Nogo Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules. They regulate membrane morphogenesis in the ER by promoting tubular ER production. They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins. However each isoform have specific functions mainly depending on their tissue expression specificities. Isoform A: 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. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. 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. Isoform B: Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation. Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation. Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. With isoform C, inhibits BACE1 activity and amyloid precursor protein processing. Isoform C: Regulates cardiomyocyte apoptosis upon hypoxic conditions. With isoform B, inhibits BACE1 activity and amyloid precursor protein processing. Isoform A: is specifically expressed in brain and testis and weakly in heart and skeletal muscle. Isoform B: widely expressed except for the liver. Highly expressed in endothelial cells and vascular smooth muscle cells, including blood vessels and mesenteric arteries (PubMed:15034570, PubMed:21183689). Isoform C: is expressed in brain, skeletal muscle and adipocytes. Isoform D is testis-specific. 6 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Cell development/differentiation; Endoplasmic reticulum; Inhibitor; Membrane protein, integral; Membrane protein, multi-pass; Motility/polarity/chemotaxis
Chromosomal Location of Human Ortholog: 11|11 A3.3
Cellular Component:  axon; cell junction; cell projection; cytoplasm; dendritic growth cone; endoplasmic reticulum; endoplasmic reticulum membrane; endoplasmic reticulum tubular network; endoplasmic reticulum tubular network membrane; glutamatergic synapse; integral component of endoplasmic reticulum membrane; integral component of membrane; integral component of postsynaptic density membrane; membrane; myelin sheath; neuron projection; neuronal cell body; nuclear envelope; plasma membrane; postsynaptic density; protein-containing complex
Molecular Function:  cadherin binding; protein binding; protein homodimerization activity; protein-containing complex binding; ubiquitin protein ligase binding
Biological Process:  angiogenesis; axonal fasciculation; blastocyst formation; cardiac epithelial to mesenchymal transition; cell adhesion involved in sprouting angiogenesis; cell migration involved in vasculogenesis; 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 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 neuron differentiation; negative regulation of neuron projection development; negative regulation of neuron projection regeneration; negative regulation of vasculogenesis; nervous system development; nuclear pore complex assembly; positive regulation of angiogenesis; positive regulation of artery morphogenesis; positive regulation of collateral sprouting of injured axon; positive regulation of dopamine secretion; positive regulation of epithelial cell migration; positive regulation of ERBB3 signaling pathway; positive regulation of glial cell differentiation; 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 branching morphogenesis of a nerve; regulation of cell migration; regulation of nervous system development; regulation of sensory perception of pain
Reference #:  Q99P72 (UniProtKB)
Alt. Names/Synonyms: 1110020G17Rik; AA407876; AA409940; AA960376; ASY; C130026I10Rik; Kiaa0886; KIAA4153; mKIAA0886; mKIAA4153; Neurite outgrowth inhibitor; NgA; Nog; Nogo; Nogo protein; Nogo-A; Nogo-B; Nogo-C; NSP-CL; OTTMUSP00000005509; OTTMUSP00000005510; OTTMUSP00000005511; OTTMUSP00000005512; OTTMUSP00000005513; reticulon 4; Reticulon-4; Rtn4
Gene Symbols: Rtn4
Molecular weight: 126,613 Da
Basal Isoelectric point: 4.47  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene