T4SS ID	2
Strain	Bartonella henselae str. Houston-1
Replicon	chromosome [Browse all T4SS(s) in this replicon]
Accession	NC_005956
Location	1512780..1525452
Name	VirB
Function	effector translocation
Classification	Type IVA; Type P
Experimental investigation has been performed on this T4SS.

Information of structure: BepA, BepE

T4SS components

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

The information of T4SS components from NC_005956
#	Locus tag (Gene)	Coordinates [+/-], size (bp)	Protein GI	Product	Component
1	BH13250	1511669..1512412 [-], 744	49476009	hypothetical protein
2	BH13260 (virB2)	1512780..1513103 [+], 324	49476010	virB2 protein	VirB2
3	BH13270 (virB3)	1513104..1513415 [+], 312	49476011	virB3 protein	VirB3
4	BH13280 (virB4)	1513421..1515775 [+], 2355	49476012	virB4 protein	VirB4
5	BH13290	1515772..1516218 [+], 447	49476013	hypothetical protein	VirB5
6	BH13300 (virB6)	1516205..1517170 [+], 966	49476014	virB protein	VirB6
7	BH13310	1517298..1517708 [+], 411	49476015	hypothetical protein	VirB7
8	BH13320 (virB8)	1517698..1518366 [+], 669	49476016	virB8 protein	VirB8
9	BH13330 (virB9)	1518366..1519229 [+], 864	49476017	virB9 protein	VirB9
10	BH13340 (virB10)	1519222..1520412 [+], 1191	49476018	virB10 protein	VirB10
11	BH13350 (virB11)	1520381..1521451 [+], 1071	49476019	virB11 protein	VirB11
12	BH13360	1521519..1521725 [+], 207	49476020	hypothetical protein
13	BH13370	1521736..1523370 [+], 1635	49476021	cell filamentation protein
14	BH13380 (traG)	1523533..1525452 [+], 1920	49476022	conjugal transfer protein TraG	VirD4
15	BH13390	1525994..1527622 [+], 1629	49476023	hypothetical protein
16	BH13400	1528692..1530290 [+], 1599	49476024	cell filamentation protein

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

Crucial for establishment of infection in the primary niche- the endothelial cells, required for colonization of endothelial cells, by mediating the intracellular delivery of effector proteins (BepA-BepG). Translocation of the Beps provokes distinct cellular phenotypes: (i) a massive cytoskeleton rearrangement, resulting in the engulfment of bacterial aggregates (a phenotype called 'invasome' formation), (ii) NF-kappaB-dependent proinflammatory activation, characterized by chemokine secretion and expression of cell adhesion proteins, and (iii) enhanced cell survival as a result of anti-apoptosis (iv) capillary-like sprout formation of endothelial cell aggregates

Effectors

BepA, BepB, BepC, BepD, BepE, BepF, BepG

The information of protein effectors
#	Locus tag (Gene)	Coordinates [+/-], size (bp)	Protein GI	Product	*
1	BH13370	1521736..1523370 [+], 1635	49476021	cell filamentation protein	BepA
2	BH13390	1525994..1527622 [+], 1629	49476023	hypothetical protein	BepB
3	BH13400	1528692..1530290 [+], 1599	49476024	cell filamentation protein	BepC
4	BH13410	1530764..1532368 [+], 1605	49476025	hypothetical protein	BepD
5	BH13420	1532694..1534088 [+], 1395	49476026	hypothetical protein	BepE
6	BH13430	1534424..1536928 [+], 2505	49476027	hypothetical protein	BepF
7	BH13440	1537113..1540244 [+], 3132	49476028	hypothetical protein	BepG

 T4SE derived from experimental literature.
 This effector contains information of interaction.

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Proteins        Genes

The information on structure of this T4ss

#	Name	Image	Resource	Detail	Reference
1	BepA		PDB (2JK8)	Type IV secretion system effector protein BepA complexed with a pyrophosphate moiety.	(1) PubMed: 21213248
2	BepE		PDB (4YK3)	Crystal Structure of the BID Domain of BepE from Bartonella henselae.	(2) PubMed: 27889208

(1) Palanivelu DV; Goepfert A; Meury M; Guye P; Dehio C; Schirmer T (2011). Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA. Protein Sci. 20(3):492-9. [PudMed:21213248]

(2) Stanger FV et al. (2017). The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook. Structure. 25(1):203-211. [PudMed:27889208]

The information on host-pathogen interaction.

#	Name(Protein GI)	Host site/Substrate	Source	Function	Reference
1	BepA (49476021)	Adenylyl cyclase	human	BepA is located on the plasma membrane and triggers the production of second messenger cyclic adenosine monophosphate to repress endothelial cell (EC) apoptosis.	(1) PubMed: 17121462
2	BepC (49476024)	unknown	unknown	The combined action of BepC and BepF triggers the formation of invasome and repress endocytic uptake of inert microspheres.	(2) PubMed: 20964799
3	BepE (49476026)	unknown	unknown	BepE protects infected migratory cells from BepC's injurious and restores normal cell migration through the RhoA signaling pathway.	(3) PubMed: 24945914
4	BepF (49476027)	unknown	unknown	The combined action of BepC and BepF triggers the formation of invasome and repress endocytic uptake of inert microspheres. Besides, BepF play a role in activation of Rac1 and Cdc42 during the invasome formation process.	(4) PubMed: 22043280
5	BepG (49476028)	unknown	unknown	BepG repress bacterial endocytosis to triggers invasome-mediated internalization.	(5) PubMed: 19302579

This T4SE is mentioned in the literature.

(1) Schmid MC; Scheidegger F; Dehio M; Balmelle-Devaux N; Schulein R; Guye P; Chennakesava CS; Biedermann B; Dehio C (2006). A translocated bacterial protein protects vascular endothelial cells from apoptosis. PLoS Pathog. 2(11):e115. [PudMed:17121462]

(2) Truttmann MC; Rhomberg TA; Dehio C (2011). Combined action of the type IV secretion effector proteins BepC and BepF promotes invasome formation of Bartonella henselae on endothelial and epithelial cells. Cell Microbiol. 13(2):284-99. [PudMed:20964799]

(3) Okujava R et al. (2014). A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors. PLoS Pathog. 10(6):e1004187. [PudMed:24945914]

(4) Truttmann MC; Guye P; Dehio C (2011). BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures. PLoS One. 6(10):e25106. [PudMed:22043280]

(5) Rhomberg TA; Truttmann MC; Guye P; Ellner Y; Dehio C (2009). A translocated protein of Bartonella henselae interferes with endocytic uptake of individual bacteria and triggers uptake of large bacterial aggregates via the invasome. Cell Microbiol. 11(6):927-45. [PudMed:19302579]

(1) Guy L; Nystedt B; Sun Y; Naslund K; Berglund EC; Andersson SG (2012). A genome-wide study of recombination rate variation in Bartonella henselae. BMC Evol Biol. 12(1):65. [PudMed:22577862]

(2) Truttmann MC; Misselwitz B; Huser S; Hardt WD; Critchley DR; Dehio C (2011). Bartonella henselae engages inside-out and outside-in signaling by integrin beta1 and talin1 during invasome-mediated bacterial uptake. J Cell Sci. 124(Pt 21):3591-602. [PudMed:22045736]

(3) Fernandez-Gonzalez E; de Paz HD; Alperi A; Agundez L; Faustmann M; Sangari FJ; Dehio C; Llosa M (2011). Transfer of R388 derivatives by a pathogenesis-associated type IV secretion system into both bacteria and human cells. J Bacteriol. 193(22):6257-65. [PudMed:21908662]

(4) Schroder G; Schuelein R; Quebatte M; Dehio C (2011). Conjugative DNA transfer into human cells by the VirB/VirD4 type IV secretion system of the bacterial pathogen Bartonella henselae. Proc Natl Acad Sci U S A. 108(35):14643-8. [PudMed:21844337]

(5) Scheidegger F; Quebatte M; Mistl C; Dehio C (2011). The Bartonella henselae VirB/Bep system interferes with vascular endothelial growth factor (VEGF) signalling in human vascular endothelial cells. Cell Microbiol. 13(3):419-31. [PudMed:21044238]

(6) Truttmann MC; Rhomberg TA; Dehio C (2011). Combined action of the type IV secretion effector proteins BepC and BepF promotes invasome formation of Bartonella henselae on endothelial and epithelial cells. Cell Microbiol. 13(2):284-99. [PudMed:20964799]

(7) Quebatte M; Dehio M; Tropel D; Basler A; Toller I; Raddatz G; Engel P; Huser S; Schein H; Lindroos HL; Andersson SG; Dehio C (2010). The BatR/BatS two-component regulatory system controls the adaptive response of Bartonella henselae during human endothelial cell infection. J Bacteriol. 192(13):3352-67. [PudMed:20418395]

(8) Scheidegger F; Ellner Y; Guye P; Rhomberg TA; Weber H; Augustin HG; Dehio C (2009). Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation. Cell Microbiol. 11(7):1088-101. [PudMed:19416269]

(9) Schulein R; Guye P; Rhomberg TA; Schmid MC; Schroder G; Vergunst AC; Carena I; Dehio C (2005). A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells. Proc Natl Acad Sci U S A. 102(3):856-61. [PudMed:15642951]

(10) Schmid MC; Schulein R; Dehio M; Denecker G; Carena I; Dehio C (2004). The VirB type IV secretion system of Bartonella henselae mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. Mol Microbiol. 52(1):81-92. [PudMed:15049812]

(11) Schmiederer M; Arcenas R; Widen R; Valkov N; Anderson B (2001). Intracellular induction of the Bartonella henselae virB operon by human endothelial cells. Infect Immun. 69(10):6495-502. [PudMed:11553594]

This literature contains experimental investigation

This literature contains bioinformatics investigation