Stable Identifier
Homo sapiens
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In the mucosal cells of the distal ileum, in preparation for internalisation, the gastric intrinsic factor:cobalamin (CBLIF:RCbl) complex interacts with cubilin (CUBN). CUBN is a cotransporter facilitating uptake of lipoproteins, vitamins and iron (Matthews et al. 2007). A CUBN trimer forms a complex with amnionless (AMN) protein, a necessary component which directs subcellular localization and endocytosis of CBLIF:RCbl (Fyfe et al. 2004, Larsen et al. 2018, 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 RCbl leads to failure of the two reactions that require RCbl-derived cofactors (Aminoff et al. 1999, Kristiansen et al. 2000, Tanner et al. 2003, Densupsoontorn et al. 2012).

Literature References
PubMed ID Title Journal Year
20237569 Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes

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

Nature 2010
14576052 The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless

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

Blood 2004
22631584 Imerslund-Gräsbeck syndrome: new mutation in amnionless

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

Pediatr Int 2012
30523278 Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption

Larsen, C, Andersen, CBF, Moestrup, SK, Etzerodt, A, Madsen, M, Skjødt, K

Nat Commun 2018
10080186 Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

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

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

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

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

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

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

Blood 2000
Catalyst Activity

cargo receptor activity of CUBN:AMN [plasma membrane]

Orthologous Events
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