Sirtilins – the new old members of the vitamin K‐dependent coagulation factor family
Author(s): ,
Sven O. Dahms
Department of Biosciences, University of Salzburg, Salzburg, Austria
Correspondence: Sven O. Dahms, Department of Biosciences, University of Salzburg, Billrothstr. 11, A‐5020 Salzburg, Austria|Tel.: +43 662 8044 7277|E‐mail:
Fatih Demir
ZEA‐3 Analytics, Central Institute for Engineering, Electronics and Analytics, Forschungszentrum Jülich, Jülich, Germany
Pitter F. Huesgen
ZEA‐3 Analytics, Central Institute for Engineering, Electronics and Analytics, Forschungszentrum Jülich, Jülich, Germany
Karina Thorn
Haemophilia Research, Novo Nordisk A/S, Måløv, Denmark
Hans Brandstetter
Department of Biosciences, University of Salzburg, Salzburg, Austria
ISTH Academy. O. Dahms S.
Mar 1, 2019; 273392
Sven O. Dahms
Sven  O. Dahms
Login now to access Regular content available to all registered users.

Access to Premium content is currently a membership benefit.

Click here to join ISTH or renew your membership.

You may also access ISTH content "anytime, anywhere" with the FREE ISTH Academy App for iOS and Android.
Journal Abstract
Discussion Forum (0)
Rate & Comment (0)

Vitamin K (VK)‐dependent proteases are major players in blood coagulation, including both the initiation and the regulation of the cascade. Five different members of this protease family have been described, comprising the following coagulation factors: factor VII, FIX, FX, protein C (PC), and prothrombin (FII). FVII, FIX, FX and PC share a typical domain architecture, with an N‐terminal γ‐carboxyglutamate (Gla) domain, two epidermal growth factor‐like (EGF) domains, and a C‐terminal trypsin‐like serine protease (SP) domain.
We have identified uncharacterized proteins in snake genomes showing the typical Gla–EGF1–EGF2–SP domain architecture but relatively low sequence conservation compared to known VK‐dependent proteases. On the basis of sequence analysis, we hypothesized that these proteins are functional members of the VK‐dependent protease family.
Using phylogenetic analyses, we confirmed the so‐called ‘sirtilins’ as an additional VK‐dependent protease class. These proteases were found in several vertebrates, including jawless fish, cartilaginous fish, bony fish, reptiles, birds, and marsupials, but not in other mammals. The recombinant zymogen form of Thamnophis sirtalis sirtilin was produced by in vitro renaturation, and was activated with human activated FXI. The activated form of sirtilin proteolytically cleaved peptide and protein substrates, including prothrombin. Mass spectrometry‐based substrate profiling of sirtilin revealed a narrower sequence specificity than those of FIX and FX.
The ubiquitous occurrence of sirtilins in many vertebrate classes might indicate an important functional role. Understanding the detailed functions of sirtilins might contribute to a deeper understanding of the evolution and function of the vertebrate coagulation system.
blood coagulation factors, hemostasis, mass spectrometry, phylogeny, sequence analysis, trypsin‐like serine protease
Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.

Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.

Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.

Save Settings