{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Factor XIII B‐subunit (encoded by F13B) is the non‐catalytic carrier of plasma coagulation factor XIII that plays a central role in the formation and stabilization of fibrin clots. The F13B gene product assembles with two catalytic A subunits to create the FXIII‐A₂B₂ heterotetramer, a structure essential not only for protecting FXIII‐A from proteolytic degradation but also for ensuring efficient activation by thrombin and subsequent cross‐linking of fibrin and antifibrinolytic proteins.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural–functional investigations have revealed that FXIII‐B contains multiple Sushi domains, where discrete domains mediate binding to the catalytic subunit and dimer formation; for instance, the first Sushi domain is crucial for FXIII‐A binding, while other domains support homodimer assembly. Such organization underpins its role as a stabilizing chaperone for FXIII‐A, thereby modulating clot cross‐linking efficiency and overall hemostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its structural role, F13B expression is under transcriptional regulation by liver‐enriched factors. Studies have shown that hepatic transcription factors such as HNF4α are essential for driving the expression of coagulation genes including F13B, thereby directly linking F13B to blood coagulation homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic analyses have identified common F13B polymorphisms (for example, the His95Arg variant) that affect the dissociation properties of the FXIII subunits in plasma. The Arg95 variant has been associated with increased subunit dissociation and a moderately elevated risk for thrombotic events, highlighting the clinical importance of F13B genetic variation in modulating coagulation balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional studies further indicate that FXIII‐B is not simply a passive carrier but actively accelerates cross‐linking reactions by participating in the formation of a ternary complex with fibrinogen and thrombin. This interaction improves the incorporation of the catalytic FXIII‐A into the fibrin clot and ensures effective fibrin cross‐linking, with implications for clot stability and regulated fibrinolysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Experimental knockdown of hepatic FXIII‐B using siRNA in animal models leads to markedly decreased plasma FXIII‐A levels, impaired activation and cross‐linking activity, and enhanced fibrinolysis. These findings suggest that FXIII‐B is essential for maintaining adequate levels and proper function of FXIII‐A in the circulation, and thus for normal hemostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, polymorphisms within the F13B gene have been linked to variations in circulating FXIII levels and have been associated with altered risks of thromboembolic and cardiovascular events. In population studies, F13B variants—as part of the broader regulation of coagulation factor levels—modulate clot stability and may contribute to disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, F13B encodes the protective and regulatory subunit of coagulation factor XIII. By mediating proper heterotetramer assembly, supporting the stabilization and activation of FXIII‐A, and being subject to genetic variation and transcriptional regulation, F13B is a key determinant of both fibrin clot structure and function, ultimately influencing hemostasis and related disease outcomes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masayoshi Souri, Hiroshi Kaetsu, Akitada Ichinose "}, {"type": "b", "children": [{"type": "t", "text": "Sushi domains in the B subunit of factor XIII responsible for oligomer assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi8006143"}], "href": "https://doi.org/10.1021/bi8006143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18652485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18652485"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yusuke Inoue, Luanne L Peters, Sun Hee Yim, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4α and C/EBPα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0038104"}], "href": "https://doi.org/10.1371/journal.pone.0038104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22675511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22675511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "N Komanasin, A J Catto, T S Futers, et al. 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