Phosphorylation of as1-casein is regulated by different genes

Bijl, E.; Valenberg, H.J.F. van; Huppertz, T.; Hooijdonk, A.C.M. van; Bovenhuis, H.


Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. aS1-Casein (as1-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (aS1-CN-8P) and 9 (aS1-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of aS1-CN-8P and aS1-CN-9P. The genetic and phenotypic correlation between aS1-CN-8P and aS1-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both aS1-CN-8P and aS1-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only aS1-CN-8P was affected by a region on BTA11 that contains the gene that encodes for ß-lactoglobulin (ß-LG), and only aS1-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of ß-LG protein genotypes showed that only aS1-CN-8P was associated with the ß-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of ß-LG was associated with a lower concentration of aS1-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only aS1-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher aS1-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of aS1-CN-8P and aS1-CN-9P, which seem to be regulated by a different set of genes.