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| Description | 165 amino acids; 18 kDa protein; different post translational modifications: Acetylation, phosphorylation, ubiquitination. UBD contains 2 ubiquitin domains, with 2 potential K involved in its ubiquitination but not in its degradation. UBD contains from N-Term to C-Term, an Ubiquitin like domain (21-76) containing K55 equivalent of the K48 of ubiquitin, an ubiquitin like domain (104-165) containing K137 equivalent of the K48 of ubiquitin. In C-terminal, UBD contains a GG motif, equivalent to Ubiquitin GG motif, important for conjugating proteins: TP53, USE. |
| Expression | Lung, brain, kidney, liver, spleen, thymus, gut, testis, lymph nodes, uterus and ovaries. |
| Localisation | Nuclear and cytoplasmic. |
| Function | UBD is involved in the immune response (expressed in spleen, thymus, and lymph nodes, involved in immunoproteasome formation and in antigen presentation). UBD is degradated by the proteasome, independently of ubiquitin pathway, but it targets also proteins to the proteasome for degradation. UBD plays a critical role in the cell cycle pro-apoptotic (by over expression, by interacting with HIV VpR), anti-apoptotic (spleens, thymuses and bone marrow), anti-proliferative (when induced by retinoids acid), pro-proliferative (in colon and liver cancer, maybe by interacting with MAD2 and p53, cancers in liver and colon). |
| Homology | With Ubiquitin. |
| Entity | Colon cancer |
| Disease | Colorectal carcinoma (CRE) is one of the most common cancers encountered in the western world and increasingly in the developing world as well. Colorectal carcinoma has a high morbidity and mortality rate. Colorectal cancer is mainly associated with the mutation of adenomatous polyposis coli (APC). Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer (CRC). Chronic inflammation is believed to promote carcinogenesis, and per consequence the increases of UBD expression. UBD could be used as a new prognostic marker for the recurrence of stage II and III of colon cancer. |
| Prognosis | The prognosis is highly dependent on the stage of the colorectal cancer (from over 90% of survival after 5 years for Stage I to less than 5% of survival, after 5 years, for Stage IV). |
| Cytogenetics | Microsatellite Instability (15-20% of the sporadic colorectal cancers), Chromosomal instability (in 80-85% of the colorectal cancers), CpG island methylator phenotype.
Loss of chromosome: 1p, 1p3, 1q22, 4, 4q26, 5, 5q, 8p, 10, 14, 15, 15q11-q21, 17, 17p, 17p12-13, 17q10, 18, 18p, 18p21-pter, 18q, 18q10, 18q21, 18q12-21, 21, 22, Y.
Gain of chromosome: 1q11, 3, 3q, 5, 5p, 5q, 6, 7, 8, 8q, 8q28, 8q23-ter, 12, 12p, 13, 13p14-31, 13q, 16q24.3, 17p, 17q, 19, 20, 20q, 20q13, X. |
| Hybrid/Mutated Gene | PMS2CL |
| Oncogenesis | An inflammatory reaction induces the up regulation of the expression of UBD. UBD amplified the inflammatory reaction by mediating NF-Kb activation. Carriage of the minor allele of UBD I68T was significantly associated with advanced stages of CRC and with CRC below 65 years of age. |
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| Entity | Gastric cancer |
| Disease | Gastric cancer is one of the most common malignant tumors in the world. The mortality of the gastric cancer is very high (especially in East Asia). The expression of UBD is upregulated in the gastric tumors and associated with a low survival rate, after the surgery. The upregulation of UBD is associated with a non-active mutant of p53, leading to the formation of the gastric cancer. |
| Prognosis | Poor. |
| Cytogenetics | Gains of 3q, 7p, 7q, 8q, 13q, 17q, 20p. Losses of 4q, 9p, 17p and 18q. |
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| Entity | Liver cancer |
| Disease | Human hepatocellular carcinoma (HCC) is the 5th most common cancer in the world and the 3rd cause of cancer mortality (high incidence in South East Asia and central Africa). The causes of HCC are due to genetic mutations, HBV or HCV infection, alcohol, toxin exposures (e.g. aflotoxins), obesity, diabetes, hemochromatosis. UBD is over expressed in more than 60% of HCC. UBD is also overexpressed in more than 75% of liver cancer stem cells. |
| Prognosis | With a liver transplant, the survival rates varies from 50% to 80%, after 5 years. |
| Hybrid/Mutated Gene | N/A |
| Abnormal Protein | N/A |
| Oncogenesis | The real mechanism associating UBD expression and liver cancer is not well defined. However, an inflammatory reaction induces the up regulation of the expression of UBD. UBD amplifies the inflammatory reaction by mediating NF-Kb activation, amplifiying the inflammatory response that is known to be a cause of the cancer. |
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| Entity | Celiac disease (6p21.3) |
| Disease | Celiac disease (CD) is a disorder of the small intestine, resulting from the intolerance of different food: prolamins, wheat, barley, rye, gluten sensitive enteropathy. The presence of specific HLA-DQ alleles, on chromosome 6p21.3, increases the susceptibility to celiac disease. This region has been designated CELIAC1. The original pathogenic mechanism of the CD is still unknown. However, it is clear that the immune system is involved. CD is associated with the presence of one copy of the HLA-DQ2 heterodimer and less frequently in 6% of the patients with the HLA-DQ8 molecule. The up regulation of UBD is associated with intestinal mucosa of active CD. |
| Prognosis | Very poor (response to removing glutens from the diet). |
| Cytogenetics | 1p36, 4p15, 5q31, 6p21.3, 7q21, 9p21-23 and 16q12 chromosomal regions are involved in Celiac disease. |
| Hybrid/Mutated Gene | N/A |
| Abnormal Protein | N/A |
| Oncogenesis | N/A |
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| Entity | HIV associated nephropathy |
| Disease | HIV-associated nephropathy (HIVAN) is a kidney disease in patients with human immunodeficiency virus (HIV) disease. HIVAN is characterized by a nephrotic range proteinuria (associated with UBD over expression), azotemia, normal to large kidneys, focal segmental glomerulosclerosis. UBD is overexpressed in HIVAN and induces apoptosis by its interaction with HIV protein Vpr. |
| Prognosis | Very poor prognosis without HIV treatment. Good prognosis with HIV treatment. |
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| Entity | Graft versus host reaction |
| Prognosis | The survival average is from 15 to 50% at 5 years. The over expression of UBD is observed during graft versus host disease. UBD could be involved or serve as a molecular marker for graft versus host disease and graft versus host reaction. |
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| A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2. |
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