LMP006483 UniProt Annotations
Gene Name cubilin (intrinsic factor-cobalamin receptor) Protein Entry CUBN_MOUSE UniProt ID Q9JLB4 Species Mouse
Comment type Description Developmental Stage Detected in yolk sac endoderm as early as day 6 and is present at the apical surface of those cells throughout the remainder of pregnancy. Apical expression is pronounced in the extraembryonic visceral endoderm (VE) of 6-9.5 dpc. Expressed by a subpopulation of cells dispersed within the 7.5 dpc embryonic endoderm and having a migratory morphology. First detected at the eight-cell stage. At the 32-cell stage expressed in all outer cells which are at the origin of the trophectoderm (TE). During the blastocyst stage, expression is predominant at the apical membrane of the TE cells. {ECO:0000269|PubMed:11856751, ECO:0000269|PubMed:14983511, ECO:0000269|PubMed:15616221}. Domain The CUB domains 5 to 8 mediate binding to GIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2 (By similarity). {ECO:0000250}. 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. {ECO:0000269|PubMed:10766831, ECO:0000269|PubMed:11278724, ECO:0000269|PubMed:11856751, ECO:0000269|PubMed:15342463}. Ptm N-glycosylated. {ECO:0000269|PubMed:11856751, ECO:0000269|PubMed:19349973}. Ptm The precursor is cleaved by a trans-Golgi proteinase furin. The result is a propeptide cleaved off (By similarity). {ECO:0000250}. Similarity Contains 27 CUB domains. {ECO:0000255|PROSITE- ProRule:PRU00059}. Similarity Contains 7 EGF-like domains. {ECO:0000255|PROSITE- ProRule:PRU00076}. Subcellular Location Endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Lysosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Colocalizes with AMN and LRP2 in the endocytotic apparatus of epithelial cells. {ECO:0000250}. Subunit Interacts with LRP2 in a dual-receptor complex in a calcium-dependent manner (By similarity). 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 (By similarity). Interacts with LRP1 and PID1/PCLI1 (By similarity). {ECO:0000250}. Tissue Specificity Expressed in kidney, thymus, ileum, placenta, small intestine and yolk sac. In kidney expressed on the apical brush border surface of proximal tubular cells, in particular in endosomes and recycling membranes vesicles, so-called dense apical tubules, which carry internalized receptors back to the cell surface. Expressed in fetal membranes of yolk sac, placenta of pregnant females. {ECO:0000269|PubMed:10766831, ECO:0000269|PubMed:11856751}.
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