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MGP003866

UniProt Annotations

Entry Information
Gene NameCD163 molecule
Protein EntryC163A_HUMAN
UniProt IDQ86VB7
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=Long tail variant 1; IsoId=Q86VB7-1; Sequence=Displayed; Name=2; Synonyms=Long tail variant 2; IsoId=Q86VB7-2; Sequence=VSP_019014; Name=3; Synonyms=Short tail variant; IsoId=Q86VB7-3; Sequence=VSP_019015; Name=4; IsoId=Q86VB7-4; Sequence=VSP_019013, VSP_019015;
Biophysicochemical PropertiesKinetic parameters: KM=2.0 nM for hemoglobin/haptoglobin of HP*1S phenotype {ECO:0000269|PubMed:11196644}; KM=0.2 nM for hemoglobin/haptoglobin of HP*1F phenotype {ECO:0000269|PubMed:11196644};
CautionIt is uncertain whether Met-1 or Met-6 is the initiator. {ECO:0000305}.
DomainThe SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes. {ECO:0000269|PubMed:15448162}.
FunctionAcute 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.
FunctionAfter 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.
InductionInduced 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. {ECO:0000269|PubMed:10577520, ECO:0000269|PubMed:10648003}.
MiscellaneousIntravenous 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.
MiscellaneousThe 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.
PtmA 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. {ECO:0000269|PubMed:10066432, ECO:0000269|PubMed:12296867, ECO:0000269|PubMed:15075364, ECO:0000269|PubMed:15448162}.
PtmPhosphorylated. {ECO:0000305|PubMed:11298324}.
Sequence CautionSequence=CAA80541.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA80542.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA80543.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA80544.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAB45233.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityContains 9 SRCR domains. {ECO:0000255|PROSITE- ProRule:PRU00196}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:10577520, ECO:0000269|PubMed:10648003}; Single-pass type I membrane protein {ECO:0000269|PubMed:10577520, ECO:0000269|PubMed:10648003}. Note=Isoform 1 and isoform 2 show a lower surface expression when expressed in cells.
Subcellular LocationSoluble CD163: Secreted.
SubunitInteracts with CSNK2B. {ECO:0000269|PubMed:11298324}.
Tissue SpecificityExpressed 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. {ECO:0000269|PubMed:10577520, ECO:0000269|PubMed:11196644, ECO:0000269|PubMed:16434690}.
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