Human Gene LRP1 (ENST00000338962.8) from GENCODE V44
Description: Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission. (from UniProt Q07954) RefSeq Summary (NM_002332): This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]. Gencode Transcript: ENST00000338962.8 Gencode Gene: ENSG00000123384.14 Transcript (Including UTRs) Position: hg38 chr12:57,128,716-57,150,059 Size: 21,344 Total Exon Count: 7 Strand: + Coding Region Position: hg38 chr12:57,128,965-57,149,018 Size: 20,054 Coding Exon Count: 7
ID:LRP1_HUMAN DESCRIPTION: RecName: Full=Prolow-density lipoprotein receptor-related protein 1; Short=LRP-1; AltName: Full=Alpha-2-macroglobulin receptor; Short=A2MR; AltName: Full=Apolipoprotein E receptor; Short=APOER; AltName: CD_antigen=CD91; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 85 kDa subunit; Short=LRP-85; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 515 kDa subunit; Short=LRP-515; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 intracellular domain; Short=LRPICD; Flags: Precursor; FUNCTION: Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission. FUNCTION: Functions as a receptor for Pseudomonas aeruginosa exotoxin A. SUBUNIT: Heterodimer of an 85-kDa membrane-bound carboxyl subunit and a non-covalently attached 515-kDa N-terminal subunit. Intracellular domain interacts with MAFB (By similarity). Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with SNX17, PID1/PCLI1, PDGF and CUBN. The intracellular domain interacts with SHC1, GULP1 and DAB1. Interacts with LRPAP1. Can weakly interact (via NPXY motif) with DAB2 (via PID domain); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with bacterial exotoxins. INTERACTION: Q63722:Jag1 (xeno); NbExp=4; IntAct=EBI-1046087, EBI-4567800; Q03350:Thbs2 (xeno); NbExp=2; IntAct=EBI-1046087, EBI-4567830; SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 85 kDa subunit: Cell membrane; Single-pass type I membrane protein. Membrane, coated pit. SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 515 kDa subunit: Cell membrane; Peripheral membrane protein; Extracellular side. Membrane, coated pit. SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 intracellular domain: Cytoplasm. Nucleus. Note=After cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm and in the nucleus. TISSUE SPECIFICITY: Most abundant in liver, brain and lung. PTM: Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non- covalently associated. Gamma-secretase-dependent cleavage of LRP- 85 releases the intracellular domain from the membrane. PTM: The N-terminus is blocked. PTM: Phosphorylated on serine and threonine residues. PTM: Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1. SIMILARITY: Belongs to the LDLR family. SIMILARITY: Contains 22 EGF-like domains. SIMILARITY: Contains 31 LDL-receptor class A domains. SIMILARITY: Contains 34 LDL-receptor class B repeats.
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 Q07954
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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.
Biological Process: GO:0001523 retinoid metabolic process GO:0002265 astrocyte activation involved in immune response GO:0006629 lipid metabolic process GO:0006897 endocytosis GO:0006898 receptor-mediated endocytosis GO:0006909 phagocytosis GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway GO:0007275 multicellular organism development GO:0007568 aging GO:0008283 cell proliferation GO:0010715 regulation of extracellular matrix disassembly GO:0010875 positive regulation of cholesterol efflux GO:0010942 positive regulation of cell death GO:0010977 negative regulation of neuron projection development GO:0014912 negative regulation of smooth muscle cell migration GO:0021987 cerebral cortex development GO:0030178 negative regulation of Wnt signaling pathway GO:0031623 receptor internalization GO:0032092 positive regulation of protein binding GO:0032370 positive regulation of lipid transport GO:0032374 regulation of cholesterol transport GO:0032429 regulation of phospholipase A2 activity GO:0032956 regulation of actin cytoskeleton organization GO:0035909 aorta morphogenesis GO:0042157 lipoprotein metabolic process GO:0042953 lipoprotein transport GO:0043277 apoptotic cell clearance GO:0043524 negative regulation of neuron apoptotic process GO:0045056 transcytosis GO:0045732 positive regulation of protein catabolic process GO:0045807 positive regulation of endocytosis GO:0051222 positive regulation of protein transport GO:0051246 regulation of protein metabolic process GO:0097242 beta-amyloid clearance GO:1900223 positive regulation of beta-amyloid clearance GO:1903078 positive regulation of protein localization to plasma membrane GO:1904646 cellular response to beta-amyloid GO:1905167 positive regulation of lysosomal protein catabolic process GO:2000587 negative regulation of platelet-derived growth factor receptor-beta signaling pathway
US Server
