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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.

May 2002 / Text revised, patterns removed and profiles added.

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

INTEIN_C_TER, PS50818; Intein C-terminal splicing motif profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS50818 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50818 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50818 • Scan Swiss-Prot/TrEMBL entries against PS50818 • view ligand binding statistics

Matching PDB structures: 1AM2 1MI8 2CW7 2CW8 ... [ALL]

INTEIN_N_TER, PS50817; Intein N-terminal splicing motif profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS50817 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50817 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50817 • Scan Swiss-Prot/TrEMBL entries against PS50817 • view ligand binding statistics

Matching PDB structures: 1AM2 1AT0 1DFA 1LWS ... [ALL]

1	Authors	Liu X.-Q.
	Title	Protein-splicing intein: Genetic mobility, origin, and evolution.
	Source	Annu. Rev. Genet. 34:61-76(2000).
	PubMed ID	11092822
	DOI	10.1146/annurev.genet.34.1.61

2	Authors	Paulus H.
	Title	Protein splicing and related forms of protein autoprocessing.
	Source	Annu. Rev. Biochem. 69:447-496(2000).
	PubMed ID	10966466
	DOI	10.1146/annurev.biochem.69.1.447

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).
	PubMed ID	9092614

4	Authors	Perler F.B.
	Title	InBase, the Intein Database.
	Source	Nucleic Acids Res. 28:344-345(2000).
	PubMed ID	10592269

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).
	PubMed ID	9437427

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.
	Source	Cell 91:85-97(1997).
	PubMed ID	9335337

E1
Source	http://www.neb.com/neb/inteins.html

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