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. Expression of TRIM5alpha variants from humans, rhesus monkeys, and African green monkeys enabled resistance to infection by various retroviruses including HIV-1 , albeit at differing efficiencies. The TRIM5delta isoform has been shown to colocalize with the topoisomerase I-interacting proteins BTBD1 and BTBD2 in punctate or elongated cytoplasmic bodies in several mouse and human cells where it appears to serve as a scaffold for the assembly of endogenous BTBD proteins. TRIM5delta also exhibits autoubiquitination activity in a RING finger- and UbcH5B-dependent manner.