ABCMdb

ABCD1 p.Leu81Val

Predicted by SNAP2:	A: N (53%), C: N (61%), D: D (75%), E: D (71%), F: D (59%), G: D (63%), H: D (53%), I: N (93%), K: D (63%), M: N (61%), N: D (66%), P: D (75%), Q: N (53%), R: D (59%), S: D (53%), T: D (59%), V: N (78%), W: D (53%), Y: D (63%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[hide] Targeting of the human adrenoleukodystrophy protei... Eur J Cell Biol. 2003 Aug;82(8):401-10. Landgraf P, Mayerhofer PU, Polanetz R, Roscher AA, Holzinger A
Targeting of the human adrenoleukodystrophy protein to the peroxisomal membrane by an internal region containing a highly conserved motif.
Eur J Cell Biol. 2003 Aug;82(8):401-10., [PMID:14533738]

Abstract [show]
In this study we addressed the targeting requirements of peroxisomal ABC transporters, in particular the human adrenoleukodystrophy protein. This membrane protein is defective or missing in X-linked adrenoleukodystrophy, a neurodegenerative disorder predominantly presenting in childhood. Using adrenoleukodystrophy protein deletion constructs and green fluorescent protein fusion constructs we identified the amino acid regions 1-110 and 67-164 to be sufficient for peroxisomal targeting. However, the minimal region shared by these constructs (amino acids 67-110) is not sufficient for peroxisomal targeting by itself. Additionally, the NH2-terminal 66 amino acids enhance targeting efficiency. Green fluorescent protein-labeled fragments of human peroxisomal membrane protein 69 and Saccharomyces cerevisiae Pxa1 corresponding to the amino acid 67-164 adrenoleukodystrophy protein region were also directed to the mammalian peroxisome. The required region contains a 14-amino-acid motif (71-84) conserved between the adrenoleukodystrophy protein and human peroxisomal membrane protein 69 and yeast Pxa1. Omission or truncation of this motif in the adrenoleukodystrophy protein abolished peroxisomal targeting. The single amino acid substitution L78F resulted in a significant reduction of targeting efficiency. The in-frame deletion of three amino acids (del78-80LLR) within the proposed targeting motif in two patients suffering from X-linked adrenoleukodystrophy resulted in the mislocalization of a green fluorescent protein fusion protein to nucleus, cytosol and mitochondria. Our data define the targeting region of human adrenoleukodystrophy protein containing a highly conserved 14-amino-acid motif.

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Sentences [show]
No. Sentence Comment
127 Construct name n Strictly peroxisomal targeting (%) 1 ± 281 ALDP-GFP1 361 313 (86.7) * 1 ± 164 ALDP-GFP1 331 277 (83.7) * 1 ± 110 ALDP-GFP1 132 108 (81.8) * 282 ± 745 ALDP-GFP 218 0 (0) * 67 ± 164 ALDP-GFP 176 90 (51.1) 67 ± 134 ALDP-GFP 275 0 (0) * 78 ± 164 ALDP-GFP2 247 2 (0.8) * 87 ± 164 ALDP-GFP2 206 1 (0.5) * 67 ± 164 ALDP(F71S)-GFP3 363 143 (39.4) 67 ± 164 ALDP(F71V)-GFP3 203 90 (44.3) 67 ± 164 ALDP(R74W)-GFP3 218 89 (40.8) 67 ± 164 ALDP(R74G)-GFP3 277 123 (44.4) 67 ± 164 ALDP(L78F)-GFP3 315 103 (32.7) * 67 ± 164 ALDP(L81V)-GFP3 363 199 (54.8) 67 ± 164 ALDP(P84A)-GFP3 413 196 (47.5) 67 ± 164 ALDP-delLLR-GFP4 224 0 (0) * Total number of cells (n) analysed that were transfected with various ALDP-GFP fusion constructs. Login to comment