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UBE2C (ubiquitin-conjugating enzyme E2C)

Written2008-06Pierlorenzo Pallante, Maria Teresa Berlingieri, Alfredo Fusco
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli Federico II, via Pansini 5, 80131 Napoli, Italy

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Alias_namesubiquitin-conjugating enzyme E2C
Alias_symbol (synonym)UBCH10
Other aliasUBE2C-PEN
LocusID (NCBI) 11065
Atlas_Id 44079
Location 20q13.12  [Link to chromosome band 20q13]
Location_base_pair Starts at 45813033 and ends at 45816957 bp from pter ( according to hg19-Feb_2009)  [Mapping UBE2C.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
UBE2C (20q13.12) / UBE2C (20q13.12)
Note UbcH10 catalyzes the covalent attachment of ubiquitin to target proteins. It is required for the destruction of mitotic cyclins.


Description UBE2C is located on chromosome 20, at 20q13.12 according to Entrez Gene. In AceView, it covers 4.40 kb, from 43874623 to 43879017 on the direct strand.
Transcription There are 6 representative transcripts annotated in RefSeq database, but, according to AceView, Homo sapiens cDNA sequences in GenBank support at least 13 spliced variants. Isoform 1, the longest isoform, is composed of 6 coding exons of varying lengths, separated by introns: NM_007019.2 (mRNA-ubiquitin-conjugating enzyme E2C): mRNA product length: 823.


Description The UbcH10 gene encodes a member of the E2 ubiquitin-conjugating enzyme family that is involved in the ubiquitin dependent proteolysis. In this pathway, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), together with ubiquitin ligase (E3), catalyze the covalent attachment of ubiquitin to target proteins, targeting them for degradation mediated by the 26S proteasome.
The full-length UbcH10 contains 179 residues for a 19.6 kDa weight. It belongs to the class III Ubc proteins that are characterized by an NH2-terminal extension followed by the "core" Ubc fold.
Like all E2 enzymes, UbcH10 contains an active site cysteine residue (position 114) that is crucial for the formation of the ubiquitin-thiolester. Alteration of this residue C(114)S strongly inhibits ubiquitination of cyclin A and Cyclin B confering a dominant-negative phenotype.
Levels of UbcH10 are modulated by autoubiquitination. This process is dependent on a motif, the "destruction box" [Arg-X-X-Leu-X-X-(Leu/Ile)-X-Asp] recognized by the mitotic-specific ubiquitination machinery.
A study suggests that a destruction box is present in the UbcH10 sequence and includes residues 129-132 (Arg-Thr-Ile-Leu). Interestingly an SNP is reported for the residue 129 (refSNP ID: rs7352110, alleles A/G, Arg>Gly).
This would be important since any change in the putative destruction box could stabilize UbcH10 against destruction.
Expression UbcH10 mRNA and protein are expressed at low levels in most adult normal tissues. In contrast, UbcH10 mRNA and protein are highly expressed in tumor tissues. Moreover, UbcH10 protein levels fluctuate during the cell cycle being abundant during M and early G1 phases, but decreasing in late G1, S and G2 phases.
Localisation Nucleoplasm.
Function UbcH10 is crucial for cell cycle progression during the G2/M phase, since its function is required for the destruction of mitotic cyclins and other mitosis-related substrates. UbcH10 interacts with the multiprotein complex APC (anaphase-promoting complex), which has E3 ubiquitin ligase activity, and targets for destruction substrates from the preceding mitosis (cyclin A, cyclin B, securin, geminin). Once these target proteins have been degraded, UbcH10 adds ubiquitins to itself, triggering its own destruction. As a result, the absence of UbcH10 allows the accumulation of cyclin A, which in turn contributes to the APC inactivation, providing a molecular switch that allows cells to proceed from cell division to a new round of DNA duplication. Hence, the function of UbcH10 is strictly linked to the progression of cell cycle through the M phase and the coupling of mitosis to S-phase entry via autonomous regulation of the anaphase-promoting complex.

Implicated in

Entity Human cancers
Note Several studies suggest a possible use of UbcH10 investigation (together with other molecular markers) in early detection of cancer. Other studies suggest that inhibition of UbcH10 could have a therapeutic potential in cancer treatment.
Disease UbcH10 overexpression was reported in a number of human cancer cell lines and primary tumors and expression data strongly support an association between high UbcH10 expression and a poor tumor differentiation. Expression studies have also shown a correlation between UbcH10 overexpression and the proliferation status since there is a good association with the proliferation marker Ki-67/MIB1. It was found overexpressed in lung carcinoma ( squamous and adenocarcinoma, poorly versus well differentiated), bladder carcinoma (grade 3 versus grade 2), prostate carcinoma(metastatic versus primary), gastric adenocarcinoma cervical, esophageal adenocarcinoma(adenocarcinoma versus Barrett's metaplasia), breast cancer (grade 3 versus grade 1, malignant versus benign neoplastic lesions), brain ( astrocytomas versus low-grade tumors or normal controls), medulloblastoma, ovarian carcinoma (grade 3 versus grade 1 and 2), thyroid carcinoma (poorly versus well differentiated), adrenocortical gland, Wilms tumor (relapsed versus relapse-free) hepatocellular carcinoma (correlation with higher frequencies of invasion to capsular formation, invasion to portal vein and tumor de-differentiation). Several expression analysis and functional studies have also shown that UbcH10 resulted up-regulated in experimental model of carcinogenesis, that its overexpression lead to the acquisition of a malignant phenotype and that its knockdown successfully resulted in growth arrest.
Prognosis It was seen that UbcH10 overexpression is a negative predictor of clinical outcome in patients affected by ovarian and hepatocellular carcinoma. Therefore, UbcH10 has been suggested as an helpful prognostic indicator for ovarian and hepatocellular carcinoma patients.
Oncogenesis 20q13.1 chromosomal region is frequently associated with genomic amplification in different malignant neoplasias and amplification of UbcH10 locus has been reported in the case of gastroesophageal carcinomas, colorectal carcinomas with liver metastases, cervical cancers, ovarian carcinomas, gliomas and culture cell lines obtained from anaplastic thyroid carcinomas.


UbcH10 is overexpressed in malignant breast carcinomas.
Berlingieri MT, Pallante P, Sboner A, Barbareschi M, Bianco M, Ferraro A, Mansueto G, Borbone E, Guerriero E, Troncone G, Fusco A.
Eur J Cancer 2007; 43: 2729-35.
PMID 17933517
Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas.
Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI.
Cancer Res 2005; 65: 8679-89.
PMID 16204036
Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen.
Campone M, Campion L, Roche H, Gouraud W, Charbonnel C, Magrangeas F, Minvielle S, Geneve J, Martin AL, Bataille R, Jezequel P.
Breast Cancer Res Treat 2008; 109: 491-501.
PMID 17659439
Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array.
Chen CC, Chang TW, Chen FM, Hou MF, Hung SY, Chong IW, Lee SC, Zhou TH, Lin SR.
Oncology 2006; 70: 438-46.
PMID 17220641
Molecular characterization of plant ubiquitin-conjugating enzymes belonging to the UbcP4/E2-C/UBCx/UbcH10 gene family.
Criqui MC, de Almeida Engler J, Camasses A, Capron A, Parmentier Y, Inze D, Genschik P.
Plant Physiol 2002; 130: 1230-40.
PMID 12427990
A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue.
Dairkee SH, Ji Y, Ben Y, Moore DH, Meng Z, Jeffrey SS.
BMC Genomics 2004; 5:47.
PMID 15260889
Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression.
Ieta K, Ojima E, Tanaka F, Nakamura Y, Haraguchi N, Mimori K, Inoue H, Kuwano H, Mori M.
Int J Cancer 2007; 121: 33-8.
PMID 17354233
In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer.
Israeli O, Goldring-Aviram A, Rienstein S, Ben-Baruch G, Korach J, Goldman B, Friedman E.
Cancer Genet Cytogenet 2005; 160: 35-42.
PMID 15949568
Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors.
Jiang L, Huang CG, Lu YC, Luo C, Hu GH, Liu HM, Chen JX, Han HX.
Brain Res 2008; 1201: 161-6.
PMID 18331723
A novel UbcH10-binding protein facilitates the ubiquitinylation of cyclin B in vitro.
Kobirumaki F, Miyauchi Y, Fukami K, Tanaka H.
J Biochem 2005; 137: 133-9.
PMID 15749827
Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models.
Lee JJ, Foukakis T, Hashemi J, Grimelius L, Heldin NE, Wallin G, Rudduck C, Lui WO, Hoog A, Larsson C.
Thyroid 2007; 17: 289-301.
PMID 17465858
Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma.
Lin J, Raoof DA, Wang Z, Lin MY, Thomas DG, Greenson JK, Giordano TJ, Orringer MB, Chang AC, Beer DG, Lin L.
Neoplasia 2006; 8: 1062-71.
PMID 17217624
Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.
Lin Y, Hwang WC, Basavappa R.
J Biol Chem 2002; 277: 21913-21.
PMID 11927573
Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes.
Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Durst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV.
Genes Chromosomes Cancer 2007; 46: 373-84.
PMID 17243165
UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme.
Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A.
Cancer Res 2003; 63: 4167-73.
PMID 12874022
UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas.
Pallante P, Berlingieri MT, Troncone G, Kruhoffer M, Orntoft TF, Viglietto G, Caleo A, Migliaccio I, Decaussin-Petrucci M, Santoro M, Palombini L, Fusco A.
Br J Cancer 2005; 93: 464-71.
PMID 16106252
The anaphase promoting complex/cyclosome: a machine designed to destroy.
Peters JM.
Nat Rev Mol Cell Biol 2006; 7: 644-56. Review.
PMID 16896351
Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry.
Rape M, Kirschner MW.
Nature 2004; 432: 588-95.
PMID 15558010
The processivity of multiubiquitination by the APC determines the order of substrate degradation.
Rape M, Reddy SK, Kirschner MW.
Cell 2006; 124: 89-103.
PMID 16413484
Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation.
Reddy SK, Rape M, Margansky WA, Kirschner MW.
Nature 2007; 446: 921-5.
PMID 17443186
Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities.
Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER 3rd, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ.
Nature 2007; 446: 876-81.
PMID 17443180
Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH.
Takahashi Y, Ishii Y, Nishida Y, Ikarashi M, Nagata T, Nakamura T, Yamamori S, Asai S.
Cancer Genet Cytogenet 2006; 168: 30-5.
PMID 16772118
APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.
Tang Z, Li B, Bharadwaj R, Zhu H, Ozkan E, Hakala K, Deisenhofer J, Yu H.
Mol Biol Cell 2001; 12: 3839-51.
PMID 11739784
Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase.
Townsley FM, Aristarkhov A, Beck S, Hershko A, Ruderman JV.
Proc Natl Acad Sci U S A 1997; 94: 2362-7.
PMID 9122200
Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin.
Wagner KW, Sapinoso LM, El-Rifai W, Frierson HF, Butz N, Mestan J, Hofmann F, Deveraux QL, Hampton GM.
Oncogene 2004; 23: 6621-9.
PMID 15208666
Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer.
Walker G, MacLeod K, Williams AR, Cameron DA, Smyth JF, Langdon SP.
Gynecol Oncol. 2007 Sep;106(3):461-8.
PMID 17624412
Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation.
Yu H, King RW, Peters JM, Kirschner MW.
Curr Biol 1996; 6: 455-66.
PMID 8723350
Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters.
Zirn B, Hartmann O, Samans B, Krause M, Wittmann S, Mertens F, Graf N, Eilers M, Gessler M.
Int J Cancer 2006; 118: 1954-62.
PMID 16287080
Before and after the spindle assembly checkpoint--an APC/C point of view.
de Gramont A, Ganier O, Cohen-Fix O.
Cell Cycle 2006; 5: 2168-71.
PMID 16969093


This paper should be referenced as such :
Pallate, P ; Berlingieri, MT ; Fusco, A
UBE2C (ubiquitin-conjugating enzyme E2C)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(5):367-370.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)UBE2C   15937
Entrez_Gene (NCBI)UBE2C  11065  ubiquitin conjugating enzyme E2 C
AliasesUBCH10; dJ447F3.2
GeneCards (Weizmann)UBE2C
Ensembl hg19 (Hinxton)ENSG00000175063 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000175063 [Gene_View]  ENSG00000175063 [Sequence]  chr20:45813033-45816957 [Contig_View]  UBE2C [Vega]
ICGC DataPortalENSG00000175063
TCGA cBioPortalUBE2C
Genatlas (Paris)UBE2C
SOURCE (Princeton)UBE2C
Genetics Home Reference (NIH)UBE2C
Genomic and cartography
GoldenPath hg38 (UCSC)UBE2C  -     chr20:45813033-45816957 +  20q13.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)UBE2C  -     20q13.12   [Description]    (hg19-Feb_2009)
GoldenPathUBE2C - 20q13.12 [CytoView hg19]  UBE2C - 20q13.12 [CytoView hg38]
Mapping of homologs : NCBIUBE2C [Mapview hg19]  UBE2C [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK311949 BC007656 BC016292 BC028161 BC050736
RefSeq transcript (Entrez)NM_001281741 NM_001281742 NM_007019 NM_181799 NM_181800 NM_181801 NM_181802 NM_181803
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)UBE2C
Cluster EST : UnigeneHs.93002 [ NCBI ]
CGAP (NCI)Hs.93002
Alternative Splicing GalleryENSG00000175063
Gene ExpressionUBE2C [ NCBI-GEO ]   UBE2C [ EBI - ARRAY_EXPRESS ]   UBE2C [ SEEK ]   UBE2C [ MEM ]
Gene Expression Viewer (FireBrowse)UBE2C [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11065
GTEX Portal (Tissue expression)UBE2C
Human Protein AtlasENSG00000175063-UBE2C [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO00762   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO00762  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO00762
Splice isoforms : SwissVarO00762
Domaine pattern : Prosite (Expaxy)UBIQUITIN_CONJUGAT_1 (PS00183)    UBIQUITIN_CONJUGAT_2 (PS50127)   
Domains : Interpro (EBI)UBQ-conjugat_E2    UBQ-conjugating_AS    UBQ-conjugating_enzyme/RWD   
Domain families : Pfam (Sanger)UQ_con (PF00179)   
Domain families : Pfam (NCBI)pfam00179   
Conserved Domain (NCBI)UBE2C
DMDM Disease mutations11065
Blocks (Seattle)UBE2C
PDB (RSDB)1I7K    4YII    5A31    5KHR    5L9U   
PDB Europe1I7K    4YII    5A31    5KHR    5L9U   
PDB (PDBSum)1I7K    4YII    5A31    5KHR    5L9U   
PDB (IMB)1I7K    4YII    5A31    5KHR    5L9U   
Structural Biology KnowledgeBase1I7K    4YII    5A31    5KHR    5L9U   
SCOP (Structural Classification of Proteins)1I7K    4YII    5A31    5KHR    5L9U   
CATH (Classification of proteins structures)1I7K    4YII    5A31    5KHR    5L9U   
Human Protein Atlas [tissue]ENSG00000175063-UBE2C [tissue]
Peptide AtlasO00762
IPIIPI00013002   IPI00335560   IPI00335561   IPI00375616   IPI00375615   
Protein Interaction databases
IntAct (EBI)O00762
Ontologies - Pathways
Ontology : AmiGOubiquitin ligase complex  ubiquitin-protein transferase activity  ubiquitin-protein transferase activity  protein binding  ATP binding  nucleus  nucleoplasm  anaphase-promoting complex  cytosol  cytosol  plasma membrane  ubiquitin-dependent protein catabolic process  ubiquitin-dependent protein catabolic process  exit from mitosis  free ubiquitin chain polymerization  protein ubiquitination  protein ubiquitination  anaphase-promoting complex-dependent catabolic process  anaphase-promoting complex-dependent catabolic process  anaphase-promoting complex-dependent catabolic process  positive regulation of exit from mitosis  ubiquitin-like protein ligase binding  cell division  ubiquitin conjugating enzyme activity  ubiquitin conjugating enzyme activity  protein K48-linked ubiquitination  protein K11-linked ubiquitination  regulation of mitotic cell cycle phase transition  positive regulation of ubiquitin protein ligase activity  
Ontology : EGO-EBIubiquitin ligase complex  ubiquitin-protein transferase activity  ubiquitin-protein transferase activity  protein binding  ATP binding  nucleus  nucleoplasm  anaphase-promoting complex  cytosol  cytosol  plasma membrane  ubiquitin-dependent protein catabolic process  ubiquitin-dependent protein catabolic process  exit from mitosis  free ubiquitin chain polymerization  protein ubiquitination  protein ubiquitination  anaphase-promoting complex-dependent catabolic process  anaphase-promoting complex-dependent catabolic process  anaphase-promoting complex-dependent catabolic process  positive regulation of exit from mitosis  ubiquitin-like protein ligase binding  cell division  ubiquitin conjugating enzyme activity  ubiquitin conjugating enzyme activity  protein K48-linked ubiquitination  protein K11-linked ubiquitination  regulation of mitotic cell cycle phase transition  positive regulation of ubiquitin protein ligase activity  
Pathways : KEGGUbiquitin mediated proteolysis   
REACTOMEO00762 [protein]
REACTOME PathwaysR-HSA-983168 [pathway]   
NDEx NetworkUBE2C
Atlas of Cancer Signalling NetworkUBE2C
Wikipedia pathwaysUBE2C
Orthology - Evolution
GeneTree (enSembl)ENSG00000175063
Phylogenetic Trees/Animal Genes : TreeFamUBE2C
Homologs : HomoloGeneUBE2C
Homology/Alignments : Family Browser (UCSC)UBE2C
Gene fusions - Rearrangements
Fusion : FusionGDB40384    40385   
Fusion : Fusion_HubUBE2C--CPNE3    UBE2C--UBE2C   
Fusion : QuiverUBE2C
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerUBE2C [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)UBE2C
Exome Variant ServerUBE2C
ExAC (Exome Aggregation Consortium)ENSG00000175063
GNOMAD BrowserENSG00000175063
Varsome BrowserUBE2C
Genetic variants : HAPMAP11065
Genomic Variants (DGV)UBE2C [DGVbeta]
DECIPHERUBE2C [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisUBE2C 
ICGC Data PortalUBE2C 
TCGA Data PortalUBE2C 
Broad Tumor PortalUBE2C
OASIS PortalUBE2C [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICUBE2C  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DUBE2C
Mutations and Diseases : HGMDUBE2C
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch UBE2C
DgiDB (Drug Gene Interaction Database)UBE2C
DoCM (Curated mutations)UBE2C (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)UBE2C (select a term)
NCG5 (London)UBE2C
Cancer3DUBE2C(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry UBE2C
NextProtO00762 [Medical]
Target ValidationUBE2C
Huge Navigator UBE2C [HugePedia]
snp3D : Map Gene to Disease11065
BioCentury BCIQUBE2C
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD11065
Chemical/Pharm GKB GenePA38057
Clinical trialUBE2C
canSAR (ICR)UBE2C (select the gene name)
DataMed IndexUBE2C
Other databaseBioGRID
Other databasePANTHER
Other databaseiHOP
Other databaseMGI GO
Other databaseCyclebase
Other databaseApropos
Other databaseYRC
Other databaseH-InvDB
Other database
PubMed180 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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