UBE2C (ubiquitin-conjugating enzyme E2C)

2008-06-01   Pierlorenzo 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





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.


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.



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.


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.




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.
Atlas Image

Implicated in

Entity name
Human cancers
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.
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 Barretts 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.
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.
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.


Pubmed IDLast YearTitleAuthors
179335172007UbcH10 is overexpressed in malignant breast carcinomas.Berlingieri MT et al
162040362005Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas.Bredel M et al
176594392008Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen.Campone M et al
172206412006Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array.Chen CC et al
124279902002Molecular characterization of plant ubiquitin-conjugating enzymes belonging to the UbcP4/E2-C/UBCx/UbcH10 gene family.Criqui MC et al
152608892004A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue.Dairkee SH et al
173542332007Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression.Ieta K et al
159495682005In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer.Israeli O et al
183317232008Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors.Jiang L et al
157498272005A novel UbcH10-binding protein facilitates the ubiquitinylation of cyclin B in vitro.Kobirumaki F et al
174658582007Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models.Lee JJ et al
172176242006Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma.Lin J et al
119275732002Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.Lin Y et al
172431652007Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes.Narayan G et al
128740222003UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme.Okamoto Y et al
161062522005UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas.Pallante P et al
168963512006The anaphase promoting complex/cyclosome: a machine designed to destroy.Peters JM et al
155580102004Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry.Rape M et al
164134842006The processivity of multiubiquitination by the APC determines the order of substrate degradation.Rape M et al
174431862007Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation.Reddy SK et al
174431802007Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities.Stegmeier F et al
167721182006Detection 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 et al
117397842001APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.Tang Z et al
91222001997Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase.Townsley FM et al
152086662004Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin.Wagner KW et al
176244122007Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer.Walker G et al
87233501996Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation.Yu H et al
162870802006Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters.Zirn B et al
169690932006Before and after the spindle assembly checkpoint--an APC/C point of view.de Gramont A et al

Other Information

Locus ID:

NCBI: 11065
MIM: 605574
HGNC: 15937
Ensembl: ENSG00000175063


dbSNP: 11065
ClinVar: 11065
TCGA: ENSG00000175063


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Ubiquitin mediated proteolysisKEGGko04120
Ubiquitin mediated proteolysisKEGGhsa04120
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Class I MHC mediated antigen processing & presentationREACTOMER-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradationREACTOMER-HSA-983168
Cell CycleREACTOMER-HSA-1640170
Cell Cycle CheckpointsREACTOMER-HSA-69620
Mitotic Spindle CheckpointREACTOMER-HSA-69618
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint componentsREACTOMER-HSA-141405
Inactivation of APC/C via direct inhibition of the APC/C complexREACTOMER-HSA-141430
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813
Regulation of mitotic cell cycleREACTOMER-HSA-453276
APC/C-mediated degradation of cell cycle proteinsREACTOMER-HSA-174143
Regulation of APC/C activators between G1/S and early anaphaseREACTOMER-HSA-176408
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176814
Phosphorylation of the APC/CREACTOMER-HSA-176412
APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176409
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpointREACTOMER-HSA-179419
Cdc20:Phospho-APC/C mediated degradation of Cyclin AREACTOMER-HSA-174184
APC-Cdc20 mediated degradation of Nek2AREACTOMER-HSA-179409
APC/C:Cdc20 mediated degradation of Cyclin BREACTOMER-HSA-174048
APC/C:Cdc20 mediated degradation of SecurinREACTOMER-HSA-174154
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphaseREACTOMER-HSA-176407
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1REACTOMER-HSA-174178
Autodegradation of Cdh1 by Cdh1:APC/CREACTOMER-HSA-174084
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Senescence-Associated Secretory Phenotype (SASP)REACTOMER-HSA-2559582
Protein ubiquitinationREACTOMER-HSA-8852135
Synthesis of active ubiquitin: roles of E1 and E2 enzymesREACTOMER-HSA-8866652

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
200650912010Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation.79
215560512011Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth.62
128740222003UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme.54
187221802008The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC.52
152086662004Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin.47
258257792015RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex.37
172176242006Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma.31
173542332007Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression.31
161062522005UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas.28


Pierlorenzo Pallante ; Maria Teresa Berlingieri ; Alfredo Fusco

UBE2C (ubiquitin-conjugating enzyme E2C)

Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

Online version: http://atlasgeneticsoncology.org/gene/44079/ube2c-(ubiquitin-conjugating-enzyme-e2c)