Affinage

HP

Haptoglobin · UniProt P00738

Round 2 corrected
Length
406 aa
Mass
45.2 kDa
Annotated
2026-04-28
130 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Haptoglobin (HP) is a liver-derived serine protease homolog that has lost catalytic activity due to replacement of active-site His-57 and Ser-195 but retains high-affinity hemoglobin binding, forming complexes recognized by the macrophage scavenger receptor CD163 for Ca²⁺-dependent endocytosis and lysosomal catabolism, thereby preventing hemoglobin-driven oxidative damage and limiting bacterial iron acquisition (PMID:6997877, PMID:11196644, PMID:7036344). The Hp2 allele arose from an intragenic non-homologous crossover duplication that extends the α-chain and alters multimerization, with recurring reversion deletions across human populations; the Hp1-1 phenotype confers superior antioxidant protection compared to Hp2-2, and this functional difference translates into differential cardiovascular risk in diabetic patients (PMID:6325933, PMID:26901066, PMID:18032779). The unprocessed precursor of Hp2 (pre-HP2/zonulin) contains an EGF-like motif that activates PAR2 and transactivates EGFR to increase intestinal tight-junction permeability—a function abolished upon proteolytic maturation into α2/β subunits—and zonulin is overexpressed in celiac disease mucosa (PMID:19805376). HP copy-number variation independently associates with hemoglobin levels and red cell counts, while cholesterol associations at the locus are driven predominantly by the adjacent HPR rs2000999 SNP in strong linkage disequilibrium (PMID:22433445, PMID:26901066).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1980 High

    Complete primary structure determination resolved a long-standing question about the evolutionary origin of haptoglobin, establishing it as a catalytically dead serine protease homolog with specific active-site substitutions (His→Lys, Ser→Ala) and a kringle-related α-chain.

    Evidence Full amino acid sequencing and disulfide mapping of Hp1-1, with statistical comparison to the serine protease family

    PMID:6997877

    Open questions at the time
    • No three-dimensional structure available at this time
    • Mechanism of high-affinity hemoglobin binding not explained by sequence alone
  2. 1982 High

    Demonstrating that haptoglobin rescues lethal bacterial infection synergized by free hemoglobin established a physiological bacteriostatic function through iron sequestration, moving beyond the prior view of HP as merely an antioxidant scavenger.

    Evidence Rat peritonitis model with E. coli + hemoglobin co-inoculation; haptoglobin co-administration fully prevented lethality

    PMID:7036344

    Open questions at the time
    • Whether bacteriostatic effect generalizes beyond E. coli
    • Relative contribution of iron withholding vs. oxidative protection in vivo
  3. 1984 High

    DNA sequencing of the Hp2 allele revealed that it arose by non-homologous crossover between Hp1F and Hp1S genes, explaining the molecular basis of the common human HP polymorphism and its effects on protein multimerization.

    Evidence Genomic DNA sequencing of HP2 allelic region with crossover breakpoint mapping

    PMID:6325933

    Open questions at the time
    • Functional consequences of multimerization differences for hemoglobin clearance efficiency not yet quantified
    • Evolutionary selective pressures on the polymorphism unknown
  4. 2001 High

    Identification of CD163 as the receptor for haptoglobin-hemoglobin complexes closed a critical gap in the clearance pathway, showing that a neoepitope exposed only upon complex formation enables Ca²⁺-dependent macrophage endocytosis, and that multimeric Hp2-2 complexes bind CD163 with higher functional affinity than dimeric Hp1-1.

    Evidence Expression cloning; binding assays in CD163-transfected and endogenously expressing cells; co-immunoprecipitation; phenotype comparison

    PMID:11196644

    Open questions at the time
    • Structural basis of the neoepitope on the Hp-Hb complex not defined
    • Whether higher CD163 affinity of Hp2-2 complexes compensates for their inferior antioxidant capacity
  5. 2007 Medium

    A promoter SNP (A-61C) in haplotype with Hp2 was shown to reduce HP expression, providing a mechanistic explanation for discordant malaria susceptibility results and establishing that HP levels are regulated at the transcriptional level independently of the structural CNV.

    Evidence Cohort malaria surveillance; pyrosequencing; in vitro promoter expression assays

    PMID:17426810

    Open questions at the time
    • Promoter effect not confirmed across diverse populations
    • Interaction between promoter SNP and acute-phase induction not tested
  6. 2007 High

    A randomized controlled trial demonstrated that vitamin E supplementation reduces cardiovascular events specifically in Hp2-2 diabetic individuals, providing clinical evidence that the genotype-dependent antioxidant deficit of Hp2-2 is physiologically consequential and pharmacologically addressable.

    Evidence Double-blind placebo-controlled RCT in 1434 Hp2-2 type 2 diabetes patients; 18-month composite cardiovascular endpoint

    PMID:18032779

    Open questions at the time
    • Mechanism linking inferior Hp2-2 antioxidant function to atherosclerosis not fully elucidated at the molecular level
    • Replication in independent trial populations needed
  7. 2009 High

    Identification of zonulin as the precursor form of Hp2 (pre-HP2) revealed a second, non-hemoglobin-related function: the uncleaved precursor activates PAR2→EGFR signaling via an EGF-like motif to open intestinal tight junctions, a function eliminated by proteolytic maturation, linking HP biology to celiac disease pathogenesis.

    Evidence Proteomic identification; siRNA knockdown; PAR2-knockout mice; EGFR activation and permeability assays; gene expression in celiac biopsies

    PMID:19805376

    Open questions at the time
    • Protease responsible for maturation cleavage not identified
    • Whether pre-HP1 also has barrier-modulatory activity not tested
    • Quantitative contribution of zonulin to celiac disease pathology vs. other permeability modulators unclear
  8. 2012 Medium

    Haplotype dissection separated the phenotypic effects at the HP/HPR locus, attributing cholesterol associations primarily to HPR rs2000999 and hematological associations (hemoglobin, red cell count) to the HP CNV itself.

    Evidence Linear regression and haplotype analysis in 2779 individuals with CNV and SNP genotyping

    PMID:22433445

    Open questions at the time
    • Mechanism by which HP CNV influences hematological parameters not established
    • Single-population cohort limits generalizability
  9. 2016 High

    Large-scale genomic analysis established that the Hp2 allele represents the ancestral derived state in hominins and that Hp1-like alleles arise by recurrent reversion deletions, linking these structural events to reduced LDL cholesterol through imputation in >22,000 individuals.

    Evidence Population genomic and SNP haplotype-based imputation; deletion breakpoint structural analysis

    PMID:26901066

    Open questions at the time
    • Molecular mechanism connecting HP structure to cholesterol metabolism not defined
    • Whether cholesterol effect is mediated by HP protein function or linkage to HPR not fully resolved
  10. 2018 Medium

    Quantification of α1-chain abundance within Hp2-1 heteromers showed that higher α1 content correlates with reduced delayed cerebral ischemia after subarachnoid hemorrhage, suggesting that α-chain composition modulates the antioxidant efficacy of heteromeric haptoglobin in cerebrovascular contexts.

    Evidence Prospective cohort (n=87); Western blot quantification of α-subunit ratios; clinical outcome correlation

    PMID:29902601

    Open questions at the time
    • Small single-center cohort
    • Causal relationship between α1 abundance and clinical outcome not established
    • Whether α1 chain proportion reflects transcriptional or post-translational regulation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of hemoglobin recognition by haptoglobin, the identity of the protease that cleaves pre-HP2/zonulin into mature subunits, and the direct molecular mechanism linking HP genotype to cholesterol metabolism remain unresolved.
  • No co-crystal structure of Hp-Hb complex at atomic resolution reported in timeline
  • Maturation protease for zonulin/pre-HP2 not identified
  • Direct mechanistic link between HP protein and LDL cholesterol levels not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 3
Pathway
GO:0016209 antioxidant activity 3 R-HSA-168256 Immune System 2 R-HSA-1500931 Cell-Cell communication 1 R-HSA-162582 Signal Transduction 1
Partners
CD163EGFRF2RL1HBA1HBB
Complex memberships
Haptoglobin-hemoglobin complex

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 Complete amino acid sequencing of human haptoglobin 1-1 established that the beta-chain (245 residues) shares 29-33% sequence identity with serine proteases (trypsin, chymotrypsin, elastase, thrombin, plasmin), identifying haptoglobin as a serine protease homolog. The active-site histidine-57 and serine-195 are replaced by lysine and alanine respectively, explaining catalytic inactivity, while Asp-102 and the trypsin specificity residue Asp-189 are retained. The alpha1 chain shows 25% identity to the fifth 'kringle' region of plasminogen activation peptide. Complete amino acid sequencing and disulfide arrangement determination; statistical comparison of primary structure to serine protease family Proceedings of the National Academy of Sciences of the United States of America High 6997877
1982 Haptoglobin functions as a natural bacteriostat by sequestering free hemoglobin and preventing its utilization by pathogenic bacteria. In rats co-inoculated intraperitoneally with E. coli and hemoglobin, simultaneous administration of haptoglobin fully protected against lethality, demonstrating that haptoglobin-hemoglobin binding limits iron availability for bacterial growth. In vivo rat lethality model with E. coli + hemoglobin challenge; haptoglobin co-administration rescue experiment Science (New York, N.Y.) High 7036344
1984 The Hp2 allele arose by an intragenic duplication within the HP gene generated by non-homologous crossing-over within different introns of two Hp1 genes (likely in an Hp1F/Hp1S heterozygote), producing a tandem partial duplication that extends the alpha-chain and alters multimerization properties of the resulting protein. DNA sequencing of the HP2 allelic region; structural analysis of crossover breakpoints Nature High 6325933
1997 Haptoglobin exerts multiple biological functions including: (1) antioxidant activity by binding and sequestering free hemoglobin for reticuloendothelial catabolism primarily in the liver; (2) antimicrobial activity; (3) stimulation of angiogenesis; (4) cholesterol-crystallization-promoting activity; and (5) immunomodulatory activity acting as an antagonist for receptor-ligand activation of the immune system. Biosynthesis occurs not only in the liver but also in adipose tissue and lung. Review integrating experimental biochemical and functional data from multiple studies European journal of clinical chemistry and clinical biochemistry Medium 9352226
2001 CD163, an acute phase-regulated macrophage scavenger receptor, was identified as the receptor that mediates endocytosis of haptoglobin-hemoglobin complexes. CD163 binds only the haptoglobin-hemoglobin complex (not free haptoglobin or free hemoglobin), indicating exposure of a receptor-binding neoepitope upon complex formation. The interaction is Ca2+-dependent and high affinity. Multimeric haptoglobin (Hp 2-2 phenotype) complexed with hemoglobin exhibits higher functional affinity for CD163 than dimeric haptoglobin (Hp 1-1 phenotype) complexes. Receptor identification by expression cloning; binding assays with transfected CD163-expressing cells and CD163-expressing myelo-monocytic lymphoma cells; co-immunoprecipitation; Ca2+-dependency assays; phenotype comparison Nature High 11196644
2002 PCR-based genotyping of the HP 1/2 polymorphism was validated against protein phenotyping in 249 individuals, confirming full concordance between DNA genotyping and protein electrophoresis. The method exploits the size difference between Hp1 and Hp2 alleles and is not confounded by Hp1F/1S subtypes or by the haptoglobin-related gene (HPR). Allele-specific PCR; agarose gel electrophoresis; restriction enzyme validation; parallel polyacrylamide gel electrophoresis protein phenotyping Clinical chemistry High 12194911
2007 A promoter SNP (A-61C) in the HP gene was found to be associated with decreased HP protein levels independent of HP phenotype, and this SNP exists in strong haplotype association with the Hp2 allele. The -61C allele was confirmed to reduce HP expression in vitro, providing a mechanistic explanation for previous conflicting results between HP phenotype and malaria susceptibility. Cohort study with active malaria surveillance; pyrosequencing; haplotype analysis; in vitro promoter expression studies PloS one Medium 17426810
2009 Human zonulin, the only known physiological modulator of intestinal epithelial tight junctions, was identified as the precursor form of haptoglobin-2 (pre-HP2). The single-chain pre-HP2/zonulin contains an EGF-like motif that activates proteinase-activated receptor 2 (PAR2), leading to transactivation of EGF receptor (EGFR) and increased intestinal permeability. siRNA silencing of PAR2 or PAR2-knockout mice prevented loss of barrier integrity. Proteolytic cleavage of zonulin/pre-HP2 into its mature alpha2- and beta-subunits abolished both EGFR activation and increased permeability. Zonulin is overexpressed in intestinal mucosa of celiac disease subjects. Proteomic identification from human sera; siRNA knockdown of PAR2; PAR2-knockout mice; EGF receptor activation assays; intestinal permeability assays; quantitative gene expression analysis in celiac disease biopsies Proceedings of the National Academy of Sciences of the United States of America High 19805376
2007 In individuals with type 2 diabetes mellitus carrying the HP 2-2 genotype (which produces a haptoglobin protein with inferior antioxidant protection compared to the Hp1 allelic product), vitamin E supplementation (400 U/day) significantly reduced the composite cardiovascular endpoint (MI, stroke, cardiovascular death) compared to placebo (2.2% vs 4.7%, P=0.01) at 18 months, demonstrating that the functional antioxidant difference between HP genotypes has clinically measurable consequences. Prospective randomized double-blind placebo-controlled clinical trial; n=1434 HP 2-2 DM individuals Arteriosclerosis, thrombosis, and vascular biology High 18032779
2012 Haplotype analysis of HP and the adjacent HPR (haptoglobin-related protein) gene revealed that the LDL-cholesterol and total cholesterol associations at this locus are driven by the HPR rs2000999 SNP, while the hemoglobin and red cell count associations derive primarily from the HP copy number variation (Hp1 vs Hp2 CNV). This dissection demonstrates distinct genotype-phenotype effects from two adjacent functionally related genes in strong linkage disequilibrium. Linear regression analysis in British Women's Heart and Health Study (n=2779); haplotype analysis; CNV genotyping; rs2000999 SNP genotyping Gene Medium 22433445
2016 The HP 1/2 copy number polymorphism has arisen from many recurring deletion events that revert an ancient hominin-specific exon duplication, making the Hp2 allele a derived state. Using SNP haplotype-based imputation in 22,288 individuals, these exonic HP deletions (reverting to Hp1-like structure) were associated with reduced LDL and total cholesterol levels. A promoter SNP affecting HP expression also contributes to cholesterol associations at this locus. Population genomic analysis; SNP haplotype imputation; association analysis in 22,288 individuals; structural analysis of deletion breakpoints Nature genetics High 26901066
2018 In patients with aneurysmal subarachnoid hemorrhage carrying the Hp2-1 phenotype, higher alpha1 chain expression in the Hp2-1 complex is associated with lower risk of delayed cerebral ischemia and angiographic vasospasm, suggesting that the relative abundance of the alpha1 subunit within the heterodimeric Hp2-1 protein modulates its protective antioxidant capacity against free hemoglobin toxicity. Prospective cohort study (n=87); Western blot quantification of alpha subunit band intensities normalized to albumin; correlation with delayed cerebral ischemia and vasospasm outcomes World neurosurgery Medium 29902601

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2873 20686565
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
2001 Identification of the haemoglobin scavenger receptor. Nature 1423 11196644
2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature genetics 817 18583979
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiological reviews 685 21248165
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
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2009 Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proceedings of the National Academy of Sciences of the United States of America 338 19805376
1992 The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation. Genetics 273 1644277
2012 Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences 249 22731712
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
1980 Covalent structure of human haptoglobin: a serine protease homolog. Proceedings of the National Academy of Sciences of the United States of America 247 6997877
1997 Biological functions of haptoglobin--new pieces to an old puzzle. European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies 242 9352226
2000 The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. The Journal of experimental medicine 238 10790422
1982 Haptoglobin: a natural bacteriostat. Science (New York, N.Y.) 238 7036344
2012 Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PloS one 222 22629362
2010 Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular psychiatry 220 20351714
2021 Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. The Journal of clinical investigation 212 34032635
1984 Duplication within the haptoglobin Hp2 gene. Nature 208 6325933
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2007 Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. Arteriosclerosis, thrombosis, and vascular biology 202 18032779
2002 Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR. Clinical chemistry 139 12194911
2009 An attenuated live vaccine based on highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) protects piglets against HP-PRRS. Veterinary microbiology 124 19339125
2013 An EAV-HP insertion in 5' Flanking region of SLCO1B3 causes blue eggshell in the chicken. PLoS genetics 101 23359636
2007 Amphipathic alpha-helical peptide, HP (2-20), and its analogues derived from Helicobacter pylori: pore formation mechanism in various lipid compositions. Biochimica et biophysica acta 98 17961502
2016 Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels. Nature genetics 85 26901066
2007 The neutrophil-activating protein of Helicobacter pylori (HP-NAP) as an immune modulating agent. FEMS immunology and medical microbiology 84 17521355
2006 Circannual control of hibernation by HP complex in the brain. Cell 82 16615897
2015 Developmental validation of the Quantifiler(®) HP and Trio Kits for human DNA quantification in forensic samples. Forensic science international. Genetics 71 26774100
2002 The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a potent stimulant of mast cells. European journal of immunology 68 11857341
2017 Secondary Haemophilus parasuis infection enhances highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection-mediated inflammatory responses. Veterinary microbiology 60 28532803
2009 Helicobacter pylori Hp(2-20) promotes migration and proliferation of gastric epithelial cells by interacting with formyl peptide receptors in vitro and accelerates gastric mucosal healing in vivo. Journal of immunology (Baltimore, Md. : 1950) 60 19692643
1995 Inheritance of unequal numbers of the genes encoding the human neutrophil defensins HP-1 and HP-3. The Journal of biological chemistry 59 8530462
1995 In-vitro biopotency and glycoform distribution of recombinant human follicle stimulating hormone (Org 32489), Metrodin and Metrodin-HP. Human reproduction (Oxford, England) 58 8583012
2001 2.1 and 1.8 A average C(alpha) RMSD structure predictions on two small proteins, HP-36 and s15. Journal of the American Chemical Society 57 11456657
1995 Cellular distribution of iron, transferrin, and ferritin in the hypotransferrinemic (Hp) mouse brain. The Journal of comparative neurology 57 7636015
1995 Studies on the metabolism of haloperidol (HP): the role of CYP3A in the production of the neurotoxic pyridinium metabolite HPP+ found in rat brain following ip administration of HP. Life sciences 54 8847965
2013 Targeted identification of glycosylated proteins in the gastric pathogen Helicobacter pylori (Hp). Molecular & cellular proteomics : MCP 53 23754784
2013 Endogenous retrovirus EAV-HP linked to blue egg phenotype in Mapuche fowl. PloS one 49 23990950
2009 The immune modulating activity of the Helicobacter pylori HP-NAP: Friend or foe? Toxicon : official journal of the International Society on Toxinology 46 19818802
1995 Cytomegalovirus (CMV) and Helicobacter pylori (HP) found in oral mucosal ulcers. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 44 7722916
2014 Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia: implications for HP-PRRSV neuropathogenesis. Veterinary microbiology 42 24581811
2003 The neutrophil-activating protein of Helicobacter pylori (HP-NAP) activates the MAPK pathway in human neutrophils. European journal of immunology 42 12672049
1986 A new location for the human adenine phosphoribosyltransferase gene (APRT) distal to the haptoglobin (HP) and fra(16)(q23)(FRA16D) loci. Cytogenetics and cell genetics 41 3780312
2007 Haplotype association between haptoglobin (Hp2) and Hp promoter SNP (A-61C) may explain previous controversy of haptoglobin and malaria protection. PloS one 39 17426810
2015 Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro. Arthritis research & therapy 35 26507974
2006 Interactions between the plasma membrane and the antimicrobial peptide HP (2-20) and its analogues derived from Helicobacter pylori. The Biochemical journal 34 16255716
2016 Pathological and immunological characteristics of piglets infected experimentally with a HP-PRRSV TJ strain. BMC veterinary research 33 27733150
2001 Neutrophil-activating protein (HP-NAP) versus ferritin (Pfr): comparison of synthesis in Helicobacter pylori. FEMS microbiology letters 33 11356582
2023 Phase 2 trial of a DNA vaccine (pTVG-HP) and nivolumab in patients with castration-sensitive non-metastatic (M0) prostate cancer. Journal for immunotherapy of cancer 32 38101860
2015 Difference in microRNA expression and editing profile of lung tissues from different pig breeds related to immune responses to HP-PRRSV. Scientific reports 32 25856272
2021 HP-β-CD for the formulation of IgG and Ig-based biotherapeutics. International journal of pharmaceutics 31 33775727
2016 HP-β-cyclodextrin as an inhibitor of amyloid-β aggregation and toxicity. Physical chemistry chemical physics : PCCP 31 27405335
1992 Haptoglobin subtypes in Norway and a review of HP subtypes in various populations. Human heredity 31 1572675
1992 The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors. Peptides 31 1620650
2013 Theoretical study on the polar hydrogen-π (Hp-π) interactions between protein side chains. Chemistry Central journal 29 23705926
2003 Association of cyclooxygenase-2 expression with Hp-cagA infection in gastric cancer. World journal of gastroenterology 29 12532440
2015 Helicobacter pylori CheZ(HP) and ChePep form a novel chemotaxis-regulatory complex distinct from the core chemotaxis signaling proteins and the flagellar motor. Molecular microbiology 26 26061894
2023 Co-encapsulation of curcumin and quercetin with zein/HP-β-CD conjugates to enhance environmental resistance and antioxidant activity. NPJ science of food 25 37316567
2021 The parasite cytokine mimic Hp-TGM potently replicates the regulatory effects of TGF-β on murine CD4+ T cells. Immunology and cell biology 25 33988885
2019 Characterization of a polysaccharide HP-02 from Honeysuckle flowers and its immunoregulatory and anti-Aeromonas hydrophila effects in Cyprinus carpio L. International journal of biological macromolecules 25 31398403
2019 HP-1 inhibits the progression of ccRCC and enhances sunitinib therapeutic effects by suppressing EMT. Carbohydrate polymers 25 31427001
2010 Phosphine ligands in the palladium-catalysed methoxycarbonylation of ethene: insights into the catalytic cycle through an HP NMR spectroscopic study. Chemistry (Weinheim an der Bergstrasse, Germany) 25 20440722
2020 Choline Chloride as a Nano-Crowder Protects HP-36 from Urea-Induced Denaturation: Insights from Solvent Dynamics and Protein-Solvent Interactions. Chemphyschem : a European journal of chemical physics and physical chemistry 24 31971306
1997 PI, GC, HP, and TF serum protein polymorphisms in Siena, Tuscany, Italy, with a review of data for Italy. American journal of human biology : the official journal of the Human Biology Council 23 28561430
1974 Beta-D-phosphogalactoside galactohydrolase from Streptococcus cremoris HP: purification and enzyme properties. Journal of bacteriology 23 4204438
2019 Ginsenoside Rg1 Suppresses Type 2 PRRSV Infection via NF-κB Signaling Pathway In Vitro, and Provides Partial Protection against HP-PRRSV in Piglet. Viruses 22 31717616
2021 Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) induces IL-6 production through TAK-1/JNK/AP-1 and TAK-1/NF-κB signaling pathways. Veterinary microbiology 21 33836390
2000 HNF-4 plays a pivotal role in the liver-specific transcription of the chipmunk HP-25 gene. European journal of biochemistry 21 10903495
1997 Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model. Journal of computational biology : a journal of computational molecular cell biology 21 9278060
2023 Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial. Molecular genetics and metabolism reports 20 37670901
2022 Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines. Antiviral research 20 35798224
2021 Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment. Pharmaceutics 20 34959278
2019 FLT PET/CT imaging of metastatic prostate cancer patients treated with pTVG-HP DNA vaccine and pembrolizumab. Journal for immunotherapy of cancer 20 30700328
2014 Development and validation of sensitive LC-MS/MS assays for quantification of HP-β-CD in human plasma and CSF. Journal of lipid research 20 24868096
1996 RFLP mapping of the dwarfing (Ddw1) and hairy peduncle (Hp) genes on chromosome 5 of rye (Secale cereale L.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 20 24166638
2020 Notch signaling contributes to the expression of inflammatory cytokines induced by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection in porcine alveolar macrophages. Developmental and comparative immunology 19 32222356
2010 Haptoglobin (HP) polymorphisms and human longevity: a cross-sectional association study in a Central Italy population. Clinica chimica acta; international journal of clinical chemistry 19 21147083
1991 The effect of HP-1 and related neutrophil granule peptides on DNA synthesis in HL60 cells. Regulatory peptides 19 1758971
2022 Suppression of airway allergic eosinophilia by Hp-TGM, a helminth mimic of TGF-β. Immunology 18 35758054
2020 Inclusion complexes of tea polyphenols with HP-β-cyclodextrin:Preparation, characterization, molecular docking, and antioxidant activity. Journal of food science 18 32175596
2015 Distribution of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in different stages of gestation sows: HP-PRRSV distribution in gestation sows. Veterinary immunology and immunopathology 18 26143005
2012 Complexity of a complex trait locus: HP, HPR, haemoglobin and cholesterol. Gene 18 22433445
2006 Exploration of the secondary structure specific differential solvation dynamics between the native and molten globule states of the protein HP-36. The journal of physical chemistry. B 18 17034252
1995 Serum amyloid-A (SAA) and haptoglobin (Hp) plasma concentrations in newborn calves. Theriogenology 18 16727630
2019 Continuous drying of a protein-type drug using scaled-up fiber formation with HP-β-CD matrix resulting in a directly compressible powder for tableting. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 17 31626967
2019 Preparation and Characterisation of Polyphenol-HP-β-Cyclodextrin Inclusion Complex that Protects Lamb Tripe Protein against Oxidation. Molecules (Basel, Switzerland) 17 31817887
2011 The total synthesis of a ganglioside Hp-s1 analogue possessing neuritogenic activity by chemoselective activation glycosylation. Organic & biomolecular chemistry 17 22179062
2007 VacA and HP-NAP, Ying and Yang of Helicobacter pylori-associated gastric inflammation. Clinica chimica acta; international journal of clinical chemistry 17 17368441
2005 Structure-approximating inverse protein folding problem in the 2D HP model. Journal of computational biology : a journal of computational molecular cell biology 17 16379538
2023 Recombination and Mutation in a New HP-PRRSV Strain (SD2020) from China. Viruses 16 36680205
2020 Oral supplementation of quercetin in PRRSV-1 modified-live virus vaccinated pigs in response to HP-PRRSV-2 challenge. Vaccine 16 32184034
2020 Silibinin-hydroxypropyl-β-cyclodextrin (SLB-HP-β-CD) complex prevents apoptosis in liver and kidney after hepatic ischemia-reperfusion injury. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 16 32891719
2014 Unique epitopes recognized by monoclonal antibodies against HP-PRRSV: deep understanding of antigenic structure and virus-antibody interaction. PloS one 16 25360600
2020 Aspartic acid at residue 185 modulates the capacity of HP-PRRSV nsp4 to antagonize IFN-I expression. Virology 15 32452419
2019 Biological effects of acid-eroded MTA Repair HP and ProRoot MTA on human periodontal ligament stem cells. Clinical oral investigations 15 30684060
2001 The tree squirrel HP-25 gene is a pseudogene. European journal of biochemistry 15 11722590
2000 Human phenol sulfotransferases hP-PST and hM-PST activate propane 2-nitronate to a genotoxicant. Carcinogenesis 15 10657971
2024 hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis. Apoptosis : an international journal on programmed cell death 14 38625481
2024 Interaction of zein/HP-β-CD nanoparticles with digestive enzymes: Enhancing curcumin bioavailability. Food chemistry 14 39126939
2023 Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β, Hp-TGM. Discovery immunology 14 36855464
2009 Identification of a secreted fatty acid and retinol-binding protein (Hp-FAR-1) from Heligmosomoides polygyrus. Journal of nematology 14 22736819
2001 Nucleotide sequence and characterization of the cell envelope proteinase plasmid in Lactococcus lactis subsp. cremoris HP. Journal of applied microbiology 14 11473599
2000 Characterization of the human complex I NDUFB7 and 17.2-kDa cDNAs and mutational analysis of 19 genes of the HP fraction in complex I-deficient-patients. Human genetics 14 10830904
2023 A potent CD8 T-cell response may be associated with partial cross-protection conferred by an attenuated Chinese HP-PRRSV vaccine against NADC30-like PRRSV challenge. The Journal of general virology 13 37159409
2022 Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model. International journal of molecular sciences 13 35163566
2021 Effect of high-intensity light on the photosynthetic activity, pigment content and expression of light-dependent genes of photomorphogenetic Solanum lycopersicum hp mutants. Plant physiology and biochemistry : PPB 13 34340026
2018 Endometrial expression of the acute phase molecule SAA is more significant than HP in reflecting the severity of endometritis. Research in veterinary science 13 30408641
2002 Cyclooxygenase-2 expression by transcription factors in Helicobacter pylori-infected gastric epithelial cells: comparison between HP 99 and NCTC 11637. Annals of the New York Academy of Sciences 13 12485915
2024 Functional chitosan/HP-β-CD hydrogel for targeted co-delivery of Rhubarb-derived nanovesicles and kaempferol for alleviating ulcerative colitis. Carbohydrate polymers 12 39843107
2020 Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells. Marine drugs 12 33003399
2019 Significance and Transformation of 3-Alkyl-2-Methoxypyrazines Through Grapes to Wine: Olfactory Properties, Metabolism, Biochemical Regulation, and the HP-MP Cycle. Molecules (Basel, Switzerland) 12 31888183
2018 Study of Correlation Between Hp α1 Expression of Haptoglobin 2-1 and Clinical Course in Aneurysmal Subarachnoid Hemorrhage. World neurosurgery 12 29902601
2015 Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats. International journal of pharmaceutics 12 25959121
1998 Development of FlexSure HP--an immunochromatographic method to detect antibodies against Helicobacter pylori. Clinical chemistry 12 9474027
2020 Effect of Ligands on HP-Induced Unfolding and Oligomerization of β-Lactoglobulin. Biophysical journal 11 33129832
1992 Expression of the human MUC1 mucin cDNA in a hamster pancreatic tumor cell line HP-1. International journal of pancreatology : official journal of the International Association of Pancreatology 11 1289420
2014 Identification of two dominant linear epitopes on the GP3 protein of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). Research in veterinary science 10 25135493
2004 Use of reversed phase HP liquid chromatography to assay conversion of N-acylglycines to primary fatty acid amides by peptidylglycine-alpha-amidating monooxygenase. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 10 15282088