Affinage

TAP1

Antigen peptide transporter 1 · UniProt Q03518

Length
748 aa
Mass
81.0 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAP1 is a half-ABC transporter that, together with TAP2, forms the ATP-dependent peptide transporter responsible for delivering cytosolic peptides into the endoplasmic reticulum for loading onto MHC class I molecules, making it essential for class I assembly, surface expression, and CD8+ T cell-mediated antigen presentation (PMID:1473153, PMID:8348620). Both subunits contribute to the peptide-recognition site and require coexpression for efficient peptide binding, while MHC class I/β2-microglobulin dimers associate specifically with TAP1 (PMID:7809108); the N-terminal domain of TAP1 mediates tapasin binding and optimal peptide loading onto class I, integrating TAP into the MHC class I peptide-loading complex (PMID:16174096, PMID:12213826). Catalysis is asymmetric: the TAP1 nucleotide-binding domain carries non-consensus Walker B and switch residues that attenuate its activity, so the consensus TAP2 NBD drives the bulk of peptide translocation, yet both intact NBDs are needed for efficient transport (PMID:11099504, PMID:17068338, PMID:11532960). Loss-of-function alleles—a near-ATP-site missense mutation, mRNA-destabilizing deletions, and human TAP1 deficiency—cause ER retention of unstable HLA class I and failure of antigen presentation, with functional rescue by wild-type TAP1 (PMID:8640228, PMID:12582163, PMID:10074495). Beyond antigen presentation, TAP1-dependent class I loading protects cells from NK lysis and shapes the NK repertoire (PMID:8022815, PMID:8120379), and TAP1 itself modulates antiviral signaling, restraining NF-κB by interacting with the TAK1 complex while promoting TBK1-IRF3-driven IFN-β production (PMID:28356387, PMID:33925089). TAP1 expression is tightly controlled: transcriptionally induced by IFN-γ through rapid STAT1/GAS and delayed IRF-1 inputs, by TNF-α via NF-κB at the shared TAP1/LMP2 bidirectional promoter, and by p53 (PMID:8617938, PMID:8885869, PMID:14735146, PMID:7699330, PMID:10618714), and post-transcriptionally repressed by multiple 3'-UTR-targeting microRNAs downstream of ER stress and in tumors (PMID:22002058, PMID:32923135, PMID:32825219).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 High

    Established that TAP1 is genetically required for MHC class I assembly and cytosolic antigen presentation, defining its core immunological function.

    Evidence Gene knockout mice with surface class I, CTL, and T cell phenotyping

    PMID:1473153

    Open questions at the time
    • Did not resolve the biochemical transport step
    • Did not distinguish TAP1's role from TAP2
  2. 1993 High

    Resolved the molecular activity as ATP-dependent, sequence-selective peptide translocation into the ER, moving from genetic requirement to biochemical mechanism.

    Evidence Cell-free peptide translocation assay using TAP1-deficient cells

    PMID:8348620

    Open questions at the time
    • Did not localize the peptide-binding site to individual subunits
    • Stoichiometry of ATP usage not defined
  3. 1994 High

    Mapped the peptide-recognition site to both TAP subunits and showed MHC class I/β2m dimers associate specifically with TAP1, defining subunit roles and the class I docking site.

    Evidence Photoaffinity labeling and Co-IP in transfectant cell lines

    PMID:7809108

    Open questions at the time
    • Did not establish how the dimer interface forms
    • Tapasin bridging not yet identified
  4. 1994 High

    Extended TAP1 function to NK biology, showing TAP-dependent class I loading shapes the NK repertoire and protects cells from NK lysis.

    Evidence NK cytotoxicity assays in Tap-1-/- mice and TAP transfection of human deficient lines

    PMID:7931074 PMID:8022815 PMID:8120379

    Open questions at the time
    • Whether a TAP1 homodimer functions physiologically remained ambiguous
    • Single-subunit transfection results conflicted across systems
  5. 1995 High

    Defined the inducible transcriptional architecture of the TAP1/LMP2 bidirectional promoter, showing NF-κB drives TNF-α induction and a GC/Sp1 box sets basal expression.

    Evidence Bidirectional reporter, mutagenesis, in vivo footprinting, EMSA

    PMID:7699330

    Open questions at the time
    • Did not address IFN-γ inputs
    • Cross-talk between the two genes' regulation unresolved
  6. 1996 High

    Dissected IFN-γ induction into a rapid STAT1/GAS arm and a delayed IRF-1 arm, and identified a p53-responsive element, establishing convergent transcriptional control.

    Evidence Promoter mutagenesis, kinetic transfectant analysis, EMSA, IRF-1 knockout mice; later p53/p73 reporter and transport assays

    PMID:10618714 PMID:8617938 PMID:8885869

    Open questions at the time
    • Did not quantify relative contribution of each factor in vivo
    • Interplay with NF-κB at the shared promoter not integrated
  7. 1996 High

    Linked a structural TAP1 defect to disease by showing an ATP-site-proximal mutation abolishes antigen presentation, rescuable by wild-type TAP1.

    Evidence Tumor allele sequencing, peptide binding/presentation assays, functional rescue transfection

    PMID:8640228

    Open questions at the time
    • Mechanism of how R659Q impairs catalysis not structurally defined
    • Frequency in tumors not established
  8. 1999 Medium

    Demonstrated human TAP1 deficiency causes ER retention of unstable HLA class I, confirming the mouse phenotype in patients.

    Evidence Clinical and biochemical analysis of TAP1-deficient patients

    PMID:10074495

    Open questions at the time
    • Small patient numbers
    • Did not define the specific molecular lesions
  9. 2000 High

    Established the asymmetry of the two nucleotide-binding domains, showing TAP1 NBD nucleotide binding is dispensable for peptide binding but both NBDs are needed for efficient translocation.

    Evidence Walker A mutagenesis (TAP1 K544M, TAP2 K509M) with nucleotide/peptide binding and translocation assays in insect cells

    PMID:11099504

    Open questions at the time
    • Did not yet explain the catalytic basis of asymmetry
    • Order of ATP binding/hydrolysis between sites unresolved
  10. 2001 High

    Provided the first atomic-resolution view of the TAP1 ABC ATPase domain bound to ADP, rationalizing nucleotide-site asymmetry structurally.

    Evidence X-ray crystallography of recombinant cTAP1 bound to ADP

    PMID:11532960

    Open questions at the time
    • No full-length or heterodimeric structure
    • Transmembrane peptide pathway not visualized
  11. 2002 High

    Defined where tapasin engages TAP and its functional effect, showing it binds the membrane-spanning domains and thermostabilizes the complex without being required for peptide binding.

    Evidence Co-IP with TAP truncation/chimera constructs, peptide binding and thermostability assays in insect cells

    PMID:12213826

    Open questions at the time
    • Did not map the precise tapasin contact residues
    • Coupling to MHC loading complex assembly inferred indirectly
  12. 2003 Medium

    Showed post-transcriptional control matters, with a 3'-region single-nucleotide deletion destabilizing TAP1 mRNA independent of NMD and abolishing protein expression despite active transcription.

    Evidence Tet-Off mRNA half-life measurement and cycloheximide chase in melanoma cells

    PMID:12582163

    Open questions at the time
    • The destabilizing element/factor not identified
    • Generality across tumors not assessed
  13. 2005 High

    Assigned the tapasin-binding and MHC-loading function to the TAP1 N-terminal domain, separating it from the transport core.

    Evidence N-terminally truncated TAP constructs with tapasin binding, translocation, and MHC reconstitution assays in insect cells

    PMID:16174096

    Open questions at the time
    • Did not resolve the structure of the N-terminal TMD0-like region
    • Recruitment of other PLC components not addressed
  14. 2006 High

    Identified the molecular basis of NBD asymmetry, showing non-consensus catalytic residues attenuate the TAP1 site (Site 1) while the consensus TAP2 site (Site 2) drives transport.

    Evidence Site-directed mutagenesis of catalytic residues with translocation and MHC surface expression assays

    PMID:17068338

    Open questions at the time
    • Conformational coupling between sites not directly observed
    • ATP hydrolysis cycle timing unresolved
  15. 2007 High

    Revealed a non-cell-intrinsic immune role, where TAP1 is needed for NK-derived IFN-γ that supports CD4+ T cell responses and resistance during Toxoplasma infection.

    Evidence Infection, NK depletion, and adoptive transfer in TAP-1-/- mice

    PMID:17923502

    Open questions at the time
    • Mechanistic link between TAP1 and NK IFN-γ production not defined
    • Class I-dependence of the effect not isolated
  16. 2017 Medium

    Uncovered a moonlighting function whereby virus-induced TAP1 dampens NF-κB signaling by binding the TAK1 complex, independent of antigen presentation.

    Evidence Co-IP and phosphorylation assays with viral replication readouts in human cell lines

    PMID:28356387

    Open questions at the time
    • Direct TAP1-TAK1 contact residues not mapped
    • Single lab without reciprocal validation
  17. 2021 Medium

    Extended the moonlighting role to positive antiviral signaling, with TAP1 activating TBK1-IRF3 to drive IFN-β against multiple viruses.

    Evidence Reciprocal overexpression/knockdown with TBK1/IRF3 phosphorylation, IFN-β, and viral replication assays

    PMID:33925089

    Open questions at the time
    • Reconciliation with NF-κB-suppressive role unclear
    • Mechanism of TBK1 engagement undefined
  18. 2020 Medium

    Established microRNA-mediated repression of TAP1 as an immune-evasion route in tumors, with multiple miRNAs directly targeting the 3'-UTR to lower class I and increase NK/T sensitivity.

    Evidence Luciferase 3'-UTR reporters, miRNA overexpression, flow cytometry, NK/T cytotoxicity (also ER stress sXBP1-miR-346 axis, GLI-driven transcription, and promoter hypermethylation)

    PMID:22002058 PMID:23340176 PMID:29341428 PMID:32108992 PMID:32825219 PMID:32923135

    Open questions at the time
    • Relative in vivo contribution of each repressive mechanism unquantified
    • Most validated in single cell-line systems

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAP1's antigen-transport function is mechanistically coordinated with its opposing roles in NF-κB suppression and TBK1-IRF3 activation during infection remains unresolved.
  • No structural model of full-length TAP1-TAP2 in the human PLC
  • Direct interaction interfaces with TAK1/TBK1 not defined
  • Conditions selecting transport vs signaling functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0140657 ATP-dependent activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-382551 Transport of small molecules 2 R-HSA-392499 Metabolism of proteins 2
Partners
B2MMHC CLASS ITAK1TAP2TAPASIN
Complex memberships
MHC class I peptide-loading complexTAP1-TAP2 peptide transporter

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 TAP1 is required for stable assembly and intracellular transport of MHC class I molecules; TAP1-deficient mice show severely reduced surface class I expression and are unable to present cytosolic antigens to class I-restricted CTL, and lack CD4-8+ T cells. Gene knockout (embryonic stem cell technology) with flow cytometry, CTL assay, T cell phenotyping Cell High 1473153
1993 TAP1 is part of an ATP-dependent, sequence-specific peptide translocator; peptide translocation in a cell-free system requires ATP and is peptide-selective. Cell-free (in vitro) peptide translocation assay using TAP1-deficient mouse cells Cell High 8348620
1994 Both TAP1 and TAP2 subunits contribute to the peptide-recognition site (both are photolabeled by peptide analogues); efficient peptide-binding site formation requires coexpression of both subunits. MHC class I/β2-microglobulin dimers associate specifically with TAP1 but not with TAP2 alone. Photoaffinity labeling of TAP1 and TAP2 with photopeptide analogues; Co-immunoprecipitation of MHC class I/β2m with individual TAP subunits in transfectant cell lines Proceedings of the National Academy of Sciences of the United States of America High 7809108
1994 Introduction of the rat TAP1 gene alone into the CMT.64 antigen-processing-deficient cell line restores CTL recognition of VSV-infected cells, indicating that a TAP1 homodimer may translocate peptides in the endoplasmic reticulum. TAP1 gene transfection into TAP1/TAP2-deficient cell line followed by CTL cytotoxicity assay The Journal of experimental medicine Medium 7931074
1994 TAP1 is required for NK cell repertoire development; Tap-1-/- mice NK cells are tolerant to autologous and allogeneic bone marrow cells and TAP-deficient tumor cells. Defective TAP1 expression renders non-transformed target cells sensitive to NK cell lysis, supporting a role for class I molecules (loaded via TAP) in protecting cells from NK killing. NK cell functional assays (cytotoxicity against multiple target cell types) in Tap-1-/- mice Proceedings of the National Academy of Sciences of the United States of America High 8022815
1994 Transfection of TAP1 and TAP2 (or TAP1 alone into 721.134 cells) into human antigen-processing-deficient cell lines (T2, 721.174, 721.134) confers resistance to NK cell lysis; intact TAP1/TAP2 dimer is required for efficient NK resistance, and single TAP gene transfection does not restore NK resistance. TAP gene transfection into MHC/TAP-deficient human cell lines; NK cytotoxicity assay with xenogeneic and allogeneic NK cells Journal of immunology Medium 8120379
1995 TAP1 and LMP2 genes are divergently transcribed from a shared bidirectional promoter of only 593 bp. An NF-κB element in the TAP1-proximal region is required for TNF-α induction of both TAP1 and LMP2. An adjacent GC box (binding Sp1) is required for basal expression and augments TNF-α induction. In vivo genomic footprinting confirmed protein-DNA contacts at NF-κB and GC box sites. Bidirectional reporter assay, site-specific mutagenesis, in vivo genomic footprinting, in vitro binding assays (EMSA) for NF-κB p50/p65, p52/p65 and Sp1 The Journal of experimental medicine High 7699330
1995 TAP1-independent class I-associated presentation of exogenous viral proteins (glycoprotein and nucleoprotein from LCMV, NP of VSV) occurs in TAP1-/- cells as efficiently as in control cells, demonstrating a TAP-independent pathway for exogenous antigen cross-presentation. In vitro antigen presentation assay using spleen cells and macrophages from TAP1-/- mice with recombinant viral proteins and CTL recognition European journal of immunology Medium 7615001
1996 A functionally defective TAP1 allele (R659Q, near the ATP-binding site) in a human small cell lung cancer cell line results in loss of MHC class I antigen presentation; defective presentation is restored by transfection of a functional TAP1 allele, confirming protein structural defect causes transport failure. Sequencing of TAP1 in tumor cells; peptide binding and antigen presentation assays; functional rescue by TAP1 transfection Nature genetics High 8640228
1996 IRF-1 directly regulates IFN-γ-mediated induction of TAP1 and LMP2. IFN-γ upregulates protein-DNA contacts at an IRF-E in the TAP1/LMP2 promoter. TAP1 and LMP2 expression is greatly reduced in IRF-1-deficient mice, with consequent reduction in surface MHC class I and CD8+ T cells. In vivo footprinting, gel shift analysis, IRF-1 knockout mouse analysis, surface class I and T cell phenotyping Immunity High 8885869
1996 IFN-γ rapidly induces TAP1 via Stat1α binding to a gamma-activating sequence (GAS) in the TAP1 promoter; this is distinct from the slower IFN-γ induction of HLA class I (mediated by IRF-1). IFN-γ activates Stat1α binding to GAS more rapidly than it induces IRF-1. Kinetic analysis of promoter activation in transfectants, site-specific mutagenesis of GAS element, gel-shift assays for Stat1α Journal of immunology High 8617938
1999 p53 induces TAP1 transcription through a p53-responsive element, enhancing transport of MHC class I peptides and surface MHC-peptide complex expression. p73 also induces TAP1 and cooperates with p53. p53-mediated induction of TAP1 cooperates with IFN-γ to activate the MHC class I pathway. Reporter assays with p53-responsive element, p53/p73 overexpression/knockdown, peptide transport assay, flow cytometry for surface MHC Oncogene Medium 10618714
1999 TAP1 deficiency in human patients causes unstable HLA class I molecules retained in the endoplasmic reticulum, establishing that TAP1 is required for stable HLA class I assembly and ER export in humans. Clinical immunological analysis of TAP1-deficient patients; biochemical analysis of HLA class I stability and intracellular localization The Journal of clinical investigation Medium 10074495
2000 Walker A lysine mutations of TAP1 (K544M) significantly impair nucleotide binding to TAP1 but do not prevent peptide binding; the analogous TAP2 (K509M) mutation does not impair nucleotide binding. Low-level peptide translocation remains detectable with TAP1(K544M).TAP2 but is abolished in TAP1.TAP2(K509M), indicating that nucleotide binding to TAP1 is not required for peptide binding and that both intact NBDs are needed for efficient translocation. Site-directed mutagenesis; nucleotide binding assay; fluorescence quenching peptide binding assay; in vitro peptide translocation assay in insect cells The Journal of biological chemistry High 11099504
2001 The crystal structure of the C-terminal ABC ATPase domain of TAP1 (cTAP1) bound to ADP reveals an L-shaped molecule with a RecA-like domain and a small α-helical domain. The diphosphate of ADP interacts with the P-loop; residues involved in γ-phosphate binding and hydrolysis show flexibility in ADP-bound state. Differences between TAP1 and TAP2 nucleotide-binding sites may underlie asymmetry in peptide transport. X-ray crystallography of recombinant cTAP1 bound to ADP The EMBO journal High 11532960
2002 Tapasin interacts with the membrane-spanning domains of both TAP1 and TAP2 (but not with truncated constructs containing only the NBDs). Tapasin enhances thermostability of TAP1·TAP2 complexes but is not required for high-affinity peptide binding; tapasin slightly reduces peptide-binding affinity while stabilizing the peptide-binding site at near-physiological temperatures. Co-immunoprecipitation of tapasin with TAP truncation/chimera constructs expressed in insect cells; peptide binding affinity assay; thermal stability assay The Journal of biological chemistry High 12213826
2003 HCV core protein induces p53-dependent TAP1 gene expression leading to upregulation of MHC class I; this increased MHC class I expression reduces NK cell cytotoxicity against HCV core-expressing liver cells (without affecting HCV-specific CTL lysis). p53 lacking DNA-binding capacity fails to induce TAP1, confirming requirement for direct p53-DNA binding. Transfection of HCV core and p53 constructs in liver cell lines; flow cytometry for MHC class I; NK and CTL cytotoxicity assays Journal of virology Medium 12857899
2003 A single-nucleotide deletion at position +1489 of the TAP1 gene (in melanoma cell SK-MEL-19) causes rapid mRNA degradation (>2-fold decrease in TAP1 mRNA half-life), independent of nonsense-mediated decay, resulting in loss of TAP1 protein and MHC class I expression even despite active TAP1 transcription. Sequencing; inducible Tet-Off system for mRNA half-life measurement; cycloheximide chase; correction by secondary mutations to rule out NMD The Journal of biological chemistry Medium 12582163
2005 N-terminal domains of TAP1 (residues 1–131) and TAP2 (residues 1–88) are important for tapasin binding and for optimal peptide loading onto MHC class I molecules. Truncated TAP variants lacking these domains retain peptide binding and nucleotide substrate binding at comparable levels to wild-type but show reduced peptide translocation efficiency and reduced tapasin-mediated enhancement of MHC class I processing. Expression and purification of N-terminally truncated TAP constructs in insect cells; tapasin binding assay; peptide binding assay; in vitro peptide translocation assay; insect cell-based MHC class I reconstitution assay Immunology and cell biology High 16174096
2006 The TAP1 nucleotide-binding domain contains non-consensus catalytic residues (Asp668 in Walker B instead of glutamate; Gln701 in switch region instead of histidine), resulting in attenuated catalytic activity at the TAP1 NBD (Site 1). The TAP2 NBD (Site 2) has consensus residues (Glu632, His661) and drives the majority of peptide transport; mutations of TAP2 Glu632 and His661 significantly reduce peptide translocation and MHC class I surface expression. Site-directed mutagenesis of catalytic residues in TAP1 and TAP2 NBDs; in vitro peptide translocation assay; MHC class I surface expression assay The Journal of biological chemistry High 17068338
2007 TAP-1 is required for induction of IFN-γ-producing NK cells during Toxoplasma gondii infection; loss of NK-derived IFN-γ in TAP-1-/- mice indirectly impairs CD4+ T cell IFN-γ responses and reduces resistance to infection. Adoptive transfer of IFN-γ+/+ but not IFN-γ-/- NK cells restores CD4+ T cell responses in TAP-1-/- mice. TAP-1-/- mouse infection model; NK cell depletion; adoptive NK cell transfer; flow cytometry for CD4+ T cell activation The Journal of experimental medicine High 17923502
2011 sXBP1 (spliced X-box-binding protein 1), activated during ER stress, induces miR-346, which directly targets the human TAP1 mRNA 3'-UTR (6-mer canonical seed site) and reduces TAP1 mRNA and protein levels. Inhibition of miR-346 with an antagomir reverses ER stress-associated reduction in TAP1 expression. miRNA microarray; miR-346 overexpression/antagomir; luciferase 3'-UTR reporter assay; mRNA and protein quantification; sXBP1 overexpression/knockdown The Journal of biological chemistry High 22002058
2011 Low basal TAP1 expression in SCCHN cells is regulated by deficiency in activated (phosphorylated) STAT1. STAT1 knockdown reduces IFN-γ-mediated TAP1 expression and impairs CTL recognition of SCCHN cells. STAT3 depletion/activation does not affect STAT1-mediated TAP1 promoter binding or expression; pSTAT1:pSTAT3 heterodimers do not interfere with IFN-γ-induced STAT1 binding to the TAP1 promoter. STAT1 and STAT3 knockdown; STAT1 ChIP on TAP1 promoter; flow cytometry for APM component expression; CTL recognition assay Cancer immunology, immunotherapy Medium 21207025
2017 TAP1 negatively regulates antiviral innate immune signaling: virus-induced TAP1 interacts with the TAK1 complex, impairing TAK1 phosphorylation and subsequently suppressing IKK complex phosphorylation, IκBα phosphorylation, and NF-κB nuclear translocation, thereby inhibiting IFN and proinflammatory cytokine production and enhancing virus replication. TAP1 overexpression/knockdown in human cell lines (A549, THP-1, HeLa, Vero); Co-IP of TAP1 with TAK1 complex; phosphorylation assays for TAK1, IKK, IκBα; NF-κB nuclear translocation assay; virus replication assay Journal of immunology Medium 28356387
2020 miR-200a-5p directly targets the 3'-UTR of TAP1 mRNA (confirmed by luciferase reporter assay), reducing TAP1 protein levels and HLA class I surface expression in melanoma cells, and increasing NK cell sensitivity. In silico prediction; luciferase 3'-UTR reporter assay; miR-200a-5p overexpression; flow cytometry for HLA class I; NK cytotoxicity assay Oncoimmunology Medium 32923135
2020 miR-26b-5p and miR-21-3p directly target the TAP1 3'-UTR (confirmed by luciferase reporter assay); overexpression in melanoma cells reduces TAP1 protein and HLA class I surface expression and decreases T cell recognition. In silico analysis; dual luciferase reporter assay; miRNA overexpression; flow cytometry; T cell recognition assay Journal of clinical medicine Medium 32825219
2021 TAP1 promotes IFN-β production by activating TBK1-IRF3 signaling, providing broadly antiviral activity independent of its antigen presentation function. TAP1 overexpression inhibits viral replication of multiple viruses (HSV-1, AdV, VSV, DENV, ZIKV, PR8); TAP1 knockdown has the opposite effect. Gain-of-function and loss-of-function (overexpression and siRNA knockdown) in human cell lines; TBK1 and IRF3 phosphorylation assays; IFN-β production assay; viral replication assays International journal of molecular sciences Medium 33925089
2013 ABCB2/TAP1 is a downstream transcriptional target of SHH (Sonic Hedgehog) signaling via GLI1/2 transcription factors; GLI1/2 binds to the TAP1 promoter and drives TAP1 expression, contributing to drug resistance in pancreatic ductal adenocarcinoma. GLI1/2 overexpression/knockdown; chromatin binding/promoter assays validating GLI-binding site in TAP1 promoter; drug sensitivity assays; in vitro and in vivo tumor experiments Cancer letters Medium 23340176
2020 GLI1/2 hedgehog transcription factors directly bind the TAP1 promoter and transcriptionally activate TAP1 expression in hepatocellular carcinoma cells; GLI1 or TAP1 inhibition (RNAi or GANT61) restores sensitivity to sorafenib, doxorubicin, and cisplatin. GLI1/2 and TAP1 RNAi; molecular promoter binding assays (GLI-binding site validation); drug cytotoxicity assay Journal of cellular and molecular medicine Medium 32108992
2004 STAT1 and IRF-1 are both required for IFN-γ induction of murine Tap-1 and Lmp-2 in macrophages; STAT1 binds to the proximal GAS box (early, ~30 min) and IRF-1 binds to the IRF-1 box (later, ≥2 h); Tap-1 induction by IFN-γ is abolished in STAT1 knockout macrophages. Promoter deletion analysis, gel shift analysis (nuclear extracts from IFN-γ-treated macrophages), STAT1 knockout macrophages, RT-PCR/Northern blot Genes and immunity High 14735146
2018 DNA hypermethylation at the TAP1 locus contributes to reduced TAP1 expression in Aldefluor+ breast cancer stem cells. TAP1 knockdown in 4T1 murine mammary cells increases tumor growth in immunocompetent mice, demonstrating a functional immune evasion consequence. Bisulfite pyrosequencing; decitabine (demethylating agent) treatment; TAP1 knockdown; in vivo tumor growth assay in immunocompetent mice Stem cells Medium 29341428
1997 EBV-encoded vIL-10 (and human IL-10) specifically downregulates TAP1 and LMP2 gene expression (but not TAP2 or LMP7) in B lymphocytes, reducing peptide transport into the ER, impairing peptide loading onto MHC class I, and reducing surface MHC class I molecules. vIL-10/hIL-10 treatment of B cells; TAP-specific peptide transporter assay; flow cytometry for surface MHC class I Blood Medium 9310490

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell 625 1473153
1993 TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. Cell 329 8348620
1994 Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. The Journal of experimental medicine 295 8270878
1999 Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. The Journal of experimental medicine 278 10377193
2001 Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing. The EMBO journal 234 11532960
1996 Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. The Journal of clinical investigation 227 8833913
1993 Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2. Immunogenetics 227 8428770
1995 Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. The Journal of experimental medicine 208 7699330
1996 A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nature genetics 165 8640228
1996 Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. British journal of cancer 164 8546899
1997 Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 158 9310490
1994 Characteristics of peptide and major histocompatibility complex class I/beta 2-microglobulin binding to the transporters associated with antigen processing (TAP1 and TAP2). Proceedings of the National Academy of Sciences of the United States of America 152 7809108
1995 Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. British journal of cancer 150 7640226
1998 HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer research 145 9485029
2011 The unfolded protein response (UPR)-activated transcription factor X-box-binding protein 1 (XBP1) induces microRNA-346 expression that targets the human antigen peptide transporter 1 (TAP1) mRNA and governs immune regulatory genes. The Journal of biological chemistry 127 22002058
2000 Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins. Oncogene 127 11039910
1994 Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours. British journal of cancer 125 8198988
1996 Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice. Immunity 123 8885869
1999 p53 induces TAP1 and enhances the transport of MHC class I peptides. Oncogene 101 10618714
2003 Upregulation of major histocompatibility complex class I on liver cells by hepatitis C virus core protein via p53 and TAP1 impairs natural killer cell cytotoxicity. Journal of virology 100 12857899
1999 HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1. The Journal of clinical investigation 98 10074495
1996 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. Journal of immunology (Baltimore, Md. : 1950) 91 8617938
2011 Deficiency of activated STAT1 in head and neck cancer cells mediates TAP1-dependent escape from cytotoxic T lymphocytes. Cancer immunology, immunotherapy : CII 89 21207025
1995 TAP1-independent loading of class I molecules by exogenous viral proteins. European journal of immunology 87 7615001
1994 Comparison of cell lines deficient in antigen presentation reveals a functional role for TAP-1 alone in antigen processing. The Journal of experimental medicine 82 7931074
1994 Altered natural killer cell repertoire in Tap-1 mutant mice. Proceedings of the National Academy of Sciences of the United States of America 82 8022815
2000 Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line. Cancer research 71 11059775
2000 Walker A lysine mutations of TAP1 and TAP2 interfere with peptide translocation but not peptide binding. The Journal of biological chemistry 64 11099504
1997 IFN-gamma-mediated coordinated transcriptional regulation of the human TAP-1 and LMP-2 genes in human renal cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 62 9815722
1994 Positive selection of self- and alloreactive CD8+ T cells in Tap-1 mutant mice. Proceedings of the National Academy of Sciences of the United States of America 62 8022816
2004 Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1. Genes and immunity 61 14735146
2007 TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production. The Journal of experimental medicine 55 17923502
1996 Development of CD8 alpha alpha+ intestinal intraepithelial T cells in beta 2-microglobulin- and/or TAP1-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 55 8609387
1995 MHC class I expression and CD8+ T cell development in TAP1/beta 2-microglobulin double mutant mice. International immunology 55 7577806
2003 TAP1, TAP2, and HLA-DR2 alleles are predictors of cervical cancer risk. Gynecologic oncology 54 12648582
1999 Analysis of MHC encoded antigen-processing genes TAP1 and TAP2 polymorphisms in sarcoidosis. American journal of respiratory and critical care medicine 53 10471632
2018 Epigenetic Silencing of TAP1 in Aldefluor+ Breast Cancer Stem Cells Contributes to Their Enhanced Immune Evasion. Stem cells (Dayton, Ohio) 52 29341428
1987 Nerve terminal anchorage protein 1 (TAP-1) is a chondroitin sulfate proteoglycan: biochemical and electron microscopic characterization. The Journal of cell biology 52 3693407
2005 Identification of domain boundaries within the N-termini of TAP1 and TAP2 and their importance in tapasin binding and tapasin-mediated increase in peptide loading of MHC class I. Immunology and cell biology 51 16174096
1999 Insertional inactivation of Treponema denticola tap1 results in a nonmotile mutant with elongated flagellar hooks. Journal of bacteriology 51 10368149
2005 Mouse endothelial cells cross-present lymphocyte-derived antigen on class I MHC via a TAP1- and proteasome-dependent pathway. Journal of immunology (Baltimore, Md. : 1950) 47 15944272
1993 Induction of a tomato anionic peroxidase gene (tap1) by wounding in transgenic tobacco and activation of tap1/GUS and tap2/GUS chimeric gene fusions in transgenic tobacco by wounding and pathogen attack. Plant molecular biology 47 7678769
2006 Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to tuberculosis. Tissue antigens 46 16634865
2000 Altered expression of TAP-1 and major histocompatibility complex class I in laryngeal papillomatosis: correlation of TAP-1 with disease. Clinical and diagnostic laboratory immunology 46 10618282
2009 Neonatal infection with neurotropic influenza A virus induces the kynurenine pathway in early life and disrupts sensorimotor gating in adult Tap1-/- mice. The international journal of neuropsychopharmacology 45 19607757
1991 Molecular characterization of two stamen-specific genes, tap1 and fil1, that are expressed in the wild type, but not in the deficiens mutant of Antirrhinum majus. Molecular & general genetics : MGG 45 1680216
2013 ABCB2 (TAP1) as the downstream target of SHH signaling enhances pancreatic ductal adenocarcinoma drug resistance. Cancer letters 43 23340176
2002 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 43 12213826
2009 Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross-presenting function. Journal of immunotherapy (Hagerstown, Md. : 1997) 42 19609238
2003 A single-nucleotide deletion leads to rapid degradation of TAP-1 mRNA in a melanoma cell line. The Journal of biological chemistry 42 12582163
1997 Polymorphisms of TAP1 and TAP2 genes in Graves' disease. Tissue antigens 41 9027960
2017 Downregulation of TAP1 and TAP2 in early stage breast cancer. PloS one 40 29091951
1996 TAP1-deficient mice select a CD8+ T cell repertoire that displays both diversity and peptide specificity. European journal of immunology 40 8617293
1994 Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells. Journal of immunology (Baltimore, Md. : 1950) 40 8120379
2018 The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins. Molecular immunology 38 29879547
2002 Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits. Immunology 38 12047747
2000 Synergistic induction of the Tap-1 gene by IFN-gamma and lipopolysaccharide in macrophages is regulated by STAT1. Journal of immunology (Baltimore, Md. : 1950) 38 10975834
1999 Induction of immunogenicity of a human renal-cell carcinoma cell line by TAP1-gene transfer. International journal of cancer 37 10077163
1995 Differential reactivity of residual CD8+ T lymphocytes in TAP1 and beta 2-microglobulin mutant mice. European journal of immunology 37 7843229
1993 Developmental and tissue-specific expression of a tomato anionic peroxidase (tap1) gene by a minimal promoter, with wound and pathogen induction by an additional 5'-flanking region. Plant molecular biology 37 8329686
2020 Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma. Journal of cellular and molecular medicine 36 32108992
2010 Down-regulation of HLA class I antigen in human papillomavirus type 16 E7 expressing HaCaT cells: correlate with TAP-1 expression. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 36 20134267
1996 Markedly decreased expression of TAP1 and LMP2 genes in HLA class I-deficient human tumor cell lines. Immunology letters 36 8803612
2020 Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients. Oncoimmunology 35 32923135
2012 TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice. PloS one 35 22479479
2006 The mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-gamma inducibility of TAP1 and LMP2. Oncogene 33 16474838
1997 Expression of transporter associated with antigen processing 1 and 2 (TAP1/2) in malignant melanoma cell lines. International journal of cancer 33 9052759
2017 A novel mutation in TAP1 gene leading to MHC class I deficiency: Report of two cases and review of the literature. Clinical immunology (Orlando, Fla.) 32 28161407
2004 Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma. Cellular immunology 31 15219464
1998 Interferon induction of TAP1: the phosphatase SHP-1 regulates crossover between the IFN-alpha/beta and the IFN-gamma signal-transduction pathways. Circulation research 31 9776728
2001 Expression of HLA class I, beta(2)-microglobulin, TAP1 and IL-10 in Epstein-Barr virus-associated nasal NK/T-cell lymphoma: Implications for tumor immune escape mechanism. International journal of cancer 30 11340574
1999 Processing of HIV-1 envelope glycoprotein for class I-restricted recognition: dependence on TAP1/2 and mechanisms for cytosolic localization. Journal of immunology (Baltimore, Md. : 1950) 29 9973386
1997 Polymorphism in transporter antigen peptides gene (TAP1) associated with atopy in Tunisians. The Journal of allergy and clinical immunology 29 9042048
1997 Reduced expression of Tap1 and Lmp2 antigen-processing genes in the nonobese diabetic (NOD) mouse due to a mutation in their shared bidirectional promoter. Journal of immunology (Baltimore, Md. : 1950) 29 9300732
2017 IRG1 increases MHC class I level in macrophages through STAT-TAP1 axis depending on NADPH oxidase mediated reactive oxygen species. International immunopharmacology 28 28477473
2013 Association of TAP1 and TAP2 gene polymorphisms with hematological malignancies. Asian Pacific journal of cancer prevention : APJCP 27 24175803
2006 Catalytic site modifications of TAP1 and TAP2 and their functional consequences. The Journal of biological chemistry 27 17068338
1996 Cell cycle-dependent expression of TAP1, TAP2, and HLA-B27 messenger RNAs in a human breast cancer cell line. Cancer research 27 8813124
1993 TAP1, a yeast gene that activates the expression of a tRNA gene with a defective internal promoter. Molecular and cellular biology 26 8497259
2017 A case-control study on association of proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1) polymorphisms and their transcript levels in vitiligo from Gujarat. PloS one 25 28700671
2003 TAP1 and TAP2 polymorphisms analysis in northwestern Colombian patients with systemic lupus erythematosus. Annals of the rheumatic diseases 25 12634240
2000 A half-type ABC transporter TAPL is highly conserved between rodent and man, and the human gene is not responsive to interferon-gamma in contrast to TAP1 and TAP2. Journal of biochemistry 25 11011155
1995 Expression of TAP1 by human trophoblast. European journal of immunology 25 7875218
1994 Analysis of HLA-class-II-encoded antigen-processing genes TAP1 and TAP2 in primary biliary cirrhosis. The Quarterly journal of medicine 25 8208914
2017 Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex. Journal of immunology (Baltimore, Md. : 1950) 24 28356387
2002 TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 24 12047361
1997 The MHC-encoded TAP1/LMP2 bidirectional promoter is down-regulated in highly oncogenic adenovirus type 12 transformed cells. FEBS letters 24 9001385
1995 Tap-1 and Tap-2 gene therapy selectively restores conformationally dependent HLA Class I expression in type I diabetic cells. Human gene therapy 24 7578413
2020 Identification of microRNAs Targeting the Transporter Associated with Antigen Processing TAP1 in Melanoma. Journal of clinical medicine 23 32825219
2003 Association of TAP1 downregulation in human primary melanoma lesions with lack of spontaneous regression. Melanoma research 23 12777979
2002 Differential regulation of the expression of transporters associated with antigen processing, TAP1 and TAP2, by cytokines and lipopolysaccharide in primary human macrophages. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 23 12234057
2015 Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations. Journal of experimental & clinical cancer research : CR 22 26205887
2008 Activation of antigen-specific cytotoxic T lymphocytes by beta 2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic embryonic stem cell-derived dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 22 18941254
2001 Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence. International journal of cancer 22 11169961
1998 Genomic organization of six tomato polygalacturonases and 5' upstream sequence identity with tap1 and win2 genes. Molecular & general genetics : MGG 22 9669329
1993 Structure of the yeast TAP1 protein: dependence of transcription activation on the DNA context of the target gene. Molecular and cellular biology 21 8497260
2016 Association of TAP1 and TAP2 Gene Polymorphisms with Susceptibility to Pulmonary Tuberculosis. Iranian journal of allergy, asthma, and immunology 20 26996113
2001 Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease. Melanoma research 20 11468516
1994 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. Lymphokine and cytokine research 20 8061113
2021 Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production. International journal of molecular sciences 19 33925089

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