CUBN:AMN binds GIF:Cbl

Stable Identifier
R-HSA-3000103
Type
Reaction [binding]
Species
Homo sapiens
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In the mucosal cells of the distal ileum, in preparation for internalisation, the gastric intrinsic factor:cobalamin (GIF:Cbl) complex interacts with cubilin (CUBN). CUBN is a cotransporter facilitating uptake of lipoproteins, vitamins and iron (Matthews et al. 2007). CUBN is in complex with protein amnionless (AMN), a necessary component which directs subcellular localization and endocytosis of GIF:Cbl (Fyfe et al. 2004, Anderson et al. 2010). Defects in CUBN and AMN both cause recessive hereditary megaloblastic anemia 1 (RH-MGA1 aka MGA1 Norwegian type or Imerslund-Grasbeck syndrome, I-GS; MIM:261100). The resultant malabsorption of Cbl (vitamin B12) leads to impaired B12-dependent folate metabolism and ultimately impaired thymine synthesis and DNA replication (Aminoff et al. 1999, Kristiansen et al. 2000, Tanner et al. 2003, Densupsoontorn et al. 2012).

Literature References
PubMed ID Title Journal Year
14576052 The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless

Fyfe, JC, Madsen, M, Højrup, P, Christensen, EI, Tanner, SM, de la Chapelle, A, He, Q, Moestrup, SK

Blood 2004
20237569 Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes

Andersen, CB, Madsen, M, Storm, T, Moestrup, SK, Andersen, GR

Nature 2010
22631584 Imerslund-Gräsbeck syndrome: new mutation in amnionless

Densupsoontorn, N, Sanpakit, K, Vijarnsorn, C, Pattaragarn, A, Kangwanpornsiri, C, Jatutipsompol, C, Tirapongporn, H, Jirapinyo, P, Shah, NP, Sturm, AC, Tanner, SM

Pediatr Int 2012
10080186 Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Aminoff, M, Carter, JE, Chadwick, RB, Johnson, C, Gräsbeck, R, Abdelaal, MA, Broch, H, Jenner, LB, Verroust, PJ, Moestrup, SK, de la Chapelle, A, Krahe, R

Nat. Genet. 1999
12590260 Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia

Tanner, SM, Aminoff, M, Wright, FA, Liyanarachchi, S, Kuronen, M, Saarinen, A, Massika, O, Mandel, H, Broch, H, de la Chapelle, A

Nat. Genet. 2003
17954916 Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution

Mathews, FS, Gordon, MM, Chen, Z, Rajashankar, KR, Ealick, SE, Alpers, DH, Sukumar, N

Proc. Natl. Acad. Sci. U.S.A. 2007
10887099 Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin

Kristiansen, M, Aminoff, M, Jacobsen, C, de la Chapelle, A, Krahe, R, Verroust, PJ, Moestrup, SK

Blood 2000
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