High-molecular-weight kininogen

High-molecular-weight kininogen

High-molecular-weight kininogen (HMWK), also known as the Williams-Fitzgerald-Flaujeac factor or the Fitzgerald factor or the HMWK-kallikrein factor, 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 in vivo. This protein circulates throughout the blood and quickly adsorbs to the material surfaces.

Nomenclature

High-molecular weight kininogen is one of the kininogens, 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.

Physiology

HMWK is one of the early participants of the "intrinsic pathway" of coagulation, together with Factor XII (Hageman factor) and prekallikrein. It is 626 amino acids long, and weighs 88 to 120 kDa (dependent on glycosylation). The kininogen is not enzymatically active, and functions only as a cofactor for the activation of kallikrein and Hageman factor. It is also necessary for the activation of factor XI by factor XIIa. The histidine-rich region (amino acids 420 to 510) participates most strongly in coagulation.

In addition to its role in blood coagulation, HMWK (just as Low-molecular-weight kininogen) is a strong inhibitor of cysteine proteinases. Responsible for this activity are three related domains on its heavy chain (Higashiyama et al., Biochemistry 25, 1669-75 (1986)).

HMWK is also a precursor of bradykinin; this vasodilator substance is released through positive feedback by kallikrein.

Genetics

The gene for both types of kininogens is located on the 3rd chromosome (3q27).

Measurement

Measurement of HMWK is usually done with mixing studies, where plasma deficient in HMWK is mixed with the patient's sample and the PTT determined. Results are expressed in % of normal - values under 60% or over 140% are abnormal.

Role in disease

The existence of HMWK was hypothesised in the 1970s when several patients were described with a deficiency of a class of plasma protein and a prolonged bleeding time and partial thromboplastin time (PTT). As in deficiency of the associated Hageman factor, there is no increased risk of bleeding.

External links

* [http://www.mgh.harvard.edu/labmed/lab/coag/handbook/CO002500.htm LMWK laboratory information]
*

Further reading

PBB_Further_reading
citations =
*cite journal | author=Iarovaia GA |title= [Kallikrein-kinin system: novel facts and concepts (literature review)] |journal=Vopr. Med. Khim. |volume=47 |issue= 1 |pages= 20–42 |year= 2001 |pmid= 11385996 |doi=
*cite journal | author=Matthews KW, Mueller-Ortiz SL, Wetsel RA |title=Carboxypeptidase N: a pleiotropic regulator of inflammation |journal=Mol. Immunol. |volume=40 |issue= 11 |pages= 785–93 |year= 2004 |pmid= 14687935 |doi= 10.1016/j.molimm.2003.10.002
*cite journal | author=Scharfstein J, Schmitz V, Svensjö E, "et al." |title=Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation |journal=Scand. J. Immunol. |volume=66 |issue= 2-3 |pages= 128–36 |year= 2007 |pmid= 17635790 |doi= 10.1111/j.1365-3083.2007.01983.x
*cite journal | author=Thompson RE, Mandle R, Kaplan AP |title=Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=76 |issue= 10 |pages= 4862–6 |year= 1980 |pmid= 291905 |doi=
*cite journal | author=Kerbiriou DM, Griffin JH |title=Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma |journal=J. Biol. Chem. |volume=254 |issue= 23 |pages= 12020–7 |year= 1980 |pmid= 500690 |doi=
*cite journal | author=Colman RW, Bagdasarian A, Talamo RC, "et al." |title=Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways |journal=J. Clin. Invest. |volume=56 |issue= 6 |pages= 1650–62 |year= 1976 |pmid= 1202089 |doi=
*cite journal | author=Gailani D, Broze GJ |title=Factor XI activation in a revised model of blood coagulation |journal=Science |volume=253 |issue= 5022 |pages= 909–12 |year= 1991 |pmid= 1652157 |doi= 10.1126/science.1652157
*cite journal | author=Cheung PP, Cannizzaro LA, Colman RW |title=Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter |journal=Cytogenet. Cell Genet. |volume=59 |issue= 1 |pages= 24–6 |year= 1992 |pmid= 1733668 |doi=
*cite journal | author=Fong D, Smith DI, Hsieh WT |title=The human kininogen gene (KNG) mapped to chromosome 3q26-qter by analysis of somatic cell hybrids using the polymerase chain reaction |journal=Hum. Genet. |volume=87 |issue= 2 |pages= 189–92 |year= 1991 |pmid= 2066106 |doi= 10.1007/BF00204179
*cite journal | author=Schmaier AH, Kuo A, Lundberg D, "et al." |title=The expression of high molecular weight kininogen on human umbilical vein endothelial cells |journal=J. Biol. Chem. |volume=263 |issue= 31 |pages= 16327–33 |year= 1988 |pmid= 2460446 |doi=
*cite journal | author=Takagaki Y, Kitamura N, Nakanishi S |title=Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens |journal=J. Biol. Chem. |volume=260 |issue= 14 |pages= 8601–9 |year= 1985 |pmid= 2989293 |doi=
*cite journal | author=Kitamura N, Kitagawa H, Fukushima D, "et al." |title=Structural organization of the human kininogen gene and a model for its evolution |journal=J. Biol. Chem. |volume=260 |issue= 14 |pages= 8610–7 |year= 1985 |pmid= 2989294 |doi=
*cite journal | author=Ishiguro H, Higashiyama S, Namikawa C, "et al." |title=Interaction of human calpains I and II with high molecular weight and low molecular weight kininogens and their heavy chain: mechanism of interaction and the role of divalent cations |journal=Biochemistry |volume=26 |issue= 10 |pages= 2863–70 |year= 1987 |pmid= 3038169 |doi=
*cite journal | author=Vogel R, Assfalg-Machleidt I, Esterl A, "et al." |title=Proteinase-sensitive regions in the heavy chain of low molecular weight kininogen map to the inter-domain junctions |journal=J. Biol. Chem. |volume=263 |issue= 25 |pages= 12661–8 |year= 1988 |pmid= 3045123 |doi=
*cite journal | author=Maeda H, Matsumura Y, Kato H |title=Purification and identification of [hydroxyprolyl3] bradykinin in ascitic fluid from a patient with gastric cancer |journal=J. Biol. Chem. |volume=263 |issue= 31 |pages= 16051–4 |year= 1988 |pmid= 3182782 |doi=
*cite journal | author=Kato H, Matsumura Y, Maeda H |title=Isolation and identification of hydroxyproline analogues of bradykinin in human urine |journal=FEBS Lett. |volume=232 |issue= 1 |pages= 252–4 |year= 1988 |pmid= 3366244 |doi= 10.1016/0014-5793(88)80427-7
*cite journal | author=Kellermann J, Lottspeich F, Henschen A, Müller-Esterl W |title=Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication |journal=Eur. J. Biochem. |volume=154 |issue= 2 |pages= 471–8 |year= 1986 |pmid= 3484703 |doi= 10.1111/j.1432-1033.1986.tb09421.x
*cite journal | author=Kellermann J, Thelen C, Lottspeich F, "et al." |title=Arrangement of the disulphide bridges in human low-Mr kininogen |journal=Biochem. J. |volume=247 |issue= 1 |pages= 15–21 |year= 1988 |pmid= 3689342 |doi=
*cite journal | author=Warn-Cramer BJ, Bajaj SP |title=Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa |journal=Biochem. Biophys. Res. Commun. |volume=133 |issue= 2 |pages= 417–22 |year= 1986 |pmid= 3936495 |doi=
*cite journal | author=Lottspeich F, Kellermann J, Henschen A, "et al." |title=The amino acid sequence of the light chain of human high-molecular-mass kininogen |journal=Eur. J. Biochem. |volume=152 |issue= 2 |pages= 307–14 |year= 1985 |pmid= 4054110 |doi= 10.1111/j.1432-1033.1985.tb09199.x

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