Title : Salmon
antithrombin has only three carbohydrate side chains, and shows functional similarities to human beta-
antithrombin
Abstract :
- Antithrombin , a major coagulation inhibitor in mammals, has for the first time been cDNA cloned from a fish species
- The predicted mature liver antithrombin of Atlantic salmon (Salmo salar) consists of 430 amino acids and shows about 67% sequence identity to mammalian and chicken antithrombins
- Due to a single nucleotide replacement, Asn135 of the antithrombin in higher vertebrates is substituted by Asp in the salmon homolog
- Hence, in contrast to the vertebrate antithrombins known so far, salmon antithrombin lacks the potential glycosylation site located close to the heparin binding site
- The existence of only three N-linked side chains is evidenced by the sequential removal of three carbohydrate chains from salmon antithrombin during timed-digestion with N-glycosidase F
- The high heparin binding affinity of the salmon inhibitor, Kd of 2.2 and 48 nM at I = 0.15 and 0.3, respectively, is very similar to that of the minor human isoform beta- antithrombin , which is not glycosylated at Asn135
- Furthermore, the invariant third- position Ser137 at this glycosylation site of mammalian and chicken antithrombins is substituted by Thr in the salmon, a replacement that has been shown to induce full glycosylation in human antithrombin
- Thus a rapidly reacting pool of antithrombin may have evolved in two different ways: absence of a glycosylation site in lower vertebrates vs. incomplete glycosylation of a part of the circulating antithrombin in higher vertebrates
- Salmon antithrombin appears to have three complex oligosaccharide side chains containing sialic acid terminally linked alpha(2-3) to galactose, while trace amounts of Galbeta(1-4)GlcNAc suggest microheterogeneity due to partial loss of sialic acid
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. has, , antithrombin, only three carbohydrate side chains, -
- 4. glycosylation, , -, -, site
- 6. glycosylated, , antithrombin, -, Asn135
- 7. glycosylation, , -, -, site
- 7. glycosylation, , antithrombin, -, -
- 8. glycosylation, , -, -, site
- 9. have, , antithrombin, three complex oligosaccharide side chains, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 6. antithrombin, -, Asn135