LRP8

This gene encodes an apolipoprotein E receptor, a member of the low density lipoprotein receptor (LDLR) family. Apolipoprotein E is a small lipophilic plasma protein and a component of lipoproteins such as chylomicron remnants, very low density lipoprotein (VLDL), and high density lipoprotein (HDL). The apolipoprotein E receptor is involved in cellular recognition and internalization of these lipoproteins. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq]

low density lipoprotein receptor-related protein 8, apolipoprotein e receptor

Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands (PubMed:20223215).
LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Binds the endoplasmic reticulum resident receptor-associated protein (RAP). Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. May also function as an endocytic receptor. Not required for endocytic uptake of SEPP1 in the kidney which is mediated by LRP2 (By similarity).
Together with its ligand, apolipoprotein E (apoE), may indirectly play a role in the suppression of the innate immune response by controlling the survival of myeloid-derived suppressor cells (By similarity).
(Microbial infection) Acts as a receptor for Semliki Forest virus.

Ammon gyrus developmentISS:BHF-UCL
Cellular response to cholesterolIEA:Ensembl
Cellular response to growth factor stimulusIEA:Ensembl
Chemical synaptic transmissionIEA:Ensembl
Cytokine-mediated signaling pathway1 PublicationNAS:UniProtKB
Dendrite morphogenesisIEA:Ensembl
EndocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Layer formation in cerebral cortexIEA:Ensembl
Lipid metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Modulation of chemical synaptic transmissionISS:BHF-UCL
Positive regulation of CREB transcription factor activityISS:BHF-UCL
Positive regulation of dendrite developmentISS:BHF-UCL
Positive regulation of dendritic spine morphogenesisISS:BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationISS:BHF-UCL
Positive regulation of protein tyrosine kinase activityISS:BHF-UCL
Proteolysis1 PublicationNAS:UniProtKB
Reelin-mediated signaling pathwayISS:BHF-UCL
Regulation of apoptotic processISS:UniProtKB
Regulation of innate immune responseISS:UniProtKB
Response to xenobiotic stimulusIEA:Ensembl
Retinoid metabolic processTAS:Reactome
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Ventral spinal cord developmentManual Assertion Based On ExperimentIBA:GO_Central

Cell membrane
Secreted
Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a secreted receptor fragment.

Myocardial infarction 1 (MCI1):
A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia.

Extracellular: 42-826
Helical: 827-847
Cytoplasmic: 848-963

O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain (By similarity).
Undergoes sequential, furin and gamma-secretase dependent, proteolytic processing, resulting in the extracellular release of the entire ligand-binding domain as a soluble polypeptide and in the intracellular domain (ICD) release into the cytoplasm. The gamma-secretase-dependent proteolytical processing occurs after the bulk of the extracellular domain has been shed, in a furin-dependent manner, in alternatively spliced isoforms carrying the furin cleavage site. Hypoglycosylation (mainly hypo-O-glycosylation) leads to increased extracellular cleavage, which in turn results in accelerating release of the intracellular domain (ICD) by the gamma-secretase. The resulting receptor fragment is able to inhibit Reelin signaling and in particular the Reelin-induced DAB1 phosphorylation (By similarity).
Tyrosine phosphorylated upon apoE binding.
Ubiquitinated by MYLIP leading to degradation.