T4SS ID	376
Strain	Brucella melitensis biovar Abortus 2308
Replicon	chromosome II [Browse all T4SS(s) in this replicon]
Accession	NC_007624
Location	56647..67080
Name	VirB
Function	effector translocation
Classification	Type IVA; Type P
Experimental investigation has been performed on this T4SS.

T4SS components

Component	VirB1	VirB2	VirB3	VirB4	VirB5	VirB6	VirB7	VirB8	VirB9
Number	1	1	1	1	1	1	1	1	1
Component	VirB10	VirB11	VirD4
Number	1	1	0

The information of T4SS components from NC_007624
#	Locus tag (Gene)	Coordinates [+/-], size (bp)	Protein GI	Product	Component
1	BAB2_0055	52960..54363 [-], 1404	83269009	amino acid transporter
2	BAB2_0056	54581..55732 [-], 1152	83269010	hypothetical protein
3	BAB2_0057	55983..56501 [-], 519	83269011	outer membrane protein OprF
4	BAB2_0058	56647..57735 [-], 1089	83269012	type II secretion system protein E	VirB11
5	BAB2_0059	57716..58882 [-], 1167	83269013	glutelin	VirB10
6	BAB2_0060	58879..59748 [-], 870	83269014	Type IV secretion system CagX conjugation protein	VirB9
7	BAB2_0061	59745..60464 [-], 720	83269015	virulence protein	VirB8
8	BAB2_0062	60467..60640 [-], 174	83269016	type IV secretion system protein VirB7	VirB7
9	BAB2_0063	60804..61847 [-], 1044	83269017	hypothetical protein	VirB6
10	BAB2_0064	62031..62747 [-], 717	83269018	type IV secretion system protein VirB5	VirB5
11	BAB2_0065	62752..65247 [-], 2496	83269019	shikimate kinase	VirB4
12	BAB2_0066	65247..65597 [-], 351	83269020	type IV secretion system protein VirB3-like protein	VirB3
13	BAB2_0067	65611..65928 [-], 318	83269021	type IV secretion system protein VirB2	VirB2
14	BAB2_0068	66364..67080 [-], 717	83269022	SLT domain-containing protein	VirB1
15	BAB2_0069	67584..68822 [-], 1239	83269023	peptidoglycan binding domain-containing protein
16	BAB2_0070 (galU)	69222..70115 [+], 894	83269024	UTP-glucose-1-phosphate uridylyltransferase
17	BAB2_0071	70168..71706 [-], 1539	83269025	hypothetical protein

Genes in the 5-Kb flanking regions if available, or non-essential genes in the T4SS gene cluster if any.

Download FASTA format files

Proteins        Genes

Effectors

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 GI	Product	*
1	BAB1_0279	275959..276711 [-], 753	82699179	hypothetical protein	btp1
2	BAB1_0678	667731..668303 [+], 573	82699546	hypothetical protein	BspA
3	BAB1_0712	696754..697317 [+], 564	82699580	hypothetical protein	BspB
4	BAB1_0756	739186..740019 [+], 834	82699619	hypothetical protein	BtpB
5	BAB1_0847	824094..824507 [-], 414	82699704	hypothetical protein	BspC
6	BAB1_1043	1004798..1009459 [-], 4662	82699875	hypothetical protein	BPE043
7	BAB1_1058	1018574..1019830 [-], 1257	82699888	hypothetical protein	VceC
8	BAB1_1275	1237345..1238106 [-], 762	82700087	rhomboid-like protein	BPE275
9	BAB1_1279	1240034..1240561 [-], 528	82700091	hexapeptide repeat-containing transferase	RicA
10	BAB1_1492	1443154..1443726 [-], 573	82700286	hypothetical protein	SepA
11	BAB1_1652	1596760..1597077 [+], 318	82700429	hypothetical protein	VceA
12	BAB1_1671	1620605..1621399 [-], 795	82700448	two-component response regulator	BspE
13	BAB1_1948	1891813..1893099 [+], 1287	82700711	hypothetical protein	BspF
14	BAB1_2005	1941656..1942117 [-], 462	82700764	cAMP-dependent protein kinase	BPE005
15	BAB2_0123	121652..122113 [-], 462	83269070	hypothetical protein	BPE123

 T4SE derived from experimental literature.
 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/Substrate	Source	Function	Reference
1	BPE005 (82700764)	Matrix metallopeptidase 9 (MMP-9)	human	BPE005 represses secretion of matrx metalloproteinase 9 (MMP-9) and induces deposition of concomitant collagen by hepatic stellate (LX-2) cells.	(1) PubMed: 26667834
2	BspA (82699546)	unknown	unknown	BspA, BspB and BspF inhibited protein secretion.	(2) PubMed: 23950720
3	BspB (82699580)	conserved oligomeric Golgi (COG)	human	BspB 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: 28844886
4	BspF (82700711)	unknown	unknown	BspA, BspB and BspF inhibited protein secretion.	(4) PubMed: 23950720
5	btp1 (82699179)	unknown	unknown	Btp1 interfere with the TLR2 signaling pathway to down-modulating maturation of infected dendritic cells.	(5) PubMed: 18266466
6	BtpB (82699619)	MYD88	murine	BtpB may interact with MYD88 to inhibit TLR signaling and interfere with activation of dendritic cells.	(6) PubMed: 23847770
7	RicA (82700091)	small GTPase Rab2	human	RicA interacts with human small GTPase Rab2 involved in trafficking.	(7) PubMed: 21501366
8	SepA (82700286)	unknown	unknown	SepA represses the fusion of Brucella containing vacuole (BCV) with the lysosome.	(8) PubMed: 24119283
9	VceC (82699888)	unknown	unknown	VceC induces significant ER stress to trigger Inflammation and IL-6 production.	(9) PubMed: 27007849

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]

(2) Myeni S et al. (2013). Brucella modulates secretory trafficking via multiple type IV secretion effector proteins. PLoS Pathog. 9(8):e1003556. [PudMed:23950720]

(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]

(4) Myeni S et al. (2013). Brucella modulates secretory trafficking via multiple type IV secretion effector proteins. PLoS Pathog. 9(8):e1003556. [PudMed:23950720]

(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]

(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]

(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]

(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]

(9) Keestra-Gounder AM et al. (2016). NOD1 and NOD2 signalling links ER stress with inflammation. Nature. 532(7599):394-7. [PudMed:27007849]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

(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]

This literature contains experimental investigation