Fig. 1From: Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autismStructural comparison of the ADNP and ADNP2 gene structure and functional protein domains. (A) The ADNP gene contains five exons of which only the last three are translated (https://www.ensembl.org/). The ADNP2 gene contains only four exons. The 5’UTR of ADNP2 corresponds with exons 1 and 2 of ADNP. The 3’UTR is comprised of a part of exon 4, correlating to exon 5 of ADNP. ATG, start codon; TAA, stop codon. (B) The relative positions of the ADNP nine zinc fingers (lines) together with the glutaredoxin active site, NAP sequence, eIF-4E interaction motif, nuclear localization signal (NLS), DNA-binding homeobox domain with ARKS and PxVxL motif are illustrated on the figure. Computational sequence analysis also revealed LC3 interaction sites (MAP1ALC3), SH3-binding sites (SHANK3), and WRD5-binding sites (SIRT1) in ADNP which could be confirmed by direct co-immunoprecipitation experiments. The ADNP gene is divided in three mutational classes: N-terminal, perinuclear (NLS destructive), and C-terminal mutations, each of them altering the subcellular localization and expression of the protein. The most recurring and prevalent ADNP mutations of the spectrum include the p.Tyr719*, p.Arg730*, and p.Asn832Lysfs*81 with the unique deceased ADNP toddler mutation c.1676Adupl/p.His559Gln*3. The three viable Adnp heterozygous mouse strains mimic in part mutation designated to each class of the mutational spectrum, e.g., haploinsufficient mouse accounting for N-terminal mutations, respectively, the p.Tyr718* Adnp mouse for the NLS-destroying group of patient mutations, and the frameshift Adnp mouse for patients with C-terminal mutations. ADNP2 shows homology to ADNP by the presence of an equal amount of zinc fingers and a DNA-binding homeoboxBack to article page