UBE2M: Ubiquitin Conjugating Enzyme E2 M
Key regulator of neddylation and cullin-RING ligase activity
Gene Information Card
| Symbol | UBE2M |
|---|---|
| Full Name | Ubiquitin Conjugating Enzyme E2 M |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.43 |
| NCBI Gene ID | 9040 ncbi.nlm.nih.gov/gene/9040 |
| Ensembl ID | ENSG00000130725 |
| UniProt ID | P61081 |
| OMIM ID | 603173 |
| HGNC ID | 12491 |
| Aliases | UBC12, hUBC12 |
Description
UBE2M (Ubiquitin Conjugating Enzyme E2 M) encodes UBC12, an E2 ubiquitin-conjugating enzyme that specifically conjugates NEDD8 to cullin proteins. This neddylation activates cullin-RING ubiquitin ligases (CRLs), regulating the ubiquitination and degradation of key cellular proteins involved in cell cycle, transcription, and signal transduction. UBE2M is essential for CRL function and is implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of UBE2M increases neddylation and CRL activity, promoting degradation of tumor suppressors like p27 and p21. | NCBI Gene, COSMIC |
| NEDD8-related developmental disorders | Loss-of-function mutations impair neddylation, disrupting CRL-mediated proteostasis. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone marrow | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Brain | 8.1 | Low |
| Liver | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | High expression |
| HeLa | 18.7 | High expression |
| K562 | 14.1 | Medium expression |
| HepG2 | 9.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.205C>T (p.Arg69Trp) | Missense | <0.01% | Impaired NEDD8 binding, reduced neddylation |
| c.347G>A (p.Arg116Gln) | Missense | <0.01% | Altered catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting the active site or NEDD8 binding reduce neddylation and CRL activity.
Gain of Function (GOF)
Not well documented; overexpression is observed in cancers.
Dominant Negative (DN)
Not reported for UBE2M.
View complete mutation data：
Gene Ontology (GO)
| • NEDD8 transferase activity | • Ubiquitin conjugating enzyme activity |
| • Protein neddylation | • Cullin deneddylation |
| • Cell cycle regulation |
Pathways
• Neddylation pathway
• Cullin-RING ubiquitin ligase activation
• Ubiquitin-proteasome system
Protein Summary
UBC12 (UBE2M) is a 183-amino acid E2 conjugating enzyme that specifically transfers NEDD8 to cullin proteins. It contains a conserved catalytic cysteine (Cys111) and a NEDD8-binding domain. UBC12 interacts with the DCN1-like protein complex to facilitate neddylation, which is critical for CRL assembly and function. Dysregulation of UBE2M contributes to oncogenesis and developmental defects.
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