Reticulon 4

 Reticulon 4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene^[5][6][7] that has been identified as an inhibitor of neurite outgrowth specific to the central nervous system. During neural development Nogo is expressed mainly by neurons and provides an inhibitory signal for the migration and sprouting of CNS endothelial (tip) cells, thereby restricting blood vessel density.

RTN4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2G31, 2JV5
Identifiers
Aliases	RTN4, ASY, NI220/250, NOGO, NOGO-A, NOGOC, NSP, NSP-CL, Nbla00271, Nbla10545, Nogo-B, Nogo-C, RTN-X, RTN4-A, RTN4-B1, RTN4-B2, RTN4-C, Reticulon 4
External IDs	OMIM: 604475 MGI: 1915835 HomoloGene: 10743 GeneCards: RTN4
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p16.1 Start 54,972,187 bp[1] End 55,112,621 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A3.3 Start 29,692,947 bp[2] End 29,744,331 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • RNA binding • cadherin binding • ubiquitin protein ligase binding Cellular component • integral component of membrane • cell projection • nuclear envelope • membrane • integral component of endoplasmic reticulum membrane • intracellular • endoplasmic reticulum • endoplasmic reticulum membrane • cell membrane • extracellular exosome • GO:0097483, GO:0097481 postsynaptic density • endoplasmic reticulum tubular network • neuronal cell body • endoplasmic reticulum tubular network membrane • cell junction Biological process • nuclear pore complex assembly • regulation of apoptotic process • cerebral cortex radial glia guided migration • regulation of branching morphogenesis of a nerve • cardiac epithelial to mesenchymal transition • negative regulation of axon extension • apoptotic process • negative regulation of axonogenesis • nervous system development • regulation of nervous system development • endoplasmic reticulum tubular network formation • endoplasmic reticulum tubular network organization • regulation of cell migration • negative regulation of cell growth • axonal fasciculation • positive regulation of epithelial cell migration • positive regulation of mammary gland epithelial cell proliferation • protein stabilization • positive regulation of protein kinase B signaling • positive regulation of protein localization to endoplasmic reticulum • positive regulation of ERBB3 signaling pathway • endoplasmic reticulum tubular network membrane organization • blastocyst formation • positive regulation of toll-like receptor 9 signaling pathway • protein localization to lysosome • cellular sphingolipid homeostasis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57142	68585
Ensembl	ENSG00000115310	ENSMUSG00000020458
UniProt	Q9NQC3	Q99P72
RefSeq (mRNA)	NM_007008 NM_020532 NM_153828 NM_207520 NM_207521 NM_001321859 NM_001321860 NM_001321861 NM_001321862 NM_001321863 NM_001321904	NM_024226 NM_194051 NM_194052 NM_194053 NM_194054
RefSeq (protein)	NP_001308788 NP_001308789 NP_001308790 NP_001308791 NP_001308792 NP_001308833 NP_008939 NP_065393 NP_722550 NP_997403 NP_997404	NP_077188 NP_918940 NP_918941 NP_918942 NP_918943
Location (UCSC)	Chr 2: 54.97 – 55.11 Mb	Chr 11: 29.69 – 29.74 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene belongs to the family of reticulon-encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. The product of this gene is a potent neurite outgrowth inhibitor that may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified.^[7] There are three isoforms: Nogo A, B and C. Nogo-A has two known inhibitory domains including amino-Nogo, at the N-terminus and Nogo-66, which makes up the molecules extracellular loop. Both amino-Nogo and Nogo-66 are involved in inhibitory responses, where amino-Nogo is a strong inhibitor of neurite outgrowth, and Nogo-66 is involved in growth cone destruction.^[8]

Research suggests that blocking Nogo-A during neuronal damage (from diseases such as multiple sclerosis) will help to protect or restore the damaged neurons.^[8][9] The investigation into the mechanisms of this protein presents a great potential for the treatment of auto-immune mediated demyelinating diseases and spinal cord injury regeneration. It has also been found to be a key player in the process whereby physical exercise enhances learning and memory processes in the brain.^[10] Nogo-A has also been shown to negatively regulate vascular growth and repair following ischemic stroke. Genetic deletion and antibody-mediated blockage of Nogo-A led to enhanced re-vascularization and functional recovery in an experimental mouse model of stroke.^[11][12][13] Moreover, vascular leakage, a major complication following stroke, was reduced following anti-Nogo-A antidbody treatment.^[14]

InteractionsEdit

Reticulon 4 has been shown to interact with WWP1,^[15] BCL2-like 1^[16] and Bcl-2.^[16]

This article uses material from the Wikipedia article  Metasyntactic variable, which is released under the  Creative Commons Attribution-ShareAlike 3.0 Unported License.