Reticulon-3 (RTN3)
The protein contains 1032 amino acids for an estimated molecular weight of 112611 Da.
May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress. In case of enteroviruses infection, RTN3 may be involved in the viral replication or pathogenesis. Induces the formation of endoplasmic reticulum tubules (PubMed:25612671). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11551944 | |
| dbSNP:rs7936660 |
Biological Process
Apoptotic process
Endoplasmic reticulum tubular network formation
Endoplasmic reticulum tubular network organization
Negative regulation of amyloid-beta formation
Vesicle-mediated transport
Viral process
Cellular Component
Endoplasmic reticulum
Endoplasmic reticulum membrane
Extracellular exosome
Extracellular space
Golgi apparatus
Golgi membrane
Integral component of membrane
Plasma membrane
Synapse
Molecular Function
The reference OMIM entry for this protein is 604249
Reticulon 3; rtn3
Neuroendocrine-specific protein-like 2; nspl2
DESCRIPTION
The reticulons are a group of highly conserved genes with preferential expression in neuroendocrine tissues (see, e.g., RTN1; 600865).CLONING
During a subtraction cloning between macula and peripheral retina, Moreira et al. (1999) isolated a novel member of the reticulon gene family, which they designated reticulon-3. The mRNA for RTN3 was approximately 3-fold more abundant in macula than in peripheral retina. The 2,527-bp cDNA encodes a predicted 236-amino acid protein that shows strong sequence similarity with other members of the RTN gene family (see, e.g., 600865). Northern blot analysis showed that RTN3 is widely expressed in human tissues, with highest expression in the brain.GENE STRUCTURE
Moreira et al. (1999) determined that the RTN3 gene contains 7 exons and spans more than 15 kb.MAPPING
By use of somatic cell hybrid and radiation hybrid panels, Moreira et al. (1999) mapped the RTN3 gene to 11q13, between markers D11S4535 and D11S4627. Southern blot analysis identified the presence of at least one pseudogene that was subsequently localized to chromosome 4.GENE FUNCTION
He et al. (2004) found that BACE1 (604252) coimmunoprecipitated with members of the reticulon family of proteins: RTN1, RTN2 (603183), RTN3, and RTN4 (604475). BACE1 colocalized with RTN3 in neurons of human brain gray matter, and with RTN4 in oligodendrocytes in white matter. Overexpression of RTN3 in vitro inhibited BACE1 activity and decreased amyloid precursor protein (APP; 104760) processing. The findings suggested that reticulon proteins are negative modulators of BACE1 activity, and that RTN3 specifically blocks access of BACE1 to APP within neurons. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604249 was added.