CD163 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | CD163 , M130, MM130, SCARI1, CD163 molecule | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 605545 MGI: 2135946 HomoloGene: 128811 GeneCards: CD163 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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CD163 (Cluster of Differentiation 163) is a protein that in humans is encoded by the CD163 gene. [5] CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex [6] and in the absence of haptoglobin - with lower affinity - for hemoglobin alone. [7] It also is a marker of cells from the monocyte/macrophage lineage. [8] CD163 functions as innate immune sensor for gram-positive and gram-negative bacteria. [9] [10] The receptor was discovered in 1987. [11]
The molecular size is 130 kDa. The receptor belongs to the scavenger receptor cysteine rich family type B and consists of a 1048 amino acid residues extracellular domain, a single transmembrane segment and a cytoplasmic tail with several splice variants.
A soluble form of the receptor exists in plasma, and cerebrospinal fluid., [12] commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor, which may represent a form of modulation of CD163 function. [13] sCD163 shedding occurs as a result of enzymatic cleavage by ADAM17. [14] sCD163 is upregulated in a large range of inflammatory diseases including liver cirrhosis, [15] type 2 diabetes, macrophage activation syndrome, Gaucher's disease, sepsis, HIV infection, rheumatoid arthritis and Hodgkin Lymphoma. [16] [17] sCD163 is also upregulated in cerebrospinal fluid after subarachnoid haemorrhage. [12] CD163 has recently been identified as expressed on neurons in the CNS following hemorrhage, although the significance of this is unclear. [18] [19] [20] The excretion of soluble CD163 into the urine is tightly associated with the presence of active glomerulonephritis in systemic lupus erythematosus and ANCA vasculitis and can be used to track response to therapy. [21]
Differences between mice and humans in CD163 biology are important to note since preclinical studies are frequently conducted in mice. sCD163 shedding occurs in humans but not mice, due to the emergence of an Arg-Ser-Ser-Arg sequence in humans, essential for enzymatic cleavage by ADAM17. [22] Human CD163, but not mouse CD163, exhibits a strikingly higher affinity to hemoglobin-haptoglobin complex compared to hemoglobin alone. [23]
Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes Porcine Reproductive and Respiratory Syndrome. [24]
Haptoglobin is the protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds with high affinity to free hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidative activity. Compared to Hp, hemopexin binds to free heme. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system.
CD36, also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids.
Hemopexin, also known as beta-1B-glycoprotein, is a glycoprotein that in humans is encoded by the HPX gene and belongs to the hemopexin family of proteins. Hemopexin is the plasma protein with the highest binding affinity for heme.
The chemokine ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 tightly regulates cellular mechanics and thereby recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.
CD14 is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.
Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a protein which in humans is encoded by the IL18 gene. The protein encoded by this gene is a proinflammatory cytokine. Many cell types, both hematopoietic cells and non-hematopoietic cells, have the potential to produce IL-18. It was first described in 1989 as a factor that induced interferon-γ (IFN-γ) production in mouse spleen cells. Originally, IL-18 production was recognized in Kupffer cells, and liver-resident macrophages. However, IL-18 is constitutively expressed in non-hematopoietic cells, such as intestinal epithelial cells, keratinocytes, and endothelial cells. IL-18 can modulate both innate and adaptive immunity and its dysregulation can cause autoimmune or inflammatory diseases.
The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).
CD68 is a protein highly expressed by cells in the monocyte lineage, by circulating macrophages, and by tissue macrophages.
The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 is a G protein-coupled receptor for C5a. It functions as a complement receptor. C5a receptor 1 modulates inflammatory responses, obesity, development and cancers. From a signaling transduction perspective, C5a receptor 1 activation is implicated in β-arrestin2 recruitment via Rab5a, coupling of Gαi proteins, ERK1/2 phosphorylation, calcium mobilization and Rho activation leading to downstream functions, such as secretion of cytokines, chemotaxis, and phagocytosis.
High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.
The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain or with IL-13Rα1.
G protein-coupled receptor 15 is a protein that in humans is encoded by the GPR15 gene.
Macrophage scavenger receptor 1, also known as MSR1, is a protein which in humans is encoded by the MSR1 gene. MSR1 has also been designated CD204.
Macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene. MARCO is a class A scavenger receptor that is found on particular subsets of macrophages. Scavenger receptors are pattern recognition receptors (PRRs) found most commonly on immune cells. Their defining feature is that they bind to polyanions and modified forms of a type of cholesterol called low-density lipoprotein (LDL). MARCO is able to bind and phagocytose these ligands and pathogen-associated molecular patterns (PAMPs), leading to the clearance of pathogens and cell signaling events that lead to inflammation. As part of the innate immune system, MARCO clears, or scavenges, pathogens, which leads to inflammatory responses. The scavenger receptor cysteine-rich (SRCR) domain at the end of the extracellular side of MARCO binds ligands to activate the subsequent immune responses. MARCO expression on macrophages has been associated with tumor development and also with Alzheimer's disease, via decreased responses of cells when ligands bind to MARCO.
Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.
Hemoglobin, alpha 2 also known as HBA2 is a gene that in humans codes for the alpha globin chain of hemoglobin.
Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.
Haptoglobin-related protein (Hpr) is a serum protein that binds to haemoglobin of red blood cells and is present only in primates. It acts as a molecule of innate immunity in association with apolipoprotein L1 -containing high-density lipoprotein (HDL) particles. In humans, together with related serum protein, haptoglobin, it acts as a cell-killing agent as part of the trypanolytic factor against the protozoan parasite Trypanosoma brucei thereby providing natural resistance to African sleeping sickness. It is produced from the gene HPR that is located on the long arm of chromosome 16 within the HP gene cluster.