Affinage

SERPINF2

Alpha-2-antiplasmin · UniProt P08697

Round 2 corrected
Length
491 aa
Mass
54.6 kDa
Annotated
2026-04-28
130 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINF2 (α2-antiplasmin) is the principal fast-acting physiological inhibitor of plasmin, forming an irreversible, covalent 1:1 complex through cleavage of its Arg364-Met365 reactive site bond, and is the dominant regulator of fibrin clot and thrombus lysis among the three major fibrinolytic inhibitors (PAI-1, α2AP, TAFIa) (PMID:134998, PMID:17388801). The inhibitor circulates in two N-terminal forms: the Met-form and the Asn-form generated by antiplasmin-cleaving enzyme (APCE), with the Asn-form cross-linked ~13-fold faster to fibrin by Factor XIIIa, a reaction that constitutes the entire antifibrinolytic mechanism of FXIII (PMID:14751930, PMID:21471521). Beyond hemostasis, α2-antiplasmin exerts plasmin-independent profibrotic effects by inducing TGF-β production via JNK signaling in fibroblasts and myofibroblast differentiation in multiple cell types, and directly promotes macrophage proinflammatory cytokine production through ERK1/2 and JNK pathways (PMID:25095732, PMID:32237065). α2AP also impairs VEGF-driven endothelial function through an ATGL/SHP2 signaling axis and is inactivated by leukocyte elastase, linking its regulation to inflammatory protease networks (PMID:28159016, PMID:6980881).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1976 High

    Identification and biochemical characterization of α2-antiplasmin as the fast-acting plasmin inhibitor in human plasma resolved the question of which molecule was primarily responsible for physiological plasmin neutralization.

    Evidence Protein purification from human plasma, SDS-PAGE, stoichiometry analysis, and antibody neutralization of plasma fibrinolytic activity

    PMID:134998 PMID:21075

    Open questions at the time
    • No primary structure determined
    • Mechanism of covalent complex formation not resolved
    • In vivo relevance not directly demonstrated
  2. 1979 High

    Establishing the suicide substrate-like serpin mechanism of the α2AP–plasmin reaction explained how the inhibitor achieves rapid, irreversible inactivation of plasmin through covalent complex formation at the reactive site bond.

    Evidence In vitro kinetic dissection with SDS-PAGE analysis of covalent enzyme–inhibitor complexes

    PMID:158022

    Open questions at the time
    • Reactive site residues not yet identified
    • Crystal structure unavailable
  3. 1981 High

    Discovery of a platelet α2AP storage pool released upon thrombin stimulation revealed a localized antifibrinolytic mechanism at sites of platelet activation, beyond the circulating plasma reservoir.

    Evidence Radioimmunoassay of platelet extracts with thrombin stimulation and cross-cell-type comparisons

    PMID:7306699

    Open questions at the time
    • Contribution of platelet-derived α2AP to clot stability vs. plasma pool not quantified
    • Mechanism of platelet storage (granule type) not determined
  4. 1982 High

    Demonstration that leukocyte elastase proteolytically inactivates α2AP established a direct link between neutrophil-mediated inflammation and local loss of antifibrinolytic protection.

    Evidence In vitro incubation of purified elastase and α2AP with SDS-PAGE and functional activity assays

    PMID:6980881

    Open questions at the time
    • In vivo significance at inflammatory sites not tested
    • Cleavage sites not mapped to sequence
  5. 1987 High

    Determination of the full primary structure by cDNA sequencing identified the Arg364-Met365 reactive site bond and placed α2AP within the serpin superfamily, enabling structure–function analysis.

    Evidence cDNA cloning from human liver mRNA, sequencing, serpin family alignment

    PMID:2433286

    Open questions at the time
    • Three-dimensional structure not resolved
    • Functional domains beyond reactive center loop not mapped
  6. 2004 High

    Discovery of APCE-mediated N-terminal processing of Met-α2AP to Asn-α2AP, which is cross-linked to fibrin by FXIIIa ~13-fold faster, explained how the relative abundance of α2AP isoforms regulates clot resistance to fibrinolysis.

    Evidence Purification of APCE from plasma, in vitro cleavage and FXIIIa cross-linking kinetics, clot lysis rate measurements

    PMID:14751930

    Open questions at the time
    • Regulation of APCE activity in vivo unknown
    • Structural basis for differential FXIIIa cross-linking rate not determined
  7. 2007 High

    Systematic depletion/neutralization epistasis among PAI-1, α2AP, and TAFIa demonstrated that α2AP is the single most important fibrinolytic inhibitor in both plasma clots and whole-blood thrombi, but maximal fibrinolysis requires neutralization of all three.

    Evidence Clot and thrombus lysis assays with neutralizing antibodies and carboxypeptidase inhibitor, single and combination depletions

    PMID:17388801

    Open questions at the time
    • In vivo arterial thrombolysis hierarchy not confirmed
    • Temporal dynamics of inhibitor contribution during thrombus maturation unknown
  8. 2011 High

    Demonstration that FXIIIa's entire antifibrinolytic function depends on cross-linking α2AP to fibrin unified the FXIII and α2AP pathways into a single obligate axis controlling thrombus stability.

    Evidence Flow-based thrombus model with FXIII and/or α2AP depletion, reconstitution, and neutralizing antibody

    PMID:21471521 PMID:25331118

    Open questions at the time
    • Whether other FXIIIa substrates contribute to thrombus stability in other contexts not excluded
    • Role of platelet-derived vs. plasma FXIII not fully separated in vivo
  9. 2014 High

    Discovery of plasmin-independent profibrotic activity of α2AP — inducing TGF-β via JNK signaling and promoting myofibroblast differentiation — expanded its functional repertoire beyond hemostasis to organ fibrosis.

    Evidence UUO renal fibrosis model in α2AP-knockout vs. wild-type mice, in vitro JNK inhibitor epistasis, multiple cell types

    PMID:25095732 PMID:26743600

    Open questions at the time
    • Receptor mediating α2AP profibrotic signaling unidentified
    • Whether profibrotic effect requires full-length vs. cleaved α2AP unknown
  10. 2017 Medium

    Identification of ATGL/SHP2 as the axis through which α2AP impairs VEGF-driven endothelial function revealed a plasmin-independent vascular dysfunction mechanism relevant to systemic sclerosis.

    Evidence Endothelial tube formation, proliferation, and junction protein assays with pathway inhibitors; bleomycin SSc mouse model

    PMID:28159016

    Open questions at the time
    • ATGL/SHP2 axis established in a single study, no independent confirmation
    • Direct binding target on endothelial cells not identified
    • Whether this pathway operates outside SSc context unknown
  11. 2020 Medium

    Dual pro-inflammatory mechanisms of α2AP in macrophages — neutralizing plasmin's AMPK-mediated anti-inflammatory effect and directly activating ERK1/2/JNK cytokine production — explained its role in promoting lupus nephritis beyond simple fibrinolysis regulation.

    Evidence Pristane-induced lupus model in α2AP-knockout vs. wild-type mice, macrophage cytokine assays with pathway inhibitors

    PMID:32237065

    Open questions at the time
    • Receptor or binding partner mediating direct macrophage activation unknown
    • Relative contribution of plasmin-dependent vs. -independent mechanisms in vivo not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The cell-surface receptor or binding partner through which α2AP initiates its plasmin-independent signaling (profibrotic TGF-β/JNK, pro-inflammatory ERK1/2/JNK, anti-angiogenic ATGL/SHP2) remains unidentified, preventing a unified model of its non-hemostatic functions.
  • No receptor identification for non-serpin signaling functions
  • Structural basis of plasmin-independent activity unknown
  • Therapeutic targeting of non-hemostatic functions not tested in clinical models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-109582 Hemostasis 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 1
Partners
DEFA1ELANEF13A1FAPPLG

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1976 α2-plasmin inhibitor (SERPINF2/α2-antiplasmin) was isolated from human plasma and characterized as a glycoprotein (~67 kDa) that instantaneously inhibits plasmin by forming a non-dissociable 1:1 stoichiometric complex involving cleavage of a specific peptide bond in the inhibitor and cross-linking to the light (active-site-containing) chain of plasmin. It also inhibits trypsin but only slowly inhibits urokinase. A neutralizing antibody abolished virtually all inhibitory activity of plasma against activator-induced clot lysis. Protein purification, SDS-PAGE, immunoelectrophoresis, kinetic inhibition assays, stoichiometry determination, antibody neutralization experiments The Journal of biological chemistry High 134998
1977 Human antiplasmin (α2-antiplasmin/SERPINF2) was purified and further characterized as the fast-acting plasmin inhibitor in plasma, establishing it as the primary physiological inhibitor of plasmin. Protein purification, functional inhibition assays European journal of biochemistry High 21075
1979 The mechanism of the reaction between α2-antiplasmin (SERPINF2) and plasmin was established: the inhibitor forms a covalent, SDS-stable 1:1 complex with plasmin via a suicide substrate-like serpin mechanism, involving cleavage at the reactive site peptide bond. In vitro kinetic assays, SDS-PAGE complex analysis, mechanistic dissection of enzyme-inhibitor interaction The Journal of biological chemistry High 158022
1981 α2-antiplasmin (SERPINF2) is stored in human platelets (33–114 ng per 10⁹ platelets) and is released upon thrombin stimulation without cell lysis. This release is specific to platelets among peripheral blood cells, identifying platelets as a cellular reservoir for α2AP distinct from the plasma pool. Radioimmunoassay of platelet extracts, thrombin stimulation assay, comparison across blood cell types Blood High 7306699
1982 Human polymorphonuclear leukocyte elastase inactivates α2-plasmin inhibitor (SERPINF2) by limited proteolytic cleavage at two separate sites, generating lower molecular weight fragments and destroying plasmin-inhibitory activity. This suggests that elastase released during inflammation can potentiate pathological proteolysis by inactivating α2AP. In vitro incubation of leukocyte elastase with purified α2-plasmin inhibitor, SDS-PAGE analysis of cleavage products, functional activity assays The Journal of biological chemistry High 6980881
1987 The primary structure of human α2-antiplasmin (SERPINF2) was determined by cDNA sequencing: mature protein contains 452 amino acids, is homologous (23–28%) to other serpins, and its reactive site (the peptide bond cleaved upon reaction with plasmin) is Arg364-Met365, corresponding to the P1-P1' position in serpin nomenclature. cDNA cloning and sequencing from human liver mRNA, oligonucleotide probe designed from peptide sequence, sequence alignment with serpin superfamily The Journal of biological chemistry High 2433286
1995 Human neutrophil defensins bind directly to α2-antiplasmin (SERPINF2) and form complexes with it. This interaction mutually inactivates both partners: defensins abolish the antiprotease activity of α2AP against plasmin, and α2AP inhibits defensin cytotoxicity toward lung carcinoma cells. In vitro binding assays, antiprotease activity assays with increasing defensin concentrations, cytotoxicity assays with serpin pre-incubation American journal of respiratory cell and molecular biology Medium 7873202
1996 α2-antiplasmin (SERPINF2) is present in atherosclerotic plaque at higher concentrations than in normal arterial wall, where it co-localizes with PAI-1. Together with reduced tissue plasminogen activator, elevated α2AP contributes to impaired fibrinolysis in atherosclerotic lesions, potentially maintaining plaque by resisting fibrin dissolution. Immunohistochemistry of normal and atherosclerotic arterial wall sections, quantitative immunoassay of tissue extracts Arteriosclerosis, thrombosis, and vascular biology Medium 8624776
2003 Human kallikrein 6 (hK6) is inhibited by α2-antiplasmin (SERPINF2) among other serpins, establishing α2AP as a physiological inhibitor of this trypsin-like serine protease. Antithrombin III was the most efficient inhibitor among those tested. In vitro enzyme inhibition assays with purified recombinant hK6 and panel of serpins Biochemical and biophysical research communications Medium 12878203
2004 A plasma proteinase named antiplasmin-cleaving enzyme (APCE), homologous to fibroblast activation protein/seprase, cleaves the Pro12-Asn13 bond of the Met-form of α2-antiplasmin (Met-α2AP, SERPINF2) to generate the Asn-form (Asn-α2AP). Asn-α2AP is cross-linked to fibrin by activated Factor XIIIa approximately 13-fold faster than Met-α2AP, making fibrin clots markedly more resistant to plasmin-mediated lysis. The ratio of Asn-α2AP to Met-α2AP directly determines clot lysis rates. Purification of APCE from human plasma, in vitro cleavage assays, Factor XIIIa cross-linking kinetics, plasma clot lysis rate measurements as a function of α2AP form ratio Blood High 14751930
2007 Among the three principal fibrinolytic inhibitors (PAI-1, α2-antiplasmin/SERPINF2, and TAFIa), α2AP plays the dominant role in regulating lysis of both plasma clots and whole-blood thrombi. Neutralizing antibodies to α2AP produced the largest single-inhibitor effect on lysis acceleration; maximal lysis occurred only when all three inhibitors were neutralized together, demonstrating complementary but non-redundant roles. Plasma clot lysis and model thrombus lysis assays with neutralizing antibodies to α2AP and PAI-1, carboxypeptidase inhibitor (CPI) for TAFIa, single and combination depletion experiments Journal of thrombosis and haemostasis High 17388801
2011 The antifibrinolytic function of Factor XIII (FXIII) is entirely dependent on its ability to cross-link α2-antiplasmin (SERPINF2) to fibrin. Depletion of either FXIII or α2AP accelerated clot lysis ~9-fold similarly; FXIII depletion had no additional effect on α2AP-depleted thrombi; and a neutralizing antibody to α2AP completely abolished the stabilizing effect of FXIII reconstitution. Clot stability correlated inversely and strongly with the amount of cross-linked α2AP. Flow-based plasma thrombus model with depletion of FXIII and/or α2AP, reconstitution experiments, neutralizing antibody to α2AP, quantitative correlation of cross-linked α2AP with lysis rates Blood High 21471521
2014 Platelet-derived FXIII-A is exposed on the surface of activated (thrombin + collagen stimulated) platelets and exerts its antifibrinolytic function by cross-linking α2-antiplasmin (SERPINF2) to fibrin, stabilizing thrombi. Incorporating a neutralizing antibody to α2AP abolished the platelet FXIII-A-mediated thrombus stabilization, demonstrating that α2AP cross-linking is the obligate mechanism of platelet FXIII-A antifibrinolytic activity. Chandler model thrombi from FXIII-depleted plasma reconstituted with platelets, fluorescence confocal microscopy and flow cytometry of FXIII-A on platelet surface, neutralizing antibody to α2AP, transglutaminase inhibitors Blood High 25331118
2014 α2-antiplasmin (α2AP/SERPINF2) accumulates in kidneys subjected to unilateral ureteral obstruction (UUO) and promotes renal fibrosis by inducing myofibroblast formation in renal tubular epithelial cells, renal fibroblasts, and bone marrow-derived mesenchymal stem cells. α2AP-deficient mice showed attenuated UUO-induced fibrosis and reduced myofibroblast formation. Mechanistically, α2AP induces TGF-β production via the c-Jun N-terminal kinase (JNK) pathway, and JNK inhibition (SP600125) blocked α2AP-induced TGF-β production. UUO mouse model in α2AP(+/+) vs α2AP(-/-) mice, in vitro treatment of multiple cell types with α2AP, JNK inhibitor (SP600125) pharmacological epistasis, TGF-β ELISA, myofibroblast marker quantification Scientific reports High 25095732
2015 α2-antiplasmin (SERPINF2) exerts profibrotic effects in systemic sclerosis (SSc) independently of its function as a plasmin inhibitor. Administration of α2AP to mice induced dermal fibrosis (increased dermal thickness, collagen, myofibroblast differentiation), and α2AP neutralization prevented profibrotic changes and autoantibody production in bleomycin-induced SSc models. α2AP treatment promoted fibrosis in normal human dermal fibroblasts, and α2AP neutralization reversed the profibrotic phenotype of SSc patient fibroblasts even in the absence of plasmin. Bleomycin SSc mouse model with α2AP administration and neutralizing antibody, human SSc patient dermal fibroblasts treated with α2AP or neutralizing antibody in absence of plasmin, histology, collagen assays, autoantibody measurement The Journal of investigative dermatology High 26743600
2017 α2-antiplasmin (SERPINF2) promotes vascular dysfunction in systemic sclerosis by attenuating VEGF-induced tube formation, cell proliferation, and endothelial junction-associated protein (VE-cadherin, PECAM1) production through the adipose triglyceride lipase (ATGL)/tyrosine phosphatase SHP2 signaling axis in vascular endothelial cells. α2AP neutralization improved vascular damage in bleomycin-induced SSc mice. Bleomycin SSc mouse model with α2AP administration/neutralization, in vitro endothelial cell tube formation, proliferation, junction protein assays, SSc fibroblast-conditioned media experiments, pathway inhibitor studies identifying ATGL/SHP2 axis Arthritis research & therapy Medium 28159016
2019 SerpinF2/α2-antiplasmin levels are significantly elevated in preeclampsia plasma, and the circulating plasmin-α2-antiplasmin (PAP) complex is positively correlated with testosterone and negatively correlated with estradiol in early-onset preeclampsia patients. In human renal and trophoblastic cells, testosterone and estradiol regulate SerpinF2 expression in opposite directions. Fibrin deposition co-localizes with SerpinF2 in the intervillous spaces of preeclamptic placenta. Proteomic analysis of plasma, longitudinal measurement of PAP complex and sex hormones, cell-based expression regulation experiments with testosterone/estradiol, immunolocalization in placenta Journal of hypertension Medium 30020241
2020 α2-antiplasmin (SERPINF2) is associated with lupus nephritis development through two mechanisms: (1) direct plasmin inhibition blocks plasmin's anti-inflammatory effect on macrophages (plasmin attenuates IFN-γ-induced proinflammatory cytokine production via the AMPK pathway, and α2AP eliminates this protective effect); and (2) α2AP directly induces proinflammatory cytokine production in macrophages via ERK1/2 and JNK pathways. IFN-γ induces α2AP production in fibroblasts via the JNK pathway. Pristane-induced lupus mouse model in α2AP-deficient vs wild-type mice, in vitro macrophage cytokine assays with plasmin ± α2AP, pathway inhibitor studies (AMPK, ERK1/2, JNK), IFN-γ stimulation of fibroblasts with JNK inhibitor Immunity, inflammation and disease Medium 32237065

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2021 PANTHER version 16: a revised family classification, tree-based classification tool, enhancer regions and extensive API. Nucleic acids research 973 33290554
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1976 Isolation and characterization of alpha2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis. The Journal of biological chemistry 465 134998
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2013 Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of periodontology 364 23631572
2013 Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of periodontology 364 23631582
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2013 Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of clinical periodontology 305 23627322
2008 VIPERdb2: an enhanced and web API enabled relational database for structural virology. Nucleic acids research 267 18981051
2013 Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of clinical periodontology 261 23627332
1982 API ZYM system for identification of Bacteroides spp., Capnocytophaga spp., and spirochetes of oral origin. Journal of clinical microbiology 236 6764781
2008 Plasmin in nephrotic urine activates the epithelial sodium channel. Journal of the American Society of Nephrology : JASN 215 19073825
1977 Purification and characterization of human antiplasmin, the fast-acting plasmin inhibitor in plasma. European journal of biochemistry 208 21075
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2013 Update of the human and mouse SERPIN gene superfamily. Human genomics 205 24172014
1995 Molecular characterization of Api g 1, the major allergen of celery (Apium graveolens), and its immunological and structural relationships to a group of 17-kDa tree pollen allergens. European journal of biochemistry 186 7588792
2017 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. Journal of proteome research 185 28675934
1982 Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase. The Journal of biological chemistry 176 6980881
2003 Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. American journal of human genetics 173 12621583
1979 On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin. The Journal of biological chemistry 166 158022
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2013 Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations. PLoS genetics 157 24068962
1982 Identification of Staphylococcus species with the API STAPH-IDENT system. Journal of clinical microbiology 153 6752190
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2011 The antifibrinolytic function of factor XIII is exclusively expressed through α₂-antiplasmin cross-linking. Blood 135 21471521
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2003 Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors. Biochemical and biophysical research communications 124 12878203
1987 Primary structure of human alpha 2-antiplasmin, a serine protease inhibitor (serpin). The Journal of biological chemistry 123 2433286
1981 Predictive value of urinary N-acetyl-beta-D-glucosaminidase (NAG), alanine-aminopeptidase (AAP) and beta-2-microglobulin (beta 2M) in evaluating nephrotoxicity of gentamicin. Clinica chimica acta; international journal of clinical chemistry 119 6172216
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
1996 Inhibitors of fibrinolysis are elevated in atherosclerotic plaque. Arteriosclerosis, thrombosis, and vascular biology 114 8624776
1995 Human neutrophil defensin and serpins form complexes and inactivate each other. American journal of respiratory cell and molecular biology 113 7873202
2004 A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion. Blood 109 14751930
2007 TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots. Journal of thrombosis and haemostasis : JTH 101 17388801
2010 Osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a novel substrate for plasmin and cathepsin D. The Journal of biological chemistry 99 20071328
2014 Functional factor XIII-A is exposed on the stimulated platelet surface. Blood 96 25331118
1981 The presence and release of alpha 2-antiplasmin from human platelets. Blood 96 7306699
2003 Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure. The Biochemical journal 94 12943529
2002 Metabolism of the analgesic drug ULTRAM (tramadol hydrochloride) in humans: API-MS and MS/MS characterization of metabolites. Xenobiotica; the fate of foreign compounds in biological systems 91 12065063
1985 API ZYM and API An-Ident reactions of fastidious oral gram-negative species. Journal of clinical microbiology 78 3930558
2006 Molecular cloning and expression in insect cells of honeybee venom allergen acid phosphatase (Api m 3). The Journal of allergy and clinical immunology 73 16630944
2003 Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 72 12588331
2003 Bet v 1, the major birch pollen allergen, initiates sensitization to Api g 1, the major allergen in celery: evidence at the T cell level. European journal of immunology 72 14635038
2017 The Proteins API: accessing key integrated protein and genome information. Nucleic acids research 70 28383659
2001 Cross-reactivity within the profilin panallergen family investigated by comparison of recombinant profilins from pear (Pyr c 4), cherry (Pru av 4) and celery (Api g 4) with birch pollen profilin Bet v 2. Journal of chromatography. B, Biomedical sciences and applications 70 11419723
2000 Cloning of the minor allergen Api g 4 profilin from celery (Apium graveolens) and its cross-reactivity with birch pollen profilin Bet v 2. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 69 10848918
2009 The terminal A domain of the fibrillar accumulation-associated protein (Aap) of Staphylococcus epidermidis mediates adhesion to human corneocytes. Journal of bacteriology 66 19749046
2018 Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development. Hepatology (Baltimore, Md.) 64 29381806
2013 The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis. Molecular cancer 64 24261825
2008 Performance of API Staph ID 32 and Staph-Zym for identification of coagulase-negative staphylococci isolated from bovine milk samples. Veterinary microbiology 64 19110383
2025 The UniProt website API: facilitating programmatic access to protein knowledge. Nucleic acids research 59 40331428
2023 Continuous Spatiotemporal Therapy of A Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis. Nature communications 59 36966149
2008 Yeast cell factories for fine chemical and API production. Microbial cell factories 59 18684335
2015 Emerging regenerative approaches for periodontal reconstruction: a systematic review from the AAP Regeneration Workshop. Journal of periodontology 55 25644297
1999 Evaluation of the API test, phosphatidylinositol-specific phospholipase C activity and PCR method in identification of Listeria monocytogenes in meat foods. FEMS microbiology letters 50 10077846
2012 Comparison of two matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry methods and API 20AN for identification of clinically relevant anaerobic bacteria. Journal of medical microbiology 49 23242640
2009 The ternary structure of the double-headed arrowhead protease inhibitor API-A complexed with two trypsins reveals a novel reactive site conformation. The Journal of biological chemistry 46 19640842
2015 Identification of clinically relevant Corynebacterium strains by Api Coryne, MALDI-TOF-mass spectrometry and molecular approaches. Pathologie-biologie 44 26300239
2020 Effect of Api-Bioxal® and ApiHerb® Treatments against Nosema ceranae Infection in Apis mellifera Investigated by Two qPCR Methods. Veterinary sciences 42 32899611
2020 Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API. Bioinformatics (Oxford, England) 40 31504201
2014 Role for the A domain of unprocessed accumulation-associated protein (Aap) in the attachment phase of the Staphylococcus epidermidis biofilm phenotype. Journal of bacteriology 40 25266380
2020 The biofilm adhesion protein Aap from Staphylococcus epidermidis forms zinc-dependent amyloid fibers. The Journal of biological chemistry 39 32102851
2009 Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway. Pathology oncology research : POR 39 19821157
2001 Screening for anemia in children: AAP recommendations--a critique. Pediatrics 38 11533374
2023 Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API). Journal of clinical immunology 37 36843153
2008 Biofilm and the role of the ica operon and aap in Staphylococcus epidermidis isolates causing neurosurgical meningitis. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 35 18558946
2013 The AAP gene family for amino acid permeases contributes to development of the cyst nematode Heterodera schachtii in roots of Arabidopsis. Plant physiology and biochemistry : PPB 34 23831821
2020 The ADC API: A Web API for the Programmatic Query of the AIRR Data Commons. Frontiers in big data 31 33693395
2010 Molecular mechanism of the interactions between white spot syndrome virus anti-apoptosis protein AAP-1 (WSSV449) and shrimp effector caspase. Developmental and comparative immunology 31 20546774
2009 The dispersin-encoding gene (aap) is not restricted to enteroaggregative Escherichia coli. Diagnostic microbiology and infectious disease 31 19679242
2000 Characterization of api g 1.0201, a new member of the Api g 1 family of celery allergens. International archives of allergy and immunology 31 10878490
1997 Effects of Ca++ mobilization on expression of androgen-regulated genes: interference with androgen receptor-mediated transactivation by AP-I proteins. The Prostate 31 9397199
2003 A comparative study of Edwardsiella ictaluri parent (EILO) and E. ictaluri rifampicin-mutant (RE-33) isolates using lipopolysaccharides, outer membrane proteins, fatty acids, Biolog, API 20E and genomic analyses. Journal of fish diseases 30 12946011
2021 Assembly of Biomolecular Gigastructures and Visualization with the Vulkan Graphics API. Journal of chemical information and modeling 29 34528431
1985 Rapid purification of nucleosome assembly protein (AP-I) and production of monoclonal antibodies against it. Cell structure and function 29 2417731
2014 Synergistic radiation protective effect of purified Auricularia auricular-judae polysaccharide (AAP IV) with grape seed procyanidins. Molecules (Basel, Switzerland) 28 25514216
2020 Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial. Alzheimer's & dementia : the journal of the Alzheimer's Association 27 32418361
2014 Emerging regenerative approaches for periodontal reconstruction: a consensus report from the AAP Regeneration Workshop. Journal of periodontology 27 25317603
2012 jmzIdentML API: A Java interface to the mzIdentML standard for peptide and protein identification data. Proteomics 27 22539429
2016 The Proline/Glycine-Rich Region of the Biofilm Adhesion Protein Aap Forms an Extended Stalk that Resists Compaction. Journal of molecular biology 26 27890783
2015 ms-data-core-api: an open-source, metadata-oriented library for computational proteomics. Bioinformatics (Oxford, England) 26 25910694
2012 A new amphipathic, amino-acid-pairing (AAP) peptide as siRNA delivery carrier: physicochemical characterization and in vitro uptake. The journal of physical chemistry. B 26 23077976
2006 Early postnatal nutritional requirements of the very preterm infant based on a presentation at the NICHD-AAP workshop on research in neonatology. Journal of perinatology : official journal of the California Perinatal Association 26 16801962
2021 Glycan-Dependent Corneocyte Adherence of Staphylococcus epidermidis Mediated by the Lectin Subdomain of Aap. mBio 25 34253065
2010 Molecular characterization of Api g 2, a novel allergenic member of the lipid-transfer protein 1 family from celery stalks. Molecular nutrition & food research 25 21462324
1992 Evaluation of the RapID ANA II and API ZYM systems for identification of Actinomyces species from clinical specimens. Journal of clinical microbiology 24 1452693
1984 Porcine haemophili and actinobacilli: characterization by means of API test strips and possible taxonomic implications. Canadian journal of microbiology 24 6509390
2022 Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial. Alzheimer's & dementia : the journal of the Alzheimer's Association 23 35103388
2022 Active pharmaceutical ingredient (API) chemicals: a critical review of current biotechnological approaches. Bioengineered 23 35135435
2019 Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API: A case study. International journal of pharmaceutics 23 31158454
2004 Evaluation of API ID 32C and VITEK-2 to identify Candida dubliniensis. Diagnostic microbiology and infectious disease 23 15541609
2016 Cytokinins and Expression of SWEET, SUT, CWINV and AAP Genes Increase as Pea Seeds Germinate. International journal of molecular sciences 22 27916945
2005 Cloning and characterisation of an aspartyl protease inhibitor (API-1) from Ancylostoma hookworms. International journal for parasitology 22 15722082
2004 Alteration of the tertiary structure of the major bee venom allergen Api m 1 by multiple mutations is concomitant with low IgE reactivity. Protein science : a publication of the Protein Society 22 15459335
2003 Identification of an in vitro insulin receptor substrate-1 phosphorylation site by negative-ion muLC/ES-API-CID-MS hybrid scan technique. Journal of the American Society for Mass Spectrometry 22 12686487
1998 Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in mice treated with the dominant T-cell epitope peptides. The Journal of allergy and clinical immunology 22 9525458
2017 Get GO! Retrieving GO Data Using AmiGO, QuickGO, API, Files, and Tools. Methods in molecular biology (Clifton, N.J.) 21 27812941
2017 The RNASeq-er API-a gateway to systematically updated analysis of public RNA-seq data. Bioinformatics (Oxford, England) 21 28369191
2012 The putative serine protease inhibitor Api m 6 from Apis mellifera venom: recombinant and structural evaluation. Journal of investigational allergology & clinical immunology 21 23397669
2015 PyPDB: a Python API for the Protein Data Bank. Bioinformatics (Oxford, England) 20 26369703
2013 Web scraping technologies in an API world. Briefings in bioinformatics 20 23632294
2012 IQGAP proteins reveal an atypical phosphoinositide (aPI) binding domain with a pseudo C2 domain fold. The Journal of biological chemistry 20 22493426
2012 Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo. Oncology letters 20 22741017
2020 Changes in microbial community in the presence of oil and chemical dispersant and their effects on the corrosion of API 5L steel coupons in a marine-simulated microcosm. Applied microbiology and biotechnology 19 32458139
2019 Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia. Journal of hypertension 19 30020241
2007 Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells. Allergy and asthma proceedings 19 17479607
2022 Active pharmaceutical ingredients (APIs) in ionic liquids: An effective approach for API physiochemical parameter optimization. Drug discovery today 18 35697283
2014 MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5). FEBS letters 18 25433291
2011 Distribution of Pathogenic Genes aatA, aap, aggR, among Uropathogenic Escherichia coli (UPEC) and Their Linkage with StbA Gene. Indian journal of microbiology 18 22754016
2020 The Honeybee Venom Major Allergen Api m 10 (Icarapin) and Its Role in Diagnostics and Treatment of Hymenoptera Venom Allergy. Current allergy and asthma reports 17 32548726
2020 UDP-Api/UDP-Xyl synthases affect plant development by controlling the content of UDP-Api to regulate the RG-II-borate complex. The Plant journal : for cell and molecular biology 17 32662159
2015 The Antifibrotic Effect of α2AP Neutralization in Systemic Sclerosis Dermal Fibroblasts and Mouse Models of Systemic Sclerosis. The Journal of investigative dermatology 17 26743600
2014 α2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction. Scientific reports 17 25095732
2012 Short communication: Identification of coagulase-negative staphylococcus species from goat milk with the API Staph identification test and with transfer RNA-intergenic spacer PCR combined with capillary electrophoresis. Journal of dairy science 17 23040022
2011 Slime layer formation and the prevalence of mecA and aap genes in Staphylococcus epidermidis isolates. Journal of infection in developing countries 17 21330738
2010 Bet v 1 and its homologous food allergen Api g 1 stimulate dendritic cells from birch pollen-allergic individuals to induce different Th-cell polarization. Allergy 17 20557297
2020 α2AP is associated with the development of lupus nephritis through the regulation of plasmin inhibition and inflammatory responses. Immunity, inflammation and disease 16 32237065
2018 JASPAR RESTful API: accessing JASPAR data from any programming language. Bioinformatics (Oxford, England) 16 29253085
2014 IgE recognition of chimeric isoforms of the honeybee (Apis mellifera) venom allergen Api m 10 evaluated by protein array technology. Molecular immunology 16 25451974
2001 Quality control Lactobacillus strains for use with the API 50CH and API ZYM systems at 37 degrees C. Journal of basic microbiology 16 11688210
2023 Outreach, Screening, and Randomization of APOE ε4 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program. The journal of prevention of Alzheimer's disease 15 37357285
2020 Incidence of SCID in Germany from 2014 to 2015 an ESPED* Survey on Behalf of the API*** Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) ** Arbeitsgemeinschaft Pädiatrische Immunologie. Journal of clinical immunology 15 32458183
2020 A novel apidaecin Api-PR19 synergizes with the gut microbial community to maintain intestinal health and promote growth performance of broilers. Journal of animal science and biotechnology 15 32551109
1991 Enzyme activities of urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) in healthy dogs. Zentralblatt fur Veterinarmedizin. Reihe A 15 1677227
2017 α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: the roles of α2AP in vascular dysfunction in systemic sclerosis. Arthritis research & therapy 14 28159016
2012 The novel Akt inhibitor API-1 induces c-FLIP degradation and synergizes with TRAIL to augment apoptosis independent of Akt inhibition. Cancer prevention research (Philadelphia, Pa.) 14 22345097
2006 Genomic and transcriptional analysis of protein heterogeneity of the honeybee venom allergen Api m 6. Insect molecular biology 14 17069633