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Conjugal DNA-protein transfer complexes. The VirB4 ATPase may mediate dislocation of the membrane-integrated VirB2 pilin (N- and C-termini out; cytoplasmic loop= residues 90-94 inside) during biogenesis of the Agrobacterium VirB/VirD4 type IV secretion system. VirB6 domains direct the ordered export of the DNA substrate through a type IV secretion System (Jakubowski et al. 2004).


VirB complex of Agrobacterium tumefaciens
VirB2 precursor

Trw conjugation system of E. coli plasmid IncP. The hexameric form of TrwK is a catalytically active ATPase, much like the structurally related protein TrwB, the conjugative coupling protein (Arechaga et al, 2008), which is a structure-specific DNA-binding protein (Matilla et al., 2010)


Trw conjugation system of E. coli plasmid R388
TrwL1 (like VirB2)
TrwM (like VirB3)
TrwK (like VirB4)
TrwJ (like VirB5)
TrwI (like VirB6)
TrwH (like VirB7)
TrwG (like VirB8)
TrwF (like VirB9)
TrwE (like VirB10)
TrwD (like VirB11)
TrwB (like TraG and VirD4)

Pertussis toxin exporter. For consideration of the requirements for assembly, see Verma and Burns, 2007.

Pertussis toxin exporter of Bordetella pertussis
PtlA (like VirB2)
PtlB (like VirB3)
PtlC (like VirB4)
PtlD (like VirB6)
PtlI (like VirB7)
PtlE (like VirB8)
PtlF (like VirB9)
PtlG (like VirB10)
PtlH (like VirB11)

Trb proteins of Enterobacter aerogenes plasmid IncP
Trb proteins of Enterobacter aerogenes plasmid IncP
TrbC (like VirB2)
TrbD (like VirB3)
TrbE (like VirB4)
TrbJ (like VirB5)
TrbL (like VirB6)
TrbK (like VirB7)
TrbF (like VirB8)
TrbG (like VirB9)
TrbI (like VirB10)
TrbB (like VirB11)

P-type conjugal transfer system

Conjugal transfer system of Ilyobacter polytropus 
TraG (620 aas; E3HE20)
TrbB (310 aas; E3HE22)
TrbC (106 aas; E3HE16)
TrbD (85 aas; E3HE23)
TrbE (804 aas; E3HE24)
TrbF (227 aas; E3HE17) 
TrbG (274 aas; E3HE18)
TrbI (364 aas; E3HE19)
TrbJ (251 aas; E3HE25)
TrbL (350 aas; E3HE26)
Uncharacterized protein (117 aas; E3HE21) 

LvhB proteins of Legionella pneumophila (De Buck et al., 2007)

LvhB proteins of Legionella pneumophila
LvhB2 (like VirB2)
LvhB3 (like VirB3)
LvhB4 (like VirB4)
LvhB5 (like VirB5)
LvhB6 (like VirB6)
LvhB7 (like VirB7)
LvhB8 (like VirB8)
LvhB9 (like VirB9)
LvhB10 (like VirB10)
LvhB11(like VirB11)
LvhD4 (like VirD4) (Q5ZW42)

Tra proteins of plasmid Inc N (Escherichia coli)
Tra proteins of plasmid Inc N (Escherichia coli)
TraM (like VirB2)
TraA (like VirB3)
TraB (like VirB4)
TraC (like VirB5)
TraD (like VirB6)
TraN (like VirB7)
TraE (like VirB8)
TraO (like VirB9)
TraF (like VirB10)
TraG (like VirB11)

Trs DNA transfer protein complex of plasmid pGO1 of Staphylococcus aureus (Grohman et al., 2003)
Trs proteins of Staphylococcus aureus plasmid pGO1
TrsA (B36891)
TrsB (C36891)
TrsC (D36891)
TrsD (E36891)
TrsE (F36891)
TrsF (G36891)
TrsG (H36891)
TrsH (I36891)
TrsI (A56976)
TrsJ (B56976)
TrsK (C56976)
TrsL (D56976)
TrsM (E56976)
TrsN (A36891)
TrsO (F56976)

Competence system for DNA uptake (ComB) (Hofreuter et al., 2003; Karnholz et al., 2006). DNA uptake into the periplasm occurs preferentially at the poles. Transport into the cytoplasm depends on ComEC. Thus, DNA uptake may occur in a two step process (Stingl et al., 2010).

ComB1-4 and ComB6-10 of Helicobacter pylori
ComB1 (CAA10655)
ComB2 (CAA10656)
ComB3 (CAA10657)
ComB4 (AAS03033)
ComB6 (hp0037; Hp26695 genome)
ComB7 (hp0038; Hp26695 genome)
ComB8 (AAM03034)
ComB9 (AAM03035)
ComB10 (AAM03036)

The Icm/Dot or Dot/Icm multicomponent protein secretion system. IcmS and IcmW form a complex that interacts with and may translocate substrate proteins (Ninio et al., 2005; De Buck et al., 2007; Cambronne and Roy, 2007). The crystal structure of the IcmR-IcmQ complex has been solved (Raychaudhury et al., 2009). Legionella pneumophila survives and replicates inside host cells by secreting ~300 effectors through the defective in organelle trafficking (Dot)/intracellular multiplication (Icm) type IVB secretion system (T4BSS). Ghosal et al. 2019, using electron cryotomography mapped the location of the core and accessory components of the Legionella core transmembrane subcomplex, revealing a well-ordered central channel that opens into a large, windowed secretion chamber with an unusual 13-fold symmetry. Immunofluorescence microscopy deciphered an early-stage assembly process that begins with the targeting of Dot/Icm components to the bacterial poles. Polar targeting of this T4BSS is mediated by two Dot/Icm proteins, DotU and IcmF, that are homologues of the T6SS membrane complex components TssL and TssM, suggesting that the Dot/Icm T4BSS is a hybrid system. Thus, the Dot/Icm complex assembles in an 'axial-to-peripheral' pattern (Ghosal et al. 2019).

The Icm/Dot system of Legionella pneumophila
IcmT1 (IM; like TraK) (AAU26538)
IcmS (Cyt) (AAU26539)
IcmR (Cyt) (AAU26540)
IcmQ (Cyt) (AAU26541)
IcmP/DotM (L Trb) (IM; like TrbA) (AAU26542)
IcmO/DotL (IM; like TrbC and VirD4) (AAU26543)
IcmN/DotK/LphA (peri) (AAU26544)
IcmM/DotJ (IM) (AAU26545)
IcmL/DotI (IM; like TraM) (AAU26546)
IcmK/DotH (peri; like TraN) (AAU26547)
IcmE/DotG (IM; like TraO and VirB10) (AAU26548)
IcmG/DotF (IM; like TraP) (AAU26549)
IcmC/DotE (IM; like TraQ) (AAU26550)
IcmD/DotP (IM; like TraR) (AAU26551)
IcmJ/DotN (Cyt; like TraT) (AAU26552)
IcmB/DotB (Cyt; like TraU and VirB4) (AAU26553)
IcmF (IM) (AAU26554)
IcmH (IM) (AAU26555)
IcmW (Cyt) (AAU28746)
IcmX (peri; like TraW) (AAU28747)
IcmV (IM; like TraX) (AAU28745)
DotA (IM; like TraY) (AAK63144)
DotB (Cyt; like TraJ and VirB11) (AAU28734)
DotC (peri; like TraI) (AAU28733)
DotD (peri; like TraH) (AAU28732)

The E. coli plasmid R64 IncI conjugation system
other sequences
The IncI conjugation system of plasmid R64 of E. coli
TrbA (BAA78018)
TrbB (BAA78019)
TrbC (BAA78020)
TraH (BAA77993)
TraI (BAA77994)
TraJ (BAA77995)
TraK (BAA77996)
TraL (BAA78000)
TraM (BAA78001)
TraN (BAA78002)
TraO (BAA78003)
TraP (BAA78004)
TraQ (BAA78005)
TraR (BAA78006)
TraS (BAA78007)
TraT (BAA78008)
TraU (BAA78009)
TraV (BAA78010)
TraW (BAA78011)
TraX (BAA78012)
TraY (BAA78013)

The type IV β-proteobacterial DNA secretion system (non contact dependent) for natural transformation)

DNA secretion system of Neisseria gonorrhoeae
TraD (Q5EPC8)
TraI (Q5EPC7)
TraA (Q5EPC3)
TraL (Q5EPC2)
TraE (Q5EPC1)
TraK (Q5EPC0)
TraB (Q5EPB9)
TraV (Q5EPB7)
TraC (Q5EPB6)
TrbI (Q5EPB4)
TraW (Q5EPB3)
TraU (Q5EPB2)
TrbC (Q5EPB1)
TraN (Q5EPA9)
TraF (Q5EPA7)
TraH (Q93NF2)
TraG (Q5EPA5)
DsbC (Q5K698)
AtlA (O30554)
ParA (Q5EP68)

The Cag pathogenicity island (PAI) proteins (Kutter et al., 2008).  CagD (Cag24) is essential for CagA translocation and maximal induction of interleukin-8 secretion (Cendron et al., 2009). It is required for a pro-inflammatory response and multiple cytoskeletal and gene regulatory effects in gastric epithelial cells. Its molecular properties are described in a review by Fischer (2011). Cag16 (CagM) (of unknown function and not dermonstrably homologous to proteins of type IV secretion systems in other bacteria) has 3-4 TMSs and is essential for CagA export. It may therefore be a core protein of the Cag complex (Ling et al. 2013).

The Cag PAI proteins of Helicobacter pylori:
Cag1 O25257
Cag2 ABO28051
Cag3 O25258
Cag4 (like VirD4) O25259
Cag5 O25260
Cag6 (like VirB10) O25261
Cag7 (like VirB9) O25262
Cag8 O25263
Cag9 (like VirB4) O25264
Cag10 O25265
Cag11 O25266
Cag12 P97245
Cag13 P97227
Cag14 O25268
Cag15 O25269
Cag16 O25270
Cag17 O25271
Cag18 O25272
Cag19 O25273
Cag20 O25274
Cag21 O25275
Cag22 O25276
Cag23 Q48252
Cag24 O25277
Cag25 O25278

The putative type IV secretion system of Bacillus anthracis (most genes are encoded on the two virulience plasmids pXO1 and pXO2; Grynberg et al., 2007).

Type IV secretion system of Bacillus anthracis
pXO1-42 (like VirD4; BXA0064; Q8KYQ0)
pXO1-57 (like VB4; BXA0083; Q8KYP1)
pXO1-58 (like CpaE; BXA0084; Q8KYP0)
pXO1-59 (like CpaF, VirB11; BXA0085; Q7CMH0)
pXO1-60 (like TadB, TadC; BXA0086; Q7CMG9)
pXO1-61 (like TadB, TadC; BXA0087; Q8KYN9)
pXO1-63 (like PilA; BXA0089; Q8KYN8)
pXO1-64 (like PilA; BXA0090; Q7CMG7)
pXO1-66 (like PapD; BXA0092; Q7CMG6)
pXO1-67 (like CheW; BXA0093; Q7CMG5)
pXO1-68 (like CpaA; BXA0068; Q8KYP9)
pXO1-77 (like VirB4; BXA0077; Q7CMH3)
pXO1-78 (like VB4; BXA0107; Q8R8B3)
pXO1-79 (like VB6; BXA0108; Q7CMF7)
pXO2-09 (like VirB4-C; BXB0008; Q6F059)
pXO2-10 (like VirB4-N; BXB0009; Q9RN22)
pXO2-15 (like VirD4-C; BXB0014; Q9RN17)
pXO2-16 (like VirD4-N; BXB0015; Q7CMB1)
pXO2-23/24 (like TadB, TadC; BXB0022; Q9RN08)
pXO2-25 (like CpaF, TadA, VirB11; BXB0023; Q6F054)
BA4072 (like VD4; Q81WB0)

The plasmid pLS20 conjugation system. Several conserved conjugation proteins carried on the Bacillus subtilis plasmid pLS20, (VirB1, VirB4, VirB11, VirD2, and VirD4 homologs) assemble at a single cell pole, but also at other sites along the cell membrane, in cells during the lag phase of growth (Bauer et al., 2011).

Plasmid pLS20 conjugation system of Bacillus subtilis 
VirB1 (Orf30) (E9RJ18)
VirB4 (Orf24) (E9RJ16)
VirB11 (Orf13) (E9RJ00)
VirD2 (Orf34) (E9RJ23)
VirD4 (Orf24) (E9RJ12) 
PO16 (E9RJ01)
PO17 (E9RJ02)
PO25 (E9RJ10)
PO26 (E9RJ11)
PO27 (E9RJ12)
PO28 (E9RJ13)
PO32 (E9RJ17)
PO34 (E9RJ19) 

Type 4 conjugal transfer (tra) system of Gram-positive bacteria, Orf1-Orf15 (Abajy et al., 2007).
other sequences
Orf1-Orf15 of Gram-positive bacterial (Enterococcus faecalis) conjugal plasmid, pIP501 (most resembles the Trs system of S. aureus; TC#3.A.7.7.1).
Orf1 (654aas) (Q52001) (A relaxase, resembles EsaA of S. aureus, 9.A.44.1.1 and MLP1 of S. cerevisiae, 9.A.14.1.1)
Orf2 (110aas) (Q52002) (homologous to TrsB of S. aureus)
Orf3 (127aas) (Q52003) (homologous to TrsC of S. aureus)
Orf4 (190aas) (Q52004) (homologous to TrsD of S. aureus)
Orf5 (653aas) (Q52005) (VirB4-like ATPase; homologous to TrsE of S. aureus)
Orf6 (450aas) (Q52006) (homologous to TrsF of S. aureus)
Orf7 (369aas) (Q8L1D1) (lytic transglycosidase; like TrsG)
Orf8 (183aas) (Q9AL12) (like TrsA)
Orf9 (143aas) (Q9AL11)
Orf10 (551aas) (Q8L1D0) (VirD4-like putative coupling protein; like TrsK)
Orf11 (307aas) (Q8L1C9) (most similar to Streptolysin O (1.C.12.1.4))
Orf12 (310aas) (Q8L1C8) (like TrsL)
Orf13 (322aas) (Q8L1C7)
Orf14 (122aas) (Q7BVV5)
Orf15 (282aas) (Q8L1C6) (contains a long stretch TEP tripeptide repeats)

Conjugation system, IntP/TcpA-J (Bannam et al., 2008; Teng et al., 2008). TcpA but not TcpB is essential for transfer of the conjugative plasmid pCW3 (Parsons et al., 2007). TcpA interacts with other pCW3-encoded proteins to form an essential part of the conjugation complex (Steen et al., 2009).

IntP/TcpA-J of Clostridium perfringens
IntP (251aas;0TMSs) (Q15HV4)
TcpA (532aas;3TMSs) (Shows similarity to proteins in 3.A.12; e.g. SpoIIIE) (Q15HV3)
TcpB (302aas;0TMSs) (Shows similarity to proteins in 3.A.12; e.g. SpoIIIE) (Q2L5Y2)
TcpC (359aas;1TMS) (Q15HV1)
TcpD (115aas;3TMSs) (Q15HV0)
TcpE (125aas;2TMSs) (Q15HU9)
TcpF (840aas;0TMSs) (shows limited sequence similarity to 3.A.7.13.1 Q8R8B3) (Q15HU7)
TcpG (334aas;1TMS) (Q15HU6)
TcpH (831aas;8TMSs(4+4)) (Contains UirB6-like domains and shows sequence similarity in the same regions to 3.A.1.14.18 (Q5HGV2) and 3.A.7.12.1 (O25262)) (Q15HU5)
TcpI (164aas;4TMSs) (Q15HU4)
TcpH (258aas;1TMS) (Q15HU3)

ICEBs1 mobile element: subunits  ConA - G and Q of the conjugation machinery (Johnson and Grossman 2015; Lee et al. 2007; Lee et al. 2012). The integrase, Int or YdcL and the excisionase (Xis or SacV) are also included. Of these subunits, only ConE, ConG and ConQ show good sequence similarity with subunits of TC# 3.A.7.14.2.

Subunits A - G and Q of the ICEBs1 mobile element of the conjugation system of Bacillus subtilis
ConA, 58 aas and 2 TMSs
ConB, 354 aas and 1 TMS
ConC, 82 aas and 2 TMSs
ConD, 174 aas and 2 TMSs
ConE, 831 aas and 0 TMSs (a VirB6-like ATPase)
ConF, 108 aas and 0 or 1 (N-terminal) TMSs
ConG, 777 aas and 8 or 9 TMSs
ConQ, 180 aas and 2 N-terminal TMSs
Int, 368 aas; P96629
Xis, 64 aas; O31490

The nonspecific tight adherence fibril (pilus) secretion septum (Flp-1, Flp-2, TadV-RcpCAB Tad ZA-G) (Kachlany et al., 2000; Bhattacharjee et al., 2001; Haase et al., 2003; Schreiner et al., 2003; Wang and Chen, 2005; Tomich et al. 2007). The outer membrane components of the Tad (tight adherence) secreton have been identified (Clock et al. 2008). The tad locus is required for tenacious, nonspecific adherence to surfaces and formation of extremely strong biofilms. This locus is dedicated to the biogenesis of Flp pili, which are required for colonization and virulence (Perez et al. 2006).

TadA-G, V, Z of Acinobacillus (Aggregatibacter) actinomycetemcomitans
Flp-1 (75aas) (Q9ANW5)
Flp-2 (76aas) (O66150)
RcpA secretin (460aas) (Q8GD00)
RcpB (167aas) (Q9X6J2)
RcpC (shows 25% identity, 41% similarity with 3.A.1.122.2; O31712)(274aas) (Q8GD01)
TadA (ATPase; Most like LvhB11; 3.A.7.5.1; Q9RLR3) (426aas) (Q9XC06)
TadB (295aas) (Q9XC05)
TadC (288aas) (Q9S4A8)
TadD (Most like 8.A.11.1.1; Q9LDC0 peptidyl prolyl isomerase) (253aas) (Q9S4A7)
TadE (191aas) (Q9S4A6)
TadF (Most like 3.A.7.14.1; Q52001) (200aas) (Q9S4A5)
TadG (Most similar to 1.A.13.1.2; Q9UNF7; Ca2+-activated Cl- channel)
(Q9S4A4) TadV (142aas) (Q8GD02)
TadZ (374aas) (Q8GCZ9)

F-like conjugation DNA transfer system (Greub et al., 2004).

The F-type conjugation system of Protochlamydia amoebophila
TraA; TrbB; RecD (721aas) (Q6MDD6)
TrbC (198aas) (Q6MB92) 
TraB (408aas) (Q6MBA0)
TraC (828aas) (Q6MB95)
TraD (556aas) (Q6MB84)
TraE (189aas) (Q6MBA2) 
TraFa (160aas) (Q6MB94)
TraFb (263aas) (Q6MB87)
TraG (927aas) (Q6MB85)
TraH (452aas) (Q6MB86)
TraN (184aas) (Q6MB88)
TraU (311aas) (Q6MB91)
TraW (210aas) (Q6MB93) 

The EsxA/B protein secretion pathway system (EPSP) (Anderson et al. 2011; Burts et al. 2005; Chen et al. 2012; Sundaramoorthy et al. 2008).  EssC is an integral component of the bacterial ""Type VII"" secretion system (T7SS). The protein is predicted to consist of an intracellular repeat of forkhead-associated (FHA) domains at the N-terminus, two transmembrane helices and three P-loop containing ATPase-type domains, D1-3, forming the C-terminal intracellular segment. Zoltner et al. 2016 presented crystal structures of the N-terminal FHA domains (EssC-N) and a C-terminal fragment EssC-C from Geobacillus thermodenitrificans, encompassing two of the ATPase-type modules, D2 and D3. Module D2 binds ATP with high affinity whereas D3 does not. The EssC-N and EssC-C constructs are monomeric in solution but the full-length recombinant protein, with molecular weight about 169 kDa, forms a multimer of approximately 1 MDa. The observation of protomer contacts in the crystal structure of EssC-C together with similarity to the DNA translocase FtsK, suggests a model for a hexameric EssC assembly. Such an observation potentially identifies the key component of pore formation required for secretion. The extreme C-terminal ATPase domain appears essential for EssC activity as a key part of the T7SS whilst D2 and FHA domains are required for the production of a stable and functional protein (Zoltner et al. 2016). TheTMSs of EssA and EssB interact, regulating secretion (Ahmed et al. 2018). This system resembles the ESX systems of Mycobacterium tuberculosis (TC# 3.A.24).


EPSP of Staphylococcus aureus (EsaA-C/EssA-C)
EsaA (1009 aas) (Q99WU3)
EsaB (80 aas) (Q99WU1)
EsaC (130 aas) (Q99WT8)
EssA (152 aas) (Q99WU2)
EssB (444 aas) (Q99WU0)
EssC (1479 aas) (Q932J9)
EsaD (617aas) (A6QDR8) 

The Cpa protein secretion system, PilA-CpaA-F. PilA (58aas) is similar to Flp pilin (1.E.52.3.2) (Tomich et al. 2007).

The Cpa system of Caulobacter crescentus
PilA (pilin) (Q9L720)
CpaA (Prepilin peptidase) (Q9L719)
CpaB (Pilus assembly protein) (Q9L718)
CpaC Secretin (Q9L717)
CpaD (Pilus assembly protein) (Q9L716)
CpaE (Pilus assembly ATPase) (Q9L715)
CpaF (Pilus assembly ATPase) (Q9L714)

Type IV-like, Tad-like protein secretion system, the Kil system, potentially containing up to 21 proteins. The genes of this system are encoded within two gene clusters, MXAN_3102-3108 and MXAN_4648-4661. All 21 gene products are included within this TC entry although it is not established that all participate in secretion. The descriptions of the proteins are as listed in UNIPROT. Myxococcus xanthus, a soil bacterium, predates collectively using motility to invade prey colonies. Prey lysis is mostly thought to rely on secreted factors, cocktails of antibiotics and enzymes as well as direct contact with Myxococcus cells. Seef et al. 2021 showed that on surfaces, the coupling of A-motility and contact-dependent killing is the central predatory mechanism driving effective prey colony invasion and consumption. At the molecular level, contact-dependent killing involves a type IV filament-like machinery (Kil) that both promotes motility arrest and prey cell plasmolysis. In this process, Kil proteins assemble at the predator-prey contact site, suggesting that they allow tight contact with prey cells for their intoxication. Kil-like systems form a new class of Tad-like machineries in predatory bacteria, suggesting a conserved function in predator-prey interactions. The system allows a novel cell-cell interaction function for bacterial pilus-like assemblages (Seef et al. 2021).

The Kil system of secretion and predation of Myxococcus xanthus

The putative Pcf type IV protein/DNA secretion (conjugation) system of the Enterococcus faecalis plasmid pCF10. All Pcf proteins with more than 100 aas were included (Hirt et al. 2005).

The Pfc system of Enterococcus faecalis pCF10 plasmid.  All Pcf proteins with more than 100 aas were included (Hirt et al. 2005).
PcfY, 206 aas, Q5G3L7
PcfC, 609 aas, 3 TMSs, Q5G3N9
PcfD, 719 aas, Q5G3N8
PcfG, 561 aas, Q7X5P3
PcfK, 258 aas, Q5G3N1
PcfJ, 445 aas, Q5G3N2
PcfV, 341 aas, 10 TMSs, Q5G3M0
PcfB, 161 aas, Q5G3P0
PcfF, 118 aas, Q5G3N6
PcfO, 149 aas, 1 TMS, Q5G3M7
PcfA, 202 aas, Q5G3P1
PcfX, 219 aas, Q5G3L8
PcfR, 164 aas, 2 TMSs, Q5G3M4
PcfU, 109 aas, Q5G3M1
PcfL, 182 aas, Q5G3N0
PcfH, 116 aas, 3 TMSs, Q5G3N4
PcfS, 150 aas, ssDNA binding protein, Q5G3M3
PcfT, 192 aas, Q5G3M2