Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

Journal Article · Tue Oct 01 00:00:00 EDT 1996 · CRC Critical Reviews in Clinical Laboratory Sciences

DOI:https://doi.org/10.3109/10408369609084691· OSTI ID:508211

Muszbek, L; Adany, R ^[1]; Mikkola, H ^[2]

---

1. Univ. Medical School of Debrecen (Hungary)
2. Univ. of Helsinki (Finland)

Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} 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 (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). 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. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance 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 crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. 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 enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 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. 328 refs., 4 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 508211
• Journal Information: CRC Critical Reviews in Clinical Laboratory Sciences, Vol. 33, Issue 5; Other Information: PBD: Oct 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BLOOD COAGULATION FACTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
GENETIC MAPPING
PROTEIN STRUCTURE
BIOSYNTHESIS
FIBRINOGEN
FIBRINOLYSIS
HUMAN CHROMOSOME 6
HUMAN CHROMOSOME 1
FIBRINOLYSIN
ENZYME ACTIVITY
WOUNDS
HEALING
MACROPHAGES
MONOCYTES
BLOOD PLASMA
CALCIUM
THROMBIN
PREGNANCY
BLOOD PLATELETS
FIBRIN