C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130

C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130 » Hemoglobin scavenger receptor;
Hydrophobic Thickness 35.2 ± 4.4 Å
Tilt Angle 26 ± 19°
ΔGtransfer -32.2 kcal/mol
ΔGfold -27.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 1048-1072 (1044-1077)
Pathways

Binding and Uptake of Ligands by Scavenger Receptors (Reactome)

PDB none
OPM none
Complexes none
Interactions

TNF12, Complex: C163A:TNF12, PubMed

Domains

AA: 54-152, PDBID: 1BY2, Subunit A, Seq Identity:44%, Scavenger receptor cysteine-rich domain

AA: 162-259, PDBID: 1BY2, Subunit A, Seq Identity:49%, Scavenger receptor cysteine-rich domain

AA: 269-366, PDBID: 5A2E, Subunit A, Seq Identity:50%, Scavenger receptor cysteine-rich domain

AA: 376-473, PDBID: 5A2E, Subunit A, Seq Identity:41%, Scavenger receptor cysteine-rich domain

AA: 481-578, PDBID: 1BY2, Subunit A, Seq Identity:41%, Scavenger receptor cysteine-rich domain

AA: 586-683, PDBID: 5A2E, Subunit A, Seq Identity:40%, Scavenger receptor cysteine-rich domain

AA: 722-819, PDBID: 1BY2, Subunit A, Seq Identity:54%, Scavenger receptor cysteine-rich domain

AA: 829-926, PDBID: 1BY2, Subunit A, Seq Identity:31%, Scavenger receptor cysteine-rich domain

AA: 932-1029, PDBID: 1BY2, Subunit A, Seq Identity:54%, Scavenger receptor cysteine-rich domain

UniProt annotation for C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130
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.

SUBUNIT: Interacts with CSNK2B.

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.

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.

UniProt features for C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130
SIGNAL 1 41 Potential.
CHAIN 42 1156 Scavenger receptor cysteine-rich type 1 protein M130.
CHAIN 42 ? Soluble CD163.
DOMAIN 51 152 SRCR 1.
DOMAIN 159 259 SRCR 2.
DOMAIN 266 366 SRCR 3.
DOMAIN 373 473 SRCR 4.
DOMAIN 478 578 SRCR 5.
DOMAIN 583 683 SRCR 6.
DOMAIN 719 819 SRCR 7.
DOMAIN 824 926 SRCR 8.
DOMAIN 929 1029 SRCR 9.
MOTIF 1096 1099 Internalization signal.
SITE 269 270 Cleavage; in calcium-free condition.
SITE 281 282 Cleavage; in calcium-free condition.
SITE 333 334 Cleavage; in calcium-free condition.
SITE 360 361 Cleavage; in calcium-free condition.
DISULFID 76 141 By similarity.
DISULFID 89 151 By similarity.
DISULFID 120 130 By similarity.
DISULFID 184 248 By similarity.
DISULFID 197 258 By similarity.
DISULFID 228 238 By similarity.
DISULFID 291 355 By similarity.
DISULFID 304 365 By similarity.
DISULFID 335 345 By similarity.
DISULFID 398 462 By similarity.
DISULFID 411 472 By similarity.
DISULFID 442 452 By similarity.
DISULFID 503 567 By similarity.
DISULFID 516 577 By similarity.
DISULFID 547 557 By similarity.
DISULFID 608 672 By similarity.
DISULFID 621 682 By similarity.
DISULFID 652 662 By similarity.
DISULFID 744 808 By similarity.
DISULFID 757 818 By similarity.
DISULFID 788 798 By similarity.
DISULFID 864 925 By similarity.
DISULFID 895 905 By similarity.
DISULFID 954 1018 By similarity.
DISULFID 967 1028 By similarity.
DISULFID 998 1008 By similarity.
Amino Acid Sequence for C163A_HUMAN » Scavenger receptor cysteine-rich type 1 protein M130
MSKLRMVLLE DSGSADFRRH FVNLSPFTIT VVLLLSACFV TSSLGGTDKE LRLVDGENKC SGRVEVKVQE EWGTVCNNGW SMEAVSVICN QLGCPTAIKA PGWANSSAGS GRIWMDHVSC RGNESALWDC KHDGWGKHSN CTHQQDAGVT CSDGSNLEMR LTRGGNMCSG RIEIKFQGRW GTVCDDNFNI DHASVICRQL ECGSAVSFSG SSNFGEGSGP IWFDDLICNG NESALWNCKH QGWGKHNCDH AEDAGVICSK GADLSLRLVD GVTECSGRLE VRFQGEWGTI CDDGWDSYDA AVACKQLGCP TAVTAIGRVN ASKGFGHIWL DSVSCQGHEP AVWQCKHHEW GKHYCNHNED AGVTCSDGSD LELRLRGGGS RCAGTVEVEI QRLLGKVCDR GWGLKEADVV CRQLGCGSAL KTSYQVYSKI QATNTWLFLS SCNGNETSLW DCKNWQWGGL TCDHYEEAKI TCSAHREPRL VGGDIPCSGR VEVKHGDTWG SICDSDFSLE AASVLCRELQ CGTVVSILGG AHFGEGNGQI WAEEFQCEGH ESHLSLCPVA PRPEGTCSHS RDVGVVCSRY TEIRLVNGKT PCEGRVELKT LGAWGSLCNS HWDIEDAHVL CQQLKCGVAL STPGGARFGK GNGQIWRHMF HCTGTEQHMG DCPVTALGAS LCPSEQVASV ICSGNQSQTL SSCNSSSLGP TRPTIPEESA VACIESGQLR LVNGGGRCAG RVEIYHEGSW GTICDDSWDL SDAHVVCRQL GCGEAINATG SAHFGEGTGP IWLDEMKCNG KESRIWQCHS HGWGQQNCRH KEDAGVICSE FMSLRLTSEA SREACAGRLE VFYNGAWGTV GKSSMSETTV GVVCRQLGCA DKGKINPASL DKAMSIPMWV DNVQCPKGPD TLWQCPSSPW EKRLASPSEE TWITCDNKIR LQEGPTSCSG RVEIWHGGSW GTVCDDSWDL DDAQVVCQQL GCGPALKAFK EAEFGQGTGP IWLNEVKCKG NESSLWDCPA RRWGHSECGH KEDAAVNCTD ISVQKTPQKA TTGRSSRQSS FIAVGILGVV LLAIFVALFF LTKKRRQRQR LAVSSRGENL VHQIQYREMN SCLNADDLDL MNSSENSHES ADFSAAELIS VSKFLPISGM EKEAILSHTE KENGNL