CDB15:0000161 C3 — 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

Metabolism of activated complement component C3 is mediated by the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor.

The Journal of biological chemistry, 1999; PubMed, Homo sapiens C3 — Homo sapiens LRP1

ABSTRACT: Complement component 3 (C3) and alpha(2)-macroglobulin evolved from a common, evolutionarily old, ancestor gene. Low density lipoprotein-receptor-related protein/alpha(2)-macroglobulin receptor (LRP/alpha(2)MR), a member of the low density lipoprotein receptor family, is responsible for the clearance of alpha(2)-macroglobulin-protease complexes. In this study, we examined whether C3 has conserved affinity for LRP/alpha(2)MR. Ligand blot experiments with human (125)I-C3 on endosomal proteins show binding to a 600-kDa protein, indistinguishable from LRP/alpha(2)MR by the following criteria: it is competed by receptor-associated protein (the 39-kDa receptor-associated protein that impairs binding of all ligands to LRP/alpha(2)MR) and by lactoferrin and Pseudomonas exotoxin, other well known ligands of the multifunctional receptor. Binding of C3 is sensitive to reduction of the receptor and is Ca(2+)-dependent. All these features are typical for cysteine-rich binding repeats of the low density lipoprotein receptor family. In LRP/alpha(2)MR, they are found in four cassettes (2, 8, 10, and 11 repeats). Ligand blotting to chicken LR8 demonstrates that a single 8-fold repeat is sufficient for binding. Confocal microscopy visualizes initial surface labeling of human fibroblasts incubated with fluorescent labeled C3, which changes after 5 min to an intracellular vesicular staining pattern that is abolished in the presence of receptor-associated protein. Cell uptake is abolished in mouse fibroblasts deficient in LRP/alpha(2)MR. Native plasma C3 is not internalized. We demonstrate that the capacity to internalize C3 is saturable and exhibits a K(D) value of 17 nM. After intravenous injection, rat hepatocytes accumulate C3 in sedimentable vesicles with a density typical for endosomes. In conclusion, our ligand blot and uptake studies demonstrate the competence of the LRP/alpha(2)MR to bind and endocytose C3 and provide evidence for an LRP/alpha(2)MR-mediated system participating in C3 metabolism.

Basic Information on C3

Ligand Name: complement C3

Other Symbols: CPAMD1, ARMD9, C3a, C3b

Ligand Location: secreted based on perplexity, uniprot

HGNC Gene Symbol Report: C3

GeneCards: C3

HGNC Gene Group: C3 and PZP like, alpha-2-macroglobulin domain containing, Complement system, Receptor ligands

Functional Annotations for C3

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 C3

C3 — C3AR1 ・ C3 — C5AR2 ・ C3 — CR1 ・ C3 — ITGAM ・ C3 — ITGAX ・ C3 — ITGB2 ・ C3 — CR2 ・ C3 — NRP1

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 ・ 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 ・ SERPING1 — 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