1. Gene Aliases

Macrophage Scavenger Receptor 1, SCARA1, SR-AIII, SR-AII, CD204, SR-AI, SR-A, Macrophage Scavenger Receptor Types I And II, Macrophage Acetylated LDL Receptor I And II, Scavenger Receptor Class A Member 1, Macrophage Scavenger Receptor Type III, CD204 Antigen, PhSR1, PhSR2, SRA

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=MSR1&keywords=Msr1]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Binding and Uptake of Ligands by Scavenger Receptors: Scavenger receptors bind free extracellular ligands as the initial step in clearance of the ligands from the body (reviewed in Ascenzi et al. 2005, Areschoug and Gordon 2009, Nielsen et al. 2010). Some scavenger receptors, such as the CD163-haptoglobin system, are specific for only one ligand. Others, such as the SCARA receptors (SR-A receptors) are less specific, binding several ligands which share a common property, such as polyanionic charges.

Brown and Goldstein originated the idea of receptors dedicated to scavenging aberrant molecules such as modified low density lipoprotein particles (Goldstein et al. 1979) and such receptors have been shown to participate in pathological processes such as atherosclerosis. Based on homology, scavenger receptors have been categorized into classes A-H (reviewed in Murphy et al. 2005).[https://reactome.org/PathwayBrowser/#/R-HSA-2173782]

Scavenging by Class A Receptors: Class A scavenger receptors contain an intracellular domain, a transmembrane region, a coiled-coil domain, a collagenous domain, and the SR cysteine-rich domain (reviewed in Areschoug and Gordon 2009, Bowdish and Gordon 2009). The coiled coil domains interact to form trimers. The collagenous domain (Rohrer et al. 1990, Acton et al. 1993) and/or the SR cysteine-rich domain (Brannstrom et al. 2002) bind ligands and determine the specificity of the receptor. [https://reactome.org/PathwayBrowser/#/R-HSA-3000480]

GO terms:

amyloid-beta clearance [The process in which amyloid-beta is removed from extracellular brain regions by mechanisms involving cell surface receptors. GO:0097242]

cellular response to organic cyclic compound [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. GO:0071407]

cholesterol transport [The directed movement of cholesterol, cholest-5-en-3-beta-ol, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0030301]

establishment of localization in cell [Any process, occuring in a cell, that localizes a substance or cellular component. This may occur via movement, tethering or selective degradation. GO:0051649]

lipoprotein transport [The directed movement of any conjugated, water-soluble protein in which the nonprotein group consists of a lipid or lipids, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. GO:0042953]

negative regulation of gene expression [Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).|This term covers any process that negatively regulates the rate of production of a mature gene product, and so includes processes that negatively regulate that rate by reducing the level, stability or availability of intermediates in the process of gene expression. For example, it covers any process that reduces the level, stability or availability of mRNA or circRNA for translation and thereby reduces the rate of production of the encoded protein via translation. GO:0010629]

phagocytosis, engulfment [The internalization of bacteria, immune complexes and other particulate matter or of an apoptotic cell by phagocytosis, including the membrane and cytoskeletal processes required, which involves one of three mechanisms: zippering of pseudopods around a target via repeated receptor-ligand interactions, sinking of the target directly into plasma membrane of the phagocytosing cell, or induced uptake via an enhanced membrane ruffling of the phagocytosing cell similar to macropinocytosis. GO:0006911]

plasma lipoprotein particle clearance [The process in which a lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded. GO:0034381]

positive regulation of cholesterol storage [Any process that increases the rate or extent of cholesterol storage. Cholesterol storage is the accumulation and maintenance in cells or tissues of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. GO:0010886]

positive regulation of macrophage derived foam cell differentiation [Any process that increases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions. GO:0010744]

receptor-mediated endocytosis [An endocytosis process in which cell surface receptors ensure specificity of transport. A specific receptor on the cell surface binds tightly to the extracellular macromolecule (the ligand) that it recognizes; the plasma-membrane region containing the receptor-ligand complex then undergoes endocytosis, forming a transport vesicle containing the receptor-ligand complex and excluding most other plasma-membrane proteins. Receptor-mediated endocytosis generally occurs via clathrin-coated pits and vesicles. GO:0006898]

MSigDB Signatures:

WP_AGE_RAGE_PATHWAY: AGE RAGE pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_AGE_RAGE_PATHWAY.html]

SHARMA_PILOCYTIC_ASTROCYTOMA_LOCATION_UP: Genes up-regulated in pilocytic astrocytoma (PA) from supratentorial regions compared to the infratentorial PA tumors. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SHARMA_PILOCYTIC_ASTROCYTOMA_LOCATION_UP.html]

BANDRES_RESPONSE_TO_CARMUSTIN_MGMT_24HR_DN: Genes down-regulated in T98G cells (glioma, express MGMT [GeneID=4255]) by carmustine [PubChem=2578] at 24 h. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BANDRES_RESPONSE_TO_CARMUSTIN_MGMT_24HR_DN.html]

BANDRES_RESPONSE_TO_CARMUSTIN_MGMT_48HR_DN: Genes down-regulated in T98G cells (glioma, express MGMT [GeneID=4255]) by carmustine [PubChem=2578] at 48 h. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BANDRES_RESPONSE_TO_CARMUSTIN_MGMT_48HR_DN.html]

VERHAAK_GLIOBLASTOMA_MESENCHYMAL: Genes correlated with mesenchymal type of glioblastoma multiforme tumors. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VERHAAK_GLIOBLASTOMA_MESENCHYMAL.html]

RODWELL_AGING_KIDNEY_NO_BLOOD_UP: Genes whose expression increases with age in normal kidney, excluding those with higher expression in blood. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RODWELL_AGING_KIDNEY_NO_BLOOD_UP.html]

REACTOME_SCAVENGING_BY_CLASS_A_RECEPTORS: Scavenging by Class A Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SCAVENGING_BY_CLASS_A_RECEPTORS.html]

CARRILLOREIXACH_MRS3_VS_LOWER_RISK_HEPATOBLASTOMA_DN: Genes significantly down-regulated in the high-risk Molecular Risk Stratification (MRS-3) hepatoblastoma (HB) as compared with intermediate-risk (MRS-2) and low-risk (MRS-1) molecular HBs, assessed by Human Transcriptome Array (HTA). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_MRS3_VS_LOWER_RISK_HEPATOBLASTOMA_DN.html]

ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY: Genes transiently induced only by the second pulse of EGF [GeneID =1950] in 184A1 cells (mammary epithelium). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY.html]

GAL_LEUKEMIC_STEM_CELL_UP: Genes up-regulated in leukemic stem cells (LSC), defined as CD34+CD38- [GeneID=947;952] cells from AML (acute myeloid leukemia patients) compared to the CD34+CD38+ cells. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GAL_LEUKEMIC_STEM_CELL_UP.html]

RODWELL_AGING_KIDNEY_UP: Genes whose expression increases with age in normal kidney. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RODWELL_AGING_KIDNEY_UP.html]

REACTOME_VESICLE_MEDIATED_TRANSPORT: Vesicle-mediated transport [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VESICLE_MEDIATED_TRANSPORT.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages. [provided by RefSeq, Jul 2008]

GeneCards Summary: MSR1 (Macrophage Scavenger Receptor 1) is a Protein Coding gene. Diseases associated with MSR1 include Barrett Esophagus and Polycystic Ovary Syndrome. Among its related pathways are Binding and Uptake of Ligands by Scavenger Receptors and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and scavenger receptor activity. An important paralog of this gene is SCARA5.

UniProtKB/Swiss-Prot Summary: Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL) [PMID: 2251254]. Isoform III does not internalize acetylated LDL [PMID: 9548586].

8. Cellular Location of Gene Product

Selective cytoplasmic expression in macrophages. Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000038945/subcellular]

9. Mechanistic Information

Summary

The Msr1 gene encodes macrophage scavenger receptor 1 (MSR1) proteins, which are integral membrane glycoproteins involved in the endocytosis of modified low-density lipoproteins (LDL), the regulation of lipid homeostasis, and the immune response to pathogens and cell debris [CS: 9]. MSR1 function includes the phagocytosis of myelin debris and apoptotic cells, contributing to clearance and inflammatory response through NF-kappaB signaling [CS: 9]. In the brain, MSR1-mediated clearance of apoptotic cells and amyloid aggregates is critical due to the organ's limited regenerative capacity and sensitivity to inflammatory damage [CS: 8].

In the context of neurodegenerative diseases like Alzheimer's disease (AD), Msr1 expression is upregulated in microglia, the brain's resident immune cells [CS: 8]. This upregulation leads to enhanced binding and phagocytosis of fibrillar beta-amyloid by microglia, a process potentially aimed at clearing amyloid plaques and mitigating their toxic impact on neural tissues [CS: 7]. Similarly, it manages the clearance of myelin debris, which could otherwise trigger chronic inflammation and damage to neurons [CS: 7]. The increase in Msr1 expression following exposure to brain insults, such as ischemia, hypoxia, or administration of pro-inflammatory agents like LPS, can be viewed as an acute response facilitating the removal of pathogenic or damaged material and aimed at restoring homeostasis [CS: 9]. This response involves the NF-kappaB pathway, enhancing the release of inflammatory mediators for the defense against pathogens and promoting apoptosis of damaged cells, which MSR1-marked microglia then phagocytose to maintain tissue health [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: lung (tissue enriched) [https://www.proteinatlas.org/ENSG00000038945/tissue]

Cell type enchanced: hofbauer cells, kupffer cells, langerhans cells, macrophages, monocytes (group enriched) [https://www.proteinatlas.org/ENSG00000038945/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: