPAAAIA ARVAGQTRNI TVDPRLFKKR RLRSPRVLFS TQPPREAADT
110 120 130 140 150
QDLDFEVGGA APFNRTHRSK RSSSHPIFHR GEFSVCDSVS VWVGDKTTAT
160 170 180 190 200
DIKGKEVMVL GEVNINNSVF KQYFFETKCR DPNPVDSGCR GIDSKHWNSY
210 220 230 240
CTTTHTFVKA LTMDGKQAAW RFIRIDTACV CVLSRKAVRR A
Length:241
Mass (Da):26,959
Last modified:March 21, 2006 - v3
Checksum:i619DFC65EB3BD671
GO

Sequence cautioni

The sequence AAH32517 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti164N → S in AAL05874 (Ref. 6) Curated1
Sequence conflicti230V → M in AAL05874 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01378335A → V7 PublicationsCorresponds to variant dbSNP:rs6330EnsemblClinVar.1
Natural variantiVAR_02555372V → M. Corresponds to variant dbSNP:rs11466110EnsemblClinVar.1
Natural variantiVAR_02555480R → Q. Corresponds to variant dbSNP:rs11466111EnsemblClinVar.1
Natural variantiVAR_068478162E → EGE in HSAN5; uncertain pathological significance. 1 Publication1
Natural variantiVAR_068479187S → N Found in a patient with congenital insensitivity to pain; uncertain pathological significance. 1 Publication1
Natural variantiVAR_030659221R → W in HSAN5; the mutant protein is unable to activate the NTRK1 receptor. 2 PublicationsCorresponds to variant dbSNP:rs11466112EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
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
CCDSiCCDS882.1
PIRiA01399 NGHUBM
RefSeqiNP_002497.2, NM_002506.2
XP_006710726.1, XM_006710663.3
UniGeneiHs.2561

Genome annotation databases

EnsembliENST00000369512; ENSP00000358525; ENSG00000134259
GeneIDi4803
KEGGihsa:4803
UCSCiuc001efu.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNGF_HUMAN
AccessioniPrimary (citable) accession number: P01138
Secondary accession number(s): A1A4E5
, Q6FHA0, Q96P60, Q9P2Q8, Q9UKL8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 21, 2006
Last modified: July 18, 2018
This is version 198 of the entry and version 3 of the sequence. See 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 1
    Human chromosome 1: 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

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