High-molecular-weight kininogen
| kininogen 1 | |
|---|---|
| Identifiers | |
| Symbol | KNG1 |
| Alt. symbols | KNG, BDK |
| Entrez | 3827 |
| HUGO | 6383 |
| OMIM | 612358 |
| RefSeq | NM_001102416 |
| UniProt | P01042 |
| Other data | |
| Locus | Chr. 3 q21-qter |
High-molecular-weight kininogen (HMWK or HK), 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, complexed 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 factor XII. 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. Importantly, the role of HMWK in the coagulation cascade relies on its interaction with various endothelial cell binding proteins.
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.[1]
HMWK is also a precursor of bradykinin;[2] 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).[citation needed]
As in deficiency of the associated Hageman factor, there is no increased risk of bleeding.
References
- ↑ Higashiyama S, Ohkubo I, Ishiguro H, Kunimatsu M, Sawaki K, Sasaki M (April 1986). "Human high molecular weight kininogen as a thiol proteinase inhibitor: presence of the entire inhibition capacity in the native form of heavy chain". Biochemistry 25 (7): 1669–75. doi:10.1021/bi00355a034. PMID 3635411.
- ↑ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
External links
- LMWK laboratory information
- Online 'Mendelian Inheritance in Man' (OMIM) 228960
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