======= LRP2 =======
== Gene Information ==
* **Official Symbol**: LRP2
* **Official Name**: LDL receptor related protein 2
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4036|4036]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P98164|P98164]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=LRP2&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20LRP2|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/600073|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009].
* **UniProt Summary**: Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (By similarity). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal uptake of metallothionein-bound heavy metals (PubMed:15126248). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (By similarity). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (By similarity). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (By similarity). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (By similarity). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (By similarity). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (By similarity). During optic nerve development, required for SHH- mediated migration and proliferation of oligodendrocyte precursor cells (By similarity). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (By similarity). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (By similarity). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (By similarity). Required for normal hearing, possibly through interaction with estrogen in the inner ear (By similarity). {ECO:0000250|UniProtKB:A2ARV4, ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158, ECO:0000269|PubMed:15126248, ECO:0000269|PubMed:23825075}.
|Ldl recept b|
|cEGF|
|Ldl recept a|
|positive regulation of lysosomal protein catabolic process|
|positive regulation of oligodendrocyte progenitor proliferation|
|folate import across plasma membrane|
|positive regulation of protein catabolic process in the vacuole|
|pulmonary artery morphogenesis|
|folate transmembrane transport|
|ventricular compact myocardium morphogenesis|
|regulation of oligodendrocyte progenitor proliferation|
|regulation of lysosomal protein catabolic process|
|coronary artery morphogenesis|
|folic acid transport|
|secondary heart field specification|
|heart field specification|
|vagina development|
|regulation of protein catabolic process in the vacuole|
|neuron projection arborization|
|heart formation|
|specification of animal organ identity|
|vitamin D metabolic process|
|vitamin transmembrane transport|
|coronary vasculature morphogenesis|
|female genitalia development|
|endosome lumen|
|modified amino acid transport|
|outflow tract septum morphogenesis|
|animal organ formation|
|fat-soluble vitamin metabolic process|
|vitamin transport|
|coronary vasculature development|
|cofactor transport|
|genitalia development|
|ventricular cardiac muscle tissue morphogenesis|
|negative regulation of BMP signaling pathway|
|aorta development|
|positive regulation of neural precursor cell proliferation|
|clathrin-coated vesicle membrane|
|brush border membrane|
|clathrin-coated pit|
|ventricular cardiac muscle tissue development|
|drug binding|
|endocytic vesicle|
|artery morphogenesis|
|cardiac muscle tissue morphogenesis|
|positive regulation of gliogenesis|
|drug transmembrane transport|
|ventricular septum development|
|outflow tract morphogenesis|
|cardiac septum morphogenesis|
|cardiac ventricle morphogenesis|
|dicarboxylic acid transport|
|muscle tissue morphogenesis|
|artery development|
|muscle organ morphogenesis|
|regulation of neural precursor cell proliferation|
|regulation of BMP signaling pathway|
|neural tube closure|
|tube closure|
|import across plasma membrane|
|primary neural tube formation|
|chaperone binding|
|retinoid metabolic process|
|neural tube formation|
|female sex differentiation|
|cardiac septum development|
|diterpenoid metabolic process|
|regulation of gliogenesis|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|terpenoid metabolic process|
|embryonic epithelial tube formation|
|vitamin metabolic process|
|cardiac chamber morphogenesis|
|cardiac ventricle development|
|carboxylic acid transmembrane transport|
|organic acid transmembrane transport|
|SH3 domain binding|
|epithelial tube formation|
|male gonad development|
|development of primary male sexual characteristics|
|isoprenoid metabolic process|
|positive regulation of cellular protein catabolic process|
|morphogenesis of embryonic epithelium|
|sensory perception of sound|
|negative regulation of cellular response to growth factor stimulus|
|tube formation|
|drug transport|
|male sex differentiation|
|neural tube development|
|cardiac muscle tissue development|
|sensory perception of mechanical stimulus|
|cardiac chamber development|
|receptor complex|
|gonad development|
|development of primary sexual characteristics|
|positive regulation of protein catabolic process|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|receptor-mediated endocytosis|
|regulation of cellular protein catabolic process|
|heart morphogenesis|
|lysosome|
|steroid metabolic process|
|sex differentiation|
|regulation of cellular response to growth factor stimulus|
|anion transmembrane transport|
|striated muscle tissue development|
|carboxylic acid transport|
|organic acid transport|
|muscle organ development|
|axon|
|muscle tissue development|
|lysosomal membrane|
|epithelial tube morphogenesis|
|apical plasma membrane|
|regionalization|
|positive regulation of cellular catabolic process|
|regulation of protein catabolic process|
|forebrain development|
|external side of plasma membrane|
|blood vessel morphogenesis|
|dendrite|
|reproductive structure development|
|reproductive system development|
|positive regulation of catabolic process|
|morphogenesis of an epithelium|
|pattern specification process|
|organic hydroxy compound metabolic process|
|organic anion transport|
|positive regulation of neurogenesis|
|muscle structure development|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|blood vessel development|
|cell projection morphogenesis|
|vasculature development|
|cell part morphogenesis|
|cardiovascular system development|
|heart development|
|positive regulation of nervous system development|
|positive regulation of cell development|
|cell population proliferation|
|endocytosis|
|tissue morphogenesis|
|embryonic morphogenesis|
|anion transport|
|chordate embryonic development|
|metal ion transport|
|embryo development ending in birth or egg hatching|
|tube morphogenesis|
|neuron projection development|
|developmental process involved in reproduction|
|import into cell|
|calcium ion binding|
|cell morphogenesis|
|brain development|
|head development|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|cation transport|
|regulation of cellular catabolic process|
|tube development|
|membrane organization|
|circulatory system development|
|anatomical structure formation involved in morphogenesis|
|positive regulation of cell population proliferation|
|regulation of nervous system development|
|regulation of cell development|
|ion transmembrane transport|
|cellular lipid metabolic process|
|animal organ morphogenesis|
|positive regulation of cell differentiation|
|sensory perception|
|embryo development|
|central nervous system development|
|Golgi apparatus|
|regulation of catabolic process|
|endoplasmic reticulum|
|neuron differentiation|
|response to drug|
|epithelium development|
|plasma membrane bounded cell projection organization|
|cell projection organization|
|lipid metabolic process|
|negative regulation of signal transduction|
|transmembrane transport|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|ion transport|
|nervous system process|
|reproductive process|
|reproduction|
|generation of neurons|
|amide transport|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|tissue development|
|regulation of cell differentiation|
|nitrogen compound transport|
|vesicle-mediated transport|
|system process|
\\
=== CRISPR Data ===
No hits were found.
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 17212
* **Expression level (log2 read counts)**: -0.31
{{:chemogenomics:nalm6 dist.png?nolink |}}