Affinage

MSR1

Macrophage scavenger receptor types I and II · UniProt P21757

Length
451 aa
Mass
49.8 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSR1 (CD204/SCARA1/SR-AI) is a trimeric macrophage, dendritic cell, and microglial scavenger receptor that couples broad ligand recognition to phagocytic clearance and tunable intracellular signaling across innate immunity, tissue repair, and neurodegeneration (PMID:31653705, PMID:28394332, PMID:23799536). Its two functional modules engage distinct ligand classes: the positively charged collagen-like domain binds extracellular dsRNA and anionic crystalline surfaces, transporting dsRNA to endosomal TLR3 to drive interferon responses (PMID:23717201, PMID:23614696), while the Ca2+-dependent SRCR domain recognizes the spectrin SPEC repeats exposed on dead cells and the complement fragment iC3b, the latter activating NF-κB and IL-8 production against opsonized bacteria (PMID:31653705, PMID:21203986). Through these modules MSR1 acts as a clearance receptor for an array of damage- and disease-associated ligands—soluble amyloid-β, myelin debris, von Willebrand factor, soluble autoantigen (glucose-6-phosphate isomerase), oxidized lipids, and DAMPs including HMGB1, peroxiredoxins, and ferritin—and these uptake functions limit or, in specific contexts, exacerbate inflammation and tissue injury (PMID:28394332, PMID:23799536, PMID:29326120, PMID:17332894, PMID:32066456, PMID:23794629). MSR1 also operates as a co-receptor, associating with Mertk at the cell surface to support Mertk phosphorylation and apoptotic cell ingestion (PMID:18511575). Its signaling output is bidirectional and context-dependent: it directly binds the TRAF-C domain of TRAF6 to block TRAF6 dimerization and K63-linked ubiquitination, suppressing TLR4-driven NF-κB activation and IL-12 production and dampening dendritic-cell-mediated T cell priming (PMID:21460221, PMID:19349620, PMID:16339540), yet in IL-4-activated M2 macrophages MSR1 itself becomes K63-polyubiquitylated, recruiting the TAK1/MKK7/JNK complex to phagosomes to drive a switch toward a pro-inflammatory state (PMID:31028084). MSR1 further engages PI3K/AKT/β-catenin and AMPK/mTOR axes to control macrophage polarization, osteogenic differentiation of co-cultured stromal cells, and leukemia stem cell behavior (PMID:24278429, PMID:21596859, PMID:31903103, PMID:36095948). N-glycosylation at paired sites and SRCR-domain structural integrity are required for proper surface targeting and ligand internalization (PMID:26892079).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2005 Medium

    Established that scavenger-receptor engagement is not merely uptake but actively modulates macrophage activation, with SR-AI specifically restraining IL-12 production in opposition to MARCO.

    Evidence SR-AI/II- and MARCO-deficient mouse macrophages with mAb ligation, IL-12 ELISA, and phagocytosis assays

    PMID:16339540

    Open questions at the time
    • Molecular mechanism linking SR-AI ligation to IL-12 suppression not defined
    • No receptor domain mapping
  2. 2007 Medium

    Defined a tissue-protective scavenging role by showing MSR1 clears proinflammatory oxidized lipids from lung lining fluid to limit pulmonary inflammation.

    Evidence SR-AI/II- and MARCO-knockout mice with intratracheal oxidized lipid instillation and in vitro uptake assays

    PMID:17332894

    Open questions at the time
    • Receptor domain responsible for oxidized lipid binding not mapped
    • Downstream signaling not addressed
  3. 2008 Medium

    Showed MSR1 functions as a co-receptor in efferocytosis, associating with Mertk to enable optimal Mertk phosphorylation during apoptotic cell uptake.

    Evidence Reciprocal Co-IP in J774 and peritoneal macrophages, SR-A blocking, and phosphorylation assays in SR-A-/- cells

    PMID:18511575

    Open questions at the time
    • Structural basis of SR-A/Mertk association unknown
    • Single lab; reciprocal validation within one study
  4. 2009 Medium

    Localized MSR1's immunosuppressive activity to dendritic cells, where it negatively regulates TLR4-driven CD8+ T cell priming.

    Evidence SRA-knockout mice, DC–T cell co-culture, siRNA knockdown, and tumor growth assays

    PMID:19349620

    Open questions at the time
    • Signaling mechanism in DCs not resolved here
    • Whether suppression requires endocytosis unclear
  5. 2011 High

    Identified the molecular basis of MSR1's anti-inflammatory signaling: a direct interaction with the TRAF-C domain of TRAF6 that blocks TRAF6 dimerization and K63-ubiquitination, uncoupling signaling from endocytosis.

    Evidence Co-IP, TRAF-C domain mutagenesis, NF-κB reporter assays, and LPS endotoxic shock in MSR1-deficient mice

    PMID:21460221

    Open questions at the time
    • Stoichiometry of MSR1-TRAF6 interaction not defined
    • How ligand binding regulates this interaction unknown
  6. 2011 Medium

    Extended the DC immunosuppression mechanism to CD4+ T cells, showing SRA inhibits STAT1, p38, and NF-κB signaling, and that SRA binds and internalizes hsp110 yet attenuates heat-shock-protein-based vaccine responses.

    Evidence SRA-/- mice, DC–OT-II co-culture, phosphorylation assays, hsp110 binding/internalization, shRNA silencing, and melanoma tumor model

    PMID:21832164 PMID:22083206

    Open questions at the time
    • Direct link between MSR1 and STAT1/p38 inhibition not mechanistically resolved
    • Relationship to TRAF6 inhibition not connected
  7. 2011 Medium

    Revealed a tumor-suppressive role in CML, where BCR-ABL downregulates Msr1 and Msr1 loss accelerates leukemia via PI3K-AKT and β-catenin.

    Evidence CML mouse model with Msr1 knockout, microarray, cell cycle/apoptosis assays, and pathway Western blotting

    PMID:21596859

    Open questions at the time
    • Direct receptor input driving PI3K-AKT/β-catenin not identified
    • Ligand in the LSC context unknown
  8. 2013 High

    Demonstrated MSR1 as an endocytic conduit delivering extracellular dsRNA to endosomal TLR3, mapping binding to basic residues of the collagen-like domain.

    Evidence RNAi knockdown, exogenous MSR1 reconstitution, collagen-domain mutagenesis, dsRNA binding, and HCV/TLR3 signaling readouts

    PMID:23717201

    Open questions at the time
    • How dsRNA is handed off to TLR3 in the endosome not defined
    • Trafficking machinery unidentified
  9. 2013 High

    Established MSR1 as a soluble amyloid-β receptor on myeloid cells controlling Aβ clearance in vivo.

    Evidence shRNA screen, Scara1-null × PS1-APP genetic cross, pharmacological upregulation, and Aβ clearance assays

    PMID:23799536

    Open questions at the time
    • Receptor domain binding Aβ not mapped here
    • Signaling consequences of Aβ binding not addressed
  10. 2013 Medium

    Showed additional scavenging roles: clearance of soluble autoantigen GPI to limit autoimmune arthritis, profibrotic M2 polarization via collagen-I/PI3K-Akt signaling, and opsonin-independent uptake of iron oxide nanoparticles via the collagen-like domain.

    Evidence Msr1-/- K/BxN mice with BM transplant; anti-CD204 blocking and PI3K inhibitor in alveolar macrophages; nanoparticle uptake with computational docking

    PMID:23614696 PMID:23794629 PMID:24278429

    Open questions at the time
    • Collagen-I receptor engagement vs collagen-like-domain binding not structurally distinguished
    • Signaling specificity across ligands unresolved
  11. 2016 Medium

    Defined post-translational and structural requirements, showing dual N-glycosylation and SRCR-domain integrity are needed for surface targeting and oAβ internalization.

    Evidence Site-directed mutagenesis of N-glycosylation sites and SRCR features, surface expression, and oAβ internalization assays

    PMID:26892079

    Open questions at the time
    • How glycosylation affects ligand affinity vs trafficking not separated
    • Single lab
  12. 2017 High

    Connected MSR1 scavenging to neuroinflammation resolution, showing Mafb-driven MSR1 clears DAMPs after stroke to protect neurons.

    Evidence In vitro DAMP internalization, ischemic stroke model with Msr1/Marco and Mafb conditional knockouts, and RAR-agonist upregulation

    PMID:28394332

    Open questions at the time
    • Whether DAMP uptake triggers signaling or pure clearance unclear
    • Individual DAMP binding sites not mapped
  13. 2018 Medium

    Identified MSR1 as a calcium-dependent macrophage clearance receptor for von Willebrand factor, with VWF mutants of increased clearance binding more tightly.

    Evidence Purified protein binding (~14 nM), SR-AI-/- BMDM cell binding, domain mapping, and in vivo VWF clearance

    PMID:29326120

    Open questions at the time
    • Receptor domain binding VWF A1/D4 not pinpointed
    • Single lab
  14. 2019 High

    Resolved the structural basis of dead-cell recognition, showing the SRCR domain binds spectrin SPEC repeats in a Ca2+-dependent manner to mediate efferocytosis.

    Evidence 1.8 Å SRCR crystal structure, MS identification of spectrin, Ca2+-dependency, and dead-erythrocyte phagocytosis assays

    PMID:31653705

    Open questions at the time
    • How spectrin recognition integrates with the Mertk co-receptor complex unknown
  15. 2019 High

    Revealed a signaling switch mechanism: K63-polyubiquitylation of MSR1 itself in M2 macrophages recruits TAK1/MKK7/JNK to phagosomes, driving a pro-inflammatory phenotypic switch.

    Evidence Phagosomal proteomics, ubiquitination and JNK phosphorylation assays, MSR1 knockout macrophages, and JNK inhibition

    PMID:31028084

    Open questions at the time
    • The ubiquitin ligase modifying MSR1 not identified
    • Trigger linking ligand engagement to MSR1 ubiquitylation unknown
  16. 2020 Medium

    Showed context-dependent roles in tissue injury and repair: myelin-debris uptake driving NF-κB-dependent neuronal damage after spinal cord injury, and PI3K/AKT/GSK3β/β-catenin signaling promoting osteogenesis and M2 polarization via PGC1α.

    Evidence MSR1-knockout mouse SCI and tibial-defect models, macrophage–BMSC co-culture, NF-κB and PI3K/AKT pathway Western blotting, and RNA-seq

    PMID:31903103 PMID:32066456

    Open questions at the time
    • How the same receptor selects NF-κB vs PI3K/AKT outputs unresolved
    • Direct vs indirect coupling to PGC1α unknown
  17. 2022 Medium

    Extended ligand range and pathology, showing ferritin engages neutrophil Msr1 to drive NET formation and cytokine storm, and linking MSR1 metabolic rewiring (arginine/proline, AMPK/mTOR) to M2 polarization in gastric cancer.

    Evidence Ferritin administration with Msr1-knockout mice and NET assays (PAD4/NE/ROS); MSR1 knockdown with metabolomics, AMPK/mTOR Western blotting, and scRNA-seq

    PMID:36095948 PMID:36357401

    Open questions at the time
    • Ferritin binding site on Msr1 not mapped
    • Gastric cancer metabolic pathway inferred from knockdown without reconstitution
  18. 2025 Medium

    Implicated MSR1 in myelin clearance in human neurodegenerative dementia, with overexpression enhancing microglial phagocytosis and MSR1+ microglia co-localizing with myelin in patient cortex.

    Evidence Microglial overexpression phagocytosis assay, myelin-induced MSR1 upregulation, human PDD cortex immunohistochemistry, and snRNA-seq

    PMID:40826098

    Open questions at the time
    • Whether myelin clearance is protective or pathogenic in dementia unresolved
    • Receptor domain binding myelin not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor selects between opposing signaling outputs—TRAF6-mediated NF-κB suppression versus phagosomal JNK activation versus NF-κB and PI3K/AKT activation—depending on ligand, activation state, and post-translational modification remains unresolved.
  • No unifying model linking ligand identity to signaling outcome
  • Ligase and adaptors controlling MSR1 ubiquitylation unidentified
  • Structural basis for collagen-domain vs SRCR-domain ligand selection incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1 GO:0008289 lipid binding 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2
Partners
MARCOMERTKTLR3TRAF6

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 MSR1/CD204 directly interacts with the TRAF-C domain of TRAF6, inhibiting TRAF6 dimerization and K63-linked ubiquitination, thereby suppressing TLR4-induced NF-κB activation. This regulatory function is independent of MSR1's ligand-binding domain, uncoupling its signaling role from its endocytic function. Co-immunoprecipitation, domain mutagenesis, NF-κB reporter assays, LPS endotoxic shock model in MSR1-deficient mice The Journal of biological chemistry High 21460221
2019 MSR1 undergoes K63-linked polyubiquitylation in IL-4-activated (M2) macrophages, which recruits the TAK1/MKK7/JNK signalling complex to phagosomes. Triggering MSR1 in this context activates JNK, promoting a phenotypic switch from anti-inflammatory to pro-inflammatory state; this switch is abolished by MSR1 deletion or JNK inhibition. Phagosomal proteomics, ubiquitination assays, JNK phosphorylation assays, MSR1 knockout macrophages, JNK inhibitor experiments The EMBO journal High 31028084
2013 MSR1 binds extracellular dsRNA via conserved basic residues in the carboxy-terminal collagen superfamily domain, mediates endocytosis and transport to the endosome where TLR3 is engaged, triggering interferon responses. RNAi knockdown of MSR1 blocks TLR3 sensing of HCV, while exogenous MSR1 restores signalling. RNAi knockdown, exogenous MSR1 expression, mutagenesis of collagen domain basic residues, dsRNA binding assays, HCV infection assays, TLR3 signalling readouts PLoS pathogens High 23717201
2019 SCARA1/MSR1 recognizes dead (but not live) cells specifically through its SRCR domain in a Ca2+-dependent manner. The binding target on dead cells is spectrin; the SRCR domain binds SPEC repeats of spectrin in the presence of Ca2+. Macrophages internalize dead cells and debris through this SCARA1–spectrin interaction. Crystal structure of SRCR domain at 1.8 Å, cell-based binding assays, mass spectrometry identification of spectrin, Ca2+-dependency assays, phagocytosis assays with dead erythrocytes The Journal of biological chemistry High 31653705
2008 SR-A/MSR1 associates with the receptor tyrosine kinase Mertk at the cell surface and is required for optimal Mertk phosphorylation during apoptotic cell uptake. Exposure to apoptotic cells induces a time-dependent increase in SR-A/Mertk association; blocking SR-A inhibits phosphorylation of both Mertk and PLCγ2, reducing apoptotic cell ingestion. Western blotting and co-immunoprecipitation in J774 macrophages and peritoneal macrophages from SR-A−/− mice, anti-SR-A blocking, phosphorylation assays Journal of leukocyte biology Medium 18511575
2017 MSR1 (and MARCO) mediates internalization of DAMPs (HMGB1, peroxiredoxins, S100A8/S100A9) in vitro and in ischemic brain in vivo. DAMP clearance in infiltrating myeloid cells 3 days after stroke requires MSR1, whose expression is upregulated by the transcription factor Mafb. Combined Msr1/Marco deficiency or Mafb deficiency impairs DAMP clearance, worsening inflammation and neuronal injury. In vitro DAMP internalization assays, murine ischemic stroke model, Msr1/Marco and Mafb conditional knockout mice, RAR agonist Am80 upregulation of Mafb/MSR1 Nature medicine High 28394332
2013 Scara1/MSR1 is a receptor for soluble amyloid-β on myeloid cells. Scara1 deficiency in PS1-APP mice markedly accelerates Aβ accumulation and increases mortality; pharmacological upregulation of Scara1 on mononuclear phagocytes increases Aβ clearance. shRNA screening to identify Scara1 as soluble Aβ receptor, genetic cross of Scara1-null with PS1-APP mice, pharmacological Scara1 upregulation, Aβ clearance assays Nature communications High 23799536
2013 Collagen type I monomers signal through CD204/MSR1 to induce phospho-Akt expression in alveolar macrophages, promoting M2 profibrotic polarization (upregulation of CCL18, IL-1ra, CCL2). This effect is abrogated by neutralizing anti-CD204 antibody and by the PI3K inhibitor LY294002. Neutralizing anti-CD204 antibody treatment of alveolar macrophages, collagen stimulation assays, phospho-Akt ELISA, cytokine ELISA (CCL18, IL-1ra, CCL2), RT-PCR and flow cytometry for CD204 PloS one Medium 24278429
2018 SR-AI/MSR1 is a macrophage clearance receptor for von Willebrand factor (VWF). VWF binds SR-AI with half-maximum binding of ~14 nM in a calcium-dependent manner, requiring the A1 and D4 domains of VWF. SR-AI−/− mice show significantly reduced VWF clearance; VWF mutants with increased clearance (R1205H, S2179F) show enhanced binding to SR-AI. Purified protein binding assays, cell-binding experiments with SR-AI-deficient bone marrow–derived macrophages, hydrodynamic gene transfer in vivo, propeptide/antigen ratio measurements Haematologica Medium 29326120
2022 Ferritin acts as a ligand for Msr1 on neutrophils, triggering NET formation and a cytokine storm. Ferritin exposure increases Msr1 surface expression on neutrophils; Msr1 ablation protects mice from ferritin-induced tissue damage and hyperinflammatory response. NET formation depends on PAD4, neutrophil elastase, and ROS downstream of Msr1. Ferritin administration in vivo, Msr1-knockout mice, neutrophil depletion, flow cytometry for Msr1 surface expression, NET formation assays (PAD4/NE/ROS dependence) Nature communications High 36357401
2011 MSR1 suppresses Msr1 expression is downregulated by BCR-ABL in CML leukemia stem cells; Msr1 deletion accelerates CML development and increases LSC function by promoting cell cycle progression and inhibiting apoptosis. Msr1 affects CML development by regulating the PI3K-AKT pathway and β-Catenin. CML mouse model, Msr1 knockout, DNA microarray, cell cycle and apoptosis assays, PI3K-AKT/β-Catenin Western blotting Blood Medium 21596859
2009 MSR1/SRA/CD204 on dendritic cells negatively regulates TLR4-mediated CD8+ T cell activation; SRA-deficient DCs are more immunostimulatory upon TLR4 engagement. siRNA-mediated knockdown of SRA in DCs improves priming of antigen-specific CD8+ T cells, demonstrating that DCs are the major cellular locus of MSR1-mediated immune suppression. SRA-knockout mice, DC–T cell co-culture assays, siRNA knockdown by RNAi, TLR4 agonist stimulation, tumor growth inhibition assays Blood Medium 19349620
2011 SRA/CD204 suppresses antigen-specific CD4+ T cell activation by reducing the intrinsic immunostimulatory capacity of dendritic cells, independently of classical endocytosis. Molecular mechanism involves SRA/CD204 inhibiting STAT1, p38 MAPK, and NF-κB signalling in DCs stimulated with anti-CD40 and IFN-γ. SRA−/− mice immunized with OVA, DC–OT-II cell co-culture, STAT1/p38/NF-κB phosphorylation assays, IL-12p35 expression upon CD40 ligation Journal of molecular medicine Medium 22083206
2011 SRA/CD204 binds exogenous hsp110 and mediates its internalization by dendritic cells; however, SRA−/− DCs pulsed with hsp110-antigen chaperone complexes show profoundly increased T cell stimulation, implicating MSR1 as an immunosuppressive receptor that attenuates heat-shock-protein–based vaccine responses via NF-κB regulation. Binding/internalization assays with hsp110 in SRA−/− DCs, NF-κB activation assays, shRNA lentiviral silencing, in vivo melanoma tumor model Journal of immunology Medium 21832164
2007 SR-AI/MSR1 and MARCO expressed on alveolar macrophages scavenge proinflammatory oxidized lipids (5β,6β-epoxycholesterol, PON-GPC) from lung lining fluid, limiting pulmonary inflammation after oxidant inhalation. SR-AI/II-deficient mice show enhanced acute lung inflammation after β-epoxide instillation; normal AMs showed greater in vitro uptake of β-epoxide than SR-AI-deficient AMs. SR-AI/II-knockout mice, MARCO-knockout mice, intratracheal instillation of oxidized lipids, in vitro lipid uptake assays, ozone exposure, BAL cell counts and cytokines The Journal of clinical investigation Medium 17332894
2020 MSR1 promotes phagocytosis of myelin debris and subsequent foamy macrophage formation after spinal cord injury. In the presence of myelin debris, MSR1 activates the NF-κB signalling pathway, leading to release of inflammatory mediators and neuronal apoptosis. MSR1-knockout mice show improved recovery from traumatic SCI. MSR1-knockout mice SCI model, in vitro macrophage myelin debris phagocytosis assays, NF-κB pathway Western blotting, immunofluorescence, qPCR Journal of neuroinflammation Medium 32066456
2020 Macrophage MSR1 activates the PI3K/AKT/GSK3β/β-catenin pathway in macrophage–BMSC co-culture to promote osteogenic differentiation of BMSCs. MSR1 also promotes M2-like macrophage polarization by enhancing mitochondrial oxidative phosphorylation through the target gene PGC1α downstream of this pathway. MSR1-knockout mice show delayed intramembranous ossification. MSR1-knockout mouse tibial defect model, macrophage–BMSC co-culture, Western blotting for PI3K/AKT/GSK3β/β-catenin, RNA sequencing, qPCR, immunofluorescence Theranostics Medium 31903103
2013 SR-AI/MSR1 mediates opsonin-independent recognition of dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles via its positively charged collagen-like domain. Recognition requires access to the iron oxide crystalline core; polymer coating sterically hinders binding. Computer modelling reveals complementarity between Fe-OH surface groups of magnetite and charged lysines in the collagen-like domain. Uptake assays in SR-AI-transfected cells and J774 macrophages, nanoparticles with varied coatings, computational docking/modelling of SR-AI collagen domain ACS nano Medium 23614696
2010 SR-AI/MSR1 binds complement fragment iC3b (but not C3 or C3b) through its SRCR domain and mediates NF-κB activation and IL-8 production in response to iC3b-opsonized bacteria. SRCR domain mutagenesis abolishes binding to serum-sensitized E. coli and iC3b. SR-AI expression in HEK 293T cells, binding assays with purified iC3b/C3/C3b, anti-C3 antibody blocking, SRCR domain mutagenesis, NF-κB/IL-8 reporter assays Protein & cell Medium 21203986
2013 Macrophage MSR1 regulates the concentration of soluble autoantigen (glucose-6-phosphate isomerase) in serum. Msr1-deficient macrophages are inefficient at taking up glucose-6-phosphate isomerase, leading to elevated serum autoantigen levels and impaired autoreactive B cell activation, thereby reducing autoantibody-dependent arthritis. Msr1-knockout K/BxN TCR transgenic mice, bone marrow transplantation, autoantigen uptake assays by macrophages, serum autoantigen measurements Journal of immunology Medium 23794629
2022 MSR1 mediates M2 macrophage polarization by regulating arginine and proline metabolism and activating the AMPK/mTOR pathway, thereby promoting gastric cancer progression. MSR1 knockdown inhibits M2 macrophage polarization and associated malignant behaviour of gastric cancer cells in vitro. MSR1 knockdown in macrophages, AMPK/mTOR pathway Western blotting, metabolomics (arginine/proline metabolism), scRNA-seq analysis, co-culture with gastric cancer cells International immunopharmacology Low 36095948
2016 N-glycosylation of SR-AI at dual N-glycosylation sites (N120Q-N143Q and N143Q-N184Q) is critical for oAβ internalization; cells expressing these SR-AI mutants show diminished oAβ uptake despite normal surface targeting. SRCR domain structural integrity (β-sheet, α-helix, disulfide bond) is required for N-glycosylation and surface targeting of SR-AI. Site-directed mutagenesis of N-glycosylation sites, cell surface expression assays, oAβ internalization assays in mutant-expressing cells Journal of biomedical science Medium 26892079
2005 SR-AI/MSR1 ligation specifically inhibits LPS/IFN-γ-stimulated IL-12 production and macrophage activation, while MARCO ligation has the opposite effect (costimulates IL-12). SR-AI/II-deficient macrophages overproduce IL-12 in response to LPS; SR-AI mediates particle uptake in untreated and IL-4-treated macrophages but not CpG-ODN-pretreated cells. MARCO- and SR-AI/II-deficient mouse macrophages, mAb ligation experiments, cytokine ELISA (IL-12), phagocytosis assays, regulatory condition comparisons Journal of immunology Medium 16339540
2025 MSR1 overexpression in microglial cells enhances phagocytic activity toward myelin; reciprocally, myelin treatment upregulates MSR1 protein levels in microglia. MSR1-positive microglia co-localise with MBP in cortical tissue of PDD patients, indicating a functional role in myelin debris clearance in neurodegenerative dementias. MSR1 overexpression in microglial cells (phagocytosis assay), myelin treatment upregulation of MSR1 (Western blot), immunohistochemistry co-localisation in human PDD cortex, snRNA-seq Genome medicine Medium 40826098

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics 256 31903103
2017 MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. Nature medicine 196 28394332
2013 Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer's-like disease progression. Nature communications 176 23799536
2013 Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer science 160 23648122
2010 Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 152 20802348
2017 CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma. Scientific reports 136 28496107
2014 Scavenger receptor-A (CD204): a two-edged sword in health and disease. Critical reviews in immunology 123 24941076
2006 The macrophage scavenger receptor SR-AI/II and lung defense against pneumococci and particles. American journal of respiratory cell and molecular biology 120 16675784
2020 Metabolic characterisation of Magnetospirillum gryphiswaldense MSR-1 using LC-MS-based metabolite profiling. RSC advances 113 35516490
2007 Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II. The Journal of clinical investigation 105 17332894
2022 Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway. Frontiers in immunology 104 35237277
2022 The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer. Frontiers in immunology 100 36325338
2011 Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA 90 21791690
2013 Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation. PloS one 87 24278429
2005 Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO. Journal of immunology (Baltimore, Md. : 1950) 85 16339540
2019 Triggering MSR1 promotes JNK-mediated inflammation in IL-4-activated macrophages. The EMBO journal 83 31028084
2014 Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma. Cancer 81 24839953
2020 Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury. Journal of neuroinflammation 79 32066456
2011 Pattern recognition scavenger receptor CD204 attenuates Toll-like receptor 4-induced NF-kappaB activation by directly inhibiting ubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6. The Journal of biological chemistry 78 21460221
2008 The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages. Journal of leukocyte biology 76 18511575
2005 Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure. American journal of physiology. Lung cellular and molecular physiology 75 15849212
2009 Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation. Blood 69 19349620
2007 Purified and sterilized magnetosomes from Magnetospirillum gryphiswaldense MSR-1 were not toxic to mouse fibroblasts in vitro. Letters in applied microbiology 69 17594464
2022 Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still's disease pathogenesis. Nature communications 67 36357401
2013 Class A scavenger receptor 1 (MSR1) restricts hepatitis C virus replication by mediating toll-like receptor 3 recognition of viral RNAs produced in neighboring cells. PLoS pathogens 66 23717201
2008 Ferrous iron transport protein B gene (feoB1) plays an accessory role in magnetosome formation in Magnetospirillum gryphiswaldense strain MSR-1. Research in microbiology 63 18639631
2015 Characterization of the plant growth promoting bacterium, Enterobacter cloacae MSR1, isolated from roots of non-nodulating Medicago sativa. Saudi journal of biological sciences 60 26858542
2012 The class A macrophage scavenger receptor CD204 is a useful immunohistochemical marker of canine histiocytic sarcoma. Journal of comparative pathology 60 22901707
2011 Semicontinuous culture of Magnetospirillum gryphiswaldense MSR-1 cells in an autofermentor by nutrient-balanced and isosmotic feeding strategies. Applied and environmental microbiology 58 21724877
2008 High-yield growth and magnetosome formation by Magnetospirillum gryphiswaldense MSR-1 in an oxygen-controlled fermentor supplied solely with air. Applied microbiology and biotechnology 56 18425510
2007 Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration and allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 56 17442975
2011 Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). Biochemical and biophysical research communications 51 21756882
2013 Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI. ACS nano 49 23614696
2019 Elevation of pulmonary CD163+ and CD204+ macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients. Journal of thoracic disease 48 31656675
2014 Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis. Atherosclerosis 44 24929820
2011 Targeting the immunoregulator SRA/CD204 potentiates specific dendritic cell vaccine-induced T-cell response and antitumor immunity. Cancer research 43 21914786
2003 No association of germline alteration of MSR1 with prostate cancer risk. Nature genetics 42 12958598
2012 FeoB2 Functions in magnetosome formation and oxidative stress protection in Magnetospirillum gryphiswaldense strain MSR-1. Journal of bacteriology 40 22636767
2010 Single and multivariate associations of MSR1, ELAC2, and RNASEL with prostate cancer in an ethnic diverse cohort of men. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 40 20086112
2018 Macrophage scavenger receptor SR-AI contributes to the clearance of von Willebrand factor. Haematologica 39 29326120
2003 Germ-line alterations in MSR1 gene and prostate cancer risk. Clinical cancer research : an official journal of the American Association for Cancer Research 36 14614006
2007 Identification of the scavenger receptors SREC-I, Cla-1 (SR-BI), and SR-AI as cellular receptors for Tamm-Horsfall protein. Journal of leukocyte biology 34 17928461
2015 Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma. Cancer medicine 33 25620088
2012 Highly upregulated expression of CD36 and MSR1 in circulating monocytes of patients with acute coronary syndromes. The protein journal 33 22763563
2011 A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia. Blood 32 21596859
2011 CD204 suppresses large heat shock protein-facilitated priming of tumor antigen gp100-specific T cells and chaperone vaccine activity against mouse melanoma. Journal of immunology (Baltimore, Md. : 1950) 32 21832164
2018 CD204-Expressing Tumor-Associated Macrophages Are Associated With Malignant, High-Grade, and Hormone Receptor-Negative Canine Mammary Gland Tumors. Veterinary pathology 31 29343199
2012 In situ vaccination with CD204 gene-silenced dendritic cell, not unmodified dendritic cell, enhances radiation therapy of prostate cancer. Molecular cancer therapeutics 30 22896667
2007 Class A scavenger receptor (CD204) attenuates hyperoxia-induced lung injury by reducing oxidative stress. The Journal of pathology 30 17370294
2003 Adenovirus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor (SR-AI) in LDL receptor knock-out mice. Atherosclerosis 30 12860255
2010 mamO and mamE genes are essential for magnetosome crystal biomineralization in Magnetospirillum gryphiswaldense MSR-1. Research in microbiology 29 20674739
2016 Low density of CD204-positive M2-type tumor-associated macrophages in Epstein-Barr virus-associated gastric cancer: a clinicopathologic study with digital image analysis. Human pathology 28 27342912
2019 Characterization of transcriptome profile and clinical features of a novel immunotherapy target CD204 in diffuse glioma. Cancer medicine 27 31140757
2013 Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-γ. Biochemical and biophysical research communications 27 23333385
2011 Suppression of antigen-specific CD4+ T cell activation by SRA/CD204 through reducing the immunostimulatory capability of antigen-presenting cell. Journal of molecular medicine (Berlin, Germany) 25 22083206
2006 Meta-analysis of association of rare mutations and common sequence variants in the MSR1 gene and prostate cancer risk. The Prostate 25 16425212
2022 Tumour-associated CD204+ microglia/macrophages accumulate in perivascular and perinecrotic niches and correlate with an interleukin-6-enriched inflammatory profile in glioblastoma. Neuropathology and applied neurobiology 24 34713474
2022 MSR1 characterized by chromatin accessibility mediates M2 macrophage polarization to promote gastric cancer progression. International immunopharmacology 24 36095948
2016 Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors. Nutrition, metabolism, and cardiovascular diseases : NMCD 24 27378395
2014 Circulating CD14+CD204+ cells predict postoperative recurrence in non-small-cell lung cancer patients. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 24 24419414
2008 Characterization of immortalized MARCO and SR-AI/II-deficient murine alveolar macrophage cell lines. Particle and fibre toxicology 24 18452625
2020 Neuroprotective Effect of Phthalide Derivative CD21 against Ischemic Brain Injury:Involvement of MSR1 Mediated DAMP peroxiredoxin1 Clearance and TLR4 Signaling Inhibition. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 22 32291602
2006 Germline mutations of the MSR1 gene in prostate cancer families from Germany. Human mutation 22 16287155
2006 Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6. The Prostate 22 16598737
2018 Development of a simple intensified fermentation strategy for growth of Magnetospirillum gryphiswaldense MSR-1: Physiological responses to changing environmental conditions. New biotechnology 21 29864580
2014 Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures. Journal of immunotoxicology 21 24491035
2014 Role of CD204-positive tumor-associated macrophages in adult T-cell leukemia/lymphoma. Journal of clinical and experimental hematopathology : JCEH 20 24942947
2022 Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation. Redox biology 19 35525025
2019 The scavenger receptor SCARA1 (CD204) recognizes dead cells through spectrin. The Journal of biological chemistry 19 31653705
2013 Expression patterns of key iron and oxygen metabolism genes during magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. FEMS microbiology letters 19 23937222
2005 Clearance of apoptotic cells is not impaired in mouse embryos deficient in class A scavenger receptor types I and II (CD204). Developmental dynamics : an official publication of the American Association of Anatomists 18 15580571
2020 Identification of Immune-Related Genes MSR1 and TLR7 in Relation to Macrophage and Type-2 T-Helper Cells in Osteosarcoma Tumor Micro-Environments as Anti-metastasis Signatures. Frontiers in molecular biosciences 17 33381518
2019 CD204-Positive Tumor-associated Macrophages Relate to Malignant Transformation of Colorectal Adenoma. Anticancer research 17 31177112
2017 Physiological characteristics of Magnetospirillum gryphiswaldense MSR-1 that control cell growth under high-iron and low-oxygen conditions. Scientific reports 17 28584275
2017 LPS enhances expression of CD204 through the MAPK/ERK pathway in murine bone marrow macrophages. Atherosclerosis 17 29032172
2016 Transcriptome analysis reveals physiological characteristics required for magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. Environmental microbiology reports 17 27043321
2015 Iron response regulator protein IrrB in Magnetospirillum gryphiswaldense MSR-1 helps control the iron/oxygen balance, oxidative stress tolerance, and magnetosome formation. Applied and environmental microbiology 17 26386052
2013 The class A scavenger receptor SR-A/CD204 and the class B scavenger receptor CD36 regulate immune functions of macrophages differently. Innate immunity 17 24257313
2010 The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation. Protein & cell 17 21203986
2007 DNA variation in MSR1, RNASEL and E-cadherin genes and prostate cancer in Poland. Urologia internationalis 17 17627168
2004 Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSR1 in sporadic prostate cancer. Genes, chromosomes & cancer 17 14695991
2018 JNK1 Mediates Lipopolysaccharide-Induced CD14 and SR-AI Expression and Macrophage Foam Cell Formation. Frontiers in physiology 16 29354064
2013 MamX encoded by the mamXY operon is involved in control of magnetosome maturation in Magnetospirillum gryphiswaldense MSR-1. BMC microbiology 16 24020498
2012 Two bifunctional enzymes with ferric reduction ability play complementary roles during magnetosome synthesis in Magnetospirillum gryphiswaldense MSR-1. Journal of bacteriology 16 23243303
2021 Fusion expression of nanobodies specific for the insecticide fipronil on magnetosomes in Magnetospirillum gryphiswaldense MSR-1. Journal of nanobiotechnology 15 33468141
2007 A novel ferric reductase purified from Magnetospirillum gryphiswaldense MSR-1. Current microbiology 15 17534559
2022 Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis. Frontiers in immunology 14 36591228
2021 The relationship between CD204 M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target. Discover oncology 13 35201470
2012 Crystallization and preliminary crystallographic analysis of the C-terminal domain of MamM, a magnetosome-associated protein from Magnetospirillum gryphiswaldense MSR-1. Acta crystallographica. Section F, Structural biology and crystallization communications 13 22869124
2007 Disruption of a fur-like gene inhibits magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. Biochemistry. Biokhimiia 13 18205608
2021 A comprehensive assessment of the biocompatibility of Magnetospirillum gryphiswaldense MSR-1 bacterial magnetosomes in vitro and in vivo. Toxicology 12 34534559
2019 Clinical and transcriptional signatures of human CD204 reveal an applicable marker for the protumor phenotype of tumor-associated macrophages in breast cancer. Aging 12 31799941
2020 CD204-positive monocytes and macrophages ameliorate septic shock by suppressing proinflammatory cytokine production in mice. Biochemistry and biophysics reports 11 32793817
2020 CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression. Oncology letters 11 33262828
2013 Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration. Journal of immunology (Baltimore, Md. : 1950) 11 23794629
2007 MSR1 variants and the risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China. Carcinogenesis 11 17768178
2022 Expression of Macrophage Scavenger Receptor (MSR1) in Peripheral Blood Cells from Patients with Different Respiratory Diseases: Beyond Monocytes. Journal of clinical medicine 10 35268530
2016 Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. Journal of biomedical science 10 26892079
2011 Effect of overexpression of human SR-AI on oxLDL uptake and apoptosis in 293T cells. International immunopharmacology 10 21782039
2025 Single-nucleus transcriptomics reveals a distinct microglial state and increased MSR1-mediated phagocytosis as common features across dementia subtypes. Genome medicine 9 40826098

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