Alternative titles; symbols
HGNC Approved Gene Symbol: UBD
Cytogenetic location: 6p22.1 Genomic coordinates (GRCh38) : 6:29,555,515-29,559,732 (from NCBI)
Using selective cDNA hybridization of a YAC containing the HLA-F locus (143110) region on chromosome 6, followed by Southern and Northern blot analyses, Fan et al. (1996) isolated a cDNA, which they called 1F12, encoding a protein similar to diubiquitin. The 1.1-kb transcript was detected only in B-cell lines transformed by Epstein-Barr virus.
By subtractive hybridization of dendritic cell (DC) libraries and EST database searching, Bates et al. (1997) obtained a full-length cDNA encoding diubiquitin. The predicted 165-amino acid protein has 2 ubiquitin-like domains, each of which has 2 cysteines. Southern blot analysis indicated that the cDNA represents a single-copy gene. RT-PCR analysis detected expression in DCs, B cells, and a kidney carcinoma cell line, but no expression was detected in T-cell, myelomonocytic, or fibroblast lines. Expression in freshly isolated cells was restricted to DCs and B cells. In situ hybridization analysis revealed clear expression of diubiquitin in isolated germinal center cells and in epithelial cells of the crypts and external epithelium, but not in basal cells.
Chiu et al. (2007) showed that E1L2 (UBE1L2; 611361) could activate FAT10 by forming a thioester between the active-site cysteine of E1L2 and the C-terminal diglycine motif of FAT10. Endogenous E1L2 and FAT10 also formed a thioester in human cells stimulated with TNF-alpha (TNF; 191160) and interferon-gamma (IFNG; 147570). Knockdown of E1L2 by RNA interference significantly reduced FAT10 conjugation in cells.
By Western blot analysis, Buchsbaum et al. (2012) showed that human FAT10 required ubiquitination for proteasomal degradation and that FAT10, devoid of its 17 lysines, disappeared due to both degradation and its accumulation in an insoluble form. FAT10 was stabilized in cells expressing nonpolymerizable ubiquitin and in cells harboring a thermolabile mutation in E1L2. Although FAT10 could serve as a degradation signal for otherwise stable proteins, further polyubiquitination was also required. In response to the induction of apoptosis, FAT10 was rapidly ubiquitinated and degraded. Buchsbaum et al. (2012) proposed that FAT10 plays a role in prosurvival pathways.
Zhang et al. (2016) observed upregulation of FAT10 following infection of human A549 respiratory epithelial cells or mice with the H5N1 avian influenza virus. Further analysis showed that FAT10 increased replication of H5N1 virus and decreased viability of infected cells. RNA from H5N1-infected cells upregulated FAT10, and this process was mediated by the RIGI (DDX58; 609631)-NFKB (see 164011) pathway. Knockdown of FAT10 in A549 cells upregulated type I IFN (e.g., IFNB1; 147640) expression and enhanced STAT1 (600555) phosphorylation during H5N1 infection. Zhang et al. (2016) proposed that FAT10 promotes H5N1 viral replication by inhibiting type I IFN.
By YAC analysis, Fan et al. (1996) mapped the diubiquitin gene to the HLA-F region of chromosome 6.
Bates, E. E. M., Ravel, O., Dieu, M.-C., Ho, S., Guret, C., Bridon, J.-M., Ait-Yahia, S., Briere, F., Caux, C., Banchereau, J., Lebecque, S. Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells. Europ. J. Immun. 27: 2471-2477, 1997. [PubMed: 9368598] [Full Text: https://doi.org/10.1002/eji.1830271002]
Buchsbaum, S., Bercovich, B., Ciechanover, A. FAT10 is a proteasomal degradation signal that is itself regulated by ubiquitination. Molec. Biol. Cell 23: 225-232, 2012. [PubMed: 22072791] [Full Text: https://doi.org/10.1091/mbc.E11-07-0609]
Chiu, Y.-H., Sun, Q., Chen, Z. J. E1-L2 activates both ubiquitin and FAT10. Molec. Cell 27: 1014-1023, 2007. [PubMed: 17889673] [Full Text: https://doi.org/10.1016/j.molcel.2007.08.020]
Fan, W., Cai, W., Parimoo, S., Lennon, G. G., Schwarz, D. C., Weissman, S. M. Identification of seven new human MHC class I region genes around the HLA-F locus. Immunogenetics 44: 97-103, 1996. Note: Erratum: Immunogenetics 46: 169 only, 1997. [PubMed: 8662070] [Full Text: https://doi.org/10.1007/BF02660056]
Zhang, Y., Tang, J., Yang, N., Liu, Q., Zhang, Q., Zhang, Y., Li, N., Zhao, Y., Li, S., Liu, S., Zhou, H., Li, X., Tian, M., Deng, J., Xie, P., Sun, Y., Lu, H., Zhang, M. Q., Jin, N., Jiang, C. FAT10 is critical in influenza A virus replication by inhibiting type I IFN. J. Immun. 197: 824-833, 2016. [PubMed: 27354218] [Full Text: https://doi.org/10.4049/jimmunol.1501563]