PMID:20088845

Citation	Pedersen, GA, Chakraborty, S, Steinhauser, AL, Traub, LM and Madsen, M (2010) AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic 11:706-20
Abstract	Cubam is a multi-ligand receptor involved in dietary uptake of intrinsic factor-vitamin B(12) in the small intestine and reabsorption of various low-molecular-weight proteins (such as albumin, transferrin, apolipoprotein A-I and vitamin D-binding protein) in the kidney. Cubam is composed of two proteins: cubilin and amnionless. Cubilin harbors ligand binding capabilities, while amnionless provides membrane anchorage and potential endocytic capacity via two FXNPXF signals within the cytosolic domain. These signals are similar to the FXNPXY signals found in members of the low-density lipoprotein receptor superfamily, which associate with clathrin-associated sorting proteins, including Disabled-2 (Dab2) and autosomal recessive hypercholesterolemia (ARH), during endocytosis. We therefore investigated the functionality of each amnionless FXNPXF signal and their respective interaction with sorting proteins. By sequential mutation and expression of a panel of amnionless mutants combined with yeast two-hybrid analyses, we demonstrate that the signals are functionally redundant and both are able to mediate endocytosis of cubam through interaction with Dab2 and ARH.
Links	PubMed PMC2964065 Online version:10.1111/j.1600-0854.2010.01042.x
Keywords	Adaptor Proteins, Vesicular Transport/genetics; Adaptor Proteins, Vesicular Transport/metabolism; Animals; Apolipoprotein A-I/genetics; Apolipoprotein A-I/metabolism; Cricetinae; Endocytosis/genetics; Endocytosis/physiology; Humans; Hypercholesterolemia/genetics; Intrinsic Factor/genetics; Intrinsic Factor/metabolism; Mutation; Protein Binding/genetics; Protein Transport/genetics; Proteins/genetics; Proteins/metabolism; Receptors, Cell Surface; Receptors, LDL/chemistry; Receptors, LDL/genetics; Receptors, LDL/metabolism; Signal Transduction/genetics; Vitamin B 12/genetics; Vitamin D-Binding Protein/genetics; Vitamin D-Binding Protein/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:AMNLS		GO:0006898: receptor-mediated endocytosis	ECO:0000315:		P		Figure 4 shows that cells not expressing AMN cannot internalize intrinsic-factor-cobalamin into the cell through receptor-mediated endocytosis, while WT cells can	complete CACAO 9855
HUMAN:AMNLS	involved_in	GO:0006898: receptor-mediated endocytosis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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