UniProtKB - P01138 (NGF_HUMAN)
Beta-nerve growth factor
NGF
Functioni
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020).
Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:20978020) (Probable).
The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (By similarity).
Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (PubMed:20164177).
Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (By similarity).
By similarity2 Publications3 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 173 | a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol); via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 209 | a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol); shared with dimeric partnerBy similarity | 1 | |
Binding sitei | 209 | a 1-acyl-sn-glycero-3-phospho-L-serine; shared with dimeric partnerBy similarity | 1 |
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
- lipid binding Source: UniProtKB-KW
- metalloendopeptidase inhibitor activity Source: UniProtKB
- nerve growth factor receptor binding Source: BHF-UCL
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
- extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
- memory Source: GO_Central
- modulation of chemical synaptic transmission Source: GO_Central
- negative regulation of cell population proliferation Source: ARUK-UCL
- negative regulation of neuron apoptotic process Source: GO_Central
- nerve development Source: GO_Central
- nerve growth factor signaling pathway Source: GO_Central
- neuron apoptotic process Source: ARUK-UCL
- neuron projection morphogenesis Source: MGI
- peripheral nervous system development Source: GO_Central
- positive regulation of collateral sprouting Source: GO_Central
- positive regulation of DNA binding Source: ARUK-UCL
- positive regulation of gene expression Source: UniProtKB
- positive regulation of neuron differentiation Source: ARUK-UCL
- positive regulation of peptidyl-serine phosphorylation Source: GO_Central
- positive regulation of Ras protein signal transduction Source: ParkinsonsUK-UCL
- regulation of neuron differentiation Source: GO_Central
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor |
Ligand | Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | P01138 |
Reactomei | R-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 |
SignaLinki | P01138 |
SIGNORi | P01138 |
Names & Taxonomyi
Protein namesi | Recommended name: Beta-nerve growth factor1 PublicationShort name: Beta-NGF1 Publication |
Gene namesi | Name:NGF Synonyms:NGFB |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7808, NGF |
MIMi | 162030, gene |
neXtProti | NX_P01138 |
VEuPathDBi | HostDB:ENSG00000134259 |
Subcellular locationi
Endosome
- Endosome lumen By similarity
Extracellular region or secreted
- Secreted 1 Publication
Note: ProNGF is endocytosed after binding to the cell surface receptor formed by SORT1 and NGFR.By similarity
Cytosol
- cytosol Source: Reactome
Endosome
- endosome lumen Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Golgi apparatus
- Golgi lumen Source: Reactome
Other locations
- axon Source: GO_Central
- dendrite Source: GO_Central
- synaptic vesicle Source: GO_Central
Keywords - Cellular componenti
Endosome, SecretedPathology & Biotechi
Involvement in diseasei
Neuropathy, hereditary sensory and autonomic, 5 (HSAN5)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_068478 | 162 | E → EGE in HSAN5; uncertain pathological significance. 1 Publication | 1 | |
Natural variantiVAR_030659 | 221 | R → W in HSAN5; impaired processing of the precursor to mature NGF; nearly abolishes secretion; loss of function in stimulating cell differentiation; loss of the ability to activate the NTRK1 receptor. 2 PublicationsCorresponds to variant dbSNP:rs11466112EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Neurodegeneration, NeuropathyOrganism-specific databases
DisGeNETi | 4803 |
GeneReviewsi | NGF |
MalaCardsi | NGF |
MIMi | 608654, phenotype |
OpenTargetsi | ENSG00000134259 |
Orphaneti | 64752, Hereditary sensory and autonomic neuropathy type 5 |
PharmGKBi | PA162397475 |
Miscellaneous databases
Pharosi | P01138, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1649058 |
DrugBanki | DB01407, Clenbuterol DB12157, Fasinumab DB09221, Polaprezinc DB05892, RI 624 |
Genetic variation databases
BioMutai | NGF |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
PropeptideiPRO_0000019599 | 19 – 121 | Add BLAST | 103 | |
ChainiPRO_0000019600 | 122 – 241 | Beta-nerve growth factorAdd BLAST | 120 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 69 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 114 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 136 ↔ 201 | Combined sources1 Publication | ||
Disulfide bondi | 179 ↔ 229 | Combined sources1 Publication | ||
Disulfide bondi | 189 ↔ 231 | Combined sources1 Publication |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, GlycoproteinProteomic databases
PaxDbi | P01138 |
PeptideAtlasi | P01138 |
PRIDEi | P01138 |
ProteomicsDBi | 51338 |
PTM databases
GlyGeni | P01138, 2 sites |
iPTMneti | P01138 |
PhosphoSitePlusi | P01138 |
Expressioni
Gene expression databases
Bgeei | ENSG00000134259, Expressed in cartilage tissue and 121 other tissues |
Genevisiblei | P01138, HS |
Organism-specific databases
HPAi | ENSG00000134259, Tissue enhanced (heart muscle, ovary) |
Interactioni
Subunit structurei
Homodimer (PubMed:10490030, PubMed:15131306, PubMed:17196528). The homodimer interacts with a single NTRK1 chain (PubMed:10490030, PubMed:17196528). The homodimer interacts with a single NGFR chain (PubMed:15131306). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (By similarity). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis. Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (By similarity). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF. The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (By similarity).
Interacts with ADAM10 in a divalent cation-dependent manner (PubMed:20164177).
By similarity4 PublicationsBinary interactionsi
P01138
P01138 (PRO_0000019599)
With | #Exp. | IntAct |
---|---|---|
SORT1 [Q99523] | 2 | EBI-9345310,EBI-1057058 |
Beta-nerve growth factor (PRO_0000019600)
With | #Exp. | IntAct |
---|---|---|
NGFR [P08138] | 2 | EBI-9249861,EBI-1387782 |
NTRK1 [P04629] | 2 | EBI-9249861,EBI-1028226 |
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
BioGRIDi | 110869, 9 interactors |
CORUMi | P01138 |
DIPi | DIP-5712N |
IntActi | P01138, 7 interactors |
MINTi | P01138 |
STRINGi | 9606.ENSP00000358525 |
Chemistry databases
BindingDBi | P01138 |
Miscellaneous databases
RNActi | P01138, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P01138 |
SASBDBi | P01138 |
SMRi | P01138 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01138 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502RYPU, Eukaryota |
GeneTreei | ENSGT00390000007725 |
HOGENOMi | CLU_059942_1_1_1 |
InParanoidi | P01138 |
OMAi | PLNRTHR |
OrthoDBi | 1156054at2759 |
PhylomeDBi | P01138 |
TreeFami | TF106463 |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11589, PTHR11589, 1 hit |
Pfami | View protein in Pfam PF00243, NGF, 1 hit |
PIRSFi | PIRSF001789, NGF, 1 hit |
PRINTSi | PR01925, MAMLNGFBETA PR00268, NGF PR01913, NGFBETA |
SMARTi | View protein in SMART SM00140, NGF, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00248, NGF_1, 1 hit PS50270, NGF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0TAZ6 | A0A7P0TAZ6_HUMAN | Beta-nerve growth factor | NGF | 84 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 164 | N → S in AAL05874 (Ref. 6) Curated | 1 | |
Sequence conflicti | 230 | V → M in AAL05874 (Ref. 6) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_013783 | 35 | A → V7 PublicationsCorresponds to variant dbSNP:rs6330EnsemblClinVar. | 1 | |
Natural variantiVAR_025553 | 72 | V → M. Corresponds to variant dbSNP:rs11466110EnsemblClinVar. | 1 | |
Natural variantiVAR_025554 | 80 | R → Q. Corresponds to variant dbSNP:rs11466111EnsemblClinVar. | 1 | |
Natural variantiVAR_068478 | 162 | E → EGE in HSAN5; uncertain pathological significance. 1 Publication | 1 | |
Natural variantiVAR_068479 | 187 | S → N Found in a patient with congenital insensitivity to pain; uncertain pathological significance. 1 Publication | 1 | |
Natural variantiVAR_030659 | 221 | R → W in HSAN5; impaired processing of the precursor to mature NGF; nearly abolishes secretion; loss of function in stimulating cell differentiation; loss of the ability 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 |
CCDSi | CCDS882.1 |
PIRi | A01399, NGHUBM |
RefSeqi | NP_002497.2, NM_002506.2 XP_006710726.1, XM_006710663.3 |
Genome annotation databases
Similar proteinsi
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 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 |
CCDSi | CCDS882.1 |
PIRi | A01399, NGHUBM |
RefSeqi | NP_002497.2, NM_002506.2 XP_006710726.1, XM_006710663.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
4EDW | X-ray | 2.48 | V | 122-241 | [»] | |
4EDX | X-ray | 2.50 | V/W | 122-241 | [»] | |
4ZBN | X-ray | 2.45 | A/B | 122-241 | [»] | |
5JZ7 | X-ray | 3.40 | A/B/E/F | 128-237 | [»] | |
6YW8 | NMR | - | A/B | 122-239 | [»] | |
AlphaFoldDBi | P01138 | |||||
SASBDBi | P01138 | |||||
SMRi | P01138 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110869, 9 interactors |
CORUMi | P01138 |
DIPi | DIP-5712N |
IntActi | P01138, 7 interactors |
MINTi | P01138 |
STRINGi | 9606.ENSP00000358525 |
Chemistry databases
BindingDBi | P01138 |
ChEMBLi | CHEMBL1649058 |
DrugBanki | DB01407, Clenbuterol DB12157, Fasinumab DB09221, Polaprezinc DB05892, RI 624 |
PTM databases
GlyGeni | P01138, 2 sites |
iPTMneti | P01138 |
PhosphoSitePlusi | P01138 |
Genetic variation databases
BioMutai | NGF |
Proteomic databases
PaxDbi | P01138 |
PeptideAtlasi | P01138 |
PRIDEi | P01138 |
ProteomicsDBi | 51338 |
Protocols and materials databases
ABCDi | P01138, 72 sequenced antibodies |
Antibodypediai | 20173, 1250 antibodies from 44 providers |
DNASUi | 4803 |
Genome annotation databases
Organism-specific databases
CTDi | 4803 |
DisGeNETi | 4803 |
GeneCardsi | NGF |
GeneReviewsi | NGF |
HGNCi | HGNC:7808, NGF |
HPAi | ENSG00000134259, Tissue enhanced (heart muscle, ovary) |
MalaCardsi | NGF |
MIMi | 162030, gene 608654, phenotype |
neXtProti | NX_P01138 |
OpenTargetsi | ENSG00000134259 |
Orphaneti | 64752, Hereditary sensory and autonomic neuropathy type 5 |
PharmGKBi | PA162397475 |
VEuPathDBi | HostDB:ENSG00000134259 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RYPU, Eukaryota |
GeneTreei | ENSGT00390000007725 |
HOGENOMi | CLU_059942_1_1_1 |
InParanoidi | P01138 |
OMAi | PLNRTHR |
OrthoDBi | 1156054at2759 |
PhylomeDBi | P01138 |
TreeFami | TF106463 |
Enzyme and pathway databases
PathwayCommonsi | P01138 |
Reactomei | R-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 |
SignaLinki | P01138 |
SIGNORi | P01138 |
Miscellaneous databases
BioGRID-ORCSi | 4803, 13 hits in 1070 CRISPR screens |
ChiTaRSi | NGF, human |
EvolutionaryTracei | P01138 |
GeneWikii | Nerve_growth_factor |
GenomeRNAii | 4803 |
Pharosi | P01138, Tchem |
PROi | PR:P01138 |
RNActi | P01138, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134259, Expressed in cartilage tissue and 121 other tissues |
Genevisiblei | P01138, HS |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11589, PTHR11589, 1 hit |
Pfami | View protein in Pfam PF00243, NGF, 1 hit |
PIRSFi | PIRSF001789, NGF, 1 hit |
PRINTSi | PR01925, MAMLNGFBETA PR00268, NGF PR01913, NGFBETA |
SMARTi | View protein in SMART SM00140, NGF, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00248, NGF_1, 1 hit PS50270, NGF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NGF_HUMAN | |
Accessioni | P01138Primary (citable) accession number: P01138 Secondary accession number(s): A1A4E5 Q9UKL8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | March 21, 2006 | |
Last modified: | May 25, 2022 | |
This is version 222 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families