This entry represents the PR/SET domain found in PR domain zinc finger protein 6 (PRDM6, also known as PRISM). PRDM6 has been shown to co-localized with histone H4 and methylates H4-K20 []. It has also been shown to act as a transcriptional repressor by interacting with class I histone deacetylases and the G9a histone methyltransferase []. It promotes thetransition from differentiated to proliferative smooth muscle by suppressing differentiation and maintaining the proliferative potential of vascular smooth muscle cells []. It also plays a role in endothelial cells by inhibiting endothelial cell proliferation, survival and differentiation []. Mutations in the PRDM6 gene have been linked to nonsyndromic patent ductus arteriosus (PDA), which is a common congenital heart defect (CHD) with both inherited and acquired causes [].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This is a zinc knuckle motif found in PRDM4 (Schwann cell factor 1, SC-1), a member of the PR protein family. PRDM4 is a transcriptional regulator that has been implied in transduction of nerve growth factor signals via the p75 neurotrophin receptor and in cell growth arrest. The short motif is also present in several other PR proteins including human PRDM6 (PRISM), PRDM7, PRDM9 (meisetz), PRDM10 (tristanin), PRDM11, and PRDM15. The conservation of cysteine and histidine residues suggested that this 20 amino acid motif binds zinc, hence the name 'PR zinc knuckle' to distinguish it from the longer (30 amino acid) C2H2-like zinc fingers that are located C-terminally of the PR domain. The PR zinc knuckle fold is similar to that of Gag-knuckles (a β-hairpin providing two zinc ligands followed by a short helix or a loop providing the other two zinc ligands) and zinc ribbons (two β-hairpins, each providing two zinc ligands) [].
