Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (PubMed:11435423). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with VCP (PubMed:12504083). Interacts with STUB1/CHIP and UNC45B (By similarity). Expressed predominantly in neuronal tissues. Also detected in liver, heart, brain, kidney and testis. The U-box domain is required for the ubiquitin protein ligase activity. Proteolytically cleaved by caspases during apoptosis. Cleaved efficiently at Asp-123 by caspase-6 and granzyme B. Cleaved with approximately 10-fold less efficiency at Asp-109 by caspase-3 and caspase-7 (By similarity). In strain C57BL/Ola, a 85 kb region on chromosome 4 containing Nmnat1 and Ube4b is triplicated. Ube4b becomes linked to Nmnat1 and encodes a fusion protein located in the nucleus which is responsible for the delayed Wallerian degeneration of injured axons in C57BL/Ola. Belongs to the ubiquitin conjugation factor E4 family.