High-molecular-weight kininogen: Difference between revisions
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'''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 [[ |
'''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 [[kinin-kallikrein system.]] HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or HMWK binds to intact endothelial cells or platelets for functions other than coagulation. |
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==Other names== |
==Other names== |
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Revision as of 00:13, 11 April 2014
 | It has been suggested that this article be merged with Kininogen 1. (Discuss) Proposed since November 2011. |
| kininogen 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | KNG1 | ||||||
| Alt. symbols | KNG, BDK | ||||||
| NCBI gene | 3827 | ||||||
| HGNC | 6383 | ||||||
| OMIM | 612358 | ||||||
| RefSeq | NM_001102416 | ||||||
| UniProt | P01042 | ||||||
| Other data | |||||||
| Locus | Chr. 3 q21-qter | ||||||
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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 kinin-kallikrein system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or HMWK binds to intact endothelial cells or platelets for functions other than coagulation.
Other names
In the past, HMWK has been called HMWK-kallikrein factor, Williams-Fitzgerald-Flaujeac factor, and FItzgerald 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.
Structure and Function
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: Domain 1 - calcium binding Domain 2 - cysteine protease inhibition Domain 3 - cysteine protease inhibition; platelet and endothelial cell binding Domain 4 - bradykinin generation Domain 5 - heparin and cell binding; antiangiogenic properties; binding to negatively charged surfaces Domain 6 - prekallikrein and factor XI binding (amino acids 420 to 510)(histidine rich)
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;[1] this vasodilator is released through positive feedback by kallikrein.
HMWK is a strong inhibitor of cysteine proteinases. Responsible for this activity are three related domains on its heavy chain.[2]
Genetics
The gene for both LMWK and HMWK is located on the 3rd chromosome (3q27).
Measurement
Measurement of HMWK is usually done with mixing studies, in which plasma deficient in HMWK is mixed with the patient's sample and apartial thromboplastin time PTT)]] is determined. Results are expressed in % of normal - a value under 60% indicates a deficiency.
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 timee and PTT.[citation needed] There is no increased risk of bleeding or any other symptoms, so the deficiency is a condition, not a disease.
References
- ^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
- ^ 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.
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