| 1 |
aidB |
I: Lipid transport and metabolism |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (PubMed: 14979322).
FUNCTION: Protection against alkylation damage to DNA (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 2 |
alkA |
L: Replication, recombination and repair |
Yes |
FUNCTIONAL GROUP: DNA/RNA metabolism, Repair (PubMed: 14979322).
FUNCTION: HhH-GPD superfamily base excision DNA repair (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 3 |
amiC |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (PubMed: 14979322).
FUNCTION: Cell-wall hydrolysis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 4 |
ansC |
K: Transcription |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 5 |
araG |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: L-arabinose transport (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages (PubMed: 14979322). |
| 6 |
aroC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Chorismate synthase (EC 4.2.3.5) (5-enolpyruvylshikimate-3-phosphate phospholyase)(Swiss-prot: P63608).
CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-prot: P63608).
COFACTOR: Reduced flavin (By similarity)(Swiss-prot: P63608).
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and PEP: step 7 [final step](Swiss-prot: P63608).
PATHWAY: Context: Aromatic amino acids biosynthesis(Swiss-prot: P63608).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: P63608).
SIMILARITY: Belongs to the chorismate synthase family(Swiss-prot: P63608).
MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models (PubMed: 11119550). |
| 7 |
arsR6 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: ArsR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 8 |
artI |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Arginine transport system (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 9 |
aspB |
K: Transcription |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Aminotransferase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 10 |
aspC |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): aspartate aminotransferase
MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth (PubMed: 12761078). |
| 11 |
bacA |
I: Lipid transport and metabolism |
Yes |
Protein name(s): bacteroid development protein BacA
MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain (PubMed: 10741969). R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis (PubMed: 10741969). The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria(PubMed: 12270820). |
| 12 |
bcsP31 |
N/A
|
No |
Protein name(s): 31 kDa immunogenic protein precursor(Swiss-prot: P0A3T2).
MISCELLANEOUS: Brucella abortus is the causative agent for brucellosis in cattle and man(Swiss-prot: P0A3T2).
MUTATION: The 31-kDa salt-extractable immunogenic protein, BCSP31, was deleted from several Brucella abortus
strains by replacement with a marker gene encoding resistance to the antibiotics kanamycin and neomycin. The BCSP31 gene replacement plasmids, constructed with ColEl-derived vectors, were introduced by electroporation into B. abortus strain 19 (S19), into a rough variant of B. abortus S19, and into B. abortus S2308, and antibiotic-resistant transformants were isolated. Loss of
the gene encoding BCSP31 and presence of the marker gene were confirmed by Southern analysis. Vector
sequences were either absent or linked to the genome, indicating that ColEl-derived plasmids are not
maintained in B. abortus. Survival of B. abortus mutant strains in the macrophagelike cell line J774 and in HeLa cells was examined and shown to be indistinguishable from that of the parental strain (PubMed: 1937745). |
| 13 |
bfr |
P: Inorganic ion transport and metabolism |
No |
Protein name(s): Bacterioferritin (BFR)(Swiss-prot: Q8FW95).
FUNCTION: May perform analogous functions in iron detoxification and storage to that of animal ferritins(Swiss-prot: Q8FW95).
COFACTOR: Binds 1 heme B (iron-protoporphyrin IX) group per dimer (By similarity)(Swiss-prot: Q8FW95).
SUBUNIT: Oligomer of 24 identical subunits (By similarity)(Swiss-prot: Q8FW95).
MISCELLANEOUS: The di-iron binding site functions as active site where iron ions are oxidized from Fe(2+) to Fe(3+) before they are stored (By similarity)(Swiss-prot: Q8FW95).
SIMILARITY: Belongs to the bacterioferritin family(Swiss-prot: Q8FW95).
SIMILARITY: Contains 1 ferritin-like diiron domain(Swiss-prot: Q8FW95).
MUTATION: Brucella bacterioferritin (BFR) is a heme -containing iron storage multimeric protein composed of 24 identical subunits, which form a roughly spherical protein shell surrounding a central iron storage cavity. A BFR deletion mutant of Brucella melitensis 16M was generated by gene replacement. The deletion was complemented with a broad -host- range vector carrying the wild-type bfr gene , pBBR-bfr. The survival and growth of the mutant, B melitensis PAD 2- 78, were similar to those of its parental strain in human monocyte -derived macrophages (MDM). These results suggest that BFR is not essential for the intracellular survival of B melitensis in human MDM (PubMed: 9317046). |
| 14 |
bicA |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: Macrolide efflux (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 15 |
BMEI0085 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 16 |
BMEI0455 |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Glutathione S-transferase, C-terminal domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 17 |
BMEI0671 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Terc dome (efflux) (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 18 |
BMEI1229 |
L: Replication, recombination and repair |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Exonuclease X-T domain (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 19 |
BMEI1258 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 20 |
BMEI1339 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Agrobacterium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 21 |
BMEI1361 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 22 |
BMEI1443 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: haloacid dehalogenase-like hydrolase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 23 |
BMEI1448 |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: EAL domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 24 |
BMEI1531 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Other genes (PubMed: 14979322).
FUNCTION: protein-protein interaction (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 25 |
BMEI1658 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 26 |
BMEI1809 |
S: Function unknown |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: ERFK/YBIS/YCFS/YNHG family (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 27 |
BMEI1844 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Domain of Unkown Function (DUF930) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 28 |
BMEI1859 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Uncharacterised protein family 0005 (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 29 |
BMEI1879 |
-: Not in COGs |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Mesorhizobium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 30 |
BMEI1902 |
H: Coenzyme transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Brucella/Mesorhizobium orphan gene (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 31 |
BMEII0128 |
S: Function unknown |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Uncharacterised protein family (DUF0261) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 32 |
BMEII0274 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: GTPase of unknown function domain, FeoB domain (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 33 |
BMEII0318 |
V: Defense mechanisms |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 34 |
BMEII0336 |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 35 |
BMEII0626 |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Dipeptidase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 36 |
BMEII0923 |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 37 |
BMEII0935 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: Bacterial protein of unknown function (DUF89) (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 38 |
BMEII1037 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: Other genes (PubMed: 14979322).
FUNCTION: Zinc protease (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 39 |
BMEII1045 |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: Unkown function (PubMed: 14979322).
FUNCTION: haloacid dehalogenase-like hydrolase domain (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 40 |
bp26 |
N/A
|
No |
Protein name(s): 26 kDa periplasmic immunogenic protein precursor (28 kDa outer membrane protein) (28 kDa cytosoluble protein) (CP28)(Swiss-prot: P0A3U9).
SUBCELLULAR LOCATION: Periplasmic(Swiss-prot: P0A3U9).
MUTATION: The periplasmic protein BP26 is an immunodominant antigen in the serological responses of Brucella infected animals. Cloning of the gene coding for BP26 has allowed the construction of a mutant of B abortus S19 vaccine strain unable to express bp26. This mutant vaccine strain protected mice from infection with pathogenic B abortus 2308 to a level similar to that of the parental S19 strain. The B abortus S19 bp26 mutant vaccine strain might be used in combination with a BP26-based serological test for the differential diagnosis between infected and vaccinated animals (PubMed: 12853399). B. melitensis Rev. 1 bp26 deletion mutant did not modify the kinetics of splenic infection nor the residual virulence of Rev. 1 in the BALBc mouse model. Vaccination of BALBc mice with the deletion mutant conferred significant protective immunity against B melitensis strain H38 or B ovis strain PA challenges, to the same extent as that induced by parental Rev. 1 strain. Thus, the Rev. 1 bp26 deletion mutant is a promising vaccine candidate against B melitensis and B ovis infections (PubMed: 15246618). |
| 41 |
bvrR |
T: Signal transduction mechanisms |
Yes |
Protein name(s): BvrR, DNA-binding response regulator
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (PubMed: 16077108).
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (PubMed: 12414153).
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (PubMed: 9826346).
B abortus bvrS bvrR mutants display reduced invasiveness and virulence (PubMed: 11401996).
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (PubMed: 12414149).
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (PubMed: 12218183).
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (PubMed: 12218183). |
| 42 |
bvrS |
T: Signal transduction mechanisms |
Yes |
Protein name(s): BvrS, sensor histidine kinase
MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly (PubMed: 16077108).
Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism (PubMed: 12414153).
In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments (PubMed: 9826346).
B abortus bvrS bvrR mutants display reduced invasiveness and virulence (PubMed: 11401996).
Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact (PubMed: 12414149).
Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments (PubMed: 12218183).
BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly (PubMed: 12218183). |
| 43 |
caiB |
C: Energy production and conversion |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: CAIB/BAIF family (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 44 |
carAB |
F: Nucleotide transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Clut. and pyr. Syntheis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 45 |
cbbE |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Ribulose-phosphate 3-epimerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 46 |
ccoN |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): cytochrome c oxidase, cbb3-type, subunit I
MUTATION: The ccoN mutation of B suis had no effect on the replication of the bacteria inside human THP-1 macrophage cells. This is consistent with the absence of expression of the ccoNOQP promoter at the intracellular state (PubMed: 16239582). The ccoNOQP locus potentially encodes another high-oxygen-affinity oxidase, the cytochrome cbb3-type terminal oxidase |
| 47 |
clpA |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): ATP-dependent Clp protease, ATP-binding subunit ClpA
MUTATION: The protein ClpA belongs to a diverse group of polypeptides named ClpATPases , which are highly conserved , and which include several molecular chaperones. In intracellular infection of human THP-1 or murine J774 macrophage -like cells , the clpA null mutant and , to a lesser extent , the strain of B suis overexpressing b-clpA behaved similarly to the wild-type strain. In a murine model of infection, however, the absence of ClpA significantly increased persistence of B suis. These results showed that in B suis the highly conserved protein ClpA by itself was dispensable for intramacrophagic growth, but was involved in temperature -dependent growth regulation, and in bacterial clearance from infected BALBc mice (PubMed: 10878125). |
| 48 |
clpB |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): Chaperone clpB(Swiss-prot: Q7CEG6).
FUNCTION: Part of a stress-induced multi-chaperone system, it is involved in the recovery of the cell from heat-induced damage, in cooperation with dnaK, dnaJ and grpE. Acts before dnaK, in the processing of protein aggregates. Protein binding stimulates the ATPase activity; ATP hydrolysis unfolds the denatured protein aggregates, which probably helps expose new hydrophobic binding sites on the surface of clpB-bound aggregates, contributing to the solubilization and refolding of denatured protein aggregates by dnaK (By similarity)(Swiss-prot: Q7CEG6).
SUBUNIT: Homohexamer. The oligomerization is ATP-dependent (By similarity)(Swiss-prot: Q7CEG6).
SUBCELLULAR LOCATION: Cytoplasm (Probable)(Swiss-prot: Q7CEG6).
INDUCTION: By heat and acid shock(Swiss-prot: Q7CEG6).
DOMAIN: The N-terminal domain probably functions as a substrate-discriminating domain, recruiting aggregated proteins to the clpB hexamer and/or stabilizing bound proteins. The NBD2 domain is responsible for oligomerization, whereas the NBD1 domain stabilizes the hexamer probably in an ATP-dependent manner. The movement of the coiled-coil domain is essential for clpB ability to rescue proteins from an aggregated state, probably by pulling apart large aggregated proteins, which are bound between the coiled-coils motifs of adjacent clpB subunits in the functional hexamer (By similarity)(Swiss-prot: Q7CEG6).
SIMILARITY: Belongs to the clpA/clpB family(Swiss-prot: Q7CEG6).
MUTATION: Simultaneous inactivation of clpA and clpB resulted in a mutant that was sensitive to oxidative stress . In B suis expressing gfp , ClpA but not ClpB participated in degradation of the green fluorescent protein at 42C We concluded that ClpB was responsible for tolerance to several stresses and that the lethality caused by harsh environmental conditions may have similar molecular origins . |
| 49 |
clpP |
U: Intracellular trafficking and secretion |
No |
Protein name(s): ATP-dependent Clp protease proteolytic subunit (EC 3.4.21.92) (Endopeptidase Clp)(Swiss-prot: Q8G0I4).
FUNCTION: Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity)(Swiss-prot: Q8G0I4).
CATALYTIC ACTIVITY: Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs)(Swiss-prot: Q8G0I4).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0I4).
SIMILARITY: Belongs to the peptidase S14 family(Swiss-prot: Q8G0I4).
MUTATION: Our hypothesis was that ClpP, the major housekeeping intracellular protease of L lactis, degraded the cytoplasmic form of L7L12. pCYT:L7L12 was then introduced in a clpP mutant of NZ9000 but no significant increase was observed, suggesting that ClpP was not involved in this putative proteolysis (PubMed: 11823235). |
| 50 |
cobB |
H: Coenzyme transport and metabolism |
Yes |
Protein name(s): Cobyrinic acid A,C-diamide synthase(Swiss-prot: Q8G020).
FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-prot: Q8G020).
PATHWAY: Cobalamin biosynthesis(Swiss-prot: Q8G020).
SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-prot: Q8G020).
MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them (PubMed: 14638795). |
| 51 |
cobW |
R: General function prediction only |
Yes |
Cobalamin synthesis protein/P47K
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 52 |
cydB |
C: Energy production and conversion |
Yes |
Protein name(s): cytochrome d ubiquinol oxidase, subunit II
MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice (PubMed: 11274104). The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (PubMed: 12761078). |
| 53 |
cydC |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Cytochrome oxidase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 54 |
cydD |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): ABC transporter, ATP-binding protein CydD
MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment (PubMed: 12761078). |
| 55 |
cysI |
P: Inorganic ion transport and metabolism |
Yes |
Protein name(s): sulfite reductase (NADPH) hemoprotein beta-component
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Sulfite reductate (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, but not in HeLa (PubMed: 14979322). |
| 56 |
cysK |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Cys. synthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 57 |
cysY |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide oxidoreducate (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 58 |
dacF |
V: Defense mechanisms |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan (PubMed: 14979322).
FUNCTION: Peptidoglycan synthesis (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 59 |
dbsA |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Ribose transport (PubMed: 14979322).
MUTATION: Attenuated in HeLa (PubMed: 14979322). |
| 60 |
degP |
N/A
|
Yes |
Protein name(s): Probable serine protease do-like precursor (EC 3.4.21.-)(Swiss-prot: P0A3Z5).
SUBCELLULAR LOCATION: Periplasmic (Potential)(Swiss-prot: P0A3Z5).
SIMILARITY: Belongs to the peptidase S1C family(Swiss-prot: P0A3Z5).
SIMILARITY: Contains 2 PDZ (DHR) domains(Swiss-prot: P0A3Z5).
MUTATION: The DegP protease, a multifunctional chaperone and protease, has been shown to be essential for virulence in gram-negative pathogens such as Salmonella enterica serovar Typhimurium, Brucella abortus. The function of DegP in pathogenesis appears to be the degradation of damaged proteins that accumulate as a result of the initial host response to infection, which includes the release of reactive oxygen intermediates. Point mutations in residues presumed to represent two members of the catalytic triad (serine 210 and histidine 105) inactivated enzymatic activity, confirming the classification of DegP as a serine protease.
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis htrA (synonym: degP) gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 61 |
deoR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 62 |
dhbC |
Q: Secondary metabolites biosynthesis, transport and catabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Sideophore sysnhesis, Fe3+ uptake (PubMed: 14979322).
MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes (PubMed: 14979322). |
| 63 |
divK |
T: Signal transduction mechanisms |
Yes |
Protein name(s): polar differentiation response regulator
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Response regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 64 |
dnaJ |
O: Posttranslational modification, protein turnover, chaperones |
No |
Protein name(s): Chaperone protein dnaJ(Swiss-prot: Q8FXX1).
FUNCTION: Participates actively in the response to hyperosmotic and heat shock by preventing the aggregation of stress-denatured proteins and by disaggregating proteins, also in an autonomous, dnaK-independent fashion. Unfolded proteins bind initially to dnaJ; upon interaction with the dnaJ-bound protein, dnaK hydrolyzes its bound ATP, resulting in the formation of a stable complex. GrpE releases ADP from dnaK; ATP binding to dnaK triggers the release of the substrate protein, thus completing the reaction cycle. Several rounds of ATP-dependent interactions between dnaJ, dnaK and grpE are required for fully efficient folding. Also involved, together with dnaK and grpE, in the DNA replication of plasmids through activation of initiation proteins (By similarity)(Swiss-prot: Q8FXX1).
COFACTOR: Binds 2 zinc ions per monomer (By similarity)(Swiss-prot: Q8FXX1).
SUBUNIT: Homodimer (By similarity)(Swiss-prot: Q8FXX1).
SUBCELLULAR LOCATION: Cytoplasm (Probable)(Swiss-prot: Q8FXX1).
DOMAIN: The J domain is necessary and sufficient to stimulate dnaK ATPase activity. Zinc center 1 plays an important role in the autonomous, dnaK-independent chaperone activity of dnaJ. Zinc center 2 is essential for interaction with dnaK and for dnaJ activity (By similarity)(Swiss-prot: Q8FXX1).
SIMILARITY: Belongs to the dnaJ family(Swiss-prot: Q8FXX1).
SIMILARITY: Contains 1 CR domain(Swiss-prot: Q8FXX1).
SIMILARITY: Contains 1 J domain(Swiss-prot: Q8FXX1).
MUTATION: dnaJ is located downstream of dnaK and forms an operon with dnaK. dnaJ is not involved in resistance to acid stress and intracellular multiplication of the pathogen. A dnaJ knockout mutant of B suis behaves like the wild-type strain (PubMed: 11854256). Insertional inactivation of dnaK and dnaJ within the dnaKJ locus led to the conclusion that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally (PubMed: 8793869). |
| 65 |
dnaK |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): Chaperone protein dnaK (Heat shock protein 70) (Heat shock 70 kDa protein) (HSP70)(Swiss-prot: Q8FXX2).
FUNCTION: Acts as a chaperone (By similarity)(Swiss-prot: Q8FXX2).
INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-prot: Q8FXX2).
SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-prot: Q8FXX2).
MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis (PubMed: 11854256).
Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication (PubMed: 8793869). |
| 66 |
dppA |
E: Amino acid transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: Dipeptide uptake (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 67 |
dsbA |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide bond formation protein (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 68 |
dsbB |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Disulfide bond formation protein (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 69 |
dut |
F: Nucleotide transport and metabolism |
Yes |
Protein name(s): Deoxyuridine 5'-triphosphate nucleotidohydrolase (EC 3.6.1.23) (dUTPase) (dUTP pyrophosphatase)(Swiss-prot: P64005).
FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-prot: P64005).
CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-prot: P64005).
PATHWAY: De novo synthesis of thymidylate(Swiss-prot: P64005).
SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). the dUTPase family(Swiss-prot: P64005). |
| 70 |
dxps |
I: Lipid transport and metabolism |
Yes |
FUNCTIONAL GROUP: Vitamines cofactors (PubMed: 14979322).
FUNCTION: Thiamine synthesis (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 71 |
entC |
Q: Secondary metabolites biosynthesis, transport and catabolism |
No |
Protein name(s): isochorismate synthase
MUTATION: 2, 3-Dihydroxybenzoic acid (DHBA ) is the only siderophore described for Brucella , and previous studies suggested that DHBA might contribute to the capacity of these organisms to persist in host macrophages. Employing an isogenic siderophore mutant (entC) constructed from virulent Brucella abortus 2308, however, it was found that production of DHBA is not required for replication in cultured murine macrophages or for the establishment and maintenance of chronic infection in the BALBc mouse model (PubMed: 10225929). |
| 72 |
entE |
Q: Secondary metabolites biosynthesis, transport and catabolism |
No |
Protein name(s): 2,3-dihydroxybenzoate-AMP ligase
MUTATION: B abortus entE mutant was unable to synthesize brucebactin, but it exhibited no defeat in intracellular infection (PubMed: 15385478). |
| 73 |
eryA |
G: Carbohydrate transport and metabolism |
No |
Protein name(s): erythritol kinase
MUTATION: EryA is an erythritol kinase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (PubMed: 10708387).
The eryA gene of the bacterial pathogen Brucella abortus expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P) (PubMed: 12639570).
|
| 74 |
eryB |
C: Energy production and conversion |
Yes |
Protein name(s): erythritol phosphate dehydrogenase
MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (PubMed: 10708387).
The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain (PubMed: 16177356). |
| 75 |
eryC |
-: Not in COGs |
Yes |
Protein name(s): D-erythrulose-1-phosphate dehydrogenase
MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (PubMed: 10708387).
Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis (PubMed: 16177356). |
| 76 |
eryD |
K: Transcription |
No |
Protein name(s): erythritol transcriptional regulator
MUTATION: The EryA protein is the erythritol kinase, and EryB and EryC are the two dehydrogenases in the catabolic chain. EryD is a transcriptional repressor, inactivated by erythritol binding
The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 (PubMed: 10708387). Sequence analysis and comparison showed that EryD was a protein with a helixturnhelix motif and probably possessed some regulatory function . To obtain further evidence for this, we constructed an eryD mutant (FJS-2) and compared the levels of ery transcription in this mutant and a wild-type strain. Transcription from the ery promoter (P1) was more active in both the mutant FJS-2 and strain B19 than in strain 2308. This result strongly suggested a repressor function for EryD (PubMed: 10708387). |
| 77 |
exbB |
U: Intracellular trafficking and secretion |
No |
Protein name(s): biopolymer transport protein ExbB
MUTATION: ExbB is part of the Ton complex , and DstC is a permease homologue of an iron ( III ) ABC transporter; in gram -negative bacteria these two complexes are involved in the uptake of iron through the outer and inner membranes, respectively. DugA is a new partner in iron utilization that exhibits homology with the bacterial conserved GTPase YchF. Analysis of these three mutants indicated that the ExbB, DstC, and DugA proteins are required for optimal assimilation of DHBA andor citrate (PubMed: 15385478). The exbB, dstC, and pthdugA mutants were not attenuated in the BALBc mice after i. p. infection (PubMed: 15385478). |
| 78 |
exsA |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Transport (PubMed: 14979322).
FUNCTION: ABC transporter (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 79 |
fbpA |
P: Inorganic ion transport and metabolism |
Yes |
FUNCTIONAL GROUP: Metal acquisition (PubMed: 14979322).
FUNCTION: Fe3+ binding (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 80 |
fdhA |
C: Energy production and conversion |
Yes |
FUNCTIONAL GROUP: Oxidoreduction (PubMed: 14979322).
FUNCTION: Formate dehydrogenase (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 81 |
feuP |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Response regulator (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages (PubMed: 14979322). |
| 82 |
feuQ |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Histidine kinase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 83 |
flgE |
N: Cell motility |
Yes |
Protein name(s): Flagellar hook protein FlgE(Swiss-prot: Q8FUS9).
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Hook (PubMed: 14979322).
SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-prot: Q8FUS9).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 84 |
flghA |
U: Intracellular trafficking and secretion |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Export apparatus (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 85 |
flgI |
N: Cell motility |
Yes |
Protein name(s): flagellar P-ring protein precursor
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: P-ring (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 86 |
fliC |
N: Cell motility |
Yes |
FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella (PubMed: 14979322).
FUNCTION: Flagellin (PubMed: 14979322).
MUTATION: Attenuated in Mice, but not in Macrophages, HeLa (PubMed: 14979322). |
| 87 |
fliF |
U: Intracellular trafficking and secretion |
Yes |
Protein name(s): Flagellar M-ring protein FliF(Swiss-prot: Q8FUS3).
FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-prot: Q8FUS3).
SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-prot: Q8FUS3).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (By similarity)(Swiss-prot: Q8FUS3).
SIMILARITY: Belongs to the fliF family(Swiss-prot: Q8FUS3).
MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc (PubMed: 14638795). |
| 88 |
ftcR |
T: Signal transduction mechanisms |
Yes |
MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria (PubMed: 17056750). |
| 89 |
galcD |
G: Carbohydrate transport and metabolism |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: D-galactarate dehydratase (PubMed: 14979322).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 90 |
galE |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: UDP-glucose 4-epimerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 91 |
gcvP |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Glycine dehydrogenase [decarboxylating] (EC 1.4.4.2) (Glycine decarboxylase) (Glycine cleavage system P-protein)(Swiss-prot: Q8FVU9).
FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-prot: Q8FVU9).
CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-prot: Q8FVU9).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8FVU9).
SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-prot: Q8FVU9).
SIMILARITY: Belongs to the gcvP family(Swiss-prot: Q8FVU9).
MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model (PubMed: 12523983). |
| 92 |
gcvT |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): glycine cleavage system T protein
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 93 |
glnA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): glutamine synthetase, type I
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 94 |
glnD |
O: Posttranslational modification, protein turnover, chaperones |
Yes |
Protein name(s): [Protein-PII] uridylyltransferase (EC 2.7.7.59) (PII uridylyl-transferase) (Uridylyl-removing enzyme) (UTase)(Swiss-prot: Q8G312).
FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-prot: Q8G312).
CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-prot: Q8G312).
SIMILARITY: Belongs to the glnD family(Swiss-prot: Q8G312).
MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella (PubMed: 10678941). |
| 95 |
glnL |
T: Signal transduction mechanisms |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Nitrogen regulatory IIA (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 96 |
gloA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): lactoylglutathione lyase
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) (PubMed: 14979322).
MUTATION: Attenuated in Differential fluorescence induction (PubMed: 14979322). |
| 97 |
glpK |
C: Energy production and conversion |
Yes |
Protein name(s): Glycerol kinase (EC 2.7.1.30) (ATP:glycerol 3-phosphotransferase) (Glycerokinase) (GK)(Swiss-prot: Q8FWK8).
FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-prot: Q8FWK8).
CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-prot: Q8FWK8).
PATHWAY: Glycerol utilization; first (rate-limiting) step(Swiss-prot: Q8FWK8).
SIMILARITY: Belongs to the FGGY kinase family(Swiss-prot: Q8FWK8).
MUTATION: Attenuated in Mice, Macrophages, HeLa (PubMed: 14979322). |
| 98 |
glt1 |
R: General function prediction only |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Synthesis (PubMed: 14979322).
FUNCTION: Glut. sunthesis (PubMed: 14979322).
MUTATION: Attenuated in Mice (PubMed: 14979322). |
| 99 |
gltD |
R: General function prediction only |
Yes |
Protein name(s): glutamate synthase, small subunit
MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus (PubMed: 10858227). |
| 100 |
gluP |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): Glucose/galactose transporter(Swiss-prot: Q8YB48).
FUNCTION: Intake of glucose and galactose (Potential)(Swiss-prot: Q8YB48).
SUBCELLULAR LOCATION: Inner membrane; multi-pass membrane protein (Probable)(Swiss-prot: Q8YB48).
SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-prot: Q8YB48).
MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse (PubMed: 12414147). |
| 101 |
glyA |
E: Amino acid transport and metabolism |
Yes |
Protein name(s): Serine hydroxymethyltransferase (EC 2.1.2.1) (Serine methylase) (SHMT)(Swiss-prot: Q8G1F1).
FUNCTION: Interconversion of serine and glycine(Swiss-prot: Q8G1F1).
CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-prot: Q8G1F1).
COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-prot: Q8G1F1).
PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-prot: Q8G1F1).
SUBUNIT: Homotetramer (By similarity)(Swiss-prot: Q8G1F1).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G1F1).
SIMILARITY: Belongs to the SHMT family(Swiss-prot: Q8G1F1).
MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells (PubMed: 12438693). |
| 102 |
gmd |
M: Cell wall/membrane biogenesis |
Yes |
Protein name(s): GDP-mannose 4,6-dehydratase
MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype (PubMed: 15099501). |
| 103 |
gnd |
G: Carbohydrate transport and metabolism |
Yes |
Protein name(s): 6-phosphogluconate dehydrogenase
MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model (PubMed: 12761078). |
| 104 |
gntR |
K: Transcription |
Yes |
FUNCTIONAL GROUP: Regulation (PubMed: 14979322).
FUNCTION: Transcriptional regulator (PubMed: 14979322).
MUTATION: Attenuated in Macrophages, HeLa (PubMed: 14979322). |
| 105 |
gntR1 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 106 |
gntR10 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 107 |
gntR17 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 108 |
gntR2 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated in mice (PubMed: 16113274). |
| 109 |
gntR4 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 110 |
gntR5 |
K: Transcription |
Yes |
FUNCTIONAL GROUP: gntR family (PubMed: 16113274).
MUTATION: Attenuated using plasmid-tagged mutagenesis method (PubMed: 16113274). |
| 111 |
gpt |
N/A
|
Yes |
Protein name(s): Xanthine phosphoribosyltransferase (EC 2.4.2.22) (Xanthine-guanine phosphoribosyltransferase) (XGPRT)(Swiss-prot: Q8G0P3).
FUNCTION: Acts on guanine, xanthine and to a lesser extent hypoxanthine (By similarity)(Swiss-prot: Q8G0P3).
CATALYTIC ACTIVITY: 9-(5-phospho-beta-D-ribosyl)xanthine + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + xanthine(Swiss-prot: Q8G0P3).
COFACTOR: Binds 1 magnesium ion per subunit (By similarity)(Swiss-prot: Q8G0P3).
COFACTOR: Binds 1 sulfate ion per subunit (By similarity)(Swiss-prot: Q8G0P3).
PATHWAY: Purine salvage(Swiss-prot: Q8G0P3).
SUBUNIT: Homotrimer (By similarity)(Swiss-prot: Q8G0P3).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: Q8G0P3).
SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase family. XGPT subfamily(Swiss-prot: Q8G0P3).
MUTATION: gpt codes for hypoxanthine-guanine phosphoribosyl transferase, an enzyme of the purine nucleotide biosynthesis pathway. A transposon insertion in the B. suis gpt-like gene has an attenuated phenotype in THP-1 human macrophages. This could be related to results in other studies where many auxotrophic mutations for purine or nucleotide biosynthesis lead to attenuated strains (PubMed: 10678941). |
| 112 |
gtrB |
M: Cell wall/membrane biogenesis |
Yes |
FUNCTIONAL GROUP: a.a. metabolism, Unkown (PubMed: 14979322).
FUNCTION: glycosyl transerase (PubMed: 14979322).
MUTATION: Attenuated in Macrophages (PubMed: 14979322). |
| 113 |
hdeA |
-: Not in COGs |
No |
Protein name(s): hdeA protein
MUTATION: HdeA is a low pH dependent periplasmic chaperone. Although mutational analysis demonstrated that HdeA contributes to acid resistance in this bacterium , this protein is not required for wild-type virulence in the BALBc mouse model. Brucella HdeA is NCBI accession no AAR98497. The B abortus hdeA mutant MWV2 displayed an approximately 10- fold greater susceptibility to killing by exposure to pH 4 during the 30 h incubation period than did the parental 2308 strain (PubMed: 15863292). It is also important to note that loss of hdeA does not impart the same degree of acid sensitivity upon the B abortus hdeA mutant as that exhibited by the isogenic hfq mutant Hfq3 in the same assay. This latter finding argues that inefficient expression of hdeA is not the sole basis for the prominent acid sensitivity displayed by stationary phase cultures of the B abortus hfq mutant (Robertson and Roop, 1999)(PubMed: 15863292). |
| 114 |
hemH |
H: Coenzyme transport and metabolism |
Yes |
Protein name(s): Ferrochelatase (EC 4.99.1.1) (Protoheme ferro-lyase) (Heme synthetase)(Swiss-prot: P0A3D7).
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-prot: P0A3D7).
CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-prot: P0A3D7).
PATHWAY: Protoheme biosynthesis; last step(Swiss-prot: P0A3D7).
SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-prot: P0A3D7).
SIMILARITY: Belongs to the ferrochelatase family(Swiss-prot: |
