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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.

Protein RTN4 PDB 2g31.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesRTN4, 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 IDsOMIM: 604475 MGI: 1915835 HomoloGene: 10743 GeneCards: RTN4
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for RTN4
Genomic location for RTN4
Band2p16.1Start54,972,187 bp[1]
End55,112,621 bp[1]
RNA expression pattern
PBB GE RTN4 211509 s at fs.png

PBB GE RTN4 210968 s at fs.png

PBB GE RTN4 214629 x at fs.png
More reference expression data
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 2: 54.97 – 55.11 MbChr 11: 29.69 – 29.74 Mb
PubMed search[3][4]
View/Edit HumanView/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]


Reticulon 4 has been shown to interact with WWP1,[11] BCL2-like 1[12] and Bcl-2.[12]

See alsoEdit


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115310 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020458 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ GrandPré T, Nakamura F, Vartanian T, Strittmatter SM (Jan 2000). "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein". Nature. 403 (6768): 439–44. doi:10.1038/35000226. PMID 10667797.
  6. ^ Yang J, Yu L, Bi AD, Zhao SY (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 101–2. doi:10.1159/000015499. PMID 10773680.
  7. ^ a b "Entrez Gene: RTN4 reticulon 4".
  8. ^ a b Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC (Jul 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination". Nature Neuroscience. 7 (7): 736–44. doi:10.1038/nn1261. PMID 15184901.
  9. ^ Sozmen, EG; et al. (2016). "Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice". PNAS USA. 113: E8453–E8462. doi:10.1073/pnas.1615322113. PMC 5206535.
  10. ^ Stopping a receptor called 'nogo' boosts the synapses
  11. ^ Qin H, Pu HX, Li M, Ahmed S, Song J (Dec 2008). "Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration". Biochemistry. 47 (51): 13647–58. doi:10.1021/bi8017976. PMID 19035836.
  12. ^ a b Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.

Further readingEdit