GeneID: 183

Description:
This gene encodes cubilin, a 460-kDa peripheral membrane glycoprotein that functions as an endocytic receptor. It is mainly expressed on epithelial cells of the renal proximal tubule, yolk sac and ileal enterocytes, usually in conjunction with another endocytic receptor, megalin. Cubilin has the potential to bind various ligands primarily owing to its extracellular region, which contains 27 CUB (complement subcomponents C1r/C1s, EGF-related sea urchin protein and bone morphogenic protein-1) domains. Cubilin was initially described as the intrinsic factor vitamin B12 receptor, involved in intestinal absorption of vitamin B12. Additional ligands of cubilin include albumin, transferrin, haemoglobin, hormones, immunoglobulin light chains, and apolipoprotein A-I/high density lipoprotein (HDL). Although cubilin lacks a transmembrane domain, the N-terminal region contains a potential cysteine palmitoylation site and an amphipathic α-helical structure, which help anchor cubilin to the membrane. The N-terminal region contains a stretch of 110 amino acids followed by 8 epidermal growth factor (EGF)-repeats, which interact with the transmembrane protein amnionless (AMN) to form the so-called cubam complex that is responsible for membrane localization of the receptor. Cubilin dysfunction causes Imerslund-Gräsbeck syndrome, characterized by defective intestinal absorption of vitamin B12 with proteinuria. Cubilin deficiency is also associated with megaloblastic anaemia. A variant of this gene was shown to exhibit a protective effect against renal damage in a pediatric cohort with sickle cell disease.

Synonyms: IFCR , MGA1 , gp280

Comments:
N/A

Number of entries/variants: 2

1. Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, Verroust PJ, Moestrup SK, The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region., Blood , 91(10), 3593-600, 1998 PubMed
2. Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, Christensen EI, Aminoff M, de la Chapelle A, Krahe R, Verroust PJ, Moestrup SK, The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein., Nat. Med. , 5(6), 656-61, 1999 PubMed
3. Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI, Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)., Proc. Natl. Acad. Sci. U.S.A. , 98(24), 13895-900, 2001 PubMed
4. Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C, Dautry-Varsat A, Gburek J, Willnow TE, Christensen EI, Moestrup SK, Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia., Proc. Natl. Acad. Sci. U.S.A. , 98(22), 12491-6, 2001 PubMed
5. Christensen EI, Birn H, Megalin and cubilin: multifunctional endocytic receptors., Nat. Rev. Mol. Cell Biol. , 3(4), 256-66, 2002 PubMed
6. Fyfe JC, Madsen M, Højrup P, Christensen EI, Tanner SM, de la Chapelle A, He Q, Moestrup SK, The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless., Blood , 103(5), 1573-9, 2004 PubMed
7. Nielsen R, Christensen EI, Birn H, Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease., Kidney Int. , 89(1), 58-67, 2016 PubMed
8. Schaefer BA, Flanagan JM, Alvarez OA, Nelson SC, Aygun B, Nottage KA, George A, Roberts CW, Piccone CM, Howard TA, Davis BR, Ware RE, Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia., PLoS ONE , 11(10), e0164364, 2016 PubMed