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Protein Domain : Tapasin

Primary Identifier  IPR008056 Type  Family
Short Name  Tapasin
description  Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8 T cells. The majority of peptides found associated with class I molecules are derived from nuclear and cytosolic proteins, and they are generated largely by the proteasome complex. These peptides are transported from cytosol into the lumen of the endoplasmic reticulum (ER) by a peptide transporter, which is known as the transporter associated with antigen processing (TAP). TAP is a trimeric complex consisting of TAP1, TAP2 and tapasin (TAP-A). TAP1 and TAP2 are required for peptide transport. Tapasin, which actually serves as a docking site on the TAP complex specific for interaction with class I MHC molecules, is essential for peptide loading (up to four MHC class I-tapasin complexes have beenfound to bind to each TAP molecule). However, since the exact mechanisms oftapasin functions are still unknown, it has also been speculated thattapasin may regulate the MHC class I release from the ER rather than directly loading peptides onto MHC class I molecules [, , , ].In studies of the interaction between MHC class I and TAP, it was found that TAP1, but not TAP2, is required for the association of TAP with class I molecules. Because tapasin is essential for the association of MHC class I to TAP, tapasin may directly interact with TAP1. Thus the predicted order of interaction between different molecules in the TAP complex is TAP2 to TAP1, TAP1 to tapasin, and tapasin to MHC class I molecules. Thus, by these linked events, the translocation and loading of peptides rapidly and efficientlyproceed in the same microenvironment [, ].Tapasin is a type I transmembrane (TM) glycoprotein with a double lysinemotif that is thought to be involved with mediating the retrieval of proteins back from the cis-Golgi, thus maintaining membrane proteins in theER []. It is encoded by an MHC-linked gene and is a member of theimmunoglobulin superfamily. Binding to TAP is mediated by the C-terminalregion, whereas its N-terminal 50 residues constitute the key element thatconverts the MHC class I molecules and TAP weak interactions into a stablecomplex [, ].

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103 Protein Domain Regions