Muszbek L, Adány R, Mikkola H
Department of Clinical Chemistry, University Medical School of Debrecen, Hungary.
Crit Rev Clin Lab Sci. 1996;33(5):357-421. doi: 10.3109/10408369609084691.
Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca2+ in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A2B2), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A2). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established, and most recently the three-dimensional structure of recombinant cellular FXIII has also been revealed. Monocytes/macrophages synthesize their own FXIII, and very likely FXIII in platelets is synthesized by the megakaryocytes. Cells of bone marrow origin seem to be the primary site for the synthesis of subunit A in plasma FXIII, but hepatocytes might also contribute. The B subunit of plasma FXIII is synthesized in the liver. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII. The most important steps of the activation of plasma FXIII are the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which cross-links peptide chains through epsilon(gamma-glutamyl)lysyl isopeptide bonds. Cellular FXIII in platelets becomes activated through a nonproteolytic process. When intracytoplasmic Ca2+ is raised during platelet activation, the zymogen--in the absence of subunit B--assumes an active configuration. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic plasmin. The latter effect is achieved mainly by covalently linking alpha 2 antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored.
凝血因子 XIII（FXIII）是一种前转谷氨酰胺酶，在凝血级联反应的最后阶段，通过凝血酶和 Ca2+ 的协同作用而被激活。除血浆外，FXIII 也存在于血小板、单核细胞及单核细胞衍生的巨噬细胞中。血浆中的 FXIII 是一种由 A 和 B 亚基配对组成的异源四聚体（A2B2），而其细胞内对应物则缺乏 B 亚基，是潜在活性 A 亚基的同型二聚体（A2）。编码 A 和 B 亚基的基因分别定位于染色体 6p24 - 25 和 1q31 - 32.1。两个亚基的基因组结构以及一级蛋白质结构均已明确，最近重组细胞 FXIII 的三维结构也已被揭示。单核细胞/巨噬细胞合成自身的 FXIII，血小板中的 FXIII 很可能是由巨核细胞合成的。骨髓来源的细胞似乎是血浆 FXIII 中 A 亚基合成的主要部位，但肝细胞也可能有贡献。血浆 FXIII 的 B 亚基在肝脏中合成。血浆 FXIII 与其底物前体纤维蛋白原结合循环。纤维蛋白（原）在血浆 FXIII 的激活中具有重要的调节作用。血浆 FXIII 激活的最重要步骤是凝血酶对激活肽的蛋白水解去除、A 和 B 亚基的解离以及游离 A 亚基上原本被掩埋的活性位点的暴露。这一过程的最终结果是形成一种活性转谷氨酰胺酶，它通过 ε（γ - 谷氨酰）赖氨酰异肽键交联肽链。血小板中的细胞 FXIII 通过非蛋白水解过程被激活。当血小板激活过程中细胞质内 Ca2+ 升高时，在没有 B 亚基的情况下，该酶原呈现出活性构象。激活的 FXIII 的蛋白质底物包括凝血 - 纤维蛋白溶解系统的成分、黏附蛋白和收缩蛋白。血浆 FXIII 的主要生理功能是交联纤维蛋白并保护其免受纤维蛋白溶解酶的降解。后一种作用主要是通过将纤溶酶最有效的生理抑制剂α2 抗纤溶酶共价连接到纤维蛋白上来实现的。血浆 FXIII 似乎参与伤口愈合和组织修复，并且对维持妊娠至关重要。细胞 FXIII 如果暴露于细胞表面，可能支持或也许接管血浆 FXIII 的止血功能；然而，其细胞内作用大多仍未被探索。
