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Gene Review

TAP1  -  transporter 1, ATP-binding cassette, sub...

Homo sapiens

Synonyms: ABC17, ABCB2, APT1, ATP-binding cassette sub-family B member 2, Antigen peptide transporter 1, ...
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Disease relevance of TAP1

  • 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].
  • 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 [4].
  • Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis [5].

High impact information on TAP1


Chemical compound and disease context of TAP1

  • After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus [9].
  • Processing of HIV-1 envelope glycoprotein for class I-restricted recognition: dependence on TAP1/2 and mechanisms for cytosolic localization [10].
  • A polyclonal antiserum, raised against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was used for the immunohistochemical analysis of TAP-1 expression in 76 cervical carcinomas [11].
  • The flash-induced Fourier transform infrared (FTIR) difference spectrum of the oxygen-evolving Mn cluster upon S1-to-S2 transition (S2/S1 spectrum) was measured using photosystem II (PS II) core complexes of Synechocystis 6803 in which tyrosine residues were specifically labeled with 13C at the ring-4 position [12].

Biological context of TAP1

  • We now report the initial characterization of the bidirectional promoter for the human transporter associated with antigen processing 1 (TAP1) and low molecular mass polypeptide 2 (LMP2) genes [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].
  • Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10 [15].
  • We have addressed this question by analyzing three human melanoma cell lines with distinct phenotypes of LMP2 and TAP1 expression [16].
  • Transfection of single TAP genes to T2 or .174 cells, whether TAP1 or TAP2, did not markedly affect NK cell susceptibility [17].

Anatomical context of TAP1

  • Downregulation of TAP1 by IL-10 hampers the transport of peptide antigens into the endoplasmatic reticulum, as shown in the TAP-specific peptide transporter assay, their loading onto empty MHC I molecules, and the subsequent translocation to the cell surface [15].
  • The peptides are generated mainly by the proteasome and are transported to the endoplasmic reticulum by a peptide transport pump consisting of two subunits, TAP1 and TAP2 [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 [17].
  • 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].
  • Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells [17].

Associations of TAP1 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 [20].
  • Mutation of the leucine or glycine (LSGGQ) in TAP1 fully abolished peptide transport [21].
  • Instead of a glutamate, proposed to act as a general base, TAP1 contains an aspartate and a glutamine instead of the conserved histidine, which has been suggested to act as the linchpin [22].
  • Photoaffinity labeling of NBD-TAP1 with the ATP analogues 8-azido-[gamma-32P]ATP and 3'-O-[(4-azido-3,5-[125I]diiodo-2-hydroxybenzoyl)-beta-alanyl]-ATP was specific [4].
  • NBD-TAP1 bound to C-8-ATP-agarose and was specifically eluted with ATP or EDTA [4].

Physical interactions of TAP1

  • All mutant TAP1 proteins were localized in the ER and were capable of forming complexes with the TAP2 subunit [23].
  • However, the TAP1 mutants analyzed transported peptides with different efficiencies and displayed a heterogeneous MHC class I surface expression pattern which was directly associated with their susceptibility to cytotoxic T lymphocyte-mediated lysis [23].
  • The dimerization of some vancomycin group antibiotics is strongly exothermic (-36 to -51 kJ.mol-1) and is promoted by a factor of 50-100 by a disaccharide attached to ring 4 (in vancomycin and eremomycin) and by a factor of ca. 1000 by an amino-sugar attached to the benzylic position of ring 6 in eremomycin [24].

Regulatory relationships of TAP1


Other interactions of TAP1

  • The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters [30].
  • TAP1 and P-gp share a significant degree of homology among their transmembrane domains, which are thought to be the primary determinants of substrate specificity, and both can apparently mediate the translocation of peptides [31].
  • The forces producing the patterns of disequilibrium observed here have implications for the mapping of train loci and disease genes: markers of TAP1, for example, would give a false impression as to the influence of DPB1 on a trait known to be associated with DQB1 [14].
  • The regulatory elements within the LMP2/TAP1 promoter and the transcription factors that bind these elements have been defined [16].
  • A gamma-activating sequence (GAS) in the TAP1 promoter is necessary for the rapid induction by IFN-gamma [32].

Analytical, diagnostic and therapeutic context of TAP1


  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. 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]
  5. Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis. Foley, P.J., Lympany, P.A., Puscinska, E., Zielinski, J., Welsh, K.I., du Bois, R.M. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  6. A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Chen, H.L., Gabrilovich, D., Tampé, R., Girgis, K.R., Nadaf, S., Carbone, D.P. Nat. Genet. (1996) [Pubmed]
  7. Membranous nephropathy and a TAP1 gene polymorphism. Chevrier, D., Giral, M., Braud, V., Soulillou, J.P., Bignon, J.D. N. Engl. J. Med. (1994) [Pubmed]
  8. 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]
  9. 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]
  10. Processing of HIV-1 envelope glycoprotein for class I-restricted recognition: dependence on TAP1/2 and mechanisms for cytosolic localization. Ferris, R.L., Hall, C., Sipsas, N.V., Safrit, J.T., Trocha, A., Koup, R.A., Johnson, R.P., Siliciano, R.F. J. Immunol. (1999) [Pubmed]
  11. Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. Cromme, F.V., Airey, J., Heemels, M.T., Ploegh, H.L., Keating, P.J., Stern, P.L., Meijer, C.J., Walboomers, J.M. J. Exp. Med. (1994) [Pubmed]
  12. Structural coupling between the oxygen-evolving Mn cluster and a tyrosine residue in photosystem II as revealed by Fourier transform infrared spectroscopy. Noguchi, T., Inoue, Y., Tang, X.S. Biochemistry (1997) [Pubmed]
  13. Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. Wright, K.L., White, L.C., Kelly, A., Beck, S., Trowsdale, J., Ting, J.P. J. Exp. Med. (1995) [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. Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Zeidler, R., Eissner, G., Meissner, P., Uebel, S., Tampé, R., Lazis, S., Hammerschmidt, W. Blood (1997) [Pubmed]
  16. Different requirements for signal transducer and activator of transcription 1alpha and interferon regulatory factor 1 in the regulation of low molecular mass polypeptide 2 and transporter associated with antigen processing 1 gene expression. Chatterjee-Kishore, M., Kishore, R., Hicklin, D.J., Marincola, F.M., Ferrone, S. J. Biol. Chem. (1998) [Pubmed]
  17. 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]
  18. 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]
  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. 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]
  21. Functional non-equivalence of ATP-binding cassette signature motifs in the transporter associated with antigen processing (TAP). Chen, M., Abele, R., Tampé, R. J. Biol. Chem. (2004) [Pubmed]
  22. Engineering ATPase Activity in the Isolated ABC Cassette of Human TAP1. Ernst, R., Koch, J., Horn, C., Tampé, R., Schmitt, L. J. Biol. Chem. (2006) [Pubmed]
  23. 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]
  24. Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics. Williams, D.H., Searle, M.S., Mackay, J.P., Gerhard, U., Maplestone, R.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  25. Presentation of viral antigen by MHC class I molecules is dependent on a putative peptide transporter heterodimer. Spies, T., Cerundolo, V., Colonna, M., Cresswell, P., Townsend, A., DeMars, R. Nature (1992) [Pubmed]
  26. 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]
  27. p53 induces TAP1 and enhances the transport of MHC class I peptides. Zhu, K., Wang, J., Zhu, J., Jiang, J., Shou, J., Chen, X. Oncogene (1999) [Pubmed]
  28. Induction of immunogenicity of a human renal-cell carcinoma cell line by TAP1-gene transfer. Kallfelz, M., Jung, D., Hilmes, C., Knuth, A., Jaeger, E., Huber, C., Seliger, B. Int. J. Cancer (1999) [Pubmed]
  29. Allelic variation at the TAP 1 locus influences disease phenotype in HLA-B27 positive individuals with ankylosing spondylitis. Maksymowych, W.P., Tao, S., Li, Y., Wing, M., Russell, A.S. Tissue Antigens (1995) [Pubmed]
  30. 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]
  31. Overexpression of the ABC transporter TAP in multidrug-resistant human cancer cell lines. Izquierdo, M.A., Neefjes, J.J., Mathari, A.E., Flens, M.J., Scheffer, G.L., Scheper, R.J. Br. J. Cancer (1996) [Pubmed]
  32. Kinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha. Min, W., Pober, J.S., Johnson, D.R. J. Immunol. (1996) [Pubmed]
  33. 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]
  34. Analysis of HLA class Ia transcripts in human leukaemias. Majumder, D., Bandyopadhyay, D., Chandra, S., Mukhopadhayay, A., Mukherjee, N., Bandyopadhyay, S.K., Banerjee, S. Immunogenetics (2005) [Pubmed]
  35. The expression of MHC class I, TAP1/2, and LMP2/7 gene in human gastric cancer cell lines. Kang, J.K., Yoon, S.J., Kim, N.K., Heo, D.S. Int. J. Oncol. (2000) [Pubmed]
  36. Association of TAP2 gene polymorphisms in Chinese patients with rheumatoid arthritis. Yu, M.C., Huang, C.M., Wu, M.C., Wu, J.Y., Tsai, F.J. Clin. Rheumatol. (2004) [Pubmed]
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