CDB15:0001378 SERPING1 — LRP1

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

Title

Journal:; Year Published:

Abstract

C1 inhibitor-C1s complexes are internalized and degraded by the low density lipoprotein receptor-related protein.

The Journal of biological chemistry, 1997; PubMed, Homo sapiens SERPING1 — Homo sapiens LRP1

ABSTRACT: Like other serpin-enzyme complexes (SECs), proteinase-complexed C1 inhibitor (C1-INH) is rapidly cleared from the circulation and thought to be a neutrophil chemoattractant, suggesting that complex formation causes structural rearrangements exposing a domain which is recognized by specific cell surface receptors. However, the cellular receptor(s) responsible for the catabolism and potential mediation of chemotaxis by C1-INH-protease complexes remained obscure. To determine whether the SEC receptor mediates the binding and potential chemotaxis of C1-INH.Cs, we performed binding assays with HepG2 cells, neutrophils, and monocytes, and the results show that C1-INH.Cs neither bind to these cells nor cause a chemotactic response of neutrophils and monocytes. Furthermore, C1-INH.Cs, the COOH-terminal C1 inhibitor peptide, or the tetrameric C1-INH.Cs.Cr. C1-INH complex were found to be significantly less effective in competing with the SEC receptor ligand 125I-peptide 105Y for the binding to HepG2 cells than unlabeled 105Y, indicating that the SEC receptor does not sufficiently recognize C1-INH-protease complexes. The asialoglycoprotein receptor was also ruled out to be responsible for the removal of the heavily glycosylated C1-INH.Cs complex, since asialoorosomucoid did not compete for the clearance of C1-INH. 125I-Cs and asialoglycoprotein receptor knockout mice showed no alterations in the C1-INH.125I-Cs clearance rate. We found that C1-INH.125I-Cs complexes were efficiently degraded by normal murine fibroblasts expressing the low density lipoprotein receptor-related protein (LRP) and cellular degradation was significantly reduced by chloroquine and the receptor-associated protein, which is a potent inhibitor of the binding of all known ligands to LRP. Moreover, receptor-associated protein inhibited the in vivo clearance of C1-INH.125I-Cs and murine fibroblasts genetically deficient for LRP did not degrade C1-INH.125I-Cs. Our results demonstrate that C1-INH. Cs complexes do not stimulate neutrophil or monocytic chemotaxis but are removed by LRP, further underscoring its role as a serpin-enzyme complex clearance receptor.

Basic Information on SERPING1

Ligand Name: serpin family G member 1

Other Symbols: C1NH, C1IN, C1-INH, HAE1, HAE2, C1INH

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: SERPING1

GeneCards: SERPING1

HGNC Gene Group: Complement system, Serpin peptidase inhibitors

Functional Annotations for SERPING1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for SERPING1

SERPING1 — SELE ・ SERPING1 — SELP

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

HGNC Gene Group: MicroRNA host genes, CD molecules, Low density lipoprotein receptors

Functional Annotations for LRP1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for LRP1

A2M — LRP1 ・ APOE — LRP1 ・ APP — LRP1 ・ C1QB — LRP1 ・ C3 — LRP1 ・ C4BPA — LRP1 ・ CALR — LRP1 ・ CCN2 — LRP1 ・ F8 — LRP1 ・ F9 — LRP1 ・ FCN2 — LRP1 ・ HSP90B1 — LRP1 ・ LIPC — LRP1 ・ LPL — LRP1 ・ LRPAP1 — LRP1 ・ LTF — LRP1 ・ MDK — LRP1 ・ MMP13 — LRP1 ・ MMP9 — LRP1 ・ PDGFB — LRP1 ・ PLAT — LRP1 ・ PLAU — LRP1 ・ PSAP — LRP1 ・ SERPINA1 — LRP1 ・ SERPINC1 — LRP1 ・ SERPINE1 — LRP1 ・ SERPINE2 — LRP1 ・ TFPI — LRP1 ・ THBS1 — LRP1 ・ ADAMTS1 — LRP1 ・ APOC3 — LRP1 ・ C1QA — LRP1 ・ CCN1 — LRP1 ・ CEMIP — LRP1 ・ HGFAC — LRP1 ・ HMGB1 — LRP1 ・ HMGB2 — LRP1 ・ HPX — LRP1 ・ HSP90AA1 — LRP1 ・ HSPA1A — LRP1 ・ HSPA4 — LRP1 ・ IGFBP7 — LRP1 ・ LIF — LRP1 ・ MBL2 — LRP1 ・ MMP1 — LRP1 ・ PF4 — LRP1 ・ PLAUR — LRP1 ・ SERPIND1 — LRP1 ・ SFTPA1 — LRP1 ・ SFTPD — LRP1 ・ SLIT2 — LRP1 ・ SPARC — LRP1 ・ TIMP1 — LRP1 ・ TIMP3 — LRP1 ・ TNFAIP6 — LRP1 ・ VWF — LRP1