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UBD (ubiquitin D)

Written2011-11Joan Oliva, Samuel W French
Department of Hematology, LA Biomed, Torrance, CA 90502, USA (JA); Department of Pathology, LA BioMed, Torrance, CA 90502, USA (SWF)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)FAT10
Other aliasGABBR1
UBD-3
HGNC (Hugo) UBD
LocusID (NCBI) 10537
Atlas_Id 43742
Location 6p22.1  [Link to chromosome band 6p22]
Location_base_pair Starts at 29523389 and ends at 29527702 bp from pter ( according to hg19-Feb_2009)  [Mapping UBD.png]
 
  The upper part of the diagram shows the loci of UbD, present in the MHCI locus of chromosome 6. The lower part of the diagram shows the mRNA of UBD.
Fusion genes
(updated 2016)
RPS16 (19q13.2) / UBD (6p22.1)ZNF708 (19p12) / UBD (6p22.1)

DNA/RNA

Description 2 exons on 4,3 kb.
Transcription In a centromeric to telomeric orientation; transcription is cell-cycle regulated, with down regulation during the G1 and G2/M phase and it is regulated by inflammatory cytokines (e.g. TNFa and IFNg).
Pseudogene UBDP1 ubiquitin D pseudogene 1, Locus ID 387062, Location 6p22.1.
LOC100286971 ubiquitin D pseudogene, Locus ID 100286971, Location 6p22.1.

Protein

 
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.

Mutations

 
  The mutations in yellow are the missense mutation. The mutation in red is the I68T, associated with advanced stages of colorectal cancer.
Germinal N/A
Somatic A missense mutation was observed in the position 376 of the mRNA changing TTG in TCG (L51S). Due to this mutation the protein goes from medium size and hydrophobic to small and polar. No report showed a link between this polymorphism and a disease.
A missense mutation was observed in the position 95 of the protein S95P. Due to this mutation the protein goes from small size and polar to medium size and hydrophobic. No report showed a link between this polymorphism and a disease.
A missense mutation was observed in the position 99 of the protein A99G. Due to this mutation the protein goes from small size and hydrophobic to glycine. No report showed a link between this polymorphism and a disease.
A missense mutation was observed in the position 120 of the protein E120K. Due to this mutation the protein goes from medium size and acidic to large size and basic. No report showed a link between this polymorphism and a disease.
A missense mutation was observed in the position 160 of the protein C160S. Due to this mutation the protein goes from medium size and polar to small size and polar. No report showed a link between this polymorphism and a disease.
A mutation in UBD I68T was significantly associated with advanced stages of colorectal cancer and with colorectal below 65 years of age.

Implicated in

Note
  
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.
  
  
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.
  
  
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.
  
  
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
  
  
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.
  
  
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.
  

Bibliography

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Genetics of hepatocellular carcinoma.
Buendia MA.
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PMID 10936068
 
Hepatocellular carcinoma: epidemiology and molecular carcinogenesis.
El-Serag HB, Rudolph KL.
Gastroenterology. 2007 Jun;132(7):2557-76. (REVIEW)
PMID 17570226
 
The ubiquitin-like protein FAT10 mediates NF-kappaB activation.
Gong P, Canaan A, Wang B, Leventhal J, Snyder A, Nair V, Cohen CD, Kretzler M, D'Agati V, Weissman S, Ross MJ.
J Am Soc Nephrol. 2010 Feb;21(2):316-26. Epub 2009 Dec 3.
PMID 19959714
 
FAT10 level in human gastric cancer and its relation with mutant p53 level, lymph node metastasis and TNM staging.
Ji F, Jin X, Jiao CH, Xu QW, Wang ZW, Chen YL.
World J Gastroenterol. 2009 May 14;15(18):2228-33.
PMID 19437562
 
FAT10 modifies p53 and upregulates its transcriptional activity.
Li T, Santockyte R, Yu S, Shen RF, Tekle E, Lee CG, Yang DC, Chock PB.
Arch Biochem Biophys. 2011 May 15;509(2):164-9. Epub 2011 Mar 9.
PMID 21396347
 
Genomewide linkage analysis of celiac disease in Finnish families.
Liu J, Juo SH, Holopainen P, Terwilliger J, Tong X, Grunn A, Brito M, Green P, Mustalahti K, Maki M, Gilliam TC, Partanen J.
Am J Hum Genet. 2002 Jan;70(1):51-9. Epub 2001 Nov 19.
PMID 11715113
 
A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2.
Liu YC, Pan J, Zhang C, Fan W, Collinge M, Bender JR, Weissman SM.
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4313-8.
PMID 10200259
 
Genetics, cytogenetics, and epigenetics of colorectal cancer.
Migliore L, Migheli F, Spisni R, Coppede F.
J Biomed Biotechnol. 2011;2011:792362. Epub 2011 Feb 14. (REVIEW)
PMID 21490705
 
Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of graft versus host disease.
Novota P, Zinocker S, Norden J, Wang XN, Sviland L, Opitz L, Salinas-Riester G, Rolstad B, Dickinson AM, Walter L, Dressel R.
PLoS One. 2011 Jan 28;6(1):e16582.
PMID 21305040
 
Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis.
Oliva J, Bardag-Gorce F, French BA, Li J, McPhaul L, Amidi F, Dedes J, Habibi A, Nguyen S, French SW.
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PMID 18280469
 
Surgical treatment for hepatocellular carcinoma.
Takayama T.
Jpn J Clin Oncol. 2011 Apr;41(4):447-54. Epub 2011 Mar 16. (REVIEW)
PMID 21411469
 
Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism.
Yagil Y, Hessner M, Schulz H, Gosele C, Lebedev L, Barkalifa R, Sapojnikov M, Hubner N, Yagil C.
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PMID 20876844
 

Citation

This paper should be referenced as such :
Oliva, J ; French, SW
UBD (ubiquitin D)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(4):289-292.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/UBDID43742ch6p22.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Nodular lymphocyte-predominant Hodgkin lymphoma


External links

Nomenclature
HGNC (Hugo)UBD   18795
Cards
AtlasUBDID43742ch6p22
Entrez_Gene (NCBI)UBD  10537  ubiquitin D
AliasesFAT10; GABBR1; UBD-3
GeneCards (Weizmann)UBD
Ensembl hg19 (Hinxton)ENSG00000213886 [Gene_View]  chr6:29523389-29527702 [Contig_View]  UBD [Vega]
Ensembl hg38 (Hinxton)ENSG00000213886 [Gene_View]  chr6:29523389-29527702 [Contig_View]  UBD [Vega]
ICGC DataPortalENSG00000213886
TCGA cBioPortalUBD
AceView (NCBI)UBD
Genatlas (Paris)UBD
WikiGenes10537
SOURCE (Princeton)UBD
Genetics Home Reference (NIH)UBD
Genomic and cartography
GoldenPath hg19 (UCSC)UBD  -     chr6:29523389-29527702 -  6p21.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)UBD  -     6p21.3   [Description]    (hg38-Dec_2013)
EnsemblUBD - 6p21.3 [CytoView hg19]  UBD - 6p21.3 [CytoView hg38]
Mapping of homologs : NCBIUBD [Mapview hg19]  UBD [Mapview hg38]
OMIM606050   
Gene and transcription
Genbank (Entrez)AA878968 AF123050 AK311914 BC012472 CB111380
RefSeq transcript (Entrez)NM_006398
RefSeq genomic (Entrez)NC_000006 NC_018917 NT_007592 NT_113891 NT_167244 NT_167245 NT_167246 NT_167247 NT_167248 NW_004929326
Consensus coding sequences : CCDS (NCBI)UBD
Cluster EST : UnigeneHs.44532 [ NCBI ]
CGAP (NCI)Hs.44532
Alternative Splicing GalleryENSG00000213886
Gene ExpressionUBD [ NCBI-GEO ]   UBD [ EBI - ARRAY_EXPRESS ]   UBD [ SEEK ]   UBD [ MEM ]
Gene Expression Viewer (FireBrowse)UBD [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10537
GTEX Portal (Tissue expression)UBD
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15205   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO15205  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO15205
Splice isoforms : SwissVarO15205
PhosPhoSitePlusO15205
Domaine pattern : Prosite (Expaxy)UBIQUITIN_2 (PS50053)   
Domains : Interpro (EBI)Ubiquitin    Ubiquitin-rel_dom    Ubiquitin_dom   
Domain families : Pfam (Sanger)ubiquitin (PF00240)   
Domain families : Pfam (NCBI)pfam00240   
Domain families : Smart (EMBL)UBQ (SM00213)  
Conserved Domain (NCBI)UBD
DMDM Disease mutations10537
Blocks (Seattle)UBD
PDB (SRS)2MBE   
PDB (PDBSum)2MBE   
PDB (IMB)2MBE   
PDB (RSDB)2MBE   
Structural Biology KnowledgeBase2MBE   
SCOP (Structural Classification of Proteins)2MBE   
CATH (Classification of proteins structures)2MBE   
SuperfamilyO15205
Human Protein AtlasENSG00000213886
Peptide AtlasO15205
HPRD09354
IPIIPI00007405   IPI00478768   
Protein Interaction databases
DIP (DOE-UCLA)O15205
IntAct (EBI)O15205
FunCoupENSG00000213886
BioGRIDUBD
STRING (EMBL)UBD
ZODIACUBD
Ontologies - Pathways
QuickGOO15205
Ontology : AmiGOprotein binding  nucleus  nucleolus  cytoplasm  proteolysis  ubiquitin-dependent protein catabolic process  response to organonitrogen compound  aggresome  protein ubiquitination  protein modification by small protein conjugation  response to interferon-gamma  response to tumor necrosis factor  myeloid dendritic cell differentiation  positive regulation of apoptotic process  positive regulation of I-kappaB kinase/NF-kappaB signaling  proteasome binding  aggresome assembly  
Ontology : EGO-EBIprotein binding  nucleus  nucleolus  cytoplasm  proteolysis  ubiquitin-dependent protein catabolic process  response to organonitrogen compound  aggresome  protein ubiquitination  protein modification by small protein conjugation  response to interferon-gamma  response to tumor necrosis factor  myeloid dendritic cell differentiation  positive regulation of apoptotic process  positive regulation of I-kappaB kinase/NF-kappaB signaling  proteasome binding  aggresome assembly  
NDEx NetworkUBD
Atlas of Cancer Signalling NetworkUBD
Wikipedia pathwaysUBD
Orthology - Evolution
OrthoDB10537
GeneTree (enSembl)ENSG00000213886
Phylogenetic Trees/Animal Genes : TreeFamUBD
HOVERGENO15205
HOGENOMO15205
Homologs : HomoloGeneUBD
Homology/Alignments : Family Browser (UCSC)UBD
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerUBD [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)UBD
dbVarUBD
ClinVarUBD
1000_GenomesUBD 
Exome Variant ServerUBD
ExAC (Exome Aggregation Consortium)UBD (select the gene name)
Genetic variants : HAPMAP10537
Genomic Variants (DGV)UBD [DGVbeta]
DECIPHER (Syndromes)6:29523389-29527702  ENSG00000213886
CONAN: Copy Number AnalysisUBD 
Mutations
ICGC Data PortalUBD 
TCGA Data PortalUBD 
Broad Tumor PortalUBD
OASIS PortalUBD [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICUBD  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDUBD
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch UBD
DgiDB (Drug Gene Interaction Database)UBD
DoCM (Curated mutations)UBD (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)UBD (select a term)
intoGenUBD
NCG5 (London)UBD
Cancer3DUBD(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606050   
Orphanet
MedgenUBD
Genetic Testing Registry UBD
NextProtO15205 [Medical]
TSGene10537
GENETestsUBD
Huge Navigator UBD [HugePedia]
snp3D : Map Gene to Disease10537
BioCentury BCIQUBD
ClinGenUBD
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10537
Chemical/Pharm GKB GenePA38682
Clinical trialUBD
Miscellaneous
canSAR (ICR)UBD (select the gene name)
Probes
Litterature
PubMed76 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineUBD
EVEXUBD
GoPubMedUBD
iHOPUBD
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:41:27 CEST 2017

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