| IED ID | IndEnz0002005464 |
| Enzyme Type ID | protease005464 |
| Protein Name |
Scavenger receptor cysteine-rich type 1 protein M130 Hemoglobin scavenger receptor CD antigen CD163 Cleaved into: Soluble CD163 sCD163 |
| Gene Name | CD163 M130 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSKLRMVLLEDSGSADFRRHFVNLSPFTITVVLLLSACFVTSSLGGTDKELRLVDGENKCSGRVEVKVQEEWGTVCNNGWSMEAVSVICNQLGCPTAIKAPGWANSSAGSGRIWMDHVSCRGNESALWDCKHDGWGKHSNCTHQQDAGVTCSDGSNLEMRLTRGGNMCSGRIEIKFQGRWGTVCDDNFNIDHASVICRQLECGSAVSFSGSSNFGEGSGPIWFDDLICNGNESALWNCKHQGWGKHNCDHAEDAGVICSKGADLSLRLVDGVTECSGRLEVRFQGEWGTICDDGWDSYDAAVACKQLGCPTAVTAIGRVNASKGFGHIWLDSVSCQGHEPAIWQCKHHEWGKHYCNHNEDAGVTCSDGSDLELRLRGGGSRCAGTVEVEIQRLLGKVCDRGWGLKEADVVCRQLGCGSALKTSYQVYSKIQATNTWLFLSSCNGNETSLWDCKNWQWGGLTCDHYEEAKITCSAHREPRLVGGDIPCSGRVEVKHGDTWGSICDSDFSLEAASVLCRELQCGTVVSILGGAHFGEGNGQIWAEEFQCEGHESHLSLCPVAPRPEGTCSHSRDVGVVCSRYTEIRLVNGKTPCEGRVELKTLGAWGSLCNSHWDIEDAHVLCQQLKCGVALSTPGGARFGKGNGQIWRHMFHCTGTEQHMGDCPVTALGASLCPSEQVASVICSGNQSQTLSSCNSSSLGPTRPTIPEESAVACIESGQLRLVNGGGRCAGRVEIYHEGSWGTICDDSWDLSDAHVVCRQLGCGEAINATGSAHFGEGTGPIWLDEMKCNGKESRIWQCHSHGWGQQNCRHKEDAGVICSEFMSLRLTSEASREACAGRLEVFYNGAWGTVGKSSMSETTVGVVCRQLGCADKGKINPASLDKAMSIPMWVDNVQCPKGPDTLWQCPSSPWEKRLASPSEETWITCDNKIRLQEGPTSCSGRVEIWHGGSWGTVCDDSWDLDDAQVVCQQLGCGPALKAFKEAEFGQGTGPIWLNEVKCKGNESSLWDCPARRWGHSECGHKEDAAVNCTDISVQKTPQKATTGRSSRQSSFIAVGILGVVLLAIFVALFFLTKKRRQRQRLAVSSRGENLVHQIQYREMNSCLNADDLDLMNSSENSHESADFSAAELISVSKFLPISGMEKEAILSHTEKENGNL |
| Enzyme Length | 1156 |
| Uniprot Accession Number | Q86VB7 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | 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. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Chain (2); Disulfide bond (26); Domain (9); Erroneous initiation (5); Glycosylation (4); Motif (1); Mutagenesis (3); Natural variant (1); Signal peptide (1); Site (4); Topological domain (2); Transmembrane (1) |
| Keywords | Acute phase;Alternative splicing;Cell membrane;Disulfide bond;Glycoprotein;Inflammatory response;Membrane;Phosphoprotein;Reference proteome;Repeat;Secreted;Signal;Transmembrane;Transmembrane helix |
| Interact With | P12314 |
| Induction | 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. {ECO:0000269|PubMed:10577520, ECO:0000269|PubMed:10648003}. |
| Subcellular Location | SUBCELLULAR LOCATION: [Soluble CD163]: Secreted {ECO:0000269|PubMed:12296867}.; SUBCELLULAR LOCATION: Cell 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. |
| Modified Residue | |
| Post Translational Modification | 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. {ECO:0000269|PubMed:10066432, ECO:0000269|PubMed:12296867, ECO:0000269|PubMed:15075364, ECO:0000269|PubMed:15448162}.; PTM: Phosphorylated. {ECO:0000305|PubMed:11298324}. |
| Signal Peptide | SIGNAL 1..41; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10975989; 11688984; 11865982; 14656926; 14962251; 15146432; 15479433; 15613100; 15624762; 15846794; 16189277; 16507898; 16517975; 16522161; 17008602; 17095719; 17102136; 17117055; 17460152; 17525367; 17548657; 17629586; 17947394; 18276779; 18316565; 18320015; 18410276; 18542032; 18563533; 18604302; 18849484; 19040468; 19131549; 19473660; 19528371; 19582880; 19885719; 19910578; 19961729; 20237496; 20299688; 20379614; 20472850; 20711500; 20807704; 21120485; 21692033; 21766094; 21799753; 21813065; 21839737; 21933102; 21962403; 22044760; 22060747; 22098563; 22211334; 22279103; 22289504; 22290142; 22309204; 22354894; 22362417; 22450890; 22453843; 22504842; 22540373; 22682876; 22807450; 22884782; 22911680; 22948049; 22949100; 23011084; 23013330; 23149357; 23150181; 23165891; 23224400; 23289476; 23326413; 23463035; 23539121; 23555776; 23557330; 23589619; 23595052; 23640944; 23660665; 23671278; 23687420; 23692821; 23792028; 23800379; 23873589; 23922818; 24118665; 24275664; 24423341; 24489836; 24498098; 24515766; 24548423; 24577568; 24597777; 24612259; 24612419; 24619759; 24623375; 24637679; 24858806; 24883329; 24934531; 24978196; 24983948; 25074267; 25109683; 25156085; 25281471; 25346048; 25366599; 25388964; 25392926; 25461761; 25499804; 25587690; 25602697; 25747973; 25869385; 25944005; 26045748; 26087825; 26135617; 26209500; 26339412; 26352275; 26376364; 26549495; 26568320; 26569178; 26616677; 26916171; 26985764; 27094919; 27100336; 27242373; 27354410; 27355513; 27591510; 27679428; 27684274; 28005267; 28084321; 28103926; 28282272; 28392117; 28406702; 28455006; 28639912; 28687956; 28715286; 28805986; 29021532; 29226859; 29288002; 29345059; 29445750; 29457790; 29468486; 29506265; 29610117; 29657141; 29663331; 29725763; 29795672; 29801971; 29802679; 29868826; 29868909; 29967280; 29973670; 30031096; 30246699; 30254632; 30258108; 30380100; 30548982; 30575644; 30734215; 30842629; 30851700; 31071174; 31109698; 31209811; 31240481; 31242338; 31268976; 31541232; 31677389; 31711674; 31752995; 31918162; 32333612; 32351512; 32431194; 32580398; 32615997; 32752088; 32901498; 32967511; 33085074; 33203735; 33216379; 33310266; 33332647; 33433406; 33498620; 33586094; 33686666; 33764002; 33777012; 33878617; 34201498; 34256095; 34395626; 34725292; 34755559; 34797860; 8921966; 9523318; |
| Motif | MOTIF 1096..1099; /note=Internalization signal |
| Gene Encoded By | |
| Mass | 125,451 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic 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}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |