ABCMdb

ABCD1 p.Gly512Ser

None has been submitted yet.

Publications

PMID: 8651290 [PubMed] Feigenbaum V et al: "Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy."

No. Sentence Comment

76 58:1135-1144, 1996 Table 2 Mutations in the ALD Gene in Studied Patients AMINO ACID MUTATIONSb HOMOLOGUE INd KINDRED CLINICAL LOCALIZATION AMINO ACID ALDP BY NUMBER PHENOTYPEa DNA CpG Exon IN PROTEINC ALTERATION h/m ALDRP hPMP70 IF/WB' CALD, AMN CALD CALD CALD, AS AD CALD, AMN CALC AD AD AD ALMD CALD CALD, AMN CALD CALD, AMN, AD AMN ALMD CALD ALMD CALD AMN ALD AD, AMN, AS CALD, AS CALD CALD AD CALD AMN, ALMD CALD CALD AMN, ALMD CALD CALD, AMN, ALMD CALD CALD, ALMD, AS ALMD CALD AMN CALD, AMN AD AD AMN CALD G416A Ins T524 C679T C679T C700T C709G G732A A829G C840T Del TA927-28 A928G A985T A1048G DeIGC1080-81 C1174T G1266A ins C1521 1636delC DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 ins TGG 1848 G 1920 A C1938T C1938T G1950A C2065T C2065T C2065T C2065T C2065G G 2166+1 A T2202C DelGC 2335 C2364T C2364T No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found 1 1 + 1 + 1 1 1 + 1 1 + 1 1 1 1 1 1 1 + 1 3 4 S 5 S S S 6 + 6 + 6 6 + 7 + 7 + 7 + 7 + 7 + 7 8 9 9 9 W10 X Frameshift at L46 TMS2 S98L TMS2 S98L T1OSI S108W G116R TMS3 N148S TMS3 R152C Frameshift at Y180 Y181C TMS4 D200V TMS4 D221G Frameshift at R231 P263L EAA-like A294T Frameshift at V378 Frameshift at T416 Frameshift at E471 Frameshift at E471 Frameshift at E471 Frameshift at E471 ins val 491 Walker A G512S Walker A R518W Walker A R518W G 522 W P560L P560L P560L P560L P56OR Splice at G593 Walker B S606P Frameshift at D649 R660W R660W Absent Not done S A Present S A Present T T Absent S D Decreased G T Absent N N Present R K Present Absent Y Y Not done D D Not done D D Absent Absent P R Decreased A A Not done Absent Absent Absent Absent Absent Absent Absent G G Absent R R Absent R R Decreased G E Absent P P Decreased P P Decreased P P Decreased P P Absent P P Absent Not done S S Absent Absent R R Absent R R Absent Not done Absent Absent Absent Present Absent Absent a CALD = cerebral ALD (5-15 years); AMN = adrenomyeloneuropathy; ALMD = adrenomyeloneuropathy with cerebral involvement; AD = Addison disease; AS = Asymptomatic. Login to comment
131 Lane 1, protein markers; lane 2, control; lane 3, patient 18 (S108W); lane 4, patient 32 (P263L); lane 5, patient 5 (P560L); lane 6, patient 4 (G116R); lane 7, patient 19 (D221G); lane 8, patient 33 (S98L); lane 9, patient 78 (S606P); lane 10, patient 3 (no mutation found); lane 11, patient 37 (P560L); lane 12, patient 22 (R660W); lane 13, control; lane 14, patient 39 (T1051); lane 15, patient 4 (G116R); lane 16, patient 43 (frameshift at Y180); lane 17, patient 5 (P560L); lane 18, patient 59 (G512S); lane 19, patient 29 (frameshift at D649); lane 20, patient 69 (P560L); lane 21, patient 19 (D221G); lane 22, patient 64 (W1OX); lane 23, patient 63 (frameshift at R231); lane 24, patient 52 (no mutation found); lane 25, patient 61 (frameshift at E471); and lane 26, patient 83 (G522W). Login to comment
144 Four missense mutations (G512S, R518W, G522W, and S606P) were found in the ATP-binding domain. Login to comment
145 Three of these mutations (G512S, G522W, and S606P) affect amino acid residues that are identical among other ABC transporters (see fig. 4 in Mosser et al. 1993 and fig. 1 in Fanen et al. 1994). Login to comment
172 Missense mutations leading to a lack of ALDP included three mutations located in the ATP-binding domain (G512S, G522W, and S606P). Login to comment
173 Four missense mutations (S108W, P263L, R518W, and P560L) resulted in decreased ALDP immunoreactivity reflecting likely instability and/or partial deficiency in the peroxisomal targeting of ALDP. Login to comment
75 58:1135-1144, 1996 Table 2 Mutations in the ALD Gene in Studied Patients AMINO ACID MUTATIONSb HOMOLOGUE INd KINDRED CLINICAL LOCALIZATION AMINO ACID ALDP BY NUMBER PHENOTYPEa DNA CpG Exon IN PROTEINC ALTERATION h/m ALDRP hPMP70 IF/WB' CALD, AMN CALD CALD CALD, AS AD CALD, AMN CALC AD AD AD ALMD CALD CALD, AMN CALD CALD, AMN, AD AMN ALMD CALD ALMD CALD AMN ALD AD, AMN, AS CALD, AS CALD CALD AD CALD AMN, ALMD CALD CALD AMN, ALMD CALD CALD, AMN, ALMD CALD CALD, ALMD, AS ALMD CALD AMN CALD, AMN AD AD AMN CALD G416A Ins T524 C679T C679T C700T C709G G732A A829G C840T Del TA927-28 A928G A985T A1048G DeIGC1080-81 C1174T G1266A ins C1521 1636delC DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 DelAG 1801-02 ins TGG 1848 G 1920 A C1938T C1938T G1950A C2065T C2065T C2065T C2065T C2065G G 2166+1 A T2202C DelGC 2335 C2364T C2364T No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found No mutation found 1 1 + 1 + 1 1 1 + 1 1 + 1 1 1 1 1 1 1 + 1 3 4 S 5 S S S 6 + 6 + 6 6 + 7 + 7 + 7 + 7 + 7 + 7 8 9 9 9 W10 X Frameshift at L46 TMS2 S98L TMS2 S98L T1OSI S108W G116R TMS3 N148S TMS3 R152C Frameshift at Y180 Y181C TMS4 D200V TMS4 D221G Frameshift at R231 P263L EAA-like A294T Frameshift at V378 Frameshift at T416 Frameshift at E471 Frameshift at E471 Frameshift at E471 Frameshift at E471 ins val 491 Walker A G512S Walker A R518W Walker A R518W G 522 W P560L P560L P560L P560L P56OR Splice at G593 Walker B S606P Frameshift at D649 R660W R660W Absent Not done S A Present S A Present T T Absent S D Decreased G T Absent N N Present R K Present Absent Y Y Not done D D Not done D D Absent Absent P R Decreased A A Not done Absent Absent Absent Absent Absent Absent Absent G G Absent R R Absent R R Decreased G E Absent P P Decreased P P Decreased P P Decreased P P Absent P P Absent Not done S S Absent Absent R R Absent R R Absent Not done Absent Absent Absent Present Absent Absent a CALD = cerebral ALD (5-15 years); AMN = adrenomyeloneuropathy; ALMD = adrenomyeloneuropathy with cerebral involvement; AD = Addison disease; AS = Asymptomatic. Login to comment

PMID: 11748843 [PubMed] Kemp S et al: "ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations."

No. Sentence Comment

280 For two missense mutations located in functional regions of the ATP-binding domain it was demonstrated that the mutations resulted in either decreased ATP-binding capacity (S606L) or reduced ATPase activity (G512S) [Roerig et al., 2001]. Login to comment

PMID: 21488864 [PubMed] Kemp S et al: "Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance."

No. Sentence Comment

259 Two X-ALD causing missense mutations located in the ATP-binding domain of ALDP resulted in either decreased ATP-binding capacity (p.Ser606Leu) or reduced ATPase activity (p.Gly512Ser), when analysed in the context of recombinant nucleotide binding domains (Roerig et al., 2001). Login to comment

PMID: 7494402 [PubMed] Moser HW et al: "Komrower Lecture. Adrenoleukodystrophy: natural history, treatment and outcome."

No. Sentence Comment

29 Mutation Predicted consequence Phenotype a 1 310 C -4 T R104C AMN 2 420 G -4 A A140T Cer 3 454 C -4 T R152C Cer 4 545 G -4 C R182P Addis 5 692 G -4 C Addis 693-4 del GG Frameshift at AA 231 6 770 G -4 T G277W Cer 7 1166 G -4 A R389H AMN 8 I224 G -4 A Spl mutation at AA 408 AMN 9 1389 G --+ A R464 stop AMN 10 1411 ins A Frameshift at AA 470 AMN 11 1412-3 del AA Frameshift at AA 470 Cer 12 1415-6 del AG Frameshift at AA 472 Cer 13 1415-6 del AG Frarneshift at AA 472 Cer 14 1415-6 del AG Frameshift at AA 472 Addis 15 1415-6 del AG Frameshift at AA 472 AMN 16 t415-6 del AG Frameshift at AA 472 AMN 17 1415-6 del AG Frameshift at AA 472 Cer 18 1534 G -4 A G512S Cer 19 1698 T -4 A M567K AMN 20 t817 C -4 T $604F Addis 1548 G -4 A L516L 21 1850 G -+ A R617H AMN 22 1978 G -4 A R660W AMN ~Cer=childhoodcerebralALD; Addis=Addisondisease the multiple binding sites on bovine albumin for shorter-chain fatty acids, there is only a single binding site for C26:0. Login to comment

PMID: 17092750 [PubMed] Kemp S et al: "X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment."

No. Sentence Comment

57 ATP-binding and ATPase activity has been demonstrated for ALDP [17], and Roerig and coworkers demonstrated that two disease causing missense mutations located in the ATP-binding domain resulted in either decreased ATP-binding capacity (Ser606Leu), or reduced ATPase activity (Gly512Ser) [18]. Login to comment
56 ATP-binding and ATPase activity has been demonstrated for ALDP [17], and Roerig and coworkers demonstrated that two disease causing missense mutations located in the ATP-binding domain resulted in either decreased ATP-binding capacity (Ser606Leu), or reduced ATPase activity (Gly512Ser) [18]. Login to comment

PMID: 17973979 [PubMed] Kim WS et al: "Role of ATP-binding cassette transporters in brain lipid transport and neurological disease."

No. Sentence Comment

208 Two ABCD1 mutations associated with X-ALD (Ser606Leu and Gly512Ser) result in decreased ATP binding and reduced ATPase activity, respectively, thereby indicating that an energy dependent transport activity is crucial to the function of ABCD1 (Roerig et al. 2001). Login to comment
212 Two ABCD1 mutations associated with X-ALD (Ser606Leu and Gly512Ser) result in decreased ATP binding and reduced ATPase activity, respectively, thereby indicating that an energy dependent transport activity is crucial to the function of ABCD1 (Roerig et al. 2001). Login to comment

PMID: 9212180 [PubMed] Imamura A et al: "Two novel missense mutations in the ATP-binding domain of the adrenoleukodystrophy gene: immunoblotting and immunocytological study of two patients."

No. Sentence Comment

63 G512S, R518W and G522W (Feigenbaum et al. 1996). Login to comment

PMID: 7561948 [PubMed] Yasutake T et al: "Molecular analysis of X-linked adrenoleukodystrophy patients."

No. Sentence Comment

85 The mutation gave a single amino acid substitution to serine from 512glycine (G512S), which was located in the ATP-binding cassette motif, and conserved among the ABC transporters (Fig. 4). Login to comment
115 So far, however, the #240 #225 G512S P534L 486 - 667 5. Login to comment
84 The mutation gave a single amino acid substitution to serine from 512glycine (G512S), which was located in the ATP-binding cassette motif, and conserved among the ABC transporters (Fig. 4). Login to comment
114 So far, however, the #240 #225 G512S P534L 486 - 667 5. Login to comment

PMID: 21068741 [PubMed] Shimozawa N et al: "X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan."

No. Sentence Comment

21 Although most probands with ALD identified by us had a unique gene mutation, 6 missense mutations (p.Gly266Arg, p.Arg401Gln, p.Gly512Ser, p.Ser514Ile, p.Arg617His and p.Arg660Trp) and 1 frame-shift mutation (p.Gln472fs) were detected in two or three families (* in Figure 2). Login to comment

PMID: 17542813 [PubMed] Takahashi N et al: "Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations."

No. Sentence Comment

255 In an early study, Yamada et al. showed that degradation of endogenous mutant ALDP (G512S and R660W) as well as wild type ALDP was suppressed by E-64 or leupeptin, which inhibit thiol proteases including lysosomal cathepsins and cytosolic calcium-activated neutral proteases in human fibroblasts (Yamada et al. 1997). Login to comment

PMID: 9242200 [PubMed] Korenke GC et al: "Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings."

No. Sentence Comment

120 Sixteen of these mutations have been published before (11, 21); the remaining 12 mutations comprise nine missense mutations (A141T, Y281H, R389H, G512S, P543L, R554H, Y559H, R617H, R679R), two frame-shift mutations (del 740, del 2132) and one splice site mutation (ins 8 bp 2252). Login to comment

PMID: 12175782 [PubMed] Guimaraes CP et al: "Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene."

No. Sentence Comment

109 After sequencing two missense mutations-R236H and G512S-were found. Login to comment

PMID: 12530690 [PubMed] Gartner J et al: "Functional characterization of the adrenoleukodystrophy protein (ALDP) and disease pathogenesis."

No. Sentence Comment

41 The mutant constructs included missense mutations of patients with X-ALD in the nucleotide binding fold regions Walker A and 19mer (ALDP-NBF-G512S, ALDP-NBF-Q544R, ALDP-NBF-P560L, ALDP-NBF-R591Q, ALDP-NBF-S606L, and ALDP-NBF-D629H) and corresponding mutations in another ABC transporter in the peroxisome membrane, the 70 kDa peroxisomal membrane protein (PMP70; PMP70-NBF-G478R, PMP70- NBF-S572I). Login to comment
59 This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc. MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016 EndocrResDownloadedfrominformahealthcare.combyUniversityofNorthCarolinaon03/06/12 patient mutation G512S in the ALD gene reduces considerable ATPase activity. Login to comment
79 The missense mutations of the first group like G512S in the ALD gene reduce considerable ATPase activity. Login to comment

PMID: 20626744 [PubMed] Kemp S et al: "Biochemical aspects of X-linked adrenoleukodystrophy."

No. Sentence Comment

47 ALDP is an integral peroxisomal membrane protein with the nucleotide-binding domain located toward the cytoplasmic surface of the peroxisomal membrane (14).ATP-binding andATPase activity has been demonstrated for ALDP (71), and Roerig et al demonstrated that two disease causing missense mutations located in the ATP-binding domain resulted in either decreased ATP-binding capacity (p.Ser606Leu) or reduced ATPase activity (p.Gly512Ser) (64). Login to comment

PMID: 21300044 [PubMed] Lan F et al: "Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations."

No. Sentence Comment

99 Pedigree Number of patient Number of carriere Phenotype of patient Base change Amino acid change Position of mutation Feature of mutation Prenatal diagnosis 1 1 2 AdolCALD 1225GNT R280L Exon 1 Missense 2 1 1 CCALD 1909CNT P508L Exon 6 Missense 3 4 3 CCALD 1987CNG P534R Exon 6 Missense Y 4 1 1 CCALD 1182GNA G266R Exon 1 Missense 5 1a +1b 1 CCALD 2235CNG R617G Exon 8 Missense Y 6 1+1a +1c 1 CCALD 1414GNT G343V Exon 2 Missense 7 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift 8 1+1b 1 CCALD 2235CNT R617C Exon 8 Missense Yh 9 1 1 CCALD 2065CNT P560L Exon 7 Y 10 1+1a 2+1b CCALD [709 NA; 1161CNT] [S108X; R259W] Exon 1 Nonsense; Missense Y 11 1 1 CCALD 1126ins GCCATCG fs I246 Exon 1 Frameshift 12 1 1 CCALD 2113TNC L576P Exon 7 Missense 13 1a +2c 3 CCALD 807GNA A141T Exon 1 Missense 14 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 15 1 1+1b CCALD 915CNA Q177X Exon 1 Nonsense Yh 16 1+1a 1 CCALD 1588GNA R401Q Exon 3 Missense 17 1 1 CCALD 1212 ANG K276E Exon 1 Missense Y 18 1 1 CCALD 907 ANG Y174C Exon 1 Missense 19 1 2 CCALD 2190 ANT K602X Exon 8 Nonsense 20 1 1 CCALD 1326GNC A314P Exon 2 Missense 21 1 1 CCALD 828 ANG N148D Exon 1 Missense Y 22 1 1 CCALD 1588GNA R401Q Exon 3 Missense Y 23 1 0f CCALD 2278GNA C631Y Exon 9 Missense 24 1a 1 CCALD 1008insG fs S207 Exon 1 Frameshift Y 25 1 0f CCALD 1920GNA G512S Exon 6 Missense 26 1+1c 3 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 27 1+1b 1 CCALD [1035ANG; 1853GNA] [K217E; V489V] Exon 1 Missense; same sense Y 28 1+3d 4 AMNg 1234ANG H283R Exon 1 Missense 29 1+2a 3 CCALD 1233CNG H283D Exon 1 Missense 30 2 3 AMN; CCALD 656_57 delGA fs R89 Exon 1 Frameshift a patient or proband died at the time of referral; b fetus by prenatal diagnosis; c presymptomatic at the time of referral; d female heterozygote patient; e determined by molecular ananlysis or deduced by the fact that the carrier was the daughter of an X-ALD, or the mother of at least one X-ALD patients; f de novo mutation; g including three heterozygote female patients; h twice for two pregnancies. Login to comment

PMID: 9051655 [PubMed] Yamada T et al: "Protease inhibitors suppress the degradation of mutant adrenoleukodystrophy proteins but do not correct impairment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts."

No. Sentence Comment

3 We investigated the stability of mutant ALDP and found from pulse-chase experiments that the respective half-lives of the normal and mutant #140 (Gly512Ser) and #249 (Arg660Trp) were 72.6, 32.1 and 26.1 min, indicative that mutant ALDPs are less stable than normal ones. Login to comment
19 Two, #240 and #249, respectively had the missense mutations Gly512Ser (G1920A) and Arg660Trp (C2364T). Login to comment
37 Normal and mutant (Gly512Ser or Arg660Trp) ALDP cDNAs synthesized by reverse-transcription and PCR were inserted into the expression vector, pCAGGS (8). Login to comment
82 Gly512Ser and Arg660Trp mutations in their patients resulted in a complete lack of immunoreactivity, as they did in our patients (2). Login to comment
94 For example, Gly512Ser mutation, which is localized in the ATP-binding domain, may critically affect such functions. Login to comment

PMID: 7581394 [PubMed] Kok F et al: "Mutational analysis of patients with X-linked adrenoleukodystrophy."

No. Sentence Comment

131 3' deletion 3' deletion 3' deletion 3' deletion R104C A141T R152C R182P Frameshift at AA 231 G277W R389H Spl mutation at AA 408 Q466 stop Frameshift at AA 470 Frameshift at AA 470 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 Frameshift at AA 472 G512S M566K S606L L516L R617H R660W - - Exons 3-10 Exons 7-10 Exons 8-10 Exons 7-10 33 Anglos 5 Scott 8 Anglos 7 Anglos 11 Jewish 36 Irish 51 Italian 37 Filipino 28 Anglos 23 Anglos 11 Anglos 8 Anglos 40 Italian 22 German 4 Anglos 5 black 8 Anglos 31 Anglos 10 Anglos 28 Anglos 22 Italian 8 German 35 German 7 Hispanic 28 German 24 Anglos 18 Jewish 9 Hispanic AMNa C E R ~ Cer Add' Cer AMN AMN AMN AMN Cer Cer Cer Add AMN AMN Cer Cer Cer AMN Add AMN AMN Cer AMN Cer AMN AMN AMN 5 Cer,AMN,Add 4 Cer,AMN 1 Cer 5 Cer,AMN,Add 1 4 2 1 2 2 5 Adopted 5 2 15 1 13 2 2 1 Cer AMN AMN,Add AMN Cer,AMN Cer,AMN Cer,AMN,Add ? Login to comment
234 Four mutations were found within the ATP bind- ing domain, one in Walker A (G512S), one in Walker B (R617H), one in the highly conserved sequence preceding Walker B (S606L),and one in the middle of the domain. Login to comment

PMID: 11248239 [PubMed] Roerig P et al: "Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters."

No. Sentence Comment

5 Mutations in conserved residues of the nucleotidases (PMP70: G478R, S572I; ALDP: G512S, S606L) altered ATPase activity. Login to comment
24 For the mutant constructs we selected X-ALD patient mutations in highly conserved residues in the Walker A and 19-mer region of the NBF of ALDP (G512S and S606L) and the corresponding PMP70 mutations (G478R and S572I). Login to comment
84 We mutated the central glycine in the Walker A motif of PMP70 and ALDP making the evolutionary severe substitutions G478R and G512S. Login to comment
85 Additionally, we changed the conserved serine in the 19-mer motif of PMP70 and ALDP to isoleucine (S572I) and leucine (S606L), respectively. Login to comment
88 The K-subunit of L-galactosidase (L-Protein Synthetic oligonucleotide Mutation ALDP 5P-CCCCAATGGCTGCAGCAAGAGCTCCC-3P G512S 5P-GGATCCGGACAGGGAGCTCTTGCTGCAGC-3P ALDP 5P-ACTGGAAGGACGTCCTGTTGGG-3P S606L 5P-CGCCACCCAACAGGACGTCCTTCC-3P PMP70 5P-GGCTGCAGAAAGAGTTCACTTTTCCG-3P G478R 5P-GGCCATAATTCACCAAGAACACGGAAA AGTGAACTCTTTCTG-3P PMP70 5P-GACGTACTCATTGGTGGAG-3P S572I 5P-CCACCAATGAGTACGTCCATCCAATCC-3P gal) in fusion with the MBP was used as a control. Login to comment
117 G512S and S606L cause X-ALD. Login to comment
136 The S606L and G478R mutants have a decreased ATP binding a¤nity while the G512S and S572I mutants decrease the maximum velocity of ATPase activity. Login to comment
141 When testing the NBF of wild type ALDP and wild type PMP70 as well as the NBF of the mutant ALDP (G512S) against full length ALDP or full length PMP70, only background levels were detected (data not shown). Login to comment
169 The missense mutation G512S in the ALD gene causes X-ALD and reduces considerable ATPase activity in our recombinant polypeptide models. Login to comment
182 Previous studies on MDR suggest that the ATPase activity of the native protein Table 1 Kinetic parameters of ATPase activity in wild type and mutant ALDP and PMP70 NBF fusion proteins Fusion protein KM (WM) Vmax (nmol/Wmol NBF/min) Speci'c activity (1033 U/mg) ALDP (wild type) 11.5 þ 0.97 641.9 þ 10.7 10.0 þ 0.17 ALDP (G512S) 17.9 þ 1.23 279.3 þ 4.2 4.4 þ 0.06 ALDP (S606L) 45.6 þ 2.40 666.0 þ 8.7 10.4 þ 0.14 PMP70 (wild type) 8.2 þ 0.52 580.8 þ 6.7 9.0 þ 0.10 PMP70 (G478R) 161.8 þ 34.40 641.2 þ 28.2 10.0 þ 0.44 PMP70 (S572I) 9.9 þ 0.82 298.1 þ 4.7 4.6 þ 0.07 The kinetic data of all fusion proteins are mean values and standard deviations of 15^20 measurements at various protein concentrations using at least two distinct protein preparations. Login to comment
89 The K-subunit of L-galactosidase (LProtein Synthetic oligonucleotide Mutation ALDP 5P-CCCCAATGGCTGCAGCAAGAGCTCCC-3P G512S 5P-GGATCCGGACAGGGAGCTCTTGCTGCAGC-3P ALDP 5P-ACTGGAAGGACGTCCTGTTGGG-3P S606L 5P-CGCCACCCAACAGGACGTCCTTCC-3P PMP70 5P-GGCTGCAGAAAGAGTTCACTTTTCCG-3P G478R 5P-GGCCATAATTCACCAAGAACACGGAAA AGTGAACTCTTTCTG-3P PMP70 5P-GACGTACTCATTGGTGGAG-3P S572I 5P-CCACCAATGAGTACGTCCATCCAATCC-3P gal) in fusion with the MBP was used as a control. Login to comment
118 G512S and S606L cause X-ALD. Login to comment
137 The S606L and G478R mutants have a decreased ATP binding a&#a4;nity while the G512S and S572I mutants decrease the maximum velocity of ATPase activity. Login to comment
142 When testing the NBF of wild type ALDP and wild type PMP70 as well as the NBF of the mutant ALDP (G512S) against full length ALDP or full length PMP70, only background levels were detected (data not shown). Login to comment
170 The missense mutation G512S in the ALD gene causes X-ALD and reduces considerable ATPase activity in our recombinant polypeptide models. Login to comment
183 Previous studies on MDR suggest that the ATPase activity of the native protein Table 1 Kinetic parameters of ATPase activity in wild type and mutant ALDP and PMP70 NBF fusion proteins Fusion protein KM (WM) Vmax (nmol/Wmol NBF/min) Speci'c activity (1033 U/mg) ALDP (wild type) 11.5 &#fe; 0.97 641.9 &#fe; 10.7 10.0 &#fe; 0.17 ALDP (G512S) 17.9 &#fe; 1.23 279.3 &#fe; 4.2 4.4 &#fe; 0.06 ALDP (S606L) 45.6 &#fe; 2.40 666.0 &#fe; 8.7 10.4 &#fe; 0.14 PMP70 (wild type) 8.2 &#fe; 0.52 580.8 &#fe; 6.7 9.0 &#fe; 0.10 PMP70 (G478R) 161.8 &#fe; 34.40 641.2 &#fe; 28.2 10.0 &#fe; 0.44 PMP70 (S572I) 9.9 &#fe; 0.82 298.1 &#fe; 4.7 4.6 &#fe; 0.07 The kinetic data of all fusion proteins are mean values and standard deviations of 15^20 measurements at various protein concentrations using at least two distinct protein preparations. Login to comment

PMID: 17202797 [PubMed] Takahashi N et al: "[Adrenoleukodystrophy: structure and function of ALDP, and intracellular behavior of mutant ALDP with naturally occurring missense mutations]."

No. Sentence Comment

49 変異型 ALDP の分解過程の解析新生タンパク質が正しいフォールディングを受けることは,そのタンパク質の正常な機能発現のために必須である．遺伝子変異などが存在すると,タンパク質がミスフォールディングされる．このミスフォールドタンパクが細胞外へ分泌されたり,細胞内に蓄積したりすると生体にとって極めて有害になるため,このようなタンパクはプロテアソーム,リソソーム等によって迅速に分解される．ちなみに,嚢胞性線維症の原因タンパク質 CFTR は細胞膜イオンチャネルとして機能する ABC タンパク質であるが,変異 CFTR は小胞体膜からプロテアソームにリクルートされ分解されることが報告されている．32,33) しかしながら,変異型 ALDP を始めとして,ペルオキシソーム膜タンパク質についての解析はほとんど行われていない．変異型 ALDP の一過性発現と安定過剰発現実験より,ALDP(S606L, R617H, H667D, R104C)は, プロテアーゼにより分解されていると推定された．そこで,ALDP-GFP(H667D)を発現している CHO 細胞に各種プロテアーゼ阻害剤を処理し,解析を行った．その結果,プロテアソーム阻害剤である lactacystin を処理した細胞では ALDP-GFP 及び ALDP のバンドが出現した ( Fig. 4 )．一方 , leupeptin, AEBSF, E64d には効果がなかった．また他のプロテアソーム阻害剤である MG132 も有効であった．さらにプロテアソーム阻害剤により分解を逃れた変異型 ALDP-GFP(H667D)の細胞内局在を蛍光抗体法で観察すると,ペルオキシソームに局在していることが確認された．一方,変異型 ALDP(R104C)のフラグメント化は上記プロテアーゼ処理では阻害されなかった．さらに ALD 患者由来細胞の内因性変異 ALDP の分解とプロテアソーム分解系の関与について確認するため,変異型 ALDP(R617H)を持つ患者由来線維芽細胞を用いてタンパク分解の阻害実験を行った．その結果,lactacystin と MG132 処理により, ALDP のバンドが出現した．以上の結果より,ペルオキシソーム膜上にはミスフォールドしたタンパク質を認識する仕組みが存在し,プロテアソーム及び他のプロテアーゼを介して排除していることが示唆された．一方,山田らは ALD 患者線維芽細胞を［35 S］メチオニンでパルスチェイスすることにより,変異型 ALDP(G512S, R660W)の分解が E-64 と leupepu- tin により抑制されることを報告している．34) 彼らの実験ではプロテアソーム阻害剤については実験していないので,プロテアソームの関与は不明であるが,変異型 ALDP の分解には,複数のプロテアーゼが関与している可能性がある． 7. Login to comment
46 ᜕ᶒɂb; ALDP Ĳe;ᑖYe3;Έe;a0b;Ĳe;Ye3;᪆ Ab0;˯f;bf;f3;d1;af;cea;İc;b63;௱௤d5;a9;fc;eb;c7;a3;f3;b0;ఔ5d7;௫ Ĵb;௭௼Ĳf;,ıd;Ĳe;bf;f3;d1;af;cea;Ĳe;b63;e38;Ĳa;a5f;Pfd;˿a;Ife;Ĳe;ıf;ఉ Ĳb;fc5;♐௻௢Ĵb;&#ff0e;΋a;f1d;b50;᜕ᶒĲa;௽İc;b58;ᙠ௳Ĵb;௼,bf;f3; d1;af;cea;İc;df;b9;d5;a9;fc;eb;c7;a3;f3;b0;௯Ĵc;Ĵb;&#ff0e;௭Ĳe;df;b9;d5; a9;fc;eb;c9;bf;f3;d1;af;İc;d30;Pde;᜜ఆᑖccc;௯Ĵc;ıf;Ĵa;,d30;Pde;ᑁ Ĳb;Tc4;a4d;௱ıf;Ĵa;௳Ĵb;௼˯f;f53;Ĳb;௼௷௺ᬿఉ௺ᨵbb3;Ĳb;Ĳa;Ĵb; ıf;ఉ,௭Ĳe;ఐ௦Ĳa;bf;f3;d1;af;Ĳf;d7;ed;c6;a2;bd;fc;e0;,ea;bd; bd;fc;e0;b49;Ĳb;ఐ௷௺fc5;΅f;Ĳb;ᑖYe3;௯Ĵc;Ĵb;&#ff0e;௵Ĳa;ĳf;Ĳb;,8a2; Pde;ឋdda;dad;Kc7;Ĳe;țf;8e0;bf;f3;d1;af;cea; CFTR Ĳf;d30;Pde;̳c;a4;aa; f3;c1;e3;cd;eb;௼௱௺a5f;Pfd;௳Ĵb; ABC bf;f3;d1;af;cea;௻௢Ĵb; İc;,᜕ᶒ CFTR Ĳf;c0f;Pde;f53;̳c;İb;఑d7;ed;c6;a2;bd;fc;e0;Ĳb; ea;af;eb;fc;c8;௯Ĵc;ᑖYe3;௯Ĵc;Ĵb;௭௼İc;ᛇȠa;௯Ĵc;௺௤ Ĵb;&#ff0e; 32,33) ௱İb;௱Ĳa;İc;఑,᜕ᶒɂb; ALDP ఔ;cb;ఉ௼௱ ௺,da;eb;aa;ad;b7;bd;fc;e0;̳c;bf;f3;d1;af;cea;Ĳb;௸௤௺Ĳe;Ye3;᪆ Ĳf;ĳb;௼క௽ʹc;Ĵf;Ĵc;௺௤Ĳa;௤&#ff0e; ᜕ᶒɂb; ALDP Ĳe;e00;Έe;ឋ˿a;Ife;௼b89;b9a;Έe;ᒖ˿a;Ife;b9f; a13; ఐĴa;,ALDP (S606L, R617H, H667D, R104C) Ĳf;, d7;ed;c6;a2;fc;bc;Ĳb;ఐĴa;ᑖYe3;௯Ĵc;௺௤Ĵb;௼?a8;b9a;௯Ĵc;ıf;&#ff0e; ıd;௭௻,ALDP-GFP(H667D)ఔ˿a;Ife;௱௺௤Ĵb; CHO d30;Pde;Ĳb;ᔜa2e;d7;ed;c6;a2;fc;bc;σb;bb3;ᒐఔ3e6;ᳮ௱,Ye3; ᪆ఔʹc;௷ıf;&#ff0e;ıd;Ĳe;d50;ʧc;,d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐ௻௢ Ĵb; lactacystin ఔ3e6;ᳮ௱ıf;d30;Pde;௻Ĳf; ALDP-GFP 5ca;ఁ ALDP Ĳe; d0; f3; c9; İc; 3fa; Ife; ௱ ıf; ( Fig. 4 ) &#ff0e; e00; Ab9; , leupeptin, AEBSF, E64d Ĳb;Ĳf;4b9;ʧc;İc;Ĳa;İb;௷ıf;&#ff0e;ĳe; ıf;ed6;Ĳe;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐ௻௢Ĵb; MG132 ఊᨵ4b9; ௻௢௷ıf;&#ff0e;௯఑Ĳb;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐĲb;ఐĴa;ᑖYe3; ఔ⌫Ĵc;ıf;᜕ᶒɂb; ALDP-GFP(H667D)Ĳe;d30;Pde;ᑁc40; ᙠఔVcd;ᐝᢙf53;cd5;௻Yb3;bdf;௳Ĵb;௼,da;eb;aa;ad;b7;bd;fc;e0;Ĳb; c40;ᙠ௱௺௤Ĵb;௭௼İc;Nba;a8d;௯Ĵc;ıf;&#ff0e;e00;Ab9;,᜕ᶒɂb; ALDP (R104C) Ĳe;d5;e9;b0;e1;f3;c8;ᓄĲf;e0a;a18;d7;ed;c6;a2;fc; bc;3e6;ᳮ௻Ĳf;σb;bb3;௯Ĵc;Ĳa;İb;௷ıf;&#ff0e; ௯఑Ĳb; ALD <a3;ὅᵫᩭd30;Pde;Ĳe;ᑁ8e0;ឋ᜕ᶒ ALDP Ĳe;ᑖYe3;௼d7;ed;c6;a2;bd;fc;e0;ᑖYe3;cfb;Ĳe;_a2;e0e;Ĳb;௸௤௺Nba;a8d; ௳Ĵb;ıf;ఉ,᜕ᶒɂb; ALDP(R617H)ఔᢝ௸<a3;ὅᵫ ᩭdda;dad;Rbd;d30;Pde;ఔᵨ௤௺bf;f3;d1;af;ᑖYe3;Ĳe;σb;bb3;b9f; a13;ఔʹc; ௷ıf;&#ff0e;ıd;Ĳe;d50;ʧc;,lactacystin ௼ MG132 3e6;ᳮĲb;ఐĴa;, ALDP Ĳe;d0;f3;c9;İc;3fa;Ife;௱ıf;&#ff0e;ee5;e0a;Ĳe;d50;ʧc;ఐĴa;,da; eb;aa;ad;b7;bd;fc;e0;̳c;e0a;Ĳb;Ĳf;df;b9;d5;a9;fc;eb;c9;௱ıf;bf;f3;d1; af;cea;ఔa8d;b58;௳Ĵb;ed5;d44;ĳf;İc;b58;ᙠ௱,d7;ed;c6;a2;bd;fc;e0;5ca; ఁed6;Ĳe;d7;ed;c6;a2;fc;bc;ఔecb;௱௺᣸◀௱௺௤Ĵb;௭௼İc;̙a; ᖂ௯Ĵc;ıf;&#ff0e; e00;Ab9;,c71;ᵪ఑Ĳf; ALD <a3;ὅdda;dad;Rbd;d30;Pde;ఔ &#ff3b;35 S&#ff3d; e1;c1; aa;cb;f3;௻d1;eb;b9;c1;a7;a4;b9;௳Ĵb;௭௼Ĳb;ఐĴa;,᜕ᶒɂb; ALDP (G512S, R660W) Ĳe;ᑖYe3;İc; E-64 ௼ leupepu- tin Ĳb;ఐĴa;ᢓᑴ௯Ĵc;Ĵb;௭௼ఔᛇȠa;௱௺௤Ĵb;&#ff0e; 34) f7c;఑ Ĳe;b9f; a13;௻Ĳf;d7;ed;c6;a2;bd;fc;e0;σb;bb3;ᒐĲb;௸௤௺Ĳf;b9f; a13;௱ ௺௤Ĳa;௤Ĳe;௻,d7;ed;c6;a2;bd;fc;e0;Ĳe;_a2;e0e;Ĳf;e0d;ʔe;௻௢Ĵb; İc;,᜕ᶒɂb; ALDP Ĳe;ᑖYe3;Ĳb;Ĳf;,⋋ᦪĲe;d7;ed;c6;a2;fc; bc;İc;_a2;e0e;௱௺௤Ĵb;5ef;Pfd;ឋİc;௢Ĵb;&#ff0e; 7. Login to comment

PMID: 22479560 [PubMed] Pereira Fdos S et al: "Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy."

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24 Family/Index case Phenotype at diagnosis Mutation Exon/IVS Mutation type Effect on protein (cDNA) Effect on protein (mRNA) Protein localization Origin of mutations Origin of family 1/Female asymptomatic p.Gly512Ser (Feigenbaum V et al. 1996) E6 Missense c.1534G.A GGC.AGC NBF de novo Southern Brazil 2/Female asymptomatic p.Ser606Leu (Fanen P et al., 1994) E8 Missense c.1817C.T UCG.UUG NBF Inherited Southern Brazil 3/Male AMN p.Trp601X (Gartner J et al.,1998) E8 Stop codon c.1802C.A Truncated NBF Inherited Southern Brazil 4/Female asymptomatic p.Arg617His (Fanen P et al., 1994) E8 Missense c.1850G.A CGC.CAC NBF ND Southern Brazil 5/Male AMN p.Pro623Leu # E9 Missense c.1868C.T CCC.CUC NBF Inherited Southern Brazil 6/Male AO p.Trp326X (Barcelo A et al, 1996) E2 Stop codon c.978G.A Truncated TMD Inherited Southern Brazil 8/Female asymptomatic p.Glu577X # E7 Stop codon c.1729G.T Truncated NBF Inherited Southern Brazil 9/Male asymptomatic p.Arg554His (Smith KD et al., 1999) E7 Missense c.1661G.A CGU.CAU NBF Inherited Southern Brazil 10/Male CALD p.Arg518Gln (Imamura A et al., 1997) E6 Missense c.1553G.A CGG.CAG NBF Inherited Southern Brazil 11/Male AO p.Tyr33_Pro34fsX34 # E1A Frameshift+stop codon c.99_102delC Truncated - Inherited Southern Brazil 12/Female asymptomatic p.Gly266Arg (Fuchs S et al., 1994) E7 Missense c.1653insG Truncated TMD ND Southern Brazil 20/Male CALD p.Arg538fs # E6 Frameshift c.1614_1615dup27 Elonged NBF de novo Southern Brazil 21/Male CALD p.Ala232fsX64 # E2 Frameshift+stop codon c.696_697del11 Truncated TMD Inherited Southern Brazil 22/Male CALD p.Trp137fsX57 # E1B Frameshift+stop codon c.411_412insC Truncated TMD Inherited Northern Brazil 23/Male asymptomatic p.Trp679X (Waterham HR et al, 1998) E10 Stop codon c.2037G.A Truncated NBF ND Southern Brazil 24/Male AO p.Tyr296Cys (Takano H et al., 1999) E2 Missense c.887A.G UAU.UGU TMD Inherited Southern Brazil 27/Male CALD p.Leu628Glu # E9 Missense c.1883T.A CUG.GAG NBF Inherited Southern Brazil 29/Male CALD p.Pro546fsX? Login to comment

PMID: 23566833 [PubMed] Niu YF et al: "ABCD1 mutations and phenotype distribution in Chinese patients with X-linked adrenoleukodystrophy."

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74 Exon Nucleotide change Amino acid change Phenotype P1 None None None CCALD P2 7 c.1661G>A p.Arg554His CCALD P3 5 c.1477_1488 + 11del 23 p.Leu493_Arg496del Adolescent ALD P4 2 c.1028G>T p.Gly343Val CCALD P5 6 c.1553G>A p.Arg518Gln CCALD P6 5 c.1415_16delAG p.Gln472fsX83 CCALD P7 6 c.1534G>A p.Gly512Ser Adolescent ALD P8 7 c.1679C>T p.Pro560Leu CCALD P9 7 c.1772G>A p.Arg591Gln ACALD P10 5 c.1415_16delAG p.Gln472fsX83 ACALD Fig. 1. Login to comment

PMID: 26609365 [PubMed] Suryawanshi A et al: "An unusual presentation of X-linked adrenoleukodystrophy."

No. Sentence Comment

57 The diagnosis of X-ALD was then confirmed by gene testing with a hemizygous mutation in the ABCD1 gene (c.1534GOA(p.Gly512Ser)). Login to comment