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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

LRP8 Gene

protein-coding GIFtS: 63
GCID: GC01M053711

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

Explore 20 diseases affiliated with
LRP8 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Low Density Lipoprotein Receptor-Related Protein 8, Apolipoprotein E Receptor¹ ²		HSZ75190²
APOER2¹ ² ³ ⁵		ApoE Receptor 2²
LRP-8² ³		Low-Density Lipoprotein Receptor-Related Protein 8²
MCI1² ⁵		Apolipoprotein E Receptor 2³

External Ids:	HGNC: 6700¹	Entrez Gene: 7804²	Ensembl: ENSG00000157193⁷	OMIM: 602600⁵	UniProtKB: Q14114³

Export aliases for LRP8 gene to outside databases

Previous GC identifers: GC01M053346 GC01M052600 GC01M053069 GC01M053081 GC01M053423 GC01M053483 GC01M051826

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for LRP8:

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)

UniProtKB/Swiss-Prot: LRP8_HUMAN, Q14114

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

Gene Wiki entry for LRP8 (Low density lipoprotein receptor-related protein 8)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000001.10 NC_018912.1 NT_032977.9

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the LRP8 gene promoter:
RORalpha1 USF1 USF-1 USF2 USF-1:USF-2
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search SABiosciences Chromatin IP Primers for LRP8

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat LRP8

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p34 Ensembl cytogenetic band: 1p32.3 HGNC cytogenetic band: 1p32.3

LRP8 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
LRP8 gene location

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M053711: view genomic region (about GC identifiers)

Start:	53,711,212 bp from pter	End:	53,793,821 bp from pter
Size:	82,610 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: LRP8_HUMAN, Q14114 (See protein sequence)

Recommended Name: Low-density lipoprotein receptor-related protein 8 precursor

Size: 963 amino acids; 105634 Da

Subunit: Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins.

Interacts with SNX17 (By similarity). Interacts with PCSK9

Subcellular location: Cell membrane; Single-pass type I membrane protein (By similarity). Secreted (By similarity).

Note=Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a

secreted receptor fragment (By similarity)

Miscellaneous: Natural isoforms of apoE (E2, E3, E4) have similar affinities for LRP8

Sequence caution: Sequence=CAA99509.1; Type=Frameshift; Positions=430, 432, 438;

1 PDB 3D structure from and Proteopedia for LRP8:

3A7Q (3D)

Secondary accessions: B1AMT6 B1AMT7 B1AMT8 O14968 Q86V27 Q99876 Q9BR78

Alternative splicing: 5 isoforms: Q14114-1 Q14114-2 Q14114-3 Q14114-4 Q14114-5 (Contains an insert in the extracellular part which carries a furin cleavage site)

Explore the universe of human proteins at neXtProt for LRP8: NX_Q14114

Post-translational modifications:

O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain (By similarity)¹

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)¹

Tyrosine phosphorylated upon apoE binding¹

Ubiquitinated by MYLIP leading to degradation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q14114

LRP8 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_001018064.1 NP_004622.2 NP_059992.3 NP_150643.2

ENSEMBL proteins:

ENSP00000303634 ENSP00000431241 ENSP00000360509 ENSP00000437009 ENSP00000346391

ENSP00000433554 ENSP00000334522 ENSP00000435346 ENSP00000436651

Reactome Protein details: Q14114
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for LRP8 (Apolipoprotein E R2/ApoE R2)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: LRP8 OriGene Protein Over-expression Lysate (see all 2): LRP8 OriGene Custom Protein Services for LRP8
	GenScript Custom Purified and Recombinant Proteins Services for LRP8
	Novus Biologicals LRP8 Protein Novus Biologicals LRP8 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for LRP8

Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0005901	caveola	IDA	11369809
GO:0016021	integral to membrane	IC	11152697

LRP8 for ontologies About GeneDecksing

LRP8 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Browse R&D Systems for Antibodies
	OriGene Antibodies (see all 2): LRP8 OriGene Custom Antibody Services for LRP8
	GenScript Custom Superior Antibodies Services for LRP8
	Novus Biologicals LRP8 Antibodies
	Abcam antibodies for LRP8
	Uscn Antibodies for LRP8
	ThermoFisher Antibodies for LRP8

Assay Products for LRP8:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for LRP8
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for LRP8

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

LRP8 for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR000033 LDLR_classB_rpt

IPR023415 LDLR_class-A_CS

IPR000742 EG-like_dom

IPR026823 cEGF

IPR000152 EGF-type_Asp/Asn_hydroxyl_site

Graphical View of Domain Structure for InterPro Entry Q14114

ProtoNet protein and cluster: Q14114

4 Blocks protein families:

IPB000033 Low-density lipoprotein receptor

IPB000152 Aspartic acid and asparagine hydroxylation site

IPB001881 EGF-like calcium-binding

IPB002172 Low density lipoprotein-receptor

UniProtKB/Swiss-Prot: LRP8_HUMAN, Q14114

Domain: The cytoplasmic domain is involved in the binding of DAB1 and in the recruitment of JNK-interacting proteins.

Isoforms, which lack part of the cytoplasmic domain, are unable to recruit members of the family of JNK interacting

proteins (JIP) to the cytoplasmic tail (By similarity)

Similarity: Belongs to the LDLR family

Similarity: Contains 2 EGF-like domains

Similarity: Contains 7 LDL-receptor class A domains

Similarity: Contains 5 LDL-receptor class B repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: