Factor XDebrecen: Gly204Arg mutation in factor X causes the synthesis of a non-secretable protein and severe factor X deficiency.
Due to a homozygous Gly204Arg mutation in the factor X (FX) gene no detectable FX antigen was found in the plasma of a one-year old patient with severe bleeding diathesis. The amino acid replacement destabilized the disulfide bond that holds the two FX chains together, decreasing the interaction between the Cys201-Cys206 loop region and the region connecting the EGF2 and serine protease domains. Both Gly204 FX and Arg204 FX were synthesized in transfected cells, but only the wild type protein became secreted. The mutant protein was diverted from the normal secretory pathway and retained at the trans Golgi-late endosome level.
Bereczky
Zsuzsanna
Z
Clinical Research Center, Thrombosis and Vascular Biology Research Group of Hungarian Academy of Sciences, Debrecen, Hungary.
Bárdos
Helga
H
Komáromi
István
I
Kiss
Csongor
C
Haramura
Gizella
G
Ajzner
Eva
E
Adány
Róza
R
Muszbek
László
L
D019943:Amino Acid Substitution; D002460:Cell Line; D004220:Disulfides / Q000378:metabolism; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D005170:Factor X / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005171:Factor X Deficiency / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary / Q000235:genetics; D014162:Transfection
D004220:Disulfides; D005170:Factor X