The inter-alpha-trypsin inhibitor (ITI) family is composed of proteaseinhibitors that are assembled from two precursor proteins: a light chain anddifferent homologous heavy chains (ITIHs). Originally identified as plasmainhibitors, recent data indicate that ITI plays a role in extracellular matrixstabilisation and in prevention of tumour metastasis [].Two domains are conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. The VIT domain is less widespread than the vWA domain and is not genetically mobile. Therefore, it can be regarded as the characteristic domain of the ITIH family. The VIT domain is approximately 135 amino acids long. Its N-terminal part contains a pattern of hydrophobic residues, interrupted by a conserved arginine. The C terminus is best characterised by its conserved aromatic residues. In the central part, an acidic amino acid resides between two basic residues [].
Members of this subfamily average about 850 amino acids in length, ending with a variant form of PEP-CTERM sorting signal. Members have a VIT (vault protein inter-alpha-trypsin inhibitor heavy chain) domain (). Other bacterial subfamilies of VIT domain proteins have members with either GlyGly-CTERM or LPXTG C-terminal sorting signals. Members of this subfamily occur only in context next to a protein sorting/processing enzyme, exosortase N (XrtN). These subsystems occur both among the Bacteriodetes and in the spirochete genus Leptospira [].
