PMC:4570552 / 28382-30227 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4570552","sourcedb":"PMC","sourceid":"4570552","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4570552","text":"Figure 1 De Novo Heterozygous Missense Mutations Affecting Residues of the GSK3 Phosphorylation Motifs within the Transactivation Domain of MAF Cause Aymé-Gripp Syndrome\n(A) Clinical features of affected subjects. Note the distinctive flat face, brachycephaly, ptosis, short nasal tip, long philtrum, small mouth, low-set and posteriorly angulated ears, and nail dystrophy. Permission to publish photographs was provided for all subjects shown.\n(B) Scheme of the MAF domain structure, and location of MAF mutations causing human disease. MAF contains an N-terminal transactivation domain (yellow) with regulatory function, and a C-terminal DNA binding domain, the latter containing an “extended homology” (green), “basic motif” (light blue), and leucine-zipper (pink) regions. The region containing the four in tandem arranged phosphorylation sites recognized by GSK3 (orange) is located within the transactivation domain. Residues mutated in subjects with Aymé-Gripp syndrome (red) and previously reported isolated cataracts/eye defects (black) are shown.\n(C) Cartoon illustrating the GSK3 recognition motifs and location of residues affected in Aymé-Gripp syndrome. The GSK3 catalytic domain is depicted with its active site (red) and the site binding to the priming phosphorylated residue (green). To phosphorylate its substrates, GSK3 requires a priming phosphorylation on the substrate four amino acids downstream the residue to be phosphorylated. The serine/threonine residues sequentially targeted by GSK3 are shown (red). Upon phosphorylation, they act as priming residues (green) to allow the subsequent phosphorylation of the upstream Ser/Thr. The kinase phosphorylating Ser70 has not been characterized yet. The residues affected by Aymé-Gripp syndrome-causing mutations (Ser54, Thr58, Pro59, Ser62, and Pro69) are indicated in bold.","divisions":[{"label":"label","span":{"begin":0,"end":8}},{"label":"p","span":{"begin":10,"end":170}},{"label":"p","span":{"begin":171,"end":445}},{"label":"p","span":{"begin":446,"end":1057}}],"tracks":[]}