Defective SLC40A1 does not transport Fe2+ from cytosol to extracellular region

Stable Identifier
R-HSA-5655733
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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Defective SLC40A1 does not transport Fe2+ from cytosol to extracellular region
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SLC40A1 (MTP1 aka ferroportin or IREG1) is highly expressed on macrophages where it mediates iron efflux from the breakdown of haem. Normally, SLC40A1 colocalises with ceruloplasmin (CP) which stablizes SLC40A1 and is necessary for the efflux reaction to occur. In addition, six copper ions are required by ceruloplasmin as a cofactor.
Defects in SLC40A1 can cause hemochromatosis 4 (HFE4; MIM:606069), a disorder of iron metabolism characterised by iron overload. Excess iron is deposited in a variety of organs leading to their failure, resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis and hypogonadotropic hypogonadism. Severe effects of the disease don't usually appear until after decades of progressive iron overloading. Mutations causing HFE4 include N144H, A77D, V162del, G80V, D181V and D157G (Njajou et al. 2001, Agarwal et al. 2006, Wallace et al. 2002, Cremonesi et al. 2005, Hetet et al. 2003).
Literature References
PubMed ID Title Journal Year
12091366 Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Wallace, DF, Pedersen, P, Dixon, JL, Stephenson, P, Searle, JW, Powell, LW, Subramaniam, VN

Blood 2002
16351644 Genetic and clinical heterogeneity of ferroportin disease

Cremonesi, L, Cemonesi, L, Forni, GL, Soriani, N, Lamagna, M, Fermo, I, Daraio, F, Galli, A, Pietra, D, Malcovati, L, Ferrari, M, Camaschella, C, Cazzola, M

Br. J. Haematol. 2005
16813613 Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent

Agarwal, S, Sankar, VH, Tewari, D, Pradhan, M

Clin. Genet. 2006
12730114 Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

Hetet, G, Devaux, I, Soufir, N, Grandchamp, B, Beaumont, C

Blood 2003
11431687 A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis

Njajou, OT, Vaessen, N, Joosse, M, Berghuis, B, van Dongen, JW, Breuning, MH, Snijders, PJ, Rutten, WP, Sandkuijl, LA, Oostra, BA, van Duijn, CM, Heutink, P

Nat. Genet. 2001
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Catalyst Activity

iron ion transmembrane transporter activity of SLC40A1 mutants:CP:6xCu2+ [plasma membrane]

Physical Entity
SLC40A1 mutants:CP:6xCu2+ [plasma membrane] (Homo sapiens)
Activity
iron ion transmembrane transporter activity (GO:0005381)
Normal reaction
SLC40A1:CP:6Cu2+ transports Fe2+ from cytosol to extracellular region (Homo sapiens)
Functional status

Loss of function of SLC40A1 mutants:CP:6xCu2+ [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
hemochromatosis DOID:2352 iron storage disorder, Hemochromatosis (disorder), diabetes bronze, Bronze diabetes (disorder), HEMOCHROMATOSIS, Hemochromatosis (disorder), Bronzed diabetes, Haemochromatosis, Haemochromatosis
Cross References
Mondo
Authored
Jassal, B  (2014-12-09)
Reviewed
Broer, S  (2015-08-04)
Created
Jassal, B  (2014-12-09)
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