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Q14114

- LRP8_HUMAN

UniProt

Q14114 - LRP8_HUMAN

Protein

Low-density lipoprotein receptor-related protein 8

Gene

LRP8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 4 (22 Sep 2009)
      Previous versions | rss
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    Functioni

    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.3 Publications

    GO - Molecular functioni

    1. apolipoprotein binding Source: BHF-UCL
    2. calcium ion binding Source: InterPro
    3. high-density lipoprotein particle binding Source: Ensembl
    4. protein binding Source: IntAct
    5. reelin receptor activity Source: BHF-UCL
    6. transmembrane signaling receptor activity Source: ProtInc
    7. very-low-density lipoprotein particle receptor activity Source: BHF-UCL

    GO - Biological processi

    1. ammon gyrus development Source: BHF-UCL
    2. blood coagulation Source: Reactome
    3. cellular response to cholesterol Source: Ensembl
    4. cellular response to growth factor stimulus Source: Ensembl
    5. cytokine-mediated signaling pathway Source: UniProtKB
    6. endocytosis Source: UniProtKB
    7. layer formation in cerebral cortex Source: Ensembl
    8. lipid metabolic process Source: UniProtKB
    9. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    10. phototransduction, visible light Source: Reactome
    11. positive regulation of CREB transcription factor activity Source: BHF-UCL
    12. positive regulation of dendrite development Source: BHF-UCL
    13. positive regulation of dendritic spine morphogenesis Source: BHF-UCL
    14. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
    15. positive regulation of protein tyrosine kinase activity Source: BHF-UCL
    16. proteolysis Source: UniProtKB
    17. receptor-mediated endocytosis Source: GOC
    18. reelin-mediated signaling pathway Source: BHF-UCL
    19. regulation of synaptic transmission Source: BHF-UCL
    20. response to drug Source: Ensembl
    21. retinoid metabolic process Source: Reactome
    22. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Endocytosis

    Keywords - Ligandi

    Calcium

    Enzyme and pathway databases

    ReactomeiREACT_23879. Platelet sensitization by LDL.
    REACT_24968. Retinoid metabolism and transport.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Low-density lipoprotein receptor-related protein 8
    Short name:
    LRP-8
    Alternative name(s):
    Apolipoprotein E receptor 2
    Gene namesi
    Name:LRP8
    Synonyms:APOER2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:6700. LRP8.

    Subcellular locationi

    Cell membrane By similarity; 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

    GO - Cellular componenti

    1. caveola Source: BHF-UCL
    2. dendrite Source: Ensembl
    3. extracellular region Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB
    5. membrane Source: UniProtKB
    6. microtubule associated complex Source: Ensembl
    7. neuronal cell body Source: Ensembl
    8. plasma membrane Source: Reactome
    9. postsynaptic density Source: Ensembl
    10. receptor complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.

    Organism-specific databases

    MIMi608446. phenotype.
    PharmGKBiPA30457.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232Sequence AnalysisAdd
    BLAST
    Chaini33 – 963931Low-density lipoprotein receptor-related protein 8PRO_0000017332Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi47 ↔ 59By similarity
    Disulfide bondi54 ↔ 72By similarity
    Disulfide bondi66 ↔ 81By similarity
    Disulfide bondi86 ↔ 98By similarity
    Disulfide bondi93 ↔ 111By similarity
    Disulfide bondi105 ↔ 122By similarity
    Disulfide bondi127 ↔ 141By similarity
    Disulfide bondi134 ↔ 154By similarity
    Disulfide bondi148 ↔ 163By similarity
    Disulfide bondi167 ↔ 179By similarity
    Disulfide bondi174 ↔ 192By similarity
    Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi186 ↔ 201By similarity
    Disulfide bondi206 ↔ 221By similarity
    Disulfide bondi213 ↔ 234By similarity
    Disulfide bondi228 ↔ 245By similarity
    Disulfide bondi259 ↔ 272By similarity
    Disulfide bondi267 ↔ 285By similarity
    Disulfide bondi279 ↔ 294By similarity
    Disulfide bondi299 ↔ 311By similarity
    Disulfide bondi306 ↔ 324By similarity
    Disulfide bondi318 ↔ 333By similarity
    Disulfide bondi340 ↔ 351By similarity
    Disulfide bondi347 ↔ 360By similarity
    Disulfide bondi362 ↔ 374By similarity
    Disulfide bondi380 ↔ 390By similarity
    Disulfide bondi386 ↔ 399By similarity
    Disulfide bondi401 ↔ 414By similarity
    Glycosylationi441 – 4411N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi518 – 5181N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi538 – 5381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi772 – 7721N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi807 – 8071N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain By similarity.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.By similarity
    Tyrosine phosphorylated upon apoE binding.1 Publication
    Ubiquitinated by MYLIP leading to degradation.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ14114.
    PaxDbiQ14114.
    PRIDEiQ14114.

    PTM databases

    PhosphoSiteiQ14114.

    Miscellaneous databases

    PMAP-CutDBB1AMT8.

    Expressioni

    Tissue specificityi

    Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver.2 Publications

    Gene expression databases

    ArrayExpressiQ14114.
    BgeeiQ14114.
    CleanExiHS_LRP8.
    GenevestigatoriQ14114.

    Interactioni

    Subunit structurei

    Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 By similarity. Interacts with PCSK9.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    APOEP026492EBI-2681187,EBI-1222467

    Protein-protein interaction databases

    BioGridi113579. 18 interactions.
    DIPiDIP-48670N.
    IntActiQ14114. 2 interactions.
    STRINGi9606.ENSP00000303634.

    Structurei

    Secondary structure

    1
    963
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi51 – 533
    Beta strandi59 – 613
    Helixi62 – 643
    Beta strandi67 – 693
    Beta strandi72 – 754
    Turni76 – 783

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3A7QX-ray2.60B42-83[»]
    ProteinModelPortaliQ14114.
    SMRiQ14114. Positions 44-734.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ14114.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini42 – 826785ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini848 – 963116CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei827 – 84721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini46 – 8237LDL-receptor class A 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini85 – 12339LDL-receptor class A 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini126 – 16439LDL-receptor class A 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini166 – 20237LDL-receptor class A 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini205 – 24642LDL-receptor class A 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini258 – 29538LDL-receptor class A 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini298 – 33437LDL-receptor class A 7PROSITE-ProRule annotationAdd
    BLAST
    Domaini336 – 37540EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini376 – 41540EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Repeati462 – 50847LDL-receptor class B 1Add
    BLAST
    Repeati509 – 55143LDL-receptor class B 2Add
    BLAST
    Repeati552 – 59544LDL-receptor class B 3Add
    BLAST
    Repeati596 – 63944LDL-receptor class B 4Add
    BLAST
    Repeati640 – 68142LDL-receptor class B 5Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni740 – 79859Clustered O-linked oligosaccharidesAdd
    BLAST

    Domaini

    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.By similarity

    Sequence similaritiesi

    Belongs to the LDLR family.Curated
    Contains 2 EGF-like domains.PROSITE-ProRule annotation
    Contains 7 LDL-receptor class A domains.PROSITE-ProRule annotation
    Contains 5 LDL-receptor class B repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG255913.
    HOVERGENiHBG006250.
    InParanoidiQ14114.
    OMAiGCLQEST.
    OrthoDBiEOG7NGQ9P.
    PhylomeDBiQ14114.
    TreeFamiTF351700.

    Family and domain databases

    Gene3Di2.120.10.30. 1 hit.
    4.10.400.10. 7 hits.
    InterProiIPR011042. 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]
    PfamiPF07645. EGF_CA. 1 hit.
    PF00057. Ldl_recept_a. 7 hits.
    PF00058. Ldl_recept_b. 5 hits.
    [Graphical view]
    PRINTSiPR00261. LDLRECEPTOR.
    SMARTiSM00181. EGF. 2 hits.
    SM00179. EGF_CA. 1 hit.
    SM00192. LDLa. 7 hits.
    SM00135. LY. 5 hits.
    [Graphical view]
    SUPFAMiSSF57424. SSF57424. 7 hits.
    PROSITEiPS00010. 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]

    Sequences (5)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist. No differences were observed in the pattern splicing between control and Alzheimer brains.

    Isoform 1 (identifier: Q14114-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD    50
    QFQCRNERCI PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH 100
    ERWKCDGEEE CPDGSDESEA TCTKQVCPAE KLSCGPTSHK CVPASWRCDG 150
    EKDCEGGADE AGCATLCAPH EFQCGNRSCL AAVFVCDGDD DCGDGSDERG 200
    CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE AAELCGRPGP 250
    GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR 300
    GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI 350
    CTDLKIGFEC TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE 400
    CYPGYEMDLL TKNCKAAAGK SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK 450
    NVVALDVEVA TNRIYWCDLS YRKIYSAYMD KASDPKEQEV LIDEQLHSPE 500
    GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS EPRAIAVDPL 550
    RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW 600
    VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA 650
    IFSANRLNGL EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC 700
    EYLCLPAPQI SSHSPKYTCA CPDTMWLGPD MKRCYRAPQS TSTTTLASTM 750
    TRTVPATTRA PGTTVHRSTY QNHSTETPSL TAAVPSSVSV PRAPSISPST 800
    LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL CMSGYLIWRN 850
    WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP 900
    LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS 950
    KRVALSLEDD GLP 963
    Length:963
    Mass (Da):105,634
    Last modified:September 22, 2009 - v4
    Checksum:iB10DCF72F62DE71C
    GO
    Isoform 2 (identifier: Q14114-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:700
    Mass (Da):77,845
    Checksum:iB996C9CAEC69C1E9
    GO
    Isoform 3 (identifier: Q14114-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         893-951: Missing.

    Show »
    Length:904
    Mass (Da):99,092
    Checksum:i043E708314261E3C
    GO
    Isoform 4 (identifier: Q14114-4) [UniParc]FASTAAdd to Basket

    Also known as: ApoER2delta4-7

    The sequence of this isoform differs from the canonical sequence as follows:
         166-166: L → W
         167-336: Missing.

    Show »
    Length:793
    Mass (Da):87,959
    Checksum:i1A414B09D40BA1BC
    GO
    Isoform 5 (identifier: Q14114-5)

    Sequence is not available

    Note: Contains an insert in the extracellular part which carries a furin cleavage site.

    Length:
    Mass (Da):

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti262 – 2621A → V in BAA09328. (PubMed:8626535)Curated
    Sequence conflicti262 – 2621A → V in BAA21824. (PubMed:9079678)Curated
    Sequence conflicti405 – 4051Y → C in CAA99509. (PubMed:11152697)Curated
    Sequence conflicti418 – 4181A → G in BAA09328. (PubMed:8626535)Curated
    Sequence conflicti418 – 4181A → G in BAA21824. (PubMed:9079678)Curated
    Sequence conflicti418 – 4181A → G in BAA21825. (PubMed:9079678)Curated
    Sequence conflicti430 – 4301H → Y in BAA09328. (PubMed:8626535)Curated
    Sequence conflicti430 – 4301H → Y in BAA21824. (PubMed:9079678)Curated
    Sequence conflicti430 – 4301H → Y in BAA21825. (PubMed:9079678)Curated
    Sequence conflicti430 – 4301H → Y in CAA99509. (PubMed:11152697)Curated
    Sequence conflicti488 – 4881Q → R in CAA99509. (PubMed:11152697)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti25 – 251Q → R.4 Publications
    Corresponds to variant rs4926972 [ dbSNP | Ensembl ].
    VAR_046974
    Natural varianti46 – 461D → E.5 Publications
    Corresponds to variant rs3820198 [ dbSNP | Ensembl ].
    VAR_018468
    Natural varianti453 – 4531V → M.
    Corresponds to variant rs5180 [ dbSNP | Ensembl ].
    VAR_037624
    Natural varianti466 – 4661W → C.
    Corresponds to variant rs5181 [ dbSNP | Ensembl ].
    VAR_037625
    Natural varianti607 – 6071Q → R.
    Corresponds to variant rs5172 [ dbSNP | Ensembl ].
    VAR_037626
    Natural varianti611 – 6111I → L.
    Corresponds to variant rs5170 [ dbSNP | Ensembl ].
    VAR_037627
    Natural varianti653 – 6531S → T.
    Corresponds to variant rs5171 [ dbSNP | Ensembl ].
    VAR_037628
    Natural varianti736 – 7361R → Q.
    Corresponds to variant rs5172 [ dbSNP | Ensembl ].
    VAR_059079
    Natural varianti952 – 9521R → Q Associated with susceptibility to myocardial infarction type 1; increases activation of MAPK14 by oxidized low density lipoprotein. 2 Publications
    Corresponds to variant rs5174 [ dbSNP | Ensembl ].
    VAR_018469

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei166 – 295130LCAPH…EADCP → S in isoform 2. 1 PublicationVSP_010305Add
    BLAST
    Alternative sequencei166 – 1661L → W in isoform 4. CuratedVSP_038181
    Alternative sequencei167 – 336170Missing in isoform 4. CuratedVSP_010306Add
    BLAST
    Alternative sequencei737 – 81276APQST…HSQHY → D in isoform 2. 1 PublicationVSP_010307Add
    BLAST
    Alternative sequencei893 – 95159Missing in isoform 2 and isoform 3. 2 PublicationsVSP_010308Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS30720.1. [Q14114-3]
    CCDS578.1. [Q14114-1]
    CCDS579.1. [Q14114-2]
    CCDS580.1. [Q14114-4]
    RefSeqiNP_001018064.1. NM_001018054.2. [Q14114-3]
    NP_004622.2. NM_004631.4. [Q14114-1]
    NP_059992.3. NM_017522.4. [Q14114-2]
    NP_150643.2. NM_033300.3. [Q14114-4]
    UniGeneiHs.280387.

    Genome annotation databases

    EnsembliENST00000306052; ENSP00000303634; ENSG00000157193. [Q14114-1]
    ENST00000347547; ENSP00000334522; ENSG00000157193. [Q14114-4]
    ENST00000354412; ENSP00000346391; ENSG00000157193. [Q14114-2]
    ENST00000371454; ENSP00000360509; ENSG00000157193. [Q14114-3]
    GeneIDi7804.
    KEGGihsa:7804.
    UCSCiuc001cvi.2. human. [Q14114-1]
    uc001cvj.2. human. [Q14114-3]
    uc001cvk.2. human. [Q14114-4]
    uc001cvl.2. human. [Q14114-2]

    Polymorphism databases

    DMDMi259016389.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS30720.1. [Q14114-3 ]
    CCDS578.1. [Q14114-1 ]
    CCDS579.1. [Q14114-2 ]
    CCDS580.1. [Q14114-4 ]
    RefSeqi NP_001018064.1. NM_001018054.2. [Q14114-3 ]
    NP_004622.2. NM_004631.4. [Q14114-1 ]
    NP_059992.3. NM_017522.4. [Q14114-2 ]
    NP_150643.2. NM_033300.3. [Q14114-4 ]
    UniGenei Hs.280387.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3A7Q X-ray 2.60 B 42-83 [» ]
    ProteinModelPortali Q14114.
    SMRi Q14114. Positions 44-734.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113579. 18 interactions.
    DIPi DIP-48670N.
    IntActi Q14114. 2 interactions.
    STRINGi 9606.ENSP00000303634.

    PTM databases

    PhosphoSitei Q14114.

    Polymorphism databases

    DMDMi 259016389.

    Proteomic databases

    MaxQBi Q14114.
    PaxDbi Q14114.
    PRIDEi Q14114.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000306052 ; ENSP00000303634 ; ENSG00000157193 . [Q14114-1 ]
    ENST00000347547 ; ENSP00000334522 ; ENSG00000157193 . [Q14114-4 ]
    ENST00000354412 ; ENSP00000346391 ; ENSG00000157193 . [Q14114-2 ]
    ENST00000371454 ; ENSP00000360509 ; ENSG00000157193 . [Q14114-3 ]
    GeneIDi 7804.
    KEGGi hsa:7804.
    UCSCi uc001cvi.2. human. [Q14114-1 ]
    uc001cvj.2. human. [Q14114-3 ]
    uc001cvk.2. human. [Q14114-4 ]
    uc001cvl.2. human. [Q14114-2 ]

    Organism-specific databases

    CTDi 7804.
    GeneCardsi GC01M053711.
    HGNCi HGNC:6700. LRP8.
    MIMi 602600. gene.
    608446. phenotype.
    neXtProti NX_Q14114.
    PharmGKBi PA30457.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG255913.
    HOVERGENi HBG006250.
    InParanoidi Q14114.
    OMAi GCLQEST.
    OrthoDBi EOG7NGQ9P.
    PhylomeDBi Q14114.
    TreeFami TF351700.

    Enzyme and pathway databases

    Reactomei REACT_23879. Platelet sensitization by LDL.
    REACT_24968. Retinoid metabolism and transport.

    Miscellaneous databases

    EvolutionaryTracei Q14114.
    GeneWikii Low_density_lipoprotein_receptor-related_protein_8.
    GenomeRNAii 7804.
    NextBioi 30188.
    PMAP-CutDB B1AMT8.
    PROi Q14114.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14114.
    Bgeei Q14114.
    CleanExi HS_LRP8.
    Genevestigatori Q14114.

    Family and domain databases

    Gene3Di 2.120.10.30. 1 hit.
    4.10.400.10. 7 hits.
    InterProi IPR011042. 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 ]
    Pfami PF07645. EGF_CA. 1 hit.
    PF00057. Ldl_recept_a. 7 hits.
    PF00058. Ldl_recept_b. 5 hits.
    [Graphical view ]
    PRINTSi PR00261. LDLRECEPTOR.
    SMARTi SM00181. EGF. 2 hits.
    SM00179. EGF_CA. 1 hit.
    SM00192. LDLa. 7 hits.
    SM00135. LY. 5 hits.
    [Graphical view ]
    SUPFAMi SSF57424. SSF57424. 7 hits.
    PROSITEi PS00010. 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 ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. Cited for: VARIANT GLN-952, CHARACTERIZATION OF VARIANT GLN-952, ASSOCIATION WITH SUSCEPTIBILITY TO MYOCARDIAL INFARCTION TYPE 1.

    Entry informationi

    Entry nameiLRP8_HUMAN
    AccessioniPrimary (citable) accession number: Q14114
    Secondary accession number(s): B1AMT6
    , B1AMT7, B1AMT8, O14968, Q86V27, Q99876, Q9BR78
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: September 22, 2009
    Last modified: October 1, 2014
    This is version 143 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3