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Protein

Beta-nerve growth factor

Gene

NGF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • growth factor activity Source: GO_Central
  • metalloendopeptidase inhibitor activity Source: UniProtKB
  • nerve growth factor receptor binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134259-MONOMER.
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

HGNCiHGNC:7808. NGF.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Neuropathy, hereditary sensory and autonomic, 5 (HSAN5)2 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 rs11466112dbSNPEnsembl.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.

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...)Sequence analysis1
Glycosylationi114N-linked (GlcNAc...)Sequence 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.

PTM databases

iPTMnetiP01138.
PhosphoSitePlusiP01138.

Miscellaneous databases

PMAP-CutDBP01138.

Expressioni

Gene expression databases

BgeeiENSG00000134259.
CleanExiHS_NGF.
GenevisibleiP01138. HS.

Organism-specific databases

HPAiCAB010286.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
NGFRP081382EBI-1028250,EBI-1387782
NgfrP071742EBI-1028250,EBI-1038810From a different organism.
NTRK1P046292EBI-1028250,EBI-1028226
SORT1Q995234EBI-1028250,EBI-1057058

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi110869. 6 interactors.
DIPiDIP-5712N.
IntActiP01138. 5 interactors.
MINTiMINT-122414.
STRINGi9606.ENSP00000358525.

Chemistry databases

BindingDBiP01138.

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SG1X-ray2.40A/B122-241[»]
1WWWX-ray2.20V/W122-241[»]
2IFGX-ray3.40E/F122-241[»]
4EDWX-ray2.48V122-241[»]
4EDXX-ray2.50V/W122-241[»]
4ZBNX-ray2.45A/B122-241[»]
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.
InterProiIPR029034. 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.
[Graphical view]
PANTHERiPTHR11589. PTHR11589. 1 hit.
PfamiPF00243. NGF. 1 hit.
[Graphical view]
PIRSFiPIRSF001789. NGF. 1 hit.
PRINTSiPR01925. MAMLNGFBETA.
PR00268. NGF.
PR01913. NGFBETA.
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.

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 → V.7 PublicationsCorresponds to variant rs6330dbSNPEnsembl.1
Natural variantiVAR_02555372V → M.Corresponds to variant rs11466110dbSNPEnsembl.1
Natural variantiVAR_02555480R → Q.Corresponds to variant rs11466111dbSNPEnsembl.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 rs11466112dbSNPEnsembl.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. 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.
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

Cross-referencesi

Web resourcesi

Wikipedia

Nerve growth factor entry

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. 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.
CCDSiCCDS882.1.
PIRiA01399. NGHUBM.
RefSeqiNP_002497.2. NM_002506.2.
XP_006710726.1. XM_006710663.3.
UniGeneiHs.2561.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SG1X-ray2.40A/B122-241[»]
1WWWX-ray2.20V/W122-241[»]
2IFGX-ray3.40E/F122-241[»]
4EDWX-ray2.48V122-241[»]
4EDXX-ray2.50V/W122-241[»]
4ZBNX-ray2.45A/B122-241[»]
ProteinModelPortaliP01138.
SMRiP01138.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110869. 6 interactors.
DIPiDIP-5712N.
IntActiP01138. 5 interactors.
MINTiMINT-122414.
STRINGi9606.ENSP00000358525.

Chemistry databases

BindingDBiP01138.
ChEMBLiCHEMBL1649058.
DrugBankiDB01407. Clenbuterol.

PTM databases

iPTMnetiP01138.
PhosphoSitePlusiP01138.

Polymorphism and mutation databases

BioMutaiNGF.

Proteomic databases

PaxDbiP01138.
PeptideAtlasiP01138.
PRIDEiP01138.

Protocols and materials databases

DNASUi4803.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4803.
DisGeNETi4803.
GeneCardsiNGF.
HGNCiHGNC:7808. NGF.
HPAiCAB010286.
MalaCardsiNGF.
MIMi162030. gene.
608654. phenotype.
neXtProtiNX_P01138.
OpenTargetsiENSG00000134259.
Orphaneti64752. Hereditary sensory and autonomic neuropathy type 5.
PharmGKBiPA162397475.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134259-MONOMER.
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.

Miscellaneous databases

EvolutionaryTraceiP01138.
GeneWikiiNerve_growth_factor.
GenomeRNAii4803.
PMAP-CutDBP01138.
PROiP01138.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134259.
CleanExiHS_NGF.
GenevisibleiP01138. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. 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.
[Graphical view]
PANTHERiPTHR11589. PTHR11589. 1 hit.
PfamiPF00243. NGF. 1 hit.
[Graphical view]
PIRSFiPIRSF001789. NGF. 1 hit.
PRINTSiPR01925. MAMLNGFBETA.
PR00268. NGF.
PR01913. NGFBETA.
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...

Entry informationi

Entry nameiNGF_HUMAN
AccessioniPrimary (citable) accession number: P01138
Secondary accession number(s): A1A4E5
, Q6FHA0, Q96P60, Q9P2Q8, Q9UKL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 21, 2006
Last modified: November 2, 2016
This is version 185 of the entry and version 3 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 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

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 one 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.