SecReT4
T4SS ID4
StrainHelicobacter pylori 26695
Repliconchromosome [Browse all T4SS(s) in this replicon]
AccessionNC_000915
Location548134..579087
NameCag
Functioneffector translocation
ClassificationType IVA; Type P
experimental Experimental investigation has been performed on this T4SS.
structure Information of structure: structureCagY, CagD, Outer membrane core complex (OMCC), HP0525, CagT, HP0525 bound by sulfate, VirB11, CagA Inhibits PAR1/MARK Family Kinases, CagX, CagS, CagZ, VirB11-like protein in complex with ATPgammaS, CagL, N-terminal domain of CagA, Periplasmic ring complex (PRC), Cag T4SS, CagA, CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2

T4SS components
ComponentCagCCagDCagECagFCagGCagHCagICagLCagN
Number111111111
ComponentCagMCagTCagUCagVCagWCagXCagYCagZCagalpha
Number111111111
ComponentCagbetaCaggammaCagdelta
Number111

The information of T4SS components from NC_000915
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProductComponent
1HP0517 (era)544336..545244 [+], 90915645144GTP-binding protein Era 
2HP0518545241..546233 [+], 99315645145hypothetical protein 
3HP0519546322..547152 [-], 83115645146hypothetical protein 
4HP0520547328..547675 [+], 34815645147cag pathogenicity island protein (cag1) 
5HP0522548134..549579 [+], 144615645148cag pathogenicity island protein (cag3)  Cagdelta
6HP0523549589..550098 [+], 51015645149cag pathogenicity island protein (cag4)  Caggamma
7HP0524550217..552463 [-], 224715645150cag pathogenicity island protein (cag5)  Cagbeta
8HP0525552472..553464 [-], 99315645151virB11-like protein  Cagalpha
9HP0526553469..554068 [-], 60015645152cag pathogenicity island protein (cag6)  CagZ
10HP0527554206..559989 [-], 578415645153cag pathogenicity island protein (cag7)  CagYinteraction
11HP0528560004..561572 [-], 156915645154cag pathogenicity island protein (cag8)  CagX
12HP0529561625..563232 [-], 160815645155cag pathogenicity island protein (cag9)  CagW
13HP0530563237..563995 [-], 75915645156cag pathogenicity island protein (cag10)  CagV
14HP0531564381..565037 [+], 65715645157cag pathogenicity island protein (cag11)  CagU
15HP0532565073..565915 [+], 84315645158cag pathogenicity island protein (cag12)  CagT
16HP0534566126..566716 [-], 59115645160cag pathogenicity island protein (cag13) 
17HP0535567142..567522 [-], 38115645161cag pathogenicity island protein (cag14) 
18HP0536567955..568299 [-], 34515645162cag pathogenicity island protein (cag15) 
19HP0537568723..569853 [+], 113115645163cag pathogenicity island protein (cag16)  CagM
20HP0538569868..570788 [+], 92115645164cag pathogenicity island protein (cag17)  CagN
21HP0539570870..571583 [-], 71415645165cag pathogenicity island protein (cag18)  CagLinteraction
22HP0540571580..572725 [-], 114615645166cag pathogenicity island protein (cag19)  CagI
23HP0541572736..573848 [-], 111315645167cag pathogenicity island protein (cag20)  CagH
24HP0542573864..574292 [-], 42915645168cag pathogenicity island protein (cag21)  CagG
25HP0543574347..575153 [-], 80715645169cag pathogenicity island protein (cag22)  CagFaccesspry protein
26HP0544575155..578106 [-], 295215645170cag pathogenicity island protein (cag23)  CagE
27HP0545578115..578738 [-], 62415645171cag pathogenicity island protein (cag24)  CagD
28HP0546578740..579087 [-], 34815645172cag pathogenicity island protein (cag25)  CagC
29HP0547579921..583481 [+], 356115645173cag pathogenicity island protein (cag26)  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.

Download FASTA format files
Proteins        Genes
As a consequence of CagA action, epithelial cells will have some of their major functions disturbed, such as cell-cell adhesion, signalling, adherence and proliferation

Effectors
CagA; Peptidoglycan

The information of protein effectors
#Locus tag (Gene)Coordinates [+/-], size (bp)Protein GIProduct  *
1HP0547 579921..583481 [+], 356115645173cag pathogenicity island protein (cag26)experimental  CagAinteraction
experimental T4SE derived from experimental literature.
interaction This effector contains information of interaction.

Download FASTA format files
Proteins        Genes
The information on structure of this T4ss

#NameImageResourceDetailReference
1CagA4DVY PDB (4DVY)Crystal structure of the Helicobacter pylori CagA oncoprotein.(1) PubMed: 22817985
2CagA4DVZ PDB (4DVZ)Crystal structure of the Helicobacter pylori CagA oncoprotein.(2) PubMed: 22817985
3CagA Inhibits PAR1/MARK Family Kinases3IEC PDB (3IEC)Helicobacter pylori CagA Inhibits PAR1/MARK Family Kinases by Mimicking Host Substrates.(3) PubMed: 19966800
4CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-24IRV PDB (4IRV)Structure of the Helicobacter pylori CagA Oncogene Bound to the Human Tumor Suppressor Apoptosis-stimulating Protein of p53-2.(4) PubMed: 24474782
5CagD3CWX PDB (3CWX)Crystal structure of cagd from helicobacter pylori pathogenicity island.(5) PubMed: 19109970
6CagL3ZCJ PDB (3ZCJ)Crystal structure of Helicobacter pylori T4SS protein CagL in a tetragonal crystal form with a helical RGD-motif (6 Mol per ASU).(6) PubMed: 24076404
7CagL3ZCI PDB (3ZCI)Crystal structure of Helicobacter pylori T4SS protein CagL in a cubic crystal form with a distorted helical conformation of the RGD-motif.(7) PubMed: 24076404
8CagL4X5U PDB (4X5U)X-ray crystal structure of CagL at pH 4.2.(8) PubMed: 25837254
9CagS2G3V PDB (2G3V)Crystal structure of CagS (HP0534, Cag13) from Helicobacter pylori.(9) PubMed: 17623849
10CagT6OEE PDB (6OEE)Structure of CagT from a cryo-EM reconstruction of a T4SS.(10) PubMed: 31210639
11Cag T4SS7474 EMDB(7474)Subtomogram average of the cag type IV secretion system in Helicobacter pylori cells (aligning periplasmic parts).(11) PubMed: 29669273
12CagX5H3V PDB (5H3V)Crystal structure of a Type IV Secretion System Component CagX in Helicobacter pylori.(12) PubMed: 28291753
13CagX6OEG PDB (6OEG)Structure of CagX from a cryo-EM reconstruction of a T4SS(13) PubMed: 31210639
14CagY6ODI PDB (6ODI)Structure of CagY from a cryo-EM reconstruction of a T4SS.(14) PubMed: 31210639
15CagY6OEF PDB (6OEF)Structure of CagY from a cryo-EM reconstruction of a T4SS.(15) PubMed: 31210639
16CagZ1S2X PDB (1S2X)Crystal structure of Cag-Z from Helicobacter pylori.(16) PubMed: 15223328
17HP05251G6O PDB (1G6O)Crystal structure of the helicobacter pylori ATPase, HP0525, in complex with ADP.(17) PubMed: 11163218
18HP0525 bound by sulfate1OPX PDB (1OPX)Crystal structure of the traffic ATPase (HP0525) of the Helicobacter pylori type IV secretion system bound by sulfate.(18) PubMed: 12727865
19N-terminal domain of CagA4G0H PDB (4G0H)Crystal structure of the N-terminal domain of Helicobacter pylori CagA protein.(19) PubMed: 22908298
20Outer membrane core complex (OMCC)6OEH PDB (6OEH)PolyAla Model of OMCC I-Layer.(20) PubMed: 31210639
21Outer membrane core complex (OMCC)20023 EMDB(20023)Reconstruction of a T4SS OMCC.(21) PubMed: 31210639
22Outer membrane core complex (OMCC)20020 EMDB(20020)Reconstruction of a T4SS OMCC.(22) PubMed: 31210639
23Outer membrane core complex (OMCC)20022 EMDB(20022)Reconstruction of a T4SS OMCC.(23) PubMed: 31210639
24Periplasmic ring complex (PRC)6ODJ PDB (6ODJ)PolyAla Model of the PRC from the Type 4 Secretion System of H. pylori.(24) PubMed: 31210639
25Periplasmic ring complex (PRC)20021 EMDB(20021)PolyAla Model of the PRC from the Type 4 Secretion System of H. pylori.(25) PubMed: 31210639
26VirB111NLZ
PDB (1NLZ )Crystal structure of unliganded traffic ATPase of the type IV secretion system of helicobacter pylori. (26) PubMed: 12727865
27VirB11-like protein in complex with ATPgammaS1NLY PDB (1NLY)Crystal structure of the traffic ATPase of the Helicobacter pylori type IV secretion system in complex with ATPgammaS.(27) PubMed: 25825348
(1) Hayashi T et al. (2012). Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe. 12(1):20-33. [PudMed:22817985] experimental
(2) Hayashi T et al. (2012). Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe. 12(1):20-33. [PudMed:22817985] experimental
(3) Nesić D et al. (2010). Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol. 17(1):130-2. [PudMed:19966800] 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) 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
(6) Barden S et al. (2013). A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL. Structure. 21(11):1931-41. [PudMed:24076404] experimental
(7) Barden S et al. (2013). A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL. Structure. 21(11):1931-41. [PudMed:24076404] experimental
(8) Bonsor DA et al. (2015). Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix. J Biol Chem. 290(20):12929-40. [PudMed:25837254] experimental
(9) Cendron L et al. (2007). The crystal structure of CagS from the Helicobacter pylori pathogenicity island. Proteins. 69(2):440-3. [PudMed:17623849] experimental
(10) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(11) Chang YW et al. (2018). In Vivo Structures of the Helicobacter pylori cag Type IV Secretion System. Cell Rep. 23(3):673-681. [PudMed:29669273] experimental
(12) Zhang J et al. (2017). Crystal structure of the type IV secretion system component CagX from Helicobacter pylori. Acta Crystallogr F Struct Biol Commun. 73(Pt 3):167-173. [PudMed:28291753] experimental
(13) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(14) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(15) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(16) Cendron L; Seydel A; Angelini A; Battistutta R; Zanotti G (2004). Crystal structure of CagZ, a protein from the Helicobacter pylori pathogenicity island that encodes for a type IV secretion system. J Mol Biol. 340(4):881-9. [PudMed:15223328] experimental
(17) Yeo HJ; Savvides SN; Herr AB; Lanka E; Waksman G (2000). Crystal structure of the hexameric traffic ATPase of the Helicobacter pylori type IV secretion system. Mol Cell. 6(6):1461-72. [PudMed:11163218] experimental
(18) Savvides SN; Yeo HJ; Beck MR; Blaesing F; Lurz R; Lanka E; Buhrdorf R; Fischer W; Haas R; Waksman G (2003). VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22(9):1969-80. [PudMed:12727865] experimental
(19) 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
(20) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(21) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(22) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(23) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(24) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(25) Chung JM et al. (2019). Structure of the Helicobacter pylori Cag type IV secretion system. Elife. 8. pii: e47644. [PudMed:31210639] experimental
(26) Savvides SN; Yeo HJ; Beck MR; Blaesing F; Lurz R; Lanka E; Buhrdorf R; Fischer W; Haas R; Waksman G (2003). VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22(9):1969-80. [PudMed:12727865] experimental
(27) Ilangovan A et al. (2015). Structural biology of the Gram-negative bacterial conjugation systems. Trends Microbiol. 23(5):301-10. [PudMed:25825348]
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) (15645169)CT20aa and an intact N terminusCagAThe CagA-binding protein CagF is a secretion chaperone-like protein that interacts with a region that is adjacent to the C-terminal secretion signal of CagA.(1) PubMed: 17768234
Tips:
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/SubstrateFunctionReference
1CagA (15645173)SHP-2CagA is translocated from the bacteria into gastric epithelial cells. It physically interacts with SHP-2 to modify cellular functions and perturb mammalian signal transduction machineries. This may induce abnormal proliferation and movement of gastric epithelial cells and promote the acquisition of a cellular transformed phenotype.(1) PubMed: 11743164insolico
2CagA (15645173)growth factor receptor bound 2 (Grb2)CagA can interact with Grb2, which result in activing the MEK/ERK pathway and leads to cell scattering and proliferation.(2) PubMed: 12419219experimental
3CagA (15645173)PAR1/MARK kinasePAR1 is a key target of H. pylori CagA in the disorganization of gastric epithelial architecture underlying mucosal damage, inflammation and carcinogenesis. H. pylori CagA specifically interacts with PAR1/MARK kinase, which inhibits PAR1 kinase activity and prevents atypical protein kinase C (aPKC)-mediated PAR1 phosphorylation.(3) PubMed: 17507984insolico
4CagA (15645173)Apoptosis-stimulating of p53 protein 2 (ASPP2)ASPP2 is a tumor suppressor that activates the p53-mediated apoptotic response upon cellular stress. Direct interaction between CagA and ASPP2 changes the function of ASPP2 and leads to the decreased survival of H. pylori infected cells.(4) PubMed: 24474782experimental
5CagA (15645173)protein kinase C-related kinase 2 (PRK2)PRK2 has been involved in establishment of cell polarity and cytoskeletal rearrangements. CagA inhibits kinase activity of PRK2 to further manipulate cancer-related signalling pathways.(5) PubMed: 26041307experimental
6CagA (15645173)Glycogen synthase kinase 3 (GSK-3)CagA binds GSK-3 to reduce its activity by cause it to shift to an insoluble fraction. Then cagA induce a Snail-mediated epithelial mesenchymal transition via the depletion of GSK-3.(6) PubMed: 25055241insolico
7CagA (15645173)c-MetCagA interacts with the c-Met receptor to modulates cellular functions via deregulating c-Met receptor signaling and is involved in invasive growth of tumor cells.(7) PubMed: 12719469insolico
8CagA (15645173)E-cadherinCagA interacts with E-cadherin to impair the complex formation between E-cadherin and beta-catenin and promotes intestinal transdifferentiation in gastric epithelial cells.(8) PubMed: 17237808insolico
9CagA (15645173)host membrane phosphatidylserineCagA interacts whith phosphatidylserine to be tethered to the inner leaflet of the plasma membrane. Then it binds the PAR1/MARK to induce polarity and junctional defects.(9) PubMed: 20478541experimental
10CagA (15645173)c-Abl tyrosine kinaseCagA directly targets to c-Abl and localizes in in focal adhesion complexes and membrane ruffles.(10) PubMed: 17160020experimental
11CagA (15645173)αPixCagA was delivered into AGS cells and interacted with αPix to activates PAK1, ERK and NF-kappaB. Then it induces IL-8 expression in infected gastric epithelial cells.(11) PubMed: 19672789insolico
12CagA (15645173)scaffolding protein ZO-1CagA associates with epithelial tight-junction ZO-1 and the transmembrane protein junctional adhesion molecule to alter the function and composition of the apical-junctional complex.(12) PubMed: 12775840insolico
13CagA (15645173)integrin α5β1 receptorCagA binds interface with α5β1 integrin.It is an essential step for the translocation process of CagA into the host cell.(13) PubMed: 22908298experimental
14CagA (15645173)TNF receptor-associated factor 1 and 4-1BB (TRAF1 and 4-1BB)CagA promotes the proliferation and inhibits the apoptosis of GES-1 cells via upregulated TRAF1/4-1BB.(14) PubMed: 28627614insolico
15CagA (15645173)Adapter molecule crkCagA binding Crk adaptor proteins is important for Helicobacter pylori-induced loss of gastric epithelial cell adhesion.(15) PubMed: 16275761experimental
16CagA (15645173)SHP-1SHP1 interacts with CagA to potentiate the phosphatase activity of SHP1 so that it dampens the oncogenic action of CagA. (16) PubMed: 27572445insolico
17CagA (15645173)Transforming growth factor-beta-activated kinase 1 (TAK1)CagA interacts with TAK1 and enhances its activity to activate NF-kappaB through the ubiquitination of TAK1.(17) PubMed: 19820695insolico
18CagA (15645173)Myeloid cell leukemia sequence-1 (MCL1)CagA Increases MCL1 via SRE/SRF and CagA/MCL1 interplay in modulating rapid turnover of pit epithelial cells via MEK/ERK/SRE activation.(18) PubMed: 18005743experimental
19CagL (15645165)integrin α5β1 receptorCagL protein is a specialized adhesin that is targeted to the pilus surface. It binds to and activates integrin α5β1 receptor on gastric epithelial cells. This interaction triggers CagA delivery into target cells.(19) PubMed: 17943123insolico
20CagL (15645165)integrin αvβ5CagL/integrin β5 signalling complex is important for H pylori induced gastrin expression.(20) PubMed: 22287591insolico
21CagL (15645165)integrin αvβ3Host cell docking of T4SS.(21) PubMed: 21915696insolico
22CagL (15645165)integrin αvβ6αvβ6 is a specific, high affinity receptor for CagL.(22) PubMed: 31197920insolico
23CagY (15645153)integrin α5β1 receptorCagY binding to α5β1 integrin acts like a molecular rheostat that modulates the host immune response to promote persistent infection.(23) PubMed: 29764950insolico
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) 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
(21) 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
(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
(23) Skoog EC et al. (2018). CagY-Dependent Regulation of Type IV Secretion in Helicobacter pylori Is Associated with Alterations in Integrin Binding. MBio. 9(3). pii: e00717-18. [PudMed:29764950] experimental
(1) Chandran Darbari V et al. (2015). Structural Biology of Bacterial Type IV Secretion Systems. Annu Rev Biochem. 84:603-29. [PudMed:26034891]
(2) 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
(3) Jimenez-Soto LF; Rohrer S; Jain U; Ertl C; Sewald X; Haas R (2012). Effects of cholesterol on Helicobacter pylori growth and virulence properties in vitro. Helicobacter. 17(2):133-9. [PudMed:22404444] experimental
(4) 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
(5) Aviles-Jimenez F; Reyes-Leon A; Nieto-Patlan E; Hansen LM; Burgueno J; Ramos IP; Camorlinga-Ponce M; Bermudez H; Blancas JM; Cabrera L; Ribas-Aparicio RM; Solnick JV; Torres-Lopez J (2012). In vivo expression of Helicobacter pylori virulence genes in patients with gastritis, ulcer, and gastric cancer. Infect Immun. 80(2):594-601. [PudMed:22124657] experimental
(6) Lai CH; Wang HJ; Chang YC; Hsieh WC; Lin HJ; Tang CH; Sheu JJ; Lin CJ; Yang MS; Tseng SF; Wang WC (2011). Helicobacter pylori CagA-mediated IL-8 induction in gastric epithelial cells is cholesterol-dependent and requires the C-terminal tyrosine phosphorylation-containing domain. FEMS Microbiol Lett. 323(2):155-63. [PudMed:22092715] experimental
(7) Wang HJ; Cheng WC; Cheng HH; Lai CH; Wang WC (2012). Helicobacter pylori cholesteryl glucosides interfere with host membrane phase and affect type IV secretion system function during infection in AGS cells. Mol Microbiol. 83(1):67-84. [PudMed:22053852] experimental
(8) Backert S; Clyne M; Tegtmeyer N (2011). Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun Signal. 9:28. [PudMed:22044679]
(9) Mori N; Ishikawa C; Senba M (2011). Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection. World J Gastroenterol. 17(32):3691-9. [PudMed:21990950] experimental
(10) Shaffer CL; Gaddy JA; Loh JT; Johnson EM; Hill S; Hennig EE; McClain MS; McDonald WH; Cover TL (2011). Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface. PLoS Pathog. 7(9):e1002237. [PudMed:21909278] experimental
(11) Backert S; Clyne M (2011). Pathogenesis of Helicobacter pylori infection. Helicobacter. 16 Suppl 1:19-25. [PudMed:21896081]
(12) Terradot L; Waksman G (2011). Architecture of the Helicobacter pylori Cag-type IV secretion system. FEBS J. 278(8):1213-22. [PudMed:21352491]
(13) 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]
(14) Jurik A; Hausser E; Kutter S; Pattis I; Prassl S; Weiss E; Fischer W (2010). The coupling protein Cagbeta and its interaction partner CagZ are required for type IV secretion of the Helicobacter pylori CagA protein. Infect Immun. 78(12):5244-51. [PudMed:20876293] experimental
(15) Hutton ML; Kaparakis-Liaskos M; Turner L; Cardona A; Kwok T; Ferrero RL (2010). Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells. Infect Immun. 78(11):4523-31. [PudMed:20713621] experimental
(16) Tegtmeyer N; Hartig R; Delahay RM; Rohde M; Brandt S; Conradi J; Takahashi S; Smolka AJ; Sewald N; Backert S (2010). A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. J Biol Chem. 285(30):23515-26. [PudMed:20507990] experimental
(17) 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
(18) 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
(19) Brandt S; Kenny B; Rohde M; Martinez-Quiles N; Backert S (2009). Dual infection system identifies a crucial role for PKA-mediated serine phosphorylation of the EPEC-Tir-injected effector protein in regulating Rac1 function. Cell Microbiol. 11(8):1254-71. [PudMed:19438518] experimental
(20) Svensson H; Hansson M; Kilhamn J; Backert S; Quiding-Jarbrink M (2009). Selective upregulation of endothelial E-selectin in response to Helicobacter pylori-induced gastritis. Infect Immun. 77(7):3109-16. [PudMed:19414551] experimental
(21) Tegtmeyer N; Zabler D; Schmidt D; Hartig R; Brandt S; Backert S (2009). Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA. Cell Microbiol. 11(3):488-505. [PudMed:19046339] experimental
(22) Hatakeyama M (2008). Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. Oncogene. 27(55):7047-54. [PudMed:19029944]
(23) Kutter S; Buhrdorf R; Haas J; Schneider-Brachert W; Haas R; Fischer W (2008). Protein subassemblies of the Helicobacter pylori Cag type IV secretion system revealed by localization and interaction studies. J Bacteriol. 190(6):2161-71. [PudMed:18178731] experimental
(24) Minohara Y; Boyd DK; Hawkins HK; Ernst PB; Patel J; Crowe SE (2007). The effect of the cag pathogenicity island on binding of Helicobacter pylori to gastric epithelial cells and the subsequent induction of apoptosis. Helicobacter. 12(6):583-90. [PudMed:18001397] experimental
(25) 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
(26) 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
(27) Oyarzabal OA; Rad R; Backert S (2007). Conjugative transfer of chromosomally encoded antibiotic resistance from Helicobacter pylori to Campylobacter jejuni. J Clin Microbiol. 45(2):402-8. [PudMed:17135441] experimental
(28) Oliveira MJ; Costa AC; Costa AM; Henriques L; Suriano G; Atherton JC; Machado JC; Carneiro F; Seruca R; Mareel M; Leroy A; Figueiredo C (2006). Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type IV secretion system-dependent manner. J Biol Chem. 281(46):34888-96. [PudMed:16990273] experimental
(29) Andrzejewska J; Lee SK; Olbermann P; Lotzing N; Katzowitsch E; Linz B; Achtman M; Kado CI; Suerbaum S; Josenhans C (2006). Characterization of the pilin ortholog of the Helicobacter pylori type IV cag pathogenicity apparatus, a surface-associated protein expressed during infection. J Bacteriol. 188(16):5865-77. [PudMed:16885455] experimental
(30) Busler VJ; Torres VJ; McClain MS; Tirado O; Friedman DB; Cover TL (2006). Protein-protein interactions among Helicobacter pylori cag proteins. J Bacteriol. 188(13):4787-800. [PudMed:16788188] experimental
(31) Hohlfeld S; Pattis I; Puls J; Plano GV; Haas R; Fischer W (2006). A C-terminal translocation signal is necessary, but not sufficient for type IV secretion of the Helicobacter pylori CagA protein. Mol Microbiol. 59(5):1624-37. [PudMed:16469000] experimental
(32) Krueger S; Hundertmark T; Kalinski T; Peitz U; Wex T; Malfertheiner P; Naumann M; Roessner A (2006). Helicobacter pylori encoding the pathogenicity island activates matrix metalloproteinase 1 in gastric epithelial cells via JNK and ERK. J Biol Chem. 281(5):2868-75. [PudMed:16321971] experimental
(33) 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
(34) Zahrl D; Wagner M; Bischof K; Bayer M; Zavecz B; Beranek A; Ruckenstuhl C; Zarfel GE; Koraimann G (2005). Peptidoglycan degradation by specialized lytic transglycosylases associated with type III and type IV secretion systems. Microbiology. 151(Pt 11):3455-67. [PudMed:16272370] experimental
(35) Backert S; Gressmann H; Kwok T; Zimny-Arndt U; Konig W; Jungblut PR; Meyer TF (2005). Gene expression and protein profiling of AGS gastric epithelial cells upon infection with Helicobacter pylori. Proteomics. 5(15):3902-18. [PudMed:16145711] experimental
(36) Bauer B; Moese S; Bartfeld S; Meyer TF; Selbach M (2005). Analysis of cell type-specific responses mediated by the type IV secretion system of Helicobacter pylori. Infect Immun. 73(8):4643-52. [PudMed:16040977] experimental
(37) Viala J; Chaput C; Boneca IG; Cardona A; Girardin SE; Moran AP; Athman R; Memet S; Huerre MR; Coyle AJ; DiStefano PS; Sansonetti PJ; Labigne A; Bertin J; Philpott DJ; Ferrero RL (2004). Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol. 5(11):1166-74. [PudMed:15489856] experimental
(38) Selbach M; Moese S; Backert S; Jungblut PR; Meyer TF (2004). The Helicobacter pylori CagA protein induces tyrosine dephosphorylation of ezrin. Proteomics. 4(10):2961-8. [PudMed:15378755] experimental
(39) Al-Ghoul L; Wessler S; Hundertmark T; Kruger S; Fischer W; Wunder C; Haas R; Roessner A; Naumann M (2004). Analysis of the type IV secretion system-dependent cell motility of Helicobacter pylori-infected epithelial cells. Biochem Biophys Res Commun. 322(3):860-6. [PudMed:15336542] experimental
(40) Aras RA; Fischer W; Perez-Perez GI; Crosatti M; Ando T; Haas R; Blaser MJ (2003). Plasticity of repetitive DNA sequences within a bacterial (Type IV) secretion system component. J Exp Med. 198(9):1349-60. [PudMed:14581606] experimental
(41) Buhrdorf R; Forster C; Haas R; Fischer W (2003). Topological analysis of a putative virB8 homologue essential for the cag type IV secretion system in Helicobacter pylori. Int J Med Microbiol. 293(2-3):213-7. [PudMed:12868658] experimental
(42) Rohde M; Puls J; Buhrdorf R; Fischer W; Haas R (2003). A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system. Mol Microbiol. 49(1):219-34. [PudMed:12823823] experimental
(43) Tanaka J; Suzuki T; Mimuro H; Sasakawa C (2003). Structural definition on the surface of Helicobacter pylori type IV secretion apparatus. Cell Microbiol. 5(6):395-404. [PudMed:12780777] experimental
(44) Savvides SN; Yeo HJ; Beck MR; Blaesing F; Lurz R; Lanka E; Buhrdorf R; Fischer W; Haas R; Waksman G (2003). VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22(9):1969-80. [PudMed:12727865] experimental
(45) Backert S; Churin Y; Meyer TF (2002). Helicobacter pylori type IV secretion, host cell signalling and vaccine development. Keio J Med. 51 Suppl 2:6-14. [PudMed:12528929] experimental
(46) Schroder G; Krause S; Zechner EL; Traxler B; Yeo HJ; Lurz R; Waksman G; Lanka E (2002). TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV secretion system: inner membrane gate for exported substrates. J Bacteriol. 184(10):2767-79. [PudMed:11976307] experimental
(47) Fischer W; Puls J; Buhrdorf R; Gebert B; Odenbreit S; Haas R (2001). Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol. 42(5):1337-48. [PudMed:11886563] experimental
(48) Selbach M; Moese S; Meyer TF; Backert S (2002). Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms. Infect Immun. 70(2):665-71. [PudMed:11796597] experimental
(49) Churin Y; Kardalinou E; Meyer TF; Naumann M (2001). Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 in Helicobacter pylori infection. Mol Microbiol. 40(4):815-23. [PudMed:11401689] experimental
(50) Backert S; Ziska E; Brinkmann V; Zimny-Arndt U; Fauconnier A; Jungblut PR; Naumann M; Meyer TF (2000). Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol. 2(2):155-64. [PudMed:11207572] experimental
(51) 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
 
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in_silico This literature contains bioinformatics investigation