Tbio LRP8 Low-density lipoprotein receptor-related protein 8

Protein Summary

Description

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. 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). This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

Uniprot Accession IDs

• Q14114
• B1AMT6
• B1AMT7
• B1AMT8
• O14968
• Q86V27
• Q99876
• Q9BR78
• LRP-8

Gene Name

• LRP8

Ensembl ID

• ENST00000306052
• ENSP00000303634
• ENSG00000157193
• ENST00000347547
• ENSP00000334522
• ENST00000354412
• ENSP00000346391
• ENST00000371454
• ENSP00000360509

Symbol

• APOER2
• MCI1
• LRP-8
• APOER2
• HSZ75190

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
biological process	0.97
kinase perturbation	0.97
transcription factor perturbation	0.97
PubMedID	0.91

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 228.36   (req: < 5)

Gene RIFs: 50   (req: <= 3)

Antibodies: 354   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 228.36   (req: >= 5)

Gene RIFs: 50   (req: > 3)

Antibodies: 354   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GENEVA

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (107)

Explore Interacting Targets

1 – 10 of 107

• See Interactions on String-DB

LRPAP1

Tbio

Novelty:  0.00214194

p_int:  0.994573648

p_ni:  1e-9

p_wrong:  0.005426351

Score:  0.959

Data Source:  BioPlex,STRINGDB

RELN

Tbio

Novelty:  0.005326

Score:  0.996

Data Source:  STRINGDB

APOE

Tbio

Novelty:  0.00005049

Score:  0.987

Data Source:  Reactome,STRINGDB

DAB1

Tbio

Novelty:  0.08538222

Score:  0.985

Data Source:  STRINGDB

FYN

Tclin

Family:  Kinase

Novelty:  0.00072167

Score:  0.977

Data Source:  STRINGDB

APOB

Tchem

Novelty:  0.00008247

Score:  0.95

Data Source:  STRINGDB

CRKL

Tbio

Novelty:  0.0051181

Score:  0.947

Data Source:  STRINGDB

RAPGEF1

Tbio

Novelty:  0.00365765

Score:  0.943

Data Source:  STRINGDB

AGRN

Tbio

Novelty:  0.00156441

Score:  0.942

Data Source:  STRINGDB

GRIN2B

Tclin

Family:  IC

Novelty:  0.00035058

Score:  0.941

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (14)

Reactome (12)

PathwayCommons (2)

G alpha (i) signalling events (R-HSA-418594)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396
Reactome	Hemostasis	666 targets	R-HSA-109582
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of fat-soluble vitamins	48 targets	R-HSA-6806667

Name	Explore in Pharos	Explore in Source
G alpha (i) signalling events	408 targets	R-HSA-418594
GPCR downstream signalling	1152 targets	R-HSA-388396
Hemostasis	666 targets	R-HSA-109582
Metabolism	2112 targets	R-HSA-1430728
Metabolism of fat-soluble vitamins	48 targets	R-HSA-6806667

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (40)

Functions (8)

Components (11)

Processes (21)

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1 – 8 of 8

GO Term	Evidence	Assigned by
very-low-density lipoprotein particle receptor activity	Inferred from Direct Assay (IDA)	BHF-UCL
reelin receptor activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
low-density lipoprotein particle receptor activity	Traceable Author Statement (TAS)	ARUK-UCL
transmembrane signaling receptor activity	Traceable Author Statement (TAS)	ProtInc
apolipoprotein binding	Inferred by Curator (IC)	BHF-UCL
calcium ion binding	Inferred from Electronic Annotation (IEA)	InterPro
high-density lipoprotein particle binding	Inferred from Electronic Annotation (IEA)	Ensembl
kinesin binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (7)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood metabolite measurement	EFO_0005664	1	1	1		78.6
metabolite measurement	EFO_0004725	1	2	2		73.3
self reported educational attainment	EFO_0004784	1	1	1		44.2
urinary metabolite measurement	EFO_0005116	1	1	1		42.3
feeling emotionally hurt measurement	EFO_0009599	1	1	0	5.8	26.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood metabolite measurement	EFO_0005664	1		78.6
metabolite measurement	EFO_0004725	2		73.3
self reported educational attainment	EFO_0004784	1		44.2
urinary metabolite measurement	EFO_0005116	1		42.3
feeling emotionally hurt measurement	EFO_0009599	0	5.8	26.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Calcium
Cell membrane
Complete proteome
Disulfide bond
EGF-like domain
Endocytosis
Glycoprotein
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
blood metabolite measurement
feeling emotionally hurt measurement
metabolite measurement
risk-taking behaviour
risky sexual behaviour measurement
self reported educational attainment
urinary metabolite measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
nervous system phenotype
reproductive system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	LDL receptor related protein 8	VGNC:6908	456865
Macaque	LDL receptor related protein 8		714317
Mouse	low density lipoprotein receptor-related protein 8, apolipoprotein e receptor	MGI:1340044	16975
Rat	LDL receptor related protein 8	RGD:1305729	362558
Dog	LDL receptor related protein 8	VGNC:42779	489584

Species	Name	OMA	EggNOG	Inparanoid
Chimp	LDL receptor related protein 8
Macaque	LDL receptor related protein 8
Mouse	low density lipoprotein receptor-related protein 8, apolipoprotein e receptor
Rat	LDL receptor related protein 8
Dog	LDL receptor related protein 8

Publication Statistics

PubMed Score 228.36

PubMed score by year

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PubTator Score 102.86

PubTator score by year

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Related Publications

Text Mined References (84)

GeneRif Annotations (50)

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PMID	Year	Title