ID:LRP8_HUMAN DESCRIPTION: RecName: Full=Low-density lipoprotein receptor-related protein 8; Short=LRP-8; AltName: Full=Apolipoprotein E receptor 2; Flags: Precursor; 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. SUBUNIT: Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 (By similarity). Interacts with PCSK9. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein (By similarity). Secreted (By similarity). Note=Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a secreted receptor fragment (By similarity). TISSUE SPECIFICITY: Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver. 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). PTM: O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain (By similarity). PTM: 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). PTM: Tyrosine phosphorylated upon apoE binding. PTM: Ubiquitinated by MYLIP leading to degradation. DISEASE: Defects in LRP8 are a cause of myocardial infarction type 1 (MCI1) [MIM:608446]. A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia. MISCELLANEOUS: Natural isoforms of apoE (E2, E3, E4) have similar affinities for LRP8. SIMILARITY: Belongs to the LDLR family. SIMILARITY: Contains 2 EGF-like domains. SIMILARITY: Contains 7 LDL-receptor class A domains. SIMILARITY: Contains 5 LDL-receptor class B repeats. SEQUENCE CAUTION: Sequence=CAA99509.1; Type=Frameshift; Positions=430, 432, 438;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q14114
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HZ466382 - JP 2015532642-A/6: MicroRNAs that Suppress Human Melanoma. HZ466383 - JP 2015532642-A/7: MicroRNAs that Suppress Human Melanoma. HZ466384 - JP 2015532642-A/8: MicroRNAs that Suppress Human Melanoma. HZ466385 - JP 2015532642-A/9: MicroRNAs that Suppress Human Melanoma. LP722498 - Sequence 11 from Patent EP2882496. LP722500 - Sequence 13 from Patent EP2882496. LP722502 - Sequence 15 from Patent EP2882496. LP722504 - Sequence 17 from Patent EP2882496. D50678 - Homo sapiens mRNA for apolipoprotein E receptor 2, complete cds. BC051836 - Homo sapiens low density lipoprotein receptor-related protein 8, apolipoprotein e receptor, mRNA (cDNA clone MGC:60136 IMAGE:6143442), complete cds. AK096482 - Homo sapiens cDNA FLJ39163 fis, clone OCBBF2002615, highly similar to Low-density lipoprotein receptor-related protein 8 precursor. Z75190 - H.sapiens mRNA for apolipoprotein E receptor 2. MA622447 - JP 2018140982-A/6: MicroRNAs that Suppress Human Melanoma. MA622448 - JP 2018140982-A/7: MicroRNAs that Suppress Human Melanoma. MA622449 - JP 2018140982-A/8: MicroRNAs that Suppress Human Melanoma. MA622450 - JP 2018140982-A/9: MicroRNAs that Suppress Human Melanoma. MP557062 - Sequence 11 from Patent EP3626309. MP557064 - Sequence 13 from Patent EP3626309. MP557066 - Sequence 15 from Patent EP3626309. MP557068 - Sequence 17 from Patent EP3626309. BC006443 - Homo sapiens, Similar to low density lipoprotein receptor-related protein 8, apolipoprotein e receptor, clone IMAGE:3534195, mRNA, partial cds. JD339082 - Sequence 320106 from Patent EP1572962. JD314863 - Sequence 295887 from Patent EP1572962. JD491656 - Sequence 472680 from Patent EP1572962. JD369165 - Sequence 350189 from Patent EP1572962. JD365525 - Sequence 346549 from Patent EP1572962. JD197927 - Sequence 178951 from Patent EP1572962. JD232850 - Sequence 213874 from Patent EP1572962. JD323948 - Sequence 304972 from Patent EP1572962. JD503899 - Sequence 484923 from Patent EP1572962. JD093595 - Sequence 74619 from Patent EP1572962. AK122887 - Homo sapiens cDNA FLJ16536 fis, clone OCBBF2032152, highly similar to Homo sapiens low density lipoprotein receptor-related protein 8, apolipoprotein e receptor (LRP8). JD407051 - Sequence 388075 from Patent EP1572962. JD407050 - Sequence 388074 from Patent EP1572962. JD095135 - Sequence 76159 from Patent EP1572962. JD407402 - Sequence 388426 from Patent EP1572962. JD138731 - Sequence 119755 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_Lis1Pathway - Lissencephaly gene (LIS1) in neuronal migration and development h_reelinPathway - Reelin Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein Q14114 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
