TAP2
Domain
The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2.
The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.
Function
ABC transporter associated with antigen processing. In complex with TAP1 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules (PubMed:25377891, PubMed:25656091). Uses the chemical energy of ATP to export peptides against the concentration gradient (PubMed:25377891). During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle (PubMed:11274390, PubMed:25377891, PubMed:25656091). Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect (PubMed:11274390, PubMed:7500034, PubMed:9256420). As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation (PubMed:1538751, PubMed:25377891, PubMed:26611325).
Involvement in disease
MHC class I deficiency 2
MHC1D2
An autosomal recessive, progressive disorder characterized by chronic bacterial infections of the upper and lower respiratory tract apparent in the first or second decades of life, nasal polyps, and ulcers with granulomatous inflammation affecting the nasal cavity, upper respiratory tract, or skin. Patients may develop bronchiectasis and respiratory failure.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- The transmembrane segments seem to form a pore in the membrane.
Alternative names
ABCB3, PSF2, RING11, Y1, TAP2, Antigen peptide transporter 2, APT2, ATP-binding cassette sub-family B member 3, Peptide supply factor 2, Peptide transporter PSF2, Peptide transporter TAP2, Peptide transporter involved in antigen processing 2, Really interesting new gene 11 protein, PSF-2