ID:LRP2_HUMAN DESCRIPTION: RecName: Full=Low-density lipoprotein receptor-related protein 2; Short=LRP-2; AltName: Full=Glycoprotein 330; Short=gp330; AltName: Full=Megalin; Flags: Precursor; FUNCTION: Acts together with cubilin to mediate HDL endocytosis (By similarity). May participate in regulation of parathyroid- hormone and para-thyroid-hormone-related protein release. SUBUNIT: Binds plasminogen, extracellular matrix components, plasminogen activator-plasminogen activator inhibitor type I complex, apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin, CLU/clusterin and calcium. Forms a multimeric complex together with a receptor-associated protein (RAP). Binds to ankyrin-repeat family A protein 2 (ANKRA2). Interacts with LRP2BP. Interacts (via NPXY motif) with DAB2; the interaction is not affected by tyrosine phosphorylation of the NPXY motif. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. Membrane, coated pit. TISSUE SPECIFICITY: Absorptive epithelia, including renal proximal tubules. DISEASE: Defects in LRP2 are the cause of Donnai-Barrow syndrome (DBS) [MIM:222448]; also known as faciooculoacousticorenal syndrome (FOAR syndrome). DBS is a rare autosomal recessive disorder characterized by major malformations including agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. The FOAR syndrome was first described as comprising facial anomalies, ocular anomalies, sensorineural hearing loss, and proteinuria. DBS and FOAR were first described as distinct disorders but the classic distinguishing features between the 2 disorders were presence of proteinuria and absence of diaphragmatic hernia and corpus callosum anomalies in FOAR. Early reports noted that the 2 disorders shared many phenotypic features and may be identical. Although there is variability in the expression of some features (e.g. agenesis of the corpus callosum and proteinuria), DBS and FOAR are now considered to represent the same entity. SIMILARITY: Belongs to the LDLR family. SIMILARITY: Contains 17 EGF-like domains. SIMILARITY: Contains 36 LDL-receptor class A domains. SIMILARITY: Contains 37 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 P98164
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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:0001843 neural tube closure GO:0003139 secondary heart field specification GO:0003148 outflow tract septum morphogenesis GO:0003223 ventricular compact myocardium morphogenesis GO:0003281 ventricular septum development GO:0006629 lipid metabolic process GO:0006766 vitamin metabolic process GO:0006897 endocytosis GO:0006898 receptor-mediated endocytosis GO:0007399 nervous system development GO:0007507 heart development GO:0007605 sensory perception of sound GO:0008283 cell proliferation GO:0008584 male gonad development GO:0030001 metal ion transport GO:0030514 negative regulation of BMP signaling pathway GO:0030900 forebrain development GO:0035904 aorta development GO:0042359 vitamin D metabolic process GO:0042953 lipoprotein transport GO:0050769 positive regulation of neurogenesis GO:0060068 vagina development GO:0060976 coronary vasculature development GO:0060982 coronary artery morphogenesis GO:0061024 membrane organization GO:0061156 pulmonary artery morphogenesis GO:0070447 positive regulation of oligodendrocyte progenitor proliferation GO:1904447 folic acid import into cell GO:1905167 positive regulation of lysosomal protein catabolic process
U33837 - Human glycoprotein receptor gp330 precursor, mRNA, complete cds. AY265358 - Homo sapiens glycoprotein receptor gp330/megalin precursor, mRNA, complete cds. AY265357 - Homo sapiens glycoprotein receptor gp330/megalin precursor, mRNA, complete cds. U04441 - Human glycoprotein 330 mRNA, partial cds. S73145 - calcium sensor protein=Heymann nephritis antigen homolog [human, parathyroid glands, mRNA Partial, 804 nt]. AK295005 - Homo sapiens cDNA FLJ61253 complete cds, highly similar to Low-density lipoprotein receptor-related protein 2 precursor. JD510723 - Sequence 491747 from Patent EP1572962. JD503928 - Sequence 484952 from Patent EP1572962. AK302843 - Homo sapiens cDNA FLJ53943 complete cds, highly similar to Low-density lipoprotein receptor-related protein 2 precursor. JD483670 - Sequence 464694 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P98164 (Reactome details) participates in the following event(s):
R-HSA-8863472 DAB2 binds LRP2 R-HSA-350168 LRP2 transports CUBN:GC:25(OH)D from extracellular region to cytosol R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit R-HSA-2404131 LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol R-HSA-8868071 Clathrin recruits PIK3C2A R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P R-HSA-8871194 RAB5 and GAPVD1 bind AP-2 R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2 R-HSA-8868236 BAR domain proteins recruit dynamin R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828 Clathrin-mediated endocytosis R-HSA-196791 Vitamin D (calciferol) metabolism R-HSA-975634 Retinoid metabolism and transport R-HSA-199991 Membrane Trafficking R-HSA-209943 Steroid hormones R-HSA-8957322 Metabolism of steroids R-HSA-2187338 Visual phototransduction R-HSA-6806667 Metabolism of fat-soluble vitamins R-HSA-5653656 Vesicle-mediated transport R-HSA-556833 Metabolism of lipids R-HSA-418594 G alpha (i) signalling events R-HSA-196854 Metabolism of vitamins and cofactors R-HSA-1430728 Metabolism R-HSA-388396 GPCR downstream signalling R-HSA-372790 Signaling by GPCR R-HSA-162582 Signal Transduction
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Common Gene Haplotype Alleles 
