Cleaved-KLKB1 (R390) Antibody

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Description

Antibody Overview

The Cleaved-KLKB1 (R390) Antibody (Catalog #A04995-1) is a polyclonal rabbit IgG targeting the cleaved heavy chain of human plasma kallikrein at residue R390. It recognizes the activated form of KLKB1 generated through proteolytic cleavage during contact system activation .

Target Biology: Plasma Kallikrein (KLKB1)

KLKB1 encodes plasma prekallikrein, which is cleaved to form active plasma kallikrein. This enzyme:

  • Activates Factor XII (FXII) in the contact pathway of coagulation .

  • Releases bradykinin from high-molecular-weight kininogen (HMWK), influencing inflammation and blood pressure .

  • Converts prorenin to renin in the renin-angiotensin system .

Genetic Deficiency: Mutations in KLKB1 cause Fletcher factor deficiency, characterized by prolonged clotting times but mild clinical symptoms .

3.1. Assay Conditions

ApplicationDilution RangeKey Protocols
WB1:500–1:2000Detects KLKB1 in HeLa cell lysates .
IHC1:100–1:300Validated in human tissue sections .
ELISA1:10,000Quantitative detection in biological fluids .

3.2. Quality Control Metrics

  • Sensitivity: Detects KLKB1 at concentrations as low as 0.094 ng/mL .

  • Specificity: No cross-reactivity with non-cleaved KLKB1 or unrelated proteins .

  • Precision: Intra- and inter-assay coefficients of variation (CV) <10% .

4.1. Coagulation Studies

  • FXII-Independent Thrombin Generation: KLKB1 supports thrombin generation in Klkb1−/− mice, even in the absence of Factor XII, highlighting its role in alternative coagulation pathways .

    • Key Finding: Silica-initiated thrombin generation in Klkb1−/− mouse whole blood showed a 60% reduction in peak thrombin levels compared to wild-type controls .

4.2. Disease Mechanisms

  • Hereditary Angioedema (HAE): KLKB1 inhibitors are therapeutic targets for HAE, a disorder linked to excessive bradykinin production .

  • Thrombosis: KLKB1 contributes to pathological clotting, making this antibody valuable for studying contact pathway dysregulation .

Limitations and Considerations

  • Species Specificity: Reacts only with human KLKB1 .

  • Post-Translational Modifications: The observed molecular weight (111 kDa) differs from theoretical calculations due to glycosylation .

Product Specs

Buffer
Liquid in PBS containing 50% glycerol, 0.5% bovine serum albumin (BSA), and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. Delivery time may vary depending on the purchasing method or location. For specific delivery timelines, please consult your local distributors.
Synonyms
Fletcher factor antibody; kallikrein B plasma antibody; Kallikrein B plasma (Fletcher factor) 1 antibody; Kallikrein B; plasma 1 antibody; Kallikrein B1 antibody; Kininogenin antibody; KLK3 antibody; KLKB1 antibody; KLKB1_HUMAN antibody; PKK antibody; PKKD antibody; Plasma kallikrein antibody; Plasma kallikrein B1 antibody; Plasma kallikrein light chain antibody; Plasma prekallikrein antibody; PPK antibody; Prekallikrein antibody
Target Names
Uniprot No.

Target Background

Function
This enzyme specifically cleaves Lys-Arg and Arg-Ser bonds. It activates factor XII in a reciprocal reaction after binding to a negatively charged surface. It also releases bradykinin from high molecular weight kininogen and might play a role in the renin-angiotensin system by converting prorenin into renin.
Gene References Into Functions
  • Our research further clarifies the interactions between keratinocyte PKK, TP63, and NF-kappaB signaling. This emphasizes the significance of PKK as a tumor suppressor in the development of skin squamous cell carcinoma. PMID: 29186361
  • Plasma kallikrein (PLK)-dependent transforming growth factor-beta (TGF-beta) activation was observed in isolated pancreatic stellate cells (PSCs) from chronic pancreatitis (CP) and pancreatic cancer. PMID: 28187111
  • High molecular weight kinin serves as a cofactor for PK activation in the presence of nucleic acids, aligning with traditional models of contact activation. PMID: 28124063
  • Genetic polymorphism is associated with the age of onset of C1 Inhibitor deficiency angioedema in European families. PMID: 29130992
  • These findings suggest that KLKB1 induces inflammatory reactions in human dental tissues through protease-activated receptor 1. PMID: 26566265
  • Both von Willebrand factor activity and prekallikrein concentration might be crucial for thrombus evolution in abdominal aortic aneurysm and potential biomarkers for aneurysm growth. PMID: 27581227
  • KLKB1 mRNA expression is a potential molecular biomarker in chronic lymphocytic leukemia. PMID: 25891023
  • Genotyping of these subjects revealed that carriers of the minor alleles at the two loci, F12 and KLKB1, had a significant association with reduced levels of active plasma renin. PMID: 26969407
  • Two genetic loci (kininogen 1 and kallikrein B) influencing key components of the RAAS, consistent with the close relationship between the kallikrein-kinin system and the RAAS. PMID: 25477429
  • PRCP1 interacts with plasma kallikrein (PK) at multiple sites for PK activation. PMID: 25324000
  • Prekallikrein deficiency in a family is attributed to a novel mutation (Arg541Gln) in exon 14. PMID: 25075649
  • FXI might play a role in the risk of ischemic stroke, but not myocardial infarct; FXII and prekallikrein might not be involved in either. PMID: 24977287
  • The acquisition of an active site in prekallikrein as a consequence of binding to high-molecular-weight kininogen (HK) is a novel concept for bradykinin formation and might be relevant in the pathogenesis of hereditary angioedema types I and II. PMID: 23672780
  • Further investigation into the relationship between circulating PK levels in children with metabolic syndrome and CVD risk factors is recommended, as PK may be involved in disease progression. PMID: 20725119
  • Case Report: Fresh frozen plasma transfusion before coronary artery bypass corrected prekallikrein deficiency. PMID: 20135073
  • Plasma kallikrein and FXIa activate pro-HGF in vitro. PMID: 12372819
  • The effect of kininogen degradation by human neutrophil elastase (HNE) on kinin generation by tissue and plasma kallikreins. PMID: 12887060
  • Prekallikrein preferential binding to endothelial cells contributes to their anticoagulant nature. PMID: 12944405
  • Crystallization and x-ray crystal structure determination have provided the first three-dimensional views of the catalytic domain of plasma kallikrein. PMID: 16199530
  • Our findings suggest that common genetic variation in the KLKB1 gene might contribute to the risk of hypertension in the northern Han Chinese population. PMID: 17318641
  • This study demonstrates, through immunohistochemistry, that plasma kallikrein (PK) is localized in cells of various embryologically derived human tissues. PMID: 17696780
  • Three-dimensional structural data for prekallikrein (PK) has been obtained; interaction between PK and high-molecular-weight kininogen is mediated by two distinct surfaces formed by the PK A1, A2, and A4 domains, with charge likely playing a crucial role in the binding process. PMID: 17922805
  • Kallikrein can directly activate prothrombin, suggesting a shortcut in the intrinsic hemostasis system that generates catalytic amounts of thrombin without following the established intrinsic clotting pathway. PMID: 18160576
  • Kallikrein is responsible for the cleavage of factor H. PMID: 18413232
  • Prekallikrein is an enzyme that can cleave high-molecular-weight kininogen to release bradykinin, and this reaction is inhibited by C1 inhibitor. PMID: 19342086
  • NPY3-35 is a new peptide generated by plasma kallikrein. PMID: 19620246

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Database Links

HGNC: 6371

OMIM: 229000

KEGG: hsa:3818

STRING: 9606.ENSP00000264690

UniGene: Hs.237642

Involvement In Disease
Prekallikrein deficiency (PKK deficiency)
Protein Families
Peptidase S1 family, Plasma kallikrein subfamily
Subcellular Location
Secreted.

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