Tapasin Explained

TAP-associated glycoprotein, also known as tapasin or TAPBP, is a protein^{[1] [2]} that in humans is encoded by the TAPBP gene.^[3]

Function

The TAPBP gene encodes a transmembrane glycoprotein that mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction facilitates optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and tapasin may be bound to a single TAP molecule. Tapasin contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. In humans, the tapasin gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms.^[3]

Tapasin is a MHC class I antigen-processing molecule present in the lumen of the endoplasmic reticulum. It plays an important role in the maturation of MHC class I molecules in the ER lumen. Tapasin is one component of the peptide-loading complex, and can be found associated with MHC class I molecules after the MHC class I heavy chain has associated with Beta₂ microglobulin. The peptide-loading complex consists of TAP, tapasin, MHC class I, calreticulin, and ERp57. Tapasin recruits MHC class I molecules to the TAP peptide transporter, and also enhances loading of MHC class I with high-affinity peptides. Following loading of MHC class I with a high-affinity ligand, the interaction between tapasin and MHC class I disappears.^[4]

Interactions

Tapasin has been shown to interact with:

• HLA-A, and
• TAP1^{[5] [6]}

See also

• Transporter associated with antigen processing ("TAP")

Further reading

• Bailey A, Dalchau N, Carter R, Emmott S, Phillips A, Werner JM, Elliott T . Selector function of MHC I molecules is determined by protein plasticity . Scientific Reports . 5 . 14928 . October 2015 . 26482009 . 10.1038/srep14928 . 5224517. 2015NatSR...514928B .
• Williams AP, Peh CA, Purcell AW, McCluskey J, Elliott T . Optimization of the MHC class I peptide cargo is dependent on tapasin . Immunity . 16 . 4 . 509–20 . April 2002 . 11970875 . 10.1016/s1074-7613(02)00304-7. free .
• Howarth M, Williams A, Tolstrup AB, Elliott T . Tapasin enhances MHC class I peptide presentation according to peptide half-life . Proceedings of the National Academy of Sciences of the United States of America . 101 . 32 . 11737–42 . August 2004 . 15286279 . 511045 . 10.1073/pnas.0306294101 . 2004PNAS..10111737H . free .
• Schneeweiss C, Garstka M, Smith J, Hütt MT, Springer S . The mechanism of action of tapasin in the peptide exchange on MHC class I molecules determined from kinetics simulation studies . Molecular Immunology . 46 . 10 . 2054–63 . June 2009 . 19362740 . 10.1016/j.molimm.2009.02.032 .
• Turnquist HR, Vargas SE, Schenk EL, McIlhaney MM, Reber AJ, Solheim JC . The interface between tapasin and MHC class I: identification of amino acid residues in both proteins that influence their interaction . Immunologic Research . 25 . 3 . 261–9 . 2002 . 12018464 . 10.1385/IR:25:3:261 . 42534968 .
• Momburg F, Tan P . Tapasin-the keystone of the loading complex optimizing peptide binding by MHC class I molecules in the endoplasmic reticulum . Molecular Immunology . 39 . 3–4 . 217–33 . October 2002 . 12200052 . 10.1016/S0161-5890(02)00103-7 .
• Dissemond J, Kothen T, Mörs J, Weimann TK, Lindeke A, Goos M, Wagner SN . Downregulation of tapasin expression in progressive human malignant melanoma . Archives of Dermatological Research . 295 . 2 . 43–9 . June 2003 . 12682852 . 10.1007/s00403-003-0393-8 . 6496902 .
• Paulsson K, Wang P . Chaperones and folding of MHC class I molecules in the endoplasmic reticulum . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1641 . 1 . 1–12 . June 2003 . 12788224 . 10.1016/S0167-4889(03)00048-X .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Sadasivan B, Lehner PJ, Ortmann B, Spies T, Cresswell P . Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP . Immunity . 5 . 2 . 103–14 . August 1996 . 8769474 . 10.1016/S1074-7613(00)80487-2 . free .
• Lewis JW, Neisig A, Neefjes J, Elliott T . Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP . Current Biology . 6 . 7 . 873–83 . July 1996 . 8805302 . 10.1016/S0960-9822(02)00611-5 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Li S, Sjögren HO, Hellman U, Pettersson RF, Wang P . Cloning and functional characterization of a subunit of the transporter associated with antigen processing . Proceedings of the National Academy of Sciences of the United States of America . 94 . 16 . 8708–13 . August 1997 . 9238042 . 23091 . 10.1073/pnas.94.16.8708 . 1997PNAS...94.8708L . free .
• Ortmann B, Copeman J, Lehner PJ, Sadasivan B, Herberg JA, Grandea AG, Riddell SR, Tampé R, Spies T, Trowsdale J, Cresswell P . A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes . Science . 277 . 5330 . 1306–9 . August 1997 . 9271576 . 10.1126/science.277.5330.1306 .
• Herberg JA, Sgouros J, Jones T, Copeman J, Humphray SJ, Sheer D, Cresswell P, Beck S, Trowsdale J . Genomic analysis of the Tapasin gene, located close to the TAP loci in the MHC . European Journal of Immunology . 28 . 2 . 459–67 . February 1998 . 9521053 . 10.1002/(SICI)1521-4141(199802)28:02<459::AID-IMMU459>3.0.CO;2-Z . 35772444 .
• Lindquist JA, Jensen ON, Mann M, Hämmerling GJ . ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly . The EMBO Journal . 17 . 8 . 2186–95 . April 1998 . 9545232 . 1170563 . 10.1093/emboj/17.8.2186 .
• Herberg JA, Beck S, Trowsdale J . TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense cluster at the centromeric end of the MHC . Journal of Molecular Biology . 277 . 4 . 839–57 . April 1998 . 9545376 . 10.1006/jmbi.1998.1637 .
• Furukawa H, Kashiwase K, Yabe T, Ishikawa Y, Akaza T, Tadokoro K, Tohma S, Inoue T, Tokunaga K, Yamamoto K, Juji T . Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population . Tissue Antigens . 52 . 3 . 279–81 . September 1998 . 9802609 . 10.1111/j.1399-0039.1998.tb03044.x .
• El Ouakfaoui S, Heitz D, Paquin R, Beaulieu AD . Granulocyte-macrophage colony-stimulating factor modulates tapasin expression in human neutrophils . Journal of Leukocyte Biology . 65 . 2 . 205–10 . February 1999 . 10088603 . 10.1002/jlb.65.2.205. 31764268 . free .
• Bangia N, Lehner PJ, Hughes EA, Surman M, Cresswell P . The N-terminal region of tapasin is required to stabilize the MHC class I loading complex . European Journal of Immunology . 29 . 6 . 1858–70 . June 1999 . 10382748 . 10.1002/(SICI)1521-4141(199906)29:06<1858::AID-IMMU1858>3.0.CO;2-C . free .
• Knittler MR, Alberts P, Deverson EV, Howard JC . Nucleotide binding by TAP mediates association with peptide and release of assembled MHC class I molecules . Current Biology . 9 . 18 . 999–1008 . September 1999 . 10508608 . 10.1016/S0960-9822(99)80448-5 . 18539813 . free .
• Li S, Paulsson KM, Chen S, Sjögren HO, Wang P . Tapasin is required for efficient peptide binding to transporter associated with antigen processing . The Journal of Biological Chemistry . 275 . 3 . 1581–6 . January 2000 . 10636848 . 10.1074/jbc.275.3.1581 . free .
• Tan P, Kropshofer H, Mandelboim O, Bulbuc N, Hämmerling GJ, Momburg F . Recruitment of MHC class I molecules by tapasin into the transporter associated with antigen processing-associated complex is essential for optimal peptide loading . Journal of Immunology . 168 . 4 . 1950–60 . February 2002 . 11823531 . 10.4049/jimmunol.168.4.1950 . free .
• Mayer WE, Klein J . Is tapasin a modified Mhc class I molecule? . Immunogenetics . 53 . 9 . 719–23 . December 2001 . 11862402 . 10.1007/s00251-001-0403-y . 43163810 .

External links

• • PDBe-KB provides an overview of all the structure information available in the PDB for Human Tapasin

Notes and References

1. Sadasivan B, Lehner PJ, Ortmann B, Spies T, Cresswell P . Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP . Immunity . 5 . 2 . 103–14 . August 1996 . 8769474 . 10.1016/S1074-7613(00)80487-2 . free .
2. Li S, Sjögren HO, Hellman U, Pettersson RF, Wang P . Cloning and functional characterization of a subunit of the transporter associated with antigen processing . Proceedings of the National Academy of Sciences of the United States of America . 94 . 16 . 8708–13 . August 1997 . 9238042 . 23091 . 10.1073/pnas.94.16.8708 . 1997PNAS...94.8708L . free .
3. Web site: Entrez Gene: TAPBP TAP binding protein (tapasin).
4. Zhang Y, Williams DB . Assembly of MHC class I molecules within the endoplasmic reticulum . Immunologic Research . 35 . 1–2 . 151–62 . 2006 . 17003517 . 10.1385/IR:35:1:151 . 27816994 .
5. Paulsson KM, Kleijmeer MJ, Griffith J, Jevon M, Chen S, Anderson PO, Sjogren HO, Li S, Wang P . Association of tapasin and COPI provides a mechanism for the retrograde transport of major histocompatibility complex (MHC) class I molecules from the Golgi complex to the endoplasmic reticulum . The Journal of Biological Chemistry . 277 . 21 . 18266–71 . May 2002 . 11884415 . 10.1074/jbc.M201388200 . free .
6. Raghuraman G, Lapinski PE, Raghavan M . Tapasin interacts with the membrane-spanning domains of both TAP subunits and enhances the structural stability of TAP1 x TAP2 Complexes . The Journal of Biological Chemistry . 277 . 44 . 41786–94 . November 2002 . 12213826 . 10.1074/jbc.M207128200 . free .