ABCB7 p.Val411Leu
| Predicted by SNAP2: | A: N (53%), C: N (53%), D: D (85%), E: D (80%), F: D (63%), G: D (75%), H: D (80%), I: N (57%), K: D (85%), L: D (66%), M: D (66%), N: D (80%), P: D (85%), Q: D (75%), R: D (80%), S: D (71%), T: N (53%), W: D (85%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Mitochondrial ABC transporters function: the role ... Biochim Biophys Acta. 2012 Oct;1823(10):1945-57. doi: 10.1016/j.bbamcr.2012.07.013. Epub 2012 Aug 3. Liesa M, Qiu W, Shirihai OS
Mitochondrial ABC transporters function: the role of ABCB10 (ABC-me) as a novel player in cellular handling of reactive oxygen species.
Biochim Biophys Acta. 2012 Oct;1823(10):1945-57. doi: 10.1016/j.bbamcr.2012.07.013. Epub 2012 Aug 3., [PMID:22884976]
Abstract [show]
Mitochondria are one of the major sources of reactive oxygen species (ROS) in the cell. When exceeding the capacity of antioxidant mechanisms, ROS production may lead to different pathologies, such as ischemia-reperfusion injury, neurodegeneration, anemia and ageing. As a consequence of the endosymbiotic origin of mitochondria, eukaryotic cells have developed different transport mechanisms that coordinate mitochondrial function with other cellular compartments. Four mitochondrial ATP-binding cassette (ABC) transporters have been described to date in mammals: ABCB6, ABCB8, ABCB7 and ABCB10. ABCB10 is located in the inner mitochondrial membrane forming homodimers, with the ATP binding domain facing the mitochondrial matrix. ABCB10 expression is highly induced during erythroid differentiation and its overexpression increases hemoglobin synthesis in erythroid cells. However, ABCB10 is also expressed in nonerythroid tissues, suggesting a role not directly related to hemoglobin synthesis. Recent evidence points toward ABCB10 as an important player in the protection from oxidative stress in mammals. In this regard, ABCB10 is required for normal erythropoiesis and cardiac recovery after ischemia-reperfusion, processes intimately related to mitochondrial ROS generation. Here, we review the current knowledge on mitochondrial ABC transporters and ABCB10 and discuss the potential mechanisms by which ABCB10 and its transport activity may regulate oxidative stress. We discuss ABCB10 as a potential therapeutic target for diseases in which increased mitochondrial ROS production and oxidative stress play a major role.
Comments [show]
None has been submitted yet.
No. Sentence Comment
96 The heritage family study shows that the amino acid change of E433K at the C-terminal of the sixth TMD [9,70] or V411L at the beginning of the sixth TMD in ABCB7 is sufficient to cause XLSA/A [56].
X
ABCB7 p.Val411Leu 22884976:96:113
status: NEW[hide] X-linked sideroblastic anemia and ataxia: A new fa... Eur J Paediatr Neurol. 2012 Nov;16(6):730-5. doi: 10.1016/j.ejpn.2012.02.003. Epub 2012 Mar 6. D'Hooghe M, Selleslag D, Mortier G, Van Coster R, Vermeersch P, Billiet J, Bekri S
X-linked sideroblastic anemia and ataxia: A new family with identification of a fourth ABCB7 gene mutation.
Eur J Paediatr Neurol. 2012 Nov;16(6):730-5. doi: 10.1016/j.ejpn.2012.02.003. Epub 2012 Mar 6., [PMID:22398176]
Abstract [show]
X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare cause of early onset ataxia, which may be overlooked due to the usually mild asymptomatic anemia. The genetic defect has been identified as a mutation in the ABCB7 gene at Xq12-q13. The gene encodes a mitochondrial ATP-binding cassette (ABC) transporter protein involved in iron homeostasis. Until now only three families have been reported, each with a distinct missense mutation in this gene. We describe a fourth family with XLSA-A and a novel mutation in the ABCB7 gene.
Comments [show]
None has been submitted yet.
No. Sentence Comment
195 Maguire A, Hellier K, Hammans S, May A. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L.
X
ABCB7 p.Val411Leu 22398176:195:157
status: NEW194 Maguire A, Hellier K, Hammans S, May A. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L.
X
ABCB7 p.Val411Leu 22398176:194:157
status: NEW[hide] Disruption of the ATP-binding cassette B7 (ABTM-1/... J Biol Chem. 2011 Jun 17;286(24):21304-14. Epub 2011 Apr 4. Gonzalez-Cabo P, Bolinches-Amoros A, Cabello J, Ros S, Moreno S, Baylis HA, Palau F, Vazquez-Manrique RP
Disruption of the ATP-binding cassette B7 (ABTM-1/ABCB7) induces oxidative stress and premature cell death in Caenorhabditis elegans.
J Biol Chem. 2011 Jun 17;286(24):21304-14. Epub 2011 Apr 4., [PMID:21464130]
Abstract [show]
X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes a member of the ATP-binding cassette transporter family. Studies in yeast, mammalian cells, and mice have shown that ABCB7 functions in the transport of iron-sulfur (Fe-S) clusters into the cytoplasm. To further investigate the mechanism of this disease, we have identified and characterized the Caenorhabditis elegans homologue of the ABCB7 gene, abtm-1. We have studied the function of abtm-1 using mutants and RNAi. abtm-1-depleted animals produce arrested embryos that have morphogenetic defects and unusual premature, putative apoptotic events. abtm-1(RNAi) animals also show accumulation of ferric iron and increased oxidative stress. Despite the increased level of oxidative stress in abtm-1(RNAi) animals, they have an increased life span. We observed accumulation of DAF-16/FOXO in the nuclei of affected animals and elevation of the expression of SOD-3, a well established target of DAF-16, which may explain the increased life span extension of these animals. abtm-1 is strongly expressed in tissues with a high energy demand, and abtm-1(RNAi) animals have phenotypes that reflect the need for abtm-1 in these tissues. Finally, we show that reducing the function of other genes involved in Fe-S cluster production produces similar phenotypic consequences to abtm-1 loss of function. Therefore, ablation of abtm-1 in C. elegans provides a model in which to investigate the mechanism underlying XLSA/A.
Comments [show]
None has been submitted yet.
No. Sentence Comment
20 Two of these are missense mutations, which cause the substitution of residues within the ABCB7 transmembrane domains: V411L (4) and I400M (2).
X
ABCB7 p.Val411Leu 21464130:20:118
status: NEW[hide] Human iron-sulfur cluster assembly, cellular iron ... Biochemistry. 2010 Jun 22;49(24):4945-56. Ye H, Rouault TA
Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease.
Biochemistry. 2010 Jun 22;49(24):4945-56., [PMID:20481466]
Abstract [show]
Iron-sulfur (Fe-S) proteins contain prosthetic groups consisting of two or more iron atoms bridged by sulfur ligands, which facilitate multiple functions, including redox activity, enzymatic function, and maintenance of structural integrity. More than 20 proteins are involved in the biosynthesis of iron-sulfur clusters in eukaryotes. Defective Fe-S cluster synthesis not only affects activities of many iron-sulfur enzymes, such as aconitase and succinate dehydrogenase, but also alters the regulation of cellular iron homeostasis, causing both mitochondrial iron overload and cytosolic iron deficiency. In this work, we review human Fe-S cluster biogenesis and human diseases that are caused by defective Fe-S cluster biogenesis. Fe-S cluster biogenesis takes place essentially in every tissue of humans, and products of human disease genes, including frataxin, GLRX5, ISCU, and ABCB7, have important roles in the process. However, the human diseases, Friedreich ataxia, glutaredoxin 5-deficient sideroblastic anemia, ISCU myopathy, and ABCB7 sideroblastic anemia/ataxia syndrome, affect specific tissues, while sparing others. Here we discuss the phenotypes caused by mutations in these different disease genes, and we compare the underlying pathophysiology and discuss the possible explanations for tissue-specific pathology in these diseases caused by defective Fe-S cluster biogenesis.
Comments [show]
None has been submitted yet.
No. Sentence Comment
228 In the third family, the affected brothers have a G-to-C transition at position 1299, which predicts a V411L substitution in the sixth putative transmembrane domain (86).
X
ABCB7 p.Val411Leu 20481466:228:103
status: NEW229 In the third family, the affected brothers have a G-to-C transition at position 1299, which predicts a V411L substitution in the sixth putative transmembrane domain (86).
X
ABCB7 p.Val411Leu 20481466:229:103
status: NEW[hide] Recent advances in the understanding of inherited ... Br J Haematol. 2008 Oct;143(1):27-38. Epub 2008 Jul 14. Camaschella C
Recent advances in the understanding of inherited sideroblastic anaemia.
Br J Haematol. 2008 Oct;143(1):27-38. Epub 2008 Jul 14., [PMID:18637800]
Abstract [show]
Sideroblastic anaemia includes a heterogeneous group of rare conditions, characterized by decreased haem synthesis and mitochondrial iron overload, which are diagnosed by the presence of ringed sideroblasts in the bone marrow aspirate. The most frequent form is X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of haem synthesis in erythroid precursors and is post-transcriptionally controlled by the iron regulatory proteins. Impaired haem production causes variable degrees of anaemia and mitochondrial iron accumulation as ringed sideroblasts. The heterogeneity and complexity of sideroblastic anaemia is explained by an increasing number of recognized molecular defects. New forms have been recognized as being linked to the deficient function of mitochondrial proteins involved in iron-sulphur cluster biogenesis, such as ABCB7 and GLRX5, which are extremely rare but represent important biological models. Local mitochondrial iron overload is present in all sideroblastic anaemias, whereas systemic iron overload occurs only in the forms because of primary or secondary deficiency of ALAS2.
Comments [show]
None has been submitted yet.
No. Sentence Comment
132 The missense mutations (Ile400 Met Glu 433Lys, Val 411Leu) reported in patients are unable to rescue the Atm1p-deficient phenotype, indicating that they are partial loss of function mutations (reviewed in Fleming, 2002).
X
ABCB7 p.Val411Leu 18637800:132:47
status: NEW[hide] RNA silencing of the mitochondrial ABCB7 transport... Blood. 2007 Apr 15;109(8):3552-9. Epub 2006 Dec 27. Cavadini P, Biasiotto G, Poli M, Levi S, Verardi R, Zanella I, Derosas M, Ingrassia R, Corrado M, Arosio P
RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload.
Blood. 2007 Apr 15;109(8):3552-9. Epub 2006 Dec 27., [PMID:17192393]
Abstract [show]
X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa cells by performing sequential transfections with siRNAs. The phenotype of the ABCB7-deficient cells was characterized by a strong reduction in proliferation rate that was not rescued by iron supplementation, by evident signs of iron deficiency, and by a large approximately 6-fold increase of iron accumulation in the mitochondria that was poorly available to mitochondrial ferritin. The cells showed an increase of protoporphyrin IX, a higher sensitivity to H(2)O(2) toxicity, and a reduced activity of mitochondrial superoxide dismutase 2 (SOD2), while the activity of mitochondrial enzymes, such as citrate synthase or succinate dehydrogenase, and ATP content were not decreased. In contrast, aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced. The results support the hypothesis that ABCB7 is involved in the transfer of iron from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In addition, the results indicate that anemia in XLSA/A is caused by the accumulation of iron in a form that is not readily usable for heme synthesis.
Comments [show]
None has been submitted yet.
No. Sentence Comment
15 They consist of missense mutations (I400M, E433K, and V411L) at the border of putative transmembrane domains of the protein and were found to rescue only partially the defects of Atm1p-deficient yeasts.6 A study on erythroid cells showed that ABCB7 expression increases the activity of ferrochelatase by binding to its C-terminus.21 The recent study of mice deficient in ABCB7 showed that the protein is essential in early gestation.
X
ABCB7 p.Val411Leu 17192393:15:54
status: NEW13 (c) 2007 by The American Society of Hematology 3552 They consist of missense mutations (I400M, E433K, and V411L) at the border of putative transmembrane domains of the protein and were found to rescue only partially the defects of Atm1p-deficient yeasts.6 A study on erythroid cells showed that ABCB7 expression increases the activity of ferrochelatase by binding to its C-terminus.21 The recent study of mice deficient in ABCB7 showed that the protein is essential in early gestation.
X
ABCB7 p.Val411Leu 17192393:13:107
status: NEW[hide] X-linked cerebellar ataxia and sideroblastic anaem... Br J Haematol. 2001 Dec;115(4):910-7. Maguire A, Hellier K, Hammans S, May A
X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L.
Br J Haematol. 2001 Dec;115(4):910-7., [PMID:11843825]
Abstract [show]
Two brothers with X-linked ataxia (XLA) were found to have hypochromic red cells and increased erythrocyte protoporphyrin despite normal iron stores. The mother was unaffected by ataxia and had normal iron stores but showed evidence of some red cell hypochromia with heavy basophilic stippling that stained positive for iron. Bone marrow biopsy confirmed the presence of ring sideroblasts in one of the brothers. The absence of mutations in the ALAS2 gene and the predominance of zinc over free protoporphyrin led to a search using a combination of DNA and cDNA analysis for the presence of mutations in the ABC7 gene. ABC7 encodes a mitochondrial half-type ATP Binding Cassette transporter involved in iron homeostasis. The published cDNA sequence was used to search databases for the genomic sequence of which 12 exons spanning 23.4 kb were mapped leaving the most 5' nucleotides unaccounted for. The identified exons and their exon-intron boundaries were amplified from DNA while the most 5' sequence including the initiation codon was amplified from cDNA of peripheral blood cells. Direct sequencing revealed hemizygosity in the brothers and heterozygosity in the mother for a G-->C transversion at position 1299 of the published cDNA. This predicts a V411L substitution at the beginning of the last of six putative transmembrane regions of the protein. Restriction enzyme digestion confirmed the presence of this mutation in the three family members but could not detect it in 200 normal alleles. An uncle affected by ataxia also carried this mutation. This study supports the recently hypothesized involvement of the ABC7 gene in XLSA/A and highlights a protein structure region of importance to this syndrome.
Comments [show]
None has been submitted yet.
No. Sentence Comment
0 910 q 2001 Blackwell Science Ltd X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L Andrew Maguire,1 Kate Hellier,2 Simon Hammans2 and Alison May1 1 Department of Haematology, University of Wales College of Medicine, Cardiff, and 2 Wessex Neurological Centre, Southampton General Hospital, Southampton, UK Received 7 February 2001; accepted for publication 16 May 2001 Summary.
X
ABCB7 p.Val411Leu 11843825:0:150
status: NEW9 This predicts a V411L substitution at the beginning of the last of six putative transmembrane regions of the protein.
X
ABCB7 p.Val411Leu 11843825:9:16
status: NEW109 Identification of a novel family specific mutation A family specific missense mutation, G1299C in the cDNA, predicting an amino acid residue change from valine to leucine (V411L), was found.
X
ABCB7 p.Val411Leu 11843825:109:172
status: NEW134 In our family we demonstrated a third mutation (cDNA: G1299C predicting V411L) in exon 9 of the ABC7 transporter gene, further strengthening the link between ABC7 and XLSA/A.
X
ABCB7 p.Val411Leu 11843825:134:72
status: NEW[hide] Crystal structures of nucleotide-free and glutathi... Science. 2014 Mar 7;343(6175):1137-40. doi: 10.1126/science.1246729. Srinivasan V, Pierik AJ, Lill R
Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1.
Science. 2014 Mar 7;343(6175):1137-40. doi: 10.1126/science.1246729., [PMID:24604199]
Abstract [show]
The yeast mitochondrial ABC transporter Atm1, in concert with glutathione, functions in the export of a substrate required for cytosolic-nuclear iron-sulfur protein biogenesis and cellular iron regulation. Defects in the human ortholog ABCB7 cause the sideroblastic anemia XLSA/A. Here, we report the crystal structures of free and glutathione-bound Atm1 in inward-facing, open conformations at 3.06- and 3.38-angstrom resolution, respectively. The glutathione binding site includes a residue mutated in XLSA/A and is located close to the inner membrane surface in a large cavity. The two nucleotide-free adenosine 5'-triphosphate binding domains do not interact yet are kept in close vicinity through tight interaction of the two C-terminal alpha-helices of the Atm1 dimer. The resulting protein stabilization may be a common structural feature of all ABC exporters.
Comments [show]
None has been submitted yet.
No. Sentence Comment
91 Three of the XLSA/A patient mutations are located in the membrane domain either on the matrix [E208D in long TM2 helix; yeast E173 (29)] or intermembrane space sides (I400M between TM5 and TM6, yeast V365 (26); V411L in TM6, yeast V376 (28)] (Fig. 2A and fig. S1A).
X
ABCB7 p.Val411Leu 24604199:91:211
status: NEW[hide] The role of mitochondria and the CIA machinery in ... Eur J Cell Biol. 2015 Jul-Sep;94(7-9):280-91. doi: 10.1016/j.ejcb.2015.05.002. Epub 2015 May 31. Lill R, Dutkiewicz R, Freibert SA, Heidenreich T, Mascarenhas J, Netz DJ, Paul VD, Pierik AJ, Richter N, Stumpfig M, Srinivasan V, Stehling O, Muhlenhoff U
The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron-sulfur proteins.
Eur J Cell Biol. 2015 Jul-Sep;94(7-9):280-91. doi: 10.1016/j.ejcb.2015.05.002. Epub 2015 May 31., [PMID:26099175]
Abstract [show]
Mitochondria have been derived from alpha-bacterial endosymbionts during the evolution of eukaryotes. Numerous bacterial functions have been maintained inside the organelles including fatty acid degradation, citric acid cycle, oxidative phosphorylation, and the synthesis of heme or lipoic acid cofactors. Additionally, mitochondria have inherited the bacterial iron-sulfur cluster assembly (ISC) machinery. Many of the ISC components are essential for cell viability because they generate a still unknown, sulfur-containing compound for the assembly of cytosolic and nuclear Fe/S proteins that perform important functions in, e.g., protein translation, DNA synthesis and repair, and chromosome segregation. The sulfur-containing compound is exported by the mitochondrial ABC transporter Atm1 (human ABCB7) and utilized by components of the cytosolic iron-sulfur protein assembly (CIA) machinery. An appealing minimal model for the striking compartmentation of eukaryotic Fe/S protein biogenesis is provided by organisms that contain mitosomes instead of mitochondria. Mitosomes have been derived from mitochondria by reductive evolution, during which they have lost virtually all classical mitochondrial tasks. Nevertheless, mitosomes harbor all core ISC components which presumably have been maintained for assisting the maturation of cytosolic-nuclear Fe/S proteins. The current review is centered around the Atm1 export process. We present an overview on the mitochondrial requirements for the export reaction, summarize recent insights into the 3D structure and potential mechanism of Atm1, and explain how the CIA machinery uses the mitochondrial export product for the assembly of cytosolic and nuclear Fe/S proteins.
Comments [show]
None has been submitted yet.
No. Sentence Comment
301 All mutated residues are located in the membrane domain either on the matrix (E208D in long TM2 helix; yeast E173 D`Hooghe et al., 2012) or intermembrane space sides (I400M between TM5-TM6, yeast V365 (Allikmets et al., 1999); V411L in TM6, yeast V376 (Maguire et al., 2001) (Fig. 4).
X
ABCB7 p.Val411Leu 26099175:301:227
status: NEW