TAP1
The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. [provided by RefSeq]
Full Name
transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Function
ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. 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. 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. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.
Biological Process
Adaptive immune response
Antigen processing and presentation of endogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Antigen processing and presentation of peptide antigen via MHC class I
Cytosol to endoplasmic reticulum transport
Defense response
Peptide transport
Protein transport
Transmembrane transport
Vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane
Viral process
Cellular Location
Endoplasmic reticulum membrane. The transmembrane segments seem to form a pore in the membrane.
Involvement in disease
A HLA class I deficiency. Contrary to bare lymphocyte syndromes type 2 and type 3, which are characterized by early-onset severe combined immunodeficiency, class I antigen deficiencies are not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract.
Topology
Cytoplasmic: 61-75 aa
Helical: 76-96 aa
Lumenal: 97-113 aa
Helical: 114-136 aa
Cytoplasmic: 137-152 aa
Helical: 153-173 aa
Lumenal: 174-193 aa
Helical: 194-214 aa
Cytoplasmic: 215-246 aa
Helical: 247-267 aa
Lumenal: 268-287 aa
Helical: 288-308 aa
Cytoplasmic: 309-358 aa
Helical: 359-379 aa
Lumenal: 380-388 aa
Helical: 389-409 aa
Cytoplasmic: 410-478 aa
Helical: 479-499 aa
Lumenal: 500-503 aa
Helical: 504-524 aa
Cytoplasmic: 525-808 aa