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Gene Review

TAP2  -  transporter 2, ATP-binding cassette, sub...

Homo sapiens

Synonyms: ABC18, ABCB3, APT2, ATP-binding cassette sub-family B member 3, Antigen peptide transporter 2, ...
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Disease relevance of TAP2

  • Cell cycle-dependent expression of TAP1, TAP2, and HLA-B27 messenger RNAs in a human breast cancer cell line [1].
  • Mutations at cMS of beta2m and genes encoding APM components (TAP1 and TAP2) were detected in at least 7 (35.0%) of 20 MSI-H colorectal cancers but in none of the MSS colorectal cancers (P = 0.0002) [2].
  • TAP1, TAP2, and HLA Class I antigen expression was more frequently (P < 0.05) down-regulated in metastatic than in primary melanoma lesions and in nevi [3].
  • Association of a new allele of the TAP2 gene, TAP2*Bky2 (Val577), with susceptibility to Sjögren's syndrome [4].
  • To elucidate the ATP binding properties of these proteins in vitro, we expressed the hydrophilic C-terminal part of human transporter associated with antigen processing (TAP1) (nucleotide binding domain (NBD)-TAP1, amino acids 452-748) and TAP2 (NBD-TAP2, amino acids 399-686) fused to a His6 tag in Escherichia coli [5].

High impact information on TAP2


Chemical compound and disease context of TAP2


Biological context of TAP2

  • The transporter associated with antigen processing (TAP), which is composed of two subunits (TAP1 and TAP2) that have different biochemical and functional properties, plays a key role in peptide loading and the cell surface expression of HLA class I molecules [13].
  • The action of two genetic process is required to account for this phenomenon: a recombinational hotspot operating between TAP1 and TAP2, to eliminate disequilibrium between these loci, and at the same time selection operating on particular combinations of alleles across the DR-DP region, to create disequilibrium in the favored haplotypes [14].
  • A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA)12 tandem repeat within the TAP2 gene [15].
  • In this study, we identify four regions, two on the TAP1 and two on the TAP2 subunit, that make major contributions to this binding site [16].
  • A synchronous TAP1, TAP2, and HLA Class I antigen down-regulation was observed in 58% of primary and 52% of metastatic lesions [3].

Anatomical context of TAP2

  • Two subunits, TAP1 and TAP2, are necessary and sufficient for peptide binding and peptide translocation across the endoplasmic reticulum membrane [17].
  • Transfection of single TAP genes to T2 or .174 cells, whether TAP1 or TAP2, did not markedly affect NK cell susceptibility [18].
  • However, restoration of Ag processing and presentation to CD8+ cytotoxic T cells can be achieved by transfecting TAP1 and TAP2 genes into the T2 and .174 cells, or the TAP1 gene into .134 cells [18].
  • The TAP heterodimer (TAP1-TAP2) introduces the final component of the MHC class I molecule by translocating peptides, predominately generated by the proteasome, from the cytosol into the ER where they can bind dimers of beta 2M and the MHC class I heavy chain [19].
  • Differential regulation of the expression of transporters associated with antigen processing, TAP1 and TAP2, by cytokines and lipopolysaccharide in primary human macrophages [20].

Associations of TAP2 with chemical compounds

  • Since neither purified nor induced ICP47 inhibited photocrosslinking of 8-azido-ATP to TAP1 and TAP2 it seems that ICP47 does not prevent ATP from binding to TAP [21].
  • The other sites of TAP2 gene were analyzed by mismatch PCR-RFLP: AccII for TAP2 codon 379 (Val-Ile), RsaI for codon 565 (Ala-Thr), and MspI for codon 665 (Thr-Ala) [22].
  • Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC class I molecules to the cell surface [10].
  • Furthermore, cell clones transfected with both, but not singularly expressed TAP1 or TAP2, reduced cellular mitoxantrone accumulation [23].
  • Sequence analysis of cDNA clones identified a seventh allele of TAP2, TAP2*F, which contains an arginine-to-cystine interchange at amino acid position 651 [24].

Physical interactions of TAP2

  • All mutant TAP1 proteins were localized in the ER and were capable of forming complexes with the TAP2 subunit [25].
  • Similarly, the distribution of TAP2-S-GFP (M1-R88) was restricted to the intracellular membranes by TAPL-DR or TAP1-DR, indicating that the M1-R88 region of TAP2 is able to interact with TAPL as well as TAP1 [26].

Regulatory relationships of TAP2


Other interactions of TAP2

  • Because TAP1 and TAP2 genes are located between HLA-DQB1 and -DPB1 loci, analysis of TAP gene polymorphisms will be useful for a better understanding of susceptibility loci in HLA class II-associated disease [30].
  • The sequence is closely related to the mammalian ABCB9 protein and the TAP1 and TAP2 proteins that transport peptides for loading onto nascent Mhc class I molecules [31].
  • Significant positive or negative RRs conferred by some TAP2 or DPB1 alleles were found [32].
  • TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France [33].
  • Peptides produced by proteasomes are transported into the endoplasmic reticulum by transporter proteins TAP-1 and TAP-2, where they bind and stabilize MHC class I molecules required for antigenic presentation on the cell surface [1].

Analytical, diagnostic and therapeutic context of TAP2


  1. Cell cycle-dependent expression of TAP1, TAP2, and HLA-B27 messenger RNAs in a human breast cancer cell line. Alpan, R.S., Zhang, M., Pardee, A.B. Cancer Res. (1996) [Pubmed]
  2. Immunoselective pressure and human leukocyte antigen class I antigen machinery defects in microsatellite unstable colorectal cancers. Kloor, M., Becker, C., Benner, A., Woerner, S.M., Gebert, J., Ferrone, S., von Knebel Doeberitz, M. Cancer Res. (2005) [Pubmed]
  3. Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Kageshita, T., Hirai, S., Ono, T., Hicklin, D.J., Ferrone, S. Am. J. Pathol. (1999) [Pubmed]
  4. Association of a new allele of the TAP2 gene, TAP2*Bky2 (Val577), with susceptibility to Sjögren's syndrome. Kumagai, S., Kanagawa, S., Morinobu, A., Takada, M., Nakamura, K., Sugai, S., Maruya, E., Saji, H. Arthritis Rheum. (1997) [Pubmed]
  5. Nucleotide binding to the hydrophilic C-terminal domain of the transporter associated with antigen processing (TAP). Müller, K.M., Ebensperger, C., Tampé, R. J. Biol. Chem. (1994) [Pubmed]
  6. Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes. Eisenlohr, L.C., Bacik, I., Bennink, J.R., Bernstein, K., Yewdell, J.W. Cell (1992) [Pubmed]
  7. Selectivity of MHC-encoded peptide transporters from human, mouse and rat. Momburg, F., Roelse, J., Howard, J.C., Butcher, G.W., Hämmerling, G.J., Neefjes, J.J. Nature (1994) [Pubmed]
  8. Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex. Kelly, A., Powis, S.H., Kerr, L.A., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B., Ziegler, A., Trowsdale, J., Townsend, A. Nature (1992) [Pubmed]
  9. Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. Arnold, D., Driscoll, J., Androlewicz, M., Hughes, E., Cresswell, P., Spies, T. Nature (1992) [Pubmed]
  10. Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly. Heintke, S., Chen, M., Ritz, U., Lankat-Buttgereit, B., Koch, J., Abele, R., Seliger, B., Tampé, R. FEBS Lett. (2003) [Pubmed]
  11. TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis. Kamarashev, J., Ferrone, S., Seifert, B., Böni, R., Nestle, F.O., Burg, G., Dummer, R. Int. J. Cancer (2001) [Pubmed]
  12. NPY upregulates genes containing cyclic AMP response element in human neuroblastoma cell lines bearing Y1 and Y2 receptors: involvement of CREB. Sheriff, S., Dayal, R., Kasckow, J., Regmi, A., Chance, W., Fischer, J., Balasubramaniam, A. Regul. Pept. (1998) [Pubmed]
  13. HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1. de la Salle, H., Zimmer, J., Fricker, D., Angenieux, C., Cazenave, J.P., Okubo, M., Maeda, H., Plebani, A., Tongio, M.M., Dormoy, A., Hanau, D. J. Clin. Invest. (1999) [Pubmed]
  14. Discordant patterns of linkage disequilibrium of the peptide-transporter loci within the HLA class II region. Klitz, W., Stephens, J.C., Grote, M., Carrington, M. Am. J. Hum. Genet. (1995) [Pubmed]
  15. Characterization of recombination in the HLA class II region. Cullen, M., Noble, J., Erlich, H., Thorpe, K., Beck, S., Klitz, W., Trowsdale, J., Carrington, M. Am. J. Hum. Genet. (1997) [Pubmed]
  16. Multiple regions of the transporter associated with antigen processing (TAP) contribute to its peptide binding site. Nijenhuis, M., Hämmerling, G.J. J. Immunol. (1996) [Pubmed]
  17. Tapasin interacts with the membrane-spanning domains of both TAP subunits and enhances the structural stability of TAP1 x TAP2 Complexes. Raghuraman, G., Lapinski, P.E., Raghavan, M. J. Biol. Chem. (2002) [Pubmed]
  18. Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells. Salcedo, M., Momburg, F., Hämmerling, G.J., Ljunggren, H.G. J. Immunol. (1994) [Pubmed]
  19. The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex. Hughes, E.A., Cresswell, P. Curr. Biol. (1998) [Pubmed]
  20. Differential regulation of the expression of transporters associated with antigen processing, TAP1 and TAP2, by cytokines and lipopolysaccharide in primary human macrophages. Schiffer, R., Baron, J., Dagtekin, G., Jahnen-Dechent, W., Zwadlo-Klarwasser, G. Inflamm. Res. (2002) [Pubmed]
  21. Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47. Ahn, K., Meyer, T.H., Uebel, S., Sempé, P., Djaballah, H., Yang, Y., Peterson, P.A., Früh, K., Tampé, R. EMBO J. (1996) [Pubmed]
  22. Lack of primary association between transporter associated with antigen processing genes and atopic dermatitis. Kuwata, S., Yanagisawa, M., Saeki, H., Nakagawa, H., Etoh, T., Tokunaga, K., Juji, T., Shibata, Y. J. Allergy Clin. Immunol. (1995) [Pubmed]
  23. Enhanced expression of human ABC-transporter tap is associated with cellular resistance to mitoxantrone. Lage, H., Perlitz, C., Abele, R., Tampé, R., Dietel, M., Schadendorf, D., Sinha, P. FEBS Lett. (2001) [Pubmed]
  24. TAP2 association with insulin-dependent diabetes mellitus is secondary to HLA-DQB1. Jackson, D.G., Capra, J.D. Hum. Immunol. (1995) [Pubmed]
  25. Identification of sequences in the human peptide transporter subunit TAP1 required for transporter associated with antigen processing (TAP) function. Ritz, U., Momburg, F., Pircher, H.P., Strand, D., Huber, C., Seliger, B. Int. Immunol. (2001) [Pubmed]
  26. Membrane localization of transporter associated with antigen processing (TAP)-like (ABCB9) visualized in vivo with a fluorescence protein-fusion technique. Kobayashi, A., Maeda, T., Maeda, M. Biol. Pharm. Bull. (2004) [Pubmed]
  27. Organization and functional analysis of the mouse transporter associated with antigen processing 2 promoter. Arons, E., Kunin, V., Schechter, C., Ehrlich, R. J. Immunol. (2001) [Pubmed]
  28. Assembly, intracellular localization, and nucleotide binding properties of the human peptide transporters TAP1 and TAP2 expressed by recombinant vaccinia viruses. Russ, G., Esquivel, F., Yewdell, J.W., Cresswell, P., Spies, T., Bennink, J.R. J. Biol. Chem. (1995) [Pubmed]
  29. Enhanced expression of HLA-A,B,C and inducibility of TAP-1, TAP-2, and HLA-A,B,C by interferon-gamma in a multidrug-resistant small cell lung cancer line. Fisk, B., Ioannides, C.G., Aggarwal, S., Wharton, J.T., O'Brian, C.A., Restifo, N., Glisson, B.S. Lymphokine Cytokine Res. (1994) [Pubmed]
  30. Polymorphisms of transporter associated with antigen processing genes in atopic dermatitis. Kuwata, S., Yanagisawa, M., Saeki, H., Nakagawa, H., Etoh, T., Tokunaga, K., Juji, T., Shibata, Y. J. Allergy Clin. Immunol. (1994) [Pubmed]
  31. Identification and characterization of a TAP-family gene in the lamprey. Uinuk-ool, T.S., Mayer, W.E., Sato, A., Takezaki, N., Benyon, L., Cooper, M.D., Klein, J. Immunogenetics (2003) [Pubmed]
  32. Reevaluation of the relative risk for susceptibility to celiac disease of HLA-DRB1, -DQA1, -DQB1, -DPB1, and -TAP2 alleles in a French population. Meddeb-Garnaoui, A., Zeliszewski, D., Mougenot, J.F., Djilali-Saiah, I., Caillat-Zucman, S., Dormoy, A., Gaudebout, C., Tongio, M.M., Baudon, J.J., Sterkers, G. Hum. Immunol. (1995) [Pubmed]
  33. TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France. Zhang, S.L., Chabod, J., Penfornis, A., Reviron, D., Tiberghien, P., Wendling, D., Toussirot, E. Eur. J. Immunogenet. (2002) [Pubmed]
  34. Analysis of the MHC class II encoded components of the HLA class I antigen processing pathway in ankylosing spondylitis. Burney, R.O., Pile, K.D., Gibson, K., Calin, A., Kennedy, L.G., Sinnott, P.J., Powis, S.H., Wordsworth, B.P. Ann. Rheum. Dis. (1994) [Pubmed]
  35. Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cells. Meyer, T.H., van Endert, P.M., Uebel, S., Ehring, B., Tampé, R. FEBS Lett. (1994) [Pubmed]
  36. Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits. Antoniou, A.N., Ford, S., Pilley, E.S., Blake, N., Powis, S.J. Immunology (2002) [Pubmed]
  37. Analysis of TAP1 and TAP2 polymorphism of mother-infant in Chinese patients with pre-eclampsia. Zhang, Z., Jia, L., Hou, L., Xiong, P., Wu, X., Wang, X., Huang, Y., Ke, H., Chang, C., Cui, S., Gong, F. Cellular & molecular immunology. (2005) [Pubmed]
  38. A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and Transporter associated with Antigen Processing 1/2 in human melanoma cells. Kurte, M., López, M., Aguirre, A., Escobar, A., Aguillón, J.C., Charo, J., Larsen, C.G., Kiessling, R., Salazar-Onfray, F. J. Immunol. (2004) [Pubmed]
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