GenomeNet

Database: UniProt
Entry: Q14114
LinkDB: Q14114
Original site: Q14114 
ID   LRP8_HUMAN              Reviewed;         963 AA.
AC   Q14114; B1AMT6; B1AMT7; B1AMT8; O14968; Q86V27; Q99876; Q9BR78;
DT   10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   22-SEP-2009, sequence version 4.
DT   13-FEB-2019, entry version 185.
DE   RecName: Full=Low-density lipoprotein receptor-related protein 8;
DE            Short=LRP-8;
DE   AltName: Full=Apolipoprotein E receptor 2;
DE   Flags: Precursor;
GN   Name=LRP8; Synonyms=APOER2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-25 AND
RP   GLU-46.
RC   TISSUE=Placenta;
RX   PubMed=8626535; DOI=10.1074/jbc.271.14.8373;
RA   Kim D.-H., Iijima H., Goto K., Sakai J., Ishii H., Kim H.-J.,
RA   Suzuki H., Kondo H., Saeki S., Yamamoto T.;
RT   "Human apolipoprotein E receptor 2. A novel lipoprotein receptor of
RT   the low density lipoprotein receptor family predominantly expressed in
RT   brain.";
RL   J. Biol. Chem. 271:8373-8380(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 4), AND VARIANTS
RP   ARG-25 AND GLU-46.
RC   TISSUE=Peripheral blood;
RX   PubMed=9079678; DOI=10.1074/jbc.272.13.8498;
RA   Kim D.-H., Magoori K., Inoue T.R., Mao C.C., Kim H.-J., Suzuki H.,
RA   Fujita T., Endo Y., Saeki S., Yamamoto T.T.;
RT   "Exon/intron organization, chromosome localization, alternative
RT   splicing, and transcription units of the human apolipoprotein E
RT   receptor 2 gene.";
RL   J. Biol. Chem. 272:8498-8504(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ARG-25 AND
RP   GLU-46.
RC   TISSUE=Umbilical vein;
RX   PubMed=11152697; DOI=10.1074/jbc.M011795200;
RA   Korschineck I., Ziegler S., Breuss J., Lang I., Lorenz M., Kaun C.,
RA   Ambros P.F., Binder B.R.;
RT   "Identification of a novel exon in apolipoprotein E receptor 2 leading
RT   to alternatively spliced mRNAs found in cells of the vascular wall but
RT   not in neuronal tissue.";
RL   J. Biol. Chem. 276:13192-13197(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 720-963 (ISOFORM 1), AND VARIANTS
RP   ARG-25 AND GLU-46.
RC   TISSUE=Eye, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX   PubMed=10218790; DOI=10.1016/S0306-4522(98)00489-8;
RA   Clatworthy A.E., Stockinger W., Christie R.H., Schneider W.J.,
RA   Nimpf J., Hyman B.T., Rebeck G.W.;
RT   "Expression and alternate splicing of apolipoprotein E receptor 2 in
RT   brain.";
RL   Neuroscience 90:903-911(1999).
RN   [7]
RP   PHOSPHORYLATION AT TYROSINE RESIDUES.
RX   PubMed=12681505; DOI=10.1016/S0014-5793(03)00261-8;
RA   Sacre S.M., Stannard A.K., Owen J.S.;
RT   "Apolipoprotein E (apoE) isoforms differentially induce nitric oxide
RT   production in endothelial cells.";
RL   FEBS Lett. 540:181-187(2003).
RN   [8]
RP   CHARACTERIZATION, AND TISSUE SPECIFICITY.
RX   PubMed=10508213;
RA   Riddell D.R., Vinogradov D.V., Stannard A.K., Chadwick N., Owen J.S.;
RT   "Identification and characterization of LRP8 (apoER2) in human blood
RT   platelets.";
RL   J. Lipid Res. 40:1925-1930(1999).
RN   [9]
RP   FUNCTION AS A RECEPTOR FOR REELIN.
RX   PubMed=12899622; DOI=10.1021/bi034475p;
RA   Andersen O.M., Benhayon D., Curran T., Willnow T.E.;
RT   "Differential binding of ligands to the apolipoprotein E receptor 2.";
RL   Biochemistry 42:9355-9364(2003).
RN   [10]
RP   FUNCTION AS A RECEPTOR FOR APOE.
RX   PubMed=12950167; DOI=10.1021/bi027093c;
RA   Li X., Kypreos K., Zanni E.E., Zannis V.;
RT   "Domains of apoE required for binding to apoE receptor 2 and to
RT   phospholipids: implications for the functions of apoE in the brain.";
RL   Biochemistry 42:10406-10417(2003).
RN   [11]
RP   FUNCTION AS A RECEPTOR FOR BETA 2-GLYCOPROTEIN I.
RX   PubMed=12807892; DOI=10.1074/jbc.M212655200;
RA   Lutters B.C., Derksen R.H., Tekelenburg W.L., Lenting P.J., Arnout J.,
RA   de Groot P.G.;
RT   "Dimers of beta 2-glycoprotein I increase platelet deposition to
RT   collagen via interaction with phospholipids and the apolipoprotein E
RT   receptor 2'.";
RL   J. Biol. Chem. 278:33831-33838(2003).
RN   [12]
RP   INTERACTION WITH PCSK9.
RX   PubMed=18039658; DOI=10.1074/jbc.M708098200;
RA   Poirier S., Mayer G., Benjannet S., Bergeron E., Marcinkiewicz J.,
RA   Nassoury N., Mayer H., Nimpf J., Prat A., Seidah N.G.;
RT   "The proprotein convertase PCSK9 induces the degradation of low
RT   density lipoprotein receptor (LDLR) and its closest family members
RT   VLDLR and ApoER2.";
RL   J. Biol. Chem. 283:2363-2372(2008).
RN   [13]
RP   UBIQUITINATION.
RX   PubMed=20427281; DOI=10.1074/jbc.M110.123729;
RA   Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V.,
RA   Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D.,
RA   Nimpf J., van Berkel T.J., Tontonoz P., Zelcer N.;
RT   "The E3 ubiquitin ligase IDOL induces the degradation of the low
RT   density lipoprotein receptor family members VLDLR and ApoER2.";
RL   J. Biol. Chem. 285:19720-19726(2010).
RN   [14]
RP   VARIANTS GLU-46 AND GLN-952.
RX   PubMed=12399018; DOI=10.1016/S0304-3940(02)00942-4;
RA   Ma S.L., Ng H.K., Baum L., Pang J.C., Chiu H.F., Woo J., Tang N.L.,
RA   Lam L.C.;
RT   "Low-density lipoprotein receptor-related protein 8 (apolipoprotein E
RT   receptor 2) gene polymorphisms in Alzheimer's disease.";
RL   Neurosci. Lett. 332:216-218(2002).
RN   [15]
RP   VARIANT GLN-952, CHARACTERIZATION OF VARIANT GLN-952, AND ASSOCIATION
RP   WITH SUSCEPTIBILITY TO MYOCARDIAL INFARCTION TYPE 1.
RX   PubMed=17847002; DOI=10.1086/521581;
RA   Shen G.-Q., Li L., Girelli D., Seidelmann S.B., Rao S., Fan C.,
RA   Park J.E., Xi Q., Li J., Hu Y., Olivieri O., Marchant K., Barnard J.,
RA   Corrocher R., Elston R., Cassano J., Henderson S., Hazen S.L.,
RA   Plow E.F., Topol E.J., Wang Q.K.;
RT   "An LRP8 variant is associated with familial and premature coronary
RT   artery disease and myocardial infarction.";
RL   Am. J. Hum. Genet. 81:780-791(2007).
CC   -!- FUNCTION: Cell surface receptor for Reelin (RELN) and
CC       apolipoprotein E (apoE)-containing ligands. LRP8 participates in
CC       transmitting the extracellular Reelin signal to intracellular
CC       signaling processes, by binding to DAB1 on its cytoplasmic tail.
CC       Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to
CC       regulate DAB1 tyrosine phosphorylation and microtubule function in
CC       neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is
CC       thus a key component of the Reelin pathway which governs neuronal
CC       layering of the forebrain during embryonic brain development.
CC       Binds the endoplasmic reticulum resident receptor-associated
CC       protein (RAP). Binds dimers of beta 2-glycoprotein I and may be
CC       involved in the suppression of platelet aggregation in the
CC       vasculature. Highly expressed in the initial segment of the
CC       epididymis, where it affects the functional expression of
CC       clusterin and phospholipid hydroperoxide glutathione peroxidase
CC       (PHGPx), two proteins required for sperm maturation. May also
CC       function as an endocytic receptor. Not required for endocytic
CC       uptake of SEPP1 in the kidney which is mediated by LRP2 (By
CC       similarity). Together with its ligand, apolipoprotein E (apoE),
CC       may indirectly play a role in the suppression of the innate immune
CC       response by controlling the survival of myeloid-derived suppressor
CC       cells (By similarity). {ECO:0000250|UniProtKB:Q924X6,
CC       ECO:0000269|PubMed:12807892, ECO:0000269|PubMed:12899622,
CC       ECO:0000269|PubMed:12950167}.
CC   -!- SUBUNIT: Reelin associates with two or more receptor molecules.
CC       Interacts with DAB1 and JNK-interacting proteins. Interacts with
CC       SNX17 (By similarity). Interacts with PCSK9. {ECO:0000250,
CC       ECO:0000269|PubMed:18039658}.
CC   -!- INTERACTION:
CC       P25054:APC; NbExp=2; IntAct=EBI-2681187, EBI-727707;
CC       P02649:APOE; NbExp=2; IntAct=EBI-2681187, EBI-1222467;
CC       P35968:KDR; NbExp=2; IntAct=EBI-2681187, EBI-1005487;
CC       Q60841:Reln (xeno); NbExp=10; IntAct=EBI-2681187, EBI-9248666;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
CC       type I membrane protein {ECO:0000250}. Secreted {ECO:0000250}.
CC       Note=Isoforms that contain the exon coding for a furin-type
CC       cleavage site are proteolytically processed, leading to a secreted
CC       receptor fragment. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC         Comment=Additional isoforms seem to exist. No differences were
CC         observed in the pattern splicing between control and Alzheimer
CC         brains.;
CC       Name=1; Synonyms=ApoER2 922;
CC         IsoId=Q14114-1; Sequence=Displayed;
CC       Name=2; Synonyms=ApoER2 906;
CC         IsoId=Q14114-2; Sequence=VSP_010305, VSP_010307, VSP_010308;
CC       Name=3;
CC         IsoId=Q14114-3; Sequence=VSP_010308;
CC       Name=4; Synonyms=ApoER2delta4-7;
CC         IsoId=Q14114-4; Sequence=VSP_038181, VSP_010306;
CC       Name=5;
CC         IsoId=Q14114-5; Sequence=Not described;
CC         Note=Contains an insert in the extracellular part which carries
CC         a furin cleavage site.;
CC   -!- TISSUE SPECIFICITY: Expressed mainly in brain and placenta. Also
CC       expressed in platelets and megakaryocytic cells. Not expressed in
CC       the liver. {ECO:0000269|PubMed:10218790,
CC       ECO:0000269|PubMed:10508213}.
CC   -!- DOMAIN: The cytoplasmic domain is involved in the binding of DAB1
CC       and in the recruitment of JNK-interacting proteins. Isoforms,
CC       which lack part of the cytoplasmic domain, are unable to recruit
CC       members of the family of JNK interacting proteins (JIP) to the
CC       cytoplasmic tail (By similarity). {ECO:0000250}.
CC   -!- PTM: O-glycosylated. Some alternatively spliced isoforms lack the
CC       O-linked sugar domain (By similarity). {ECO:0000250}.
CC   -!- PTM: Undergoes sequential, furin and gamma-secretase dependent,
CC       proteolytic processing, resulting in the extracellular release of
CC       the entire ligand-binding domain as a soluble polypeptide and in
CC       the intracellular domain (ICD) release into the cytoplasm. The
CC       gamma-secretase-dependent proteolytical processing occurs after
CC       the bulk of the extracellular domain has been shed, in a furin-
CC       dependent manner, in alternatively spliced isoforms carrying the
CC       furin cleavage site. Hypoglycosylation (mainly hypo-O-
CC       glycosylation) leads to increased extracellular cleavage, which in
CC       turn results in accelerating release of the intracellular domain
CC       (ICD) by the gamma-secretase. The resulting receptor fragment is
CC       able to inhibit Reelin signaling and in particular the Reelin-
CC       induced DAB1 phosphorylation (By similarity). {ECO:0000250}.
CC   -!- PTM: Tyrosine phosphorylated upon apoE binding.
CC       {ECO:0000269|PubMed:12681505}.
CC   -!- PTM: Ubiquitinated by MYLIP leading to degradation.
CC       {ECO:0000269|PubMed:20427281}.
CC   -!- DISEASE: Myocardial infarction 1 (MCI1) [MIM:608446]: A condition
CC       defined by the irreversible necrosis of heart muscle secondary to
CC       prolonged ischemia. {ECO:0000269|PubMed:17847002}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- MISCELLANEOUS: Natural isoforms of apoE (E2, E3, E4) have similar
CC       affinities for LRP8.
CC   -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA99509.1; Type=Frameshift; Positions=430, 432, 438; Evidence={ECO:0000305};
DR   EMBL; D50678; BAA09328.1; -; mRNA.
DR   EMBL; D86407; BAA21824.1; -; Genomic_DNA.
DR   EMBL; D86407; BAA21825.1; -; Genomic_DNA.
DR   EMBL; Z75190; CAA99509.1; ALT_FRAME; mRNA.
DR   EMBL; AL355483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL606760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC006443; AAH06443.1; -; mRNA.
DR   EMBL; BC051836; AAH51836.2; -; mRNA.
DR   CCDS; CCDS30720.1; -. [Q14114-3]
DR   CCDS; CCDS578.1; -. [Q14114-1]
DR   CCDS; CCDS579.1; -. [Q14114-2]
DR   CCDS; CCDS580.1; -. [Q14114-4]
DR   RefSeq; NP_001018064.1; NM_001018054.2. [Q14114-3]
DR   RefSeq; NP_004622.2; NM_004631.4. [Q14114-1]
DR   RefSeq; NP_059992.3; NM_017522.4. [Q14114-2]
DR   RefSeq; NP_150643.2; NM_033300.3. [Q14114-4]
DR   UniGene; Hs.280387; -.
DR   PDB; 3A7Q; X-ray; 2.60 A; B=42-83.
DR   PDB; 5B4X; X-ray; 3.20 A; B/D=42-736.
DR   PDB; 5B4Y; X-ray; 1.90 A; B=42-124.
DR   PDBsum; 3A7Q; -.
DR   PDBsum; 5B4X; -.
DR   PDBsum; 5B4Y; -.
DR   ProteinModelPortal; Q14114; -.
DR   SMR; Q14114; -.
DR   BioGrid; 113579; 38.
DR   DIP; DIP-48670N; -.
DR   ELM; Q14114; -.
DR   IntAct; Q14114; 24.
DR   STRING; 9606.ENSP00000303634; -.
DR   iPTMnet; Q14114; -.
DR   PhosphoSitePlus; Q14114; -.
DR   SwissPalm; Q14114; -.
DR   BioMuta; LRP8; -.
DR   DMDM; 259016389; -.
DR   EPD; Q14114; -.
DR   jPOST; Q14114; -.
DR   PaxDb; Q14114; -.
DR   PeptideAtlas; Q14114; -.
DR   PRIDE; Q14114; -.
DR   ProteomicsDB; 59819; -.
DR   ProteomicsDB; 59820; -. [Q14114-2]
DR   ProteomicsDB; 59821; -. [Q14114-3]
DR   ProteomicsDB; 59822; -. [Q14114-4]
DR   Ensembl; ENST00000306052; ENSP00000303634; ENSG00000157193. [Q14114-1]
DR   Ensembl; ENST00000347547; ENSP00000334522; ENSG00000157193. [Q14114-4]
DR   Ensembl; ENST00000354412; ENSP00000346391; ENSG00000157193. [Q14114-2]
DR   Ensembl; ENST00000371454; ENSP00000360509; ENSG00000157193. [Q14114-3]
DR   GeneID; 7804; -.
DR   KEGG; hsa:7804; -.
DR   UCSC; uc001cvi.4; human. [Q14114-1]
DR   CTD; 7804; -.
DR   DisGeNET; 7804; -.
DR   EuPathDB; HostDB:ENSG00000157193.14; -.
DR   GeneCards; LRP8; -.
DR   HGNC; HGNC:6700; LRP8.
DR   HPA; HPA073031; -.
DR   MalaCards; LRP8; -.
DR   MIM; 602600; gene.
DR   MIM; 608446; phenotype.
DR   neXtProt; NX_Q14114; -.
DR   OpenTargets; ENSG00000157193; -.
DR   PharmGKB; PA30457; -.
DR   eggNOG; ENOG410IPT5; Eukaryota.
DR   eggNOG; ENOG410YQ6J; LUCA.
DR   GeneTree; ENSGT00940000154819; -.
DR   HOVERGEN; HBG006250; -.
DR   InParanoid; Q14114; -.
DR   KO; K20052; -.
DR   OMA; GEKDCES; -.
DR   OrthoDB; 359795at2759; -.
DR   PhylomeDB; Q14114; -.
DR   TreeFam; TF351700; -.
DR   Reactome; R-HSA-432142; Platelet sensitization by LDL.
DR   Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR   SIGNOR; Q14114; -.
DR   ChiTaRS; LRP8; human.
DR   EvolutionaryTrace; Q14114; -.
DR   GeneWiki; Low_density_lipoprotein_receptor-related_protein_8; -.
DR   GenomeRNAi; 7804; -.
DR   PRO; PR:Q14114; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000157193; Expressed in 200 organ(s), highest expression level in pigmented layer of retina.
DR   ExpressionAtlas; Q14114; baseline and differential.
DR   Genevisible; Q14114; HS.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IC:UniProtKB.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005875; C:microtubule associated complex; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR   GO; GO:0043235; C:receptor complex; IDA:MGI.
DR   GO; GO:0034185; F:apolipoprotein binding; IC:BHF-UCL.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0008035; F:high-density lipoprotein particle binding; IEA:Ensembl.
DR   GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR   GO; GO:0005041; F:low-density lipoprotein particle receptor activity; TAS:ARUK-UCL.
DR   GO; GO:0038025; F:reelin receptor activity; ISS:BHF-UCL.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; IDA:BHF-UCL.
DR   GO; GO:0021541; P:ammon gyrus development; ISS:BHF-UCL.
DR   GO; GO:0071397; P:cellular response to cholesterol; IEA:Ensembl.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; IDA:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR   GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:BHF-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR   GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:BHF-UCL.
DR   GO; GO:1900006; P:positive regulation of dendrite development; ISS:BHF-UCL.
DR   GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR   GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:BHF-UCL.
DR   GO; GO:0006508; P:proteolysis; NAS:UniProtKB.
DR   GO; GO:0038026; P:reelin-mediated signaling pathway; ISS:BHF-UCL.
DR   GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR   GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd00112; LDLa; 6.
DR   Gene3D; 2.120.10.30; -; 1.
DR   InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR   InterPro; IPR018097; EGF_Ca-bd_CS.
DR   InterPro; IPR036055; LDL_receptor-like_sf.
DR   InterPro; IPR023415; LDLR_class-A_CS.
DR   InterPro; IPR000033; LDLR_classB_rpt.
DR   InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR   Pfam; PF00057; Ldl_recept_a; 7.
DR   Pfam; PF00058; Ldl_recept_b; 5.
DR   PRINTS; PR00261; LDLRECEPTOR.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00179; EGF_CA; 2.
DR   SMART; SM00192; LDLa; 7.
DR   SMART; SM00135; LY; 5.
DR   SUPFAM; SSF57424; SSF57424; 7.
DR   PROSITE; PS00010; ASX_HYDROXYL; 2.
DR   PROSITE; PS01186; EGF_2; 2.
DR   PROSITE; PS50026; EGF_3; 2.
DR   PROSITE; PS01187; EGF_CA; 1.
DR   PROSITE; PS01209; LDLRA_1; 7.
DR   PROSITE; PS50068; LDLRA_2; 7.
DR   PROSITE; PS51120; LDLRB; 5.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Cell membrane;
KW   Complete proteome; Disulfide bond; EGF-like domain; Endocytosis;
KW   Glycoprotein; Membrane; Phosphoprotein; Polymorphism; Receptor;
KW   Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   SIGNAL        1     32       {ECO:0000255}.
FT   CHAIN        33    963       Low-density lipoprotein receptor-related
FT                                protein 8.
FT                                /FTId=PRO_0000017332.
FT   TOPO_DOM     42    826       Extracellular. {ECO:0000255}.
FT   TRANSMEM    827    847       Helical. {ECO:0000255}.
FT   TOPO_DOM    848    963       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       46     82       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN       85    123       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      126    164       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      166    202       LDL-receptor class A 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      205    246       LDL-receptor class A 5.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      258    295       LDL-receptor class A 6.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      298    334       LDL-receptor class A 7.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      336    375       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      376    415       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REPEAT      462    508       LDL-receptor class B 1.
FT   REPEAT      509    551       LDL-receptor class B 2.
FT   REPEAT      552    595       LDL-receptor class B 3.
FT   REPEAT      596    639       LDL-receptor class B 4.
FT   REPEAT      640    681       LDL-receptor class B 5.
FT   REGION      740    798       Clustered O-linked oligosaccharides.
FT   CARBOHYD    176    176       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    441    441       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    518    518       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    538    538       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    772    772       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    807    807       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     47     59       {ECO:0000250}.
FT   DISULFID     54     72       {ECO:0000250}.
FT   DISULFID     66     81       {ECO:0000250}.
FT   DISULFID     86     98       {ECO:0000250}.
FT   DISULFID     93    111       {ECO:0000250}.
FT   DISULFID    105    122       {ECO:0000250}.
FT   DISULFID    127    141       {ECO:0000250}.
FT   DISULFID    134    154       {ECO:0000250}.
FT   DISULFID    148    163       {ECO:0000250}.
FT   DISULFID    167    179       {ECO:0000250}.
FT   DISULFID    174    192       {ECO:0000250}.
FT   DISULFID    186    201       {ECO:0000250}.
FT   DISULFID    206    221       {ECO:0000250}.
FT   DISULFID    213    234       {ECO:0000250}.
FT   DISULFID    228    245       {ECO:0000250}.
FT   DISULFID    259    272       {ECO:0000250}.
FT   DISULFID    267    285       {ECO:0000250}.
FT   DISULFID    279    294       {ECO:0000250}.
FT   DISULFID    299    311       {ECO:0000250}.
FT   DISULFID    306    324       {ECO:0000250}.
FT   DISULFID    318    333       {ECO:0000250}.
FT   DISULFID    340    351       {ECO:0000250}.
FT   DISULFID    347    360       {ECO:0000250}.
FT   DISULFID    362    374       {ECO:0000250}.
FT   DISULFID    380    390       {ECO:0000250}.
FT   DISULFID    386    399       {ECO:0000250}.
FT   DISULFID    401    414       {ECO:0000250}.
FT   VAR_SEQ     166    295       LCAPHEFQCGNRSCLAAVFVCDGDDDCGDGSDERGCADPAC
FT                                GPREFRCGGDGGGACIPERWVCDRQFDCEDRSDEAAELCGR
FT                                PGPGATSAPAACATASQFACRSGECVHLGWRCDGDRDCKDK
FT                                SDEADCP -> S (in isoform 2).
FT                                {ECO:0000303|PubMed:11152697}.
FT                                /FTId=VSP_010305.
FT   VAR_SEQ     166    166       L -> W (in isoform 4). {ECO:0000305}.
FT                                /FTId=VSP_038181.
FT   VAR_SEQ     167    336       Missing (in isoform 4). {ECO:0000305}.
FT                                /FTId=VSP_010306.
FT   VAR_SEQ     737    812       APQSTSTTTLASTMTRTVPATTRAPGTTVHRSTYQNHSTET
FT                                PSLTAAVPSSVSVPRAPSISPSTLSPATSNHSQHY -> D
FT                                (in isoform 2).
FT                                {ECO:0000303|PubMed:11152697}.
FT                                /FTId=VSP_010307.
FT   VAR_SEQ     893    951       Missing (in isoform 2 and isoform 3).
FT                                {ECO:0000303|PubMed:11152697,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_010308.
FT   VARIANT      25     25       Q -> R (in dbSNP:rs4926972).
FT                                {ECO:0000269|PubMed:11152697,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:8626535,
FT                                ECO:0000269|PubMed:9079678}.
FT                                /FTId=VAR_046974.
FT   VARIANT      46     46       D -> E (in dbSNP:rs3820198).
FT                                {ECO:0000269|PubMed:11152697,
FT                                ECO:0000269|PubMed:12399018,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:8626535,
FT                                ECO:0000269|PubMed:9079678}.
FT                                /FTId=VAR_018468.
FT   VARIANT     453    453       V -> M (in dbSNP:rs5180).
FT                                /FTId=VAR_037624.
FT   VARIANT     466    466       W -> C (in dbSNP:rs5181).
FT                                /FTId=VAR_037625.
FT   VARIANT     607    607       Q -> R (in dbSNP:rs5172).
FT                                /FTId=VAR_037626.
FT   VARIANT     611    611       I -> L (in dbSNP:rs5170).
FT                                /FTId=VAR_037627.
FT   VARIANT     653    653       S -> T (in dbSNP:rs5171).
FT                                /FTId=VAR_037628.
FT   VARIANT     736    736       R -> Q (in dbSNP:rs5172).
FT                                /FTId=VAR_059079.
FT   VARIANT     952    952       R -> Q (associated with susceptibility to
FT                                myocardial infarction type 1; increases
FT                                activation of MAPK14 by oxidized low
FT                                density lipoprotein; dbSNP:rs5174).
FT                                {ECO:0000269|PubMed:12399018,
FT                                ECO:0000269|PubMed:17847002}.
FT                                /FTId=VAR_018469.
FT   CONFLICT    262    262       A -> V (in Ref. 1; BAA09328 and 2;
FT                                BAA21824). {ECO:0000305}.
FT   CONFLICT    405    405       Y -> C (in Ref. 3; CAA99509).
FT                                {ECO:0000305}.
FT   CONFLICT    418    418       A -> G (in Ref. 1; BAA09328 and 2;
FT                                BAA21824/BAA21825). {ECO:0000305}.
FT   CONFLICT    430    430       H -> Y (in Ref. 1; BAA09328, 2; BAA21824/
FT                                BAA21825 and 3; CAA99509). {ECO:0000305}.
FT   CONFLICT    488    488       Q -> R (in Ref. 3; CAA99509).
FT                                {ECO:0000305}.
FT   STRAND       51     53       {ECO:0000244|PDB:5B4Y}.
FT   STRAND       59     61       {ECO:0000244|PDB:5B4Y}.
FT   HELIX        62     64       {ECO:0000244|PDB:5B4Y}.
FT   STRAND       67     69       {ECO:0000244|PDB:5B4Y}.
FT   STRAND       72     75       {ECO:0000244|PDB:5B4Y}.
FT   HELIX        76     78       {ECO:0000244|PDB:5B4Y}.
FT   STRAND       88     92       {ECO:0000244|PDB:5B4Y}.
FT   STRAND       98    100       {ECO:0000244|PDB:5B4Y}.
FT   HELIX       101    103       {ECO:0000244|PDB:5B4Y}.
FT   STRAND      106    108       {ECO:0000244|PDB:5B4Y}.
FT   HELIX       115    117       {ECO:0000244|PDB:5B4X}.
FT   TURN        119    121       {ECO:0000244|PDB:5B4Y}.
FT   TURN        339    341       {ECO:0000244|PDB:5B4X}.
FT   HELIX       342    344       {ECO:0000244|PDB:5B4X}.
FT   STRAND      348    352       {ECO:0000244|PDB:5B4X}.
FT   STRAND      355    357       {ECO:0000244|PDB:5B4X}.
FT   STRAND      359    361       {ECO:0000244|PDB:5B4X}.
FT   STRAND      368    372       {ECO:0000244|PDB:5B4X}.
FT   HELIX       379    381       {ECO:0000244|PDB:5B4X}.
FT   STRAND      385    393       {ECO:0000244|PDB:5B4X}.
FT   STRAND      396    400       {ECO:0000244|PDB:5B4X}.
FT   STRAND      405    407       {ECO:0000244|PDB:5B4X}.
FT   STRAND      409    412       {ECO:0000244|PDB:5B4X}.
FT   STRAND      414    416       {ECO:0000244|PDB:5B4X}.
FT   STRAND      418    420       {ECO:0000244|PDB:5B4X}.
FT   STRAND      423    427       {ECO:0000244|PDB:5B4X}.
FT   STRAND      429    439       {ECO:0000244|PDB:5B4X}.
FT   STRAND      442    458       {ECO:0000244|PDB:5B4X}.
FT   TURN        459    462       {ECO:0000244|PDB:5B4X}.
FT   STRAND      463    468       {ECO:0000244|PDB:5B4X}.
FT   TURN        469    472       {ECO:0000244|PDB:5B4X}.
FT   STRAND      473    478       {ECO:0000244|PDB:5B4X}.
FT   HELIX       479    481       {ECO:0000244|PDB:5B4X}.
FT   HELIX       485    487       {ECO:0000244|PDB:5B4X}.
FT   STRAND      489    492       {ECO:0000244|PDB:5B4X}.
FT   STRAND      501    505       {ECO:0000244|PDB:5B4X}.
FT   TURN        506    509       {ECO:0000244|PDB:5B4X}.
FT   STRAND      510    515       {ECO:0000244|PDB:5B4X}.
FT   TURN        516    519       {ECO:0000244|PDB:5B4X}.
FT   STRAND      520    525       {ECO:0000244|PDB:5B4X}.
FT   STRAND      530    535       {ECO:0000244|PDB:5B4X}.
FT   STRAND      540    548       {ECO:0000244|PDB:5B4X}.
FT   TURN        549    552       {ECO:0000244|PDB:5B4X}.
FT   STRAND      553    558       {ECO:0000244|PDB:5B4X}.
FT   STRAND      560    562       {ECO:0000244|PDB:5B4X}.
FT   STRAND      564    569       {ECO:0000244|PDB:5B4X}.
FT   STRAND      576    579       {ECO:0000244|PDB:5B4X}.
FT   STRAND      586    592       {ECO:0000244|PDB:5B4X}.
FT   TURN        593    596       {ECO:0000244|PDB:5B4X}.
FT   STRAND      597    602       {ECO:0000244|PDB:5B4X}.
FT   TURN        603    606       {ECO:0000244|PDB:5B4X}.
FT   STRAND      607    612       {ECO:0000244|PDB:5B4X}.
FT   STRAND      619    622       {ECO:0000244|PDB:5B4X}.
FT   TURN        625    627       {ECO:0000244|PDB:5B4X}.
FT   STRAND      629    637       {ECO:0000244|PDB:5B4X}.
FT   STRAND      640    645       {ECO:0000244|PDB:5B4X}.
FT   TURN        646    649       {ECO:0000244|PDB:5B4X}.
FT   STRAND      650    655       {ECO:0000244|PDB:5B4X}.
FT   TURN        656    658       {ECO:0000244|PDB:5B4X}.
FT   STRAND      663    666       {ECO:0000244|PDB:5B4X}.
FT   STRAND      675    678       {ECO:0000244|PDB:5B4X}.
FT   HELIX       680    682       {ECO:0000244|PDB:5B4X}.
FT   TURN        689    691       {ECO:0000244|PDB:5B4X}.
FT   STRAND      692    695       {ECO:0000244|PDB:5B4X}.
FT   HELIX       696    699       {ECO:0000244|PDB:5B4X}.
FT   STRAND      701    706       {ECO:0000244|PDB:5B4X}.
FT   STRAND      710    714       {ECO:0000244|PDB:5B4X}.
FT   STRAND      716    720       {ECO:0000244|PDB:5B4X}.
FT   STRAND      731    735       {ECO:0000244|PDB:5B4X}.
SQ   SEQUENCE   963 AA;  105634 MW;  B10DCF72F62DE71C CRC64;
     MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI
     PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA
     TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL
     AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE
     AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR
     GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC
     TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK
     SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD
     KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS
     EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW
     VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL
     EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA
     CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL
     TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL
     CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP
     LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS KRVALSLEDD
     GLP
//
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