TAP2 Gene

The TAP2 gene (TAP2 stands for Transporter 2. ATP Binding Cassette Subfamily B Member) is a protein-coding gene located on chromosome 6p21.32. Related signaling pathways include class I MHC-mediated antigen processing and presentation and antigen processing cross-presentation.

The protein encoded by the TAP2 gene, the ATP Binding Cassette Subfamily B member is an ABC transporter involved in antigen processing. The protein, in complex with TAP1, mediates the unidirectional translocation of peptide antigens from the cytosol to the endoplasmic reticulum for loading onto MHC class I molecules (MHCI). Here, the chemical energy of ATP is used to export peptides against the concentration gradient.

During the transport cycle, it alternates between an inward-facing state with a peptide-binding site facing the cytosol and an outward-facing state with a peptide-binding site facing the ER lumen. Binding of the peptide antigen to the ATP-loaded TAP1-TAP2 results in a switch to a hydrolysis-ready "outward-facing" conformation ready to load the peptide onto the nascent MHCI molecules. Subsequently, energy-releasing ATP hydrolysis resets the transporter to the inward-facing state for a new cycle.

The TAP2 protein binds peptides with free N- and C-termini, the first three and the C-terminal residues being crucial. As a component of the peptide loading complex (PLC), it functions as a molecular scaffold essential for peptide MHCI assembly and antigen presentation.

Diseases associated with TAP2 include:

Bare Lymphocyte Syndrome, Type I

and

immunodeficiency due to defective expression of MHC class I(MHC class I defect).

1. Momburg F et al (1994) Peptide selection by MHC-encoded TAP transporters. Curr Opin Immunol 6:32-37.
2. Rezaieyazdi Z et al (2021): Correlations and Influence of TAP2 Genes Polymorphisms and Systemic Lupus Erythematosus Propensity. Curr Rheumatol Rev 17:404-411
3. Song YW et al (2005) Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients. Hum Immunol 66:810-817.