Affinage

ERAP2

Endoplasmic reticulum aminopeptidase 2 · UniProt Q6P179

Length
960 aa
Mass
110.5 kDa
Annotated
2026-06-09
92 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERAP2 is an endoplasmic reticulum-resident zinc aminopeptidase that trims N-terminally extended peptide precursors to optimize the HLA class I immunopeptidome (PMID:15908954, PMID:31092671). It acts in concert with ERAP1, forming heterodimers in the ER whose assembly increases trimming efficiency above that of the unassociated enzymes and allosterically improves ERAP1 substrate-binding affinity (PMID:15908954, PMID:24928998); the heterodimer can trim not only free precursors but also MHC class I-bound precursors, increasing the conformational stability of the resulting MHC/peptide complexes (PMID:27514473). Functionally, ERAP2 shows a characteristic preference for removing N-terminal basic residues, and its activity is largely distinct from, yet partially redundant with, that of ERAP1 — each enzyme can consume the other's products, and their optimal substrates competitively inhibit one another so that the two activities self-modulate toward optimal peptide lengths (PMID:24223975, PMID:36569828, PMID:31530632). Across multiple HLA allotypes (B*27:05, A*29:02, B*51:01, B*40:02), ERAP2 perturbation reshapes N-terminal residue usage, peptide length distributions, and overall binding affinity, and ERAP2 alone can generate functional tumor and viral epitopes in the absence of ERAP1, including imprinting allotype-restricted internal sequence motifs (PMID:28063628, PMID:29769354, PMID:31092671, PMID:32265295, PMID:33717175). ERAP2 expression is genetically controlled: the splice-region variant rs2248374 directs a haplotype B transcript to nonsense-mediated decay, producing protein deficiency that lowers surface MHC class I, and disease-associated variation in the downstream LNPEP promoter independently regulates ERAP2 via long-range chromatin contacts (PMID:20976248, PMID:38190099). Beyond canonical antigen processing, a macrophage-specific short form of ERAP2 is generated by autocatalytic cleavage under acidic conditions and binds IRAP in endosomes and at the cell membrane, and full-length ERAP2 is secreted from activated macrophages where it reduces HIV-1 replication in PBMCs (PMID:35563348, PMID:31379846). Crystallographic and inhibitor studies have defined ERAP2 active-site and allosteric determinants and yielded selective nanomolar inhibitors that engage the enzyme in cells and block antigen presentation (PMID:35767698, PMID:35904863).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    Established that ERAP2 is not an isolated aminopeptidase but physically partners with ERAP1 to complete peptide trimming, answering how distinct trimming specificities are integrated for HLA class I presentation.

    Evidence Co-localization, reciprocal Co-IP, in vitro digestion, and cellular antigen presentation assays

    PMID:15908954

    Open questions at the time
    • Stoichiometry and structural basis of the heterodimer not resolved
    • Did not quantify allosteric kinetic changes
  2. 2010 High

    Showed that a naturally occurring splice variant routes one ERAP2 haplotype to NMD, defining the genetic basis of ERAP2 deficiency and linking it to reduced surface MHC class I.

    Evidence Population genetics, RT-PCR splicing analysis, and flow cytometry of surface MHC I across genotypes

    PMID:20976248

    Open questions at the time
    • Specific epitopes lost in deficiency not mapped
    • Mechanism by which deficiency alters disease risk not addressed
  3. 2013 Medium

    Demonstrated concerted, sequential processing in which each enzyme uses the other's products, clarifying how ERAP1 and ERAP2 cooperate at the substrate level.

    Evidence In vitro single vs. combined ERAP1/ERAP2 digestion with MS product identification; Co-IP/MS in breast cancer cells for an EpCAM interaction

    PMID:23988446 PMID:24223975

    Open questions at the time
    • Limited substrate set in trimming assays
    • EpCAM interaction is a single Co-IP/MS without functional validation
  4. 2014 High

    Reconstitution of stabilized heterodimers established that dimerization itself, not mere enzyme co-presence, enhances trimming and allosterically reshapes ERAP1 kinetics.

    Evidence Stabilized ERAP1-ERAP2 heterodimers vs. non-dimerizing mixtures with kinetic measurement

    PMID:24928998

    Open questions at the time
    • In vivo prevalence of heterodimers vs. monomers not quantified
    • Structural interface not defined
  5. 2016 High

    Extended ERAP function to MHC-bound precursors, showing trimming can occur on loaded complexes and improves their stability, refining the timing of editing in the loading pathway.

    Evidence In vitro trimming of free and HLA-B*0801-bound precursors with conformational stability assays

    PMID:27514473

    Open questions at the time
    • Relative in vivo contribution of bound vs. free trimming unknown
    • Single HLA allotype tested
  6. 2018 High

    Defined ERAP2's allotype-specific imprint on the immunopeptidome, showing largely distinct effects from ERAP1 and a possible protective role against ERAP1 over-trimming.

    Evidence Quantitative immunopeptidomics of HLA-B*27:05 and HLA-A*29:02 with ERAP perturbation across cell lines

    PMID:28063628 PMID:29769354

    Open questions at the time
    • Mechanism of 'unproductive binding' protection inferred, not directly shown
    • Effects compared across only a few allotypes
  7. 2020 High

    CRISPR knockouts across multiple HLA allotypes nailed ERAP2's substrate signature — preferential N-terminal basic-residue trimming — and revealed partial redundancy with mutual dependence on ERAP1.

    Evidence Reciprocal CRISPR KO of ERAP1/ERAP2 in HLA-B*51:01 and B*40:02 cells with quantitative immunopeptidomics

    PMID:31092671 PMID:31530632

    Open questions at the time
    • Molecular basis of substrate preference not structurally explained here
    • Functional consequences for T-cell repertoire not measured
  8. 2020 Medium

    Identified non-canonical ERAP2 biology: a microbially induced, trimming-dead isoform that still dimerizes, and a UPR/autophagy-linked role in pancreatic stellate cells.

    Evidence RT-qPCR/western of ERAP2/Iso3 with trimming and dimerization assays; siRNA knockdown in PSCs with xenograft model

    PMID:32847031 PMID:34642112

    Open questions at the time
    • Functional purpose of trimming-dead Iso3 dimers unknown
    • How ERAP2 aminopeptidase activity links to UPR/autophagy not mechanistically established
  9. 2021 High

    Showed ERAP2 imprints internal (not just N-terminal) sequence specificity, generating allotype-restricted submotifs relevant to autoantigen presentation.

    Evidence Quantitative immunopeptidomics in patient-derived APCs across HLA allotypes, replicated

    PMID:33717175

    Open questions at the time
    • Causal link between submotif and autoimmunity not established
    • Restricted to HLA-A29 context
  10. 2022 Medium

    Resolved the self-modulation logic: ERAP1's optimal substrates inhibit ERAP2 and vice versa, explaining how the pair converges on optimal peptide lengths.

    Evidence Biochemical inhibition assays with defined peptides plus proteomic verification

    PMID:36569828

    Open questions at the time
    • Single lab, limited independent replication
    • Inhibition constants in cellular context not measured
  11. 2022 High

    Structural and inhibitor work defined ERAP2 active-site and allosteric determinants and produced selective cell-active inhibitors, enabling pharmacological dissection of ERAP2 in antigen presentation.

    Evidence Co-crystallization, enzyme kinetics, site-directed mutagenesis, and cellular engagement/antigen presentation assays

    PMID:35163832 PMID:35767698 PMID:35904863

    Open questions at the time
    • Inhibitor effects on full immunopeptidome only partially mapped
    • Allosteric site His904 function beyond compound binding unclear
  12. 2022 Medium

    Characterized extracellular and macrophage-specific ERAP2 forms, expanding its role beyond intracellular peptide editing to secreted immunomodulation and IRAP binding.

    Evidence Secretome MS, recombinant ERAP2 anti-HIV assays in PBMCs, autocatalytic cleavage and IRAP Co-IP/co-localization in macrophages

    PMID:31379846 PMID:35563348

    Open questions at the time
    • Mechanism of extracellular anti-HIV action not defined
    • Physiological function of the short ERAP2-IRAP complex unknown
  13. 2023 Medium

    Demonstrated that ERAP2 alone can generate functional tumor epitopes, establishing an ERAP1-independent contribution to CTL recognition.

    Evidence ERAP2 expression in ERAP-deficient cells, in vitro precursor trimming, and CTL/T-cell recognition assays for Tyrosinase, gp100, and MART-1 epitopes

    PMID:36608422

    Open questions at the time
    • Single lab
    • Breadth of ERAP2-independent epitope generation across tumors not assessed
  14. 2024 High

    Established two independent causal regulatory mechanisms for ERAP2 expression — the rs2248374 splice variant and long-range LNPEP promoter chromatin contacts — connecting expression control to autoimmune disease risk.

    Evidence Reciprocal CRISPR allelic replacement and allele-specific chromosome conformation capture

    PMID:38190099

    Open questions at the time
    • Downstream immune consequences of altered expression in carriers not measured
    • Interplay between the two regulatory mechanisms not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ERAP2's multiple non-canonical activities — secreted immunomodulation, the IRAP-bound macrophage short form, trimming-dead dimerizing isoforms, and UPR/autophagy effects — integrate with its core role in MHC class I peptide editing remains unresolved.
  • No unified model connecting intracellular trimming and extracellular/non-canonical roles
  • Physiological relevance of macrophage short form and IRAP complex undefined
  • Mechanistic basis of UPR/autophagy link untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005576 extracellular region 2 GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
EPCAMERAP1IRAP
Complex memberships
ERAP1-ERAP2 heterodimer

Evidence

Reading pass · 23 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 act with concerted, complementary aminopeptidase activities to trim N-terminally extended peptide precursors for HLA class I presentation; ERAP2 efficiently removed N-terminal residues that ERAP1 could not trim, and combined action was required both in vitro and in vivo for full processing of some epitopes. Co-localization in vivo, physical co-immunoprecipitation demonstrating heterodimer formation, in vitro peptide digestion assays comparing single vs. dual enzyme activity, cellular antigen presentation assays Nature immunology High 15908954
2014 ERAP1-ERAP2 heterodimer formation increases peptide-trimming efficiency above that of a mixture 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; comparison of peptide-trimming kinetics (epitope production) between heterodimers and non-dimerizing enzyme mixtures; enzymatic parameter measurement Journal of immunology High 24928998
2016 ERAP1/ERAP2 heterodimers can trim MHC class I-bound precursor peptides (not only free peptides) to their correct final lengths, albeit more slowly than free precursors; trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes. In vitro trimming assays using purified ERAP1/ERAP2 heterodimers with free and HLA-B*0801-bound N-terminally extended model and natural peptides; conformational stability measurements of MHC I/peptide complexes Scientific reports High 27514473
2010 A splice variant of ERAP2 encoded by Haplotype B undergoes nonsense-mediated decay (NMD), resulting in ERAP2 protein deficiency; Haplotype B homozygotes have lower levels of MHC class I on B cell surfaces compared to Haplotype A homozygotes, demonstrating that naturally occurring ERAP2 deficiency affects MHC class I antigen presentation. Population genetic analysis of six human populations; RT-PCR demonstrating differential splicing; correlation of surface MHC class I expression with ERAP2 genotype in primary lymphocytes by flow cytometry PLoS genetics High 20976248
2017 ERAP1 and ERAP2 have significant and largely distinct effects on the HLA-B*27:05 peptidome in human cells; ERAP1 increases the proportion of nonamers relative to longer ligands and reduces Ala1 usage, while ERAP2 (in a low-activity ERAP1 context) additionally reduces peptides with N-terminal basic residues and lowers overall peptidome affinity. Both enzymes largely act as separate entities in vivo rather than obligate partners. Quantitative mass spectrometry comparison of HLA-B*27:05 peptidomes from cells with various ERAP1/ERAP2 phenotypes; label-free quantitative proteomics Journal of autoimmunity High 28063628
2019 ERAP2 deletion from HLA-B*51:01-expressing cells by CRISPR/Cas9 reduces HLA-B*51 surface expression and alters the B*51:01 peptidome; in the absence of ERAP1, ERAP2 alone shows significant processing of B*51:01 ligands (functional redundancy), but effects of each enzyme differ substantially, revealing mutual dependence and partially redundant roles. CRISPR/Cas9 knockout of ERAP1, ERAP2, or both in transfectant 721.221-HLA-B*51:01 cells; label-free quantitative mass spectrometry comparison of HLA-B*51:01 peptidomes Molecular & cellular proteomics High 31092671
2018 ERAP2 expression alters the HLA-A*29:02 peptidome by increasing peptides >9-mers and shifting N-terminal residue composition toward less ERAP2-susceptible and more hydrophobic residues; unproductive ERAP2 binding may protect some peptides from ERAP1 over-trimming. ERAP2 effects are allele-specific and differ from its effects on HLA-B*27. Lentiviral transduction of ERAP2 into ERAP2-negative cells; label-free quantitative mass spectrometry of A*29:02-bound peptidomes; comparison across two independent A*29:02-positive cell lines Molecular & cellular proteomics High 29769354
2020 ERAP2 CRISPR knockout in cells expressing HLA-B*27:05 alters the natural ligandome: absence of ERAP2 enriches peptides with N-terminal basic residues and minority canonical P2 residues, and affects hydrophobicity profiles at P3, P7, and PΩ positions; one ERAP2-dependent human peptide was found fully conserved in a Campylobacter jejuni protein (potential molecular mimicry). CRISPR/Cas9 editing of ERAP2 in human cells; high-throughput and quantitative tandem mass spectrometry of HLA-B*27:05-bound peptidome; bioinformatics sequence alignment to arthritogenic bacteria Molecular & cellular proteomics High 32265295
2022 The optimal ligands for ERAP1 (octamers) act as competitive inhibitors of ERAP2 activity, while peptides longer than nonamers inhibit ERAP1; ERAP1 and ERAP2 thus synergize to self-modulate their respective activities and jointly shape the MHC-I peptidome toward optimal peptide lengths. Biochemical inhibition assays with defined peptide substrates; proteomic studies; biological verification of inhibition model Frontiers in immunology Medium 36569828
2013 ERAP1 and ERAP2 show concerted in vitro trimming of HLA-B27-restricted viral ligand precursors: each enzyme can use the degradation products of the other as substrates, resulting in increased detection of natural HLA-B27 ligands with combined versus single enzyme digestion. In vitro peptide digestion comparing single ERAP1, single ERAP2, and combined ERAP1+ERAP2 digestions; mass spectrometry identification of peptide products PloS one Medium 24223975
2019 ERAP2 depletion (CRISPR KO) from HLA-B*40:02-expressing cells induces significant quantitative changes in the HLA-B*40:02 peptidome; the major effect is on N-terminal residue frequencies—basic and small residues increased, aliphatic/aromatic decreased—consistent with ERAP2's preferential trimming of N-terminal basic residues. CRISPR/Cas9 knockout of ERAP2 in C1R-B*40:02 transfectant cells; label-free quantitative mass spectrometry comparison of wildtype vs. ERAP2-KO peptidomes Molecular & cellular proteomics High 31530632
2021 ERAP2 generates a peptide submotif specifically bound by HLA-A29 (not by other HLA allotypes tested); this ERAP2-dependent peptide motif is present in sequences of putative autoantigens, and ERAP2 imprints internal sequence specificity in the immunopeptidome. HLA-A29-based and pan-class I immunopurifications in patient-derived antigen-presenting cells; isotope-labeled quantitative mass spectrometry of naturally processed and presented HLA-bound peptides; replicated in independent datasets Frontiers in immunology High 33717175
2022 ERAP2 inhibition with a selective small-molecule inhibitor in MOLT-4 leukemia cells induces significant shifts in the MHC class I immunopeptidome; >20% of detected peptides were novel or significantly upregulated, with most inhibitor-induced peptides being 9-mers with appropriate HLA-binding motifs, providing evidence that ERAP2 enzymatic activity shapes the cancer cell immunopeptidome. Pharmacological ERAP2 inhibition in MOLT-4 cells; MHC class I immunopurification; LC-MS/MS sequencing of bound peptides International journal of molecular sciences Medium 35163832
2022 Crystal structure of ERAP2 bound to a novel phenylsulfamoyl benzoic acid inhibitor (compound 61) revealed it binds near the catalytic center at a site distinct from peptidomimetic inhibitors and inhibits by an uncompetitive mechanism; active-site residue specificity determinants were identified: His904 in an allosteric site of ERAP2 governs binding and the absence of activation by compound 3 (H904A mutation reveals a cryptic allosteric site), while ERAP1 Lys380 in the S1' pocket governs binding of related compounds. Co-crystallization and X-ray crystal structure determination of ERAP2-inhibitor complex; enzyme kinetics (uncompetitive mechanism); site-directed mutagenesis of active site and allosteric residues ACS chemical biology High 35767698
2022 Kinetic target-guided synthesis identified the first nanomolar, selective ERAP2 inhibitors; co-crystallization experiments revealed the binding mode of three inhibitors with increasing potency and selectivity; selected compounds engage ERAP2 in cells and inhibit antigen presentation in a cellular context. Kinetic target-guided synthesis; co-crystallization with X-ray structure determination; cellular ERAP2 engagement assays; cellular antigen presentation inhibition assays Angewandte Chemie High 35904863
2020 ERAP2 knockdown in pancreatic stellate cells inhibits unfolded protein response (UPR)-mediated autophagy, leading to PSC inactivation and attenuation of IL-6 and fibronectin production; in vivo, ERAP2 knockdown in PSCs inhibited xenograft tumor growth and fibrosis. siRNA knockdown of ERAP2 in patient-derived pancreatic stellate cells; measurement of UPR markers, autophagy, IL-6, and fibronectin; orthotopic xenograft mouse model with ERAP2-knockdown PSCs Pancreatology Medium 34642112
2022 ERAP2 is secreted from activated macrophages (stimulated with IFNγ/LPS) as detected by mass spectrometry of the secretome; the secreted full-length recombinant ERAP2 reduces HIV-1 replication in PBMCs in vitro (statistically significant), associated with increased IFNγ and CD69 expression and increased perforin-expressing CD107+CD8+ T cells. Mass spectrometry of MDM secretome after IFNγ/LPS stimulation; addition of recombinant human ERAP2 to PBMC cultures; HIV-1 p24 viral antigen quantification; flow cytometry for T cell markers Frontiers in immunology Medium 31379846
2022 ERAP2 expression is directly regulated by the splice region variant rs2248374 (established by reciprocal allelic replacement); disease-associated variants in the downstream LNPEP gene promoter independently regulate ERAP2 expression through long-range chromatin contacts, with allele-specific conformation capture assays showing stronger LNPEP-ERAP2 promoter interactions in autoimmune disease-risk allele carriers. Reciprocal allelic replacement (CRISPR-based); allele-specific chromosome conformation capture (4C/Hi-C); ERAP2 expression quantification by allele replacement Cell genomics High 38190099
2020 An alternative ERAP2 isoform (ERAP2/Iso3) is expressed from the rs2248374-G haplotype in response to multiple microbial stimuli (influenza, LPS, CMV, HIV, SARS-CoV-2 antigens); unlike ERAP2-wt, ERAP2/Iso3 is unable to trim peptides for MHC class I loading but can still dimerize with both ERAP2-wt and ERAP1-wt; ERAP2/Iso3 mRNA is translated into protein. RT-qPCR of ERAP2/Iso3 mRNA in stimulated PBMCs and MDMs; western blot confirmation of protein translation; in vitro peptide trimming assay demonstrating loss of function; dimerization assessment Cells Medium 32847031
2022 Macrophages (but not monocytes or other blood mononuclear cells) express and secrete an ERAP2 'short' form independent of haplotype; this short form is generated by autocatalytic cleavage within a distinctive structural motif requiring an acidic microenvironment; the short ERAP2 binds IRAP and both molecules are co-expressed in endosomes and on the cell membrane. Western blot detecting short ERAP2 form in macrophage lysates and secretome; autocatalytic cleavage demonstrated with recombinant protein under acidic conditions; co-immunoprecipitation of short ERAP2 with IRAP; co-localization by immunofluorescence in endosomes and cell membrane International journal of molecular sciences Medium 35563348
2013 EpCAM co-immunoprecipitates with ERAP2 in breast cancer cell lines and the two proteins co-localize in the cytoplasm/ER and at the plasma membrane; in vitro expression in ER vesicles confirmed N-linked glycosylation and ER processing of EpCAM, suggesting ERAP2 may regulate EpCAM processing. Co-immunoprecipitation followed by mass spectrometry; in vitro expression in dog pancreas rough microsomes (ER vesicles); co-localization imaging Biochemical and biophysical research communications Low 23988446
2016 A regulatory variant (rs75862629 G vs. A) in the ERAP2 gene promoter region inversely coordinates expression of ERAP1 and ERAP2: presence of G at this SNP results in down-modulation of ERAP2 coupled with significantly higher ERAP1 expression in B-lymphoblastoid cell lines. Correlation of ERAP1 and ERAP2 transcript and protein levels with promoter region SNP genotype across 44 B-lymphoblastoid cell line donors; quantitative RT-PCR and protein quantification Scientific reports Medium 29991817
2023 ERAP2, when expressed alone in ERAP-deficient cells, elicits a strong CTL response to the Tyrosinase368-376 HLA-A*02:01-restricted tumor epitope; ERAP2 alone can process TAP-dependent N-terminally extended epitope precursors of Tyrosinase368-376 in vitro; ERAP2 also independently enhances T cell recognition of gp100209-217 and MART-126/27-35 epitopes in the absence of ERAP1. Expression of ERAP2 alone in ERAP-deficient cells; CTL activation assays; in vitro peptide trimming assays with defined precursor peptides; T cell recognition assays Molecular immunology Medium 36608422

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 383 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 136 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 102 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 84 19578876
2008 Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. Journal of cellular physiology 83 18393273
2016 ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing. Scientific reports 82 27514473
2014 ERAP1-ERAP2 dimerization increases peptide-trimming efficiency. Journal of immunology (Baltimore, Md. : 1950) 71 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 56 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 51 30825518
2017 The interplay between HLA-B27 and ERAP1/ERAP2 aminopeptidases: from anti-viral protection to spondyloarthritis. Clinical and experimental immunology 51 28759104
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
2018 Intracellular antigen processing by ERAP2: Molecular mechanism and roles in health and disease. Human immunology 49 30414458
2019 Influence of ERAP1 and ERAP2 gene polymorphisms on disease susceptibility in different populations. Human immunology 47 30797823
2018 Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis. Human molecular genetics 47 30215709
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
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 33 36496055
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
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
2020 The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia. Frontiers in immunology 27 32210971
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
2023 Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease. American journal of human genetics 24 36889308
2017 ERAP1 and ERAP2 Gene Variations Influence the Risk of Psoriatic Arthritis in Romanian Population. Archivum immunologiae et therapiae experimentalis 24 28083616
2021 ERAP2 Increases the Abundance of a Peptide Submotif Highly Selective for the Birdshot Uveitis-Associated HLA-A29. Frontiers in immunology 23 33717175
2021 ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19? International journal of molecular sciences 22 33567739
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
2023 Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2). Genes and immunity 21 37925533
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
2021 ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers. Investigative ophthalmology & visual science 20 34727153
2019 ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients. Human immunology 20 30794838
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 19 26088389
2022 Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis. Angewandte Chemie (International ed. in English) 18 35904863
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
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 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
2024 ERAP1 and ERAP2 gene variants as potential clinical biomarkers of anti-interleukin-17A response in psoriasis vulgaris. Clinical and experimental dermatology 5 38616723
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
2025 Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions. Frontiers in cell and developmental biology 4 39839670
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 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
2024 Epistatic interaction between ERAP2 and HLA modulates HIV-1 adaptation and disease outcome in an Australian population. PLoS pathogens 3 38980912
2006 No association of type 1 diabetes with a functional polymorphism of the LRAP gene. Molecular immunology 3 17129607
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
2026 ERAP2 inhibitor -incorporated nanofibers: Characterization and biological assessment. International journal of pharmaceutics 1 41485621
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 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

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