Large tumor antigen

The large tumor antigen (also called the large T-antigen and abbreviated LTag or LT) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essential for viral proliferation. Containing four well-conserved protein domains as well as several intrinsically disordered regions, LTag is a fairly large multifunctional protein; in most polyomaviruses, it ranges from around 600-800 amino acids in length. LTag has two primary functions, both related to replication of the viral genome: it unwinds the virus's DNA to prepare it for replication, and it interacts with proteins in the host cell to dysregulate the cell cycle so that the host's DNA replication machinery can be used to replicate the virus's genome. Some polyomavirus LTag proteins - most notably the well-studied SV40 large tumor antigen from the SV40 virus - are oncoproteins that can induce neoplastic transformation in the host cell. Polyomavirus LTag proteins contain four well-conserved, globular protein domains: from N- to C-terminus, these are the J domain, the origin-binding domain (OBD), the zinc-binding domain, and the AAA+ ATPase domain. The domains are linked by intrinsically disordered regions, which are themselves often functionally important and whose length varies among polyomaviruses; both the folded globular domains and the disordered regions form protein-protein interactions with a number of host cell proteins. Some LTag homologs also have a disordered C-terminal tail called the host range domain, which can be phosphorylated and in some strains is essential, although the molecular mechanism of its essentiality is unclear. In some polyomaviruses, truncated variants of the LTag protein are produced through alternative splicing that do not include the helicase (zinc-binding and ATPase) components. These truncated LTags retain their ability to interact with some cell cycle regulatory proteins and are involved in cell transformation but not in viral genome replication.