A Novel Asn344 Deletion in the Core Domain of Coagulation Factor
XIII A Subunit: Its Effects on Protein Structure and Function
Sasichai Kangsadalampai,
Gareth Chelvanayagam,
Rohan T. Baker,
Pa-thai Yenchitsomanus,
Parichat Pung-amritt,
Chularatana Mahasandana, and
Philip G. Board
From the Molecular Genetics Group, John Curtin School of Medical
Research, Australian National University, Canberra, Australia; the
Medical Molecular Biology Unit, Office for Research and Development,
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok; and
the Department of Paediatrics, Faculty of Medicine Siriraj Hospital,
Mahidol University, Bangkok, Thailand.
In this study a previously undescribed 3 bp deletion,
AAT1030-1032, in the factor XIII A subunit gene,
has been detected in a Thai patient. The inframe deletion results in
the translation of a factor XIII A subunit that lacks Asn344. This is
the first inframe deletion to be identified in the factor XIII A
subunit gene because six previously reported deletions have all caused
frameshifts. The deletion has been introduced into a factor XIII A
subunit cDNA and the deleted polypeptide expressed in yeast. The mRNA encoding the mutant enzyme appears to have normal stability but the
translated protein is subject to premature degradation. In addition,
the mutated enzyme exhibited very little transglutaminase activity
compared with the wild-type enzyme. Structural modeling of the deleted
enzyme suggests that the absence of Asn344 would have a potent impact
on the catalytic activity by reorienting the residues associated with
the catalytic center. Thus, the Asn344 deletion strongly confirms the
significance of the residues surrounding the catalytic center of the
factor XIII A subunit.
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 481-487
© 1998 by the American Society of Hematology.
