Supplementary information

Overview

Spread of the PmrAB two-component system
PmrA motif model
PmrA motif scan results
Phylogenetic footprinting by Gibbs sampling
Phylogenetic footprint results
References

Spread of the PmrAB two component system

The spread of respectively the BasS and BasR among prokaryotes was verified by blastX BasS blast result,BasR blast result; For the response regulator (PmrA) considerably more high scoring blast hits could be retrieved as compared to the corresponding sensor protein (PmrB), reflecting the high versatility of two-component systems. The sensor seems relatively specific, while the universal DNA binding and phosphorylation capacities of the response regulators are more conserved and contribute to higher number of blasthits. Footprints of the PmrA motif can most likely be detected in species that contain a functional homologue of the PmrAB system and for which at least part of the PmrAB regulon is conserved. At least for Yersinia, Shigella and E. coli, there are clear experimental (see previous literature on the PmrAB system) and in silico indications that these assumptions are fulfilled. Indeed, close homologs of the sensor BasS that contained the amino acid residues that have been implicated in Fe3+ binding could only be detected in E. coli, Shigella and Yersinia. At least in those species part of the PmrAB signaling mechanism should be similar. In these species the residues involved in DNA binding were conserved as well (DNA binding domain of 2-component systems, PF00486), indicating that the respective PmrA orthologs could recognize a similar DNA motif.

Alignments were obtained by ClustalW (Thompson et al. 1994). The residues of PmrA involved in DNA binding and the residues of PmrB postulated to be involved in Fe3+ are indicated. The represented alignment of BasS contains a sample of the 14 most similar homologs to BasS of S. typhimurium (min blast score 1e-20) of different species (including E. coli, Yersinia, Shigella, Ralstonia, Burkholderia, Desufitobacterium, Shewanella, Pseudomonas).

BasS	BasR
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PmrA motif model

To construct a motif model representative for the PmrA site, a set of genes known to be PmrA regulated was compiled (ugd, yfbe, pmrC). Using Gibbs sampling the following motif model could be retrieved. This motif corresponds to the direct repeat that has been described by Aguirre et al. 2000.
PmrA Motif Logo

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PmrA Motif Logo
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PmrA motif scan results

Motif Scan
The intergenics of the complete genome of S. typhimurium LT2 (NC_003197) were screened using Motif Locator (http://www.esat.kuleuven.ac.be/~thijs/Work/MotifScanner.html). This algorithm uses the motif model (represented by a position specific probability matrix) to calculate a score for each window (length similar to the length of the motif model) in the sequence. Both the plus and minus strand were screened with the following parameter settings (background order 3). Results of the genome wide screening of the S. typhimurium genome with the PmrA motif model using MotifLocator can be found here Motif Scan Results high scoring genome .
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Phylogenetic footprinting by Gibbs sampling

A biological relevant local alignment of the intergenic regions seems a better summary of the degree of conservation between the intergenics than a listing of the highest scoring motifs. Therefore, the general aim is to use motif detection to locally align the intergenic sequences of the homologous sequences.

To find motifs that can be used as seeds for the local alignments, each dataset was subjected to motif detection by Gibbs sampling using different parameter settings (motif lengths 6, 8, 10, 12, background order 0, 100 runs, prior probability default value 0.7), which results in a listing of potential alignment seeds (motifs).
Motifs that potentially could result in a biological relevant local alignment were selected using a heuristic:

Motifs obtained by Motif Sampling were ranked according to their log likelihood as a first selection criterion.

From these high scoring motifs, the ones for which the number of instances equalled the number of sequences in which a motif was detected were analysed first (i.e. the motif occurs preferentially once in each sequence)

Usually the optimal alignment was obtained for motifs of which the number of instances was equal to the number of sequences in which a motif was detected and for which the number of sequences in which a motif was found was the same as the number of sequences in the genuine dataset.

However, if for some species more paralogs were present, motifs that occurred in fewer sequences (in true orthologs only) resulted in a considerable increase in consensus score and resulted in the best alignments.

Alignments were judged based on a visual inspection. Because of the observed high overall homology between the intergenic sequences of close homologs derived from E. coli, Shigella, Salmonella and Yersinia species, we expect that in general in a good local multiple alignment the pairwise homology reflects the phylogenetic distance between the species (degree of conservation decreases gradually with the phylogenetic distance).
An example is given below:
Three different alignments obtained for yjdB. Alignment A was obtained by using a motif (length 10) with high LL-score (48.3) as seed but of which the number of instances (15) exceeded the number of sequences (10). The E. coli intergenics are aligned but for the Salmonella intergenics the alignment is less clear (bad alignment, not reflecting the phylogenetic relationship). Alignment B was obtained by using a motif (length 10) with a lower LL-score (45) as seed of which the number of instances (9) was equal to the number of sequences (9). The dataset contained 3 close homologs in E. coli O157 in which the motif was detected. However, the motif was not really conserved (the consensus score was low) decreasing the confidence in this alignment. Alignment C was obtained by using a motif (length 10) with a lower LL-score (38) as seed of which the number of instances (7) was equal to the number of sequences (7). These 7 sequences were true orthologs. In this case the highest consensus score was obtained. As compared to the alignment A, here the degree of conservation between the sequences in this alignment reflects the phylogenetic relationship between E. coli and Shigella and between E. coli and Salmonella. This alignment was retained.

Alignments obtained from 3 different motif seeds

Fig 1 Fig 2 Fig 3

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Fig 1	Fig 2	Fig 3
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For a detailed description on how the heuristic was obtained see IRheuristic IRheuristic.

For a detailed description on how the biological relevance of the alignments was judged see IRalignment.

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Phylogenetic footprint results

To guarantee the quality of the footprints, all alignments of the motifs were individually analyzed. Results of the separate alignments are displayed below.

Gene name: gene name of the S. typhmurium gene. If the intergenics is shared between two divergently transcribed genes, both genes are separated by a "/" and the motif was detected on the plus strand of the first gene indicated.

Gene Function: The description is derived from the annotation available in NCBI.

Annotation: derived from the SANGER annotation of S. typhi.

Site: motif site as detected in the corresponding gene

Remarks:
indicates whether a motif could be detected (nd : no motif detected, m motif detected; If orthologs were only detected in Salmonella species, no informative local alignments can be detected (indicated by /). If the motif detected by the genome wide screening was conserved in more orthologous species, this is indicated by (+). If an alignment could be obtained but the putative PmrA motif detected by the screening was not conserved in the alignment, this is indicated by a (-).* PmrA motif experimentally validated; (PmrA): a motif not deviating from the PmrA consensus was observed in the S. typhimurium sequence.

Distribution: distribution of the corresponding protein as derived from McClelland et al. 2001. In this paper the distribution of each S. typhimurium protein was analyzed in other Salmonella species (5 strains), E. coli (2 strains) and K. pneumoniae. Proteins that have close homologs in at least one Salmonella strain but not E. coli or K. pneumoniae are indicated by some Salmonella only. Genes that contain close homologs in all genomes are indicated by all nine genomes. Other combinations are indicated by other distributions.

Gene Name Gene Function Annotation Location Site Remarks Distribution

STM1273 " putative nitric oxide reductase Putative RBS for STM1273; RegulonDB:STMS1H001525" SANGER GENOME LOCATION " site ""CTTAATGTTTTCTTAAT""" / (PmrA) All Salmonella only

STM2132 " pseudogene; frameshift Putative RBS for STM2133; RegulonDB:STMS1H002278" SANGER GENOME LOCATION " site ""TTTTAGATTCACTTAAT""" / Some or all Salmonella only

STM4596 " Paralog of E. coli orf, hypothetical protein (AAC73478.1); Blastp hit to AAC73478.1 (222 aa), 31% identity in aa 55 - 222 putative inner membrane protein Putative RBS for STM4596; RegulonDB:STMS1H004455" SANGER GENOME LOCATION " site ""TTTAATATTCACTTAAA""" / Some Salmonella only

STM3131 " putative cytoplasmic protein Putative RBS for STM3130; RegulonDB:STMS1H003167; putative first gene of operon with STN3130 (putative hypothetical protein)" SANGER GENOME LOCATION " site ""CTTAATTTTTACTTATT""" / All Salmonella only

STM1020 Gifsy-2 prophage SANGER GENOME LOCATION " site ""CTTATTGTTAAGTCAAT""" / Other distributions

stdA " STM3029 Paralog of E. coli putative fimbrial-like protein (AAC73813.1); Blastp hit to AAC73813.1 (188 aa), 32% identity in aa 8 - 187 putative fimbrial-like protein" SANGER GENOME LOCATION " site ""CAAAACATTAACTTAAT""" / Subspecies 1 only?

udg STM2080 S. typhimurium UDP-glucose 6-dehydrogenase. (SW:UDG_SALTY) UDP-glucose*GDP-mannose dehydrogenase SANGER GENOME LOCATION " site ""CTCAGAATTAACTTAAT""" m (+) All nine genomes

sinR " STM0304 S. typhimurium SINR protein. (SW:SINR_SALTY) transcriptional regulator Putative RBS for sinR; RegulonDB:STMS1H000662" SANGER GENOME LOCATION " site ""CTTGATATCATCTTAAT""" / Subspecies 1 only

STM3131 " putative cytoplasmic protein Putative RBS for STM3130; RegulonDB:STMS1H003167" SANGER GENOME LOCATION " site ""CTTAATACTCACATTAT""" / Other distributions

STM4413 " putative imidazolonepropionase and related amidohydrolases Putative RBS for STM4412; RegulonDB:STMS1H004296; first gene of operon with STM4413 (D-galactonate transport)" SANGER GENOME LOCATION " site ""GTGAATGTTAAATTAAT""" / Some or all Salmonella only

ybdO " STM0606 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC73704.1); Blastp hit to AAC73704.1 (300 aa), 54% identity in aa 1 - 298 putative transcriptional regulator, LysR family" SANGER GENOME LOCATION " site ""CTTAATGTAGAGTTTAT""" m (+ PmrA) All Salmonella only

oraA " STM2828 Ortholog of E. coli regulator, OraA protein (AAC75740.1); Blastp hit to AAC75740.1 (166 aa), 87% identity in aa 1 - 166 regulator" SANGER GENOME LOCATION " site ""CTTGATGGTAATTTAAC""" m (-) All nine genomes

sdhC " STM0732 Ortholog of E. coli succinate dehydrogenase, cytochrome b556 (AAC73815.1); Blastp hit to AAC73815.1 (129 aa), 92% identity in aa 1 - 129 succinate dehydrogenase, cytochrome b556 Putative RBS for sdhD; RegulonDB:STMS1H001043; first gene of putative operon encoding succinate dehydrogenase" SANGER GENOME LOCATION " site ""CTTATTATTCCCTTAAG""" / All nine genomes

ycaR " STM0987 Ortholog of E. coli orf, hypothetical protein (AAC74003.1); Blastp hit to AAC74003.1 (60 aa), 93% identity in aa 1 - 60 putative inner membrane protein Putative RBS for kdsB; RegulonDB:STMS1H001272; first gene of a putative operon with ksdB (CMP-3-deoxy-D-manno-octulosanate transferase" SANGER GENOME LOCATION " site ""TTCAATATTAACATAAT""" / All nine genomes

lasT " STM4600 Ortholog of E. coli orf, hypothetical protein (AAC77356.1); Blastp hit to AAC77356.1 (228 aa), 82% identity in aa 1 - 228 putative tRNA*tRNA methyltransferase" SANGER GENOME LOCATION " site ""ATTTAGGATAATTTAAT""" nd (pmrA) All nine genomes

STM2137 putative cytoplasmic protein SANGER GENOME LOCATION " site ""TTTAACCTTAATTTAAT""" nd Some Salmonella only

STM1672 putative cytoplasmic protein SANGER GENOME LOCATION " site ""ATTAATAGTCACTTATT""" / Subspecies 1 only?

gcvA " STM2982 Ortholog of E. coli positive regulator of gcv operon (AAC75850.1); Blastp hit to AAC75850.1 (305 aa), 98% identity in aa 1 - 305 regulator of gcv operon (LysR family); first gene of putative operon (gcvA,ygdD,ygdE containing a SAM dependent methyltransferase)" SANGER GENOME LOCATION " site ""CTTAATGTCGAATGAAT""" m (+) All nine genomes

ycgO " STM1801 Ortholog of E. coli orf, hypothetical protein (AAC74275.1); Blastp hit to AAC74275.1 (536 aa), 92% identity in aa 1 - 535 putative CPA1 family, Na:H transport protein" SANGER GENOME LOCATION " site ""TTTAACATTAACATAAT""" m (+) All nine genomes?

STM2287 " Paralog of E. coli putative sulfatase * phosphatase (AAC75329.1); Blastp hit to AAC75329.1 (403 aa), 30% identity in aa 27 - 294, 29 503321556dentity in aa 297 - 363 putative cytoplasmic protein" SANGER GENOME LOCATION " site ""CTTATTATTCACATAAC""" / Some or all Salmonella only?

yebW " STM1852 Ortholog of E. coli orf, hypothetical protein (AAC74907.1); Blastp hit to AAC74907.1 (91 aa), 87% identity in aa 29 - 91 putative inner membrane lipoprotein" SANGER GENOME LOCATION " site ""CTCAATGTTAACTACTT""" / All nine genomes?

STM0897 " hypothetical protein Fels-1 prophage Putative RBS for STM0897; RegulonDB:STMS1H001190" SANGER GENOME LOCATION " site ""CGTAAGGCTCTTTTAAT""" / Some Salmonella only

lpfA " STM3640 S. typhimurium long polar fimbria protein A precursor. (SW:LPFA_SALTY) long polar fimbria; first gene of a putative fimbriae synthesis operon" SANGER GENOME LOCATION " site ""ATTAAGAATAAATTAAT""" / (PmrA) Other distributions

positive strand

yjdB* " STM4293 S. typhimurium hypothetical 61.6 Kda protein in basS*pmrA-adiY intergenic region. (SW:YJDB_SALTY) putative integral membrane protein Putative RBS for basR; RegulonDB:STMS1H004188" SANGER GENOME LOCATION " site ""CTTAAGGTTCACTTAAT""" m (+ PmrA) All nine genomes

udg* STM2080 S. typhimurium UDP-glucose 6-dehydrogenase. (SW:UDG_SALTY) UDP-glucose*GDP-mannose dehydrogenase SANGER GENOME LOCATION " site ""CTTAATATTAACTTAAT""" m (+ PmrA) All nine genomes

yfbE/ais* " STM2297 Ortholog of E. coli putative enzyme (AAC75313.1); Blastp hit to AAC75313.1 (390 aa), 82% identity in aa 6 - 390 putative DegT*DnrJ*EryC1*StrS family Putative RBS for pmrF; RegulonDB:STMS1H002430; first gene of the yfbE operon; shared intergenic with ais" SANGER GENOME LOCATION " site ""CTTAATGTTAATTTAAT""" m (+ PmrA) All nine genomes?

STM1269/STM1268* " putative chorismate mutase; intergenic shared with STM1268" SANGER GENOME LOCATION " site ""CTTAATGTTATCTTAAT""" / (PmrA) All Salmonella only

STM0692 " Paralog of E. coli nitrogen assimilation control protein (AAC75050.1); Blastp hit to AAC75050.1 (305 aa), 32% identity in aa 1 - 301 putative transcriptional regulator, LysR family" SANGER GENOME LOCATION " site ""CTTGATGTTGATTTAAT""" / All Salmonella only

ybjG/mdfA* " STM0865 Ortholog of E. coli orf, hypothetical protein (AAC73928.1); Blastp hit to AAC73928.1 (198 aa), 78% identity in aa 1 - 198 putative permease; intergenic shared with mdfA (multidrug translocase)" SANGER GENOME LOCATION " site ""TTTAAGGTTAATTTAAG""" m (+PmrA) All nine genomes

STM2901 " hypothetical protein putative cytoplasmic protein; located downstream of pathogenicity island 1" SANGER GENOME LOCATION " site ""CTTAATATCAATATAAT""" / Other distributions

yhjC/yhjB " STM3607 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC76546.1); Blastp hit to AAC76546.1 (323 aa), 66% identity in aa 25 - 320 putative transcriptional regulator, LysR family; intergenic shared with yhjB (putative transcriptional regulator)" SANGER GENOME LOCATION " site ""TTGAATATTAATTTAAT""" nd All nine genomes?

yjbE/pgi " STM4222 Ortholog of E. coli orf, hypothetical protein (AAC76996.1); Blastp hit to AAC76996.1 (80 aa), 96% identity in aa 1 - 80 putative outer membrane protein; first gene of the putative operon (yjbE, yjbF, yjbG, yjbH) consisting of putative outer membrane (lipo)proteins; intergenic shared with pgi (glucosephosphate isomerase)" SANGER GENOME LOCATION " site ""TTTAATTTTAACTTATT""" / All nine genomes?

yibD* " STM3707 Ortholog of E. coli putative regulator (AAC76639.1); Blastp hit to AAC76639.1 (344 aa), 80% identity in aa 1 - 343 putative glycosyltransferase" SANGER GENOME LOCATION " site ""CTTAATAGTTTCTTAAT""" m (+ PmrA) Other distributions

STM1926/flhC " hypothetical protein putative cytoplasmic protein Putative RBS for STM1926; RegulonDB:STMS1H002089 Putative RBS for yecG; RegulonDB:STMS1H002090; first gene of a putative operon with yecG (putative universal stres protein); shared intergenic with flhC en flhD (flagellar transcriptional activator)" SANGER GENOME LOCATION " site ""CCTAATGTTCACTTTTT""" / Some or all Salmonella only

STM0334/STM0335 " putative cytoplasmic protein; shared intergenic with STM0335 " SANGER GENOME LOCATION " site ""TTTCATATTCATTTAAT""" / Some Salmonella only

ybdN " STM0605 Ortholog of E. coli orf, hypothetical protein (AAC73703.1); Blastp hit to AAC73703.1 (406 aa), 82% identity in aa 1 - 406 putative 3-phosphoadenosine 5-phosphosulfate sulfotransferase (PAPS reductase)*FAD synthetase Putative RBS for ybdM; RegulonDB:STMS1H000931; first gene of a putative operon with ybdM (hypothetical transcriptional regulator)" SANGER GENOME LOCATION " site ""ATTAATATAAATTTAAT""" nd PmrA All nine genomes?

glgB " STM3538 Ortholog of E. coli 1,4-alpha-glucan branching enzyme (AAC76457.1); Blastp hit to AAC76457.1 (728 aa), 93% identity in aa 1 - 728 1,4-alpha-glucan branching enzyme Putative RBS for glgX; RegulonDB:STMS1H003528; putative first gene of operon involved in glycogen synthesis" SANGER GENOME LOCATION " site ""TTTAAGGGTAGCTTAAT""" m (-) All nine genomes

leuO STM0115 S. typhimurium probable activator protein in leuabcd operon. (SW:LEUO_SALTY) putative transcriptional regulator (LysR family) SANGER GENOME LOCATION " site ""ATTAATGTTAACTTTTT""" m (-) All nine genomes

STM0343 " Paralog of E. coli orf, hypothetical protein (AAC75237.1); Blastp hit to AAC75237.1 (518 aa), 31% identity in aa 10 - 512 putative Diguanylate cyclase*phosphodiesterase domain 1 Putative RBS for STM0343; RegulonDB:STMS1H000699" SANGER GENOME LOCATION " site ""ATTAATGTTACTTTAGT""" nd Subspecies 1 only

orf242 STM1390 S. typhimurium ORF 242 (gi|4456866) putative regulatory proteins, merR family SANGER GENOME LOCATION " site ""CTTAGTCTTCATTTGAT""" / Other distributions

STM1868A/mig-3 " lytic enzyme;intergenic shared with mig-3 (phage assembly protein)" SANGER GENOME LOCATION " site ""CTTAATGATTATTTATT""" / ?

STM2763/STM2726 " Paralog of E. coli prophage CP4-57 integrase (AAC75670.1); Blastp hit to AAC75670.1 (413 aa), 47% identity in aa 1 - 185 putative integrase; intergenic shared with STM2726 (putative inner membrane)" SANGER GENOME LOCATION " site ""ATTAATGTCCATTTAGT""" / S. typhimurium only

pntA " STM1479 Ortholog of E. coli pyridine nucleotide transhydrogenase, alpha subunit (AAC74675.1); Blastp hit to AAC74675.1 (510 aa), 92% identity in aa 1 - 510 pyridine nucleotide transhydrogenase (proton pump), alpha subunit Putative RBS for pntB; RegulonDB:STMS1H001700; first gene of the putative operon (pntA,pntB)" SANGER GENOME LOCATION " site ""TTTAATGTTAATTTCTT""" m (-) All nine genomes

STM0057 " putative citrate-sodium symport; intergenic shared with citC2 (citrate lyase synthetase)" SANGER GENOME LOCATION " site ""CTCATGGTTCATTGAAT""" nd Other distributions

yrbF " STM3313 Ortholog of E. coli putative ATP-binding component of a transport system (AAC76227.1); Blastp hit to AAC76227.1 (269 aa), 94% identity in aa 1 - 266 putative ABC superfamily (atp_bind) transport protein Putative RBS for yrbE; RegulonDB:STMS1H003330" SANGER GENOME LOCATION " site ""CCTAATTTTGACTTTAT""" m (+ PmrA) All nine genomes

yejG " STM2220 Paralog of E. coli orf, hypothetical protein (AAC75242.1); Blastp hit to AAC75242.1 (114 aa), 90% identity in aa 1 - 114 putative cytoplasmic protein" SANGER GENOME LOCATION " site ""CTTTATGTTTATTTTAT""" m (+PmrA) All nine genomes

slsA STM3761 S. typhimurium SlsA (gi|4324613) putative inner membrane protein SANGER GENOME LOCATION " site ""CTTTATGTTATTTAAAT""" nd Other distributions

yhcN " STM3361 Ortholog of E. coli orf, hypothetical protein (AAC76270.1); Blastp hit to AAC76270.1 (104 aa), 79% identity in aa 18 - 104 putative outer membrane protein" SANGER GENOME LOCATION " site ""ATTAGTGTATACTTAAT""" m (+) All nine genomes?

yceP " STM1161 Ortholog of E. coli orf, hypothetical protein (AAC74144.1); Blastp hit to AAC74144.1 (84 aa), 94% identity in aa 1 - 84 putative cytoplasmic protein" SANGER GENOME LOCATION " site ""TTTATTGTTCATATAAT""" m (+) All nine genomes

STM4098 " putative arylsulfate sulfotransferase Putative RBS for STM4098; RegulonDB:STMS1H004022" SANGER GENOME LOCATION " site ""TCTAATATTTATTTAAT""" nd Subspecies 1 only?

stfA STM0195 S. typhimurium major fimbrial subunit StfA (gi|3747029) putative fimbrial subunit SANGER GENOME LOCATION " site ""ATCAATTTTAATTTAAT""" / Some Salmonella only

atpF " STM3869 Ortholog of E. coli membrane-bound ATP synthase, F0 sector, subunit b (AAC76759.1); Blastp hit to AAC76759.1 (156 aa), 96% identity in aa 1 - 156 membrane-bound ATP synthase, F0 sector, subunit b Putative RBS for atpH; RegulonDB:STMS1H003824; first gene of a putative operon encoding putative ATP synthase" SANGER GENOME LOCATION " site ""CAGAAGGTTAACTAGAT""" m (+) All nine genomes

yegH/wza " STM2119 Ortholog of E. coli putative transport protein (AAC75124.1); Blastp hit to AAC75124.1 (549 aa), 90% identity in aa 23 - 549 putative inner membrane protein; intergenic shared with wza (putative polysaccharide export protein)" SANGER GENOME LOCATION " site ""ATTAATATTAAATGAAT""" m (-) All nine genomes

yjgD/argI " STM4470 S. typhimurium hypothetical 15.7 dda protein in argI-miaE intergenic region (ORF15.6). (SW:YJGD_SALTY) putative cytoplasmic protein Putative binding site for ArgR, RegulonDB: STMS1H000025;shared intergenics with argI (arginine ornithine transferase); first gene of a putative operon with miaE (tRNA hydroxylase)" SANGER GENOME LOCATION " site ""ATTAAAATTCACTTTAT""" m (PmrA) All nine genomes

sseJ/STM1630 " STM1631 S. typhimurium secreted effector J SseJ (gi|9931614) Salmonella translocated effector: regulated by SPI-2; shared intergenic with STM1630 (putative inner membrane protein)" SANGER GENOME LOCATION " site ""CTTAAGAAATATTTAAT""" / (PmrA) Some Salmonella only

csrA STM2826 S. typhimurium carbon storage regulator (SW:CSRA_ECOLI) carbon storage regulator SANGER GENOME LOCATION " site ""CTTAGGTTTAACAGAAT""" m (+) All nine genomes

dinP/yafK " STM0313 Ortholog of E. coli damage-inducible protein P; putative tRNA synthetase (AAC73335.1); Blastp hit to AAC73335.1 (351 aa), 91% identity in aa 1 - 351 DNA polymerase IV, devoid of proofreading, damage-inducible protein P; intergenic shared with yafKJ (periplasmic protein, putative amido transferase)" SANGER GENOME LOCATION " site ""CATACTGTACACTTAAA""" m (+) All nine genomes

STM0346 " S. typhimurium unknown (gi|6707276) putative outer membrane protein; Homolog of ail and ompX" SANGER GENOME LOCATION " site ""CATTAGGTGCTCTTAAT""" m Some Salmonella only

ybfA/STM0707 " STM0708 Ortholog of E. coli orf, hypothetical protein (AAC73793.1); Blastp hit to AAC73793.1 (68 aa), 82% identity in aa 1 - 68 putative periplasmic protein; intergenic shared with STM0707 (hypothetical protein)" SANGER GENOME LOCATION " site ""ATTAGTATTAATTTAAC""" m All nine genomes?

yncD/STM1587 " STM1587 Ortholog of E. coli putative outer membrane receptor for iron transport (AAC74533.1); Blastp hit to AAC74533.1 (700 aa), 84% identity in aa 1 - 700 paral putative outer membrane receptor; intergenic shared with STM1586 (putative receptor)" SANGER GENOME LOCATION " site ""CATTTTCTTAACTTAAT""" m (-) All nine genomes

yafC/STM0275 " STM0256 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC73313.1); Blastp hit to AAC73313.1 (304 aa), 90% identity in aa 1 - 303 putative transcriptional regulator, LysR family; intergenic shared STM0275 (drug efflux protein)" SANGER GENOME LOCATION " site ""CAAAATATCAATTTAAT""" m (-) Other distributions

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Gene Name	Gene Function	Annotation	Location	Site	Remarks	Distribution
STM1273	" putative nitric oxide reductase Putative RBS for STM1273; RegulonDB:STMS1H001525"	SANGER	GENOME LOCATION	" site ""CTTAATGTTTTCTTAAT"""	/ (PmrA)	All Salmonella only
STM2132	" pseudogene; frameshift Putative RBS for STM2133; RegulonDB:STMS1H002278"	SANGER	GENOME LOCATION	" site ""TTTTAGATTCACTTAAT"""	/	Some or all Salmonella only
STM4596	" Paralog of E. coli orf, hypothetical protein (AAC73478.1); Blastp hit to AAC73478.1 (222 aa), 31% identity in aa 55 - 222 putative inner membrane protein Putative RBS for STM4596; RegulonDB:STMS1H004455"	SANGER	GENOME LOCATION	" site ""TTTAATATTCACTTAAA"""	/	Some Salmonella only
STM3131	" putative cytoplasmic protein Putative RBS for STM3130; RegulonDB:STMS1H003167; putative first gene of operon with STN3130 (putative hypothetical protein)"	SANGER	GENOME LOCATION	" site ""CTTAATTTTTACTTATT"""	/	All Salmonella only
STM1020	Gifsy-2 prophage	SANGER	GENOME LOCATION	" site ""CTTATTGTTAAGTCAAT"""	/	Other distributions
stdA	" STM3029 Paralog of E. coli putative fimbrial-like protein (AAC73813.1); Blastp hit to AAC73813.1 (188 aa), 32% identity in aa 8 - 187 putative fimbrial-like protein"	SANGER	GENOME LOCATION	" site ""CAAAACATTAACTTAAT"""	/	Subspecies 1 only?
udg	*STM2080 S. typhimurium UDP-glucose 6-dehydrogenase. (SW:UDG_SALTY) UDP-glucoseGDP-mannose dehydrogenase**	SANGER	GENOME LOCATION	" site ""CTCAGAATTAACTTAAT"""	m (+)	All nine genomes
sinR	" STM0304 S. typhimurium SINR protein. (SW:SINR_SALTY) transcriptional regulator Putative RBS for sinR; RegulonDB:STMS1H000662"	SANGER	GENOME LOCATION	" site ""CTTGATATCATCTTAAT"""	/	Subspecies 1 only
STM3131	" putative cytoplasmic protein Putative RBS for STM3130; RegulonDB:STMS1H003167"	SANGER	GENOME LOCATION	" site ""CTTAATACTCACATTAT"""	/	Other distributions
STM4413	" putative imidazolonepropionase and related amidohydrolases Putative RBS for STM4412; RegulonDB:STMS1H004296; first gene of operon with STM4413 (D-galactonate transport)"	SANGER	GENOME LOCATION	" site ""GTGAATGTTAAATTAAT"""	/	Some or all Salmonella only
ybdO	" STM0606 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC73704.1); Blastp hit to AAC73704.1 (300 aa), 54% identity in aa 1 - 298 putative transcriptional regulator, LysR family"	SANGER	GENOME LOCATION	" site ""CTTAATGTAGAGTTTAT"""	m (+ PmrA)	All Salmonella only
oraA	" STM2828 Ortholog of E. coli regulator, OraA protein (AAC75740.1); Blastp hit to AAC75740.1 (166 aa), 87% identity in aa 1 - 166 regulator"	SANGER	GENOME LOCATION	" site ""CTTGATGGTAATTTAAC"""	m (-)	All nine genomes
sdhC	" STM0732 Ortholog of E. coli succinate dehydrogenase, cytochrome b556 (AAC73815.1); Blastp hit to AAC73815.1 (129 aa), 92% identity in aa 1 - 129 succinate dehydrogenase, cytochrome b556 Putative RBS for sdhD; RegulonDB:STMS1H001043; first gene of putative operon encoding succinate dehydrogenase"	SANGER	GENOME LOCATION	" site ""CTTATTATTCCCTTAAG"""	/	All nine genomes
ycaR	" STM0987 Ortholog of E. coli orf, hypothetical protein (AAC74003.1); Blastp hit to AAC74003.1 (60 aa), 93% identity in aa 1 - 60 putative inner membrane protein Putative RBS for kdsB; RegulonDB:STMS1H001272; first gene of a putative operon with ksdB (CMP-3-deoxy-D-manno-octulosanate transferase"	SANGER	GENOME LOCATION	" site ""TTCAATATTAACATAAT"""	/	All nine genomes
lasT	*" STM4600 Ortholog of E. coli orf, hypothetical protein (AAC77356.1); Blastp hit to AAC77356.1 (228 aa), 82% identity in aa 1 - 228 putative tRNAtRNA methyltransferase"**	SANGER	GENOME LOCATION	" site ""ATTTAGGATAATTTAAT"""	nd (pmrA)	All nine genomes
STM2137	putative cytoplasmic protein	SANGER	GENOME LOCATION	" site ""TTTAACCTTAATTTAAT"""	nd	Some Salmonella only
STM1672	putative cytoplasmic protein	SANGER	GENOME LOCATION	" site ""ATTAATAGTCACTTATT"""	/	Subspecies 1 only?
gcvA	" STM2982 Ortholog of E. coli positive regulator of gcv operon (AAC75850.1); Blastp hit to AAC75850.1 (305 aa), 98% identity in aa 1 - 305 regulator of gcv operon (LysR family); first gene of putative operon (gcvA,ygdD,ygdE containing a SAM dependent methyltransferase)"	SANGER	GENOME LOCATION	" site ""CTTAATGTCGAATGAAT"""	m (+)	All nine genomes
ycgO	" STM1801 Ortholog of E. coli orf, hypothetical protein (AAC74275.1); Blastp hit to AAC74275.1 (536 aa), 92% identity in aa 1 - 535 putative CPA1 family, Na:H transport protein"	SANGER	GENOME LOCATION	" site ""TTTAACATTAACATAAT"""	m (+)	All nine genomes?
STM2287	*" Paralog of E. coli putative sulfatase phosphatase (AAC75329.1); Blastp hit to AAC75329.1 (403 aa), 30% identity in aa 27 - 294, 29 503321556dentity in aa 297 - 363 putative cytoplasmic protein"**	SANGER	GENOME LOCATION	" site ""CTTATTATTCACATAAC"""	/	Some or all Salmonella only?
yebW	" STM1852 Ortholog of E. coli orf, hypothetical protein (AAC74907.1); Blastp hit to AAC74907.1 (91 aa), 87% identity in aa 29 - 91 putative inner membrane lipoprotein"	SANGER	GENOME LOCATION	" site ""CTCAATGTTAACTACTT"""	/	All nine genomes?
STM0897	" hypothetical protein Fels-1 prophage Putative RBS for STM0897; RegulonDB:STMS1H001190"	SANGER	GENOME LOCATION	" site ""CGTAAGGCTCTTTTAAT"""	/	Some Salmonella only
lpfA	" STM3640 S. typhimurium long polar fimbria protein A precursor. (SW:LPFA_SALTY) long polar fimbria; first gene of a putative fimbriae synthesis operon"	SANGER	GENOME LOCATION	" site ""ATTAAGAATAAATTAAT"""	/ (PmrA)	Other distributions
positive strand
yjdB*	*" STM4293 S. typhimurium hypothetical 61.6 Kda protein in basSpmrA-adiY intergenic region. (SW:YJDB_SALTY) putative integral membrane protein Putative RBS for basR; RegulonDB:STMS1H004188"**	SANGER	GENOME LOCATION	" site ""CTTAAGGTTCACTTAAT"""	m (+ PmrA)	All nine genomes
udg*	*STM2080 S. typhimurium UDP-glucose 6-dehydrogenase. (SW:UDG_SALTY) UDP-glucoseGDP-mannose dehydrogenase**	SANGER	GENOME LOCATION	" site ""CTTAATATTAACTTAAT"""	m (+ PmrA)	All nine genomes
yfbE/ais*	" STM2297 Ortholog of E. coli putative enzyme (AAC75313.1); Blastp hit to AAC75313.1 (390 aa), 82% identity in aa 6 - 390 putative DegTDnrJEryC1*StrS family Putative RBS for pmrF; RegulonDB:STMS1H002430; first gene of the yfbE operon; shared intergenic with ais"	SANGER	GENOME LOCATION	" site ""CTTAATGTTAATTTAAT"""	m (+ PmrA)	All nine genomes?
STM1269/STM1268*	" putative chorismate mutase; intergenic shared with STM1268"	SANGER	GENOME LOCATION	" site ""CTTAATGTTATCTTAAT"""	/ (PmrA)	All Salmonella only
STM0692	" Paralog of E. coli nitrogen assimilation control protein (AAC75050.1); Blastp hit to AAC75050.1 (305 aa), 32% identity in aa 1 - 301 putative transcriptional regulator, LysR family"	SANGER	GENOME LOCATION	" site ""CTTGATGTTGATTTAAT"""	/	All Salmonella only
ybjG/mdfA*	" STM0865 Ortholog of E. coli orf, hypothetical protein (AAC73928.1); Blastp hit to AAC73928.1 (198 aa), 78% identity in aa 1 - 198 putative permease; intergenic shared with mdfA (multidrug translocase)"	SANGER	GENOME LOCATION	" site ""TTTAAGGTTAATTTAAG"""	m (+PmrA)	All nine genomes
STM2901	" hypothetical protein putative cytoplasmic protein; located downstream of pathogenicity island 1"	SANGER	GENOME LOCATION	" site ""CTTAATATCAATATAAT"""	/	Other distributions
yhjC/yhjB	" STM3607 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC76546.1); Blastp hit to AAC76546.1 (323 aa), 66% identity in aa 25 - 320 putative transcriptional regulator, LysR family; intergenic shared with yhjB (putative transcriptional regulator)"	SANGER	GENOME LOCATION	" site ""TTGAATATTAATTTAAT"""	nd	All nine genomes?
yjbE/pgi	" STM4222 Ortholog of E. coli orf, hypothetical protein (AAC76996.1); Blastp hit to AAC76996.1 (80 aa), 96% identity in aa 1 - 80 putative outer membrane protein; first gene of the putative operon (yjbE, yjbF, yjbG, yjbH) consisting of putative outer membrane (lipo)proteins; intergenic shared with pgi (glucosephosphate isomerase)"	SANGER	GENOME LOCATION	" site ""TTTAATTTTAACTTATT"""	/	All nine genomes?
yibD*	" STM3707 Ortholog of E. coli putative regulator (AAC76639.1); Blastp hit to AAC76639.1 (344 aa), 80% identity in aa 1 - 343 putative glycosyltransferase"	SANGER	GENOME LOCATION	" site ""CTTAATAGTTTCTTAAT"""	m (+ PmrA)	Other distributions
STM1926/flhC	" hypothetical protein putative cytoplasmic protein Putative RBS for STM1926; RegulonDB:STMS1H002089 Putative RBS for yecG; RegulonDB:STMS1H002090; first gene of a putative operon with yecG (putative universal stres protein); shared intergenic with flhC en flhD (flagellar transcriptional activator)"	SANGER	GENOME LOCATION	" site ""CCTAATGTTCACTTTTT"""	/	Some or all Salmonella only
STM0334/STM0335	" putative cytoplasmic protein; shared intergenic with STM0335 "	SANGER	GENOME LOCATION	" site ""TTTCATATTCATTTAAT"""	/	Some Salmonella only
ybdN	" STM0605 Ortholog of E. coli orf, hypothetical protein (AAC73703.1); Blastp hit to AAC73703.1 (406 aa), 82% identity in aa 1 - 406 putative 3-phosphoadenosine 5-phosphosulfate sulfotransferase (PAPS reductase)*FAD synthetase Putative RBS for ybdM; RegulonDB:STMS1H000931; first gene of a putative operon with ybdM (hypothetical transcriptional regulator)"	SANGER	GENOME LOCATION	" site ""ATTAATATAAATTTAAT"""	nd PmrA	All nine genomes?
glgB	" STM3538 Ortholog of E. coli 1,4-alpha-glucan branching enzyme (AAC76457.1); Blastp hit to AAC76457.1 (728 aa), 93% identity in aa 1 - 728 1,4-alpha-glucan branching enzyme Putative RBS for glgX; RegulonDB:STMS1H003528; putative first gene of operon involved in glycogen synthesis"	SANGER	GENOME LOCATION	" site ""TTTAAGGGTAGCTTAAT"""	m (-)	All nine genomes
leuO	STM0115 S. typhimurium probable activator protein in leuabcd operon. (SW:LEUO_SALTY) putative transcriptional regulator (LysR family)	SANGER	GENOME LOCATION	" site ""ATTAATGTTAACTTTTT"""	m (-)	All nine genomes
STM0343	" Paralog of E. coli orf, hypothetical protein (AAC75237.1); Blastp hit to AAC75237.1 (518 aa), 31% identity in aa 10 - 512 putative Diguanylate cyclase*phosphodiesterase domain 1 Putative RBS for STM0343; RegulonDB:STMS1H000699"	SANGER	GENOME LOCATION	" site ""ATTAATGTTACTTTAGT"""	nd	Subspecies 1 only
orf242	STM1390 S. typhimurium ORF 242 (gi\|4456866) putative regulatory proteins, merR family	SANGER	GENOME LOCATION	" site ""CTTAGTCTTCATTTGAT"""	/	Other distributions
STM1868A/mig-3	" lytic enzyme;intergenic shared with mig-3 (phage assembly protein)"	SANGER	GENOME LOCATION	" site ""CTTAATGATTATTTATT"""	/	?
STM2763/STM2726	" Paralog of E. coli prophage CP4-57 integrase (AAC75670.1); Blastp hit to AAC75670.1 (413 aa), 47% identity in aa 1 - 185 putative integrase; intergenic shared with STM2726 (putative inner membrane)"	SANGER	GENOME LOCATION	" site ""ATTAATGTCCATTTAGT"""	/	S. typhimurium only
pntA	" STM1479 Ortholog of E. coli pyridine nucleotide transhydrogenase, alpha subunit (AAC74675.1); Blastp hit to AAC74675.1 (510 aa), 92% identity in aa 1 - 510 pyridine nucleotide transhydrogenase (proton pump), alpha subunit Putative RBS for pntB; RegulonDB:STMS1H001700; first gene of the putative operon (pntA,pntB)"	SANGER	GENOME LOCATION	" site ""TTTAATGTTAATTTCTT"""	m (-)	All nine genomes
STM0057	" putative citrate-sodium symport; intergenic shared with citC2 (citrate lyase synthetase)"	SANGER	GENOME LOCATION	" site ""CTCATGGTTCATTGAAT"""	nd	Other distributions
yrbF	" STM3313 Ortholog of E. coli putative ATP-binding component of a transport system (AAC76227.1); Blastp hit to AAC76227.1 (269 aa), 94% identity in aa 1 - 266 putative ABC superfamily (atp_bind) transport protein Putative RBS for yrbE; RegulonDB:STMS1H003330"	SANGER	GENOME LOCATION	" site ""CCTAATTTTGACTTTAT"""	m (+ PmrA)	All nine genomes
yejG	" STM2220 Paralog of E. coli orf, hypothetical protein (AAC75242.1); Blastp hit to AAC75242.1 (114 aa), 90% identity in aa 1 - 114 putative cytoplasmic protein"	SANGER	GENOME LOCATION	" site ""CTTTATGTTTATTTTAT"""	m (+PmrA)	All nine genomes
slsA	STM3761 S. typhimurium SlsA (gi\|4324613) putative inner membrane protein	SANGER	GENOME LOCATION	" site ""CTTTATGTTATTTAAAT"""	nd	Other distributions
yhcN	" STM3361 Ortholog of E. coli orf, hypothetical protein (AAC76270.1); Blastp hit to AAC76270.1 (104 aa), 79% identity in aa 18 - 104 putative outer membrane protein"	SANGER	GENOME LOCATION	" site ""ATTAGTGTATACTTAAT"""	m (+)	All nine genomes?
yceP	" STM1161 Ortholog of E. coli orf, hypothetical protein (AAC74144.1); Blastp hit to AAC74144.1 (84 aa), 94% identity in aa 1 - 84 putative cytoplasmic protein"	SANGER	GENOME LOCATION	" site ""TTTATTGTTCATATAAT"""	m (+)	All nine genomes
STM4098	" putative arylsulfate sulfotransferase Putative RBS for STM4098; RegulonDB:STMS1H004022"	SANGER	GENOME LOCATION	" site ""TCTAATATTTATTTAAT"""	nd	Subspecies 1 only?
stfA	STM0195 S. typhimurium major fimbrial subunit StfA (gi\|3747029) putative fimbrial subunit	SANGER	GENOME LOCATION	" site ""ATCAATTTTAATTTAAT"""	/	Some Salmonella only
atpF	" STM3869 Ortholog of E. coli membrane-bound ATP synthase, F0 sector, subunit b (AAC76759.1); Blastp hit to AAC76759.1 (156 aa), 96% identity in aa 1 - 156 membrane-bound ATP synthase, F0 sector, subunit b Putative RBS for atpH; RegulonDB:STMS1H003824; first gene of a putative operon encoding putative ATP synthase"	SANGER	GENOME LOCATION	" site ""CAGAAGGTTAACTAGAT"""	m (+)	All nine genomes
yegH/wza	" STM2119 Ortholog of E. coli putative transport protein (AAC75124.1); Blastp hit to AAC75124.1 (549 aa), 90% identity in aa 23 - 549 putative inner membrane protein; intergenic shared with wza (putative polysaccharide export protein)"	SANGER	GENOME LOCATION	" site ""ATTAATATTAAATGAAT"""	m (-)	All nine genomes
yjgD/argI	" STM4470 S. typhimurium hypothetical 15.7 dda protein in argI-miaE intergenic region (ORF15.6). (SW:YJGD_SALTY) putative cytoplasmic protein Putative binding site for ArgR, RegulonDB: STMS1H000025;shared intergenics with argI (arginine ornithine transferase); first gene of a putative operon with miaE (tRNA hydroxylase)"	SANGER	GENOME LOCATION	" site ""ATTAAAATTCACTTTAT"""	m (PmrA)	All nine genomes
sseJ/STM1630	" STM1631 S. typhimurium secreted effector J SseJ (gi\|9931614) Salmonella translocated effector: regulated by SPI-2; shared intergenic with STM1630 (putative inner membrane protein)"	SANGER	GENOME LOCATION	" site ""CTTAAGAAATATTTAAT"""	/ (PmrA)	Some Salmonella only
csrA	STM2826 S. typhimurium carbon storage regulator (SW:CSRA_ECOLI) carbon storage regulator	SANGER	GENOME LOCATION	" site ""CTTAGGTTTAACAGAAT"""	m (+)	All nine genomes
dinP/yafK	" STM0313 Ortholog of E. coli damage-inducible protein P; putative tRNA synthetase (AAC73335.1); Blastp hit to AAC73335.1 (351 aa), 91% identity in aa 1 - 351 DNA polymerase IV, devoid of proofreading, damage-inducible protein P; intergenic shared with yafKJ (periplasmic protein, putative amido transferase)"	SANGER	GENOME LOCATION	" site ""CATACTGTACACTTAAA"""	m (+)	All nine genomes
STM0346	" S. typhimurium unknown (gi\|6707276) putative outer membrane protein; Homolog of ail and ompX"	SANGER	GENOME LOCATION	" site ""CATTAGGTGCTCTTAAT"""	m	Some Salmonella only
ybfA/STM0707	" STM0708 Ortholog of E. coli orf, hypothetical protein (AAC73793.1); Blastp hit to AAC73793.1 (68 aa), 82% identity in aa 1 - 68 putative periplasmic protein; intergenic shared with STM0707 (hypothetical protein)"	SANGER	GENOME LOCATION	" site ""ATTAGTATTAATTTAAC"""	m	All nine genomes?
yncD/STM1587	" STM1587 Ortholog of E. coli putative outer membrane receptor for iron transport (AAC74533.1); Blastp hit to AAC74533.1 (700 aa), 84% identity in aa 1 - 700 paral putative outer membrane receptor; intergenic shared with STM1586 (putative receptor)"	SANGER	GENOME LOCATION	" site ""CATTTTCTTAACTTAAT"""	m (-)	All nine genomes
yafC/STM0275	" STM0256 Ortholog of E. coli putative transcriptional regulator LYSR-type (AAC73313.1); Blastp hit to AAC73313.1 (304 aa), 90% identity in aa 1 - 303 putative transcriptional regulator, LysR family; intergenic shared STM0275 (drug efflux protein)"	SANGER	GENOME LOCATION	" site ""CAAAATATCAATTTAAT"""	m (-)	Other distributions

References

Aguirre A., Lejona S., Vescovi E.G., and Soncini, F.C. 2000. Phosphorylated PmrA interacts with the promoter region of ugd in Salmonella enterica serovar Typhimurium. J. Bacteriol. 182: 3874-3876.

Marchal K., Thijs G., De Keersmaecker S., Monsieurs P., De Moor B., and Vanderleyden J. 2003. Genome-specific higher-order background models to improve motif detection. Trends Micr. 11:61-66.

McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D., Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E., Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R., Wilson R.K. 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852-856.

Thijs G., Marchal K., Lescot M., Rombauts S., De Moor B., Rouze P., and Moreau Y. 2002. A gibbs sampling method to detect overrepresented motifs in the upstream regions of coexpressed genes. J. Comput. Biol. 9: 447-464.

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