Affinage

AMBP

Protein AMBP · UniProt P02760

Round 2 corrected
Length
352 aa
Mass
39.0 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AMBP encodes a liver-expressed precursor that is proteolytically cleaved in the Golgi to release two functionally distinct plasma proteins: alpha-1-microglobulin (A1M), a lipocalin with radical-scavenging, heme-binding/degrading, and reductase activities mediated by its Cys34 thiol and cooperating lysine residues (Lys92/118/130), and bikunin, a Kunitz-type serine protease inhibitor covalently cross-linked to inter-alpha-inhibitor heavy chains via a chondroitin 4-sulfate glycosaminoglycan bridge at Ser-10 (PMID:2430261, PMID:15683711, PMID:1898736). A1M circulates in free form and in covalent complexes with IgA, prothrombin, and albumin, functions as an extracellular antioxidant scavenging heme and organic radicals, and inhibits neutrophil chemotaxis and lymphocyte immunological functions (PMID:6196366, PMID:9183005, PMID:2419908, PMID:11877257, PMID:17766242). In valvular interstitial cells, AMBP suppresses osteoblastic differentiation by competitively binding the zinc finger domain of FHL3, promoting proteasomal degradation of phospho-ERK1/2 and phospho-JNK and thereby reducing RUNX2/OSTERIX-driven calcification (PMID:40225558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1977 High

    Establishing the biochemical identity of alpha-1-microglobulin (protein HC) as a discrete low-molecular-weight plasma glycoprotein resolved its existence as a measurable circulating protein distinct from other lipocalins.

    Evidence Sequential gel filtration and ion-exchange chromatography purification from human urine with physicochemical characterization

    PMID:72071

    Open questions at the time
    • No knowledge of biosynthetic origin or gene structure
    • Functional role unknown
  2. 1983 High

    Discovery that A1M forms a covalent complex with IgA in plasma revealed that A1M exists in both free and macromolecular-bound pools, raising the question of the biological significance of complex formation.

    Evidence Immunosorption, gel chromatography, SDS-PAGE, and immunoblotting of plasma from normal and IgA-deficient individuals

    PMID:6196366

    Open questions at the time
    • Nature of covalent bond to IgA not fully characterized
    • Functional consequence of complex formation unclear
  3. 1986 High

    Cloning of the AMBP cDNA resolved the surprising finding that a single precursor polypeptide encodes two structurally unrelated secreted proteins—A1M and the Kunitz-type inhibitor bikunin—separated by dibasic residues, establishing the gene's unique bipartite architecture.

    Evidence cDNA cloning and sequencing from human liver library with protein sequence alignment

    PMID:2430261

    Open questions at the time
    • Protease responsible for precursor cleavage not identified
    • Regulatory logic for co-expression of two unrelated proteins unknown
  4. 1986 High

    Demonstration that A1M and its IgA complex inhibit neutrophil chemotaxis at physiological concentrations established the first immunomodulatory function for A1M.

    Evidence In vitro neutrophil chemotaxis assay with purified A1M and A1M–IgA complex, dose-response analysis

    PMID:2419908

    Open questions at the time
    • Receptor or molecular target on neutrophils unknown
    • In vivo relevance of chemotaxis inhibition undemonstrated
  5. 1991 High

    Elucidation of the protein–glycosaminoglycan–protein (PGP) cross-link, in which bikunin's Ser-10-linked chondroitin 4-sulfate chain is esterified to the C-terminal Asp of the heavy chain, resolved the molecular basis of inter-alpha-inhibitor assembly.

    Evidence Chondroitin sulfate-degrading enzyme digestion, NaOH sensitivity, and biochemical analysis of cross-link chemistry, confirmed by mass spectrometry in a 1993 follow-up

    PMID:1898736 PMID:7682553

    Open questions at the time
    • Enzyme(s) catalyzing the ester cross-link not identified
    • Stoichiometry and dynamics of heavy chain exchange not resolved
  6. 1997 High

    Identification of covalent disulfide-linked A1M complexes with prothrombin and albumin expanded the repertoire of A1M binding partners and showed that complex formation does not impair partner functions (prothrombin cleavage, albumin fatty-acid binding).

    Evidence Anti-A1M affinity chromatography, SDS-PAGE under reducing/non-reducing conditions, functional cleavage and binding assays

    PMID:9183005

    Open questions at the time
    • Physiological purpose of these complexes remains unclear
    • Cysteine residue(s) on A1M mediating the disulfide bonds not mapped
  7. 2002 High

    Discovery that A1M undergoes C-terminal truncation (releasing the LIPR tetrapeptide to expose Cys34) and subsequently binds and degrades heme established a direct heme-scavenging function linking A1M to protection against hemolysis-induced oxidative stress.

    Evidence In vitro incubation of A1M with erythrocyte membranes and oxyhemoglobin, spectroscopic analysis, detection of truncated form in human urine

    PMID:11877257

    Open questions at the time
    • Protease responsible for C-terminal truncation not identified
    • Products of heme degradation not fully characterized
  8. 2005 High

    Site-directed mutagenesis of Cys34, Lys92, Lys118, and Lys130 demonstrated that A1M possesses intrinsic reductase and dehydrogenase activities with the Cys34 thiolate as the primary catalytic group cooperating with the three lysine residues, unifying its radical-scavenging and reductase functions under a single active-site mechanism.

    Evidence In vitro reductase assays with multiple substrates (cytochrome c, methemoglobin, NBT, ferricyanide), SOD inhibition, NADH/NADPH enhancement, site-directed mutagenesis

    PMID:15683711

    Open questions at the time
    • Three-dimensional structural basis of catalytic mechanism not resolved at atomic level
    • Physiological electron donor in vivo not established
  9. 2005 High

    Demonstration that the AMBP gene is expressed in kidney proximal tubular cells under HNF-4 transcriptional control and induced by oxalate, with the precursor remaining uncleaved in renal cells, revealed tissue-specific processing and a potential role outside the liver.

    Evidence EMSA, supershift assay, transfection reporter studies, co-immunoprecipitation, in situ hybridization in rat kidney and LLC-PK1 cells

    PMID:15533056

    Open questions at the time
    • Function of uncleaved AMBP precursor in kidney not defined
    • Whether oxalate induction is protective or pathological not established
  10. 2007 High

    Kinetic and mass spectrometric characterization of A1M–ABTS radical reactions revealed a dual mechanism—radical reduction and covalent radical trapping on tyrosine residues—both dependent on the Cys34 thiolate, defining A1M as a broad-spectrum radical scavenger.

    Evidence In vitro radical scavenging kinetics and LC/MS identification of covalent ABTS–tyrosine adducts with Cys34-blocking controls

    PMID:17766242

    Open questions at the time
    • Identity and relevance of physiological radical substrates not fully characterized
    • Relative contribution of reduction vs. covalent trapping in vivo unknown
  11. 2025 High

    Identification of FHL3 as a direct binding partner through which AMBP suppresses aortic valve calcification—by competing for FHL3's zinc finger domain and thereby promoting proteasomal degradation of phospho-ERK1/2 and phospho-JNK—revealed a previously unknown signaling function for AMBP in cardiovascular disease beyond its classical antioxidant role.

    Evidence RNA-seq, co-immunoprecipitation, AlphaFold3 structural modeling, AAV-mediated AMBP overexpression in ApoE−/− mice, in vitro knockdown, pathway inhibitor/agonist validation

    PMID:40225558

    Open questions at the time
    • Whether the anti-calcification effect is mediated by the uncleaved precursor or the released A1M moiety is not resolved
    • Independent replication in a second in vivo model is lacking
    • Whether FHL3 interaction occurs in tissues other than valvular interstitial cells is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the protease(s) responsible for precursor cleavage and A1M C-terminal truncation, the in vivo electron donor for A1M reductase activity, the structural basis of radical trapping at atomic resolution, and the function of the uncleaved AMBP precursor in extrahepatic tissues such as kidney.
  • No crystal or cryo-EM structure of full-length AMBP or A1M–heme complex
  • Physiological reductase substrates in vivo remain unidentified
  • Protease(s) for precursor cleavage and C-terminal processing unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 3 GO:0016491 oxidoreductase activity 3 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 4 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-162582 Signal Transduction 1
Partners
ALBF2FHL3IGAITIH2
Complex memberships
inter-alpha-trypsin inhibitor (bikunin–heavy chain complex)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The AMBP mRNA encodes both alpha-1-microglobulin (protein HC) at the amino-terminus and the Kunitz-type proteinase inhibitor HI-30 (bikunin) at the carboxy-terminus, preceded by a signal sequence; the two protein sequences are separated by two arginine residues, establishing that a single gene precursor produces two structurally unrelated plasma proteins. cDNA cloning and sequencing from human liver library; protein sequence alignment Nucleic acids research High 2430261
1977 Alpha-1-microglobulin (protein HC) was purified from human urine and characterized as a low-molecular-weight glycoprotein (~26 kDa) with heterogeneous charge, establishing its basic biochemical identity as a plasma/urine protein. Sequential biochemical purification (gel filtration, ion-exchange chromatography), physicochemical characterization The Journal of biological chemistry High 72071
1983 Alpha-1-microglobulin (protein HC) forms a covalent high-molecular-weight complex with IgA in human plasma; the complex is absent in patients with selective IgA deficiency, and the complex-bound alpha-1-microglobulin carries the same yellow-brown chromophore as the free form. Immunosorption, gel chromatography, SDS-PAGE, immunoblotting, quantitative crossed immunoelectrophoresis The Journal of biological chemistry High 6196366
1981 Bikunin (urinary trypsin inhibitor, the light chain product of AMBP) carries two glycosaminoglycan chains: one O-glycosidically linked to Ser-10 via the N-terminal extension peptide, and one N-glycosidically linked via Asn-24 in the inhibitory Kunitz-type domain. Affinity chromatography purification, carbohydrate composition analysis, sequence analysis Hoppe-Seyler's Zeitschrift fur physiologische Chemie High 6171497
1991 The heavy and light protein chains of pre-alpha-inhibitor (which includes bikunin, the AMBP light-chain product) are covalently cross-linked by a protein-glycosaminoglycan-protein (PGP) structure: a chondroitin 4-sulfate chain O-glycosidically linked to Ser-10 of bikunin is esterified via its C-6 of an internal N-acetylgalactosamine to the alpha-carbon of the C-terminal Asp of the heavy chain. Protein and carbohydrate analytical techniques, chondroitin sulfate-degrading enzyme sensitivity assays, NaOH sensitivity The Journal of biological chemistry High 1898736
1993 The protein-glycosaminoglycan-protein (PGP) cross-link in HC2/bikunin (the AMBP-derived light chain complexed with heavy chain 2) is mediated by a chondroitin-4-sulfate chain O-linked to Ser-10 of bikunin, with the C-terminal Asp648 of heavy chain 2 esterified to C-6 of an internal N-acetylgalactosamine, confirmed by mass spectrometry and enzyme sensitivity. Biochemical assays, chondroitin sulfate-degrading enzyme digestion, NaOH treatment, SDS-PAGE, mass spectrometric analysis of cross-linking peptides The Journal of biological chemistry High 7682553
1986 Protein HC (alpha-1-microglobulin) and its IgA complex inhibit neutrophil chemotaxis in a dose-dependent manner in response to endotoxin-activated serum, without affecting random migration; concentrations sufficient for significant inhibition occur in plasma from healthy and diseased individuals and in synovial fluid from rheumatoid arthritis patients. In vitro neutrophil chemotaxis assay with purified protein HC and protein HC–IgA complex; plasma from IgA-deficient patients Proceedings of the National Academy of Sciences of the United States of America High 2419908
2000 Alpha-1-microglobulin is a lipocalin with a hydrophobic ligand-binding pocket and carries a heterogeneous yellow-brown chromophore consisting of small prosthetic groups covalently attached to amino acid residues at the entrance of the lipocalin pocket; it also has immunosuppressive properties inhibiting immunological functions of white blood cells in vitro. Biochemical characterization, structural analysis, in vitro immunosuppression assays Biochimica et biophysica acta High 11058759
2002 Exposure of alpha-1-microglobulin to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin releases a C-terminally truncated form (t-alpha-1-microglobulin) lacking the LIPR tetrapeptide and with a free Cys34 thiol group; this t-form binds heme and the resulting complex undergoes spectral rearrangement indicative of heme degradation with concomitant formation of a heterogeneous chromophore on the protein. In vitro incubation with erythrocyte membranes/oxyhemoglobin; spectroscopic analysis; identification of t-form in normal and pathologic human urine Blood High 11877257
1997 Alpha-1-microglobulin forms covalent complexes with prothrombin and albumin in human plasma via disulfide bonds (for prothrombin, 1:1 and 1:2 complexes of ~110 and ~145 kDa); the alpha-1-microglobulin molecules bind to peptides released upon prothrombin activation and do not inhibit prothrombin cleavage by factor Xa; the albumin complex does not block fatty-acid binding by albumin. Anti-(alpha1-microglobulin) affinity chromatography, immunoblotting, SDS-PAGE under reducing/non-reducing conditions, functional cleavage assays European journal of biochemistry High 9183005
2002 The AMBP protein (alpha-1-microglobulin/bikunin precursor) can self-associate and form dimers; alpha-1-microglobulin binds to its precursor AMBP, whereas bikunin does not; in renal tubular cells, A1M and bikunin co-precipitate indicating the precursor protein is not cleaved in this compartment (unlike in liver Golgi). Yeast two-hybrid system, in vitro dimerization assay, co-immunoprecipitation in renal tubular cells Archives of biochemistry and biophysics Medium 11883904
2004 The HEV ORF3 phosphoprotein specifically interacts with AMBP (alpha-1-microglobulin/bikunin precursor) and with alpha-1-microglobulin alone; ORF3 co-localizes with alpha-1-microglobulin and causes its disappearance from the Golgi compartment; pulse-labeling experiments show that ORF3 expedites secretion of alpha-1-microglobulin from hepatocytes, as confirmed by co-localization with fluorescence resonance energy transfer analysis. Yeast two-hybrid screen of human liver cDNA library; COS-1 cell co-immunoprecipitation; His6 pull-down; co-localization by fluorescence microscopy; FRET analysis; pulse-labeling; secretory pathway inhibitor studies The Journal of biological chemistry High 15037615
2005 The AMBP gene is inducible by oxalate in renal proximal tubular cells (LLC-PK1 and rat kidney), in addition to liver; in renal tubular cells the precursor protein is not cleaved (A1M and bikunin co-precipitate); the transcription factor HNF-4 (or an HNF-4-like protein) is present in kidney and regulates AMBP gene expression via A1M-specific cis elements, as demonstrated by EMSA, supershift assay, and transfection studies; expression is restricted to renal tubular cells by in situ hybridization. Western blotting, EMSA, supershift assay, immunoreactivity assay, transfection-based reporter studies, co-immunoprecipitation, in situ hybridization, immunocytochemistry The Biochemical journal High 15533056
2005 Alpha-1-microglobulin has catalytic reductase and NADH-dehydrogenase-like activities: it reduces cytochrome c, methemoglobin, nitroblue tetrazolium, and ferricyanide; reduction of cytochrome c and NBT is mediated via superoxide anions (inhibited by superoxide dismutase); biological electron donors (NADH, NADPH, ascorbate) enhance cytochrome c reduction ~30-fold; site-directed mutagenesis of Cys34, Lys92, Lys118, and Lys130 shows that the Cys34 thiol group mediates redox activity in cooperation with the lysyl residues. In vitro reductase assays, superoxide dismutase inhibition, NADH/NADPH/ascorbate supplementation, site-directed mutagenesis of Cys34 and Lys residues, thiol group chemistry Free radical biology & medicine High 15683711
2007 Alpha-1-microglobulin reacts with ABTS radicals via two mechanisms: reduction of ABTS radical to ABTS (apparent rate constant ~6.3 × 10³ M⁻¹ s⁻¹), and covalent attachment of ABTS radical to tyrosine residues forming a purple derivative; both reactions depend on the Cys34 thiolate group; LC/MS confirmed covalent ABTS attachment to tyrosines. In vitro radical scavenging assay, LC/MS analysis of reaction products, Cys34 thiol group chemistry (blocking experiments) The Journal of biological chemistry High 17766242
2009 In preeclampsia, plasma concentrations of alpha-1-microglobulin and the heme-degrading truncated form t-alpha-1-microglobulin (in urine) are significantly increased; alpha-1-microglobulin levels correlate strongly with plasma hemoglobin concentrations and placental expression, consistent with alpha-1-microglobulin functioning as an extracellular heme scavenger and antioxidant responding to hemoglobin-induced oxidative stress. ELISA, immunoblotting, mRNA quantitation, correlation analysis in plasma/urine/placenta from preeclamptic vs. normal pregnant women Free radical biology & medicine Medium 19879940
2025 AMBP protects valvular interstitial cells from osteoblastic differentiation and aortic valve calcification by competitively binding to the zinc finger domain of FHL3 (four-and-a-half LIM domain protein 3); this disrupts FHL3-mediated protection of phospho-ERK1/2 and phospho-JNK from ubiquitin-proteasome-mediated degradation, reducing ERK1/2 and JNK phosphorylation and suppressing RUNX2/OSTERIX expression and calcium deposition. RNA sequencing, co-immunoprecipitation, AlphaFold3-based crystal structure simulations, adeno-associated virus-mediated AMBP overexpression in ApoE-/- mice, AMBP knockdown in vitro, western blotting, immunofluorescence, histopathology, echocardiography, ERK1/2 and JNK inhibitor/agonist validation Theranostics High 40225558

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
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1994 Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Molecular and cellular biology 840 7511210
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
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1996 Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor. Immunity 527 8574854
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
1986 The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-alpha-trypsin inhibitor also encodes alpha-1-microglobulin (protein HC). Nucleic acids research 215 2430261
2005 Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science (New York, N.Y.) 210 15774723
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2017 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. Journal of proteome research 185 28675934
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1991 Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor. The Journal of biological chemistry 157 1898736
2013 Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis. Journal of proteomics 139 24211404
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2015 The future of host cell protein (HCP) identification during process development and manufacturing linked to a risk-based management for their control. Biotechnology and bioengineering 125 25998019
2008 Secretome analysis uncovers an Hcp-family protein secreted via a type VI secretion system in Agrobacterium tumefaciens. Journal of bacteriology 124 18263727
1977 Human alpha1-microglobulin. Purification procedure, chemical and physiochemical properties. The Journal of biological chemistry 115 72071
2002 Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties. Blood 108 11877257
2009 Quorum sensing regulation of the two hcp alleles in Vibrio cholerae O1 strains. PloS one 105 19701456
2000 alpha(1)-Microglobulin: a yellow-brown lipocalin. Biochimica et biophysica acta 105 11058759
1993 Presence of the protein-glycosaminoglycan-protein covalent cross-link in the inter-alpha-inhibitor-related proteinase inhibitor heavy chain 2/bikunin. The Journal of biological chemistry 102 7682553
2007 The lipocalin alpha1-microglobulin has radical scavenging activity. The Journal of biological chemistry 97 17766242
1989 Human plasma inter-alpha-trypsin inhibitor is encoded by four genes on three chromosomes. European journal of biochemistry 95 2465147
2009 Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidative heme scavenger alpha(1)-microglobulin in preeclampsia. Free radical biology & medicine 90 19879940
2001 HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres. The Journal of cell biology 89 11402064
1981 Kunitz-type proteinase inhibitors derived by limited proteolysis of the inter-alpha-trypsin inhibitor, V. Attachments of carbohydrates in the human urinary trypsin inhibitor isolated by affinity chromatography. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 89 6171497
2012 Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability. Journal of proteomics 81 22516433
1996 Vibrio cholerae Hcp, a secreted protein coregulated with HlyA. Infection and immunity 80 8557353
2005 The yeast EDC1 mRNA undergoes deadenylation-independent decapping stimulated by Not2p, Not4p, and Not5p. The EMBO journal 78 15706350
1986 Human protein HC and its IgA complex are inhibitors of neutrophil chemotaxis. Proceedings of the National Academy of Sciences of the United States of America 78 2419908
2006 Human colostrum: identification of minor proteins in the aqueous phase by proteomics. Proteomics 77 16502470
1983 Isolation of human complex-forming glycoprotein, heterogeneous in charge (protein HC), and its IgA complex from plasma. Physiochemical and immunochemical properties, normal plasma concentration. The Journal of biological chemistry 76 6196366
1997 Prothrombin, albumin and immunoglobulin A form covalent complexes with alpha1-microglobulin in human plasma. European journal of biochemistry 75 9183005
2005 Redox properties of the lipocalin alpha1-microglobulin: reduction of cytochrome c, hemoglobin, and free iron. Free radical biology & medicine 74 15683711
1997 Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction. Experimental hematology 72 9216734
1999 HCP-1, a protein involved in chromosome segregation, is localized to the centromere of mitotic chromosomes in Caenorhabditis elegans. The Journal of cell biology 67 10545493
2016 The roles of the hybrid cluster protein, Hcp and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress. Molecular microbiology 65 26879449
2016 Adhesive Pili in UTI Pathogenesis and Drug Development. Pathogens (Basel, Switzerland) 65 26999218
2013 Association of procalcitonin with acute pyelonephritis and renal scars in pediatric UTI. Pediatrics 65 23629615
2004 The ORF3 protein of hepatitis E virus interacts with liver-specific alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin precursor (AMBP) and expedites their export from the hepatocyte. The Journal of biological chemistry 65 15037615
2016 Modulating fcc and hcp Ruthenium on the Surface of Palladium-Copper Alloy through Tunable Lattice Mismatch. Angewandte Chemie (International ed. in English) 60 27010243
2003 Antibiotic activity against urinary tract infection (UTI) isolates of vancomycin-resistant enterococci (VRE): results from the 2002 North American Vancomycin Resistant Enterococci Susceptibility Study (NAVRESS). The Journal of antimicrobial chemotherapy 60 12888592
2006 Cation exchange chromatography in antibody purification: pH screening for optimised binding and HCP removal. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 55 17113367
2013 Evaluation of the roles played by Hcp and VgrG type 6 secretion system effectors in Aeromonas hydrophila SSU pathogenesis. Microbiology (Reading, England) 53 23519162
2007 Urinary symptoms in adolescent females: STI or UTI? The Journal of adolescent health : official publication of the Society for Adolescent Medicine 53 17448399
2017 Whole-genome comparison of urinary pathogenic Escherichia coli and faecal isolates of UTI patients and healthy controls. International journal of medical microbiology : IJMM 50 29031453
2010 Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in modulating activation of host immune cells. Microbiology (Reading, England) 49 20798163
2018 The gp27-like Hub of VgrG Serves as Adaptor to Promote Hcp Tube Assembly. Journal of molecular biology 47 30031895
1995 Sequential correlation of anomeric ribose protons and intervening phosphorus in RNA oligonucleotides by a 1H, 13C, 31P triple resonance experiment: HCP-CCH-TOCSY. Journal of biomolecular NMR 44 7533570
2002 Utility of blood cultures in febrile children with UTI. The American journal of emergency medicine 41 12098170
2013 Structural characterization and immunomodulatory effect of a polysaccharide HCP-2 from Houttuynia cordata. Carbohydrate polymers 38 24528726
2010 The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells. PloS one 38 20711431
2014 Improved detection of host cell proteins (HCPs) in a mammalian cell-derived antibody drug using liquid chromatography/mass spectrometry in conjunction with an HCP-enrichment strategy. Rapid communications in mass spectrometry : RCM 37 24623688
2000 Hybrid-cluster protein (HCP) from Desulfovibrio vulgaris (Hildenborough) at 1.6 A resolution. Biochemistry 36 11106482
2018 Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis. Nature communications 34 29559651
1976 Isolation of a novel glycoprotein (EDC1) from the urine of a patient with acute myelocytic leukemia. Cancer research 34 57827
2022 Immunomodulation therapy offers new molecular strategies to treat UTI. Nature reviews. Urology 32 35732832
2020 The oxidative fumarase FumC is a key contributor for E. coli fitness under iron-limitation and during UTI. PLoS pathogens 32 32106241
2015 Virulence characteristics of hcp (+) Campylobacter jejuni and Campylobacter coli isolates from retail chicken. Gut pathogens 32 26207145
2019 Immunogenicity and protective efficacy of mucosal delivery of recombinant hcp of Campylobacter jejuni Type VI secretion system (T6SS) in chickens. Molecular immunology 31 31078054
2003 Reduced hybrid cluster proteins (HCP) from Desulfovibrio desulfuricans ATCC 27774 and Desulfovibrio vulgaris (Hildenborough): X-ray structures at high resolution using synchrotron radiation. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 31 12764602
2019 Fabrication of Ultra-Pure Anisotropic Zinc Oxide Nanoparticles via Simple and Cost-Effective Route: Implications for UTI and EAC Medications. Biological trace element research 30 31529241
2015 Crystal Structure of Hcp from Acinetobacter baumannii: A Component of the Type VI Secretion System. PloS one 30 26079269
2008 Procalcitonin for the early prediction of renal parenchymal involvement in children with UTI: preliminary results. International urology and nephrology 30 18836845
2021 The Breadth and Molecular Basis of Hcp-Driven Type VI Secretion System Effector Delivery. mBio 29 34061601
2020 Virulence, resistance and clonality of Proteus mirabilis isolated from patients with community-acquired urinary tract infection (CA-UTI) in Brazil. Microbial pathogenesis 29 33246088
2013 Hcp and VgrG1 are secreted components of the Helicobacter hepaticus type VI secretion system and VgrG1 increases the bacterial colitogenic potential. Cellular microbiology 29 23278999
2008 Detection of urinary tract infection (UTI) in long-term care setting: Is the multireagent strip an adequate diagnostic tool? Archives of gerontology and geriatrics 29 18314207
2021 Sensing of intracellular Hcp levels controls T6SS expression in Vibrio cholerae. Proceedings of the National Academy of Sciences of the United States of America 28 34161288
2017 Dual Data-Independent Acquisition Approach Combining Global HCP Profiling and Absolute Quantification of Key Impurities during Bioprocess Development. Analytical chemistry 28 29235848
2016 Roles of Hcp family proteins in the pathogenesis of the porcine extraintestinal pathogenic Escherichia coli type VI secretion system. Scientific reports 28 27229766
2005 Oxalate-inducible AMBP gene and its regulatory mechanism in renal tubular epithelial cells. The Biochemical journal 28 15533056
2023 Antimicrobial efficacy of Mentha piperata-derived biogenic zinc oxide nanoparticles against UTI-resistant pathogens. Scientific reports 27 37696980
2016 Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI. American journal of physiology. Renal physiology 27 27335375
2005 HCP-4/CENP-C promotes the prophase timing of centromere resolution by enabling the centromere association of HCP-6 in Caenorhabditis elegans. Molecular and cellular biology 27 15767665
2020 Anti-platelet adhesion and in situ capture of circulating endothelial progenitor cells on ePTFE surface modified with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and hemocompatible peptide 1 (HCP-1). Colloids and surfaces. B, Biointerfaces 26 32447201
2013 Clinical factors associated with shock in bacteremic UTI. International urology and nephrology 26 23616061
2018 Diverse roles of Hcp family proteins in the environmental fitness and pathogenicity of Aeromonas hydrophila Chinese epidemic strain NJ-35. Applied microbiology and biotechnology 24 29862449
2019 Metagenomics in diagnosis and improved targeted treatment of UTI. World journal of urology 23 30944967
2016 The S. pombe mRNA decapping complex recruits cofactors and an Edc1-like activator through a single dynamic surface. RNA (New York, N.Y.) 23 27354705
2011 Association and expression quantitative trait loci (eQTL) analysis of porcine AMBP, GC and PPP1R3B genes with meat quality traits. Molecular biology reports 23 21947951
2004 Importance of shear in the bcc-to-hcp transformation in iron. Physical review letters 22 15447350
2016 Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia compared to normotensive pregnant women. Proteomics. Clinical applications 21 27615121
2016 Urine Concentration and Pyuria for Identifying UTI in Infants. Pediatrics 21 27940788
2012 The critical role of adrenomedullin and its binding protein, AMBP-1, in neuroprotection. Biological chemistry 21 22628306
2002 Expression of the AMBP gene transcript and its two protein products, alpha(1)-microglobulin and bikunin, in mouse embryogenesis. Mechanisms of development 21 12204273
2021 Targeted CHO cell engineering approaches can reduce HCP-related enzymatic degradation and improve mAb product quality. Biotechnology and bioengineering 20 34125434
2021 Proteus mirabilis from community-acquired urinary tract infections (UTI-CA) shares genetic similarity and virulence factors with isolates from chicken, beef and pork meat. Microbial pathogenesis 20 34280499
2002 The liver-specific human alpha(1)-microglobulin/bikunin precursor (AMBP) is capable of self-association. Archives of biochemistry and biophysics 19 11883904
2022 Structural connectivity of the ANT region based on human ex-vivo and HCP data. Relevance for DBS in ANT for epilepsy. NeuroImage 17 35948264
2023 A novel HCP (heparin-binding protein-C reactive protein-procalcitonin) inflammatory composite model can predict severe acute pancreatitis. Scientific reports 16 37296194
2019 Incompatibility of Vibrio fischeri Strains during Symbiosis Establishment Depends on Two Functionally Redundant hcp Genes. Journal of bacteriology 16 31331977
2018 The different roles of hcp1 and hcp2 of the type VI secretion system in Escherichia coli strain CE129. Journal of basic microbiology 16 30247772
2016 Constraints on Earth's inner core composition inferred from measurements of the sound velocity of hcp-iron in extreme conditions. Science advances 16 26933678
2015 Protective efficacy of recombinant hemolysin co-regulated protein (Hcp) of Aeromonas hydrophila in common carp (Cyprinus carpio). Fish & shellfish immunology 16 26093203
1980 Effect of plasma inter-alpha trypsin inhibitor and cancer-related glycoprotein EDC1 on phytohemagglutinin-induced thymidine uptake in lymphocytes. Cancer research 16 6162547
2020 Roles of the Hcp family proteins in the pathogenicity of Salmonella typhimurium 14028s. Virulence 15 33300449
2018 TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain. Scientific reports 14 29739958
2016 Antibiotic Resistance, RAPD- PCR Typing of Multiple Drug Resistant Strains of Escherichia Coli From Urinary Tract Infection (UTI). Journal of clinical and diagnostic research : JCDR 14 27134870
2002 Reagent strip diagnosis of UTI in a high-risk population. The American journal of emergency medicine 14 11880876
2024 Inflammatory markers for improved recurrent UTI diagnosis in postmenopausal women. Life science alliance 13 38331474
2021 Bladder Exposure to Gardnerella Activates Host Pathways Necessary for Escherichia coli Recurrent UTI. Frontiers in cellular and infection microbiology 13 34938672
2020 Genetic analysis of ESBL-producing Klebsiella pneumoniae isolated from UTI patients in Indonesia. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 13 32888833
2019 The Porphyromonas gingivalis Hybrid Cluster Protein Hcp Is Required for Growth with Nitrite and Survival with Host Cells. Infection and immunity 13 30670550
2019 UTI patients have pre-existing antigen-specific antibody titers against UTI vaccine antigens. Vaccine 13 31320216
2013 Development of a method for urine bikunin/urinary trypsin inhibitor (UTI) quantitation and structural characterization: Application to type 1 and type 2 diabetes. Electrophoresis 13 24115191
1990 Plasma inter-alpha-trypsin inhibitor-related urinary glycoprotein EDC1 inhibits the growth of a Burkitt's lymphoma cell line. Journal of cellular biochemistry 13 1692840
2020 Genomic Analysis of CTX-M-Group-1-Producing Extraintestinal Pathogenic E. coli (ExPEc) from Patients with Urinary Tract Infections (UTI) from Colombia. Antibiotics (Basel, Switzerland) 12 33322118
2015 Relative stability of the FCC and HCP polymorphs with interacting polymers. Soft matter 12 25408554
2010 Unusual organization, complexity and redundancy at the Escherichia coli hcp-hcr operon promoter. The Biochemical journal 12 20533909
2002 Protective effects of urinary trypsin inhibitor (UTI) on hepatic microvasculature in hypotensive brain-dead rats. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 12 12145560
2022 Effect of Hcp Iron Ion Regulation on the Interaction Between Acinetobacter baumannii With Human Pulmonary Alveolar Epithelial Cells and Biofilm Formation. Frontiers in cellular and infection microbiology 11 35281445
2023 Synergistic stabilization of microtubules by BUB-1, HCP-1, and CLS-2 controls microtubule pausing and meiotic spindle assembly. eLife 10 36799894
2023 Rapid purification of mAb using protein a membranes yielding high HCP clearance. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 10 38154412
2023 Psychosocial burden and healthcare disillusionment in recurrent UTI: a large-scale international survey of patient perspectives. Frontiers in urology 10 40778078
2020 Questioning coverage values determined by 2D western blots: A critical study on the characterization of anti-HCP ELISA reagents. Biotechnology and bioengineering 10 33241851
2016 Biomimickry of UPEC Cytoinvasion: A Novel Concept for Improved Drug Delivery in UTI. Pathogens (Basel, Switzerland) 10 26861401
2014 Immunization with H7-HCP-tir-intimin significantly reduces colonization and shedding of Escherichia coli O157:H7 in goats. PloS one 10 24632795
2010 Quantitative 2D and 3D Gamma-HCP experiments for the determination of the angles alpha and zeta in the phosphodiester backbone of oligonucleotides. Journal of the American Chemical Society 10 20614918
2025 AMBP protects against aortic valve calcification by inhibiting ERK1/2 and JNK pathways mediated by FHL3. Theranostics 9 40225558
2022 Effect of the Type VI Secretion System Secreted Protein Hcp on the Virulence of Aeromonas salmonicida. Microorganisms 9 36557560
2021 An innovative standard for LC-MS-based HCP profiling and accurate quantity assessment: Application to batch consistency in viral vaccine samples. Proteomics 9 33459490
2017 Application of a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme for transcription start site mapping. RNA (New York, N.Y.) 9 29101277
2023 The molybdate-binding protein ModA is required for Proteus mirabilis-induced UTI. Frontiers in microbiology 8 37180242
2022 The salmonella effector Hcp modulates infection response, and affects salmonella adhesion and egg contamination incidences in ducks. Frontiers in cellular and infection microbiology 8 36262184