Reticulon-4 (RTN4)
The protein contains 1192 amino acids for an estimated molecular weight of 129931 Da.
Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:27619977, PubMed:25612671, PubMed:24262037). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:27619977, PubMed:25612671, PubMed:24262037, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable).', 'Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity).', 'Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modu (updated: Dec. 11, 2019)
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.
- 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 annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Angiogenesis
Apoptotic process
Axonal fasciculation
Blastocyst formation
Cardiac epithelial to mesenchymal transition
Cell adhesion involved in sprouting angiogenesis
Cell migration involved in vasculogenesis
Cellular response to calcium ion
Cellular response to hypoxia
Cellular sphingolipid homeostasis
Central nervous system vasculogenesis
Cerebral cortex radial glia guided migration
Endoplasmic reticulum organization
Endoplasmic reticulum tubular network formation
Endoplasmic reticulum tubular network membrane organization
Endoplasmic reticulum tubular network organization
Leukocyte migration involved in inflammatory response
Negative regulation of amyloid-beta formation
Negative regulation of axon extension
Negative regulation of axonogenesis
Negative regulation of cell growth
Negative regulation of dendrite extension
Negative regulation of formation of growth cone in injured axon
Negative regulation of vasculogenesis
Neurotrophin TRK receptor signaling pathway
Nuclear pore complex assembly
Positive regulation of angiogenesis
Positive regulation of artery morphogenesis
Positive regulation of collateral sprouting of injured axon
Positive regulation of epithelial cell migration
Positive regulation of ERBB3 signaling pathway
Positive regulation of hepatocyte proliferation
Positive regulation of macrophage cytokine production
Positive regulation of macrophage migration
Positive regulation of mammary gland epithelial cell proliferation
Positive regulation of neutrophil migration
Positive regulation of protein kinase B signaling
Positive regulation of protein localization to endoplasmic reticulum
Positive regulation of Rac protein signal transduction
Positive regulation of toll-like receptor 9 signaling pathway
Protein localization to lysosome
Protein stabilization
Regulation of apoptotic process
Regulation of axonogenesis
Regulation of branching morphogenesis of a nerve
Regulation of cell migration
Cellular Component
Axon
Cell junction
Cell projection
Dendritic growth cone
Endoplasmic reticulum
Endoplasmic reticulum membrane
Endoplasmic reticulum tubular network
Endoplasmic reticulum tubular network membrane
Extracellular exosome
Integral component of endoplasmic reticulum membrane
Intracellular anatomical structure
Neuronal cell body
Nuclear envelope
Obsolete cell
Plasma membrane
Postsynaptic density
The reference OMIM entry for this protein is 604475
Reticulon 4; rtn4
Neurite outgrowth inhibitor; nogo nogoa, included
Nogob, included
Nogoc, included
Neurite growth inhibitor 220, included; ni220, included
Ni220/250, included
DESCRIPTION
Adult mammalian axon regeneration is generally successful in the peripheral nervous system but poor in the central nervous system. Inhibition results from physical barriers imposed by glial scars, a lack of neurotrophic factors, and growth-inhibitory molecules associated with myelin, the insulating axon sheath. These molecules include NI35, myelin-associated glycoprotein (159460), and Nogo.CLONING
Spillmann et al. (1998) identified and purified Nogo, a novel myelin-associated neurite growth inhibitory protein, from bovine spinal cord. They referred to Nogo as NI220 in reference to its neurite growth inhibitory activity and molecular weight. As part of the Kazusa DNA Research Institute effort to sequence random high molecular weight human brain-derived cDNAs, Nagase et al. (1998) isolated a 4.1-kb cDNA clone (KIAA0886) encoding a protein of molecular mass 135,000 that matched all 6 of the peptide sequences derived from bovine Nogo. Prinjha et al. (2000) cloned human NOGO cDNAs encoding 3 splice variants. The longest cDNA, designated NOGOA, has an open reading frame of 1,192 amino acids. An intermediate-length splice variant, designated NOGOB, lacks residues 186 to 1004, in the putative extracellular domain. The shortest splice variant, NOGOC, had been described as rat vp20 and foocen-s. NOGOC also lacks residues 186 to 1004 and has a smaller, alternative N-terminal domain. The N-terminal region of NOGO showed no significant homology to any known protein, whereas the C-terminal region was found to share significant homology with neuroendocrine-specific proteins and other members of the reticulon gene family. Prinjha et al. (2000) suggested that NOGO may be a membrane-associated protein consisting of a putative large extracellular domain of 1,024 residues with 7 predicted N-linked glycosylation sites, 2 or 3 transmembrane domains, and a short C-terminal region of 43 residues. Prinjha et al. (2000) developed a soluble version of NOGOA with a relative molecular mass of 220 kD and found it to be a dose-dependent inhibitor of nerve growth. GrandPre et al. (2000) independently identified NOGO as a member of the reticulon family and designated it reticulon-4A. NOGO is expressed by oligodendrocytes but not by Schwann cells, and associates primarily with the endoplasmic reticulum (ER). A 66-residue luminal/extracellular domain inhibits axonal extension and collapses dorsal root ganglion growth cones. In contrast to NOGO, neither reticulon-1 (600865) nor reticulon-3 (604249) are expressed by oligodendrocytes, and the luminal/extracellular domains from reticulon-1, -2 (603183), and -3 do not inhibit axonal regeneration. GrandPre et al. (2000) suggested that their data provided a molecular basis to assess the contribution of NOGO to the failure of axonal regeneration in the adult central nervous system. Chen et al. (2000) cloned the rat Nogo cDNA and found 3 isoforms within that species. Antibodies against rat NOGOA were found to stain central nervous system myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on central nervous system myelin and into optic nerve explants. Chen et al. (2000) concluded that NOGOA is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and suggested that their data may allow the generation of new reagents to enhance central nervous system regeneration and plasticity.GENE FUNCTION
The IN-1 antibody recognizes NI35 and ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604475 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed