InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LRP8

Summary

InnateDB Protein

IDBP-98746.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LRP8

Protein Name

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

Synonyms

APOER2; HSZ75190; LRP-8; MCI1;

Species

Homo sapiens

Ensembl Protein

ENSP00000360509

InnateDB Gene

IDBG-98740 (LRP8)

Protein Structure

UniProt Annotation

Function

Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. 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. {ECO:0000269PubMed:12807892, ECO:0000269PubMed:12899622, ECO:0000269PubMed:12950167}.

Subcellular Localization

Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Secreted {ECO:0000250}. Note=Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a secreted receptor fragment. {ECO:0000250}.

Disease Associations

Myocardial infarction 1 (MCI1) [MIM:608446]: A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver. {ECO:0000269PubMed:10218790, ECO:0000269PubMed:10508213}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 24 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	24 [view]
Protein-Protein	24 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004888	transmembrane signaling receptor activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0030229	very-low-density lipoprotein particle receptor activity
GO:0034185	apolipoprotein binding
GO:0038025	reelin receptor activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001523	retinoid metabolic process
GO:0006508	proteolysis
GO:0006629	lipid metabolic process
GO:0006897	endocytosis
GO:0006898	receptor-mediated endocytosis
GO:0007165	signal transduction
GO:0007596	blood coagulation
GO:0007603	phototransduction, visible light
GO:0019221	cytokine-mediated signaling pathway
GO:0021541	ammon gyrus development
GO:0032793	positive regulation of CREB transcription factor activity
GO:0038026	reelin-mediated signaling pathway
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0050804	regulation of synaptic transmission
GO:0061003	positive regulation of dendritic spine morphogenesis
GO:0061098	positive regulation of protein tyrosine kinase activity
GO:1900006	positive regulation of dendrite development

Cellular Component

GO:0005576	extracellular region
GO:0005886	plasma membrane
GO:0005901	caveola
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000033 LDLR class B repeat
IPR000742 Epidermal growth factor-like domain
IPR001881 EGF-like calcium-binding domain
IPR002172 Low-density lipoprotein (LDL) receptor class A repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal

PFAM

PF00058
PF00008
PF07645
PF00057

PRINTS

PR00261

PIRSF

SMART

SM00135
SM00181
SM00179
SM00192

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt