Ubiquitin D is aprotein that in humans is encoded by theUBDgene, also known as FAT10.[5][6][7]UBD is a member of the ubiquitin-like protein family and participates in protein turnover by targeting substrates for degradation by the proteasome.
TheUBD gene is located within the human major histocompatibility complex (MHC) class I locus on chromosome 6 and was initially identified in reticuloendothelial tissues and mucosal-associated lymphoid systems.[5][6]The encoded protein has a molecular weight of approximately 18 kDa and contains N- and C-terminal regions that share 29% and 36% sequence identity with ubiquitin, respectively. Unlike other ubiquitin-like modifiers, UBD contains a free C-terminal diglycine motif that allows direct conjugation to target proteins.
UBD functions in a manner analogous to ubiquitin by covalently modifying proteins and directing them to proteasomal degradation. Among ubiquitin-like proteins, UBD is unique in that it can also directly guide noncovalently bound proteins to the proteasome. In addition to its role in protein degradation, UBD has been implicated in the regulation of mitosis, chromosome stability, apoptosis, and immune responses.
Dysregulation of UBD expression has been associated with altered apoptosis, abnormal cell division, and chromosomal instability, processes that are linked to neoplastic transformation. Increased UBD expression has been reported in several tumor types, including liver, cervical, ovarian, pancreatic, gastric, and small intestine adenocarcinomas, while little or no upregulation has been observed in thyroid, prostate, or kidney cancers.[8]In hepatocellular carcinoma, elevated UBD expression has been associated with increased levels of proliferating cell nuclear antigen, a marker of cell proliferation, and with enhanced tumor growth in experimental models. Overexpression of UBD has also been linked to the formation of Mallory–Denk bodies in chronic liver disease. In gastric cancer, increased UBD expression has been correlated with metastasis, tumor stage, and prognosis, and both UBD mRNA and protein levels have been reported as independent prognostic indicators. UBD expression can be induced by interferon-γ and tumor necrosis factor-α through an interferon sequence–responsive element in its promoter, suggesting a link between inflammatory signaling and UBD regulation.
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^abBates EE, Ravel O, Dieu MC, Ho S, Guret C, Bridon JM, et al. (October 1997). "Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells".European Journal of Immunology.27 (10):2471–2477.doi:10.1002/eji.1830271002.PMID9368598.S2CID21652482.
^abFan W, Cai W, Parimoo S, Schwarz DC, Lennon GG, Weissman SM (Aug 1996). "Identification of seven new human MHC class I region genes around the HLA-F locus".Immunogenetics.44 (2):97–103.doi:10.1007/BF02660056.PMID8662070.S2CID21628804.
Mazzé FM, Degrève L (2006). "The role of viral and cellular proteins in the budding of human immunodeficiency virus".Acta Virologica.50 (2):75–85.PMID16808324.
Brès V, Kiernan RE, Linares LK, Chable-Bessia C, Plechakova O, Tréand C, et al. (August 2003). "A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter".Nature Cell Biology.5 (8):754–761.doi:10.1038/ncb1023.PMID12883554.S2CID8414608.
