TRIM5 is a member of a broad family of otherwise unrelated proteins defined by the presence of a tripartite motif containing a RING domain, a B-box type 1, and a B-box type 2, followed by a coiled-coil region. TRIM5 has five alternately spliced isoforms, the longest of which is the alpha variant which also contains a carboxy-terminal B30.2 (SPRY) domain. While a function has not yet been assigned to TRIM5gamma, it is known that expression of TRIM5alpha variants from humans, rhesus monkeys, and African green monkeys enable resistance to infection by various retroviruses including HIV-1, albeit at differing efficiencies. Furthermore, the TRIM5delta isoform appears to serve as a scaffold for the assembly of endogenous BTBD1 and BTBD2 proteins and also exhibits autoubiquitination activity in a RING finger- and UbcH5B-dependent manner.