Catalytic domain, repeat 1, of Deoxyribonuclease II alpha and similar proteins
Catalytic domain, repeat 1, of Deoxyribonuclease II alpha (DNase II alpha, EC 3.1.22.1) and similar proteins. DNase II is a monomeric nuclease that contains two copies of a variant HKD motif, where the aspartic acid residue is not conserved. The HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) characterizes the phospholipase D (PLD, EC 3.1.4.4) superfamily. The catalytic center of DNase II is formed by the two variant HKD motifs from the N- and C-terminal domains in a pseudodimeric way. Members of this family are mainly found in metazoans, and vertebrate proteins have been further classified into DNase II alpha and beta. DNase II alpha is an acidic endonuclease found in lysosomes, nuclei, and various secretions. It plays a critical role in the degradation of nuclear DNA expelled from erythroid precursor cells, as well as in the degradation of the apoptotic DNA after macrophages engulf them. It cleaves double-stranded DNA to short 3'-phosphoryl oligonucleotides, rather than 3'-hydroxyl groups, and functions optimally at acidic pH in the absence of divalent metal ion cofactors.
Comment:Based on similarity with phospholipase D, which functions as a bi-lobed monomer with two catalytic domains. Each domain carries one copy of the conserved HKD motif and two domains form a single active site.
Comment:The HKD signature motif (expanded to H-x-K-x(4)-D-x(6)-G-S-x-N, where x represents any amino acid residue) characterizes the PLD superfamily. The DNase II subfamily carries a variant HKD motif.
Comment:Most residues in the HKD motif are part of the active site.
Jiyao W et al.(2023). "The conserved domain database in 2023.",