ABCD1 p.Leu279Val
| Predicted by SNAP2: | A: D (66%), C: D (59%), D: D (85%), E: D (85%), F: N (57%), G: D (85%), H: D (80%), I: D (53%), K: D (85%), M: D (59%), N: D (80%), P: D (85%), Q: D (75%), R: D (85%), S: D (80%), T: D (75%), V: D (53%), W: D (80%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] The gene responsible for adrenoleukodystrophy enco... Hum Mol Genet. 1994 Feb;3(2):265-71. Mosser J, Lutz Y, Stoeckel ME, Sarde CO, Kretz C, Douar AM, Lopez J, Aubourg P, Mandel JL
The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein.
Hum Mol Genet. 1994 Feb;3(2):265-71., [PMID:8004093]
Abstract [show]
Adrenoleukodystrophy is a severe genetic demyelinating disease associated with an impairment of beta-oxidation of very long chain fatty acids (VLCFA) in peroxisomes. Earlier studies had suggested that a deficiency in VLCFA CoA synthetase was the primary defect. A candidate adrenoleukodystrophy gene has recently been cloned and was found unexpectedly to encode a putative ATP-binding cassette transporter. We have raised monoclonal antibodies against this protein, that detect a 75kDa band. This protein was absent in several patients with adrenoleukodystrophy. Immunofluorescence and immunoelectron microscopy showed that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane. Distinct immunofluorescence patterns were observed in cell lines from patients with Zellweger syndrome (a peroxisomal biogenesis disorder) belonging to different complementation groups.
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No. Sentence Comment
27 The three constructs contain the sequences corresponding to codons Ala 57 to Val 301 (AC25), Leu 279 to Val 482 (AC 13) and De 495 to Lys 648 (AC3), respectively (fig. 1).
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ABCD1 p.Leu279Val 8004093:27:93
status: NEW[hide] Topology of ATP-binding domain of adrenoleukodystr... Arch Biochem Biophys. 1996 Oct 15;334(2):369-79. Contreras M, Sengupta TK, Sheikh F, Aubourg P, Singh I
Topology of ATP-binding domain of adrenoleukodystrophy gene product in peroxisomes.
Arch Biochem Biophys. 1996 Oct 15;334(2):369-79., [PMID:8900413]
Abstract [show]
Adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of saturated very-long-chain fatty acids (> C22:0) due to the impaired activity of lignoceroyl-CoA ligase. The gene responsible for the disease was found to code for a 84-kDa peroxisomal integral membrane protein. Its amino acid sequence has high homology with the ATP-binding cassette superfamily of transporters and it is predicted to have six membrane-spanning segments and a putative ATP-binding domain. To define the function of ALDP, we studied the topology of its ATP-binding domain by using antibodies (1D6) against a hydrophobic domain (amino acid residues 279 to 482) and antibodies (Abct) against the C-terminal 15-amino-acid hydrophilic domain (amino acid residues 731 to 745) of ALDP. The observation of punctate fluorescence in permeabilized ALD fibroblasts, using Abct antibodies but not with antibodies against catalase, suggests that the C-terminal segment of ALDP is projected toward the cytoplasm from the peroxisomal membrane. Trypsinization of intact peroxisomes under isotonic conditions abolishes the Abct antibody recognition site, whereas the 1D6 antibodies identify a degradation product of 43-kDa protein that has been protected and retained by the membrane. This again suggests that the C-terminal portion of the ALDP protein is located on the outside (cytoplasmic) face of the peroxisomal membrane. Additional support for this conclusion was obtained by purification of the ALDP C-terminal domain, released from purified rat liver peroxisomes incubated with the cytosolic fraction, using blue-Sepharose affinity chromatography. A 47-kDa peptide retained by the column was recognized by Western blot analysis with Abct antibodies against the C-terminal sequence of ALDP and this polypeptide on polyvinylidene difluoride membrane was able to bind [gamma-32P]ATP in vitro in the presence of Mg2+. These results demonstrate that the C-terminal peptide containing the ATP-binding domains of ALDP is on the cytoplasmic surface of the peroxisomal membrane where this domain may function as an ATPase to support the functional role of ALDP in the peroxisomal membrane.
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No. Sentence Comment
42 ALDP contains one unit of six membrane-spanning ing to codons Leu 279 to Val 482), was prepared as described pre- segments and a putative ATP-binding domain (equiva- viously (9).
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ABCD1 p.Leu279Val 8900413:42:62
status: NEW44 ALDP contains one unit of six membrane-spanning ing to codons Leu 279 to Val 482), was prepared as described pre- segments and a putative ATP-binding domain (equiva- viously (9).
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ABCD1 p.Leu279Val 8900413:44:62
status: NEW