Evidence map›Paper›PMID 36863563›Full record

ArticleJournal of thrombosis and haemostasis : JTH2023

A site on factor XII required for productive interactions with polyphosphate.

Aleksandr Shamanaev, Maxim Litvak, Qiufang Cheng, Michal Ponczek, S Kent Dickeson, Stephanie A Smith, James H Morrissey, David Gailani

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Crystal structure of coagulation factor XII N-terminal domains 1-5.Acta crystallographica. Section D, Structural biology · 2025
    Article
  4. Review
  5. Article
  6. Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024
    Review
  7. The Protein Scaffolding Functions of Polyphosphate.Journal of molecular biology · 2024
    Review
  8. 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 4 institutions in 2 countries.

Aleksandr ShamanaevDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: https://twitter.com/Aleksan18944927.
Maxim LitvakDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Qiufang ChengDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Michal PonczekDepartment of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
S Kent DickesonDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Stephanie A SmithDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
James H MorrisseyDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
David GailaniDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: dave.gailani@vanderbilt.edu.
Vanderbilt University Medical Center · USUniversity of Michigan · USTwitter (United States) · USUniversity of Łódź · PL

Funding

Biochemistry and Pathophysiology of Factor XI and Contact ActivationR35HL140025 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 2018 to 2024
$5.5M
Mechanisms in Blood ClottingR35HL135823 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORRISSEY, JAMES H. · 2017 to 2023
$4.8M
NHLBI NIH HHS R35 HL135823NHLBI NIH HHS R35 HL140025
6 · The paper itself

Abstract

backgroundDuring plasma contact activation, factor XII (FXII) binds to surfaces through its heavy chain and undergoes conversion to the protease FXIIa. FXIIa activates prekallikrein and factor XI (FXI). Recently, we showed that the FXII first epidermal growth factor-1 (EGF1) domain is required for normal activity when polyphosphate is used as a surface.

objectivesThe aim of this study was to identify amino acids in the FXII EGF1 domain required for polyphosphate-dependent FXII functions.

methodsFXII with alanine substitutions for basic residues in the EGF1 domain were expressed in HEK293 fibroblasts. Wild-type FXII (FXII-WT) and FXII containing the EGF1 domain from the related protein Pro-HGFA (FXII-EGF1) were positive and negative controls. Proteins were tested for their capacity to be activated, and to activate prekallikrein and FXI, with or without polyphosphate, and to replace FXII-WT in plasma clotting assays and a mouse thrombosis model.

resultsFXII and all FXII variants were activated similarly by kallikrein in the absence of polyphosphate. However, FXII with alanine replacing Lys

conclusionFXII Lys

Indexed as

Factor XIIThrombosisAnimalsFactor XIFactor XIIaHEK293 CellsHumansMicePolyphosphatesPrekallikreinFactor XIFactor XIIFactor XIIaPolyphosphatesPrekallikreinFactor XIFactor XIIkallikrein-kinin systempolyphosphateprekallikrein

Identifiers

PMID36863563
PMCPMC10192085
OpenAlexW4322615247

What OpenQuestion holds

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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.