Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin
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. Du...
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crwiley:10.1046/j.1432-1327.2000.01171.x 2024-09-09T19:30:50+00:00 Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin Andersen, Øivind Flengsrud, Ragnar Norberg, Kari Salte, Ragnar 2000 http://dx.doi.org/10.1046/j.1432-1327.2000.01171.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1432-1327.2000.01171.x https://febs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1432-1327.2000.01171.x en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor European Journal of Biochemistry volume 267, issue 6, page 1651-1657 ISSN 0014-2956 1432-1033 journal-article 2000 crwiley https://doi.org/10.1046/j.1432-1327.2000.01171.x 2024-08-20T04:15:44Z 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, K d of 2.2 and 48 n m at I = 0.15 and 0.3, respectively, is very similar to that of the minor human isoform β‐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 α(2–3) to galactose, while trace amounts of Galβ(1–4)GlcNAc suggest microheterogeneity due to partial loss of sialic acid. Article in Journal/Newspaper Atlantic salmon Salmo salar Wiley Online Library European Journal of Biochemistry 267 6 1651 1657 |
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Wiley Online Library |
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English |
description |
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, K d of 2.2 and 48 n m at I = 0.15 and 0.3, respectively, is very similar to that of the minor human isoform β‐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 α(2–3) to galactose, while trace amounts of Galβ(1–4)GlcNAc suggest microheterogeneity due to partial loss of sialic acid. |
format |
Article in Journal/Newspaper |
author |
Andersen, Øivind Flengsrud, Ragnar Norberg, Kari Salte, Ragnar |
spellingShingle |
Andersen, Øivind Flengsrud, Ragnar Norberg, Kari Salte, Ragnar Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
author_facet |
Andersen, Øivind Flengsrud, Ragnar Norberg, Kari Salte, Ragnar |
author_sort |
Andersen, Øivind |
title |
Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
title_short |
Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
title_full |
Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
title_fullStr |
Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
title_full_unstemmed |
Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
title_sort |
salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human β‐antithrombin |
publisher |
Wiley |
publishDate |
2000 |
url |
http://dx.doi.org/10.1046/j.1432-1327.2000.01171.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1432-1327.2000.01171.x https://febs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1432-1327.2000.01171.x |
genre |
Atlantic salmon Salmo salar |
genre_facet |
Atlantic salmon Salmo salar |
op_source |
European Journal of Biochemistry volume 267, issue 6, page 1651-1657 ISSN 0014-2956 1432-1033 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1046/j.1432-1327.2000.01171.x |
container_title |
European Journal of Biochemistry |
container_volume |
267 |
container_issue |
6 |
container_start_page |
1651 |
op_container_end_page |
1657 |
_version_ |
1809899804621275136 |