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Last update 08 May 2025

STAB2

Last update 08 May 2025

Basic Info

Synonyms

190 kDa form stabilin-2, 190 kDa hyaluronan receptor for endocytosis, DKFZP434E0321

+ [13]

Introduction

Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalization as well as HA and CS.

Drugs associated with STAB2

HG-1263

Target

STAB2 x Scavenger receptor

Mechanism

STAB2 modulators [+1]

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Cardiovascular Diseases [+3]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STAB2

100 Translational Medicine associated with STAB2

0 Patents (Medical) associated with STAB2

212

Literatures (Medical) associated with STAB2

18 Feb 2025·Proceedings of the National Academy of Sciences

Scavenger endothelial cells alleviate tissue damage by engulfing toxic molecules derived from hemolysis

Article

Author: Li, Feifei ; Xu, Jin ; Xu, Yongtai ; Dai, Yimei ; Gao, Meng ; Jiang, Yunyun ; Cao, Canran ; Lai, Siting ; Zhu, Wenchao ; He, Sicong

Hemolysis induces tissue damage by releasing cellular contents into the plasma. It is widely accepted that hemolysis-derived toxic molecules are cleared by macrophages or metabolized in hepatocytes. In zebrafish, we found that scavenger endothelial cells (SECs), a specialized endothelium with remarkable endocytosis capability, engulf both macromolecular hemoglobin (Hb) and small molecular unconjugated bilirubin (UCB), two primary toxic byproducts of hemolysis. These engulfment processes are mediated by the scavenger receptor Stab2. To demonstrate the protective function of SECs during hemolysis, we employed a zebrafish model of erythropoietic porphyria, characterized by excessive protoporphyrin IX (PPIX) accumulation due to ferrochelatase mutation, leading to light-sensitive hemolysis and larva death. We found that SECs facilitate the clearance of excess PPIX via Stab2, thereby mitigating PPIX-induced larval mortality. In addition, mouse SECs possess a conserved capability of scavenging Hb/UCB/PPIX. In conclusion, our study identifies SECs as a detoxification system during physiological and pathological hemolysis, shedding light on their protective role against hemolysis-induced damage.

01 Feb 2025·Journal of Thrombosis and Haemostasis

Identification of multiple novel procoagulant plasma ligands for stabilin-2

Article

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

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.

01 Feb 2025·Neurology Genetics

Novel Phenotypes and Genotypes Identified by Genome Sequencing

Article

Author: Mercimek-Andrews, Saadet ; Wyszynska, Agnieszka ; McNiven, Vanda ; Underwood, Mary ; Desch, Karl ; Ambrose, Anastasia ; Malik, Anna R. ; Tempes, Aleksandra ; Wilson, Diane ; Schulze, Andreas ; Chau, Vann

Background and ObjectivesNeonatal encephalopathy (NE) is characterized by an abnormal level of consciousness with or without seizures in the neonatal period. It affects 1-6/1,000 live term newborns. We applied genome sequencing (GS) in term newborns with NE to investigate the underlying genetic causes.MethodsWe enrolled term newborns according to inclusion/exclusion criteria during their Neonatal Intensive Care admission. We performed GS trio and applied bioinformatic tools. We developed pipelines for manual filters. We applied in silico prediction tools, protein 3D modeling, and functional characterization to assess the pathogenicity of variants.ResultsSeventeen newborns fulfilled inclusion criteria. We identified 12 variants in 10 genes. We classified 4 variants in PPP2R5D, BCOR, CFL2, and SCN2A (previously established disease genes) as pathogenic/likely pathogenic; 7 variants in DST (previously established disease gene), STAB2, CELF4, SORCS2, CTNND2, and ASTN1 (5 candidate genes) as variants of uncertain significance (VUS); and one variant in STAB2 as likely benign. The CELF4 and ASTN1 copy number variants (CNVs) resulted in structural changes in protein 3D models. The functional characterization of SORCS2 VUS revealed disruption of SorCS2 dimer formation and confirmed its pathogenicity. The functional characterization of STAB2 variants updated their characterization from VUS/likely benign to benign. The CTNND2 VUS resulted in a shift in 3D protein structure. We were not able to perform protein 3D modeling and functional characterization of two DST VUS. We are not certain whether CTNND2 and DST variants may be causative of NE in our study.DiscussionThe diagnostic rate of research GS was 41% in our prospective study. We broaden the phenotypic spectrum of PPP2R5D-associated Hogue-Janssens syndrome 1, CFL2-associated nemaline myopathy 7, and BCOR-associated oculo-facio-cardio-dental syndrome to include NE and/or neonatal seizures. We identified 3 candidate genes (SORCS2, CELF4, ASTN1) that may cause NE. We believe that protein 3D modeling is an important tool to assess the pathogenicity of CNVs and may advance the discoveries of novel genetic diseases. However, functional characterization of missense variants is essential for discoveries of novel genetic diseases. It seems that GS can help identify more candidate genes compared with ES.

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STAB2

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