Probing into the role of conserved N-glycosylation sites in the Tyrosinase glycoprotein family

N-linked glycosylation has a profound effect on the proper folding, oligomerization and stability of glycoproteins. These glycans impart many properties to proteins that may be important for their proper functioning, besides having a tendency to exert a chaperone-like effect on them. Certain glycosylation sites in a protein however, are more important than other sites for their function and stability. It has been observed that some N-glycosylation sites are conserved over families of glycoproteins over evolution, one such being the tyrosinase related protein family. The role of these conserved N-glycosylation sites in their trafficking, sorting, stability and activity has been examined here. By scrutinizing the different glycosylation sites on this family of glycoproteins it was inferred that different sites in the same family of polypeptides can perform distinct functions and conserved sites across the paralogues may perform diverse functions.

Strauss family portrait; Würzburg.

Seated front center is grandmother Ernestine Strauss nee Uhlfelder (died before 1914, second wife of Leopold (Laemmle) Strauss) surrounded by six grandchildren; Benno Strauss is standing far left

Studio portrait of the women of the Oppenheimer family.

l-r: Thekla Oppenheimer-Benedick, Jenny Oppenheimer-Frank, Fanny Oppenheimer and Adele Oppenheimer-Nathan

Studio portrait of the women of the Oppenheimer family.

l-r: Sisters Adele Oppenheimer-Nathan, Thekla Oppenheimer-Benedick, Jenny Oppenheimer-Frank and their mother Fanny Oppenheimer

Benno Strauss with unidentified family members; Edel-Str. 6, Würzburg.

Verso: handwritten correspondence

Portrait of brothers Moshe Chayim Eliasberg (on left) and Samuel Eliasberg playing chess watched by Moshe's son Mulek Eliasberg Portraits Family

Moshe Chayim Eliasberg died 1920; Samuel Eliasberg died 1929; Mulek Eliasberg, 1886-1942

Portrait of a family and their dog sitting in a park Portraits Family

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Portrait of brother, mother and sister of Max Rieser seated outdoors; Franzensbad Portraits Family

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Schloss and Schoeneberg family portrait on the occasion of the 80th birthday of Jeanette Bildesheim nee Schoeneberg.

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Benno Strauss (far right) with unidentified family members.

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Pedigree of the Jacob family of Stavenhagen, Mecklenburg, Germany.

Family tree and genealogy of Jacob family in Stavenhagen, Mecklenburg, 1690-1975.

Family portrait at double wedding ceremony of the Heimann and Rosenfelder families Portraits; Family

Double Wedding Ceremony Heimann-Rosenfelder August 17, 1909

Painting of Freiherr Martin von Magnus Family Portraits Family

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GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE and secondary associations with metabolic risk factors

Serum butyrylcholinesterase (BCHE) activity is associated with obesity, blood pressure and biomarkers of cardiovascular and diabetes risk. We have conducted a genome-wide association scan to discover genetic variants affecting BCHE activity, and to clarify whether the associations between BCHE activity and cardiometabolic risk factors are caused by variation in BCHE or whether BCHE variation is secondary to the metabolic abnormalities. We measured serum BCHE in adolescents and adults from three cohorts of Australian twin and family studies. The genotypes from approximately 2.4 million single-nucleotide polymorphisms (SNPs) were available in 8791 participants with BCHE measurements. We detected significant associations with BCHE activity at three independent groups of SNPs at the BCHE locus (P = 5.8 x 10(-262), 7.8 x 10(-47), 2.9 x 10(-12)) and at four other loci: RNPEP (P = 9.4 x 10(-16)), RAPH1-ABI2 (P = 4.1 x 10(-18)), UGT1A1 (P = 4.0 x 10(-8)) and an intergenic region on chromosome 8 (P = 1.4 x 10(-8)). These loci affecting BCHE activity were not associated with metabolic risk factors. On the other hand, SNPs in genes previously associated with metabolic risk had effects on BCHE activity more often than can be explained by chance. In particular, SNPs within FTO and GCKR were associated with BCHE activity, but their effects were partly mediated by body mass index and triglycerides, respectively. We conclude that variation in BCHE activity is due to multiple variants across the spectrum from uncommon/large effect to common/small effect, and partly results from (rather than causes) metabolic abnormalities.

Achtentuch family portrait; Odessa Portraits Family

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