Affinage

ERAP2

Endoplasmic reticulum aminopeptidase 2 · UniProt Q6P179

Length
960 aa
Mass
110.5 kDa
Annotated
2026-04-28
92 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERAP2 is an endoplasmic reticulum-resident zinc aminopeptidase that trims N-terminal residues from peptide precursors to shape the MHC class I immunopeptidome, with a preference for shorter substrates (<9-mers) and N-terminal basic residues (PMID:15908954, PMID:28063628, PMID:36569828). It physically heterodimerizes with ERAP1, and this complex exhibits allosterically enhanced trimming efficiency and complementary substrate specificity that together optimize the length and sequence composition of HLA class I ligands across multiple allotypes (PMID:24928998, PMID:27514473, PMID:31092671). ERAP2 expression is governed by the splice-region variant rs2248374, which directs nonsense-mediated decay of the haplotype B transcript, and by long-range chromatin contacts from the LNPEP promoter that independently modulate transcription (PMID:20976248, PMID:38190099). Beyond its canonical ER function, an autocatalytically generated short form of ERAP2 is secreted by macrophages, binds IRAP in endosomes, and full-length ERAP2 secreted from activated macrophages modulates immune cell activation (PMID:35563348, PMID:31379846).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 High

    The foundational question of whether ERAP2 functions independently or cooperatively with ERAP1 was resolved: the two enzymes form ER-resident heterodimers with complementary specificities required for concerted trimming of MHC class I peptide precursors.

    Evidence Co-immunoprecipitation, in vitro peptide digestion, and cellular antigen presentation assays

    PMID:15908954

    Open questions at the time
    • Stoichiometry and structural basis of the heterodimer were unknown
    • Whether dimerization alters enzymatic kinetics was not addressed
    • In vivo relevance to specific HLA allotypes was untested
  2. 2010 High

    The mechanism controlling natural ERAP2 deficiency was identified: a haplotype-specific splice variant (rs2248374) directs nonsense-mediated decay, and homozygous carriers show reduced surface MHC class I, establishing ERAP2 as a non-redundant contributor to antigen presentation in humans.

    Evidence Haplotype analysis, RT-PCR for splice forms, flow cytometry for MHC class I on primary lymphocytes

    PMID:20976248

    Open questions at the time
    • Whether the splicing variant also affects ERAP2 isoform diversity was not explored
    • Impact on specific peptidome repertoires was uncharacterized
  3. 2013 Medium

    The concerted trimming model was extended to viral epitopes: ERAP1 and ERAP2 sequentially use each other's products as substrates, increasing generation of natural HLA-B27 ligands beyond what either enzyme achieves alone.

    Evidence In vitro digestion of viral precursors with mass spectrometry product identification

    PMID:24223975

    Open questions at the time
    • Whether sequential processing reflects ordered recruitment or stochastic encounter was unclear
    • Trimming was studied in vitro, not confirmed in live cells for these substrates
  4. 2014 High

    Heterodimerization was shown to be more than co-localization: stabilized ERAP1–ERAP2 heterodimers display allosterically enhanced kinetics—improved substrate binding affinity and trimming efficiency—compared to equimolar mixtures of non-interacting enzymes.

    Evidence Stabilized heterodimer production, enzymatic kinetic parameter measurements

    PMID:24928998

    Open questions at the time
    • Structural basis of allosteric communication was unresolved
    • Whether allosteric modulation is reciprocal (ERAP2 kinetics altered by ERAP1) was not tested
  5. 2016 High

    The substrate scope of ERAP1/ERAP2 heterodimers was expanded beyond free peptides: the complex trims MHC class I-bound precursor peptides, increasing conformational stability of resulting pMHC complexes and supporting a peptide-editing model.

    Evidence In vitro trimming of HLA-B*08:01-bound N-terminally extended peptides with stability measurements

    PMID:27514473

    Open questions at the time
    • Whether trimming of MHC-bound peptides occurs in the ER lumen was not demonstrated
    • Contribution of tapasin-mediated editing relative to ERAP trimming was unaddressed
  6. 2017 High

    Quantitative peptidomics across multiple HLA allotypes established that ERAP2 and ERAP1 exert distinct effects on the immunopeptidome: ERAP2 specifically depletes peptides with N-terminal basic residues, while ERAP1 primarily controls length—and the two enzymes largely act as separate entities in vivo despite their ability to heterodimerize.

    Evidence Label-free quantitative mass spectrometry of HLA-B*27:05, B*51:01, B*40:02, and A*29:02 peptidomes from CRISPR KO or genotype-defined cell lines

    PMID:28063628 PMID:29769354 PMID:31092671 PMID:31530632

    Open questions at the time
    • Relative contributions of heterodimer vs. monomer activity in live cells were not resolved
    • How ERAP2 effects translate to T cell immunodominance was not systematically tested
  7. 2019 Medium

    A secretory function was established: activated macrophages secrete full-length ERAP2, and exogenous ERAP2 reduces HIV-1 replication in PBMCs while enhancing CD8+ T cell activation, revealing an extracellular immunomodulatory role.

    Evidence Mass spectrometry of activated macrophage secretome; recombinant ERAP2 addition to PBMC cultures with viral replication and immune activation assays

    PMID:31379846

    Open questions at the time
    • Mechanism by which extracellular ERAP2 activates CD8+ T cells is unknown
    • Whether the enzymatic activity of secreted ERAP2 is required was not tested
  8. 2020 Medium

    A catalytically inactive ERAP2 isoform (Iso3) was discovered to be induced by microbial stimulation; it retains heterodimerization capacity with ERAP1 and wild-type ERAP2, introducing a dominant-negative regulatory mechanism that reshapes the immunopeptidome.

    Evidence RT-PCR, Western blot, and dimerization assays in PBMCs and macrophages stimulated with influenza, LPS, CMV, HIV, SARS-CoV-2

    PMID:32847031

    Open questions at the time
    • Whether Iso3 dimerization actually inhibits ERAP1 function in vivo was not directly shown
    • Structural basis for loss of trimming by Iso3 is uncharacterized
  9. 2022 High

    Structural determination of ERAP2 with multiple inhibitors revealed a catalytic-site proximal allosteric site governed by His904, providing a molecular framework for selective pharmacological modulation of ERAP2 independent of ERAP1.

    Evidence Crystal structures of ERAP2–inhibitor complexes, site-directed mutagenesis of His904, kinetic analysis

    PMID:35767698 PMID:35904863

    Open questions at the time
    • Whether allosteric inhibitors affect ERAP1–ERAP2 heterodimer function is untested
    • No co-crystal structure of the heterodimer exists
  10. 2022 Medium

    A self-modulation mechanism between ERAP1 and ERAP2 was uncovered: ERAP2 preferentially trims <9-mer substrates that simultaneously inhibit ERAP1, while longer substrates preferred by ERAP1 inhibit ERAP2, creating a synergistic length-selection filter.

    Evidence Biochemical enzymatic assays with defined-length peptide substrates

    PMID:36569828

    Open questions at the time
    • Whether mutual inhibition operates in the heterodimer complex or only between free enzymes is unknown
    • In vivo validation of the self-modulation model is lacking
  11. 2022 Medium

    An autocatalytically generated short form of ERAP2 was identified in macrophages; it localizes to endosomes and plasma membrane where it binds IRAP, suggesting a function in angiotensin processing outside the ER.

    Evidence Western blot, co-immunoprecipitation with IRAP, co-localization microscopy, autocatalytic cleavage assays in acidic conditions

    PMID:35563348

    Open questions at the time
    • Whether short ERAP2 actually cleaves angiotensin substrates is not demonstrated
    • The physiological trigger for autocatalytic cleavage in vivo is uncharacterized
    • Single-lab finding without independent replication
  12. 2023 High

    The regulatory architecture of ERAP2 expression was completed: reciprocal allelic replacement confirmed rs2248374 as the causal splice-regulatory variant, and chromosome conformation capture revealed that disease-associated variants in the LNPEP promoter independently regulate ERAP2 through long-range chromatin contacts.

    Evidence CRISPR reciprocal allelic replacement, allele-specific 3C chromatin conformation capture, reporter assays

    PMID:38190099

    Open questions at the time
    • Whether LNPEP-ERAP2 chromatin contacts are tissue-specific is unknown
    • Mechanism by which LNPEP promoter variants alter ERAP2 transcription is not molecularly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the ERAP1–ERAP2 heterodimer and whether allosteric communication is bidirectional, the physiological substrate repertoire of the secreted short ERAP2 form, and whether dominant-negative Iso3 dimerization provides a feedback mechanism that calibrates immunopeptidome diversity during infection.
  • No structure of the ERAP1–ERAP2 heterodimer exists
  • Enzymatic substrates of extracellular/endosomal ERAP2 are undefined
  • Functional impact of Iso3 on immunopeptidome in vivo is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 7 GO:0140096 catalytic activity, acting on a protein 6
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005576 extracellular region 1 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-392499 Metabolism of proteins 3
Partners
EPCAMERAP1IRAP
Complex memberships
ERAP1–ERAP2 heterodimer

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ERAP1 and ERAP2 form heterodimeric complexes in the endoplasmic reticulum and have complementary, concerted aminopeptidase activities: ERAP1 cannot remove certain N-terminal amino acids that ERAP2 trims efficiently, and trimming of longer peptide precursors requires the concerted action of both enzymes both in vitro and in vivo for MHC class I antigen presentation. Co-immunoprecipitation (physical association), in vitro peptide digestion assays, cellular antigen presentation assays, in vivo co-localization Nature immunology High 15908954
2010 ERAP2 Haplotype B undergoes differential splicing, encoding a truncated protein that is degraded by nonsense-mediated decay (NMD), resulting in ERAP2 deficiency. Haplotype B homozygotes have lower surface MHC class I expression on B cells, demonstrating that naturally occurring ERAP2 deficiency functionally affects MHC class I antigen presentation. Genetic analysis of haplotypes, RT-PCR for splice forms, flow cytometry for surface MHC class I expression in primary lymphocytes with defined ERAP2 genotypes PLoS genetics High 20976248
2014 ERAP1-ERAP2 dimerization increases peptide-trimming efficiency: stabilized ERAP1-ERAP2 heterodimers produce mature MHC class I epitopes more efficiently than a mix of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity through allosteric effects. Production of stabilized ERAP1-ERAP2 heterodimers, enzymatic assays comparing heterodimers vs. enzyme mixtures unable to dimerize, kinetic parameter measurements Journal of immunology High 24928998
2016 ERAP1/ERAP2 heterodimers can trim MHC class I-bound precursor peptides to their correct and final lengths (albeit more slowly than free precursors), and trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes, supporting a peptide editing model. In vitro trimming assays using ERAP1/2 heterodimers with free and HLA-B*0801-bound N-terminally extended model and natural peptides; conformational stability measurements Scientific reports High 27514473
2013 ERAP1 and ERAP2 act concertedly in trimming viral HLA-B27-restricted peptide precursors: each enzyme can use the degradation products of the other as substrates for new N-terminal trimming, with double enzyme digestions producing increased amounts of natural HLA-B27 ligands compared to single enzyme digestions. In vitro peptide digestion with ERAP1 and/or ERAP2, mass spectrometry identification of products PloS one Medium 24223975
2017 ERAP1 and ERAP2 have significant but distinct and largely separate effects on the HLA-B*27 peptidome in human cells: ERAP1 effects relate primarily to peptide length and N-terminal Ala1 frequency, while ERAP2 effects additionally reduce peptides with N-terminal basic residues and lower the affinity of the peptidome. Both enzymes largely act as separate entities in vivo. Quantitative label-free mass spectrometry comparison of HLA-B*27:05 peptidomes from cells with various ERAP1/ERAP2 phenotypes Journal of autoimmunity High 28063628
2018 ERAP2 alters the HLA-A*29:02 peptidome in a manner distinct from HLA-B*27: presence of ERAP2 increases amounts of peptides >9-mers and alters N-terminal residues toward less ERAP2-susceptible, more hydrophobic residues. Unproductive binding to ERAP2 may protect some peptides from ERAP1 over-trimming. Lentiviral transduction of ERAP2 into ERAP2-negative cell lines, label-free quantitative mass spectrometry of A*29:02 peptidomes Molecular & cellular proteomics High 29769354
2019 ERAP2 depleted by CRISPR/Cas9 knockout shows functional redundancy with ERAP1 in processing HLA-B*51:01 ligands: in the absence of ERAP1, ERAP2 alone can perform similar and significant processing of B*51:01 ligands. ERAP1 and ERAP2 have distinct but complementary and partially redundant effects on the B*51:01 peptidome, required for its optimization and maximal surface expression. CRISPR/Cas9 knockout of ERAP1, ERAP2, or both; label-free quantitative mass spectrometry of HLA-B*51:01 peptidomes; surface HLA expression measurement Molecular & cellular proteomics High 31092671
2020 ERAP2 shapes the natural HLA-B*27:05 ligandome in live cells: in absence of ERAP2, peptides with N-terminal basic residues and minority canonical P2 residues are enriched, and alterations in residue frequencies at P3, P7, and PΩ positions are observed. Additionally, ERAP2-dependent cellular peptides show high similarity to sequences from arthritogenic bacteria including Campylobacter jejuni. CRISPR/Cas9 editing of ERAP2 in HLA-B*27:05-expressing cells, quantitative tandem mass spectrometry of natural ligandome, bioinformatics sequence alignment Molecular & cellular proteomics High 32265295
2019 ERAP2 has substantial influence on the HLA-B*40:02 peptidome: depletion of ERAP2 by CRISPR KO causes major effects on N-terminal residue frequencies (increased basic and small residues, decreased aliphatic/aromatic ones) and quantitative changes in peptide amounts, with ERAP2 affecting the generation/destruction balance of HLA-B*40:02 ligands. CRISPR/Cas9 knockout of ERAP2 in C1R-B*40:02, label-free quantitative mass spectrometry peptidome comparison Molecular & cellular proteomics High 31530632
2022 ERAP2 preferentially trims peptides shorter than 9 residues, while ERAP1 efficiently trims peptides longer than 9 residues. The optimal ligands for either enzyme act as inhibitors of the other: octamers reduce long-peptide trimming by ERAP1, while peptides longer than nonamers inhibit ERAP2 activity. This mutual inhibition constitutes a synergistic self-modulation mechanism shaping the MHC-I peptidome. Biochemical enzymatic assays and proteomic studies with defined peptide substrates, biological verification Frontiers in immunology Medium 36569828
2021 ERAP2 increases the abundance of a specific peptide submotif in the HLA-A29 immunopeptidome that is highly selective for HLA-A29. ERAP2 also imprints internal sequence specificity in the immunopeptidome. The effects of ERAP2 on N-terminal residues of HLA-A29 ligands are shared across HLA allotypes, but the A29-specific motif is uniquely generated in the presence of ERAP2. HLA-A29-based and pan-class I immunopurification, isotope-labeled naturally processed peptide sequencing by mass spectrometry in patient-derived antigen-presenting cells with and without ERAP2 Frontiers in immunology High 33717175
2022 Crystal structure of ERAP2 bound to a phenylsulfamoyl benzoic acid inhibitor (compound 61) reveals that the inhibitor binds near the catalytic center of ERAP2 at a distinct site from peptidomimetic inhibitors, and inhibits by an uncompetitive mechanism. His904 in ERAP2 is a key selectivity determinant governing compound binding at the allosteric site; mutation of His904 to alanine reveals a cryptic allosteric site permitting activation of ERAP2 by compound 3. Crystal structure determination of ERAP2-inhibitor complex, enzymatic inhibition assays, site-directed mutagenesis of His904 ACS chemical biology High 35767698
2022 Co-crystallization of ERAP2 with three different inhibitors discovered by kinetic target-guided synthesis reveals the binding mode of selective ERAP2 inhibitors; selected analogues engage ERAP2 in cells and inhibit antigen presentation in a cellular context. Kinetic target-guided synthesis, co-crystallization and X-ray structure determination, cellular ERAP2 engagement assays, antigen presentation assays Angewandte Chemie High 35904863
2022 A shorter form of ERAP2 is generated in macrophages by autocatalytic cleavage within a distinctive structural motif in an acidic microenvironment, independently of ERAP2 haplotype. This 'short' ERAP2 binds IRAP (insulin-regulated aminopeptidase), and the two molecules are co-expressed in endosomes and on the cell membrane, suggesting a function for ERAP2 outside the ER in the angiotensin system. Western blot characterization of short ERAP2 form, co-immunoprecipitation of ERAP2 short with IRAP, co-localization by microscopy, subcellular fractionation, autocatalytic cleavage assays International journal of molecular sciences Medium 35563348
2019 ERAP2 is secreted from activated human monocyte-derived macrophages (MDMs) in response to IFNγ/LPS stimulation. Exogenous recombinant ERAP2-FL reduces HIV-1 viral replication in PBMCs, associated with increased IFNγ and CD69 mRNA expression and increased perforin-expressing CD8+ T cells. Mass spectrometry identification of ERAP2 in secretome of activated MDMs; addition of recombinant ERAP2 to PBMC cultures with p24 viral antigen quantification; flow cytometry and gene expression analysis Frontiers in immunology Medium 31379846
2013 EpCAM associates with ERAP2 in breast cancer cells: ERAP2 co-precipitates with EpCAM and co-localizes in the cytoplasm/ER and plasma membrane, suggesting a novel interaction that may regulate EpCAM processing and antigen presentation in cancer. Co-immunoprecipitation followed by mass spectrometry, co-localization by microscopy, in vitro expression in dog pancreas rough microsomes Biochemical and biophysical research communications Low 23988446
2021 ERAP2 plays a role in autophagy and activation of pancreatic stellate cells (PSCs) via the unfolded protein response (UPR) signaling pathway: ERAP2 knockdown by siRNA inhibited UPR-mediated autophagy and led to inactivation of PSCs, attenuating tumor-stromal interactions by inhibiting IL-6 and fibronectin production. In vivo, ERAP2 knockdown suppressed xenografted tumor growth and fibrosis. siRNA knockdown of ERAP2 in PSCs, autophagy and ER stress assays, gene expression microarray, IL-6 and fibronectin measurement, orthotopic xenograft mouse model Pancreatology Medium 34642112
2022 ERAP2 inhibition in MOLT-4 T lymphoblast leukemia cells induces significant shifts in the MHC class I immunopeptidome: more than 20% of detected peptides are either novel or significantly upregulated, with inhibitor-induced peptides being predominantly 9-mers with sequence motifs and predicted affinity consistent with optimal MHC class I ligands. Selective ERAP2 inhibitor treatment, MHC class I immunopurification, LC-MS/MS peptidomics of MOLT-4 cells International journal of molecular sciences Medium 35163832
2023 ERAP2 alone, when expressed in ERAP-deficient cells, elicits strong CTL responses toward the Tyrosinase368-376 tumor epitope; ERAP2 also influences recognition of gp100209-217 and enhances T cell recognition of MART-126/27-35 in the absence of ERAP1 expression. In vitro, ERAP1 and ERAP2 differently customize TAP-dependent N-terminally extended epitope precursor peptides. Expression of ERAP2 in ERAP-deficient cells, CTL recognition assays, in vitro peptide trimming assays with TAP-dependent precursors Molecular immunology Medium 36608422
2020 A new ERAP2 isoform (ERAP2/Iso3) is expressed from the major haplotype following microbial stimulation (influenza, LPS, CMV, HIV, SARS-CoV-2 antigens) in PBMCs and MDMs. Unlike ERAP2-wt, ERAP2/Iso3 is unable to trim peptides for MHC class I loading but retains the ability to dimerize with both ERAP2-wt and ERAP1-wt, contributing to an alternative cellular immune-peptidome. RT-PCR/Quantigene for isoform mRNA expression, Western blot for protein, dimerization assays, stimulation with multiple pathogens Cells Medium 32847031
2023 ERAP2 expression is directly controlled by the splice region variant rs2248374, demonstrated by reciprocal allelic replacement. Additionally, disease-associated variants in the downstream LNPEP gene promoter independently regulate ERAP2 expression through long-range chromatin contacts between LNPEP and ERAP2 promoters, with stronger interactions in patients carrying autoimmune disease-susceptibility alleles. Reciprocal allelic replacement (CRISPR), allele-specific conformation capture (3C) assays measuring chromatin contacts, reporter assays Cell genomics High 38190099
2016 Discovery of potent inhibitors selective for ERAP2 (Ki=100–350 nM) among phosphinic dipeptide analogues; N'-substituted α,β-diaminophosphonates and phosphinates showed selectivity toward ERAP2 only, consistent with the P1 basic substrate-oriented specificity of ERAP2, distinguishing it from ERAP1. In vitro enzymatic inhibition screening of 50 phosphonic/phosphinic acid compounds against ERAP1 and ERAP2, Ki determination Bioorganic & medicinal chemistry letters Medium 27390066
2022 ERAP2 contributes to modulation of neutrophil function when secreted extracellularly: recombinant ERAP2 is internalized by neutrophils and triggers their activation (increased MAC-1+CD66b+, cytokine release), increases migration capacity, autophagy, and phagocytosis activity, and reduces ROS accumulation. Recombinant human ERAP2 supplementation to neutrophil cultures, Western blot for internalization, flow cytometry for activation markers, transwell migration assay, ROS measurement, autophagy assay Frontiers in cell and developmental biology Low 39839670

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nature immunology 382 15908954
2010 Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS genetics 196 20976248
2018 How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins. Frontiers in immunology 134 30425713
1993 Amelogenin post-translational modifications: carboxy-terminal processing and the phosphorylation of bovine and porcine "TRAP" and "LRAP" amelogenins. Biochemical and biophysical research communications 106 8250931
1991 Identification of the leucine-rich amelogenin peptide (LRAP) as the translation product of an alternatively spliced transcript. Biochemical and biophysical research communications 104 1996994
2014 A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. Human molecular genetics 100 24957906
2004 The COOH terminus of the amelogenin, LRAP, is oriented next to the hydroxyapatite surface. The Journal of biological chemistry 100 15299015
2009 Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Annals of the rheumatic diseases 90 19433412
2009 The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Human genetics 83 19578876
2016 ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing. Scientific reports 82 27514473
2008 Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. Journal of cellular physiology 81 18393273
2014 ERAP1-ERAP2 dimerization increases peptide-trimming efficiency. Journal of immunology (Baltimore, Md. : 1950) 70 24928998
2018 Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection. Genome research 58 30446528
2011 Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study. BMC medical genetics 55 21569342
2020 The roles of ERAP1 and ERAP2 in autoimmunity and cancer immunity: New insights and perspective. Molecular immunology 53 32135401
2019 Regulation of ERAP1 and ERAP2 genes and their disfunction in human cancer. Human immunology 50 30825518
2017 Separate effects of the ankylosing spondylitis associated ERAP1 and ERAP2 aminopeptidases determine the influence of their combined phenotype on the HLA-B*27 peptidome. Journal of autoimmunity 50 28063628
2017 The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis. Clinical and experimental immunology 50 28759104
2018 Intracellular antigen processing by ERAP2: Molecular mechanism and roles in health and disease. Human immunology 49 30414458
2018 Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis. Human molecular genetics 47 30215709
2019 Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations. Human immunology 46 30797823
2008 The structure and orientation of the C-terminus of LRAP. Biophysical journal 38 18192371
2020 The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease. Frontiers in immunology 34 32793222
1994 Isolation and characterisation of an alternatively-spliced rat amelogenin cDNA: LRAP--a highly conserved, functional alternatively-spliced amelogenin? Biochimica et biophysica acta 34 7948026
2003 The small bovine amelogenin LRAP fails to rescue the amelogenin null phenotype. Calcified tissue international 33 12958690
2020 A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? Cells 32 32847031
2022 Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate. Gastroenterology 31 36496055
2018 An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes. Scientific reports 31 29991817
2019 Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) Is Released in the Secretome of Activated MDMs and Reduces in vitro HIV-1 Infection. Frontiers in immunology 27 31379846
2008 Structure, orientation, and dynamics of the C-terminal hexapeptide of LRAP determined using solid-state NMR. The journal of physical chemistry. B 26 19368031
2020 The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia. Frontiers in immunology 24 32210971
2017 ERAP1 and ERAP2 Gene Variations Influence the Risk of Psoriatic Arthritis in Romanian Population. Archivum immunologiae et therapiae experimentalis 24 28083616
2023 Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease. American journal of human genetics 23 36889308
2021 ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19? International journal of molecular sciences 22 33567739
2021 ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29. Frontiers in immunology 22 33717175
2019 Redundancy and Complementarity between ERAP1 and ERAP2 Revealed by their Effects on the Behcet's Disease-associated HLA-B*51 Peptidome. Molecular & cellular proteomics : MCP 22 31092671
2013 Neutron reflectometry studies of the adsorbed structure of the amelogenin, LRAP. The journal of physical chemistry. B 22 23477285
2016 Discovery of potent and selective inhibitors of human aminopeptidases ERAP1 and ERAP2 by screening libraries of phosphorus-containing amino acid and dipeptide analogues. Bioorganic & medicinal chemistry letters 21 27390066
2013 Phosphorylation and ionic strength alter the LRAP-HAP interface in the N-terminus. Biochemistry 21 23477367
2013 Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases. PloS one 21 24223975
2007 The effect of LRAP on enamel organ epithelial cell differentiation. Journal of dental research 21 17959903
2023 Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2). Genes and immunity 20 37925533
2019 ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients. Human immunology 20 30794838
2021 ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers. Investigative ophthalmology & visual science 18 34727153
2018 Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy. Molecular & cellular proteomics : MCP 18 29769354
2015 ERAP2 functional knockout in humans does not alter surface heavy chains or HLA-B27, inflammatory cytokines or endoplasmic reticulum stress markers. Annals of the rheumatic diseases 18 26088389
2007 Enamel formation in vitro in mouse molar explants exposed to amelogenin polypeptides ATMP and LRAP on enamel development. Archives of oral biology 18 17679105
2022 Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis. Angewandte Chemie (International ed. in English) 17 35904863
2022 The emerging multifunctional roles of ERAP1, ERAP2 and IRAP between antigen processing and renin-angiotensin system modulation. Frontiers in immunology 17 36203608
2013 EpCAM associates with endoplasmic reticulum aminopeptidase 2 (ERAP2) in breast cancer cells. Biochemical and biophysical research communications 17 23988446
2009 The leucine rich amelogenin protein (LRAP) adsorbs as monomers or dimers onto surfaces. Journal of structural biology 17 19850130
2021 Genetic association of ERAP1 and ERAP2 with eclampsia and preeclampsia in northeastern Brazilian women. Scientific reports 16 33762660
2020 Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2). Molecular & cellular proteomics : MCP 16 32265295
2018 ERAP1/ERAP2 and RUNX3 polymorphisms are not associated with ankylosing spondylitis susceptibility in Chinese Han. Clinical and experimental immunology 16 29480940
2023 Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis. The Journal of investigative dermatology 15 36716917
2021 ERAP2 is a novel target involved in autophagy and activation of pancreatic stellate cells via UPR signaling pathway. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 13 34642112
2022 ERAP2 Inhibition Induces Cell-Surface Presentation by MOLT-4 Leukemia Cancer Cells of Many Novel and Potentially Antigenic Peptides. International journal of molecular sciences 12 35163832
2015 Truncated amelogenin and LRAP transgenes improve Amelx null mouse enamel. Matrix biology : journal of the International Society for Matrix Biology 12 26607574
2014 The leucine-rich amelogenin protein (LRAP) is primarily monomeric and unstructured in physiological solution. Journal of structural biology 12 25449314
2010 A solution NMR investigation into the murine amelogenin splice-variant LRAP (Leucine-Rich Amelogenin Protein). Biochimica et biophysica acta 12 20304108
2014 The flexible structure of the K24S28 region of Leucine-Rich Amelogenin Protein (LRAP) bound to apatites as a function of surface type, calcium, mutation, and ionic strength. Frontiers in physiology 11 25071599
2023 A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs. Cell genomics 10 38190099
2016 Leucine-Rich Amelogenin Peptide (LRAP) Uptake by Cementoblast Requires Flotillin-1 Mediated Endocytosis. Journal of cellular physiology 10 27277399
2022 A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation. International journal of molecular sciences 8 35563348
2019 Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis. Molecular & cellular proteomics : MCP 8 31530632
2016 Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids. Clinical and experimental rheumatology 8 27384923
2023 ERAP2 supports TCR recognition of three immunotherapy targeted tumor epitopes. Molecular immunology 7 36608422
2023 ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes. International journal of molecular sciences 7 37686141
2020 Association of ERAP2 polymorphisms in Colombian HLA-B27+ or HLA-B15+ patients with SpA and its relationship with clinical presentation: axial or peripheral predominance. RMD open 7 32917832
2022 Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation. Frontiers in immunology 6 35514997
2022 ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer. Aging 6 36214762
2019 Association of ERAP2 gene variants with risk of pre-eclampsia among Iranian women. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 6 30933316
2022 The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities. Frontiers in immunology 5 36569828
2020 Synergy of endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) polymorphisms in atopic dermatitis: Effects on disease prevalence. Human immunology 5 33309189
2024 ERAP1 and ERAP2 gene variants as potential clinical biomarkers of anti-interleukin-17A response in psoriasis vulgaris. Clinical and experimental dermatology 4 38616723
2024 The effect of rs2910686 on ERAP2 expression in IBD and epithelial inflammatory response. Journal of translational medicine 4 39123229
2022 Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition. ACS chemical biology 4 35767698
2019 Novel LRAP-binding partner revealing the plasminogen activation system as a regulator of cementoblast differentiation and mineral nodule formation in vitro. Journal of cellular physiology 4 31621902
2025 Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions. Frontiers in cell and developmental biology 3 39839670
2025 Association of ERAP1 and ERAP2 gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population. Frontiers in immunology 3 39906739
2024 A study of the association between single nucleotide polymorphisms of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene and the risk of ankylosing spondylitis in Egyptians. Molecular biology reports 3 38704785
2006 No association of type 1 diabetes with a functional polymorphism of the LRAP gene. Molecular immunology 3 17129607
2024 Epistatic interaction between ERAP2 and HLA modulates HIV-1 adaptation and disease outcome in an Australian population. PLoS pathogens 2 38980912
2016 Polymorphisms in ERAP1 and ERAP2 are shared by Caninae and segregate within and between random- and pure-breeds of dogs. Veterinary immunology and immunopathology 2 27590425
2025 The important roles of ERAP1, ERAP2 genes polymorphisms and their DNA methylation levels in pulmonary tuberculosis. BMC infectious diseases 1 39910453
2025 The role of endoplasmic reticulum aminopeptidase ERAP2 pathogenic mutation rs1363907 in amoxicillin clavulanate-induced liver injury: a special case report. Frontiers in pharmacology 1 40469972
2026 Expression, Purification, and Functional Analysis Methods of Antigen-Processing Aminopeptidases ERAP1, ERAP2, and IRAP. Methods in molecular biology (Clifton, N.J.) 0 41479007
2026 ERAP2 inhibitor -incorporated nanofibers: Characterization and biological assessment. International journal of pharmaceutics 0 41485621
2026 The Impact of ERAP1 and ERAP2 Haplotype Combinations on Susceptibility and Severity of Birdshot Chorioretinitis. Investigative ophthalmology & visual science 0 41575441
2026 Comparative Analysis of Amelogenin-Derived Peptides LRAP and SP on Osteogenic Differentiation of Human Dental Pulp and Bone Marrow-Derived Stem Cells. Dentistry journal 0 41744933
2025 Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response. Frontiers in cell and developmental biology 0 40226591
2025 Rare and common variants in ERAP1 and ERAP2 selected for in response to Yersinia pestis infection contribute to autoimmune disease including inflammatory bowel disease. Mammalian genome : official journal of the International Mammalian Genome Society 0 41428259