UBE2C

Summary

UBE2C (ubiquitin conjugating enzyme E2 C, HGNC:15937) is a protein-coding gene on chromosome 20q13.12, encoding Ubiquitin-conjugating enzyme E2 C (O00762). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. It is a selective cancer dependency (DepMap: 70.4% of cell lines).

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin-protein ligases. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is required for the destruction of mitotic cyclins and for cell cycle progression, and may be involved in cancer progression. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been defined on chromosomes 4, 14, 15, 18, and 19.

Source: NCBI Gene 11065 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 70.4% of screened cell lines
• MANE Select transcript: NM_007019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15937
Approved symbol	UBE2C
Name	ubiquitin conjugating enzyme E2 C
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	UBCH10
Ensembl gene	ENSG00000175063
Ensembl biotype	protein_coding
OMIM	605574
Entrez	11065

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000243893, ENST00000335046, ENST00000352551, ENST00000356455, ENST00000372568, ENST00000405520, ENST00000496085, ENST00000617055, ENST00000934111, ENST00000934112, ENST00000934113

RefSeq mRNA: 6 — MANE Select: NM_007019 NM_001281741, NM_001281742, NM_007019, NM_181799, NM_181800, NM_181801

CCDS: CCDS13370, CCDS13371, CCDS13372, CCDS13374, CCDS74733, CCDS74734

Canonical transcript exons

ENST00000356455 — 6 exons

Exon	Start	End
ENSE00000845041	45814384	45814470
ENSE00001258938	45815541	45815745
ENSE00003530898	45815854	45815913
ENSE00003636555	45813437	45813464
ENSE00003843033	45816709	45816952
ENSE00003845276	45812644	45812796

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 151.2657 / max 1228.2280, expressed in 1542 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184945	119.3101	1496
184946	23.6670	1361
184944	7.1952	1119
184947	0.7423	487
184948	0.3511	209

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.31	gold quality
embryo	UBERON:0000922	98.40	gold quality
ganglionic eminence	UBERON:0004023	98.31	gold quality
oocyte	CL:0000023	98.27	gold quality
endometrium epithelium	UBERON:0004811	95.76	gold quality
mucosa of transverse colon	UBERON:0004991	95.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.17	gold quality
lower esophagus mucosa	UBERON:0035834	94.89	gold quality
tongue squamous epithelium	UBERON:0006919	93.64	gold quality
bone marrow	UBERON:0002371	93.43	gold quality
secondary oocyte	CL:0000655	93.15	gold quality
thymus	UBERON:0002370	92.53	gold quality
trabecular bone tissue	UBERON:0002483	92.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.02	gold quality
rectum	UBERON:0001052	91.01	gold quality
esophagus mucosa	UBERON:0002469	90.72	gold quality
bone marrow cell	CL:0002092	90.08	gold quality
gingival epithelium	UBERON:0001949	89.58	gold quality
stromal cell of endometrium	CL:0002255	89.54	gold quality
vermiform appendix	UBERON:0001154	88.38	gold quality
cartilage tissue	UBERON:0002418	87.84	gold quality
hair follicle	UBERON:0002073	87.81	gold quality
ileal mucosa	UBERON:0000331	87.69	gold quality
gingiva	UBERON:0001828	87.54	gold quality
lymph node	UBERON:0000029	85.84	gold quality
duodenum	UBERON:0002114	85.77	gold quality
caecum	UBERON:0001153	85.55	gold quality
squamous epithelium	UBERON:0006914	85.48	gold quality
epithelium of esophagus	UBERON:0001976	85.15	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.66	gold quality

Single-cell (SCXA)

Detected in 45 experiment(s), a significant marker in 41.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	3859.11
E-MTAB-10485	yes	3499.10
E-HCAD-5	yes	2667.70
E-MTAB-11121	yes	2033.93
E-HCAD-10	yes	2033.53
E-MTAB-9435	yes	2028.63
E-HCAD-56	yes	1930.58
E-MTAB-10662	yes	1432.52
E-HCAD-24	yes	1392.26
E-GEOD-124472	yes	1215.41
E-MTAB-6911	yes	1201.37
E-CURD-79	yes	1140.76
E-HCAD-6	yes	1089.24
E-MTAB-9154	yes	912.95
E-GEOD-75140	yes	864.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, E2F4, FOXA1, MED1, MYC, NCOA1, NCOA3

miRNA regulators (miRDB)

14 targeting UBE2C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-4521	97.73	67.64	684

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 70.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• UbcH10 is highly expressed in various human primary tumors and UbcH10 has an ability to promote cell growth and malignant transformation. (PMID:12874022)
• UbcH10 plays an important role in tumor development and that its inhibition in combination with agonists of the TRAIL receptor may provide an enhanced therapeutic index (PMID:15208666)
• UbcH10 overexpression is involved in thyroid cell proliferation and may represent a marker of thyroid anaplastic carcinomas (PMID:16106252)
• results showing aberrations in levels of gene expression and locus copy number of ubiquitin-conjugating enzyme E2C gene (UBE2C) suggest that this gene may play an important role in tumor progression leading to advanced colon cancer with liver metastasis (PMID:16772118)
• Transfection of dominant-negative UBE2C into Seg-1 esophageal adenocarcinoma cells decreases proliferation and increased mitotic arrest compared to vector controls. (PMID:17217624)
• Ube2c gene appeared to be associated with hepatocellular carcinoma progression (PMID:17354233)
• These data suggest that overexpression of UbcH10 may serve as one important molecular mechanism that underlies the astrocytic carcinogenesis. (PMID:18331723)
• The rate-limiting role of UbcH10 is only at the end of G1 phase, just before DNA replication begins. (PMID:18559889)
• a clear correlation between UbcH10 expression and the histological grade of the astrocytic tumors. (PMID:18666437)
• UbcH10 combines a specific E2-E3 interface and regulation via its N-terminal extension to limit anaphase-promoting complex activity for substrate selection and checkpoint control. (PMID:18722180)
• Cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma. (PMID:18753363)
• Elevated expression of UbcH10 is associated with breast cancer. (PMID:19038004)
• Results show the clinicopathological significance of UbcH10 in the progression of colon cancer, and thus UbcH10 may act as a novel biomarker in patients with colon cancer. (PMID:19302711)
• Taken together, these results indicate that UbcH10 is a novel lymphoid proliferation marker encompassing the cell cycle window associated with exit from mitosis (PMID:19438748)
• One of those genes, UBE2C, seems to be a powerful biomarker for NSCLC survival prediction. (PMID:19638491)
• Data imply that knocking-down UbcH10 protein expression may represent a potential therapeutic option for glioma. (PMID:19657671)
• The overexpression of UbcH10 gene plays a critical role in the carcinogenesis and tumor progression of colorectal cancer. (PMID:19779934)
• The unstructured N-terminal region of UbcH10 directly binds the 19 S regulatory complex of the 26 S proteasome, and it mediates the initiation of substrate translocation. (PMID:20007692)
• show that UbcH10 overexpression leads to precocious degradation of cyclin B by the anaphase-promoting complex/cyclosome, supernumerary centrioles, lagging chromosomes, and aneuploidy. (PMID:20065091)
• elevated levels of Ubch10 and Cdc20 degrade cyclin B in hpv-16 iinfected cells, required for exit from mitosis, permitting initiation of the next round of DNA synthesis and cell cycle progression. (PMID:20739533)
• UbcH10 expression was associated with tumor invasion of the portal vein, tumor size, TNM staging, and tumor differentiation in hepatocellular carcinoma. (PMID:21354912)
• Spindle assembly checkpoint protein Cdc20 transcriptionally activates expression of ubiquitin carrier protein UbcH10. (PMID:21454660)
• Mediator complex subunit (MED)1 phosphorylation leads to UBE2C locus looping, UBE2C gene expression and cell growth in castration-resistant prostate cancer. (PMID:21556051)
• Effect of UBE2C overexpression on the proliferation of 293T cell line (PMID:21651863)
• High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients (PMID:22056852)
• Overexpression of UbcH10 may be a useful indicator of endometrial carcinoma. (PMID:22415060)
• growth rate of SiHa and HeLa transfected with dominant negative-UBE2C was significantly reduced compared to vector control (PMID:22694363)
• Data sugggest that UbcH10 may play an important role in non-small cell lung cancer (NSCLC) carcinogenesis, and silencing UbcH10 may represent a potential therapeutic strategy for NSCLC. (PMID:22760214)
• UbcH10 overexpression has a critical role in lung carcinogenesis, and the evaluation of UbcH10 expression levels may be a new tool for the characterisation of non small cell lung carcinoma. (PMID:23102841)
• the expression of cyclin D1, MCM7, TRIM29, and UBE2C was found to be significantly associated with progression to muscle-invasive bladder cancer. (PMID:23201130)
• High expression of UbcH10 was associated with pancreatic ductal adenocarcinoma. (PMID:23355337)
• Data indicate that expression-based risk indices of three genes UBE2C, TPX2, and MELK were more strongly associated with poor 5-year survival in adenocarcinoma patients. (PMID:23357462)
• UBE2C positivity is independently associated with shorter cancer-specific survival in bladder cancer patients who underwent radical cystectomy. (PMID:23826418)
• Data suggest that ubiquitin conjugating enzyme UBE2C may serve as a potential therapeutic target aimed at inducing radiation and chemo sensitization. (PMID:24072565)
• Elevated levels of S100A8 and UBE2C were observed. (PMID:24114735)
• Results suggest that UBE2C acts as an oncogene in prostate cancer progression. (PMID:24512726)
• UBE2C may be a marker for diagnosis of nonpalpable breast lesions but not benign or malignant tumors in mammography core biopsies. Suppression of UBE2C may be a potential therapy target in breast cancer. (PMID:24699941)
• the UBE2C gene is capable of promoting proliferation and invasion of lung cancer cells. Therefore, UBE2C may play a pivotal role in development and invasion of lung cancer. (PMID:24815438)
• excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome to deregulate the expression of UBCH10 (PMID:25368385)
• UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer. (PMID:25376843)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	UBE2C	ENSDARG00000114670
mus_musculus	Ube2c	ENSMUSG00000001403
rattus_norvegicus	Ube2c	ENSRNOG00000015131
drosophila_melanogaster	vih	FBGN0264848

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), CDC34 (ENSG00000099804), UBE2I (ENSG00000103275), UBE2W (ENSG00000104343), UBE2R2 (ENSG00000107341), UBE2S (ENSG00000108106), UBE2B (ENSG00000119048), UBE2G1 (ENSG00000132388), UBE2Z (ENSG00000159202), UBE2J2 (ENSG00000160087), AKTIP (ENSG00000166971), UBE2V2 (ENSG00000169139), UBE2O (ENSG00000175931), UBE2U (ENSG00000177414), UBE2N (ENSG00000177889), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 C — O00762 (reviewed: O00762)

Alternative names: (E3-independent) E2 ubiquitin-conjugating enzyme C, E2 ubiquitin-conjugating enzyme C, UbcH10, Ubiquitin carrier protein C, Ubiquitin-protein ligase C

All UniProt accessions (5): A0A087WVK1, A0A0A0MSE8, O00762, K4DI81, Q5TZN3

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes ‘Lys-11’- and ‘Lys-48’-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating ‘Lys-11’-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit.

Subunit / interactions. Component of the APC/C complex, composed of at least 14 distinct subunits that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa. Within this complex, directly interacts with ANAPC2.

Post-translational modifications. Autoubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Its degradation plays a central role in APC/C regulation, allowing cyclin-A accumulation before S phase entry. APC/C substrates inhibit the autoubiquitination of UBE2C/UBCH10 but not its E2 function, hence APC/C remaining active until its substrates have been destroyed.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (4)

UniProt ID	Names	Canonical?
O00762-1	1	yes
O00762-2	2
O00762-3	3
O00762-4	4

RefSeq proteins (6): NP_001268670, NP_001268671, NP_008950, NP_861515, NP_861516, NP_861517 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR050113	Ub_conjugating_enzyme-E2-like	Family

Pfam: PF00179

Enzyme classification (BRENDA):

• EC 2.3.2.23 — E2 ubiquitin-conjugating enzyme (BRENDA: 20 organisms, 93 substrates, 28 inhibitors, 12 Km, 8 kcat entries)
• EC 2.3.2.24 — (E3-independent) E2 ubiquitin-conjugating enzyme (BRENDA: 5 organisms, 56 substrates, 7 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.2203–0.3014	2
[HISTONE H2A]-L-LYSINE	0.0008–0.0028	2
[HISTONE H2B]-L-LYSINE	0.0015–0.012	2
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1
[CYTOCHROME C]-L-LYSINE	0.125	1
[HISTONE H3]-L-LYSINE	0.0013	1

UniProt features (24 total): helix 5, strand 5, splice variant 3, turn 2, modified residue 2, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4YII	X-RAY DIFFRACTION	1.8
1I7K	X-RAY DIFFRACTION	1.95
8TAU	ELECTRON MICROSCOPY	3.5
9N9R	ELECTRON MICROSCOPY	3.9
9N9S	ELECTRON MICROSCOPY	3.9
8TAR	ELECTRON MICROSCOPY	4
5A31	ELECTRON MICROSCOPY	4.3
5KHR	ELECTRON MICROSCOPY	6.1
5L9U	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00762-F1	89.66	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 114 (glycyl thioester intermediate)

Post-translational modifications (2): 2, 3

Mutagenesis-validated functional residues (1):

Position	Phenotype
114	loss of function; inhibition of cyclin-b degradation.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176407	Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176412	Phosphorylation of the APC/C
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-68867	Assembly of the pre-replicative complex
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-9687136	Aberrant regulation of mitotic exit in cancer due to RB1 defects
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 492 (showing top): GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, REACTOME_DNA_REPLICATION, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, GNF2_CENPF, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_PHOSPHORYLATION_OF_THE_APC_C

GO Biological Process (16): protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), exit from mitosis (GO:0010458), free ubiquitin chain polymerization (GO:0010994), protein ubiquitination (GO:0016567), regulation of mitotic metaphase/anaphase transition (GO:0030071), anaphase-promoting complex-dependent catabolic process (GO:0031145), positive regulation of exit from mitosis (GO:0031536), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of mitotic metaphase/anaphase transition (GO:0045842), cell division (GO:0051301), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), positive regulation of ubiquitin protein ligase activity (GO:1904668), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (9): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin-like protein ligase binding (GO:0044389), ubiquitin protein ligase activity (GO:0061630), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
APC/C-mediated degradation of cell cycle proteins	4
APC/C:Cdc20 mediated degradation of mitotic proteins	2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Mitotic Anaphase	1
Cellular Senescence	1
DNA Replication Pre-Initiation	1
Switching of origins to a post-replicative state	1
Generic Transcription Pathway	1
Protein ubiquitination	1
Aberrant regulation of mitotic cell cycle due to RB1 defects	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
metaphase/anaphase transition of mitotic cell cycle	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
positive regulation of mitotic cell cycle phase transition	2
protein polyubiquitination	2
ubiquitin-protein transferase activity	2
cellular anatomical structure	2
modification-dependent protein catabolic process	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
ubiquitin recycling	1
protein polymerization	1
protein modification by small protein conjugation	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
regulation of exit from mitosis	1
exit from mitosis	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
regulation of mitotic metaphase/anaphase transition	1
positive regulation of mitotic nuclear division	1
positive regulation of mitotic sister chromatid separation	1
positive regulation of metaphase/anaphase transition of cell cycle	1
cellular process	1
positive regulation of ubiquitin-protein transferase activity	1
ubiquitin protein ligase activity	1
regulation of ubiquitin protein ligase activity	1
protein modification by small protein conjugation or removal	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme binding	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

3928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2C	UBE3D	Q7Z6J8	935
UBE2C	CDC20	Q12834	891
UBE2C	CCNB1	P14635	878
UBE2C	CCNA2	P20248	859
UBE2C	TOP2A	P11388	837
UBE2C	AURKA	O14965	829
UBE2C	BIRC5	O15392	820
UBE2C	PTTG1	O95997	814
UBE2C	CCNA1	P78396	810
UBE2C	ANAPC11	Q9NYG5	796
UBE2C	CCNB2	O95067	774
UBE2C	BUB1B	O60566	769
UBE2C	UBA1	P22314	760
UBE2C	CDK1	P06493	758
UBE2C	NUSAP1	Q9BXS6	755

IntAct

22 interactions, top by confidence:

A	B	Type	Score
UBE2C	MAPK7	psi-mi:“MI:0915”(physical association)	0.560
UBE2C	GNB2	psi-mi:“MI:0915”(physical association)	0.560
UBE2C	DTX1	psi-mi:“MI:0915”(physical association)	0.370
UBE2C	RANBP9	psi-mi:“MI:0915”(physical association)	0.370
PCGF3	UBE2C	psi-mi:“MI:0915”(physical association)	0.370
EBNA1BP2	UBE2C	psi-mi:“MI:0915”(physical association)	0.370
UBE2C	E6	psi-mi:“MI:0915”(physical association)	0.370
UBE2C	CXCR1	psi-mi:“MI:0915”(physical association)	0.370
TNNC1	UBE2C	psi-mi:“MI:0915”(physical association)	0.370
PVR	QSOX1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
P/V	ESYT2	psi-mi:“MI:0914”(association)	0.350
UBE2C	MAPK7	psi-mi:“MI:0915”(physical association)	0.000
ENO2	UBE2C	psi-mi:“MI:0915”(physical association)	0.000
UBE2V1	UBE2C	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (216): PCGF3 (Two-hybrid), UBE2C (Biochemical Activity), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), UBE2C (Two-hybrid), KLHL2 (Two-hybrid), UBE2C (Reconstituted Complex), UBE2C (Reconstituted Complex), ANAPC2 (Reconstituted Complex), UBE2C (Biochemical Activity), PSMC2 (Reconstituted Complex)

ESM2 similar proteins: A1ZBR5, A7RRG3, B0X6E8, B3MEZ6, B3MGT3, B3N6U7, B3NK72, B4GD81, B4H581, B4HPU1, B4HT57, B4J613, B4JWF5, B4KMF8, B4KS18, B4LNV5, B4LPP8, B4MQY1, B4MRW2, B4NWM2, B4PAP8, B4QHS6, O00762, O09181, O60015, P52484, P56616, Q17PP1, Q1RMW1, Q28XA5, Q28YD9, Q32PA5, Q3UWQ3, Q4R9D1, Q5M8Y2, Q5U203, Q6IRC7, Q6NY82, Q75AF2, Q7K4V4

Diamond homologs: A0A1B0GUS4, A3KN22, A5PKP9, D3ZDK2, O00103, O00762, O13685, O74196, O74549, P0CS16, P0CS17, P15731, P15732, P21734, P25867, P35128, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42746, P43102, P46595, P49459, P51668, P52478, P52490, P52491, P52492, P61077, P61078, P61079, P61080, P61081, P61082, P62837, P62838

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AR	“up-regulates quantity by expression”	UBE2C	“transcriptional regulation”
UBE2C	down-regulates	Mitotic_checkpoint
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2C	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2C	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

33 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

651 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45814471:G:GG	donor_gain	1.0000
20:45815532:AAAT:A	acceptor_gain	1.0000
20:45815849:CACA:C	acceptor_loss	1.0000
20:45815850:ACAG:A	acceptor_loss	1.0000
20:45815851:CA:C	acceptor_loss	1.0000
20:45815852:A:AG	acceptor_gain	1.0000
20:45815853:G:GG	acceptor_gain	1.0000
20:45815911:CAGG:C	donor_loss	1.0000
20:45815912:AGGTG:A	donor_loss	1.0000
20:45815913:GGTG:G	donor_loss	1.0000
20:45812751:GAGC:G	donor_gain	0.9900
20:45812794:AAGGT:A	donor_loss	0.9900
20:45812795:AGGT:A	donor_loss	0.9900
20:45812797:G:GA	donor_loss	0.9900
20:45812797:G:GG	donor_gain	0.9900
20:45812798:T:A	donor_loss	0.9900
20:45814378:CCCCA:C	acceptor_loss	0.9900
20:45814379:CCCA:C	acceptor_loss	0.9900
20:45814381:CA:C	acceptor_loss	0.9900
20:45814382:A:AG	acceptor_gain	0.9900
20:45814382:A:T	acceptor_loss	0.9900
20:45814383:G:GG	acceptor_gain	0.9900
20:45814383:GAT:G	acceptor_gain	0.9900
20:45814470:AGTAA:A	donor_loss	0.9900
20:45814472:TA:T	donor_loss	0.9900
20:45814473:A:AG	donor_loss	0.9900
20:45815532:A:AG	acceptor_gain	0.9900
20:45815535:T:TA	acceptor_gain	0.9900
20:45815535:TGCCA:T	acceptor_loss	0.9900
20:45815538:CAG:C	acceptor_loss	0.9900

AlphaMissense

1162 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45814411:T:C	F53L	1.000
20:45814413:C:A	F53L	1.000
20:45814413:C:G	F53L	1.000
20:45814438:T:A	W62R	1.000
20:45814438:T:C	W62R	1.000
20:45814444:G:T	G64W	1.000
20:45814445:G:A	G64E	1.000
20:45815605:C:A	P94H	1.000
20:45815656:G:T	G111V	1.000
20:45815690:G:C	W122C	1.000
20:45815690:G:T	W122C	1.000
20:45813447:G:A	E38K	0.999
20:45813451:T:C	L39P	0.999
20:45814409:C:A	A52D	0.999
20:45814415:C:A	P54H	0.999
20:45814440:G:C	W62C	0.999
20:45814440:G:T	W62C	0.999
20:45814444:G:A	G64R	0.999
20:45814444:G:C	G64R	0.999
20:45814451:T:A	I66N	0.999
20:45814457:G:A	G68E	0.999
20:45815566:T:C	L81P	0.999
20:45815572:T:C	L83P	0.999
20:45815578:T:C	F85S	0.999
20:45815604:C:T	P94S	0.999
20:45815616:T:C	F98L	0.999
20:45815617:T:C	F98S	0.999
20:45815618:C:A	F98L	0.999
20:45815618:C:G	F98L	0.999
20:45815634:C:G	H104D	0.999

dbSNP variants (sampled 300 via entrez): RS1000133927 (20:45813221 G>A), RS1001117166 (20:45811909 A>C,G), RS1001280343 (20:45810823 G>A,C), RS1001371810 (20:45812501 G>C,T), RS1001764447 (20:45816344 A>G), RS1001794176 (20:45816559 T>C), RS1002095034 (20:45815027 C>A,G,T), RS1002129404 (20:45815200 G>A), RS1003642433 (20:45812466 G>A,T), RS1003661947 (20:45814057 C>T), RS1004318524 (20:45815277 G>C), RS1005054989 (20:45814836 T>TTTTC), RS1006114792 (20:45816119 A>C), RS1006706209 (20:45816999 G>A,T), RS1006868685 (20:45816937 T>A,C)

Disease associations

OMIM: gene MIM:605574 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008839_179	Height	4.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105834 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

114 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
Fluorouracil	increases reaction, decreases expression, decreases reaction, increases acetylation, increases expression (+2 more)	4
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	4
sodium arsenite	affects reaction, decreases expression, increases abundance, increases expression	3
Doxorubicin	decreases expression, increases acetylation, increases expression, decreases reaction	3
Cyclosporine	decreases expression	3
Benzo(a)pyrene	decreases expression	2
Cisplatin	decreases expression	2
Curcumin	decreases expression	2
Etoposide	decreases reaction, affects reaction, decreases expression, increases acetylation, increases expression	2
Methotrexate	affects cotreatment, decreases expression	2
Nicotine	decreases expression, increases expression, decreases reaction	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Fenretinide	decreases expression, increases expression	2
Sodium Selenite	decreases expression	2
Genistein	increases expression, affects expression	2
NVP-BHG712	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	decreases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
gossypol acetic acid	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4030867	Binding	Inhibition of UbcH10 (unknown origin) at 2.5 to 10 uM preincubated for 15 mins followed by E1, Ub and ATP addition measured after 40 mins by Western blot analysis	Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B9VW	Abcam HeLa UBE2C KO	Cancer cell line	Female
CVCL_TV50	HAP1 UBE2C (-) 1	Cancer cell line	Male
CVCL_TV51	HAP1 UBE2C (-) 2	Cancer cell line	Male
CVCL_TV52	HAP1 UBE2C (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.