Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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This record defines the annotation-generation method represented by the GO_REF.
"Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity"
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
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This record defines the annotation-generation method represented by the GO_REF.
"Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt"
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
UniProtKB/Swiss-Prot record for human LRP8 (Q14114)
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The reviewed human LRP8 entry is a 963-residue protein record.
"ID LRP8_HUMAN Reviewed; 963 AA."
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The entry maps seven LDL-receptor class A domains in the extracellular region.
"DR Pfam; PF00057; Ldl_recept_a; 7."
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The four listed experimental structures cover restricted residue ranges rather than full-length LRP8.
"DR PDB; 3A7Q; X-ray; 2.60 A; B=42-83."
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The PANTHER assignment has a broad low-density-lipoprotein-receptor-related label.
"DR PANTHER; PTHR22722:SF15; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1."
Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain.
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Human ApoER2 expressed in LDLR-deficient CHO cells bound and internalized apoE-rich beta-migrating VLDL with high affinity.
"LDL receptor deficient
Chinese hamster ovary cells expressing human apoER2 bound apoE rich
beta-migrating VLDL with high affinity and internalized."
Expression and alternate splicing of apolipoprotein E receptor 2 in brain.
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Human brain and placenta contained LRP8 splice forms that remove defined extracellular, O-glycosylation, or cytoplasmic regions.
"Apolipoprotein E receptor 2
messages lacking exon 8, encoding an epidermal growth factor precursor repeat,
exon 15, encoding the O-glycosylation region, or exon 18, encoding a cytoplasmic
domain, were also present as minor splice variants in the brain and placenta."
Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2.
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Loss of both VLDLR and ApoER2 in mice phenocopied Reelin/Dab1 neuronal-layering defects.
"Inversion of
cortical layers and absence of cerebellar foliation in these animals precisely
mimic the phenotype of mice lacking Reelin or mDab1."
Identification and characterization of LRP8 (apoER2) in human blood platelets.
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Human platelets express LRP8, with the major platelet transcript lacking ligand-binding repeats 4-6 while retaining the full cytoplasmic tail.
"Immunoprecipitation of platelet membranes with
anti-peptide antisera confirmed protein expression, while analysis of RNA from
platelets and two megakaryocytic cell lines (Meg-01 and HEL) disclosed that the
major LRP8 transcript lacked binding repeats 4-6 (LRP8delta4-6) but contained
the full-length cytoplasmic tail."
Reelin is a ligand for lipoprotein receptors.
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Reelin binds directly to VLDLR and ApoER2 in a calcium-dependent interaction inhibited by apoE.
"Here, we demonstrate that Reelin binds directly to
lipoprotein receptors, preferably the very low-density lipoprotein receptor
(VLDLR) and apolipoprotein E receptor 2 (ApoER2)."
Identification of a novel exon in apolipoprotein E receptor 2 leading to alternatively spliced mRNAs found in cells of the vascular wall but not in neuronal tissue.
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Human vascular cells express multiple LRP8 splice variants affecting ligand-binding, O-linked-sugar, and cytoplasmic regions.
"Four novel mRNA transcripts could be identified as isoforms of the
apolipoprotein E receptor 2 (apoEr2): one form lacking three ligand binding
repeats (nucleotides 497-883) but containing a novel ligand binding repeat
adjacent to a unique cysteine-rich domain preceding the epidermal growth factor
precursor domain of apoEr2, forms lacking the O-linked sugar domain, and forms
containing a 59-amino acid deletion within the cytoplasmic tail."
Localization of apolipoprotein E receptor 2 to caveolae in the plasma membrane.
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ApoER2, unlike LDLR, localized to caveolae in the tested plasma-membrane system.
"Here, we show that
apoER2, but not LDL-R, is localized to caveolae, supporting the concept that its
physiological role is in cell signaling, rather than in endocytosing ligands."
Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'.
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Dimeric beta2-glycoprotein I interacted with platelet ApoER2 and promoted ApoER2-dependent platelet adhesion and thrombus formation.
"Using
co-immunoprecipitation, it was shown that dimeric beta 2GPI can interact with
apolipoprotein E receptor 2 (apoER2'), a member of the low density lipoprotein
receptor family present on platelets."
Differential binding of ligands to the apolipoprotein E receptor 2.
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Surface plasmon resonance found higher ApoER2 affinity for Reelin than VLDLR and implicated ApoER2 LDLRA repeats 1 and 3.
"By surface plasmon resonance we demonstrate that apoER2 exhibits
6-fold higher affinity for Reelin than the very low density lipoprotein receptor
(VLDLR), which also functions as a Reelin receptor (K(D) 0.2 nM versus K(D) 1.2
nM)."
Domains of apoE required for binding to apoE receptor 2 and to phospholipids: implications for the functions of apoE in the brain.
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Receptor-expressing-cell assays measured specific binding of phospholipid-associated apoE particles to ApoER2.
"Specific binding to apoER2 was obtained
by subtracting from the total binding to the receptor-expressing cells the
nonspecific binding values of the untransfected cells."
Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors.
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A Reelin R5-6 fragment was sufficient for receptor binding and Dab1 phosphorylation, with oligomerization increasing activity.
"We found that both receptor-binding and subsequent Dab1
phosphorylation occur solely in the segment spanning the fifth and sixth reelin
repeats (R5-6)."
The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2.
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PCSK9 promoted degradation of ApoER2 as well as LDLR and VLDLR in expression and re-internalization assays.
"Our results show that wild type PCSK9 and more so its natural
gain of function mutant D374Y can efficiently degrade the LDLR, VLDLR, and
ApoER2 either following cellular co-expression or re-internalization of secreted
human PCSK9."
Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells.
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Activated protein C bound ApoER2 and triggered ApoER2-dependent Dab1, Akt, and GSK3beta phosphorylation in human U937 cells.
"Here we used human monocytic-like U937 cells to
evaluate apolipoprotein E receptor 2 (ApoER2)-dependent signaling by APC and
found that APC initiated rapid phosphorylation of Tyr-220 in the adaptor protein
disabled-1 (Dab1) and of Ser-473 in Akt."
Defining the membrane proteome of NK cells.
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This source is a broad membrane-proteomics survey of the NK-like YTS cell line.
"The present study was initiated to define the composition of the membrane
proteome of the Natural Killer (NK) like cell line YTS."
Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance.
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The accessible abstract studies LDLR overexpression in transgenic mouse brain rather than LRP8.
"To test our hypothesis, we created
several transgenic mice that overexpress LDLR in the brain and found that apoE
levels in these mice decreased by 50%-90%."
Structural basis for specific recognition of reelin by its receptors.
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A 2.6-angstrom complex structure used the Reelin receptor-binding fragment and the ApoER2 LA1 module.
"Analysis of a 2.6 A crystal structure of the reelin
receptor-binding fragment in complex with the LA1 of ApoER2 revealed that
Lys2467 of reelin is recognized by both a conserved Trp residue and
calcium-coordinating acidic residues from LA1, which together with Lys2360 plays
a critical role in the interaction."
The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2.
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IDOL ubiquitinated the ApoER2 cytoplasmic tail and promoted receptor degradation.
"Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails,
leading to their degradation."
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
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The paper establishes broad PX-FERM cargo recognition but its cached main-text abstract is not LRP8-specific.
"We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins."
Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and signals via the Reelin-signaling pathway.
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Clusterin bound ApoER2 and VLDLR, was internalized by receptor-expressing cells, and triggered Dab1-dependent Reelin-like signaling.
"Here we report, that clusterin binds to apolipoprotein E receptor 2
(ApoER2) and very low density lipoprotein receptor (VLDLR) and is internalized
by cells expressing either one of these receptors."
Differential Action of Reelin on Oligomerization of ApoER2 and VLDL Receptor in HEK293 Cells Assessed by Time-Resolved Anisotropy and Fluorescence Lifetime Imaging Microscopy.
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In HEK293 cells, full-length Reelin rearranged preformed ApoER2/VLDLR oligomers into higher-order clusters associated with Dab1 phosphorylation.
"These findings demonstrate that the primary event in the
canonical Reelin pathway is the rearrangement of preformed receptor
homo-oligomers to higher order clusters."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex generated large AP-MS interaction networks in 293T and HCT116 cells.
"Through affinity-purification
mass spectrometry, we have created two proteome-scale, cell-line-specific
interaction networks."
VLDLR and ApoER2 are receptors for multiple alphaviruses.
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ApoER2 ligand-binding domains interacted with multiple alphavirus glycoproteins, and ectopic receptor expression facilitated particle attachment and internalization.
"We show that the E2 and E1 glycoproteins (E2-E1) of Semliki forest
virus, eastern equine encephalitis virus and Sindbis virus interact with the
ligand-binding domains (LBDs) of VLDLR and apolipoprotein E receptor 2 (ApoER2),
two closely related receptors."
Structural basis for VLDLR recognition by eastern equine encephalitis virus.
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The cryo-EM structures in this paper contain alphavirus spikes bound to a VLDLR ligand-binding domain, not LRP8.
"Here, we use
single-particle cryo-electron microscopy (cryo-EM) to determine structures of
the EEEV and SFV spike glycoproteins bound to the VLDLR ligand-binding domain
and found that EEEV and SFV interact with the same cellular receptor through
divergent binding modes."
LRP8 is a receptor for tick-borne encephalitis virus.
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LRP8 loss and gain altered tick-borne encephalitis virus infection in human cells, and LRP8 directly bound the viral E glycoprotein to mediate entry.
"LRP8
downregulation reduced TBEV infection in human cells, and its overexpression
enhanced infection. LRP8 bound directly to the TBEV E glycoprotein and mediated
viral attachment and internalization into cells."
LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
FGR binds and phosphorylates LRP8
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Reactome links platelet LDL stimulation to FGR association and LRP8 tyrosine phosphorylation.
"Tyrosine phosphorylation of LDL:LRP8 is mediated by the Src-family kinase FGR, based on a correlation of increased LRP8 phosphorylation on LDL stimulation of platelets, and a transient increased co-precipitation of FGR with LRP8 upon LDL stimulation."
FGR binds LDL:LRP8
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Reactome represents transient FGR association with LDL-stimulated LRP8 in platelets.
"Tyrosine phosphorylation of LDL:LRP8 is mediated by the Src-family kinase FGR, based on a correlation of increased LRP8 phosphorylation in LDL-stimulated platelets and a transient increased co-precipitation of FGR and LRP8 upon LDL stimulation."
Retinoid metabolism and transport