Evidence map›Paper›PMID 20308596›Full record

ArticleBlood2010

Activated protein C cofactor function of protein S: a critical role for Asp95 in the EGF1-like domain.

Helena M Andersson, Márcia J Arantes, James T B Crawley, Brenda M Luken, Sinh Tran, Björn Dahlbäck, David A Lane, Suely M Rezende

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Protein S K196E mutation reduces its cofactor activity for APC but not for TFPI.Research and practice in thrombosis and haemostasis · 2018
    Article
  15. Article
  16. TAM receptor signaling in immune homeostasis.Annual review of immunology · 2015
    Review
  17. Article
  18. Phosphorylation of protein S by platelet kinases enhances its activated protein C cofactor activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    Article
  19. Article
  20. Down-regulation of the clotting cascade by the protein C pathway.Hematology education. European Hematology Association. Congress. Education Program · 2013
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Helena M AnderssonDepartment of Haematology, Faculty of Medicine, Imperial College London, London, UK.
Márcia J Arantes
James T B Crawley
Brenda M Luken
Sinh Tran
Björn Dahlbäck
David A Lane
Suely M Rezende
Imperial College London · GBLund University · SEUniversidade Federal de Minas Gerais · BR

Funding

British Heart Foundation PG/07/005British Heart Foundation PG/09/105/28138Wellcome Trust 075160
6 · The paper itself

Abstract

Protein S has an established role in the protein C anticoagulant pathway, where it enhances the factor Va (FVa) and factor VIIIa (FVIIIa) inactivating property of activated protein C (APC). Despite its physiological role and clinical importance, the molecular basis of its action is not fully understood. To clarify the mechanism of the protein S interaction with APC, we have constructed and expressed a library of composite or point variants of human protein S, with residue substitutions introduced into the Gla, thrombin-sensitive region (TSR), epidermal growth factor 1 (EGF1), and EGF2 domains. Cofactor activity for APC was evaluated by calibrated automated thrombography (CAT) using protein S-deficient plasma. Of 27 variants tested initially, only one, protein S D95A (within the EGF1 domain), was largely devoid of functional APC cofactor activity. Protein S D95A was, however, gamma-carboxylated and bound phospholipids with an apparent dissociation constant (Kd(app)) similar to that of wild-type (WT) protein S. In a purified assay using FVa R506Q/R679Q, purified protein S D95A was shown to have greatly reduced ability to enhance APC-induced cleavage of FVa Arg306. It is concluded that residue Asp95 within EGF1 is critical for APC cofactor function of protein S and could define a principal functional interaction site for APC.

Indexed as

Amino Acid SubstitutionAspartic AcidMutation, MissenseFactor VaFactor VIIIaHumansProtein CProtein SProtein Structure, TertiaryAspartic AcidFactor VaFactor VIIIaProtein CProtein S

Identifiers

PMID20308596
PMCPMC2884152
OpenAlexW1973965500

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.