NGF

Protein identityUniProt · HPA

UniProt accession

P01138

Gene

NGF

Ensembl

ENSG00000134259

Chromosome

1

Canonical length

241 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins, RAS pathway related proteins

Secretome location

Secreted in other tissues

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

241 residues, UniProt reviewed canonical sequence.

>P01138|NGF
     1  MSMLFYTLIT AFLIGIQAEP HSESNVPAGH TIPQAHWTKL QHSLDTALRR ARSAPAAAIA
    61  ARVAGQTRNI TVDPRLFKKR RLRSPRVLFS TQPPREAADT QDLDFEVGGA APFNRTHRSK
   121  RSSSHPIFHR GEFSVCDSVS VWVGDKTTAT DIKGKEVMVL GEVNINNSVF KQYFFETKCR
   181  DPNPVDSGCR GIDSKHWNSY CTTTHTFVKA LTMDGKQAAW RFIRIDTACV CVLSRKAVRR
   241  A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NGF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

22 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NGF.

Disease | AllUniProt

Conditions NGF is implicated in, by any mechanism.

• Neuropathy, hereditary sensory and autonomic, 5 (HSAN5) MIM:608654

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 194 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital sensory neuropathy with selective loss of small myelinated fibers
• Peripheral neuropathy

Disease | AutoantibodyPubMed

Conditions in which antibodies against NGF are reported. Each links to that disease's full target list.

• Alzheimer Disease 3

ReferencesPubMed · IEDB

Publications for NGF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.53

gnomAD pLI

0.82

gnomAD missense Z

0.9

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon extension
• cell surface receptor protein tyrosine kinase signaling pathway
• circadian rhythm
• extrinsic apoptotic signaling pathway in absence of ligand
• extrinsic apoptotic signaling pathway via death domain receptors
• modulation of chemical synaptic transmission
• negative regulation of cell population proliferation
• negative regulation of neuron apoptotic process
• nerve development
• nerve growth factor signaling pathway
• neuron apoptotic process
• neuron projection morphogenesis
• neurotrophin TRK receptor signaling pathway
• peripheral nervous system development
• positive regulation of axon extension
• positive regulation of collateral sprouting
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of gene expression
• positive regulation of neuron differentiation
• positive regulation of neuron maturation
• positive regulation of neuron projection development
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of protein ubiquitination
• positive regulation of Ras protein signal transduction
• regulation of neurotransmitter secretion
• regulation of release of sequestered calcium ion into cytosol
• sensory perception of pain

Molecular functions

• growth factor activity
• lipid binding
• metalloendopeptidase inhibitor activity
• nerve growth factor receptor binding
• transmembrane receptor protein tyrosine kinase activator activity

Cellular components

• axon
• cytosol
• dendrite
• endosome lumen
• extracellular region
• extracellular space
• Golgi lumen
• synaptic vesicle

Protein domainsUniProt · Pfam · InterPro

• Nerve growth factor-related
• Nerve growth factor conserved site
• Nerve growth factor-like
• Cystine-knot cytokine
• Nerve growth factor family
• Nerve growth factor, beta subunit
• Nerve growth factor, beta subunit, mammalian

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• Endosome
• Glycoprotein
• Growth factor
• Lipid-binding
• Metalloenzyme inhibitor
• Metalloprotease inhibitor
• Neurodegeneration
• Neuropathy
• Protease inhibitor
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of NGF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ADAM10
• SORCS3
• NGFR
• NTRK1
• SORT1