CDB25:0003739 HPX — LRP1

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Identification of the receptor scavenging hemopexin-heme complexes.

Blood, 2005; PubMed, Homo sapiens HPX — Homo sapiens LRP1
ABSTRACT: Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin-heme complex established the ability of LRP/CD91 to mediate hemopexin-heme internalization resulting in cellular heme uptake and lysosomal hemopexin degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme-oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation.
Basic Information on HPX
Ligand Name: hemopexin
Other Symbols: N/A
Ligand Location: secreted based on perplexity, uniprot
HGNC Gene Symbol Report: HPX
GeneCards: HPX
HGNC Gene Group: unknown
Interactions with other Receptors for HPX
Basic Information on LRP1
Receptor Name: LDL receptor related protein 1
Other Symbols: APR, A2MR, LRP, CD91, LRP1A, APOER, IGFBP3R1, IGFBP-3R
Receptor Location: cell membrane based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: LRP1
GeneCards: LRP1