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Gene Review

Ube4b  -  ubiquitination factor E4B

Mus musculus

Synonyms: 4930551I19Rik, 4933406G05Rik, AU014668, D4Bwg0973e, UFD2, ...
 
 
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Disease relevance of Ube4b

 

High impact information on Ube4b

  • The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2, the C-terminal 302 amino acids of D4Cole1e, and an aspartic acid formed at the junction [2].
  • Transfection of HEK293 cells with constructs comprising either full-length Nmnat-1 or the truncated Ube4b fragment (N70-Ube4b) demonstrated selective effects of Nmnat-1 (down-regulated pttg1) and N70-Ube4b (up-regulated edr1l-EST) on mRNA levels [3].
  • Here, we show that mice lacking UFD2a die in utero, manifesting marked apoptosis in the developing heart [1].
  • Furthermore, Ufd2a(+/-) mice displayed axonal dystrophy in the nucleus gracilis, as well as degeneration of Purkinje cells accompanied by endoplasmic reticulum stress [1].
  • Polyubiquitylation activity for an E4 substrate was greatly reduced in Ufd2a(-/-) mouse embryonic fibroblasts [1].
 

Biological context of Ube4b

  • Luciferase reporter gene analysis of the 5(') flanking region of Ube4b revealed that nucleotides -1018 to -943 (relative to the translation initiation site) possess promoter activity [4].
  • A full-length (approximately 5700 bp) Ube4b cDNA was isolated and the corresponding gene spans >100 kb, comprising 27 exons [4].
  • Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues [5].
  • It encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ube4b and 303 amino acids derived from the D4Cole1e gene.We have identified the human homologue of D4Cole1e, and mapped it to chromosome 1p36 [6].
  • The dominant slow Wallerian degeneration phenotype is conferred by a hybrid gene within the triplication, comprising a gene of previously unknown function, D4Cole1e, and the 5' end of ubiquitination factor E4B (Ube4b) [6].
 

Anatomical context of Ube4b

 

Enzymatic interactions of Ube4b

 

Other interactions of Ube4b

  • Therefore, axon protection in Wld s mice does not appear to be controlled by expression of Wld s protein in the axons per se and also is unlikely to be related to the different activity of Ube4b either in general ubiquitination or toward this particular substrate [10].
  • We also show that UFD2a interacts with VCP (a AAA-family ATPase) that is thought to mediate protein folding [4].

References

  1. Mammalian E4 is required for cardiac development and maintenance of the nervous system. Kaneko-Oshikawa, C., Nakagawa, T., Yamada, M., Yoshikawa, H., Matsumoto, M., Yada, M., Hatakeyama, S., Nakayama, K., Nakayama, K.I. Mol. Cell. Biol. (2005) [Pubmed]
  2. A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse. Conforti, L., Tarlton, A., Mack, T.G., Mi, W., Buckmaster, E.A., Wagner, D., Perry, V.H., Coleman, M.P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells. Gillingwater, T.H., Wishart, T.M., Chen, P.E., Haley, J.E., Robertson, K., MacDonald, S.H., Middleton, S., Wawrowski, K., Shipston, M.J., Melmed, S., Wyllie, D.J., Skehel, P.A., Coleman, M.P., Ribchester, R.R. Hum. Mol. Genet. (2006) [Pubmed]
  4. Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a. Kaneko, C., Hatakeyama, S., Matsumoto, M., Yada, M., Nakayama, K., Nakayama, K.I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  5. The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus. Laser, H., Conforti, L., Morreale, G., Mack, T.G., Heyer, M., Haley, J.E., Wishart, T.M., Beirowski, B., Walker, S.A., Haase, G., Celik, A., Adalbert, R., Wagner, D., Grumme, D., Ribchester, R.R., Plomann, M., Coleman, M.P. Mol. Biol. Cell (2006) [Pubmed]
  6. Human homologue of a gene mutated in the slow Wallerian degeneration (C57BL/Wld(s)) mouse. Fernando, F.S., Conforti, L., Tosi, S., Smith, A.D., Coleman, M.P. Gene (2002) [Pubmed]
  7. Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wld(s) mutant and Ube4b/Nmnat transgenic mice. Gillingwater, T.H., Thomson, D., Mack, T.G., Soffin, E.M., Mattison, R.J., Coleman, M.P., Ribchester, R.R. J. Physiol. (Lond.) (2002) [Pubmed]
  8. A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. Adalbert, R., Gillingwater, T.H., Haley, J.E., Bridge, K., Beirowski, B., Berek, L., Wagner, D., Grumme, D., Thomson, D., Celik, A., Addicks, K., Ribchester, R.R., Coleman, M.P. Eur. J. Neurosci. (2005) [Pubmed]
  9. The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis. Mahoney, J.A., Odin, J.A., White, S.M., Shaffer, D., Koff, A., Casciola-Rosen, L., Rosen, A. Biochem. J. (2002) [Pubmed]
  10. The cellular distribution of the Wld s chimeric protein and its constituent proteins in the CNS. Fang, C., Bernardes-Silva, M., Coleman, M.P., Perry, V.H. Neuroscience (2005) [Pubmed]
 
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