Reactome | CUBN:AMN binds GIF:Cbl

CUBN:AMN binds GIF:Cbl

Stable Identifier

R-HSA-3000103

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

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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