| IED ID | IndEnz0018001258 |
| Enzyme Type ID | peroxidase001258 |
| Protein Name |
Low-density lipoprotein receptor-related protein 8 LRP-8 Apolipoprotein E receptor 2 |
| Gene Name | LRP8 APOER2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGLPEPGPLRLLALLLLLLLLLLLQLQHLAAAAADPLLGGQGPAKDCEKDQFQCRNERCIPSVWRCDEDDDCLDHSDEDDCPKKTCADSDFTCDNGHCIHERWKCDGEEECPDGSDESEATCTKQVCPAEKLSCGPTSHKCVPASWRCDGEKDCEGGADEAGCATLCAPHEFQCGNRSCLAAVFVCDGDDDCGDGSDERGCADPACGPREFRCGGDGGGACIPERWVCDRQFDCEDRSDEAAELCGRPGPGATSAPAACATASQFACRSGECVHLGWRCDGDRDCKDKSDEADCPLGTCRGDEFQCGDGTCVLAIKHCNQEQDCPDGSDEAGCLQGLNECLHNNGGCSHICTDLKIGFECTCPAGFQLLDQKTCGDIDECKDPDACSQICVNYKGYFKCECYPGYEMDLLTKNCKAAAGKSPSLIFTNRHEVRRIDLVKRNYSRLIPMLKNVVALDVEVATNRIYWCDLSYRKIYSAYMDKASDPKEQEVLIDEQLHSPEGLAVDWVHKHIYWTDSGNKTISVATVDGGRRRTLFSRNLSEPRAIAVDPLRGFMYWSDWGDQAKIEKSGLNGVDRQTLVSDNIEWPNGITLDLLSQRLYWVDSKLHQLSSIDFSGGNRKTLISSTDFLSHPFGIAVFEDKVFWTDLENEAIFSANRLNGLEISILAENLNNPHDIVIFHELKQPRAPDACELSVQPNGGCEYLCLPAPQISSHSPKYTCACPDTMWLGPDMKRCYRAPQSTSTTTLASTMTRTVPATTRAPGTTVHRSTYQNHSTETPSLTAAVPSSVSVPRAPSISPSTLSPATSNHSQHYANEDSKMGSTVTAAVIGIIVPIVVIALLCMSGYLIWRNWKRKNTKSMNFDNPVYRKTTEEEDEDELHIGRTAQIGHVYPAAISSFDRPLWAEPCLGETREPEDPAPALKELFVLPGEPRSQLHQLPKNPLSELPVVKSKRVALSLEDDGLP |
| Enzyme Length | 963 |
| Uniprot Accession Number | Q14114 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands (PubMed:20223215). 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. Not required for endocytic uptake of SEPP1 in the kidney which is mediated by LRP2 (By similarity). Together with its ligand, apolipoprotein E (apoE), may indirectly play a role in the suppression of the innate immune response by controlling the survival of myeloid-derived suppressor cells (By similarity). {ECO:0000250|UniProtKB:Q924X6, ECO:0000269|PubMed:12807892, ECO:0000269|PubMed:12899622, ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:20223215, ECO:0000269|PubMed:30873003}.; FUNCTION: (Microbial infection) Acts as a receptor for Semliki Forest virus. {ECO:0000269|PubMed:34929721}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (5); Beta strand (46); Chain (1); Disulfide bond (27); Domain (9); Frameshift (1); Glycosylation (6); Helix (10); Metal binding (6); Natural variant (9); Region (2); Repeat (5); Sequence conflict (11); Signal peptide (1); Topological domain (2); Transmembrane (1); Turn (13) |
| Keywords | 3D-structure;Alternative splicing;Calcium;Cell membrane;Disulfide bond;EGF-like domain;Endocytosis;Glycoprotein;Host-virus interaction;Membrane;Metal-binding;Phosphoprotein;Receptor;Reference proteome;Repeat;Secreted;Signal;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | P25054; P02649; Q60841; Q06481-5; P02649; Q9UGL9; P48730-2; P35222; Q9UJY5-5; Q92993-2; Q99683; Q96P71-2; I6L9F6; P10599 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30873003}; Single-pass type I membrane protein {ECO:0000250}. Secreted {ECO:0000250}. Note=Isoforms that contain the exon coding for a furin-type cleavage site are proteolytically processed, leading to a secreted receptor fragment. {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain (By similarity). {ECO:0000250}.; 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). {ECO:0000250}.; PTM: Tyrosine phosphorylated upon apoE binding. {ECO:0000269|PubMed:12681505}.; PTM: Ubiquitinated by MYLIP leading to degradation. {ECO:0000269|PubMed:20427281}. |
| Signal Peptide | SIGNAL 1..32; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 3A7Q; 5B4X; 5B4Y; |
| Mapped Pubmed ID | 12621059; 12871934; 15459198; 15950758; 16034672; 16332682; 16481437; 16642433; 16951405; 17470198; 17614163; 18089558; 18489431; 18592168; 19116273; 19282863; 19439088; 19661487; 19720620; 19913121; 19948739; 20195357; 20331378; 20493228; 20628086; 21157031; 21316997; 21347244; 21601501; 22170052; 22404453; 22419519; 22589174; 22889673; 23524007; 23739027; 24076391; 24344333; 24844606; 24867879; 26496610; 26637325; 26638075; 26800564; 26817215; 26902204; 27853278; 28255385; 28446613; 29032149; 29442527; 30227220; 30552869; 30575334; 32312520; 33054597; 33079740; 33779882; 7683668; |
| Motif | |
| Gene Encoded By | |
| Mass | 105,634 |
| Kinetics | |
| Metal Binding | METAL 64; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q"; METAL 67; /note="Calcium"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q"; METAL 69; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q"; METAL 71; /note="Calcium"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q"; METAL 77; /note="Calcium"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q"; METAL 78; /note="Calcium"; /evidence="ECO:0000269|PubMed:20223215, ECO:0007744|PDB:3A7Q" |
| Rhea ID | |
| Cross Reference Brenda |