ID:C163A_HUMAN DESCRIPTION: RecName: Full=Scavenger receptor cysteine-rich type 1 protein M130; AltName: Full=Hemoglobin scavenger receptor; AltName: CD_antigen=CD163; Contains: RecName: Full=Soluble CD163; Short=sCD163; Flags: Precursor; FUNCTION: Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes of hemoglobin and multimeric haptoglobin of HP*1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP*1S phenotype. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1. Isoform 3 exhibits the higher capacity for ligand endocytosis and the more pronounced surface expression when expressed in cells. FUNCTION: After shedding, the soluble form (sCD163) may play an anti-inflammatory role, and may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.0 nM for hemoglobin/haptoglobin of HP*1S phenotype; KM=0.2 nM for hemoglobin/haptoglobin of HP*1F phenotype; SUBUNIT: Interacts with CSNK2B. SUBCELLULAR LOCATION: Soluble CD163: Secreted. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=Isoform 1 and isoform 2 show a lower surface expression when expressed in cells. TISSUE SPECIFICITY: Expressed in monocytes and mature macrophages such as Kupffer cells in the liver, red pulp macrophages in the spleen, cortical macrophages in the thymus, resident bone marrow macrophages and meningeal macrophages of the central nervous system. Expressed also in blood. Isoform 1 is the lowest abundant in the blood. Isoform 2 is the lowest abundant in the liver and the spleen. Isoform 3 is the predominant isoform detected in the blood. INDUCTION: Induced by anti-inflammatory mediators such as glucocorticoids, interleukin-6/IL6 and interleukin-10/IL10; suppressed by proinflammatory mediators like bacterial lipopolysaccharides (LPS), IFNG/IFN-gamma and TNF. DOMAIN: The SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes. PTM: A soluble form (sCD163) is produced by proteolytic shedding which can be induced by lipopolysaccharide, phorbol ester and Fc region of immunoglobulin gamma. This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound metalloproteinases ADAMs. PTM: Phosphorylated (Probable). MISCELLANEOUS: Intravenous lipopolysaccharide (LPS) produces a rapid rise of sCD163 in plasma of patient as it induces metalloproteinase-mediated shedding from monocytes surface. Long- term LPS infusion finally increases expression of the membrane- bound form on circulating monocytes. MISCELLANEOUS: The soluble form (sCD163) in plasma is a novel parameter in diseases affecting macrophage function and monocyte/macrophage load in the body. The concentration of sCD163 is probably reflecting the number of macrophages of the 'alternative macrophage activation' phenotype with a high CD163 expression playing a major role in dampening the inflammatory response and scavenging components of damaged cells. This has initiated a number of clinical studies for evaluation of sCD163 as a disease marker in inflammatory conditions e.g. infection, autoimmune disease, transplantation, atherosclerosis and cancer. SIMILARITY: Contains 9 SRCR domains. CAUTION: It is uncertain whether Met-1 or Met-6 is the initiator. SEQUENCE CAUTION: Sequence=CAA80541.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA80542.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA80543.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAA80544.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAB45233.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q86VB7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
