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) is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the Kallikrein-kinin system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation.
In the past, HMWK has been called HMWK-kallikrein factor, Flaujeac factor (1975), Fitzgerald factor (1975), and Williams-Fitzgerald-Flaujeac factor, - the eponyms being for people first reported to have HMWK deficiency. Its current accepted name is to contrast it with low molecular weight kininogen (LMWK) which has a similar function to HMWK in the tissue (as opposed to serum) kinin-kallikrein system.
HMWK is an alpha-globulin with six functional domains. It circulates as a single-chain 626 amino acid polypeptide . The heavy chain contains domains 1, 2, and 3; the light chain, domains 5 and 6. Domain 4 links the heavy and light chains.
The domains contain the following functional sites:
HMWK is one of four proteins which interact to initiate the contact activation pathway (also called the intrinsic pathway) of coagulation: the other three are Factor XII, Factor XI and prekallikrein. HMWK 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.
HMWK is also a precursor of bradykinin; this vasodilator is released through positive feedback by kallikrein.
HMWK is a strong inhibitor of cysteine proteinases. Responsible for this activity are domains 2 and 3 on its heavy chain.
The gene for both LMWK and HMWK is located on the 3rd chromosome (3q26).
Measurement of HMWK is usually done with mixing studies, in which plasma deficient in HMWK is mixed with the patient's sample and a partial thromboplastin time (PTT) is determined. Results are expressed in % of normal - a value under 60% indicates a deficiency.
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