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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/11 12:18:46」(JST)

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Kininogens are proteins that are defined by their role as precursors for kinin, but that also can have additional roles.

The two main types are:

High-molecular-weight kininogen, which is produced by the liver together with prekallikrein. It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity. These high molecular weight kininogens are cleaved into bradykinin and kallidin by tissue and plasma kallikreins.
Low-molecular-weight kininogen, which is produced locally by numerous tissues, and secreted together with tissue kallikrein.

They are both spliced from the same precursor.

A third type, T-kininogen, is found in rats but not humans.^[1]

References

^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 673–. ISBN 978-3-540-38916-3. http://books.google.com/books?id=iwwo5gx8aX8C&pg=PA673. Retrieved 11 December 2010.

External links

Kininogens at the US National Library of Medicine Medical Subject Headings (MeSH)
The kinin-forming system at sav.sk

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English Journal

Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.

Roberts JL1, Hovanes K2, Dasouki M3, Manzardo AM1, Butler MG4.Author information 1Departments of Psychiatry, Behavioral Sciences and Pediatrics, The University of Kansas, Medical Center, Kansas City, KS, USA.2CombiMatrix Diagnostics, Irvine, CA, USA.3Department of Neurology, The University of Kansas Medical Center, Kansas City, KS, USA; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.4Departments of Psychiatry, Behavioral Sciences and Pediatrics, The University of Kansas, Medical Center, Kansas City, KS, USA. Electronic address: mbutler4@kumc.edu.AbstractChromosomal microarray analysis is now commonly used in clinical practice to identify copy number variants (CNVs) in the human genome. We report our experience with the use of the 105K and 180K oligonucleotide microarrays in 215 consecutive patients referred with either autism or autism spectrum disorders (ASD) or developmental delay/learning disability for genetic services at the University of Kansas Medical Center during the past 4years (2009-2012). Of the 215 patients [140 males and 75 females (male/female ratio=1.87); 65 with ASD and 150 with learning disability], abnormal microarray results were seen in 45 individuals (21%) with a total of 49 CNVs. Of these findings, 32 represented a known diagnostic CNV contributing to the clinical presentation and 17 represented non-diagnostic CNVs (variants of unknown significance). Thirteen patients with ASD had a total of 14 CNVs, 6 CNVs recognized as diagnostic and 8 as non-diagnostic. The most common chromosome involved in the ASD group was chromosome 15. For those with a learning disability, 32 patients had a total of 35 CNVs. Twenty-six of the 35 CNVs were classified as a known diagnostic CNV, usually a deletion (n=20). Nine CNVs were classified as an unknown non-diagnostic CNV, usually a duplication (n=8). For the learning disability subgroup, chromosomes 2 and 22 were most involved. Thirteen out of 65 patients (20%) with ASD had a CNV compared with 32 out of 150 patients (21%) with a learning disability. The frequency of chromosomal microarray abnormalities compared by subject group or gender was not statistically different. A higher percentage of individuals with a learning disability had clinical findings of seizures, dysmorphic features and microcephaly, but not statistically significant. While both groups contained more males than females, a significantly higher percentage of males were present in the ASD group.
Gene.Gene.2014 Feb 1;535(1):70-8. doi: 10.1016/j.gene.2013.10.020. Epub 2013 Nov 2.
Chromosomal microarray analysis is now commonly used in clinical practice to identify copy number variants (CNVs) in the human genome. We report our experience with the use of the 105K and 180K oligonucleotide microarrays in 215 consecutive patients referred with either autism or autism spectrum dis
PMID 24188901

Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway.

Kaplan AP1, Joseph K2.Author information 1Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: kaplana@musc.edu.2Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.AbstractBinding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor XIIa followed by factor XII fragment (factor XIIf). PK circulates bound to HK and binding induces a conformational change in PK so that it acquires enzymatic activity and can stoichiometrically cleave HK to produce bradykinin. This reaction is prevented from occurring in plasma by the presence of C1 inhibitor (C1 INH). The same active site leads to autoactivation of the PK-HK complex to generate kallikrein if a phosphate containing buffer is used. Theoretically, formation of kallikrein by this factor XII-independent route can activate surface-bound factor XII to generate factor XIIa resulting in a marked increase in the rate of bradykinin formation as stoichiometric reactions are replaced by Michaelis-Menton, enzyme-substrate, kinetics. Zinc-dependent binding of the constituents of the bradykinin-forming cascade to the surface of endothelial cells is mediated by gC1qR and bimolecular complexes of gC1qR-cytokeratin 1 and cytokeratin 1-u-PAR (urokinase plasminogen activator receptor). Factor XII and HK compete for binding to free gC1qR (present in excess) while cytokeratin 1-u-PAR preferentially binds factor XII and gC1qR-cytokeratin 1 preferentially binds HK. Autoactivation of factor XII can be initiated as a result of binding to gC1qR but is prevented by C1 INH. Yet stoichiometric activation of PK-HK to yield kallikrein in the absence of factor XII can be initiated by heat shock protein 90 (HSP-90) which forms a zinc-dependent trimolecular complex by binding to HK. Thus, endothelial cell-dependent activation can be initiated by activation of factor XII or by activation of PK-HK. Hereditary angioedema (HAE), types I and II, are due to autosomal dominant mutations of the C1 INH gene. In type I disease, the level of C1 INH protein and function is proportionately low, while type II disease has a normal protein level but diminished function. There is trans-inhibition of the one normal gene so that functional levels are 30% or less and severe angioedema affecting peripheral structures, the gastrointestinal tract, and the larynx results. Prolonged incubation of plasma of HAE patients (but not normal controls) leads to bradykinin formation and conversion of PK to kallikrein which is reversed by reconstitution with C1 INH. The disorder can be treated by C1 INH replacement, inhibition of plasma kallikrein, or blockade at the bradykinin B-2 receptor. A recently described HAE with normal C1 INH (based on inhibition of activated C1s) presents similarly; the defect is not yet clear, however one-third of patients have a mutant factor XII gene. We have shown that this HAE has a defect in bradykinin overproduction whether the factor XII mutation is present or not, that patients' C1 INH is capable of inhibiting factor XIIa and kallikrein (and not just activated C1) but the functional level is approximately 40-60% of normal, and that α2 macroglobulin protein levels are normal. In vitro abnormalities can be suppressed by raising C1 INH to twice normal levels. Finally, aggregated proteins have been shown to activate the bradykinin-forming pathway by catalyzing factor XII autoactivation. Those include the amyloid β protein of Alzheimer's disease and cryoglobulins. This may represent a new avenue for kinin-dependent research in human disease. In allergy (anaphylaxis; perhaps other mast cell-dependent reactions), the oversulfated proteoglycan of mast cells, liberated along with histamine, also catalyze factor XII autoactivation.
Advances in immunology.Adv Immunol.2014;121:41-89. doi: 10.1016/B978-0-12-800100-4.00002-7.
Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikr
PMID 24388213

Kininogen 1 and insulin-like growth factor binding protein 6: candidate serum biomarkers of proliferative vitreoretinopathy.

Yu J, Peng R, Chen H, Cui C, Ba J, Wang F.Author information Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. jingyuchn@126.com.AbstractBACKGROUND: The aim was to validate whether kininogen 1 (KNG1) or insulin-like growth factor binding protein 6 (IGFBP-6) are serum biomarkers of proliferative vitreoretinopathy (PVR).
Clinical & experimental optometry : journal of the Australian Optometrical Association.Clin Exp Optom.2014 Jan;97(1):72-9. doi: 10.1111/cxo.12088. Epub 2013 Jul 1.
BACKGROUND: The aim was to validate whether kininogen 1 (KNG1) or insulin-like growth factor binding protein 6 (IGFBP-6) are serum biomarkers of proliferative vitreoretinopathy (PVR).METHODS: Samples from vitreous and corresponding serum samples were collected from patients with PVR. The donor vitre
PMID 23808406