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Description

Adrenocortical dysplasia protein homolog (UniProt: A0A590TQL1, also known as TPP1, ACD) is encoded by the ACD (also known as hCG_27140) gene (Gene ID: 65057) in human. ACD (TPP1) is one of the shelterin components that is involved in both telomere protection and telomere length regulation. Shelterin is known to associate with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without this protection, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. ACD/TPP1 contains an oligosaccharide binding-fold (OB-fold) domain that provides an interface to recruit telomerase. Within its OB-fold domain is a cluster of amino acids known as the TEL patch (TPP1-Glu-Leu) that contains an interaction interface with telomerase. In the G2/M phase, it interacts with the cell cycle regulator kinase NEK6 that phosphorylates a highly conserved serine 255 that is located in the intervening region between the telomerase recruiting OB-fold and the POT1 (Protection Of Telomeres 1) recruiting domain. POT1 is reported to negatively regulate ACD/TPP1 phosphorylation. Phosphorylation of serine 255 is shown to be important in the interaction between ACD/TPP1 and telomerase. (Ref.: Henslee, G., et al. (2021). Cold Spring Harb. Mol. Case Stud. 7(1), a005454, Hirai, Y., et al. (2016). Genes Cells. 21(8), 874-889).