Reticulon 4

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; OMA:RTN4 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	55,112,621 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	29,694,331 bp
RNA expression pattern
	Top expressed in
	Pons; ; parietal lobe; ; postcentral gyrus; ; superior vestibular nucleus; ; subthalamic nucleus; ; lateral nuclear group of thalamus; ; orbitofrontal cortex; ; pars compacta; ; pars reticulata; ; inferior ganglion of vagus nerve;
	Top expressed in
	dorsal striatum; ; pontine nuclei; ; habenula; ; cingulate gyrus; ; lateral geniculate nucleus; ; deep cerebellar nuclei; ; medial dorsal nucleus; ; endothelial cell of lymphatic vessel; ; Epithelium of choroid plexus; ; olfactory tubercle;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	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 anatomical structure; endoplasmic reticulum; endoplasmic reticulum membrane; plasma membrane; extracellular exosome; postsynaptic density; endoplasmic reticulum tubular network; soma; 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
	57142
	68585
	ENSG00000115310
	ENSMUSG00000020458
	Q9NQC3
	Q99P72
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
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
	Wikidata
View/Edit Human	View/Edit Mouse

Reticulon 4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene 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.

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. 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.

Research suggests that blocking Nogo-A during neuronal damage (from diseases such as multiple sclerosis) will help to protect or restore the damaged neurons. 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. 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. Moreover, vascular leakage, a major complication following stroke, was reduced following anti-Nogo-A antibody treatment.