|PROSITE documentation PDOC00687|
Inteins (for INternal proTEINs) are protein insertion sequences that are embedded in host protein sequences. They are post-translationally excised from the host protein by a self-catalytic protein splicing process, in which the intein sequence is precisely excised, and the flanking host protein sequences (N- and C-exteins) are religated to create a functional protein. Intein and protein splicing may be viewed as the protein equivalent of intron and RNA splicing, respectively. Inteins were initially discovered as translated intervening sequences that were present in the host gene but absent in homologous genes. Inteins occur in organisms spanning all three kingdoms of life (eubacteria, archaea and eukaryote). Although many inteins are in host proteins involved in nucleic acid metabolism, several inteins are located in metabolic enzymes, such as phosphoenolpyruvate synthase, anaerobic ribonucleoside triphosphate reductase, UDP-glucose dehydrogenase, ClpP protease/chaperone, vacuolar ATPase proton pump (VMA) and glutamine-fructose 6-phosphate transaminase. It should be noted that protein splicing can also occur in trans as in Synechocystis sp. PCC 6803, where the replicative DNA polymerase catalytic subunit (DnaE) is generated from two separate precursor fragments [1,2,3,4,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, which are separated by a small linker in mini-inteins or a homing endonuclease of 200-250 amino acids in larger inteins (see <PDOC50819>) [1,4]. The N-terminal splicing region spans the about 100 N-terminal amino acids and contains the conserved intein blocks A and B which are similar to the motifs found in the C-terminal autoprocessing domain of the hedgehog protein. The C-terminal splicing region is composed of the two conserved blocks F and G located in the about 50 C-terminal amino acids. Although, no single residue is invariant, the Ser and Cys in block A, the His in block B, the His, Asn and Ser/Cys/Thr in block G are the most conserved residues in the splicing motifs. Protein splicing requires neither cofactors nor auxiliary enzymes and involves a series of four intramolecular reactions in which several of these most conserved residues are implicated [1,3,E1].
Resolution of the crystal structure of the Mxe GyrA mini-intein (see <PDB:1AM2>) revealed a flattened 'horseshoe shaped' protein composed primarily of β-strands forming two homologous subdomains that are related by a pseudo twofold axis of symmetry. Despite a low level of sequence conservation, the two subdomains are nearly superimposable, suggesting that they could have arisen by tandem duplication of a primordial gene. However, the duplicated sequences do not correspond directly to the two subdomains as the two subdomains have exchanged homologous loop regions [1,2,5,6].
The first profile we have developed is directed against the N-terminal splicing region and covers the intein blocks A and B. It starts with the first N-terminal amino acid of the intein.
The second profile we have developed is directed against the C-terminal splicing region and covers the intein blocks F and G. It extends to the first extein residue following the intein.Last update:
May 2002 / Text revised, patterns removed and profiles added.
PROSITE methods (with tools and information) covered by this documentation:
|Title||Protein-splicing intein: Genetic mobility, origin, and evolution.|
|Source||Annu. Rev. Genet. 34:61-76(2000).|
|Title||Protein splicing and related forms of protein autoprocessing.|
|Source||Annu. Rev. Biochem. 69:447-496(2000).|
|3||Authors||Perler F.B. Olsen G.J. Adam E.|
|Title||Compilation and analysis of intein sequences.|
|Source||Nucleic Acids Res. 25:1087-1093(1997).|
|Title||InBase, the Intein Database.|
|Source||Nucleic Acids Res. 28:344-345(2000).|
|5||Authors||Klabunde T. Sharma S. Telenti A. Jacobs W.R. Jr. Sacchettini J.C.|
|Title||Crystal structure of GyrA intein from Mycobacterium xenopi reveals structural basis of protein splicing.|
|Source||Nat. Struct. Biol. 5:31-36(1998).|
|6||Authors||Hall T.M.T. Porter J.A. Young K.E. Koonin E.V. Beachy P.A. Leahy D.J.|
|Title||Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins.|