Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant signal peptidase cleavage site.
Antithrombin Dublin is an electrophoretically fast variant of antithrombin which has normal heparin affinity. Direct sequencing of amplified exon 2 revealed a Val----Glu substitution at position -3. N-terminal sequencing of antithrombin from two individuals, heterozygous for the Dublin mutation, showed the presence of a truncated antithrombin in which the N-terminal dipeptide is absent. We propose that the prepeptide mutation redirects signal peptidase cleavage to a site two amino acids downstream into the mature protein.
Daly
M
M
Department of Haematology, MRC Centre, Cambridge, UK.
Bruce
D
D
Perry
D J
DJ
Price
J
J
Harper
P L
PL
O'Meara
A
A
Carrell
R W
RW
D000328:Adult; D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D010450:Endopeptidases / Q000378:metabolism*; D005091:Exons; D005784:Gene Amplification; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D005971:Glutamates; D018698:Glutamic Acid; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012016:Reference Values; D012697:Serine Endopeptidases; D014633:Valine
D005971:Glutamates; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; C052721:antithrombin III Dublin; D018698:Glutamic Acid; D000990:Antithrombin III; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase; D014633:Valine