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Q14114 (LRP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Low-density lipoprotein receptor-related protein 8

Short name=LRP-8
Alternative name(s):
Apolipoprotein E receptor 2
Gene names
Name:LRP8
Synonyms:APOER2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length963 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.9 Ref.10 Ref.11

Subunit structure

Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 By similarity. Interacts with PCSK9. Ref.12

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.

Tissue specificity

Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver. Ref.6 Ref.8

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.

Post-translational modification

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. Ref.7

Ubiquitinated by MYLIP leading to degradation. Ref.13

Involvement in disease

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.

Miscellaneous

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

Sequence similarities

Belongs to the LDLR family.

Contains 2 EGF-like domains.

Contains 7 LDL-receptor class A domains.

Contains 5 LDL-receptor class B repeats.

Sequence caution

The sequence CAA99509.1 differs from that shown. Reason: Frameshift at positions 430, 432 and 438.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processammon gyrus development

Inferred from sequence or structural similarity. Source: BHF-UCL

blood coagulation

Traceable author statement. Source: Reactome

cellular response to cholesterol

Inferred from electronic annotation. Source: Ensembl

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Non-traceable author statement Ref.3. Source: UniProtKB

endocytosis

Inferred from direct assay Ref.1. Source: UniProtKB

layer formation in cerebral cortex

Inferred from electronic annotation. Source: Ensembl

lipid metabolic process

Non-traceable author statement Ref.3. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

phototransduction, visible light

Traceable author statement. Source: Reactome

positive regulation of CREB transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of dendrite development

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of dendritic spine morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

proteolysis

Non-traceable author statement Ref.3. Source: UniProtKB

receptor-mediated endocytosis

Inferred from direct assay Ref.1. Source: GOC

reelin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of synaptic transmission

Inferred from sequence or structural similarity. Source: BHF-UCL

response to drug

Inferred from electronic annotation. Source: Ensembl

retinoid metabolic process

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement PubMed 10380922. Source: ProtInc

   Cellular_componentcaveola

Inferred from direct assay PubMed 11369809. Source: BHF-UCL

dendrite

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred by curator Ref.3. Source: UniProtKB

microtubule associated complex

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionapolipoprotein binding

Inferred by curator Ref.1. Source: BHF-UCL

calcium ion binding

Inferred from electronic annotation. Source: InterPro

high-density lipoprotein particle binding

Inferred from electronic annotation. Source: Ensembl

reelin receptor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

transmembrane signaling receptor activity

Traceable author statement Ref.1. Source: ProtInc

very-low-density lipoprotein particle receptor activity

Inferred from direct assay Ref.1. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

APOEP026492EBI-2681187,EBI-1222467

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. No differences were observed in the pattern splicing between control and Alzheimer brains.
Isoform 1 (identifier: Q14114-1)

Also known as: ApoER2 922;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q14114-2)

Also known as: ApoER2 906;

The sequence of this isoform differs from the canonical sequence as follows:
     166-295: LCAPHEFQCG...KDKSDEADCP → S
     737-812: APQSTSTTTL...PATSNHSQHY → D
     893-951: Missing.
Isoform 3 (identifier: Q14114-3)

The sequence of this isoform differs from the canonical sequence as follows:
     893-951: Missing.
Isoform 4 (identifier: Q14114-4)

Also known as: ApoER2delta4-7;

The sequence of this isoform differs from the canonical sequence as follows:
     166-166: L → W
     167-336: Missing.
Isoform 5 (identifier: Q14114-5)

The sequence of this isoform is not available.
Note: Contains an insert in the extracellular part which carries a furin cleavage site.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 963931Low-density lipoprotein receptor-related protein 8
PRO_0000017332

Regions

Topological domain42 – 826785Extracellular Potential
Transmembrane827 – 84721Helical; Potential
Topological domain848 – 963116Cytoplasmic Potential
Domain46 – 8237LDL-receptor class A 1
Domain85 – 12339LDL-receptor class A 2
Domain126 – 16439LDL-receptor class A 3
Domain166 – 20237LDL-receptor class A 4
Domain205 – 24642LDL-receptor class A 5
Domain258 – 29538LDL-receptor class A 6
Domain298 – 33437LDL-receptor class A 7
Domain336 – 37540EGF-like 1
Domain376 – 41540EGF-like 2; calcium-binding Potential
Repeat462 – 50847LDL-receptor class B 1
Repeat509 – 55143LDL-receptor class B 2
Repeat552 – 59544LDL-receptor class B 3
Repeat596 – 63944LDL-receptor class B 4
Repeat640 – 68142LDL-receptor class B 5
Region740 – 79859Clustered O-linked oligosaccharides

Amino acid modifications

Glycosylation1761N-linked (GlcNAc...) Potential
Glycosylation4411N-linked (GlcNAc...) Potential
Glycosylation5181N-linked (GlcNAc...) Potential
Glycosylation5381N-linked (GlcNAc...) Potential
Glycosylation7721N-linked (GlcNAc...) Potential
Glycosylation8071N-linked (GlcNAc...) Potential
Disulfide bond47 ↔ 59 By similarity
Disulfide bond54 ↔ 72 By similarity
Disulfide bond66 ↔ 81 By similarity
Disulfide bond86 ↔ 98 By similarity
Disulfide bond93 ↔ 111 By similarity
Disulfide bond105 ↔ 122 By similarity
Disulfide bond127 ↔ 141 By similarity
Disulfide bond134 ↔ 154 By similarity
Disulfide bond148 ↔ 163 By similarity
Disulfide bond167 ↔ 179 By similarity
Disulfide bond174 ↔ 192 By similarity
Disulfide bond186 ↔ 201 By similarity
Disulfide bond206 ↔ 221 By similarity
Disulfide bond213 ↔ 234 By similarity
Disulfide bond228 ↔ 245 By similarity
Disulfide bond259 ↔ 272 By similarity
Disulfide bond267 ↔ 285 By similarity
Disulfide bond279 ↔ 294 By similarity
Disulfide bond299 ↔ 311 By similarity
Disulfide bond306 ↔ 324 By similarity
Disulfide bond318 ↔ 333 By similarity
Disulfide bond340 ↔ 351 By similarity
Disulfide bond347 ↔ 360 By similarity
Disulfide bond362 ↔ 374 By similarity
Disulfide bond380 ↔ 390 By similarity
Disulfide bond386 ↔ 399 By similarity
Disulfide bond401 ↔ 414 By similarity

Natural variations

Alternative sequence166 – 295130LCAPH…EADCP → S in isoform 2.
VSP_010305
Alternative sequence1661L → W in isoform 4.
VSP_038181
Alternative sequence167 – 336170Missing in isoform 4.
VSP_010306
Alternative sequence737 – 81276APQST…HSQHY → D in isoform 2.
VSP_010307
Alternative sequence893 – 95159Missing in isoform 2 and isoform 3.
VSP_010308
Natural variant251Q → R. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs4926972 [ dbSNP | Ensembl ].
VAR_046974
Natural variant461D → E. Ref.1 Ref.2 Ref.3 Ref.5 Ref.14
Corresponds to variant rs3820198 [ dbSNP | Ensembl ].
VAR_018468
Natural variant4531V → M.
Corresponds to variant rs5180 [ dbSNP | Ensembl ].
VAR_037624
Natural variant4661W → C.
Corresponds to variant rs5181 [ dbSNP | Ensembl ].
VAR_037625
Natural variant6071Q → R.
Corresponds to variant rs5172 [ dbSNP | Ensembl ].
VAR_037626
Natural variant6111I → L.
Corresponds to variant rs5170 [ dbSNP | Ensembl ].
VAR_037627
Natural variant6531S → T.
Corresponds to variant rs5171 [ dbSNP | Ensembl ].
VAR_037628
Natural variant7361R → Q.
Corresponds to variant rs5172 [ dbSNP | Ensembl ].
VAR_059079
Natural variant9521R → Q Associated with susceptibility to myocardial infarction type 1; increases activation of MAPK14 by oxidized low density lipoprotein. Ref.14 Ref.15
Corresponds to variant rs5174 [ dbSNP | Ensembl ].
VAR_018469

Experimental info

Sequence conflict2621A → V in BAA09328. Ref.1
Sequence conflict2621A → V in BAA21824. Ref.2
Sequence conflict4051Y → C in CAA99509. Ref.3
Sequence conflict4181A → G in BAA09328. Ref.1
Sequence conflict4181A → G in BAA21824. Ref.2
Sequence conflict4181A → G in BAA21825. Ref.2
Sequence conflict4301H → Y in BAA09328. Ref.1
Sequence conflict4301H → Y in BAA21824. Ref.2
Sequence conflict4301H → Y in BAA21825. Ref.2
Sequence conflict4301H → Y in CAA99509. Ref.3
Sequence conflict4881Q → R in CAA99509. Ref.3

Secondary structure

........... 963
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ApoER2 922) [UniParc].

Last modified September 22, 2009. Version 4.
Checksum: B10DCF72F62DE71C

FASTA963105,634
        10         20         30         40         50         60 
MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI 

        70         80         90        100        110        120 
PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA 

       130        140        150        160        170        180 
TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL 

       190        200        210        220        230        240 
AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE 

       250        260        270        280        290        300 
AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR 

       310        320        330        340        350        360 
GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC 

       370        380        390        400        410        420 
TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK 

       430        440        450        460        470        480 
SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD 

       490        500        510        520        530        540 
KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS 

       550        560        570        580        590        600 
EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW 

       610        620        630        640        650        660 
VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL 

       670        680        690        700        710        720 
EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA 

       730        740        750        760        770        780 
CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL 

       790        800        810        820        830        840 
TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL 

       850        860        870        880        890        900 
CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP 

       910        920        930        940        950        960 
LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS KRVALSLEDD 


GLP 

« Hide

Isoform 2 (ApoER2 906) [UniParc].

Checksum: B996C9CAEC69C1E9
Show »

FASTA70077,845
Isoform 3 [UniParc].

Checksum: 043E708314261E3C
Show »

FASTA90499,092
Isoform 4 (ApoER2delta4-7) [UniParc].

Checksum: 1A414B09D40BA1BC
Show »

FASTA79387,959
Isoform 5 (Sequence not available).

References

« Hide 'large scale' references
[1]"Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain."
Kim D.-H., Iijima H., Goto K., Sakai J., Ishii H., Kim H.-J., Suzuki H., Kondo H., Saeki S., Yamamoto T.
J. Biol. Chem. 271:8373-8380(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-25 AND GLU-46.
Tissue: Placenta.
[2]"Exon/intron organization, chromosome localization, alternative splicing, and transcription units of the human apolipoprotein E receptor 2 gene."
Kim D.-H., Magoori K., Inoue T.R., Mao C.C., Kim H.-J., Suzuki H., Fujita T., Endo Y., Saeki S., Yamamoto T.T.
J. Biol. Chem. 272:8498-8504(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 4), VARIANTS ARG-25 AND GLU-46.
Tissue: Peripheral blood.
[3]"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."
Korschineck I., Ziegler S., Breuss J., Lang I., Lorenz M., Kaun C., Ambros P.F., Binder B.R.
J. Biol. Chem. 276:13192-13197(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-25 AND GLU-46.
Tissue: Umbilical vein.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 720-963 (ISOFORM 1), VARIANTS ARG-25 AND GLU-46.
Tissue: Eye and Lung.
[6]"Expression and alternate splicing of apolipoprotein E receptor 2 in brain."
Clatworthy A.E., Stockinger W., Christie R.H., Schneider W.J., Nimpf J., Hyman B.T., Rebeck G.W.
Neuroscience 90:903-911(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[7]"Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells."
Sacre S.M., Stannard A.K., Owen J.S.
FEBS Lett. 540:181-187(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES.
[8]"Identification and characterization of LRP8 (apoER2) in human blood platelets."
Riddell D.R., Vinogradov D.V., Stannard A.K., Chadwick N., Owen J.S.
J. Lipid Res. 40:1925-1930(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.
[9]"Differential binding of ligands to the apolipoprotein E receptor 2."
Andersen O.M., Benhayon D., Curran T., Willnow T.E.
Biochemistry 42:9355-9364(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A RECEPTOR FOR REELIN.
[10]"Domains of apoE required for binding to apoE receptor 2 and to phospholipids: implications for the functions of apoE in the brain."
Li X., Kypreos K., Zanni E.E., Zannis V.
Biochemistry 42:10406-10417(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A RECEPTOR FOR APOE.
[11]"Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'."
Lutters B.C., Derksen R.H., Tekelenburg W.L., Lenting P.J., Arnout J., de Groot P.G.
J. Biol. Chem. 278:33831-33838(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A RECEPTOR FOR BETA 2-GLYCOPROTEIN I.
[12]"The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2."
Poirier S., Mayer G., Benjannet S., Bergeron E., Marcinkiewicz J., Nassoury N., Mayer H., Nimpf J., Prat A., Seidah N.G.
J. Biol. Chem. 283:2363-2372(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCSK9.
[13]"The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2."
Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V., Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J., van Berkel T.J., Tontonoz P., Zelcer N.
J. Biol. Chem. 285:19720-19726(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[14]"Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease."
Ma S.L., Ng H.K., Baum L., Pang J.C., Chiu H.F., Woo J., Tang N.L., Lam L.C.
Neurosci. Lett. 332:216-218(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLU-46 AND GLN-952.
[15]"An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction."
Shen G.-Q., Li L., Girelli D., Seidelmann S.B., Rao S., Fan C., Park J.E., Xi Q., Li J., Hu Y., Olivieri O., Marchant K., Barnard J., Corrocher R., Elston R., Cassano J., Henderson S., Hazen S.L. expand/collapse author list , Plow E.F., Topol E.J., Wang Q.K.
Am. J. Hum. Genet. 81:780-791(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-952, CHARACTERIZATION OF VARIANT GLN-952, ASSOCIATION WITH SUSCEPTIBILITY TO MYOCARDIAL INFARCTION TYPE 1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D50678 mRNA. Translation: BAA09328.1.
D86407 Genomic DNA. Translation: BAA21824.1.
D86407 Genomic DNA. Translation: BAA21825.1.
Z75190 mRNA. Translation: CAA99509.1. Frameshift.
AL606760, AL355483 Genomic DNA. Translation: CAI18908.1.
AL606760, AL355483 Genomic DNA. Translation: CAI18909.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22782.1.
AL606760, AL355483 Genomic DNA. Translation: CAI18910.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22780.1.
AL355483, AL606760 Genomic DNA. Translation: CAI22781.1.
BC006443 mRNA. Translation: AAH06443.1.
BC051836 mRNA. Translation: AAH51836.2.
RefSeqNP_001018064.1. NM_001018054.2.
NP_004622.2. NM_004631.4.
NP_059992.3. NM_017522.4.
NP_150643.2. NM_033300.3.
UniGeneHs.280387.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3A7QX-ray2.60B42-83[»]
ProteinModelPortalQ14114.
SMRQ14114. Positions 44-737.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113579. 18 interactions.
DIPDIP-48670N.
IntActQ14114. 2 interactions.
STRING9606.ENSP00000303634.

PTM databases

PhosphoSiteQ14114.

Polymorphism databases

DMDM259016389.

Proteomic databases

PaxDbQ14114.
PRIDEQ14114.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000306052; ENSP00000303634; ENSG00000157193. [Q14114-1]
ENST00000347547; ENSP00000334522; ENSG00000157193. [Q14114-4]
ENST00000354412; ENSP00000346391; ENSG00000157193. [Q14114-2]
ENST00000371454; ENSP00000360509; ENSG00000157193. [Q14114-3]
GeneID7804.
KEGGhsa:7804.
UCSCuc001cvi.2. human. [Q14114-1]
uc001cvj.2. human. [Q14114-3]
uc001cvk.2. human. [Q14114-4]
uc001cvl.2. human. [Q14114-2]

Organism-specific databases

CTD7804.
GeneCardsGC01M053711.
HGNCHGNC:6700. LRP8.
MIM602600. gene.
608446. phenotype.
neXtProtNX_Q14114.
PharmGKBPA30457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255913.
HOVERGENHBG006250.
InParanoidQ14114.
OMAGCLQEST.
OrthoDBEOG7NGQ9P.
PhylomeDBQ14114.
TreeFamTF351700.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ14114.
BgeeQ14114.
CleanExHS_LRP8.
GenevestigatorQ14114.

Family and domain databases

Gene3D2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProIPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
[Graphical view]
PfamPF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]
PRINTSPR00261. LDLRECEPTOR.
SMARTSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view]
SUPFAMSSF57424. SSF57424. 7 hits.
PROSITEPS00010. ASX_HYDROXYL. 2 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 1 hit.
PS01209. LDLRA_1. 7 hits.
PS50068. LDLRA_2. 7 hits.
PS51120. LDLRB. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14114.
GeneWikiLow_density_lipoprotein_receptor-related_protein_8.
GenomeRNAi7804.
NextBio30188.
PMAP-CutDBB1AMT8.
PROQ14114.
SOURCESearch...

Entry information

Entry nameLRP8_HUMAN
AccessionPrimary (citable) accession number: Q14114
Secondary accession number(s): B1AMT6 expand/collapse secondary AC list , B1AMT7, B1AMT8, O14968, Q86V27, Q99876, Q9BR78
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: September 22, 2009
Last modified: April 16, 2014
This is version 138 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM