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Gene Review

UBD  -  ubiquitin D

Homo sapiens

Synonyms: Diubiquitin, FAT10, GABBR1, UBD-3, Ubiquitin D, ...
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Disease relevance of UBD


High impact information on UBD

  • The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface [2].
  • Here, I give an overview of important ubiquitin-related protein motifs, including the UBA, UIM, UBD and UBX domains, and propose a model for the role of subclasses of UBA-domain-containing proteins in ubiquitin-mediated proteolysis [3].
  • Although the interaction of UBA2 with Lys48-linked diubiquitin involves the same hydrophobic surface on each ubiquitin unit as that utilized in monoubiquitin:UBA complexes, our results show how the "closed" conformation of Lys48-linked diubiquitin is crucial for high-affinity binding [4].
  • Thus, FAT10 may modulate cell growth during B cell or dendritic cell development and activation [5].
  • In various cell lines, FAT10 expression was shown to be induced by gamma interferon or by tumor necrosis factor alpha [6].

Biological context of UBD


Anatomical context of UBD

  • FAT10 expression was also found to be highly upregulated in other cancers of the gastrointestinal tract and female reproductive system [7].
  • FAT10 mRNA is expressed constitutively in some lymphoblastoid lines and dendritic cells and in certain other cells after gamma-interferon induction [5].
  • FAT10-green fluorescent protein fusion proteins were not cleaved but entirely degraded, suggesting that FAT10-specific deconjugating enzymes were not present in the analyzed cell lines [10].
  • UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells [11].
  • Here, we report the identification of the ubiquitin-like gene UBD as a downstream element of FOXP3 in human activated regulatory CD4(+)CD25(hi) T cells (T(reg)) [11].

Associations of UBD with chemical compounds

  • FAT10 bears a diglycine motif at its C terminus that can form isopeptide bonds to so far unidentified target proteins [12].
  • A yeast two-hybrid screen identified NEDD8 ultimate buster-1L (NUB1L) as a non-covalent binding partner of FAT10, and this interaction was confirmed by coimmunoprecipitation and glutathione S-transferase pull-down experiments [12].
  • In the presence of ionomycin, overexpression of UBD in T(h) cells leads to the induction of IL1R2 that resemble FOXP3-transduced T(h) cells and naturally derived T(reg) cells [11].
  • More nocodazole-treated FAT10-overexpressing cells escape mitotic controls and are multinucleate compared with parental cells [13].

Physical interactions of UBD


Enzymatic interactions of UBD

  • SARS CoV-PLpro hydrolyzed both diubiquitin and ubiquitin-7-amino-4-methylcoumarin (AMC) substrates, and hydrolysis of ubiquitin-AMC is approximately 180-fold more efficient than hydrolysis of a peptide substrate that mimics the PLpro replicase recognition sequence [15].

Regulatory relationships of UBD


Other interactions of UBD

  • The coexpression of NUB1L enhanced the degradation rate of FAT10 8-fold, whereas NEDD8 degradation was only accelerated 2-fold [12].
  • Because NUB1 was shown to bind to the proteasome subunit RPN10 in vitro and to be contained in 26 S proteasome preparations, it may function as a linker that targets FAT10 for degradation by the proteasome [12].
  • Rather, FAT10 may modulate tumorigenesis through its reported interaction with the MAD2 spindle-assembly checkpoint protein [7].
  • This purification scheme can be applied to other small ubiquitin-like proteins, especially those with limited protein targets such as the SUMOs (1, 2, and 3), Isg15, or FAT10 [16].
  • We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients [17].

Analytical, diagnostic and therapeutic context of UBD


  1. Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease. Ross, M.J., Wosnitzer, M.S., Ross, M.D., Granelli, B., Gusella, G.L., Husain, M., Kaufman, L., Vasievich, M., D'Agati, V.D., Wilson, P.D., Klotman, M.E., Klotman, P.E. J. Am. Soc. Nephrol. (2006) [Pubmed]
  2. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Penengo, L., Mapelli, M., Murachelli, A.G., Confalonieri, S., Magri, L., Musacchio, A., Di Fiore, P.P., Polo, S., Schneider, T.R. Cell (2006) [Pubmed]
  3. From UBA to UBX: new words in the ubiquitin vocabulary. Buchberger, A. Trends Cell Biol. (2002) [Pubmed]
  4. Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. Varadan, R., Assfalg, M., Raasi, S., Pickart, C., Fushman, D. Mol. Cell (2005) [Pubmed]
  5. A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2. Liu, Y.C., Pan, J., Zhang, C., Fan, W., Collinge, M., Bender, J.R., Weissman, S.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences. Canaan, A., Yu, X., Booth, C.J., Lian, J., Lazar, I., Gamfi, S.L., Castille, K., Kohya, N., Nakayama, Y., Liu, Y.C., Eynon, E., Flavell, R., Weissman, S.M. Mol. Cell. Biol. (2006) [Pubmed]
  7. Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers. Lee, C.G., Ren, J., Cheong, I.S., Ban, K.H., Ooi, L.L., Yong Tan, S., Kan, A., Nuchprayoon, I., Jin, R., Lee, K.H., Choti, M., Lee, L.A. Oncogene (2003) [Pubmed]
  8. FAT10, a gene up-regulated in various cancers, is cell-cycle regulated. Lim, C.B., Zhang, D., Lee, C.G. Cell division [electronic resource]. (2006) [Pubmed]
  9. Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. Ustinova, E.E., Gutkin, D.W., Pezzone, M.A. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  10. FAT10, a ubiquitin-independent signal for proteasomal degradation. Hipp, M.S., Kalveram, B., Raasi, S., Groettrup, M., Schmidtke, G. Mol. Cell. Biol. (2005) [Pubmed]
  11. UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells. Ocklenburg, F., Moharregh-Khiabani, D., Geffers, R., Janke, V., Pfoertner, S., Garritsen, H., Groebe, L., Klempnauer, J., Dittmar, K.E., Weiss, S., Buer, J., Probst-Kepper, M. Lab. Invest. (2006) [Pubmed]
  12. NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation. Hipp, M.S., Raasi, S., Groettrup, M., Schmidtke, G. J. Biol. Chem. (2004) [Pubmed]
  13. FAT10 plays a role in the regulation of chromosomal stability. Ren, J., Kan, A., Leong, S.H., Ooi, L.L., Jeang, K.T., Chong, S.S., Kon, O.L., Lee, C.G. J. Biol. Chem. (2006) [Pubmed]
  14. Structural basis for monoubiquitin recognition by the Ede1 UBA domain. Swanson, K.A., Hicke, L., Radhakrishnan, I. J. Mol. Biol. (2006) [Pubmed]
  15. The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. Barretto, N., Jukneliene, D., Ratia, K., Chen, Z., Mesecar, A.D., Baker, S.C. J. Virol. (2005) [Pubmed]
  16. Analysis of Nedd8-associated polypeptides: a model for deciphering the pathway for ubiquitin-like modifications. Norman, J.A., Shiekhattar, R. Biochemistry (2006) [Pubmed]
  17. p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers. Zhang, D.W., Jeang, K.T., Lee, C.G. Oncogene (2006) [Pubmed]
  18. Distinct gene expression profiles characterize cellular phenotypes of follicle-associated epithelium and m cells. Hase, K., Ohshima, S., Kawano, K., Hashimoto, N., Matsumoto, K., Saito, H., Ohno, H. DNA Res. (2005) [Pubmed]
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