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Fig. 1 | Clinical Epigenetics

Fig. 1

From: Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

Fig. 1

Structural 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 homeobox

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