T4SS ID376
StrainBrucella melitensis biovar Abortus 2308
Repliconchromosome II [Browse all T4SS(s) in this replicon]
Functioneffector translocation
ClassificationType IVA; Type P
experimental Experimental investigation has been performed on this T4SS.

T4SS components

The information of T4SS components from NC_007624
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProductComponent
1BAB2_005552960..54363 [-], 140483269009amino acid transporter 
2BAB2_005654581..55732 [-], 115283269010hypothetical protein 
3BAB2_005755983..56501 [-], 51983269011outer membrane protein OprF 
4BAB2_005856647..57735 [-], 108983269012type II secretion system protein E  VirB11
5BAB2_005957716..58882 [-], 116783269013glutelin  VirB10
6BAB2_006058879..59748 [-], 87083269014Type IV secretion system CagX conjugation protein  VirB9
7BAB2_006159745..60464 [-], 72083269015virulence protein  VirB8
8BAB2_006260467..60640 [-], 17483269016type IV secretion system protein VirB7  VirB7
9BAB2_006360804..61847 [-], 104483269017hypothetical protein  VirB6
10BAB2_006462031..62747 [-], 71783269018type IV secretion system protein VirB5  VirB5
11BAB2_006562752..65247 [-], 249683269019shikimate kinase  VirB4
12BAB2_006665247..65597 [-], 35183269020type IV secretion system protein VirB3-like protein  VirB3
13BAB2_006765611..65928 [-], 31883269021type IV secretion system protein VirB2  VirB2
14BAB2_006866364..67080 [-], 71783269022SLT domain-containing protein  VirB1
15BAB2_006967584..68822 [-], 123983269023peptidoglycan binding domain-containing protein 
16BAB2_0070 (galU)69222..70115 [+], 89483269024UTP-glucose-1-phosphate uridylyltransferase 
17BAB2_007170168..71706 [-], 153983269025hypothetical protein 
flank Genes in the 5-Kb flanking regions if available, or non-essential genes in the T4SS gene cluster if any.

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Proteins        Genes

btp1, BspA, BspB, BtpB, BspC, BPE043, VceC, BPE275, RicA, SepA, VceA, BspE, BspF, BPE005, BPE123

The information of protein effectors
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProduct  *
1BAB1_0279 275959..276711 [-], 75382699179hypothetical proteinexperimental  btp1interaction
2BAB1_0678 667731..668303 [+], 57382699546hypothetical proteinexperimental  BspAinteraction
3BAB1_0712 696754..697317 [+], 56482699580hypothetical proteinexperimental  BspBinteraction
4BAB1_0756 739186..740019 [+], 83482699619hypothetical proteinexperimental  BtpBinteraction
5BAB1_0847 824094..824507 [-], 41482699704hypothetical proteinexperimental  BspC
6BAB1_1043 1004798..1009459 [-], 466282699875hypothetical proteinexperimental  BPE043
7BAB1_1058 1018574..1019830 [-], 125782699888hypothetical proteinexperimental  VceCinteraction
8BAB1_1275 1237345..1238106 [-], 76282700087rhomboid-like proteinexperimental  BPE275
9BAB1_1279 1240034..1240561 [-], 52882700091hexapeptide repeat-containing transferaseexperimental  RicAinteraction
10BAB1_1492 1443154..1443726 [-], 57382700286hypothetical proteinexperimental  SepAinteraction
11BAB1_1652 1596760..1597077 [+], 31882700429hypothetical proteinexperimental  VceA
12BAB1_1671 1620605..1621399 [-], 79582700448two-component response regulatorexperimental  BspE
13BAB1_1948 1891813..1893099 [+], 128782700711hypothetical proteinexperimental  BspFinteraction
14BAB1_2005 1941656..1942117 [-], 46282700764cAMP-dependent protein kinaseexperimental  BPE005interaction
15BAB2_0123 121652..122113 [-], 46283269070hypothetical proteinexperimental  BPE123
experimental T4SE derived from experimental literature.
interaction This effector contains information of interaction.

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Proteins        Genes
The information on regulatory element

The information on host-pathogen interaction.

#Name(Protein GI)Host site/SubstrateSourceFunctionReference
1BPE005 (82700764)Matrix metallopeptidase 9 (MMP-9)humanBPE005 represses secretion of matrx metalloproteinase 9 (MMP-9) and induces deposition of concomitant collagen by hepatic stellate (LX-2) cells.(1) PubMed: 26667834experimental
2BspA (82699546)unknownunknownBspA, BspB and BspF inhibited protein secretion.(2) PubMed: 23950720experimental
3BspB (82699580)conserved oligomeric Golgi (COG)humanBspB interacts with tethering complex of GOG which is a major coordinator of Golgi vesicular trafficking to contribute to biogenesis of rBCV and replication of Brucella.(3) PubMed: 28844886experimental
4BspF (82700711)unknownunknownBspA, BspB and BspF inhibited protein secretion.(4) PubMed: 23950720experimental
5btp1 (82699179)unknownunknownBtp1 interfere with the TLR2 signaling pathway to down-modulating maturation of infected dendritic cells.(5) PubMed: 18266466experimental
6BtpB (82699619)MYD88murineBtpB may interact with MYD88 to inhibit TLR signaling and interfere with activation of dendritic cells. (6) PubMed: 23847770experimental
7RicA (82700091)small GTPase Rab2humanRicA interacts with human small GTPase Rab2 involved in trafficking.(7) PubMed: 21501366experimental
8SepA (82700286)unknownunknownSepA represses the fusion of Brucella containing vacuole (BCV) with the lysosome.(8) PubMed: 24119283experimental
9VceC (82699888)unknownunknownVceC induces significant ER stress to trigger Inflammation and IL-6 production.(9) PubMed: 27007849experimental
experimental This T4SE is mentioned in the literature.

(1) Arriola Benitez PC et al. (2015). The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor β1 in Hepatic Stellate Cells. Infect Immun. 84(2):598-606. [PudMed:26667834] experimental
(2) Myeni S et al. (2013). Brucella modulates secretory trafficking via multiple type IV secretion effector proteins. PLoS Pathog. 9(8):e1003556. [PudMed:23950720] experimental in_silico
(3) Miller CN et al. (2017). A Brucella Type IV Effector Targets the COG Tethering Complex to Remodel Host Secretory Traffic and Promote Intracellular Replication. Cell Host Microbe. 22(3):317-329.e7. [PudMed:28844886] experimental
(4) Myeni S et al. (2013). Brucella modulates secretory trafficking via multiple type IV secretion effector proteins. PLoS Pathog. 9(8):e1003556. [PudMed:23950720] experimental in_silico
(5) Salcedo SP et al. (2008). Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog. 4(2):e21. [PudMed:18266466] experimental
(6) Salcedo SP et al. (2013). BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions. . Front. Cell. Infect. Microbiol. . 2013.00028 . [PudMed:23847770] experimental
(7) de Barsy M; Jamet A; Filopon D; Nicolas C; Laloux G; Rual JF; Muller A; Twizere JC; Nkengfac B; Vandenhaute J; Hill DE; Salcedo SP; Gorvel JP; Letesson JJ; De Bolle X (2011). Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2. Cell Microbiol. 13(7):1044-58. [PudMed:21501366] experimental
(8) Döhmer PH et al. (2014). Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival. Cell Microbiol. 16(3):396-410. [PudMed:24119283] experimental
(9) Keestra-Gounder AM et al. (2016). NOD1 and NOD2 signalling links ER stress with inflammation. Nature. 532(7599):394-7. [PudMed:27007849] experimental
(1) Sieira R; Arocena GM; Zorreguieta A; Comerci DJ; Ugalde RA (2012). A MarR-type regulator directly activates transcription from the Brucella abortus virB promoter by sharing a redundant role with HutC. J Bacteriol. . [PudMed:23002224] experimental
(2) Sa JC; Silva TM; Costa EA; Silva AP; Tsolis RM; Paixao TA; Carvalho Neta AV; Santos RL (2012). The virB-encoded type IV secretion system is critical for establishment of infection and persistence of Brucella ovis infection in mice. Vet Microbiol. . [PudMed:22483850] experimental
(3) de Jong MF; Tsolis RM (2012). Brucellosis and type IV secretion. Future Microbiol. 7(1):47-58. [PudMed:22191446]
(4) Caswell CC; Gaines JM; Roop RM 2nd (2012). The RNA chaperone Hfq independently coordinates expression of the VirB type IV secretion system and the LuxR-type regulator BabR in Brucella abortus 2308. J Bacteriol. 194(1):3-14. [PudMed:22020650] experimental
(5) Paschos A; den Hartigh A; Smith MA; Atluri VL; Sivanesan D; Tsolis RM; Baron C (2011). An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation. Infect Immun. 79(3):1033-43. [PudMed:21173315] experimental
(6) Martinez-Nunez C; Altamirano-Silva P; Alvarado-Guillen F; Moreno E; Guzman-Verri C; Chaves-Olarte E (2010). The two-component system BvrR/BvrS regulates the expression of the type IV secretion system VirB in Brucella abortus. J Bacteriol. 192(21):5603-8. [PudMed:20833814] experimental
(7) Arocena GM; Sieira R; Comerci DJ; Ugalde RA (2010). Identification of the quorum-sensing target DNA sequence and N-Acyl homoserine lactone responsiveness of the Brucella abortus virB promoter. J Bacteriol. 192(13):3434-40. [PudMed:20400542] experimental
(8) Sieira R; Arocena GM; Bukata L; Comerci DJ; Ugalde RA (2010). Metabolic control of virulence genes in Brucella abortus: HutC coordinates virB expression and the histidine utilization pathway by direct binding to both promoters. J Bacteriol. 192(1):217-24. [PudMed:19854911] experimental
(9) Lapaque N; Muller A; Alexopoulou L; Howard JC; Gorvel JP (2009). Brucella abortus induces Irgm3 and Irga6 expression via type-I IFN by a MyD88-dependent pathway, without the requirement of TLR2, TLR4, TLR5 and TLR9. Microb Pathog. 47(6):299-304. [PudMed:19747534] experimental
(10) Rolan HG; Xavier MN; Santos RL; Tsolis RM (2009). Natural antibody contributes to host defense against an attenuated Brucella abortus virB mutant. Infect Immun. 77(7):3004-13. [PudMed:19364836] experimental
(11) Delpino MV; Fossati CA; Baldi PC (2009). Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte interaction upon infection with Brucella spp. Infect Immun. 77(3):984-95. [PudMed:19103778] experimental
(12) de Jong MF; Sun YH; den Hartigh AB; van Dijl JM; Tsolis RM (2008). Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella type IV secretion system. Mol Microbiol. 70(6):1378-96. [PudMed:19019140] experimental
(13) den Hartigh AB; Rolan HG; de Jong MF; Tsolis RM (2008). VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system. J Bacteriol. 190(13):4427-36. [PudMed:18469100] experimental
(14) Rolan HG; Tsolis RM (2008). Inactivation of the type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection. Infect Immun. 76(7):3207-13. [PudMed:18458071] experimental
(15) Rolan HG; den Hartigh AB; Kahl-McDonagh M; Ficht T; Adams LG; Tsolis RM (2008). VirB12 is a serological marker of Brucella infection in experimental and natural hosts. Clin Vaccine Immunol. 15(2):208-14. [PudMed:18077620] experimental
(16) Roux CM; Rolan HG; Santos RL; Beremand PD; Thomas TL; Adams LG; Tsolis RM (2007). Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice. Cell Microbiol. 9(7):1851-69. [PudMed:17441987] experimental
(17) Rolan HG; Tsolis RM (2007). Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization. Infect Immun. 75(6):2965-73. [PudMed:17420243] experimental
(18) Sun YH; Rolan HG; den Hartigh AB; Sondervan D; Tsolis RM (2005). Brucella abortus virB12 is expressed during infection but is not an essential component of the type IV secretion system. Infect Immun. 73(9):6048-54. [PudMed:16113325] experimental
(19) Celli J; Salcedo SP; Gorvel JP (2005). Brucella coopts the small GTPase Sar1 for intracellular replication. Proc Natl Acad Sci U S A. 102(5):1673-8. [PudMed:15632218] experimental
(20) Sieira R; Comerci DJ; Pietrasanta LI; Ugalde RA (2004). Integration host factor is involved in transcriptional regulation of the Brucella abortus virB operon. Mol Microbiol. 54(3):808-22. [PudMed:15491369] experimental
(21) den Hartigh AB; Sun YH; Sondervan D; Heuvelmans N; Reinders MO; Ficht TA; Tsolis RM (2004). Differential requirements for VirB1 and VirB2 during Brucella abortus infection. Infect Immun. 72(9):5143-9. [PudMed:15322008] experimental
(22) Celli J; de Chastellier C; Franchini DM; Pizarro-Cerda J; Moreno E; Gorvel JP (2003). Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J Exp Med. 198(4):545-56. [PudMed:12925673] experimental
(23) Rouot B; Alvarez-Martinez MT; Marius C; Menanteau P; Guilloteau L; Boigegrain RA; Zumbihl R; O'Callaghan D; Domke N; Baron C (2003). Production of the type IV secretion system differs among Brucella species as revealed with VirB5- and VirB8-specific antisera. Infect Immun. 71(3):1075-82. [PudMed:12595417] experimental
(24) Sanchez DO; Zandomeni RO; Cravero S; Verdun RE; Pierrou E; Faccio P; Diaz G; Lanzavecchia S; Aguero F; Frasch AC; Andersson SG; Rossetti OL; Grau O; Ugalde RA (2001). Gene discovery through genomic sequencing of Brucella abortus. Infect Immun. 69(2):865-8. [PudMed:11159979]
(25) Sieira R; Comerci DJ; Sanchez DO; Ugalde RA (2000). A homologue of an operon required for DNA transfer in Agrobacterium is required in Brucella abortus for virulence and intracellular multiplication. J Bacteriol. 182(17):4849-55. [PudMed:10940027] experimental
(26) Hong PC; Tsolis RM; Ficht TA (2000). Identification of genes required for chronic persistence of Brucella abortus in mice. Infect Immun. 68(7):4102-7. [PudMed:10858227] experimental
experimental This literature contains experimental investigation