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EMBO J. Feb 1986; 5(2): 433–440.
PMCID: PMC1166749

The integrase family of site-specific recombinases: regional similarities and global diversity.


A combination of two methods for detecting distant relationships in protein primary sequences was used to compare the site-specific recombination proteins encoded by bacteriophage lambda, phi 80, P22, P2, 186, P4 and P1. This group of proteins exhibits an unexpectedly large diversity of sequences. Despite this diversity, all of the recombinases can be aligned in their C-terminal halves. A 40-residue region near the C terminus is particularly well conserved in all the proteins and is homologous to a region near the C terminus of the yeast 2 mu plasmid Flp protein. This family of recombinases does not appear to be related to any other site-specific recombinases. Three positions are perfectly conserved within this family: histidine, arginine and tyrosine are found at respective alignment positions 396, 399 and 433 within the well-conserved C-terminal region. We speculate that these residues contribute to the active site of this family of recombinases, and suggest that tyrosine-433 forms a transient covalent linkage to DNA during strand cleavage and rejoining.

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  • Abremski K, Hoess R. Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem. 1984 Feb 10;259(3):1509–1514. [PubMed]
  • Abremski K, Hoess R, Sternberg N. Studies on the properties of P1 site-specific recombination: evidence for topologically unlinked products following recombination. Cell. 1983 Apr;32(4):1301–1311. [PubMed]
  • Abremski K, Wierzbicki A, Frommer B, Hoess RH. Bacteriophage P1 Cre-loxP site-specific recombination. Site-specific DNA topoisomerase activity of the Cre recombination protein. J Biol Chem. 1986 Jan 5;261(1):391–396. [PubMed]
  • Andrews BJ, Proteau GA, Beatty LG, Sadowski PD. The FLP recombinase of the 2 micron circle DNA of yeast: interaction with its target sequences. Cell. 1985 Apr;40(4):795–803. [PubMed]
  • Argos P. Evidence for a repeating domain in type I restriction enzymes. EMBO J. 1985 May;4(5):1351–1355. [PMC free article] [PubMed]
  • Argos P, Hanei M, Wilson JM, Kelley WN. A possible nucleotide-binding domain in the tertiary fold of phosphoribosyltransferases. J Biol Chem. 1983 May 25;258(10):6450–6457. [PubMed]
  • Argos P, Palau J. Amino acid distribution in protein secondary structures. Int J Pept Protein Res. 1982 Apr;19(4):380–393. [PubMed]
  • Argos P, Schwarz J, Schwarz J. An assessment of protein secondary structure prediction methods based on amino acid sequence. Biochim Biophys Acta. 1976 Aug 9;439(2):261–273. [PubMed]
  • Austin S, Ziese M, Sternberg N. A novel role for site-specific recombination in maintenance of bacterial replicons. Cell. 1981 Sep;25(3):729–736. [PubMed]
  • Babineau D, Vetter D, Andrews BJ, Gronostajski RM, Proteau GA, Beatty LG, Sadowski PD. The FLP protein of the 2-micron plasmid of yeast. Purification of the protein from Escherichia coli cells expressing the cloned FLP gene. J Biol Chem. 1985 Oct 5;260(22):12313–12319. [PubMed]
  • Bertani LE, Bertani G. Genetics of P2 and related phages. Adv Genet. 1971;16:199–237. [PubMed]
  • BERTANI G, SIX E. Inheritance of prophage P2 in bacterial crosses. Virology. 1958 Oct;6(2):357–381. [PubMed]
  • Bushman W, Thompson JF, Vargas L, Landy A. Control of directionality in lambda site specific recombination. Science. 1985 Nov 22;230(4728):906–911. [PMC free article] [PubMed]
  • Calendar R, Lindahl G. Attachment of prophage P2: gene order at different host chromosomal sites. Virology. 1969 Dec;39(4):867–881. [PubMed]
  • Calendar R, Ljungquist E, Deho G, Usher DC, Goldstein R, Youderian P, Sironi G, Six EW. Lysogenization by satellite phage P4. Virology. 1981 Aug;113(1):20–38. [PubMed]
  • Champoux JJ. Strand breakage by the DNA untwisting enzyme results in covalent attachment of the enzyme to DNA. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3800–3804. [PMC free article] [PubMed]
  • Chan RK, Botstein D. Specialized transduction by bacteriophage P22 in Salmonella typhimurium: genetic and physical structure of the transducing genomes and the prophage attachment site. Genetics. 1976 Jul;83(3 PT2):433–458. [PMC free article] [PubMed]
  • Craig NL, Nash HA. The mechanism of phage lambda site-specific recombination: site-specific breakage of DNA by Int topoisomerase. Cell. 1983 Dec;35(3 Pt 2):795–803. [PubMed]
  • Davies RW. DNA sequence of the int-xis-Pi region of the bacteriophage lambda; overlap of the int and xis genes. Nucleic Acids Res. 1980 Apr 25;8(8):1765–1782. [PMC free article] [PubMed]
  • Gronostajski RM, Sadowski PD. The FLP protein of the 2-micron plasmid of yeast. Inter- and intramolecular reactions. J Biol Chem. 1985 Oct 5;260(22):12328–12335. [PubMed]
  • Gronostajski RM, Sadowski PD. Determination of DNA sequences essential for FLP-mediated recombination by a novel method. J Biol Chem. 1985 Oct 5;260(22):12320–12327. [PubMed]
  • Hartley JL, Donelson JE. Nucleotide sequence of the yeast plasmid. Nature. 1980 Aug 28;286(5776):860–865. [PubMed]
  • Hiestand-Nauer R, Iida S. Sequence of the site-specific recombinase gene cin and of its substrates serving in the inversion of the C segment of bacteriophage P1. EMBO J. 1983;2(10):1733–1740. [PMC free article] [PubMed]
  • Hocking SM, Egan JB. Genetic map of coliphage 186 from a novel use of marker rescue frequencies. Mol Gen Genet. 1982;187(1):87–95. [PubMed]
  • Hoess RH, Abremski K. Mechanism of strand cleavage and exchange in the Cre-lox site-specific recombination system. J Mol Biol. 1985 Feb 5;181(3):351–362. [PubMed]
  • Hoess RH, Foeller C, Bidwell K, Landy A. Site-specific recombination functions of bacteriophage lambda: DNA sequence of regulatory regions and overlapping structural genes for Int and Xis. Proc Natl Acad Sci U S A. 1980 May;77(5):2482–2486. [PMC free article] [PubMed]
  • Hsu PL, Ross W, Landy A. The lambda phage att site: functional limits and interaction with Int protein. Nature. 1980 May 8;285(5760):85–91. [PMC free article] [PubMed]
  • Jessop AP. Specialized transducing phages derived from phage P22 that carry the pro AB region of the host, Salmonella typhimurium: genetic evidence for their structure and mode of transduction. Genetics. 1976 Jul;83(3 PT2):459–475. [PMC free article] [PubMed]
  • Kamp D, Kardas E, Ritthaler W, Sandulache R, Schmucker R, Stern B. Comparative analysis of invertible DNA in phage genomes. Cold Spring Harb Symp Quant Biol. 1984;49:301–311. [PubMed]
  • Keim P, Heinrikson RL, Fitch WM. An examination of the expected degree of sequence similarity that might arise in proteins that have converged to similar conformational states. The impact of such expectations on the search for homology between the structurally similar domains of rhodanese. J Mol Biol. 1981 Sep 5;151(1):179–197. [PubMed]
  • Kikuchi Y, Nash HA. Nicking-closing activity associated with bacteriophage lambda int gene product. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3760–3764. [PMC free article] [PubMed]
  • Kitts P, Symington L, Burke M, Reed R, Sherratt D. Transposon-specified site-specific recombination. Proc Natl Acad Sci U S A. 1982 Jan;79(1):46–50. [PMC free article] [PubMed]
  • Krasnow MA, Cozzarelli NR. Site-specific relaxation and recombination by the Tn3 resolvase: recognition of the DNA path between oriented res sites. Cell. 1983 Apr;32(4):1313–1324. [PubMed]
  • Leong JM, Nunes-Düby S, Lesser CF, Youderian P, Susskind MM, Landy A. The phi 80 and P22 attachment sites. Primary structure and interaction with Escherichia coli integration host factor. J Biol Chem. 1985 Apr 10;260(7):4468–4477. [PubMed]
  • Leong JM, Nunes-Düby SE, Landy A. Generation of single base-pair deletions, insertions, and substitutions by a site-specific recombination system. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6990–6994. [PMC free article] [PubMed]
  • Lindahl G, Sunshine M. Excision-deficient mutants of bacteriophage P2. Virology. 1972 Jul;49(1):180–187. [PubMed]
  • MATSUSHIRO A. Specialized transduction of tryptophan markers in Escherichia coli K12 by bacteriophage phi-80. Virology. 1963 Apr;19:475–482. [PubMed]
  • McLeod M, Volkert F, Broach J. Components of the site-specific recombination system encoded by the yeast plasmid 2-micron circle. Cold Spring Harb Symp Quant Biol. 1984;49:779–787. [PubMed]
  • McLachlan AD. Tests for comparing related amino-acid sequences. Cytochrome c and cytochrome c 551 . J Mol Biol. 1971 Oct 28;61(2):409–424. [PubMed]
  • Meyer-Leon L, Senecoff JF, Bruckner RC, Cox MM. Site-specific genetic recombination promoted by the FLP protein of the yeast 2-micron plasmid in vitro. Cold Spring Harb Symp Quant Biol. 1984;49:797–804. [PubMed]
  • Mizuuchi K, Weisberg R, Enquist L, Mizuuchi M, Buraczynska M, Foeller C, Hsu PL, Ross W, Landy A. Structure and function of the phage lambda att site: size, int-binding sites, and location of the crossover point. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 1):429–437. [PubMed]
  • Nash HA. Integrative recombination of bacteriophage lambda DNA in vitro. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1072–1076. [PMC free article] [PubMed]
  • Nash HA. Integration and excision of bacteriophage lambda: the mechanism of conservation site specific recombination. Annu Rev Genet. 1981;15:143–167. [PubMed]
  • Nash HA, Robertson CA. Purification and properties of the Escherichia coli protein factor required for lambda integrative recombination. J Biol Chem. 1981 Sep 10;256(17):9246–9253. [PubMed]
  • Pierson LS, 3rd, Kahn ML. Cloning of the integration and attachment regions of bacteriophage P4. Mol Gen Genet. 1984;195(1-2):44–51. [PubMed]
  • Plasterk RH, Brinkman A, van de Putte P. DNA inversions in the chromosome of Escherichia coli and in bacteriophage Mu: relationship to other site-specific recombination systems. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5355–5358. [PMC free article] [PubMed]
  • Reed RR, Grindley ND. Transposon-mediated site-specific recombination in vitro: DNA cleavage and protein-DNA linkage at the recombination site. Cell. 1981 Sep;25(3):721–728. [PubMed]
  • Reed RR, Moser CD. Resolvase-mediated recombination intermediates contain a serine residue covalently linked to DNA. Cold Spring Harb Symp Quant Biol. 1984;49:245–249. [PubMed]
  • Reed RR, Shibuya GI, Steitz JA. Nucleotide sequence of gamma delta resolvase gene and demonstration that its gene product acts as a repressor of transcription. Nature. 1982 Nov 25;300(5890):381–383. [PubMed]
  • Ross W, Landy A. Bacteriophage lambda int protein recognizes two classes of sequence in the phage att site: characterization of arm-type sites. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7724–7728. [PMC free article] [PubMed]
  • Ross W, Landy A. Patterns of lambda Int recognition in the regions of strand exchange. Cell. 1983 May;33(1):261–272. [PMC free article] [PubMed]
  • Ross W, Landy A, Kikuchi Y, Nash H. Interaction of int protein with specific sites on lambda att DNA. Cell. 1979 Oct;18(2):297–307. [PMC free article] [PubMed]
  • Rossmann MG, Argos P. Protein folding. Annu Rev Biochem. 1981;50:497–532. [PubMed]
  • Rowe TC, Tewey KM, Liu LF. Identification of the breakage-reunion subunit of T4 DNA topoisomerase. J Biol Chem. 1984 Jul 25;259(14):9177–9181. [PubMed]
  • Sadowski PD, Lee DD, Andrews BJ, Babineau D, Beatty L, Morse MJ, Proteau G, Vetter D. In vitro systems for genetic recombination of the DNAs of bacteriophage T7 and yeast 2-micron circle. Cold Spring Harb Symp Quant Biol. 1984;49:789–796. [PubMed]
  • Six EW, Klug CA. Bacteriophage P4: a satellite virus depending on a helper such as prophage P2. Virology. 1973 Feb;51(2):327–344. [PubMed]
  • Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. [PMC free article] [PubMed]
  • Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol. 1981 Aug 25;150(4):467–486. [PubMed]
  • Tse YC, Kirkegaard K, Wang JC. Covalent bonds between protein and DNA. Formation of phosphotyrosine linkage between certain DNA topoisomerases and DNA. J Biol Chem. 1980 Jun 25;255(12):5560–5565. [PubMed]
  • Wolfenden RV, Cullis PM, Southgate CC. Water, protein folding, and the genetic code. Science. 1979 Nov 2;206(4418):575–577. [PubMed]
  • Woods WH, Egan JB. Integration stie of noninducible coliphage 186. J Bacteriol. 1972 Aug;111(2):303–307. [PMC free article] [PubMed]
  • Yin S, Bushman W, Landy A. Interaction of the lambda site-specific recombination protein Xis with attachment site DNA. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1040–1044. [PMC free article] [PubMed]
  • Zalkin H, Argos P, Narayana SV, Tiedeman AA, Smith JM. Identification of a trpG-related glutamine amide transfer domain in Escherichia coli GMP synthetase. J Biol Chem. 1985 Mar 25;260(6):3350–3354. [PubMed]

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