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

• ACE-enhanced antigen presentation requires the expression of the putative antigenic peptide transporters, TAP1 and TAP2 [6].
• These peptides are translocated in an ATP-dependent fashion into the lumen of the endoplasmic reticulum (ER) for binding to class I molecules by means of the MHC-encoded transporters associated with antigen processing, TAP1 and TAP2 [7].
• Defects in the genes encoding TAP1 or TAP2 account for impaired class I assembly and antigen presentation in several human and rodent cell lines [7].
• 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 [8].
• The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region [9].

Chemical compound and disease context of TAP2

• 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 [10].
• Seventeen formalin-fixed, paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2-microglobulin monoclonal antibodies [11].
• NPY upregulates genes containing cyclic AMP response element in human neuroblastoma cell lines bearing Y1 and Y2 receptors: involvement of CREB [12].

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

• An IFN regulatory factor 1 (IRF1)/IRF2 binding site is located in this region and is involved in both basal and IRF1-induced TAP2 promoter activity [27].
• By confocal immunofluorescence microscopy, TAP1 when expressed alone or with TAP2 is largely, if not exclusively, localized to the endoplasmic reticulum [28].
• TAP-2 expression was enhanced in both lines with IFN-gamma, but to a greater degree in VPR-2 [29].

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

• TAP1 and TAP2 alleles were assigned by ARMS PCR, and LMP2 alleles were assigned by restriction enzyme digestion of a PCR product [34].
• Immunoprecipitation and immobilized metal affinity chromatography revealed complex formation between TAP1 and TAP2 [35].
• Immunoprecipitation of rat TAP1 and TAP2 expressed individually in the human TAP-deficient cell line, T2, revealed that both bound the endogenously expressed HLA-A2 and -B51 class I molecules [36].
• Our results showed that, with totally eight alleles of TAP1 and TAP2 examined in the samples, no significant difference was found in allelic frequencies between pre-eclampsia group and control group, as well as between mothers and their neonates [37].
• We demonstrated, using Western blot and flow cytometry, that IT9302 inhibits the expression of TAP1 and TAP2 proteins, but not MHC class I H chain or low molecular protein molecules [38].

References