Defective AMN does not transport GIF:Cbl

Stable Identifier
R-HSA-3296477
Type
Reaction [transition]
Species
Homo sapiens
Compartment
extracellular region, plasma membrane
ReviewStatus
5/5
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Defective AMN does not transport GIF:Cbl
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In preparation for internalisation, the gastric intrinsic factor:cobalamin (GIF:Cbl) complex interacts with the cubilin:protein amnionless complex (CUBN:AMN, Cubam). CUBN is a multisubstrate cell surface receptor facilitating uptake of lipoproteins, vitamins and iron. Protein amnionless (AMN) is a necessary component which directs subcellular localization and endocytosis of GIF:Cbl. Defects in AMN cause recessive hereditary megaloblastic anemia 1 (RH-MGA1 aka MGA1 Norwegian type or Imerslund-Grasbeck syndrome, I-GS; MIM:261100). The Finnish cases described by Grasbeck et al. were caused by defects in CUBN whereas the Norwegian cases described by Imerslund were due to defects in AMN (Grasbeck et al. 1960, Imerslund 1960 respectively). The resultant malabsorption of Cbl (vitamin B12) leads to impaired B12-dependent folate metabolism and ultimately impaired thymine synthesis and DNA replication. Cells involved in erythropoiesis are particularly affected. Two common mutations in AMN are T34I and G5Afs*12 (Tanner et al. 2003).
Literature References
PubMed ID Title Journal Year
13852753 Idiopathic chronic megaloblastic anemia in children

IMERSLUND, O

Acta Paediatr Suppl 1960
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
13828999 Selective vitamin B12 malabsorption and proteinuria in young people. A syndrome

GRASBECK, R, GORDIN, R, KANTERO, I, KUHLBACK, B

Acta Med Scand 1960
Participants
Input
Participates
as an event of
Normal reaction
CUBN:AMN binds CBLIF:RCbl (Homo sapiens)
Functional status

Loss of function of CUBN:AMN mutants [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
megaloblastic anemia DOID:13382 megaloblastic anemia, Megaloblastic anemia (disorder), Anaemia - megaloblastic, Megaloblastic anemia NOS (disorder), Megaloblastic anaemia, ANEMIA MEGALOBLASTIC, Megaloblastic anemia NOS, Megaloblastic Anemia, Megaloblastic anemia NOS (disorder), Anaemia - megaloblastic, Megaloblastic anemia, NOS, Megaloblastic anemia NOS
Cross References
Mondo
Authored
Jassal, B  (2013-04-18)
Reviewed
Watkins, D  (2013-08-14)
Created
Jassal, B  (2013-04-18)
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