Reactome | CUBN:AMN binds CBLIF:RCbl

CUBN:AMN binds CBLIF:RCbl

Stable Identifier

R-HSA-3000103

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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