Affinage

SERPINB1

Leukocyte elastase inhibitor · UniProt P30740

Length
379 aa
Mass
42.7 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINB1 is a cytoplasmic ovalbumin-family serpin that serves as a broad-spectrum suicide inhibitor of neutrophil serine proteases and a cell-autonomous guardian of myeloid cell survival and inflammatory homeostasis. It inhibits elastase-like proteases (neutrophil elastase, proteinase-3) via its P1 Cys344 reactive site and chymotrypsin-like proteases (cathepsin G, granzyme H) via its P2 Phe343 site, forming SDS-stable covalent complexes both in vitro and in vivo (PMID:11747453, PMID:23269243, PMID:16617093). By restraining cathepsin G, SerpinB1 maintains the bone marrow neutrophil reserve, prevents programmed necrosis (both GSDMD-dependent and -independent), limits NETosis through cytoplasm-to-nucleus translocation, and restricts pro-inflammatory cytokine production during infection (PMID:23532733, PMID:31216481, PMID:23002442, PMID:21791661). Beyond its antiprotease function, cleavage of its reactive center loop—triggered by intracellular acidification or receptor signaling—converts SERPINB1 into the endonuclease L-DNase II, which exposes a nuclear localization signal and mediates caspase-independent DNA fragmentation; additionally, hepatocyte-secreted SerpinB1 promotes pancreatic β cell proliferation during insulin resistance (PMID:12728253, PMID:16538380, PMID:26701651).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Mapping SERPINB1 to chromosome 6p25 and defining its ovalbumin-serpin gene structure established its evolutionary identity among intracellular serpins, distinguishing it from secretory serpins such as α1-antitrypsin.

    Evidence Somatic cell hybrid PCR mapping and intron characterization in human genomic DNA

    PMID:8530031 PMID:9630619 PMID:9858835

    Open questions at the time
    • Regulatory elements controlling tissue-specific expression not defined
    • No functional data from this structural work alone
  2. 2001 High

    Demonstrating that SERPINB1 uses two distinct reactive sites—Cys344 for elastase-like and Phe343 for chymotrypsin-like proteases—to form covalent inhibitory complexes resolved how a single serpin achieves dual protease specificity.

    Evidence In vitro kinetic assays, N-terminal sequencing, and mass spectrometry of reaction products with purified proteases

    PMID:11747453

    Open questions at the time
    • Whether both sites can be engaged simultaneously on a single molecule
    • Structural basis of dual-site inhibition not resolved at atomic level
  3. 2003 High

    Discovery that intracellular acidification converts SERPINB1 (LEI) into the endonuclease L-DNase II—with opposing effects on cell survival—revealed that a single polypeptide can switch between protease inhibitor and nuclease functions depending on its conformational state.

    Evidence Na+/H+ antiport inhibition in BHK cells, L-DNase II activity assays, gain-of-function overexpression of LEI versus L-DNase II forms

    PMID:12728253

    Open questions at the time
    • Identity of the protease that cleaves the reactive center loop in vivo
    • Structural basis of endonuclease activity not determined
  4. 2006 High

    Showing that EGF triggers LEI-to-L-DNase II conversion and nuclear translocation to drive caspase-independent (paraptotic) cell death established that this conformational switch operates downstream of receptor tyrosine kinase signaling, not only acidification.

    Evidence Western blot, immunocytochemistry, enzymatic activity measurement, and paraptosis inhibitor (AIP-1/Alix) pharmacology in GH4C1 pituitary cells

    PMID:16538380

    Open questions at the time
    • Signaling intermediates linking EGF receptor to reactive loop cleavage unknown
    • Generalizability to other cell types not shown
  5. 2006 High

    Detection of SERPINB1–elastase and SERPINB1–cathepsin G covalent complexes in lung tissue by co-immunoprecipitation and mass spectrometry proved that in vitro inhibitory activity operates in vivo during inflammation.

    Evidence Co-IP and HPLC ion-trap mass spectrometry in baboon bronchopulmonary dysplasia lung tissue and lavage

    PMID:15633200 PMID:16617093

    Open questions at the time
    • Quantitative stoichiometry of serpin versus free protease in tissue not established
    • Contribution of other serpins in the same compartment not delineated
  6. 2007 High

    SerpinB1-knockout mice demonstrated that cytoplasmic protease inhibition is essential for neutrophil survival and pulmonary bacterial clearance, moving SerpinB1 from a biochemical inhibitor to a non-redundant host defense factor.

    Evidence Serpinb1−/− mouse, Pseudomonas aeruginosa infection, recombinant SERPINB1 rescue of bacterial clearance

    PMID:17664292

    Open questions at the time
    • Specific protease target responsible for neutrophil death not yet identified at this stage
    • Whether SerpinB1 acts beyond neutrophils in host defense unclear
  7. 2012 High

    Two breakthroughs identified new targets and processes: SERPINB1 was shown to inhibit granzyme H via Phe343 to suppress cytotoxic lymphocyte killing, and SerpinB1 was found to translocate to the nucleus to restrain NETosis, expanding its role from protease inhibition to regulation of neutrophil chromatin dynamics.

    Evidence Crystal structures of GzmH and SERPINB1, covalent complex formation, cytotoxicity rescue assays; in vitro NETosis assays in serpinb1−/− neutrophils with live-cell imaging of nuclear translocation

    PMID:23002442 PMID:23269243

    Open questions at the time
    • Which nuclear protease target mediates NETosis restraint not identified
    • Mechanism of cytoplasm-to-nucleus translocation undefined
  8. 2013 High

    Genetic epistasis (serpinb1/cathepsin G double knockout) identified cathepsin G as the critical protease whose unchecked activity causes bone marrow neutropenia, establishing that SerpinB1 maintains the neutrophil reserve by specifically counteracting cathepsin G-driven cell death.

    Evidence Serpinb1−/−/CatG−/− double-KO rescue, bone marrow chimera demonstrating cell autonomy, lysosomotropic agent treatment

    PMID:23532733

    Open questions at the time
    • Downstream substrates of cathepsin G that execute cell death not identified
    • Whether partial caspase involvement reflects a distinct parallel pathway is unresolved
  9. 2015 High

    Identification of SerpinB1 in the hepatocyte secretome and demonstration that it promotes pancreatic β cell proliferation revealed an unexpected endocrine-like function, linking liver-derived protease inhibition to islet compensation during insulin resistance.

    Evidence Hepatocyte secretome proteomics in LIRKO mice, serpinb1−/− attenuation of β cell expansion, recombinant SerpinB1 on islets from three species, elastase-inhibitor small-molecule mimics

    PMID:26701651

    Open questions at the time
    • Receptor or pathway on β cells directly engaged by secreted SerpinB1 not identified
    • Whether β cell effect requires protease inhibition or a distinct mechanism is unclear
  10. 2019 High

    Combined deletion of SerpinB1a and SerpinB6a showed that cathepsin G drives both GSDMD-dependent inflammatory signaling in macrophages and GSDMD-independent programmed necrosis in neutrophils, positioning SerpinB1 at the intersection of pyroptotic and non-pyroptotic cell death pathways.

    Evidence Triple genetic epistasis (Sb1a/Sb6a/GSDMD knockouts), in vitro CatG cleavage of GSDMD, cytokine ELISA, in vivo endotoxin challenge

    PMID:31216481

    Open questions at the time
    • Identity of the GSDMD-independent necrosis executioner downstream of CatG unknown
    • Relative contribution of SerpinB1 vs. SerpinB6 in different myeloid compartments not fully resolved
  11. 2019 Medium

    Demonstration that EZH2-mediated H3K27me3 and DNMT-mediated DNA methylation silence SERPINB1 in prostate cancer—with functional consequences for proliferation, apoptosis, and EMT—linked epigenetic loss of protease inhibition to tumor progression.

    Evidence ChIP for H3K27me3, promoter pyrosequencing, siRNA knockdown in normal prostate cells, stable overexpression in cancer cells, xenograft model

    PMID:30610107

    Open questions at the time
    • Which downstream protease target mediates the tumor-suppressive effect not identified
    • Whether L-DNase II conversion contributes to the pro-apoptotic effect in cancer cells is untested
    • Independent cohort validation of epigenetic silencing not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of L-DNase II endonuclease activity; the identity of the cathepsin G substrate(s) that execute GSDMD-independent necrosis; the receptor or signaling mechanism by which secreted SerpinB1 drives β cell proliferation; and the mechanism of SERPINB1 nuclear translocation during NETosis.
  • No atomic structure of L-DNase II conformation
  • No identified CatG substrate mediating necrosis execution
  • No receptor for secreted SerpinB1 on β cells
  • Mechanism of nuclear import during NETosis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0140096 catalytic activity, acting on a protein 3 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 2
Partners
AIFM1CTSGELANEGSDMDGZMHPRTN3

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 SERPINB1 (MNEI) inhibits neutrophil elastase-like proteases (neutrophil elastase, proteinase-3, porcine pancreatic elastase) and chymotrypsin-like proteases (cathepsin G, mast cell chymase, chymotrypsin, PSA) through two distinct reactive sites: Cys344 (P1 site, equivalent to Met358 in alpha1-antitrypsin) for elastase-like proteases and Phe343 (P2 site) for chymotrypsin-like proteases, forming SDS-stable covalent inhibitory complexes. In vitro inhibition assays with rate constant measurements, N-terminal sequencing and mass spectrometry of reaction products, stoichiometry of inhibition analysis Biochemistry High 11747453
1995 The SERPINB1 (ELANH2/M/NEI) gene was localized to chromosome 6p24-pter by somatic cell hybrid panel analysis, and its intron positions were found homologous to chicken ovalbumin and human PAI-2, establishing it as a member of the 'ovalbumin-related serpin' (Ov-serpin) family. Somatic cell hybrid panel PCR mapping, intron amplification and characterization Genomics High 8530031
1998 The SERPINB1 (M/NEI) gene has a 9.5 kb structure with 7 exons and 6 introns, a single gene copy, multiple polyadenylation signals, and shares a promoter motif (TATAAGAG) with its target proteases neutrophil elastase and proteinase-3. Southern blotting, primer extension, recombinant lambda phage clone sequencing Gene High 9630619
1998 SERPINB1 (ELANH2/PI-6/PI-9 cluster) maps to a 200-kb region on chromosome 6p25 with gene order tel-PI6-PI9-ELANH2-cen; PI6 and ELANH2 share a 7-exon, 6-intron structure nearly identical to the ovalbumin serpin genes at 18q21.3, confirming two structurally distinct Ov-serpin clusters. Fine mapping with radiation and somatic cell hybrids, structural analysis of gene organization Cytogenetics and cell genetics High 9858835
2002 Four murine homologs of human SERPINB1 (MNEI) were identified: EIA (Serpinb1), EIB (Serpinb1b), EIC (Serpinb1c), and EID (pseudogene). EIA forms inhibitory covalent complexes with pancreatic and neutrophil elastases, cathepsin G, proteinase-3, and chymotrypsin (same spectrum as human MNEI), while EIB only inhibits cathepsin G, establishing EIA as the functional mouse ortholog. Gene sequencing, RT-PCR, in vitro incubation with serine proteases and SDS-PAGE analysis of covalent complexes The Journal of biological chemistry High 12189154
2006 SERPINB1 forms high-molecular-mass inhibitory complexes with neutrophil elastase and cathepsin G in vivo in lung tissue and bronchoalveolar lavage fluid, as demonstrated by coimmunoprecipitation and HPLC ion trap mass spectrometry in a baboon model of bronchopulmonary dysplasia. Coimmunoprecipitation, HPLC ion trap mass spectrometry American journal of physiology. Lung cellular and molecular physiology High 16617093
2007 SerpinB1 is required for neutrophil survival and pulmonary host defense against Pseudomonas aeruginosa; serpinb1-deficient mice show intrinsic neutrophil survival defects with release of neutrophil protease activity, sustained inflammatory cytokine production, and proteolysis of surfactant protein-D (SP-D). Coadministration of recombinant SERPINB1 rescued bacterial clearance. Serpinb1 knockout mouse model, survival analysis, bacterial clearance assay, cytokine measurement, recombinant protein rescue experiment The Journal of experimental medicine High 17664292
2011 SerpinB1 restricts pro-inflammatory cytokine production (TNF-α, IL-6, KC/CXCL1, G-CSF, IL-17A, MCP-1) during pulmonary influenza infection; monocyte-derived cells from serpinb1-deficient mice produce excessive IL-6 and TNF-α ex vivo, demonstrating a cell-autonomous anti-inflammatory role of SerpinB1 in myeloid cells. Serpinb1 knockout mouse, influenza challenge model, cytokine ELISA, ex vivo cytokine production assay from isolated lung immune cells The Journal of infectious diseases High 21791661
2012 SerpinB1 is a regulatory mechanism that restricts NETosis (neutrophil extracellular trap generation); serpinb1-deficient neutrophils are hypersusceptible to NETosis, SerpinB1 migrates from the cytoplasm to the nucleus coincident with nuclear delobulation, and exogenous recombinant SerpinB1 abrogates NET production. In vitro NETosis assays with multiple stimuli in serpinb1-deficient bone marrow neutrophils, live cell imaging of SerpinB1 subcellular localization, nuclear expansion measurement, in vivo NETosis quantification during P. aeruginosa infection Journal of immunology High 23002442
2013 SerpinB1 maintains the bone marrow neutrophil reserve by cell-autonomously inhibiting cathepsin G (CatG); genetic deletion of CatG (but not neutrophil elastase) fully rescues bone marrow neutropenia in serpinb1-deficient mice. CatG-mediated PMN cytotoxicity is only partly blocked by caspase inhibition, indicating CatG cleaves distinct targets during apoptosis. Lysosomotropic agent-induced cytosolic release of granule contents triggers rapid CG-dependent PMN death. Bone marrow chimera experiments, serpinb1/cathepsin G double-knockout genetic epistasis, mixed bone marrow chimera and in vitro survival assays, lysosomotropic agent (LLOMe) treatment Blood High 23532733
2012 SERPINB1 is a potent intracellular inhibitor of human granzyme H (GzmH); upon cleavage of its reactive center loop at Phe343, SERPINB1 forms an SDS-stable covalent complex with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell-mediated cytotoxicity. Crystal structures of active GzmH (3.0 Å) and SERPINB1 LM-DD mutant (2.9 Å) were determined, and molecular modeling reveals conformational changes in GzmH during suicide inhibition. Co-IP/pull-down with SDS-PAGE to detect covalent complex, SERPINB1 overexpression cytotoxicity assay, X-ray crystallography of GzmH and SERPINB1 Journal of immunology High 23269243
2013 SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells; serpinb1a-deficient mice show expanded Vγ4+ and Vγ6/Vδ1+ γδ T cells and CD4+ Th17 cells in lungs and spleen with elevated Ki-67 and IL-17A, while SerpinB1 is preferentially expressed in these IL-17A+ T cell subsets. Flow cytometry analysis of T cell populations in serpinb1a knockout mice, Ki-67 proliferation marker, transcriptional profiling of sorted T cells Journal of leukocyte biology Medium 24249741
2015 SerpinB1 promotes pancreatic β cell proliferation; it is abundant in the hepatocyte secretome and sera of liver insulin receptor knockout (LIRKO) mice (an insulin resistance model with islet hyperplasia). SerpinB1 treatment of isolated islets modulates proteins in growth/survival pathways, and mice lacking serpinb1 show attenuated β cell compensation in response to insulin resistance. Small molecules that mimic its elastase-inhibitory activity also enhance β cell proliferation. Proteomics of hepatocyte secretome, serpinb1 knockout mouse with insulin resistance model, recombinant SerpinB1 treatment of human/mouse/zebrafish islets, small-molecule elastase inhibitor studies Cell metabolism High 26701651
2016 SERPINB1 (LEI) has two distinct enzymatic activities: an antiprotease activity dependent on its reactive site loop, and an endonuclease (L-DNase II) activity that is unveiled upon cleavage of the reactive site loop. This conformational change also exposes a bipartite nuclear localization signal, enabling nuclear translocation. Biochemical characterization reviewed; reference to original experimental demonstrations of L-DNase II activity and nuclear localization signal Seminars in cell & developmental biology Medium 27422329
2003 Intracellular acidification induced by Na+/H+ antiport inhibition (HMA treatment) converts LEI (SERPINB1) into L-DNase II, increases L-DNase II enzymatic activity and immunoreactivity, and induces apoptosis. LEI overexpression increases cell survival in etoposide-induced apoptosis, whereas L-DNase II overexpression promotes apoptosis, demonstrating differential roles of the two forms. HMA treatment of BHK cells, L-DNase II immunoreactivity and enzymatic activity assay, overexpression of LEI and L-DNase II, cell survival assay Cell death and differentiation High 12728253
2006 EGF triggers cleavage of LEI (SERPINB1) into L-DNase II in GH4C1 pituitary cells, followed by enzymatic activation and nuclear translocation of L-DNase II, mediating caspase-independent internucleosomal DNA fragmentation (paraptosis). EGF-induced cell death is blocked by the paraptosis inhibitor AIP-1/Alix but not by its anti-apoptotic C-terminal fragment. Western blot for LEI/L-DNase II conversion, immunocytochemistry for localization, enzymatic activity measurement, paraptosis inhibitor pharmacology Apoptosis High 16538380
2013 Apoptosis-inducing factor (AIF) and L-DNase II (derived from SERPINB1/LEI) physically interact and cooperate to induce caspase-independent cell death. Protein interaction assay (co-immunoprecipitation implied), cell death assays Apoptosis Medium 23673989
2019 Serpinb1a and Serpinb6a together prevent programmed necrosis (GSDMD-independent) in neutrophils and monocytes by inhibiting cathepsin G (CatG). CatG efficiently cleaves GSDMD to generate the N-terminal p30 domain, but GSDMD deletion does not rescue neutrophil survival in double-knockout mice. CatG also drives elevated pro-inflammatory cytokine release in a GSDMD-dependent manner in macrophages; canonical inflammasome activation leads to increased IL-1β release dependent on both CatG and GSDMD. Double-knockout mouse model (Sb1a.Sb6a-/-), GSDMD single and double-knockout genetic epistasis, CatG cleavage of GSDMD in vitro, cytokine ELISA, endotoxin challenge in vivo Cell reports High 31216481
2017 SERPINB1 ameliorates acute lung injury via ERK1/2-mediated STAT3-dependent induction of HO-1; SERPINB1 knockdown increases post-liver-transplantation lung injury, recombinant SerpinB1 enhances HO-1 and STAT3 protein expression, and these protective effects are abolished by ERK1/2 inhibition (U0126) but not p38 MAPK or JNK inhibition. Rat orthotopic liver transplantation model, siRNA knockdown, recombinant protein treatment, pathway inhibitors (ERK, p38, JNK, STAT3), gene knockdown in alveolar epithelial cells Free radical biology & medicine Medium 28427999
2019 SERPINB1 expression is epigenetically suppressed in prostate cancer by EZH2-mediated H3K27me3 methylation and DNA methyltransferase-mediated DNA methylation of the SERPINB1 promoter. Knockdown of SERPINB1 in non-malignant prostatic cells increases proliferation, decreases apoptosis, and stimulates EMT marker expression; stable SERPINB1 expression in prostate cancer cells reduces xenograft growth in vivo. ChIP for H3K27me3, pyrosequencing of promoter methylation, siRNA knockdown, stable overexpression, xenograft model Molecular cancer research Medium 30610107
2020 piR-39980 negatively regulates SERPINB1 in osteosarcoma; knockdown of piR-39980 enhances SERPINB1 expression, and SERPINB1 overexpression suppresses proliferation, migration, MMP-2 activation, and invasion of osteosarcoma cells. The piR-39980/SERPINB1 regulatory relationship was confirmed by dual luciferase reporter assay. piRNA mimic/inhibitor transfection, SERPINB1 overexpression, dual luciferase reporter assay, gelatin zymography for MMP-2, western blotting Biology of the cell Medium 31879982
2005 Aerosolized recombinant MNEI (SERPINB1) forms in vivo inhibitory complexes with pulmonary elastase (detected as 66 kDa complex in lavage fluid), reduces inflammatory histopathology, and enhances bacterial clearance of P. aeruginosa from chronically infected rat lungs without direct bactericidal activity. Rat chronic P. aeruginosa infection model, aerosol MNEI treatment, HPLC/SDS-PAGE analysis of lavage complexes, histopathology scoring, bacterial CFU counting Pediatric pulmonology High 15633200

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Epilepsy, E/I Balance and GABA(A) Receptor Plasticity. Frontiers in molecular neuroscience 230 18946538
2019 Cathepsin G Inhibition by Serpinb1 and Serpinb6 Prevents Programmed Necrosis in Neutrophils and Monocytes and Reduces GSDMD-Driven Inflammation. Cell reports 221 31216481
1997 Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. The Biochemical journal 218 9396714
2006 The eight amino-acid differences within three leucine-rich repeats between Pi2 and Piz-t resistance proteins determine the resistance specificity to Magnaporthe grisea. Molecular plant-microbe interactions : MPMI 216 17073304
1975 Polymorphism of red cell glyoxalase I (EI: 4.4.1.5); a new genetic marker in man. Investigation of 169 mother-child combinations. Humangenetik 215 1150236
2015 SerpinB1 Promotes Pancreatic β Cell Proliferation. Cell metabolism 204 26701651
1998 Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line. The Journal of biological chemistry 186 9478986
2020 GABAergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 168 32543726
2017 Commentary on "Integrative clinical genomics of advanced prostate cancer". Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu EY, Mostaghel EA, Cheng HH, Mulcahy H, True LD, Plymate SR, Dvinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson BD, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PS, Garraway LA, Sawyers CL, Chinnaiyan AM.Cell. 21 May 2015;161(5):1215-1228. Urologic oncology 157 28623072
2001 The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites. Biochemistry 132 11747453
2002 Two broad-spectrum blast resistance genes, Pi9( t) and Pi2( t), are physically linked on rice chromosome 6. Molecular genetics and genomics : MGG 95 12111554
2007 The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection. The Journal of experimental medicine 94 17664292
1995 alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity. Biochemistry 94 7578057
2012 A serpinB1 regulatory mechanism is essential for restricting neutrophil extracellular trap generation. Journal of immunology (Baltimore, Md. : 1950) 83 23002442
2015 Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron 79 26004914
2015 Conformational Analysis, Thermal Rearrangement, and EI-MS Fragmentation Mechanism of (1(10)E,4E,6S,7R)-Germacradien-6-ol by (13)C-Labeling Experiments. Angewandte Chemie (International ed. in English) 78 26361082
2006 Genetic characterization and fine mapping of the blast resistance locus Pigm(t) tightly linked to Pi2 and Pi9 in a broad-spectrum resistant Chinese variety. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 72 16832648
1997 Molecular identification of the equilibrative NBMPR-sensitive (es) nucleoside transporter and demonstration of an equilibrative NBMPR-insensitive (ei) transport activity in human erythroleukemia (K562) cells. Neuropharmacology 72 9364472
2007 Simultaneous GC-EI-MS determination of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol in human urine following tandem enzyme-alkaline hydrolysis. Journal of analytical toxicology 70 17988462
2023 Enantioselective, Intermolecular [π2+σ2] Photocycloaddition Reactions of 2(1H)-Quinolones and Bicyclo[1.1.0]butanes. Journal of the American Chemical Society 68 37917070
2016 The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI-101 prevents cisplatin-induced nephrotoxicity. British journal of pharmacology 66 26398481
2022 Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/- mouse model of ASD-like behavior. Nature communications 65 35241668
1992 Secretion of melanin-concentrating hormone and neuropeptide-EI from cultured rat hypothalamic cells. Endocrinology 63 1327720
2006 The wild-derived inbred mouse strain SPRET/Ei is resistant to LPS and defective in IFN-beta production. Proceedings of the National Academy of Sciences of the United States of America 56 16455798
2013 LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO molecular medicine 55 23495141
2011 Critical role of serpinB1 in regulating inflammatory responses in pulmonary influenza infection. The Journal of infectious diseases 55 21791661
2016 The hidden side of SERPINB1/Leukocyte Elastase Inhibitor. Seminars in cell & developmental biology 54 27422329
2013 SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G. Blood 54 23532733
2001 Solution structure of a sweet protein: NMR study of MNEI, a single chain monellin. Journal of molecular biology 54 11152608
2002 Characterization of four murine homologs of the human ov-serpin monocyte neutrophil elastase inhibitor MNEI (SERPINB1). The Journal of biological chemistry 49 12189154
2006 SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia. American journal of physiology. Lung cellular and molecular physiology 48 16617093
2001 Probing the surface of a sweet protein: NMR study of MNEI with a paramagnetic probe. Protein science : a publication of the Protein Society 47 11468346
2003 Apoptosis induced by Na+/H+ antiport inhibition activates the LEI/L-DNase II pathway. Cell death and differentiation 46 12728253
2012 The identification of Pi50(t), a new member of the rice blast resistance Pi2/Pi9 multigene family. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 45 22270148
2018 Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders. Molecular psychiatry 44 29743582
2003 Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice. Journal of lipid research 44 12588951
2018 Development of precise GC-EI-MS method to determine the residual fipronil and its metabolites in chicken egg. Food chemistry 43 30658770
2015 Functional divergence of duplicated genes results in a novel blast resistance gene Pi50 at the Pi2/9 locus. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 43 26183036
2007 The genomic dynamics and evolutionary mechanism of the Pi2/9 locus in rice. Molecular plant-microbe interactions : MPMI 43 17249423
2007 Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors. The FEBS journal 42 17635581
2006 A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells. Apoptosis : an international journal on programmed cell death 39 16538380
2003 The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI. Journal of molecular biology 39 12706725
1993 The clastogen-suppressing effects of green tea, Po-lei tea and Rooibos tea in CHO cells and mice. Mutation research 37 7681534
2006 Toward the understanding of MNEI sweetness from hydration map surfaces. Biophysical journal 36 16461400
2005 Aerosol treatment with MNEI suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection. Pediatric pulmonology 35 15633200
2021 Depression-like behavior associated with E/I imbalance of mPFC and amygdala without TRPC channels in mice of knockout IL-10 from microglia. Brain, behavior, and immunity 34 34224823
2020 piR-39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma. Biology of the cell 34 31879982
2017 SERPINB1 ameliorates acute lung injury in liver transplantation through ERK1/2-mediated STAT3-dependent HO-1 induction. Free radical biology & medicine 34 28427999
2016 Sweeter and stronger: enhancing sweetness and stability of the single chain monellin MNEI through molecular design. Scientific reports 33 27658853
1998 Neuronal and behavioral differences between Mus musculus domesticus (C57BL/6JBy) and Mus musculus castaneus (CAST/Ei). Behavioural brain research 33 9754885
1987 Simultaneous phenotyping of pig plasma alpha-protease inhibitors (PI1, PO1A, PO1B, PI2) and four other proteins (PO2, TF, CP, HPX) by a simple method of 2D horizontal electrophoresis. Animal genetics 33 3662119
2012 Identification of SERPINB1 as a physiological inhibitor of human granzyme H. Journal of immunology (Baltimore, Md. : 1950) 32 23269243
2013 SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells. Journal of leukocyte biology 31 24249741
2006 Chronic restraint stress decreases the expression of glutathione S-transferase pi2 in the mouse hippocampus. Brain research 31 16643866
2015 Molecular breeding of thermo-sensitive genic male sterile (TGMS) lines of rice for blast resistance using Pi2 gene. Rice (New York, N.Y.) 30 25844116
2014 Biochemical characterization of a nitrogen-type phosphotransferase system reveals that enzyme EI(Ntr) integrates carbon and nitrogen signaling in Sinorhizobium meliloti. Journal of bacteriology 29 24633875
2016 Allele-specific marker-based assessment revealed that the rice blast resistance genes Pi2 and Pi9 have not been widely deployed in Chinese indica rice cultivars. Rice (New York, N.Y.) 27 27142801
2014 Pseudomonas aeruginosa quorum-sensing molecule homoserine lactone modulates inflammatory signaling through PERK and eI-F2α. Journal of immunology (Baltimore, Md. : 1950) 27 24990083
2012 Molecular mapping of the Pi2/9 allelic gene Pi2-2 conferring broad-spectrum resistance to Magnaporthe oryzae in the rice cultivar Jefferson. Rice (New York, N.Y.) 27 27234247
2004 Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice. Physiological genomics 27 14701919
2016 Epitope imprinting enhanced IMAC (EI-IMAC) for highly selective purification of His-tagged protein. Journal of materials chemistry. B 26 32263073
2000 A caspase-independent cell clearance program. The LEI/L-DNase II pathway. Annals of the New York Academy of Sciences 26 11193035
2016 Molecular Dynamics Driven Design of pH-Stabilized Mutants of MNEI, a Sweet Protein. PloS one 25 27340829
2003 Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains. Journal of lipid research 25 12810825
2021 A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model. Chinese medicine 24 34627325
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