<p>Inteins (for INternal proTEINs) are in frame intervening sequences that disrupt the coding region of a host gene. They are post-translationallyexcised from a protein precursor by a self-catalytic protein splicing process[<cite idref="PUB00007299"/>, <cite idref="PUB00007300"/>, <cite idref="PUB00007301"/>]. Most inteins are bifunctional proteins mediating both protein splicing and DNA clivage. The domain involved in splicing is formed by the two terminal splicing regions, which are separated by a small linker in mini-inteins or a 200- to 250-amino-acid homing endonuclease in larger inteins [<cite idref="PUB00007299"/>, <cite idref="PUB00007301"/>]. Homing endonucleases are rare-cutting enzymes encoded by inteins and introns. By making a site-specific double-strand break in the intronless or inteinless alleles, these nucleases create recombinogenic ends which engage in a gene conversion process that duplicates the intron or intein [<cite idref="PUB00004478"/>, <cite idref="PUB00006563"/>]. There are four families of homing endonucleases classified by conserved sequence motifs. Homing endonucleases found in inteins generally belong to the dodecapetide (DOD) family, but an HNH endonuclease is also found. Endonucleases of the DOD family contain one or two copies of a 10-residue sequence known as a dodecapeptide or LAGLIDADG motif. They recognise long, pseudopalindromic homing sites of 14-30 bp in length and cleave their homing site DNA to generate 4nt, 3' extensions. The DOD endonucleases found in inteins contain 2 dodecapeptide motifs and are active as monomers. Resolution of the 3D structure of PI-Sce revealed that the endonuclease domain consist of alpha/beta motifs related by pseudo two-fold symmetry. The two alpha-helices containing the dodecapeptide motifs form the axis of symmetry [<cite idref="PUB00004478"/>, <cite idref="PUB00006563"/>].</p><p>This entry covers the conserved central intein Blocks C,D, E and H. Blocks C and E are the dodecapeptide motifs that are required forendonuclease activity and each contains an endonuclease active site Asp or Glu[<cite idref="PUB00007300"/>].</p> Intein DOD homing endonuclease