Ubiquitin-conjugating enzyme E2 H

UBE2H (ubiquitin-conjugating enzyme E2 H) is an E2 enzyme that catalyzes the transfer of ubiquitin from E1 complexes to target proteins, mediating both 'Lys-11'- and 'Lys-48'-linked polyubiquitination (UniProt: P62256). The enzyme specifically transfers ubiquitin to MAEA, a component of the CTLH E3 ligase complex, and can ubiquitinate histone H2A in vitro, indicating roles in protein modification and chromatin regulation.

UBE2H functions broadly in ubiquitin-proteasome system pathways that regulate protein quality control and cellular signaling across tissues (UniProt: P62256). The enzyme has not been directly associated with specific genetic diseases documented in UniProt, though ubiquitin-conjugating enzymes are implicated in multiple cellular processes.

In Alzheimer's Disease, UBE2H is downregulated in post-mortem AD brain compared to age-matched controls, with a mean log2 fold-change of −0.51 (Chaparral AD proteomics). This reduction was detected in human post-mortem tissue using quantitative proteomics across four subcellular fractions, suggesting impaired ubiquitin-mediated protein modification capacity may contribute to AD pathology.