UBE2D2 UniProt P62837
1 alternative isoform · canonical 147 aa · cytosol; endosome
UBE2D2 (UbcH5B/UBC4) is a promiscuous ubiquitin-conjugating E2 enzyme central to proteasomal turnover of short-lived and abnormal proteins, a role first established genetically in yeast where loss of UBC4/UBC5 selectively impairs degradation of unstable substrates [PMID:2154373]. After charging with ubiquitin via E1, it transfers ubiquitin to substrate lysines in cooperation with a broad array of RING and HECT E3 ligases, including E6AP for p53 [PMID:7724550], Mdm2 for p53 [PMID:15280377], the APC11 RING for securin and cyclin B [PMID:10922056], SCF complexes for IκBα and the transcription factor GCM1 [PMID:10918611, PMID:18703417], and c-Cbl for EGFR [PMID:18508924]. Its catalytic mechanism is governed by conformational control: RING-domain binding (e.g., cIAP1, MUL1) and non-covalent ubiquitin engagement at the E2 backside surface stabilize a closed UbcH5B~Ub conformation that primes the thioester for transfer [PMID:30523153, PMID:35048531], and self-assembly of the UbcH5b~Ub conjugate into a spiral via backside interactions provides multiple active sites for processive ubiquitination [PMID:20152160]. UBE2D2 supports diverse cellular processes, contributing to PINK1-Parkin-dependent mitophagy through ubiquitination of mitochondrial proteins [PMID:24906799], to VEGFR2 trafficking and angiogenic signaling in endothelial cells [PMID:37226882], and—via genetic analysis in yeast—it performs an essential HECT-E3-dependent function while acting as a monoubiquitinating E2 in RING-E3 pathways [PMID:21357418].
Isoform tracks
Protein-residue axis (canonical frame). Top bar = canonical; each bar below is an isoform aligned on its shared region — extensions reach left of residue 1 (green), the lost region of a truncation is shaded on the canonical bar (red). Variant rows sit above (ClinVar/gnomAD/COSMIC, red = pathogenic, one row per consequence); below the bars are InterPro domains, disorder / coiled-coil / motifs, and per-cell-line initiation efficiency (dot size). Features are deduplicated across isoforms; hover any glyph for detail.