Functional Analysis of the Factor IX Epidermal Growth Factor-Like Domain Mutation Ile66Thr Associated with Mild Hemophilia B.
Knobe, Karin LU ; Persson, Kristina LU ; Sjörin, Elsy LU ; Villoutreix, Bruno O and Ljung, Rolf LU
(2006)
In Pathophysiology of Haemostasis and Thrombosis
35(5).
p.370-375
- Abstract
- he present study focused on the functional role of the mutation Ile66Thr located in the N-terminal epidermal growth factor-like domain of coagulation factor IX (FIX). This mutation causes mild hemophilia B with approximately 25% FIX coagulant activity and FIX antigen levels of around 90% of normal. In the 3-dimensional structure of porcine FIXa and in the subsequent 3-dimensional model of human FIXa that we have previously developed, residue 66 is exposed to the solvent and can be replaced by many amino acids, including Thr, without affecting the major folding/stability of the molecule. This is consistent with the basically normal antigen levels observed. We found that the FIX Ile66Thr mutant was activated to a normal extent by FVIIa/TF... (More)
- he present study focused on the functional role of the mutation Ile66Thr located in the N-terminal epidermal growth factor-like domain of coagulation factor IX (FIX). This mutation causes mild hemophilia B with approximately 25% FIX coagulant activity and FIX antigen levels of around 90% of normal. In the 3-dimensional structure of porcine FIXa and in the subsequent 3-dimensional model of human FIXa that we have previously developed, residue 66 is exposed to the solvent and can be replaced by many amino acids, including Thr, without affecting the major folding/stability of the molecule. This is consistent with the basically normal antigen levels observed. We found that the FIX Ile66Thr mutant was activated to a normal extent by FVIIa/TF and FXIa. However, the ability of FIX Ile66Thr to activate FX was impaired in both the presence and absence of FVIIIa, indicating that Ile66 is not directly involved in the binding of FIX to FVIIIa. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/164812
- author
- Knobe, Karin
LU
; Persson, Kristina
LU
; Sjörin, Elsy
LU
; Villoutreix, Bruno O
and Ljung, Rolf
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- mutation Ile66Thr, hemophilia B, epidermal growth factor domain, factor IX, coagulation
- in
- Pathophysiology of Haemostasis and Thrombosis
- volume
- 35
- issue
- 5
- pages
- 370 - 375
- publisher
- Karger
- external identifiers
-
- wos:000243565000003
- scopus:33846465549
- pmid:17230038
- ISSN
- 1424-8832
- DOI
- 10.1159/000097691
- language
- English
- LU publication?
- yes
- id
- 8f82cc1d-2c29-42ec-b6e5-03054f5e17e7 (old id 164812)
- date added to LUP
- 2016-04-01 12:30:56
- date last changed
- 2022-03-29 01:57:20
@article{8f82cc1d-2c29-42ec-b6e5-03054f5e17e7,
abstract = {{he present study focused on the functional role of the mutation Ile66Thr located in the N-terminal epidermal growth factor-like domain of coagulation factor IX (FIX). This mutation causes mild hemophilia B with approximately 25% FIX coagulant activity and FIX antigen levels of around 90% of normal. In the 3-dimensional structure of porcine FIXa and in the subsequent 3-dimensional model of human FIXa that we have previously developed, residue 66 is exposed to the solvent and can be replaced by many amino acids, including Thr, without affecting the major folding/stability of the molecule. This is consistent with the basically normal antigen levels observed. We found that the FIX Ile66Thr mutant was activated to a normal extent by FVIIa/TF and FXIa. However, the ability of FIX Ile66Thr to activate FX was impaired in both the presence and absence of FVIIIa, indicating that Ile66 is not directly involved in the binding of FIX to FVIIIa.}},
author = {{Knobe, Karin and Persson, Kristina and Sjörin, Elsy and Villoutreix, Bruno O and Ljung, Rolf}},
issn = {{1424-8832}},
keywords = {{mutation Ile66Thr; hemophilia B; epidermal growth factor domain; factor IX; coagulation}},
language = {{eng}},
number = {{5}},
pages = {{370--375}},
publisher = {{Karger}},
series = {{Pathophysiology of Haemostasis and Thrombosis}},
title = {{Functional Analysis of the Factor IX Epidermal Growth Factor-Like Domain Mutation Ile66Thr Associated with Mild Hemophilia B.}},
url = {{http://dx.doi.org/10.1159/000097691}},
doi = {{10.1159/000097691}},
volume = {{35}},
year = {{2006}},
}