Recombinant Human Kininogen 1 Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-3076

Recombinant Human Kininogen 1 Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-3076
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Product Overview

Tag His
Host Species Human
Accession NP_001095886.1
Synonym BDK, BK, KNG
Background Kininogen-1, also known as high molecular weight kininogen, williams-Fitzgerald-Flaujeac factor, Alpha-2-thiol proteinase inhibitor, Fitzgerald factor, KNG1 and BDK, is a secreted protein which contains threecystatin domains. Kininogen-1 / KNG1 is a protein from the blood coagulation system as well as the kinin-kallikrein system. It is a protein that adsorbs to the surface of biomaterials that come in contact with blood. Kininogen-1 / KNG1 circulates throughout the blood and quickly adsorbs to the material surfaces. Kininogen-1 / KNG1 is one of the early participants of the intrinsic pathway of coagulation, together with Factor XII (Hageman factor) and prekallikrein. Kininogen-1 / KNG1 is one of thekininogens, a class of proteins. As with many other coagulation proteins, the protein was initially named after the patients in whom deficiency was first observed. When the clinical data were combined, it turned out that all patients, in fact, had a deficiency of the same protein. Defects in KNG1 are the cause of high molecular weight kininogen deficiency (HMWK deficiency) which is an autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.
Description A DNA sequence encoding the human KNG1 isoform 1 (NP_001095886.1) (Gln 19-Ser 644) was fused with a His tag at the C-terminus, and a signal peptide at the N-terminus.
Source HEK293
Predicted N Terminal Gln 19
AA Sequence Gln 19-Ser 644
Molecular Weight The recombinant human KNG1 consists of 637 a.a. and has a predicted molecular mass of 71.3 kDa. As a result of glycosylation, the apparent molecular mass of rhKNG1 is approximately 100-110 kDa in SDS-PAGE under reducing conditions.
Purity >85% as determined by SDS-PAGE
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity Measured by its ability to inhibit papain cleavage of a fluorogenic peptide substrate Z-FR-AMC, R&D Systems, Catalog # ES009. The IC50 value is < 7 nM.
Formulation Lyophilized from sterile 25mM Tris, 100mM NaCl, pH 7.5.
Stability The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage For Research Use Only
Storage Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.
Subcellular Location Secreted, extracellular space.
Database References
Associated Diseases High molecular weight kininogen deficiency (HMWK deficiency)
Tissue Specificity Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors.

Gene Functions References

  1. Kininogen binds to the cell surface-exposed proteins of Candida parapsilosis. PMID: 28651026
  2. Three loci showed robust, replicating association with circulating FXI levels: KNG1 (rs710446, P-value = 2.07 x 10-302), F11 (rs4253417, P-value = 2.86 x 10-193), and a novel association in GCKR (rs780094, P-value = 3.56 x10-09), here for the first time implicated in FXI regulation. The two first SNPs (rs710446 and rs4253417) also associated with partial thromboplastin time PMID: 28053049
  3. findings show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation PMID: 28005926
  4. Urinary KNG1 and RBP4 clearly respond to AKI. Additionally, RBP4 could predict recovery by monitoring this protein levels over time after AKI, as RBP4 reflects patient's normalization earlier than sCr values do. PMID: 26792617
  5. KNG1 rs710446/ rs2304456 SNPs are not related to the incidence of Alzheimer's disease in a Hunan Han Chinese population. PMID: 26884824
  6. Low urine KNG1 expression is associated with clear cell renal cell carcinoma. PMID: 26420021
  7. The results of this study supported the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility. PMID: 26159646
  8. Bradykinin stimulates pro-contractile signalling mechanisms in human myometrial cells and arrestin proteins play key roles in their regulation. PMID: 25766502
  9. Measuring plasma levels of cleaved HK may be a sensitive mean of assessing disease severity in HAE-C1-INH patients. PMID: 24552232
  10. The antimicrobial protein kininogen evolved adaptively in mammals and human populations. PMID: 23505046
  11. results demonstrate that HKa accelerates the onset of EPC senescence by stimulating JNK/FOXO4/MnSOD pathway, its effect is mediated by the HC PMID: 24984152
  12. When the concentrations of IGFBP-6 or KNG1 were greater than 98.5 pg/ml or 88.5 ng/ml, respectively, they predicted the proliferative vitreoretinopathy prognosis. PMID: 23808406
  13. uPAR mediates efferocytosis through high molecular weight kininogen interaction with phosphatidylserine on apoptotic cells PMID: 24688027
  14. these results suggest that D5(H) of high molecular weight kininogen may modulate cell adhesion and invasion together with actinin-4. PMID: 23000411
  15. KNG1 and F11 are the main genetic regulators of plasma FXI level. PMID: 22701019
  16. The results showed that bradykinin stimulates Toll-like receptor 2 transcription and translation by activation of protein kinase C as well as proto-oncogene protein AKT. PMID: 21982724
  17. kininogen-1 and thymosin-beta(4) are potential new biomarkers for human chronic hepatitis C. PMID: 21496200
  18. Bacteroides fragilis and Bacteroides thetaiotaomicron, were found to bind HK and fibrinogen PMID: 21527472
  19. High molecular weight kininogen activates B2 receptor signaling pathway in human vascular endothelial cells. PMID: 21586566
  20. Kininogen-1 and IGFBP-6 are expressed in serum and vitreous humor in proliferative vitreoretinopathy patients. PMID: 21054968
  21. Bradykinin, acting via bradykinin 2 receptors, initiates an important signal directing the invasion of glioma patients' cells toward blood vessels. PMID: 21451024
  22. KNG1 Ile581Thr and susceptibility to venous thrombosis. PMID: 21270443
  23. expression of ACE is lowest in elderly women, despite the presence of similar BK degradation in pericardial fluid PMID: 19592120
  24. These findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1-ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos. PMID: 20876611
  25. KNG1 SNP rs710448 (allele frequency 42%) was associated with decreased risk (OR 0.44, 95% CI 0.3-0.8) among women but not men. PMID: 19716087
  26. High-glucose stimulates tubular proinflammatory, profibrotic and angiogenic signals, which is partly mediated through bradykinin via MAPK signalling and partly through protein kinase C independent of bradykinin. PMID: 19923143
  27. Single Nucleotide Polymorphisms in KNG1 is associated with activated partial thromboplastin time. PMID: 20303064
  28. our findings suggest that bradykinin and bradykinin B2 receptors are involved in the modulation of mechanisms participating in inflammatory synovitis PMID: 20050188
  29. Bradykinin enhances the migration of chondrosarcoma cells by increasing alpha2beta1 integrin expression through the BK receptors/PLC/PKCdelta/NF-kappaB signal transduction pathway. PMID: 19885862
  30. High molecular weight kininogen (HKa) mimics lipopolysaccharides by triggering a paracrine pathway in monocytes that depends on TNF-alpha and IL-1beta. Upregulation of tissue factor in monocytes by cleaved HKa is dependent on TNF-alpha and IL-1beta. PMID: 19966052
  31. inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 PMID: 11689005
  32. Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of factor XII. PMID: 11792853
  33. down-regulates cathepsin G-induced platelet activation by forming a complex with cathepsin G and thus prevents binding of cathepsin G to platelets PMID: 11920276
  34. a defined region can abolish platelet adhesion to vitronectin and block platelet aggregation PMID: 11970955
  35. Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release. PMID: 12071855
  36. kininogen has as role as a antithrombotic agent by inhibiting plasminogen activator inhibitor-1 PMID: 12082110
  37. Bradykinin induces IL-6 production in human airway smooth muscle cells. PMID: 12594059
  38. free HK, or HK in complex with prekallikrein but not in complex with factor XI, interacts with the endothelium and can maintain endothelial cell quiescence by preventing endothelial stimulation by thrombin. PMID: 12663668
  39. transcriptional activation of the interleukin-8 promoter by bradykinin involves the prostanoid-independent activation of nuclear factor-kappaB, and prostanoid-dependent activation of activating protein-1 and nuclear factor-interleukin-6 PMID: 12748173
  40. kininogen is a novel and direct target of farnesoid X receptor PMID: 12761213
  41. Bradykinin is a powerful spasmogen via B(2) receptor activation in the normal and, especially, in the inflamed human gallbladder. PMID: 12851878
  42. sequences in domain 5 of high molecular weight kininogen interact with heparin and zinc PMID: 12911595
  43. High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib PMID: 12952972
  44. His-Gly-Lys motif and lysine residue (Lys487) play essential roles in inhibition of cell adhesion and invasion in vitro and in prevention of metastasis of cancer cells in vivo PMID: 14506238
  45. COX-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, EP2 receptor, and EP4 receptor PMID: 14517215
  46. binds with high specificity and affinity to microvascular endothelial cells, but with lower affinity to astrocytes; cytokeratin 1, u-PAR,and gC1qR were found to be high molecular weight kininogen binding proteins present at the surface of these cells PMID: 14597972
  47. The rate of kallikrein formation by the assembly of factor XII, high molecular weight KNG and PK were similar in both heparinase-treated and non-treated HUVEC, indicating that heparan sulfate does not contribute significantly to HK binding to HUVEC. PMID: 14629481
  48. physically disrupts the formation of a signaling complex containing uPAR, integrin alpha(v)beta3 or alpha5beta1, caveolin, and Src kinase Yes in endothelial cells in a manner that parallels its apoptotic effect PMID: 15044324
  49. ACE-I-induced renoprotection, in the context of macrophage-stimulated mesangial cell scarring, is mediated, at least in part, via the actions of bradykinin. PMID: 15086463
  50. high molecular weight kininogen has an antibacterial domain, called domain 5 PMID: 16091369

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