StrainHelicobacter pylori G27
Repliconchromosome [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_011333
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProductComponent
1HPG27_476 (era)510908..511813 [+], 906208434439GTP-binding protein Era 
2HPG27_477511810..512802 [+], 993208434440hypothetical protein 
3HPG27_478512885..513766 [-], 882208434441hypothetical protein 
4HPG27_479 (cag1)513910..514257 [+], 348208434442cag pathogenicity island protein 1 
5HPG27_480514464..514715 [+], 252208434443hypothetical protein 
6HPG27_481 (cag3)514715..516160 [+], 1446208434444cag pathogenicity island protein 3  Cagdelta
7HPG27_482 (cag4)516165..516674 [+], 510208434445cag pathogenicity island protein 4  Caggamma
8HPG27_483 (cag5)516793..519039 [-], 2247208434446cag pathogenicity island protein 5  Cagbeta
9HPG27_484519048..520040 [-], 993208434447virB11-like cag pathogenicity islandencoded protein / ATPase  Cagalpha
10HPG27_485 (cagZ)520045..520644 [-], 600208434448cag pathogenicity island protein Z  CagZ
11HPG27_487 (cagX)526506..528071 [-], 1566208434449cag pathogenicity island protein X  CagX
12HPG27_488 (cagW)528123..529730 [-], 1608208434450cag pathogenicity island protein W  CagW
13HPG27_489 (cagV)529735..530493 [-], 759208434451cag pathogenicity island protein V  CagV
14HPG27_490 (cagU)530890..531540 [+], 651208434452cag pathogenicity island protein U  CagU
15HPG27_491 (cagT)531553..532395 [+], 843208434453cag pathogenicity island protein T  CagT
16HPG27_492 (cagS)532592..533191 [-], 600208434454cag pathogenicity island protein S 
17HPG27_493 (cagQ)535518..535823 [-], 306208434455cag pathogenicity island protein Q 
18HPG27_494535835..536014 [-], 180208434456hypothetical protein 
19HPG27_495 (cagM)537100..538230 [+], 1131208434457cag pathogenicity island protein M  CagM
20HPG27_496 (cagN)538245..539165 [+], 921208434458cag pathogenicity island protein N  CagN
21HPG27_497 (cagL)539247..539960 [-], 714208434459cag pathogenicity island protein L  CagLinteraction
22HPG27_498 (cagI)539957..541033 [-], 1077208434460cag pathogenicity island protein I  CagI
23HPG27_499 (cagH)541113..542045 [-], 933208434462cag pathogenicity island protein H  CagH
24HPG27_500542044..542244 [+], 201208434461hypothetical protein 
25HPG27_501 (cagG)542241..542669 [-], 429208434463cag pathogenicity island protein G  CagG
26HPG27_502 (cagF)542724..543530 [-], 807208434464cag pathogenicity island protein F  CagFaccesspry protein
27HPG27_503 (cagE)543532..546483 [-], 2952208434465cag pathogenicity island protein E  CagE
28HPG27_504 (cagD)546492..547115 [-], 624208434466cag pathogenicity island protein D  CagD
29HPG27_505 (cagC)547117..547464 [-], 348208434467cag pathogenicity island protein C  CagC
30HPG27_506 (cagB)547609..547836 [-], 228208434468cag pathogenicity island protein B 
31HPG27_507 (cagA)548263..551955 [+], 3693208434469cytotoxin-associated protein A  interaction
accesspry protein This T4SS contains information of accessory protein.
interaction This T4SS contains information of interaction.
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

CagA; Peptidoglycan

The information of protein effectors
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProduct  *
1HPG27_507 (cagA)548263..551955 [+], 3693208434469cytotoxin-associated protein Aexperimental  CagAinteraction
experimental T4SE derived from experimental literature.
interaction This effector contains information of interaction.

Download FASTA format files
Proteins        Genes
The information on requirements for T4SS substrate-channel docking

Certain T4SS substrates require secretion chaperones for translocation. These chaperones often possess physical properties (small size of 15 kDa, acidic pI, and amphipathic helices) resembling those of chaperones associated with the type III secretion systems, a family of macromolecular translocation systems ancestrally related to bacterial flagella.

#Accessory protein(GI)motif(s)Substrate(s)FunctionReference
1CagF (chaperone) (208434464)CT20aa and an intact N terminusCagAThe CagA-binding protein CagF is a secretion chaperone-like protein that interacts with a 100 aa region that is adjacent to the C-terminal secretion signal of CagA.CagF is a translocation factor for CagA, but is not translocated by the type IV apparatus.(1) PubMed: 17768234
1.Substrate(s): For the conjugation systems, the listed proteins are relaxases that bind a cognate T4CP and are delivered to recipient cells. For the effector translocator systems, the listed proteins are effectors that play a role in the infection processes of the bacterial pathogen.
2.motif(s):The motifs listed are required for substrate translocation. In some cases, the protein or its C-terminal fragment (CT) is sufficient to mediate translocation to target cells, as shown by fusion to a reporter protein such as Cre recombinase or adenylate cyclase. Amino acids (aa) at positions listed relative to the C-terminal fragment (subscript) are required for translocation, as shown by mutational analysis. ND, not determined. Parentheses indicate that the interaction between a protein substrate and a cognate T4CP has been experimentally shown.
3.Accessory protein: Accessory factors required for T4SS channel docking or translocation. The proposed function in mediating substrate-T4SS channel docking is shown in parentheses.PubMed:19946141

(1) Pattis I; Weiss E; Laugks R; Haas R; Fischer W (2007). The Helicobacter pylori CagF protein is a type IV secretion chaperone-like molecule that binds close to the C-terminal secretion signal of the CagA effector protein. Microbiology. 153(Pt 9):2896-909. [PudMed:17768234] experimental
The information on host-pathogen interaction.

#Name(Protein GI)Host site/SubstrateSourceFunctionReference
1CagA (208434469)SHP-2humanCagA is translocated into gastric epithelial cells. It physically interacts with SHP-2 to modify cellular functions and perturb mammalian signal transduction machineries. This may induce gastric epithelial cells to move and proliferate abnormally and help to acquire a cellular transformed phenotype.(1) PubMed: 11743164insolico
2CagA (208434469)growth factor receptor bound 2 (Grb2)unknownCagA targets to Grb2 and this process leads to activing the MEK/ERK pathway and results in cell scattering and proliferation.(2) PubMed: 12419219insolico
3CagA (208434469)PAR1/MARK kinasehumanCagA interacts with PAR1/MARK kinase to inhibit the activity of PAR1 kinase and prevent PAR1 phosphorylation which mediated by atypical protein kinase C (aPKC).(3) PubMed: 17507984insolico
4CagA (208434469)Apoptosis-stimulating of p53 protein 2 (ASPP2)humanASPP2 is a tumor suppressor that activates the apoptotic response upon cellular stress which mediated by p53. CagA interacts with ASPP2 to change the function of ASPP2 and this process leads to the decreased survival of cells which infected by H. pylori.(4) PubMed: 24474782insolico
5CagA (208434469)protein kinase C-related kinase 2 (PRK2)humanCagA represses kinase activity of PRK2, which has been involved in establishment of cell polarity and rearrangements of cytoskeleton, to further control signalling pathways associated with cancer.(5) PubMed: 26041307insolico
6CagA (208434469)Glycogen synthase kinase 3 (GSK-3)humanCagA interacts with GSK-3 to reduce its activity by cause it to transform into an insoluble fraction. CagA then induce a epithelial mesenchymal transition mediated by Snail via the comsuming of GSK-3.(6) PubMed: 25055241insolico
7CagA (208434469)c-MethumanCagA interacts with the c-Met receptor to modulates cellular functions through deregulating c-Met receptor signaling and participates in invasive growth of tumor cells.(7) PubMed: 12719469insolico
8CagA (208434469)E-cadherinhumanCagA interacts with E-cadherin to impair the complex formation between E-cadherin and beta-catenin and facilitate transdifferentiation of intestines in gastric epithelial cells.(8) PubMed: 17237808insolico
9CagA (208434469)host membrane phosphatidylserineunknownCagA can be tethered to the inner leaflet of the plasma membrane by interacting with phosphatidylserine. Then it binds the PAR1/MARK to induce polarity and junctional defects.(9) PubMed: 20478541experimental
10CagA (208434469)c-Abl tyrosine kinasehumanCagA targets to c-Abl directly and localizes in focal adhesion complexes and membrane ruffles.(10) PubMed: 17160020insolico
11CagA (208434469)αPixhumanCagA interacted with αPix to activates PAK1, ERK and NF-kappaB after being delivered into AGS cells. Then it induces the expression of IL-8 in infected gastric epithelial cells.(11) PubMed: 19672789insolico
12CagA (208434469)scaffolding protein ZO-1human, canineCagA interacts with epithelial tight-junction ZO-1 and the transmembrane protein junctional adhesion molecule to change the function and composition of the apical-junctional complex.(12) PubMed: 12775840experimental
13CagA (208434469)integrin α5β1 receptorhumanCagA binds interface with α5β1 integrin.It is an essential step for the translocation process of CagA into the host cell.(13) PubMed: 22908298insolico
14CagA (208434469)TNF receptor-associated factor 1 and 4-1BB (TRAF1 and 4-1BB)humanCagA facilitates the proliferation and represses the apoptosis of GES-1 cells by upregulated TRAF1/4-1BB.(14) PubMed: 28627614insolico
15CagA (208434469)Adapter molecule crkhumanThe interaction between CagA and Crk adaptor proteins is important for loss of gastric epithelial cell adhesion induced by Helicobacter pylori-induced Helicobacter pylori.(15) PubMed: 16275761insolico
16CagA (208434469)SHP-1humanCagA interacts with SHP1 to enhance the phosphatase activity of SHP1 so that it dampens the oncogenic action of CagA.(16) PubMed: 27572445insolico
17CagA (208434469)Transforming growth factor-beta-activated kinase 1 (TAK1)humanCagA interacts with TAK1 and improves its activity to activate NF-kappaB through the ubiquitination of TAK1.(17) PubMed: 19820695experimental
18CagA (208434469)Myeloid cell leukemia sequence-1 (MCL1)mongolian gerbilCagA increases MCL1 thorough the interaction between SRE/SRF and CagA/MCL1 in modulating rapid turnover of pit epithelial cells via MEK/ERK/SRE activation.(18) PubMed: 18005743insolico
19CagL (208434459)integrin α5β1 receptorhumanCagL, which is targeted to the pilus surface, is a specialized adhesin. It binds to and activates integrin α5β1 receptor on gastric epithelial cells. This interaction triggers CagA delivery into target cells.(19) PubMed: 17943123insolico
20CagL (208434459)integrin αvβ3humanHost cell docking of T4SS.(20) PubMed: 21915696insolico
21CagL (208434459)integrin αvβ5humanCagL/integrin β5 signalling complex is important for gastrin expression induced by H. pylori.(21) PubMed: 22287591insolico
22CagL (208434459)integrin αvβ6humanαvβ6 is a specific, high affinity receptor for CagL.(22) PubMed: 31197920experimental
experimental This T4SE is mentioned in the literature.
insolico This T4SE is highly identical with the protein mentioned in the literature.
(1) Higashi H et al. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 295(5555):683-6. [PudMed:11743164] experimental
(2) Mimuro H et al. (2002). Grb2 is a key mediator of helicobacter pylori CagA protein activities. Mol Cell. 10(4):745-55. [PudMed:12419219] experimental
(3) Saadat I et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 447(7142):330-3. [PudMed:17507984] experimental
(4) Nešić D et al. (2014). Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proc Natl Acad Sci U S A. 111(4):1562-7. [PudMed:24474782] experimental
(5) Mishra JP et al. (2015). CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2. Cell Microbiol. 17(11):1670-82. [PudMed:26041307] experimental
(6) Lee DG et al. (2014). Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity. Nat Commun. 5:4423. [PudMed:25055241] experimental
(7) Churin Y et al. (2003). Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol. 161(2):249-55. [PudMed:12719469] experimental
(8) Murata-Kamiya N et al. (2007). Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 26(32):4617-26. [PudMed:17237808] experimental
(9) Murata-Kamiya N; Kikuchi K; Hayashi T; Higashi H; Hatakeyama M (2010). Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe. 7(5):399-411. [PudMed:20478541] experimental
(10) Poppe M; Feller SM; Romer G; Wessler S (2007). Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene. 26(24):3462-72. [PudMed:17160020] experimental
(11) Lim JW et al. (2009). alphaPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells. Scand J Gastroenterol. 44(10):1166-72. [PudMed:19672789] experimental
(12) Amieva MR et al. (2003). Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 300(5624):1430-4. [PudMed:12775840] experimental
(13) Kaplan-Türköz B et al. (2012). Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin. Proc Natl Acad Sci U S A. 109(36):14640-5. [PudMed:22908298] experimental
(14) Wang F et al. (2017). CagA promotes proliferation and inhibits apoptosis of GES-1 cells by upregulating TRAF1/4-1BB. Mol Med Rep. 16(2):1262-1268. [PudMed:28627614] experimental
(15) Suzuki M et al. (2005). Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med. 202(9):1235-47. [PudMed:16275761] experimental
(16) Saju P et al. (2016). Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus. Nat Microbiol. 1:16026. [PudMed:27572445] experimental
(17) Lamb A et al. (2009). Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination. EMBO Rep. 10(11):1242-9. [PudMed:19820695] experimental
(18) Mimuro H et al. (2007). Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. Cell Host Microbe. 2(4):250-63. [PudMed:18005743] experimental
(19) Kwok T; Zabler D; Urman S; Rohde M; Hartig R; Wessler S; Misselwitz R; Berger J; Sewald N; Konig W; Backert S (2007). Helicobacter exploits integrin for type IV secretion and kinase activation. Nature. 449(7164):862-6. [PudMed:17943123] experimental
(20) Conradi J; Huber S; Gaus K; Mertink F; Royo Gracia S; Strijowski U; Backert S; Sewald N (2012). Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins alpha(V)beta (3) and alpha (5)beta (1). Amino Acids. 43(1):219-32. [PudMed:21915696] experimental
(21) Wiedemann T et al. (2012). Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex. Gut. 61(7):986-96. [PudMed:22287591] experimental
(22) Buß M et al. (2019). Specific high affinity interaction of Helicobacter pylori CagL with integrin αV β6 promotes type IV secretion of CagA into human cells. FEBS J. . [PudMed:31197920] experimental
(1) You Y; He L; Zhang M; Fu J; Gu Y; Zhang B; Tao X; Zhang J (2012). Comparative Genomics of Helicobacter pylori Strains of China Associated with Different Clinical Outcome. PLoS One. 7(6):e38528. [PudMed:22701658] experimental in_silico
(2) Rizzato C; Torres J; Plummer M; Munoz N; Franceschi S; Camorlinga-Ponce M; Fuentes-Panana EM; Canzian F; Kato I (2012). Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention. PLoS One. 7(1):e29605. [PudMed:22235308] experimental in_silico
(3) Tegtmeyer N; Backert S (2011). Role of Abl and Src family kinases in actin-cytoskeletal rearrangements induced by the Helicobacter pylori CagA protein. Eur J Cell Biol. 90(11):880-90. [PudMed:21247656]
(4) Fischer W; Windhager L; Rohrer S; Zeiller M; Karnholz A; Hoffmann R; Zimmer R; Haas R (2010). Strain-specific genes of Helicobacter pylori: genome evolution driven by a novel type IV secretion system and genomic island transfer. Nucleic Acids Res. 38(18):6089-101. [PudMed:20478826] experimental in_silico
(5) Fehri LF; Rechner C; Janssen S; Mak TN; Holland C; Bartfeld S; Bruggemann H; Meyer TF (2009). Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation. Epigenetics. 4(8):577-86. [PudMed:20081355] experimental
(6) Allison CC; Kufer TA; Kremmer E; Kaparakis M; Ferrero RL (2009). Helicobacter pylori induces MAPK phosphorylation and AP-1 activation via a NOD1-dependent mechanism. J Immunol. 183(12):8099-109. [PudMed:20007577] experimental
(7) Pinto-Santini DM; Salama NR (2009). Cag3 is a novel essential component of the Helicobacter pylori Cag type IV secretion system outer membrane subcomplex. J Bacteriol. 191(23):7343-52. [PudMed:19801411] experimental
(8) Cendron L; Couturier M; Angelini A; Barison N; Stein M; Zanotti G (2009). The Helicobacter pylori CagD (HP0545, Cag24) protein is essential for CagA translocation and maximal induction of interleukin-8 secretion. J Mol Biol. 386(1):204-17. [PudMed:19109970] experimental
(9) Couturier MR; Stein M (2008). Helicobacter pylori produces unique filaments upon host contact in vitro. Can J Microbiol. 54(7):537-48. [PudMed:18641700] experimental
(10) Hilleringmann M; Pansegrau W; Doyle M; Kaufman S; MacKichan ML; Gianfaldoni C; Ruggiero P; Covacci A (2006). Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag virulence. Microbiology. 152(Pt 10):2919-30. [PudMed:17005973] experimental
(11) Bourzac KM; Satkamp LA; Guillemin K (2006). The Helicobacter pylori cag pathogenicity island protein CagN is a bacterial membrane-associated protein that is processed at its C terminus. Infect Immun. 74(5):2537-43. [PudMed:16622188] experimental
(12) Couturier MR; Tasca E; Montecucco C; Stein M (2006). Interaction with CagF is required for translocation of CagA into the host via the Helicobacter pylori type IV secretion system. Infect Immun. 74(1):273-81. [PudMed:16368981] experimental
(13) Backert S; Kwok T; Konig W (2005). Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and TraG-like proteins. Microbiology. 151(Pt 11):3493-503. [PudMed:16272373] experimental
(14) Guillemin K; Salama NR; Tompkins LS; Falkow S (2002). Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc Natl Acad Sci U S A. 99(23):15136-41. [PudMed:12411577] experimental
(15) Ramarao N; Gray-Owen SD; Backert S; Meyer TF (2000). Helicobacter pylori inhibits phagocytosis by professional phagocytes involving type IV secretion components. Mol Microbiol. 37(6):1389-404. [PudMed:10998171] experimental
(16) Stein M; Rappuoli R; Covacci A (2000). Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A. 97(3):1263-8. [PudMed:10655519] experimental
experimental This literature contains experimental investigation
in_silico This literature contains bioinformatics investigation