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A number of human diseases involve defects in metal ion uptake and disposal, including anemia, haemochromatosis, Menkes disease and Wilson's disease. Even some infectious diseases may have associations to metal ion transporters. This recent review concentrates on metal ion trafficking and roles
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These authors have isolated two vitamin C transporters from the rat, named SVCT1 and SVCT2. These proteins, of which SVCT1 is expressed in the intestine, kidneys and liver, are high-affinity Na-dependent L-ascorbic acid transporters
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Hoglund P., Haila S., Socha J., Tomaszewski L., Saarialho-Kere U., Karjalainen-Lindsberg M.L., Airola K., Holmberg C., de la Chapelle A., Kere J. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nat Genet. 14:1996;316-319.
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A recent review highlighting the three known 'sulfate transporter' family genes and their associated diseases. Phylogenetic analysis of the gene family suggests that the human family is likely to be much larger than presently known
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Kere J., Lohi H., HÖglund P. Congenital chloride diarrhea. Am J Physiol. 276:1999;G7-G13. A recent review highlighting the three known 'sulfate transporter' family genes and their associated diseases. Phylogenetic analysis of the gene family suggests that the human family is likely to be much larger than presently known.
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Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum
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The HFE protein defective in hemochromatosis is normally expressed in crypt enterocytes of the duodenum. The HFE protein may modulate the uptake of transferrin-bound iron from plasma and impairment of this function may lead enterocytes to absorb more dietary iron
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Waheed A., Parkkila S., Saarnio J., Fleming R.E., Zhou X.Y., Tomatsu S., Britton R.S., Bacon B.R., Sly W.S. Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci USA. 96:1999;1579-1584. The HFE protein defective in hemochromatosis is normally expressed in crypt enterocytes of the duodenum. The HFE protein may modulate the uptake of transferrin-bound iron from plasma and impairment of this function may lead enterocytes to absorb more dietary iron.
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Waheed, A.1
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Mechanisms of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1
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+/+ littermates. These data support the model of increased absorption of dietary iron
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+/+ littermates. These data support the model of increased absorption of dietary iron.
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Fleming, R.E.1
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22
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Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis
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Increased NRAMP-2 mRNA expression in duodenal mucosa in hereditary haemochromatosis supports the idea of duodenal iron uptake and lead to iron overload
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Zoller H., Pietrangelo A., Vogel W., Weiss G. Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis. Lancet. 353:1999;2120-2123. Increased NRAMP-2 mRNA expression in duodenal mucosa in hereditary haemochromatosis supports the idea of duodenal iron uptake and lead to iron overload.
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Zoller, H.1
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23
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Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse
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Mice carrying the sex-linked anaemia mutation (sla) develop microcytic hypochromic anaemia. In sla, iron accumulates in enterocytes because of mutations in a transmembrane-bound ceruloplasmin homologue, hephaestin
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Vulpe C.D., Kuo Y-M., Murphy T.L., Cowley L., Askwith C., Libina N., Gitschier J., Anderson G.J. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 21:1999;195-199. Mice carrying the sex-linked anaemia mutation (sla) develop microcytic hypochromic anaemia. In sla, iron accumulates in enterocytes because of mutations in a transmembrane-bound ceruloplasmin homologue, hephaestin.
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Vulpe, C.D.1
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0032837679
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The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellularcopper using a C-terminal di-leucine endocytic signal
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This group studied the distribution of MNK, or ATP7A protein at the surface of living cells. The results suggest that copper stimulates exocytic movement of MNK to the plasma membrane. Mutation prevented the exocytic movement
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Petris M.J., Mercer J.F.B. The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellularcopper using a C-terminal di-leucine endocytic signal. Hum Mol Genet. 8:1999;2107-2115. This group studied the distribution of MNK, or ATP7A protein at the surface of living cells. The results suggest that copper stimulates exocytic movement of MNK to the plasma membrane. Mutation prevented the exocytic movement.
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Petris, M.J.1
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26
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0033590450
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Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol
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hTRPC6 and hTRPC3 seem to be non-selective cation channels that are activated by diacylglycerol independently of protein kinase C. They appear as secondary messenger operated cation channels activated by diacylglycerol
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Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T., Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 397:1999;259-263. hTRPC6 and hTRPC3 seem to be non-selective cation channels that are activated by diacylglycerol independently of protein kinase C. They appear as secondary messenger operated cation channels activated by diacylglycerol.
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Nature
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Hofmann, T.1
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Schultz, G.6
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27
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0033529713
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Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption
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Calcium is an essential component of bone and also an intracellular second messenger. Calcium transport protein (CaT1) was cloned from rat duodenum and is structurally related to the TRP family of ion channels. CaT1 transport is electrogenic, pH sensitive, voltage-dependent and uncoupled to other ions
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Peng J-B., Chen X-Z., Berger U.V., Vassilev P.M., Tsukaguchi H., Brown E.M., Hediger M.A. Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J Biol Chem. 274:1999;22739-22746. Calcium is an essential component of bone and also an intracellular second messenger. Calcium transport protein (CaT1) was cloned from rat duodenum and is structurally related to the TRP family of ion channels. CaT1 transport is electrogenic, pH sensitive, voltage-dependent and uncoupled to other ions.
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J Biol Chem
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Peng, J.-B.1
Chen, X.-Z.2
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Tsukaguchi, H.5
Brown, E.M.6
Hediger, M.A.7
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28
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0033583827
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Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine
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A novel type II sodium-dependent phosphate transporter (NaPi-3) was isolated from human small intestine and lung
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Feild J.A., Zhang L., Brun K.A., Brooks D.P., Edwards R.M. Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem Biophys Res Commun. 258:1999;578-582. A novel type II sodium-dependent phosphate transporter (NaPi-3) was isolated from human small intestine and lung.
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Biochem Biophys Res Commun
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Feild, J.A.1
Zhang, L.2
Brun, K.A.3
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Edwards, R.M.5
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29
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0032921421
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Isolation and chromosomal mapping of a novel human gene showing homology to Na+/PO4 cotransporter
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A novel colon, liver, and pancreas specific Na+/phosphate cotransporter was cloned
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Shibui A., Tsunoda T., Seki N., Suzuki Y., Sugane K., Sugano S. Isolation and chromosomal mapping of a novel human gene showing homology to Na+/PO4 cotransporter. J Hum Genet. 44:1999;190-192. A novel colon, liver, and pancreas specific Na+/phosphate cotransporter was cloned.
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J Hum Genet
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Shibui, A.1
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Sugano, S.6
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30
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0344699322
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Identification of SLC7A7, encoding Y+Lat-1, as the lysinuric protein intolerance gene
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Lysinuric protein intolerance causes growth retardation, muscle hypotonia and hepatosplenomegaly. A novel dibasic amino-acid transporter is defective in this disorder, acting at the basolateral membrane of epithelial cells in small intestine. Mutations were found in Finnish and Spanish patients
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Torrents D., Mykkanen J., Pineda M., Feliubadalo L., Estevez R., De Cid R., Sanjurjo P., Zorzano A., Nunes V., Huoponen K.et al. Identification of SLC7A7, encoding Y+Lat-1, as the lysinuric protein intolerance gene. Nat Genet. 21:1999;293-296. Lysinuric protein intolerance causes growth retardation, muscle hypotonia and hepatosplenomegaly. A novel dibasic amino-acid transporter is defective in this disorder, acting at the basolateral membrane of epithelial cells in small intestine. Mutations were found in Finnish and Spanish patients.
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(1999)
Nat Genet
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Torrents, D.1
Mykkanen, J.2
Pineda, M.3
Feliubadalo, L.4
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De Cid, R.6
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Nunes, V.9
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31
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0032821201
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Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+at) of Rbat
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Cystinuria affects renal reabsorption of cystine and dibasic amino acids. A new gene expressed in kidney, liver, small intestine and placenta can mediate the uptake of L-arginine in a cell model. Mutations were found in several populations in non-type I cystinuria patients
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Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+at) of Rbat. Nat Genet. 23:1999;52-57. Cystinuria affects renal reabsorption of cystine and dibasic amino acids. A new gene expressed in kidney, liver, small intestine and placenta can mediate the uptake of L-arginine in a cell model. Mutations were found in several populations in non-type I cystinuria patients.
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32
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0033197543
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Identification of the major intestinal fatty acid transport protein
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Fatty acid (FA) transport across the apical membrane of enterocytes in the small intestine is mediated by a novel protein designated FATP4. It seems to emerge as the principal fatty acid transporter in enterocytes
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Stahl A., Hirsch D.J., Gimeno R.E., Punreddy S., Ge P., Watson N., Patel S., Kotler M., Raimondi A., Tartaglia L.A., Lodish H.F. Identification of the major intestinal fatty acid transport protein. Mol Cell. 4:1999;299-308. Fatty acid (FA) transport across the apical membrane of enterocytes in the small intestine is mediated by a novel protein designated FATP4. It seems to emerge as the principal fatty acid transporter in enterocytes.
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(1999)
Mol Cell
, vol.4
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Stahl, A.1
Hirsch, D.J.2
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Ge, P.5
Watson, N.6
Patel, S.7
Kotler, M.8
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Tartaglia, L.A.10
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