Neudesin (NENF)
The protein contains 172 amino acids for an estimated molecular weight of 18856 Da.
Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival (PubMed:31536960). Promotes cell proliferation and neurogenesis in undifferentiated neural progenitor cells at the embryonic stage and inhibits differentiation of astrocytes (By similarity). Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways (By similarity). Neurotrophic activity is enhanced by binding to heme (By similarity). Acts also as an anorexigenic neurotrophic factor that contributes to energy balance (By similarity). (updated: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Negative regulation of appetite
Negative regulation of neuron death
Positive regulation of MAPK cascade
Cellular Component
Endomembrane system
Endoplasmic reticulum
Extracellular space
Membrane
Mitochondrion
Nucleoplasm
The reference OMIM entry for this protein is 611874
Neuron-derived neurotrophic factor; nenf
Neudesin
Cell immortalization-related protein 2; cir2
CLONING
Using differential display to identify transcripts up-regulated in immortalized cells, Ma et al. (1998) identified a transcript, which they named CIR2, that was 2- to 3-fold elevated in human embryonic kidney cells transformed with SV40. Kimura et al. (2005) identified and cloned cDNA for the same protein in mouse, which they called neudesin. The deduced 171-amino acid secreted protein contains a 24-amino acid signal peptide. Kimura et al. (2005) also cloned the human cDNA for neudesin from brain and found that it encodes a deduced 172-amino acid protein with 90% sequence similarity to the mouse protein. In mice, in situ hybridization showed abundant expression of neudesin in developing brain and spinal cord, and RT-PCR of postnatal tissues demonstrated expression in brain, heart, lung, and kidney. The protein was expressed in neurons but not in glial cells.GENE FUNCTION
Kimura et al. (2006) showed that neudesin was expressed in early development in mouse embryonic cerebral cortex in neural precursor cells. Studies in culture showed that neudesin promoted neuronal differentiation and inhibited differentiation of astrocytes. Kimura et al. (2008) observed that siRNA targeted against neudesin resulted in decreased survival of Neuro2a cells. Kimura et al. (2008) noted that neudesin has a predicted cytochrome b5-like heme/steroid-binding domain, and determined that Fe(III)-protoporphyrin IX is required for its neurotrophic activity. An anti-neudesin antibody detected a 15.6-kD band in media from cultured Neuro2a cells and was used in experiments to confirm that the protein binds heme. Kimura et al. (2008) stated that neudesin was the first extracellular heme-binding protein found to be involved in intercellular signal transduction.MAPPING
Kimura et al. (2005) stated that the NENF gene maps to chromosome 1p33; however, Scott (2008) mapped the gene to 1q32.3 based on an alignment of the NENF sequence (GenBank GENBANK AB126219) with the genomic sequence (build 36.2). ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 611874 was added.
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).