UBE2C (ubiquitin-conjugating enzyme E2C)
2008-06-01 Pierlorenzo Pallante , Maria Teresa Berlingieri , Alfredo Fusco AffiliationIstituto 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
Identity
HGNC
LOCATION
20q13.12
LOCUSID
ALIAS
UBCH10,dJ447F3.2
FUSION GENES
DNA/RNA
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.
Proteins
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.
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.
Cytosol.
Cytosol.
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 name
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 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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17933517 | 2007 | UbcH10 is overexpressed in malignant breast carcinomas. | Berlingieri MT et al |
| 16204036 | 2005 | Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. | Bredel M et al |
| 17659439 | 2008 | Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen. | Campone M et al |
| 17220641 | 2006 | Combination 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 |
| 12427990 | 2002 | Molecular characterization of plant ubiquitin-conjugating enzymes belonging to the UbcP4/E2-C/UBCx/UbcH10 gene family. | Criqui MC et al |
| 15260889 | 2004 | A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue. | Dairkee SH et al |
| 17354233 | 2007 | Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. | Ieta K et al |
| 15949568 | 2005 | In silico chromosomal clustering of genes displaying altered expression patterns in ovarian cancer. | Israeli O et al |
| 18331723 | 2008 | Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors. | Jiang L et al |
| 15749827 | 2005 | A novel UbcH10-binding protein facilitates the ubiquitinylation of cyclin B in vitro. | Kobirumaki F et al |
| 17465858 | 2007 | Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models. | Lee JJ et al |
| 17217624 | 2006 | Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on esophageal adenocarcinoma. | Lin J et al |
| 11927573 | 2002 | Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10. | Lin Y et al |
| 17243165 | 2007 | Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. | Narayan G et al |
| 12874022 | 2003 | UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. | Okamoto Y et al |
| 16106252 | 2005 | UbcH10 overexpression may represent a marker of anaplastic thyroid carcinomas. | Pallante P et al |
| 16896351 | 2006 | The anaphase promoting complex/cyclosome: a machine designed to destroy. | Peters JM et al |
| 15558010 | 2004 | Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. | Rape M et al |
| 16413484 | 2006 | The processivity of multiubiquitination by the APC determines the order of substrate degradation. | Rape M et al |
| 17443186 | 2007 | Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. | Reddy SK et al |
| 17443180 | 2007 | Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. | Stegmeier F et al |
| 16772118 | 2006 | 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 et al |
| 11739784 | 2001 | APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. | Tang Z et al |
| 9122200 | 1997 | Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. | Townsley FM et al |
| 15208666 | 2004 | Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. | Wagner KW et al |
| 17624412 | 2007 | Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer. | Walker G et al |
| 8723350 | 1996 | Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. | Yu H et al |
| 16287080 | 2006 | Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters. | Zirn B et al |
| 16969093 | 2006 | Before 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
Variants:
dbSNP: 11065
ClinVar: 11065
TCGA: ENSG00000175063
COSMIC: UBE2C
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38637730 | 2024 | UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation. | 0 |
| 38949026 | 2024 | UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer. | 0 |
| 38637730 | 2024 | UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation. | 0 |
| 38949026 | 2024 | UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer. | 0 |
| 36548081 | 2023 | The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. | 12 |
| 37168048 | 2023 | Expression significance of Emi1, UBCH10 and CyclinB1 in esophageal squamous cell carcinoma. | 1 |
| 37335710 | 2023 | Aberrant expression of UBE2C in endometrial cancer and its correlation to epithelial mesenchymal transition. | 1 |
| 37486389 | 2023 | Restored UBE2C expression in islets promotes β-cell regeneration in mice by ubiquitinating PER1. | 1 |
| 37496990 | 2023 | FOXM1-regulated ZIC2 promotes the malignant phenotype of renal clear cell carcinoma by activating UBE2C/mTOR signaling pathway. | 1 |
| 37535572 | 2023 | System analysis identifies UBE2C as a novel oncogene target for adrenocortical carcinoma. | 2 |
| 37580802 | 2023 | Comprehensive analysis of UBE2C expression and its potential roles and mechanisms in hepatocellular carcinoma. | 1 |
| 37848988 | 2023 | Identification of transcriptome characteristics of granulosa cells and the possible role of UBE2C in the pathogenesis of premature ovarian insufficiency. | 1 |
| 37958776 | 2023 | Role of UBE2C in Brain Cancer Invasion and Dissemination. | 3 |
| 38009019 | 2023 | UBE2C promotes malignancy of cutaneous squamous cell carcinoma. | 0 |
| 38102624 | 2023 | Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma. | 0 |
Citation
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
