Evidence map›Paper›PMID 39970990›Full record

ArticleJournal of thrombosis and haemostasis : JTH2025

Identification of multiple novel procoagulant plasma ligands for stabilin-2.

Mary Underwood, Felipe Da Veiga Leprevost, Venkatesha Basrur, Alexey I Nesvizhskii, Orla Rawley, Krista Golden, Brian Emmer, David Lillicrap, Karl Desch

Abstract read
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In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024
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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

9 authors.

Mary UnderwoodDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Felipe Da Veiga LeprevostDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Venkatesha BasrurDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Alexey I NesvizhskiiDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Orla RawleyDepartment of Pathology and Molecular Medicine, Richardson Laboratory, Queen's University, Kingston, Ontario, Canada.
Krista GoldenDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Brian EmmerDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
David LillicrapDepartment of Pathology and Molecular Medicine, Richardson Laboratory, Queen's University, Kingston, Ontario, Canada.
Karl DeschDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: kdesch@med.umich.edu.

Funding

COMPUTATIONAL TOOLS FOR MASS SPECTROMETRY-BASED INTERACTOME DATAR01GM094231 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 2010 to 2026
$5.4M
The Molecular Genetics of Von Willebrand Factor SecretionR01HL172780 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Karl C Desch · 2024 to 2026
$1.8M
NHLBI NIH HHS R01 HL172780NIGMS NIH HHS R01 GM094231
6 · The paper itself

Abstract

backgroundDamaging STAB2 gene variants are associated with increased venous thromboembolic risk. STAB2 encodes stabilin-2, a clearance receptor, expressed by the liver and spleen. Given its function, it is likely that the prothrombotic state associated with stabilin-2 deficiency is due to reduced procoagulant protein clearance, but the identity of these ligands is unknown.

objectivesTo identify plasma stabilin-2 ligands using proximity biotinylation proteomics.

methodsCells stably expressing stabilin-2-TurboID were incubated with human plasma and biotin to initiate TurboID labeling of plasma ligands in endocytic vesicles. Biotinylated proteins were purified and identified using mass spectrometry. Candidate plasma ligands with roles in hemostasis were fluorescently labeled and incubated with stabilin-2 expressing and control cells. Flow cytometry assessed ligand surface binding and confocal microcopy assessed colocalization with stabilin-2 and lysosomes. Furthermore, plasma levels of ligands were measured in Stab2-deficient mice and littermate controls.

resultsTwenty-eight stabilin-2 specific ligands were identified. Interactions with von Willebrand factor, fibrinogen, pro(thrombin), heparin cofactor II, high molecular weight kininogen, plasminogen, and C4b-binding protein were probed. Heparin cofactor II, high molecular weight kininogen, plasminogen, and fibrinogen showed binding to stabilin-2 using flow cytometry (>2-fold higher than controls). Confocal microscopy demonstrated stabilin-2 dependent colocalization of all ligands with lysosomes. In Stab2-deficient mice, ligand levels were not significantly increased, suggesting in mice stabilin-2 is not their main clearance receptor.

conclusionThese results confirm the value of proximity labeling proteomics in identifying receptor ligands and suggest damaging STAB2 variants may increase venous thromboembolic risk potentially through altered hemostatic protein clearance.

Indexed as

Blood CoagulationCell Adhesion Molecules, NeuronalAnimalsBiotinylationFlow CytometryHEK293 CellsHumansLigandsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingProteomicsCell Adhesion Molecules, NeuronalLigandsSTAB2 protein, humanStab2 protein, mousefibrinogenproteomicsprothrombinstabilin-2venous thrombosisvon Willebrand factor

Identifiers

PMID39970990
PMCPMC13007390

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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.