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PROSITE documentation PDOC50819

Intein DOD-type homing endonuclease domain profile


Inteins (for INternal proTEINs) are in frame intervening sequences that disrupt the coding region of a host gene. They are post-translationally excised from a protein precursor by a self-catalytic protein splicing process [1,2,3,E1]. Most inteins are bifunctional proteins mediating both protein splicing and DNA cleavage. The domain involved in splicing is formed by the two terminal splicing regions (see <PDOC00687>), which are separated by a small linker in mini-inteins or a 200- to 250-amino-acid homing endonuclease in larger inteins [1,3]. 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 [4,5]. 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 recognize 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 α/β motifs related by pseudo two-fold symmetry (see <PDB:1DFA>). The two α-helices containing the dodecapeptide motifs form the axis of symmetry [4,5,E1].

The profile we have developed covers the conserved central intein blocks C, D, E and H. Blocks C and E are the dodecapeptide motifs that are required for endonuclease activity and each contains an endonuclease active site Asp or Glu [2,E1].

Last update:

May 2002 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

INTEIN_ENDONUCLEASE, PS50819; Intein DOD-type homing endonuclease domain profile  (MATRIX)


1AuthorsLiu X.-Q.
TitleProtein-splicing intein: Genetic mobility, origin, and evolution.
SourceAnnu. Rev. Genet. 34:61-76(2000).
PubMed ID11092822

2AuthorsPerler F.B. Olsen G.J. Adam E.
TitleCompilation and analysis of intein sequences.
SourceNucleic Acids Res. 25:1087-1093(1997).
PubMed ID9092614

3AuthorsPerler F.B.
TitleInBase, the Intein Database.
SourceNucleic Acids Res. 28:344-345(2000).
PubMed ID10592269

4AuthorsBelfort M. Roberts R.J.
TitleHoming endonucleases: keeping the house in order.
SourceNucleic Acids Res. 25:3379-3388(1997).
PubMed ID9254693

5AuthorsJurica M.S. Stoddard B.L.
TitleHoming endonucleases: structure, function and evolution.
SourceCell. Mol. Life Sci. 55:1304-1326(1999).
PubMed ID10487208


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