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103  structures 2701  species 1  interaction 3180  sequences 23  architectures

Family: RecA (PF00154)

Summary: recA bacterial DNA recombination protein

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This is the Wikipedia entry entitled "RecA". More...

RecA Edit Wikipedia article

recA bacterial DNA recombination protein
Homologous recombination 3cmt.png
Crystal structure of a RecA-DNA complex. PDB ID: 3cmt.[1]
Identifiers
Symbol RecA
Pfam PF00154
Pfam clan CL0023
InterPro IPR013765
PROSITE PDOC00131
SCOP 2reb
SUPERFAMILY 2reb

RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA.[2] A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is called RAD51 in eukaryotes and RadA in archaea.

RecA has multiple activities, all related to DNA repair. In the bacterial SOS response, it has a co-protease [3] function in the autocatalytic cleavage of the LexA repressor and the λ repressor.[4]

RecA's association with DNA major is based on its central role in homologous recombination. The RecA protein binds strongly and in long clusters to ssDNA to form a nucleoprotein filament. The protein has more than one DNA binding site, and thus can hold a single strand and double strand together. This feature makes it possible to catalyze a DNA synapsis reaction between a DNA double helix and a complementary region of single stranded DNA. The RecA-ssDNA filament searches for sequence similarity along the dsDNA. The search process induces stretching of the DNA duplex, which enhances sequence complimentarity recognition (a mechanism termed conformational proofreading [5] [6]). The reaction initiates the exchange of strands between two recombining DNA double helices. After the synapsis event, in the heteroduplex region a process called branch migration begins. In branch migration an unpaired region of one of the single strands displaces a paired region of the other single strand, moving the branch point without changing the total number of base pairs. Spontaneous branch migration can occur, however as it generally proceeds equally in both directions it is unlikely to complete recombination efficiently. The RecA protein catalyzes unidirectional branch migration and by doing so makes it possible to complete recombination, producing a region of heteroduplex DNA that is thousands of base pairs long.

Since it is a DNA-dependent ATPase, RecA contains an additional site for binding and hydrolyzing ATP. RecA associates more tightly with DNA when it has ATP bound than when it has ADP bound.

E. coli strains deficient in RecA are useful for cloning procedures in molecular biology laboratories. E. coli strains are often genetically modified to contain a mutant recA allele and thereby ensure the stability of extrachromosomal segments of DNA, known as plasmids. In a process called transformation, plasmid DNA is taken up by the bacteria under a variety of conditions. Bacteria containing exogenous plasmids are called "transformants". Transformants retain the plasmid throughout cell divisions such that it can be recovered and used in other applications. Without functional RecA protein, the exogenous plasmid DNA is left unaltered by the bacteria. Purification of this plasmid from bacterial cultures can then allow high-fidelity PCR amplification of the original plasmid sequence.

Potential as a drug target

Wigle and Singleton at the University of North Carolina have shown that small molecules interfering with RecA function in the cell may be useful in the creation of new antibiotic drugs.[7] Since many antibiotics lead to DNA damage, and all bacteria rely on RecA to fix this damage, inhibitors of RecA could be used to enhance the toxicity of antibiotics. Additionally the activities of RecA are synonymous with antibiotic resistance development, and inhibitors of RecA may also serve to delay or prevent the appearance of bacterial drug resistance.

Role of RecA in natural transformation

Based on analysis of the molecular properties of the RecA system, Cox[8] concluded that the data “provide compelling evidence that the primary mission of RecA protein is DNA repair.” In a further essay on the function of the RecA protein, Cox[9] summarized data demonstrating that “RecA protein evolved as the central component of a recombinational DNA repair system, with the generation of genetic diversity as a sometimes useful byproduct.”

Natural bacterial transformation involves the transfer of DNA from one bacterium to another (ordinarily of the same species) and the integration of the donor DNA into the recipient chromosome by homologous recombination, a process mediated by the RecA protein (see Transformation (genetics)). Transformation, in which RecA plays a central role, depends on expression of numerous additional gene products (e.g. about 40 gene products in Bacillus subtilis) that specifically interact to carry out this process indicating that it is an evolved adaptation for DNA transfer. In B. subtilis the length of the transferred DNA can be as great as a third and up to the size of the whole chromosome.[10][11] In order for a bacterium to bind, take up and recombine exogenous DNA into its chromosome, it must first enter a special physiological state termed “competence” (see Natural competence). Transformation is common in the prokaryotic world, and thus far 67 species are known to be competent for transformation.[12]

One of the most well studied transformation systems is that of B. subtilis. In this bacterium, the RecA protein interacts with the incoming single-stranded DNA (ssDNA) to form striking filamentous structures.[13] These RecA/ssDNA filaments emanate from the cell pole containing the competence machinery and extend into the cytosol. The RecA/ssDNA filamentous threads are considered to be dynamic nucleofilaments that scan the resident chromosome for regions of homology. This process brings the incoming DNA to the corresponding site in the B. subtilis chromosome where informational exchange occurs.

Michod et al.[14] have reviewed evidence that RecA-mediated transformation is an adaptation for homologous recombinational repair of DNA damage in B. subtilis, as well as in several other bacterial species (i.e. Neisseria gonorrhoeae, Hemophilus influenzae, Streptococcus pneumoniae, Streptococcus mutans and Helicobacter pylori). In the case of the pathogenic species that infect humans, it was proposed that RecA-mediated repair of DNA damages may be of substantial benefit when these bacteria are challenged by the oxidative defenses of their host.

References

  1. ^ Chen, Z.; Yang, H.; Pavletich, N. P. (2008). "Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures". Nature 453 (7194): 489–484. doi:10.1038/nature06971. PMID 18497818. 
  2. ^ Horii T.; Ogawa T. & Ogawa H. (1980). "Organization of the recA gene of Escherichia coli.". Proc. Natl. Acad. Sci. U.S.A. 77 (1): 313–317. doi:10.1073/pnas.77.1.313. PMC 348260. PMID 6244554. 
  3. ^ Horii T.; Ogawa T.; Nakatani T.; Hase T.; Matsubara H. & Ogawa H. (1981). "Regulation of SOS functions: Purification of E. coli LexA protein and determination of its specific site cleaved by the RecA protein.". Cell 27 (3): 515–522. doi:10.1016/0092-8674(81)90393-7. PMID 6101204. 
  4. ^ Little JW (1984). "Autodigestion of lexA and phage lambda repressors". Proc Natl Acad Sci USA 81 (5): 1375–1379. doi:10.1073/pnas.81.5.1375. PMC 344836. PMID 6231641. 
  5. ^ Savir Y & Tlusty T (2010). "RecA-mediated homology search as a nearly optimal signal detection system". Molecular Cell 40 (3): 388–96. doi:10.1016/j.molcel.2010.10.020. PMID 21070965. 
  6. ^ De Vlaminck I, van Loenhout MT, Zweifel L, den Blanken J, Hooning K, Hage S, Kerssemakers J, Dekker C (2012). "Mechanism of Homology Recognition in DNA Recombination from Dual-Molecule Experiments". Molecular Cell 46 (5): 616–624. doi:10.1016/j.molcel.2012.03.029. PMID 22560720. 
  7. ^ Wigle TJ, Singleton SF (June 2007). "Directed molecular screening for RecA ATPase inhibitors". Bioorg. Med. Chem. Lett. 17 (12): 3249–53. doi:10.1016/j.bmcl.2007.04.013. PMC 1933586. PMID 17499507. 
  8. ^ Cox MM (June 1991). "The RecA protein as a recombinational repair system". Mol. Microbiol. 5 (6): 1295–9. doi:10.1111/j.1365-2958.1991.tb00775.x. PMID 1787786. 
  9. ^ Cox MM (September 1993). "Relating biochemistry to biology: how the recombinational repair function of RecA protein is manifested in its molecular properties". BioEssays 15 (9): 617–23. doi:10.1002/bies.950150908. PMID 8240315. 
  10. ^ Akamatsu T, Taguchi H (April 2001). "Incorporation of the whole chromosomal DNA in protoplast lysates into competent cells of Bacillus subtilis". Biosci. Biotechnol. Biochem. 65 (4): 823–9. doi:10.1271/bbb.65.823. PMID 11388459. 
  11. ^ Saito Y, Taguchi H, Akamatsu T (March 2006). "Fate of transforming bacterial genome following incorporation into competent cells of Bacillus subtilis: a continuous length of incorporated DNA". J. Biosci. Bioeng. 101 (3): 257–62. doi:10.1263/jbb.101.257. PMID 16716928. 
  12. ^ Johnsborg O, Eldholm V, Håvarstein LS (December 2007). "Natural genetic transformation: prevalence, mechanisms and function". Res. Microbiol. 158 (10): 767–78. doi:10.1016/j.resmic.2007.09.004. PMID 17997281. 
  13. ^ Kidane D, Graumann PL (July 2005). "Intracellular protein and DNA dynamics in competent Bacillus subtilis cells". Cell 122 (1): 73–84. doi:10.1016/j.cell.2005.04.036. PMID 16009134. 
  14. ^ Michod RE, Bernstein H, Nedelcu AM (May 2008). "Adaptive value of sex in microbial pathogens". Infect. Genet. Evol. 8 (3): 267–85. doi:10.1016/j.meegid.2008.01.002. PMID 18295550. 
  • Joo C, McKinney SA, Nakamura M, Rasnik I, Myong S, Ha T (August 2006). "Real-time observation of RecA filament dynamics with single monomer resolution". Cell 126 (3): 515–27. doi:10.1016/j.cell.2006.06.042. PMID 16901785. 

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recA bacterial DNA recombination protein Provide feedback

RecA is a DNA-dependent ATPase and functions in DNA repair systems. RecA protein catalyses an ATP-dependent DNA strand-exchange reaction that is the central step in the repair of dsDNA breaks by homologous recombination [1].

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013765

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response [PUBMED:1896024]. In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs [PUBMED:1896024]. RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage [PUBMED:1896024].

RecA is a protein of about 350 amino-acid residues. Its sequence is very well conserved [PUBMED:9187054, PUBMED:7592482, PUBMED:8587109] among eubacterial species. It is also found in the chloroplast of plants [PUBMED:1518831]. RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament visualised by X-ray crystallography, beta-strand 3, the loop C-terminal to beta-strand 2, and alpha-helix D of the core domain form one surface that packs against alpha-helix A and beta-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation [PUBMED:12045091]. The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between beta-strand 1 and alpha-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another nucleotide binding motif, the Walker B box is found at beta-strand 4 in the RecA structure. The Walker B box is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP binding interactions are contributed by the amino acid residues at beta-strand 2 and the loop C-terminal to that strand, all of which are greater than 90% conserved among bacterial RecA proteins.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 199 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_PrkA ABC_ATPase ABC_tran Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA CbiA CBP_BcsQ CDC73_C CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1611 DUF2075 DUF2326 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK Hydin_ADK IIGP IPPT IPT IstB_IS21 KAP_NTPase KdpD Kinesin KTI12 Lon_2 LpxK MCM MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 NTPase_P4 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase Roc RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SSE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE Zeta_toxin Zot

Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(15)
Full
(3180)
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(27821)
NCBI
(28181)
Meta
(4656)
RP15
(902)
RP35
(2463)
RP55
(4085)
RP75
(6217)
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  Seed
(15)
Full
(3180)
Representative proteomes UniProt
(27821)
NCBI
(28181)
Meta
(4656)
RP15
(902)
RP35
(2463)
RP55
(4085)
RP75
(6217)
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  Seed
(15)
Full
(3180)
Representative proteomes UniProt
(27821)
NCBI
(28181)
Meta
(4656)
RP15
(902)
RP35
(2463)
RP55
(4085)
RP75
(6217)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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HMM logo

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: recA;
Type: Family
Author: Sonnhammer ELL
Number in seed: 15
Number in full: 3180
Average length of the domain: 248.60 aa
Average identity of full alignment: 62 %
Average coverage of the sequence by the domain: 70.78 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 20.9 20.9
Noise cut-off 20.8 20.8
Model length: 263
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There is 1 interaction for this family. More...

RecA

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RecA domain has been found. There are 103 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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