The family of type 2 integral membrane protein (ITM2) consists of three members, ITM2A, ITM2B and ITM2C []. Members of this family contain a BRICHOS domain, which possesses chaperone activity [,].ITM2A is a target gene of GATA-3, a T cell-specific transcription factor [].ITM2B is proteolytically cleaved at three locations; cleavage by furin in the C-terminal region generates a 23-residue peptide (ABri23), processing by ADAM10 results in release of the BRICHOS domain from the membrane-bound N-terminal part and intramembrane cleavage by SPPL2a/2b liberates the intracellular domain []. ITM2B (BRI2) is a target of BCL6 transcriptional repression and a short form of the ITM2B protein, similarly to other targets of BCL6, induces apoptosis in hematopoietic cell lines []. ITM2B interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production [, ]. ITM2C (BRI3) also inhibits amyloid precursor protein processing, but through a different mechanism to ITM2B [].
