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Gene Review

RTN3  -  reticulon 3

Homo sapiens

Synonyms: ASYIP, HAP, Homolog of ASY protein, NSP-like protein 2, NSP-like protein II, ...
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Disease relevance of RTN3


High impact information on RTN3

  • In brain, BACE1 mainly colocalizes with RTN3 in neurons, whereas RTN4 is more enriched in oligodendrocytes [2].
  • Our previous study demonstrated that the overexpression of reticulon 3 (RTN3, also named HAP, homologue of ASY protein) caused apoptosis with the depletion of ER Ca(2+) stores [3].
  • These results supported that the release of ER Ca(2+) stores triggered the initial signal-transducing pathways for EOR induced by overexpressed RTN3 [3].
  • Our studies showed that overexpressed RTN3 induced EOR, eliciting ER-specific apoptosis with activation of caspase-12 and mitochondrial dysfunction through ER Ca(2+) depletion and the sustained elevation of cytosolic Ca(2+) [3].
  • ER Ca2+ depletion triggers apoptotic signals for endoplasmic reticulum (ER) overload response induced by overexpressed reticulon 3 (RTN3/HAP) [3].

Biological context of RTN3

  • In the present paper, we describe the existence of five new isoforms of RTN3 that differ in their N-termini, and analysed their tissue distribution and expression in neurons [4].
  • Specifically, RTN3A1 expression was down-regulated upon cell death of cerebellar granule neurons triggered by potassium deprivation [4].
  • We redefined the structure of human and murine rtn3 genes, and identified two supplementary exons that may generate up to seven putative isoforms arising by alternative splicing or differential promoter usage [4].
  • In cells where RTN3 displayed a filamentous/reticular distribution, protein transport between the ER and Golgi was blocked, and Golgi proteins were dispersed [5].
  • Although RTN3 can form homo- or heterodimers in cells, BACE1 mainly binds to the RTN monomer and disruption of the QID triplet does not interfere with the dimerization [6].

Anatomical context of RTN3


Associations of RTN3 with chemical compounds

  • Furthermore, we demonstrated that endogenous FADD was recruited by ER-bound endogenous RTN3 to the ER membrane under the tunicamycin stimulation [8].
  • The ASYIP protein contains two hydrophobic regions and a double lysine endoplasmic reticulum (ER) retrieval motif at its C-terminus, which was shown to be identical to RTN3, a reticulon family protein of unknown function [9].

Physical interactions of RTN3

  • Here, we focused our study on RTN3 and further show that a C-terminal QID triplet conserved among mammalian RTN members is required for the binding of RTN to BACE1 [6].
  • Subtle changes in RTN3 membrane topology can disrupt its binding to BACE1 and its inhibitory effects on BACE1 activity [11].

Co-localisations of RTN3


Other interactions of RTN3

  • Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13 [12].

Analytical, diagnostic and therapeutic context of RTN3

  • To investigate the mechanism of ASY-induced apoptosis or inhibition of neuronal regeneration, we cloned a cDNA for the ASY-interacting protein from the human cDNA library using the yeast two-hybrid method, and obtained a cDNA we designated as ASYIP [9].
  • With Western blot analysis, the expected 100-kDa RTN3-A1 protein was detected in mouse brain [10].


  1. Overexpression of human reticulon 3 (hRTN3) in astrocytoma. Huang, X., Yang, H., Zhou, Y., Liu, J., Yin, B., Peng, X., Qiang, B., Yuan, J. Clin. Neuropathol. (2004) [Pubmed]
  2. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. He, W., Lu, Y., Qahwash, I., Hu, X.Y., Chang, A., Yan, R. Nat. Med. (2004) [Pubmed]
  3. ER Ca2+ depletion triggers apoptotic signals for endoplasmic reticulum (ER) overload response induced by overexpressed reticulon 3 (RTN3/HAP). Kuang, E., Wan, Q., Li, X., Xu, H., Liu, Q., Qi, Y. J. Cell. Physiol. (2005) [Pubmed]
  4. Tissue specificity and regulation of the N-terminal diversity of reticulon 3. Di Scala, F., Dupuis, L., Gaiddon, C., De Tapia, M., Jokic, N., Gonzalez de Aguilar, J.L., Raul, J.S., Ludes, B., Loeffler, J.P. Biochem. J. (2005) [Pubmed]
  5. Reticulon 3 is involved in membrane trafficking between the endoplasmic reticulum and Golgi. Wakana, Y., Koyama, S., Nakajima, K., Hatsuzawa, K., Nagahama, M., Tani, K., Hauri, H.P., Melançon, P., Tagaya, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  6. Mapping of Interaction Domains Mediating Binding between BACE1 and RTN/Nogo Proteins. He, W., Hu, X., Shi, Q., Zhou, X., Lu, Y., Fisher, C., Yan, R. J. Mol. Biol. (2006) [Pubmed]
  7. Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with Reticulon 1 an endoplasmic reticulum protein. Mannan, A.U., Boehm, J., Sauter, S.M., Rauber, A., Byrne, P.C., Neesen, J., Engel, W. Neurogenetics (2006) [Pubmed]
  8. Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes. Xiang, R., Liu, Y., Zhu, L., Dong, W., Qi, Y. Apoptosis (2006) [Pubmed]
  9. Pro-apoptotic ASY/Nogo-B protein associates with ASYIP. Qi, B., Qi, Y., Watari, A., Yoshioka, N., Inoue, H., Minemoto, Y., Yamashita, K., Sasagawa, T., Yutsudo, M. J. Cell. Physiol. (2003) [Pubmed]
  10. Identification of a new RTN3 transcript, RTN3-A1, and its distribution in adult mouse brain. Cai, Y., Saiyin, H., Lin, Q., Zhang, P., Tang, L., Pan, X., Yu, L. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  11. The membrane topology of RTN3 and its effect on binding of RTN3 to BACE1. He, W., Shi, Q., Hu, X., Yan, R. J. Biol. Chem. (2007) [Pubmed]
  12. Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13. Moreira, E.F., Jaworski, C.J., Rodriguez, I.R. Genomics (1999) [Pubmed]
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