词条 | High-molecular-weight kininogen |
释义 |
|Name=kininogen 1 |caption= |image= |width= |HGNCid=6383 |Symbol=KNG1 |AltSymbols=KNG, BDK |EntrezGene=3827 |OMIM=612358 |RefSeq=NM_001102416 |UniProt= P01042 |PDB= |ECnumber= |Chromosome=3 |Arm=q |Band=21 |LocusSupplementaryData=-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. Other namesIn the past, HMWK has been called HMWK-kallikrein factor, Flaujeac factor (1975),[1] Fitzgerald factor (1975),[2] 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. Structure and functionHMWK 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;[3] 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.[4] GeneticsThe gene for both LMWK and HMWK is located on the 3rd chromosome (3q26).[5] MeasurementMeasurement 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. Clinical featuresThe existence of HMWK was hypothesised in 1975 when several patients were described with a deficiency of a class of plasma protein and a prolonged bleeding time and PTT.[6] There is no increased risk of bleeding or any other symptoms, so the deficiency is a trait, not a disease. References1. ^{{cite journal | vauthors = Wuepper KD, Miller DR, Lacombe MJ | title = Flaujeac trait. Deficiency of human plasma kininogen | journal = The Journal of Clinical Investigation | volume = 56 | issue = 6 | pages = 1663–72 | date = December 1975 | pmid = 127805 | pmc = 333145 | doi = 10.1172/JCI108248 }} {{Coagulation}}{{Autacoids}}2. ^{{cite journal | vauthors = Waldmann R, Abraham JP, Rebuck JW, Caldwell J, Saito H, Ratnoff OD | title = Fitzgerald factor: a hitherto unrecognised coagulation factor | journal = Lancet | volume = 1 | issue = 7913 | pages = 949–51 | date = April 1975 | pmid = 48123 | doi = 10.1016/s0140-6736(75)92008-5 }} 3. ^{{cite book|author1=Stefan Offermanns|author2=Walter Rosenthal|title=Encyclopedia of Molecular Pharmacology|url=https://books.google.com/?id=iwwo5gx8aX8C&pg=PA673|access-date=11 December 2010|year=2008|publisher=Springer|isbn=978-3-540-38916-3|pages=673– | name-list-format = vanc }} 4. ^{{cite journal | vauthors = Higashiyama S, Ohkubo I, Ishiguro H, Kunimatsu M, Sawaki K, Sasaki M | title = Human high molecular weight kininogen as a thiol proteinase inhibitor: presence of the entire inhibition capacity in the native form of heavy chain | journal = Biochemistry | volume = 25 | issue = 7 | pages = 1669–75 | date = April 1986 | pmid = 3635411 | doi = 10.1021/bi00355a034 }} 5. ^{{cite journal | vauthors = 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 = Human Genetics | volume = 87 | issue = 2 | pages = 189–92 | date = June 1991 | pmid = 2066106 | doi = 10.1007/BF00204179 }} 6. ^{{cite journal | vauthors = Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP | title = Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways | journal = The Journal of Clinical Investigation | volume = 56 | issue = 6 | pages = 1650–62 | date = December 1975 | pmid = 1202089 | pmc = 333144 | doi = 10.1172/JCI108247 }} 3 : Coagulation system|Kinin–kallikrein system|Cofactors |
随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识,基本涵盖了大多数领域的百科知识,是一部内容自由、开放的电子版国际百科全书。