Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
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Growth factor activity, extracellular space, negative regulation of appetite, and positive regulation of MAPK cascade annotations transferred from ortholog data
Automatic assignment of GO terms using logical inference, based on inter-ontology links.
Combined Automated Annotation using Multiple IEA Methods.
Rewiring of the Human Mitochondrial Interactome during Neuronal Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.
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NENF interacts with PINK1 and PARK7/DJ-1 at mitochondria and ER
"PINK1 and DJ-1 immunoprecipitates in whole-cell extract (WCE) as well as in mt, ER, and MAM lysates from ECSCs, DNLCs, and mouse brain"
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NENF is secreted and detected in conditioned medium
"NENF secretion in the conditioned medium and cell lysates immunoblotted (IB) with anti-NENF antibody"
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NENF-PINK1-DJ-1 interaction is vital for neurotrophic activity
"NENF Binding with DJ-1 and PINK1 Is Vital for Neurotrophic Activity in DNLCs"
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NENF promotes neuronal survival in differentiated neuron-like cells
"Model of NENF role with DJ-1 and PINK1 in neurotrophic activity and neuronal survival/death"
Neurotrophic activity of neudesin, a novel extracellular heme-binding protein, is dependent on the binding of heme to its cytochrome b5-like heme/steroid-binding domain.
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Neudesin is the first extracellular heme-binding protein with signal-transducing activity; heme binding to its cytochrome b5-like heme/steroid-binding domain is required for neurotrophic activity.
"Neudesin is a secreted protein with neurotrophic activity in neurons and undifferentiated neural cells. We report here that neudesin is an extracellular heme-binding protein and that its neurotrophic activity is dependent on the binding of heme to its cytochrome b(5)-like heme/steroid-binding domain."
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Activity is enhanced specifically by Fe(III)-protoporphyrin IX.
"The neurotrophic activity of neudesin was enhanced by the binding of Fe(III)-protoporphyrin IX, but neither Fe(II)-protoporphyrin IX nor protoporphyrin IX alone."
Neurotrophic effects of neudesin in the central nervous system.
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Neudesin is a CNS-enriched neurotrophic factor that signals via MAPK and PI3K.
"Neudesin (neuron-derived neurotrophic factor; NENF) was identified as a neurotrophic factor that is involved in neuronal differentiation and survival. It is abundantly expressed in the central nervous system, and its neurotrophic activity is exerted via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways."
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Intracerebroventricular neudesin decreases food intake via hypothalamic melanocortin signaling.
"recombinant neudesin that was administered via an interacerebroventricular cannula decreased food intake and body weight through activation of melanocortin signaling, by increasing the hypothalamic Pomc and Mc4r mRNA expression."
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ERK1/2 phosphorylation by neudesin is inhibited by pertussis toxin, implicating a Gi/Go-coupled receptor.
"pertussis toxin (PTX), a Gi/Go protein inhibitor, significantly inhibits the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 by neudesin"
Deletion of the Neurotrophic Factor neudesin Prevents Diet-induced Obesity by Increased Sympathetic Activity.
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neudesin KO mice are resistant to high-fat diet-induced obesity with increased energy expenditure, sympathetic activity, BAT thermogenesis, and WAT lipolysis.
"We found that neudesin knockout (KO) mice were resistant to high-fat diet-induced obesity and obesity-related metabolic dysfunctions. neudesin KO mice exhibited increased energy expenditure due to increased sympathetic activity, which resulted in increased heat production and fatty acid oxidation in brown adipose tissue and enhanced lipolysis in white adipose tissue."
Neudesin as a unique secreted protein with multi-functional roles in neural functions, energy metabolism, and tumorigenesis.
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Human neudesin is a 172-aa secreted protein with a conserved cytochrome b5-like heme/steroid-binding domain; Tyr-82 and Tyr-88 are essential for heme binding.
"Human Neudesin is a secreted protein of 172 amino acids with a conserved cytochrome 5-like heme/steroid-binding domain of ~100 amino acids"
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Neudesin is neurotrophic on neurons (but not astrocytes), consistent with growth-factor activity acting on receptive cells.
"Neudesin exhibits significant neurotrophic activity in primary cultured neurons, but not mitogenic activity in primary cultured astrocytes, indicating that it is a neurotrophic factor."
The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis.
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GIG47/NENF is overexpressed in multiple tumors; ectopic expression promotes invasiveness and tumorigenicity via MAPK and PI3K pathways.
"involving GIG47 might be mediated by the activation of MAPK and PI3K pathways. These results indicate that GIG47 plays a role in the breast tumorigenesis, thus representing a novel target for the treatment of breast cancer."
Identification of the tumor metastasis-related tumor subgroups overexpressed NENF in triple-negative breast cancer by single-cell transcriptomics.
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NENF is amplified and upregulated in TNBC (88/114, 77.2% in TCGA-TNBC) and promotes invasion/migration through EMT regulation.
"In TCGA-TNBC specimens, NENF was the most significantly amplified candidate gene (88/114, 77.2%)"
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NENF knockdown reduces TNBC cell invasion and migration via EMT.
"cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC"
Deep research on NENF function
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Neudesin is a secreted neurotrophic factor belonging to MAPR family
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Contains cytochrome b5-like heme-binding domain that binds Fe(III)-protoporphyrin IX
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Activates MAPK/ERK and PI3K/AKT pathways via GPCRs
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Negative regulation of appetite through hypothalamic melanocortin signaling
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Suppresses energy expenditure via sympathetic nervous system inhibition
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Overexpressed in multiple cancers
Falcon (Edison) deep research on NENF function
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Neudesin is best annotated as a secreted/extracellular MAPR-family heme-binding signaling protein whose activity depends on heme binding to a cytochrome b5-like heme/steroid-binding domain and which activates MAPK/ERK and PI3K/AKT signaling.
"Neudesin (NENF; UniProt Q9UMX5) is best annotated as a **secreted/extracellular MAPR-family heme-binding signaling protein** whose activity depends on **heme binding** to a **cytochrome b5-like heme/steroid-binding domain** and which activates **MAPK/ERK** and **PI3K/AKT** signaling"
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Strongest experimentally supported physiological roles are neurotrophic/neurogenic functions and regulation of energy expenditure/sympathetic tone; receptor identity remains an open problem.
"Its strongest experimentally supported physiological roles include **neurotrophic/neurogenic functions** and **regulation of energy expenditure/sympathetic tone**"
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NENF is amplified/overexpressed in TNBC and promotes EMT-linked metastasis; no definitive receptor has been identified.
"Despite GPCR-linked pharmacological features (e.g., PTX sensitivity in some contexts), reviews emphasize that **no definitive receptor has been identified**"