ID:CUBN_HUMAN DESCRIPTION: RecName: Full=Cubilin; AltName: Full=460 kDa receptor; AltName: Full=Intestinal intrinsic factor receptor; AltName: Full=Intrinsic factor-cobalamin receptor; AltName: Full=Intrinsic factor-vitamin B12 receptor; Flags: Precursor; FUNCTION: Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface. SUBUNIT: Interacts with LRP2 in a dual-receptor complex in a calcium-dependent manner. Component of the cubam complex composed of CUBN and AMN. The cubam complex can oligomerize and form cubam trimers. Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1. SUBCELLULAR LOCATION: Endosome membrane; Peripheral membrane protein (By similarity). Lysosome membrane; Peripheral membrane protein (By similarity). Note=Colocalizes with AMN and LRP2 in the endocytotic apparatus of epithelial cells (By similarity). TISSUE SPECIFICITY: Expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells and in absorptive intestinal cells. Expressed in the epithelium of intestine and kidney. DOMAIN: The CUB domains 5 to 8 mediate binding to GIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2. PTM: The precursor is cleaved by a trans-Golgi proteinase furin. The result is a propeptide cleaved off. PTM: N-glycosylated. DISEASE: Defects in CUBN are a cause of recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:261100]; also known as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS). RH-MGA1 is due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected. SIMILARITY: Contains 27 CUB domains. SIMILARITY: Contains 7 EGF-like domains. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CUBN";
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 O60494
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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.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
