Affinage

SCARB1

Scavenger receptor class B member 1 · UniProt Q8WTV0

Length
552 aa
Mass
60.9 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCARB1 (SR-BI) is the principal cell-surface HDL receptor, a class B scavenger receptor that mediates selective uptake of HDL-derived cholesteryl esters into liver and steroidogenic tissues by a non-endocytic mechanism distinct from the LDL-receptor pathway (PMID:7520436, PMID:8560269). It binds HDL with high affinity and transfers core lipid to cells without internalizing the lipoprotein particle; in vivo, hepatic SR-BI controls plasma HDL levels and biliary cholesterol secretion (PMID:9163428), and is required for HDL-dependent cholesterol delivery that sustains adrenal glucocorticoid synthesis (PMID:18064300). Selective uptake is a two-step process — high-affinity HDL binding followed by CE transfer — that requires discrete extracellular subdomains including a critical C323 residue subject to redox regulation, with the bulk of CE transfer occurring at the plasma membrane rather than via retroendocytosis (PMID:16705213, PMID:21917726, PMID:25211142, PMID:18840501). Surface retention and function depend on receptor multimerization into metastable clusters driven by the C-terminal leucine zipper and actin polymerization, which excludes SR-BI from endocytic pathways (PMID:31231038). Receptor abundance and stability are tuned post-transcriptionally: the PDZ adaptor PDZK1 stabilizes hepatic SR-BI in a PKA/Ser-509-dependent manner (PMID:16174736), Nedd4-1 ubiquitinates SR-BI at K500/K508 to drive its turnover (antagonized by lipocalin-2) (PMID:37863040), and RBFOX2-controlled alternative splicing sets the hepatic isoform profile governing lipid homeostasis (PMID:36536133). Beyond lipoprotein metabolism, SR-BI binds phosphatidylserine to drive efferocytosis of apoptotic cells through GULP–MAPK–Rac1 signaling and a Src–PI3K–Rac1 cascade in macrophages (PMID:19122200, PMID:26059978), couples endothelial LDL binding to transcytosis via a cytoplasmic DOCK4–RAC1 module (PMID:31019307), localizes to autophagosomes to recruit the VPS34–Beclin-1 complex via a PPARα–TFEB axis (PMID:33661763), and recognizes silica through an extracellular α-helix to trigger inflammasome activation (PMID:28147282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1994 High

    Established SR-BI as a distinct (class B) scavenger receptor, defining a new receptor class by showing it binds both modified and native LDL with high affinity.

    Evidence Expression cloning and direct binding/competition assays in CHO cells

    PMID:7520436

    Open questions at the time
    • Did not identify the physiological ligand or the in vivo function
    • No structural basis for ligand binding
  2. 1996 High

    Identified SR-BI's physiological role as the HDL receptor mediating selective cholesterol uptake, distinguishing it mechanistically from the endocytic LDL receptor and resolving how cells acquire HDL core lipid.

    Evidence HDL binding and selective lipid uptake assays in transfected cells with tissue expression profiling

    PMID:8560269

    Open questions at the time
    • Cell-surface vs. internalized site of CE transfer not yet resolved
    • Binding-site residues unmapped
  3. 1996 Medium

    Extended SR-BI ligand recognition beyond lipoproteins to anionic phospholipid surfaces, linking the receptor to apoptotic cell clearance.

    Evidence Gain-of-function endocytosis assays in stable CHO transfectants with apoptotic cells and charged liposomes

    PMID:8549669

    Open questions at the time
    • Downstream engulfment signaling unknown
    • Single-lab gain-of-function without genetic validation
  4. 1997 High

    Demonstrated in vivo that hepatic SR-BI controls plasma HDL and routes cholesterol into bile, establishing its central role in reverse cholesterol transport.

    Evidence Adenoviral hepatic overexpression in mice with plasma HDL and biliary cholesterol quantification

    PMID:9163428

    Open questions at the time
    • Overexpression rather than physiological levels
    • Mechanism of biliary secretion downstream of uptake not addressed
  5. 2002 Medium

    Showed SR-BI routes HDL-CE to a specific neutral hydrolase compartment distinct from CD36-mediated acidic routing, clarifying the intracellular fate of selectively taken-up lipid.

    Evidence In vitro CE hydrolysis assays with inhibitors and subcellular fractionation comparing SR-BI and CD36 transfectants

    PMID:12576515

    Open questions at the time
    • Identity of the hydrolase/compartment not molecularly defined
    • Single lab
  6. 2004 Medium

    Resolved the membrane microenvironment of SR-BI, placing it in caveolin-1-independent rafts and extending its cholesterol-uptake function to intestinal enterocytes.

    Evidence Detergent-free fractionation, membrane perturbations, and antisense/antibody loss-of-function in HepG2 and Caco-2/organ culture

    PMID:14676281 PMID:15226391

    Open questions at the time
    • Caveolin-1's regulatory role context-dependent and unresolved across cell types
    • Tissue-specific uptake mechanisms not unified
  7. 2005 High

    Defined post-transcriptional control of hepatic SR-BI by the PDZK1 adaptor through PKA phosphorylation, linking hormonal (glucagon) signaling to receptor abundance and plasma HDL.

    Evidence PKA kinase assays, S509A mutagenesis, phospho-specific antibodies, and in vivo glucagon treatment

    PMID:16174736

    Open questions at the time
    • Molecular mechanism by which PDZK1 stabilizes SR-BI not detailed
    • Whether other tissues use this control unknown
  8. 2006 Medium

    Quantitatively settled that SR-BI-mediated CE uptake occurs predominantly at the cell surface, with retroendocytosis a >30-fold minor route.

    Evidence Pulse-chase with biotinylated [125I]-HDL comparing selective uptake and retroendocytosis rates in COS-7 and HepG2 cells

    PMID:16705213

    Open questions at the time
    • Molecular machinery of surface CE transfer not defined
    • Single lab
  9. 2008 Medium

    Defined the structural and ultrastructural basis of selective uptake — homo-oligomerization via the C-terminus and ACTH-regulated microvillar channels — and a two-step binding/transfer model.

    Evidence FRET oligomerization spectroscopy, electron microscopy of adrenal microvillar channels, and ACTH regulation studies

    PMID:18840501

    Open questions at the time
    • Compiled primary data, single lab
    • Functional necessity of oligomerization for uptake not isolated here
  10. 2008 High

    Established the physiological consequence of SR-BI-dependent cholesterol delivery to the adrenal, showing it is required for glucocorticoid synthesis and survival of endotoxic challenge.

    Evidence SR-BI knockout mice, LPS challenge, corticosterone rescue, and ACTH stimulation tests

    PMID:18064300

    Open questions at the time
    • Whether SR-BI has direct anti-inflammatory roles independent of cholesterol delivery not separated here
  11. 2009 High

    Identified the cytoplasmic GULP–MAPK–Rac1 signaling axis through which SR-BI transduces phosphatidylserine recognition into actin-driven phagocytosis of apoptotic cells.

    Evidence Yeast two-hybrid, cell-free binding, co-IP, GULP knockdown, MAPK inhibitors, and Rac1-GTP pulldowns

    PMID:19122200

    Open questions at the time
    • Cell-type generality vs. macrophage-specific pathways not reconciled
    • In vivo relevance not tested here
  12. 2011 High

    Mapped C323 in the extracellular domain as part of the HDL binding site and showed CE uptake is redox-regulated through this residue.

    Evidence C323G mutagenesis, blocking antibody, transgenic mice, and redox-reagent CE uptake assays

    PMID:21917726

    Open questions at the time
    • Atomic structure of the binding site unresolved
    • Source/specificity of physiological H2O2 modulation in vivo unclear
  13. 2012 High

    Defined macrophage SR-BI as an in vivo efferocytosis receptor signaling through Src–PI3K–Rac1, demonstrating that hematopoietic SR-BI deficiency impairs apoptotic-cell clearance in atherosclerotic lesions.

    Evidence Bone marrow transplantation, efferocytosis assays, Src/PI3K/Rac1 inhibitors, Rac1 rescue, and SR-BI−/− macrophages

    PMID:26059978

    Open questions at the time
    • Relationship between GULP-based and Src-based pathways not unified
    • Receptor proximal coupling to Src undefined
  14. 2012 Medium

    Showed macrophage SR-BI dampens LPS-induced inflammation independent of cellular cholesterol, implicating NF-κB/JNK/p38 signaling.

    Evidence Reciprocal bone marrow transplantation and J774 overexpression with cytokine and inhibitor studies

    PMID:22589557

    Open questions at the time
    • Molecular mechanism linking SR-BI to NF-κB suppression unknown
    • Single lab
  15. 2012 Medium

    Demonstrated oxidative/electrophilic stress (cigarette smoke H2O2 and aldehyde adducts) drives SR-BI ubiquitination and loss, identifying environmental redox control of receptor stability.

    Evidence Immunoblot/IP, confocal microscopy, NOX inhibitors, catalase rescue, and aldehyde adduct detection in keratinocytes

    PMID:22442701

    Open questions at the time
    • Ubiquitin ligase not identified here
    • Keratinocyte-specific relevance to lipoprotein metabolism unclear
  16. 2014 High

    Systematically mapped extracellular N- and C-terminal subdomains required for HDL binding, CE uptake, and bidirectional free-cholesterol flux, showing these functions are separable from oligomerization status.

    Evidence Panel of 16 SR-BI/CD36 chimeras with binding, uptake, efflux, and membrane cholesterol redistribution assays in COS-7

    PMID:25211142

    Open questions at the time
    • No high-resolution structure to position the subdomains
    • How separate subdomains coordinate during transfer unknown
  17. 2017 High

    Identified SR-B1 as a silica receptor recognizing the particle via an extracellular α-helix and required for silica-induced inflammasome activation and pulmonary inflammation.

    Evidence Functional expression cloning, SR-B1 knockout mice, antibody blockade, and caspase-1 activation assays

    PMID:28147282

    Open questions at the time
    • Coupling of surface silica binding to cytosolic inflammasome assembly undefined
    • Relationship to lipoprotein-binding subdomains unclear
  18. 2017 Medium

    Established SCARB1 as a carotenoid uptake transporter, using a natural splice mutation in canaries to show isoform-dependent loss of carotenoid transport.

    Evidence Genetic mapping and carotenoid uptake assays comparing wild-type and exon-4-deficient isoforms

    PMID:28465440

    Open questions at the time
    • Mammalian relevance of carotenoid transport not addressed
    • Single study
  19. 2019 High

    Revealed an endothelial SR-B1 function — LDL transcytosis — driven by a cytoplasmic eight-residue motif recruiting DOCK4 to couple LDL binding to RAC1 activation and internalization, promoting atherosclerosis.

    Evidence In vivo vesicle colocalization, transcytosis assays, cytoplasmic deletion mutants, DOCK4 recruitment, RAC1 assays, and endothelial-specific knockout

    PMID:31019307

    Open questions at the time
    • How transcytosis is reconciled with non-endocytic surface retention in other tissues unresolved
    • Regulation of DOCK4 recruitment unknown
  20. 2019 High

    Explained how SR-B1 avoids endocytosis: it multimerizes into metastable plasma-membrane clusters dependent on the C-terminal leucine zipper and actin, and this clustering is required for function.

    Evidence ScFv-based live-cell single-molecule imaging, leucine zipper mutagenesis, actin inhibitors, and endocytosis assays

    PMID:31231038

    Open questions at the time
    • Stoichiometry of functional clusters undefined
    • How clustering interfaces with transcytosis machinery unclear
  21. 2021 High

    Connected SR-BI to autophagy regulation, showing intracellular SR-BI forms autophagosomal cholesterol domains that recruit the VPS34–Beclin-1 complex via a PPARα–TFEB axis.

    Evidence SR-BI knockout macrophages, autophagosome fractionation, co-IP of the VPS34–Beclin-1 complex, and TFEB/VPS34 rescue

    PMID:33661763

    Open questions at the time
    • How SR-BI traffics to autophagosomes unknown
    • Relationship between surface receptor pool and autophagosomal pool unclear
  22. 2022 High

    Identified RBFOX2-controlled alternative splicing as a determinant of the hepatic Scarb1 isoform profile governing lipid homeostasis, exploitable with splice-switching oligonucleotides.

    Evidence iCLIP demonstrating RBFOX2 binding to Scarb1 pre-mRNA, diet-induced obesity model, and splice-switching oligonucleotide rescue

    PMID:36536133

    Open questions at the time
    • Functional differences between the swapped isoforms not fully defined
    • Human relevance of the isoform switch not established here
  23. 2023 High

    Defined a Nedd4-1/lipocalin-2 axis controlling SR-BI degradation, mapping ubiquitination to K500/K508 and showing hepatocyte Lcn2 protects the receptor to improve HDL metabolism and limit atherosclerosis.

    Evidence Ubiquitination site mapping, SR-BI(K500A/K508A) knock-in, hepatocyte Lcn2 and Nedd4-1 conditional mice, and atherosclerosis quantification

    PMID:37863040

    Open questions at the time
    • How Lcn2 mechanistically blocks Nedd4-1 access unresolved
    • Interplay with PDZK1 stabilization not integrated
  24. 2023 Medium

    Placed intestinal SR-B1 under FXR/bile-acid and microbiome control, linking dietary intervention to receptor expression and systemic lipid homeostasis.

    Evidence Intestine-specific SR-B1 knockout mice, Caco-2 CDCA treatment, fecal microbiota transplantation, and FXR pathway analysis

    PMID:37160898

    Open questions at the time
    • Direct vs. microbiome-indirect transcriptional control not fully separated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and mechanistic model of how SR-BI's extracellular subdomains, clustering state, and divergent cytoplasmic adaptors (PDZK1, DOCK4, GULP, Nedd4-1) are coordinated to switch between surface CE transfer, transcytosis, efferocytosis, and degradation remains undefined.
  • No atomic structure of HDL- or silica-bound SR-BI
  • Rules selecting among competing cytoplasmic effectors unknown
  • How surface non-endocytic retention coexists with endothelial transcytosis unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0001618 virus receptor activity 3 GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-1643685 Disease 2 R-HSA-9612973 Autophagy 1
Partners
BECN1CAV1DOCK4GULP1LCN2NEDD4PDZK1RBFOX2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 SR-BI (SRB1/CLA-1/CD36L1) was cloned by expression from a CHO cell variant and identified as a new member of the CD36 family of membrane proteins. It binds acetylated LDL, oxidized LDL, and maleylated BSA with high affinity (Kd ~5 µg protein/ml), and unexpectedly also binds native LDL with high affinity, defining a second class (class B) of scavenger receptors. Expression cloning, direct binding and competition assays in CHO cells, Northern blot The Journal of biological chemistry High 7520436
1996 SR-BI is an HDL receptor: it binds HDL with high affinity, is expressed primarily in liver and nonplacental steroidogenic tissues, and mediates selective cholesterol uptake (transfer of cholesterol but not HDL outer-shell proteins to cells) by a mechanism distinct from the classic LDL receptor endocytic pathway. HDL binding assays, selective lipid uptake assays in transfected cells, tissue expression analysis Science (New York, N.Y.) High 8560269
1996 SR-BI (SRB1) recognizes negatively charged liposomes and mediates endocytosis of apoptotic cells; CHO transfectants constitutively expressing SRB1 took up apoptotic cells and negatively charged liposomes, whereas cells expressing class A scavenger receptors (type I or II) could not. Stable CHO cell transfection, endocytosis assays with apoptotic cells and liposomes Experimental cell research Medium 8549669
1997 Adenovirus-mediated hepatic overexpression of SR-BI in mice results in virtual disappearance of plasma HDL and a substantial increase in biliary cholesterol, demonstrating that SR-BI directly mediates hepatic HDL cholesterol uptake and increases cholesterol secretion into bile. Adenovirus-mediated gene transfer in mice, plasma HDL measurement, biliary cholesterol quantification Nature High 9163428
1997 An alternative splice variant of SR-BI, designated SR-BI.2, differs in its putative cytoplasmic C-terminal domain. CHO cells transfected with SR-BI.2 cDNA expressed protein and acquired the ability to take up fluorescent lipid (DiI) from DiI-HDL, indicating functional selective lipid uptake activity. cDNA cloning, CHO cell transfection, fluorescent DiI-HDL uptake assay, Northern blot Journal of lipid research Medium 9254074
2001 Caveolin-1 negatively regulates SR-BI-dependent selective HDL cholesteryl ester uptake. Stable overexpression of caveolin-1 in RAW, J-774, and SR-BI-transfected CHO cells decreased selective HDL [3H]cholesteryl ether uptake by ~50-60% without altering cell-associated HDL. Caveolae depleted of cholesterol (by beta-cyclodextrin) facilitated SR-BI-dependent uptake, while excess cholesterol in caveolae inhibited it. Stable caveolin-1 overexpression, adenoviral gene transfer, [3H]cholesteryl ether selective uptake assay, blocking antibodies, beta-cyclodextrin treatment European journal of biochemistry Medium 11683884
2002 SR-BI, but not CD36, efficiently directs HDL-derived cholesteryl ester (CE) to a neutral CE hydrolase pathway for hydrolysis at a metabolically active membrane compartment. HDL-CE hydrolytic activity was recovered in a membrane fraction. LDL-CE delivered by SR-BI was also hydrolyzed by neutral CE hydrolase, while CD36-delivered LDL-CE was processed by an acidic CE hydrolase, indicating distinct routing. In vitro CE hydrolysis assays with enzyme inhibitors, subcellular fractionation, comparison of SR-BI and CD36 transfected cells Journal of lipid research Medium 12576515
2004 SR-BI is localized in membrane rafts devoid of caveolin-1 in HepG2 hepatoma cells (demonstrated by detergent-free sucrose gradient fractionation). Both LDL-CE and HDL3-CE selective uptake in HepG2 cells occur via a retroendocytic pathway. Perturbation of membrane raft structure differentially affects LDL-CE vs HDL3-CE selective uptake. Detergent-free sucrose gradient fractionation, cholesterol oxidase/sphingomyelinase/filipin/beta-cyclodextrin treatments, retroendocytosis assays Journal of cell science Medium 15226391
2004 SR-BI is expressed in human intestinal enterocytes from week 14 of gestation, localized mainly over microvilli, and not associated with caveolin-1 or caveolae. Antisense knockdown of SR-BI in Caco-2 cells proportionally decreased free cholesterol uptake (without altering phospholipid or cholesteryl ester capture), and SR-BI antibodies lowered cholesterol uptake in intestinal organ culture. Immunofluorescence, immunogold electron microscopy, antisense transfection in Caco-2 cells, organ culture with blocking antibodies Journal of cell science Medium 14676281
2005 The adaptor protein PDZK1 binds SR-BI (via its first PDZ domain) and controls hepatic SR-BI expression posttranscriptionally. PDZK1 is phosphorylated at Ser-509 by PKA (cAMP-dependent protein kinase); a S509A mutant PDZK1 lost the ability to upregulate SR-BI protein. Glucagon administration increased PDZK1 phosphorylation at Ser-509 and hepatic SR-BI levels while decreasing plasma HDL. Metabolic labeling, phosphoamino acid analysis, site-directed mutagenesis (S509A), in vitro PKA phosphorylation assay, phospho-specific antibody, in vivo glucagon treatment in rats Proceedings of the National Academy of Sciences of the United States of America High 16174736
2006 SR-BI-dependent selective cholesterol uptake and HDL resecretion (retroendocytosis) were quantitatively measured in COS-7 and HepG2 cells. The rate of SR-BI-dependent HDL retroendocytosis (~0.5 ng HDL/mg/min) was >30-fold slower than the rate of selective CE uptake (~17 ng HDL/mg/min) in COS-7 cells, demonstrating that the vast majority of SR-BI-dependent selective uptake occurs at the cell surface, not via retroendocytosis. Pulse-chase assay with biotinylated [125I]-HDL3, streptavidin precipitation, quantitative comparison of selective CE uptake vs. retroendocytosis rates Journal of lipid research Medium 16705213
2008 SR-BI is required for normal glucocorticoid synthesis and LPS hepatic clearance. SR-BI-null mice showed glucocorticoid insufficiency due to primary adrenal malfunction from deficient cholesterol delivery from HDL, resulting in uncontrolled inflammatory cytokine response and markedly higher lethality in LPS-induced endotoxic shock. Corticosterone supplementation decreased LPS sensitivity in SR-BI-null mice. SR-BI knockout mice, LPS challenge, corticosterone supplementation rescue, ACTH stimulation tests, hepatocyte LPS clearance assays The Journal of clinical investigation High 18064300
2009 SR-BI binds to the engulfment adaptor protein GULP via its C-terminal intracellular domain (demonstrated by yeast two-hybrid and cell-free binding assay). SR-BI-GULP complex exists prior to activation. Upon PS binding, SR-BI activates GULP, which induces MAPK (p38 and ERK1/2) phosphorylation, which in turn activates Rac1-GTP, leading to actin cytoskeleton rearrangement and phagocytosis of apoptotic cells. Yeast two-hybrid, cell-free binding assay, co-immunoprecipitation, GULP siRNA knockdown, MAPK inhibitor treatment, Rac1-GTP pulldown assay Journal of biochemistry High 19122200
2011 C323 in the extracellular domain of SR-BI is required for HDL binding and cholesteryl ester uptake. C323G mutant SR-BI lost HDL binding and CE uptake activity. A blocking antibody against the C323 region inhibited HDL binding, directly implicating C323 as part of the HDL binding site. In C323G transgenic mice, plasma cholesterol regulation was impaired. Physiological levels of H2O2 upregulated SR-BI-mediated CE uptake by 65%, while GSH/DTT decreased it by 45%, indicating redox regulation via C323. Site-directed mutagenesis (C323G), blocking antibody, C323G transgenic mice, redox reagent treatment, CE uptake assays Journal of lipid research High 21917726
2012 SR-BI mediates efferocytosis of apoptotic cells by binding phosphatidylserine and inducing Src phosphorylation and membrane recruitment, leading to downstream activation of PI3K and Rac1 for engulfment. Pharmacological inhibition of Src decreased PI3K, Rac1-GTP, and efferocytosis; Rac1 activation rescued defective efferocytosis in SR-BI−/− macrophages. Bone marrow transplantation showed hematopoietic SR-BI deficiency causes severely defective efferocytosis in atherosclerotic lesions. Bone marrow transplantation, in vitro/in vivo efferocytosis assays, Src/PI3K/Rac1 inhibitors, Rac1-GTP pulldown, SR-BI−/− macrophages Journal of lipid research High 26059978
2012 Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling. Bone marrow transplantation experiments showed SR-BI-null bone marrow enhances inflammatory response to LPS in wild-type recipient mice; WT bone marrow reduces response in SR-BI-null mice. SR-BI overexpression in J774 macrophages attenuated LPS-induced inflammation. The increased signaling in SR-BI-null cells was not related to changes in cellular cholesterol content and involved NFκB, JNK, and p38 pathways. Bone marrow transplantation, SR-BI overexpression in J774 cells, cytokine measurement, signaling pathway inhibitor studies Journal of lipid research Medium 22589557
2014 Discrete subdomains of SR-BI's extracellular (EC) domain, particularly in the N-terminal and C-terminal regions, are critical for HDL binding, HDL-CE selective uptake, free cholesterol efflux to HDL, and plasma membrane free cholesterol redistribution. This was shown using a panel of 16 SR-BI/CD36 chimeric receptors; changes in function were independent of receptor oligomerization status. SR-BI/CD36 chimeric receptor panel (16 constructs), transient expression in COS-7 cells, HDL binding assay, CE selective uptake assay, cholesterol efflux assay, plasma membrane cholesterol redistribution assay Biochemistry High 25211142
2017 SR-B1 is a silica receptor: through an extracellular α-helix, both mouse and human SR-B1 specifically recognize amorphous and crystalline silica (but not other nanoparticles). SR-B1-mediated silica recognition is associated with caspase-1-mediated (canonical) inflammasome activation in macrophages. SR-B1 genetic deletion and masking by monoclonal antibodies showed its requirement for silica-induced pulmonary inflammation in mice. Functional expression cloning, SR-B1 knockout mice, monoclonal antibody blockade, caspase-1 activation assays, murine pulmonary inflammation model Cell reports High 28147282
2017 SCARB1 mediates cellular carotenoid uptake in birds. Wild-type SCARB1 promotes cellular uptake of carotenoids, but a splice donor site mutation in white recessive canaries causes abnormal splicing (loss of exon 4), producing a predominant isoform that lacks this function. Functional assays confirmed carotenoid uptake activity is lost in the mutant isoform. Genetic mapping, functional carotenoid uptake assays comparing wild-type and mutant SCARB1 isoforms, biochemical analysis of carotenoid tissue levels Proceedings of the National Academy of Sciences of the United States of America Medium 28465440
2019 SR-B1 in endothelial cells mediates LDL transcytosis across the endothelium to promote atherosclerosis. LDL co-localizes with SR-B1 in endothelial intracellular vesicles in vivo. Transcytosis requires direct LDL binding to SR-B1 and an eight-amino-acid cytoplasmic domain that recruits the guanine nucleotide exchange factor DOCK4. DOCK4 promotes SR-B1 internalization and LDL transport by coupling LDL binding to SR-B1 with RAC1 activation. In vivo vesicle co-localization, endothelial monolayer transcytosis assays, cytoplasmic domain deletion mutagenesis, DOCK4 recruitment assays, RAC1 activation assays, SR-B1 endothelial-specific knockout Nature High 31019307
2019 SR-B1 undergoes multimerization into large metastable clusters at the plasma membrane, which prevents its entry into endocytic pathways and is critical for its function. Multimerization requires the C-terminal leucine zipper of SR-B1 and actin polymerization; mutating the leucine zipper or disrupting actin caused rapid receptor internalization. The C-terminal PDZ-binding domain and cortical cytoskeleton attachment are not responsible for plasmalemmal retention. Single-chain variable fragment (ScFv) antibody-based live-cell imaging, single-molecule tracking, leucine zipper mutagenesis, actin polymerization inhibitors, endocytosis assays Developmental cell High 31231038
2021 Macrophage SR-BI regulates autophagy via TFEB expression and recruitment of the VPS34-Beclin-1 complex. SR-BI deletion reduced PPARα-dependent TFEB expression and VPS34/Beclin-1 levels. Intracellular SR-BI localizes to autophagosomes, where it forms cholesterol domains that recruit Barkor and the VPS34-Beclin-1 complex. Overexpression of TFEB or VPS34 rescued defective autophagy in SR-BI−/− macrophages. SR-BI knockout macrophages, autophagosome fractionation, co-immunoprecipitation of SR-BI with VPS34-Beclin-1 complex, PPARα pathway analysis, TFEB/VPS34 overexpression rescue The Journal of clinical investigation High 33661763
2022 The splicing factor RBFOX2 maintains a specific Scarb1 isoform profile in mouse liver; decreased RBFOX2 function in diet-induced obesity causes a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. RBFOX2 binding to Scarb1 pre-mRNA was confirmed by enhanced iCLIP. Splice-switching oligonucleotides targeting this network alleviated obesity-induced liver inflammation and promoted an anti-atherogenic lipoprotein profile. Enhanced individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP), diet-induced obesity mouse model, splice-switching oligonucleotides, lipoprotein profiling Nature metabolism High 36536133
2023 Hepatocyte lipocalin-2 (Lcn2) improves HDL metabolism and alleviates atherosclerosis by blocking Nedd4-1-mediated ubiquitination of SR-BI at K500 and K508. Overexpression of Lcn2 attenuated atherosclerosis via SR-BI; hepatocyte-specific Lcn2 ablation had the opposite effect. Lcn2-improved HDL metabolism was abolished in SR-BI(K500A/K508A) mutation mice and in mice with hepatic SR-BI or Nedd4-1 deletion. Hepatocyte-specific overexpression and knockout mice, ubiquitination site mapping (K500/K508), SR-BI(K500A/K508A) knock-in mice, Nedd4-1 deletion mice, atherosclerosis quantification Developmental cell High 37863040
2023 Intestinal SR-B1 expression is regulated by the FXR pathway. Resveratrol intervention reduces fecal bile acid levels and FXR activity, suppressing jejunal SR-B1 expression via gut microbiome-mediated changes. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1 expression. Intestinal mucosa-specific SR-B1−/− mice on HFD showed improved lipid homeostasis and did not respond further to resveratrol intervention. Intestinal-specific SR-B1 knockout mice, Caco-2 cell treatment, fecal microbiota transplantation, bile acid quantification, FXR pathway analysis Nature communications Medium 37160898
2012 Cigarette smoke causes translocation and loss of SR-B1 from human keratinocytes through H2O2 production (primarily from NADPH oxidase activation). This effect was reversed by NOX inhibitors or catalase pretreatment. CS also caused formation of SR-B1-aldehyde adducts (acrolein and 4-HNE) and increased SR-B1 ubiquitination, contributing to receptor loss. Immunoblotting, immunoprecipitation, RT-PCR, confocal microscopy, NOX inhibitors, catalase pretreatment, aldehyde adduct detection PloS one Medium 22442701
2008 SR-BI-mediated HDL-CE delivery in the adrenal gland occurs at specialized plasma membrane compartments called microvillar channels. Formation of microvillar channels requires SR-BI expression and is regulated by ACTH. SR-BI forms homo-oligomers in the plasma membrane via its C-terminal region (demonstrated by FRET spectroscopy). SR-BI-mediated CE selective uptake is a two-step process: high-affinity HDL binding followed by CE transfer to the membrane. Electron microscopy of adrenal microvillar channels, FRET spectroscopy for oligomerization, ACTH regulation studies, SR-BI expression requirement experiments Molecular and cellular endocrinology Medium 18840501

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science (New York, N.Y.) 1988 8560269
1994 Expression cloning of SR-BI, a CD36-related class B scavenger receptor. The Journal of biological chemistry 659 7520436
1997 Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 610 9163428
1999 Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI. Annual review of biochemistry 440 10872459
2000 CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 355 10821819
2003 The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Endocrine reviews 349 12788804
2017 SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux. Annual review of physiology 314 29125794
2006 Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. Journal of molecular medicine (Berlin, Germany) 297 16501936
2019 SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature 267 31019307
2003 Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 193 12920050
2017 SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis. Trends in endocrinology and metabolism: TEM 162 28259375
2000 The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Current opinion in lipidology 157 10787173
2008 SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance. The Journal of clinical investigation 132 18064300
1996 SRB1, a class B scavenger receptor, recognizes both negatively charged liposomes and apoptotic cells. Experimental cell research 130 8549669
2015 Macrophage SR-BI mediates efferocytosis via Src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis. Journal of lipid research 121 26059978
2004 The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders. The international journal of biochemistry & cell biology 121 14592533
2016 Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging. Frontiers in pharmacology 109 28018216
1995 The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution. Genomics 102 7539776
2017 High-density lipoprotein receptor SCARB1 is required for carotenoid coloration in birds. Proceedings of the National Academy of Sciences of the United States of America 96 28465440
2017 SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation. Cell reports 89 28147282
1997 Alternative forms of the scavenger receptor BI (SR-BI). Journal of lipid research 89 9254074
2003 Cholesterol uptake in adrenal and gonadal tissues: the SR-BI and 'selective' pathway connection. Frontiers in bioscience : a journal and virtual library 85 12957864
2012 Cigarette smoke affects keratinocytes SRB1 expression and localization via H2O2 production and HNE protein adducts formation. PloS one 82 22442701
2004 Localization and regulation of SR-BI in membrane rafts of HepG2 cells. Journal of cell science 81 15226391
2014 Scavenger receptor class B type I (SR-BI): a versatile receptor with multiple functions and actions. Metabolism: clinical and experimental 77 24854385
2009 Role of the adaptor protein PDZK1 in controlling the HDL receptor SR-BI. Current opinion in lipidology 66 19421056
2021 Macrophage SR-BI modulates autophagy via VPS34 complex and PPARα transcription of Tfeb in atherosclerosis. The Journal of clinical investigation 65 33661763
2017 Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release. eLife 65 29160205
2003 SR-BI and cholesterol uptake into steroidogenic cells. Trends in endocrinology and metabolism: TEM 64 14643062
2001 Caveolin-1 negatively regulates SR-BI mediated selective uptake of high-density lipoprotein-derived cholesteryl ester. European journal of biochemistry 64 11683884
2016 SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer. Frontiers in pharmacology 62 27774064
2010 Tupaia CD81, SR-BI, claudin-1, and occludin support hepatitis C virus infection. Journal of virology 62 21177818
2018 Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease. European heart journal 59 29596577
2012 Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages. Journal of lipid research 59 22589557
1999 Influence of the HDL receptor SR-BI on atherosclerosis. Current opinion in lipidology 59 10680042
2011 Scavenger receptor SR-BI in macrophage lipid metabolism. Atherosclerosis 57 21481393
2011 Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism. Atherosclerosis 57 21741044
2004 Population-based study of SR-BI genetic variation and lipid profile. Atherosclerosis 56 15186961
2000 Cellular and physiological roles of SR-BI, a lipoprotein receptor which mediates selective lipid uptake. Biochimica et biophysica acta 54 11111095
2016 Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice. Journal of immunology (Baltimore, Md. : 1950) 53 26936883
2007 Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. Journal of lipid research 52 18057374
2017 SR-BI as target in atherosclerosis and cardiovascular disease - A comprehensive appraisal of the cellular functions of SR-BI in physiology and disease. Atherosclerosis 51 28162236
2005 Regulation of SR-BI protein levels by phosphorylation of its associated protein, PDZK1. Proceedings of the National Academy of Sciences of the United States of America 48 16174736
2004 Ontogeny, immunolocalisation, distribution and function of SR-BI in the human intestine. Journal of cell science 47 14676281
2012 Extrahepatic high-density lipoprotein receptor SR-BI and apoA-I protect against deep vein thrombosis in mice. Arteriosclerosis, thrombosis, and vascular biology 45 22652597
2009 Signalling pathway involving GULP, MAPK and Rac1 for SR-BI-induced phagocytosis of apoptotic cells. Journal of biochemistry 43 19122200
2002 SR-BI-directed HDL-cholesteryl ester hydrolysis. Journal of lipid research 43 12576515
2016 Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy. Frontiers in pharmacology 42 27729859
2005 Regulation of SR-BI-mediated high-density lipoprotein metabolism by the tissue-specific adaptor protein PDZK1. Current opinion in lipidology 42 15767854
2004 SR-BI and HDL cholesteryl ester metabolism. Endocrine research 42 15666814
2023 Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1. Nature communications 41 37160898
2009 Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice. Journal of lipid research 40 19252221
2005 Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages. Cardiovascular research 40 15769457
2019 Multimerization and Retention of the Scavenger Receptor SR-B1 in the Plasma Membrane. Developmental cell 39 31231038
2013 Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease. Hepatobiliary & pancreatic diseases international : HBPD INT 37 24322749
2014 SR-BI mediates high density lipoprotein (HDL)-induced anti-inflammatory effect in macrophages. Biochemical and biophysical research communications 36 25528585
2008 SR-BI-mediated HDL cholesteryl ester delivery in the adrenal gland. Molecular and cellular endocrinology 36 18840501
2017 ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs. Journal of physiology and biochemistry 35 28181168
1999 The HDL receptor SR-BI: a new therapeutic target for atherosclerosis? Molecular medicine today 35 10562717
2020 Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats. Toxicology and applied pharmacology 34 33383043
2004 SR-BI- and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome. Journal of lipid research 34 15210845
2022 Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice. Nature metabolism 33 36536133
2021 High HDL-Cholesterol Paradox: SCARB1-LAG3-HDL Axis. Current atherosclerosis reports 32 33398433
2016 SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a). Circulation. Cardiovascular genetics 32 27651445
2008 The SCARB1 gene is associated with lipid response to dietary and pharmacological interventions. Journal of human genetics 30 18542840
2006 Quantitative analysis of SR-BI-dependent HDL retroendocytosis in hepatocytes and fibroblasts. Journal of lipid research 30 16705213
2021 SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies. Biomedicines 29 34072125
2013 Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice. Journal of lipid research 29 23564696
2023 SCARB1 in extracellular vesicles promotes NPC metastasis by co-regulating M1 and M2 macrophage function. Cell death discovery 28 37644041
2017 SR-B1 and PDZK1: partners in HDL regulation. Current opinion in lipidology 28 28134663
2017 Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR-B1. European journal of immunology 27 28504304
2016 ACTH Regulation of Adrenal SR-B1. Frontiers in endocrinology 27 27242666
2013 The atherogenic Scarb1 null mouse model shows a high bone mass phenotype. American journal of physiology. Endocrinology and metabolism 27 24253048
2009 Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet. Investigative ophthalmology & visual science 27 19420333
2022 SR-B1's Next Top Model: Structural Perspectives on the Functions of the HDL Receptor. Current atherosclerosis reports 26 35107765
2018 Hepatocyte-Specific SR-BI Gene Transfer Corrects Cardiac Dysfunction in Scarb1-Deficient Mice and Improves Pressure Overload-Induced Cardiomyopathy. Arteriosclerosis, thrombosis, and vascular biology 26 29976771
2017 Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load. Journal of hepatology 25 28363797
2014 SR-BI/CD36 chimeric receptors define extracellular subdomains of SR-BI critical for cholesterol transport. Biochemistry 25 25211142
2021 Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis. Journal of cardiovascular development and disease 23 34940525
2018 Erchen Decoction Ameliorates Lipid Metabolism by the Regulation of the Protein CAV-1 and the Receptors VLDLR, LDLR, ABCA1, and SRB1 in a High-Fat Diet Rat Model. Evidence-based complementary and alternative medicine : eCAM 23 30402126
2011 ABCA1, ABCG1, and SR-BI: Transit of HDL-associated sphingosine-1-phosphate. Clinica chimica acta; international journal of clinical chemistry 23 22115863
2010 SR-BI, CD36, and caveolin-1 contribute positively to cholesterol efflux in hepatic cells. Cell biochemistry and function 23 20629037
2019 The SR-B1 Receptor as a Potential Target for Treating Glioblastoma. Journal of oncology 22 31275377
2020 CircRNA SCARB1 Promotes Renal Cell Carcinoma Progression Via Mir- 510-5p/SDC3 Axis. Current cancer drug targets 21 32271695
2019 DHA and vitamin E antagonized the Aβ25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells. Food & function 21 30706921
2011 C323 of SR-BI is required for SR-BI-mediated HDL binding and cholesteryl ester uptake. Journal of lipid research 21 21917726
2008 NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors. Lipids 21 18373109
2023 H19 recruited N 6 -methyladenosine (m 6 A) reader YTHDF1 to promote SCARB1 translation and facilitate angiogenesis in gastric cancer. Chinese medical journal 20 37279381
2020 SR-BI as a target of natural products and its significance in cancer. Seminars in cancer biology 20 31935456
2018 Significance of Cholesterol-Binding Motifs in ABCA1, ABCG1, and SR-B1 Structure. The Journal of membrane biology 20 30519876
2015 Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder. Free radical biology & medicine 20 26006105
2023 Hepatocytic lipocalin-2 controls HDL metabolism and atherosclerosis via Nedd4-1-SR-BI axis in mice. Developmental cell 19 37863040
2016 Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway. Cardiovascular therapeutics 19 27225585
1998 Cloning and sequencing of the Candida albicans homologue of SRB1/PSA1/VIG9, the essential gene encoding GDP-mannose pyrophosphorylase in Saccharomyces cerevisiae. Microbiology (Reading, England) 19 9782489
2025 CircABCA1 promotes ccRCC by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through IGF2BP3-mediated stabilization of SCARB1 mRNA. Molecular cancer 18 40684174
2018 Curcumin increases cholesterol efflux via heme oxygenase‑1‑mediated ABCA1 and SR‑BI expression in macrophages. Molecular medicine reports 18 29436680
1992 Complementation of the Saccharomyces cerevisiae srb1-1 mutation: an autoselection system for stable plasmid maintenance. Current genetics 18 1525862
2021 Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI-Mediated High-Density Lipoprotein Uptake. Arteriosclerosis, thrombosis, and vascular biology 17 34551590
2018 SCARB1 rs5888 gene polymorphisms in coronary heart disease: A systematic review and a meta-analysis. Gene 17 30103009
2015 Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001 with Incident Coronary Heart Disease. PloS one 16 25993026

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