ABCC11 p.Asn844Gln
Predicted by SNAP2: | A: D (71%), C: D (80%), D: D (75%), E: D (80%), F: D (85%), G: D (71%), H: D (75%), I: D (80%), K: D (80%), L: D (85%), M: D (75%), P: D (85%), Q: D (71%), R: D (91%), S: D (63%), T: D (63%), V: D (71%), W: D (91%), Y: D (85%), |
Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Earwax, osmidrosis, and breast cancer: why does on... FASEB J. 2009 Jun;23(6):2001-13. Epub 2009 Apr 21. Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, Sakai Y, Ota I, Lezhava A, Hayashizaki Y, Niikawa N, Ishikawa T
Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?
FASEB J. 2009 Jun;23(6):2001-13. Epub 2009 Apr 21., [PMID:19383836]
Abstract [show]
One single-nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in the ABCC11 gene determines the type of earwax. The G/G and G/A genotypes correspond to the wet type of earwax, whereas A/A corresponds to the dry type. Wide ethnic differences exist in the frequencies of those alleles, reflecting global migratory waves of the ancestors of humankind. We herein provide the evidence that this genetic polymorphism has an effect on the N-linked glycosylation of ABCC11, intracellular sorting, and proteasomal degradation of the variant protein. Immunohistochemical studies with cerumen gland-containing tissue specimens revealed that the ABCC11 WT protein was localized in intracellular granules and large vacuoles, as well as at the luminal membrane of secretory cells in the cerumen gland, whereas granular or vacuolar localization was not detected for the SNP (Arg180) variant. This SNP variant lacking N-linked glycosylation is recognized as a misfolded protein in the endoplasmic reticulum and readily undergoes ubiquitination and proteasomal degradation, which determines the dry type of earwax as a mendelian trait with a recessive phenotype. For rapid genetic diagnosis of axillary osmidrosis and potential risk of breast cancer, we developed specific primers for the SmartAmp method that enabled us to clinically genotype the ABCC11 gene within 30 min.
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No. Sentence Comment
73 The resulting expression construct [ABCC11 WT-pcDNA3.1/ Hygro(-)] was used as the template for site-directed mutagenesis to obtain ABCC11 variants, i.e., N838Q, N844Q, and N838Q/N844Q.
X
ABCC11 p.Asn844Gln 19383836:73:161
status: NEWX
ABCC11 p.Asn844Gln 19383836:73:178
status: NEW75 To generate the N838Q/N844Q variant, ABCC11 N838Q- pcDNA3.1/Hygro(-) was used as the template.
X
ABCC11 p.Asn844Gln 19383836:75:22
status: NEW165 Substitution of both Asn838 and Asn844 to Gln residues completely diminished N-linked glycosylation of the ABCC11 WT (Fig. 5B), demonstrating that these two Asn residues are N-linked glycosylation sites in the ABCC11 WT protein.
X
ABCC11 p.Asn844Gln 19383836:165:32
status: NEW198 B) Effect of substitution of Asn838 and Asn844 to Gln on N-linked glycosylation status of ABCC11.
X
ABCC11 p.Asn844Gln 19383836:198:40
status: NEW74 The resulting expression construct [ABCC11 WT-pcDNA3.1/ Hygro(afa;)] was used as the template for site-directed mutagenesis to obtain ABCC11 variants, i.e., N838Q, N844Q, and N838Q/N844Q.
X
ABCC11 p.Asn844Gln 19383836:74:167
status: NEWX
ABCC11 p.Asn844Gln 19383836:74:184
status: NEW76 To generate the N838Q/N844Q variant, ABCC11 N838Q- pcDNA3.1/Hygro(afa;) was used as the template.
X
ABCC11 p.Asn844Gln 19383836:76:22
status: NEW166 Substitution of both Asn838 and Asn844 to Gln residues completely diminished N-linked glycosylation of the ABCC11 WT (Fig. 5B), demonstrating that these two Asn residues are N-linked glycosylation sites in the ABCC11 WT protein.
X
ABCC11 p.Asn844Gln 19383836:166:32
status: NEW199 B) Effect of substitution of Asn838 and Asn844 to Gln on N-linked glycosylation status of ABCC11.
X
ABCC11 p.Asn844Gln 19383836:199:40
status: NEW