ABCC11 p.Gly180His
| Predicted by SNAP2: | A: D (85%), C: D (95%), D: D (91%), E: D (95%), F: D (91%), H: D (91%), I: D (91%), K: D (91%), L: D (91%), M: D (91%), N: D (95%), P: D (95%), Q: D (85%), R: D (66%), S: D (75%), T: D (85%), V: D (91%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: 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
77 To substitute Gly180 to Arg, Lys, His, Asp, Glu, AL, or Pro in the ABCC11 WT protein, the codon (GGG) encoding the Gly residue in TM1 was changed by site-directed mutagenesis, as described above.
X
ABCC11 p.Gly180His 19383836:77:14
status: NEW167 To examine our hypothesis, we substituted Gly180 to Arg, Lys, His, Asp, Glu, AL, and Pro in the ABCC11 WT protein.
X
ABCC11 p.Gly180His 19383836:167:42
status: NEW78 To substitute Gly180 to Arg, Lys, His, Asp, Glu, AL, or Pro in the ABCC11 WT protein, the codon (GGG) encoding the Gly residue in TM1 was changed by site-directed mutagenesis, as described above.
X
ABCC11 p.Gly180His 19383836:78:14
status: NEW168 To examine our hypothesis, we substituted Gly180 to Arg, Lys, His, Asp, Glu, AL, and Pro in the ABCC11 WT protein.
X
ABCC11 p.Gly180His 19383836:168:42
status: NEW