| # | Name(Protein GI) | Host site/Substrate | Source | Function | Reference | |
| 1 | CagA (15611562) | SHP-2 | human | CagA 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: 11743164 |  |
| 2 | CagA (15611562) | growth factor receptor bound 2 (Grb2) | unknown | CagA targets to Grb2 and this process leads to activing the MEK/ERK pathway and results in cell scattering and proliferation. | (2) PubMed: 12419219 | |
| 3 | CagA (15611562) | PAR1/MARK kinase | human | CagA 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: 17507984 | |
| 4 | CagA (15611562) | Apoptosis-stimulating of p53 protein 2 (ASPP2) | human | ASPP2 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: 24474782 | |
| 5 | CagA (15611562) | protein kinase C-related kinase 2 (PRK2) | human | CagA 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: 26041307 | |
| 6 | CagA (15611562) | Glycogen synthase kinase 3 (GSK-3) | human | CagA 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: 25055241 | |
| 7 | CagA (15611562) | c-Met | human | CagA 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: 12719469 | |
| 8 | CagA (15611562) | E-cadherin | human | CagA 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: 17237808 | |
| 9 | CagA (15611562) | host membrane phosphatidylserine | unknown | CagA 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: 20478541 |  |
| 10 | CagA (15611562) | c-Abl tyrosine kinase | human | CagA targets to c-Abl directly and localizes in focal adhesion complexes and membrane ruffles. | (10) PubMed: 17160020 | |
| 11 | CagA (15611562) | αPix | human | CagA 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: 19672789 | |
| 12 | CagA (15611562) | scaffolding protein ZO-1 | human, canine | CagA 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: 12775840 | |
| 13 | CagA (15611562) | integrin α5β1 receptor | human | CagA binds interface with α5β1 integrin.It is an essential step for the translocation process of CagA into the host cell. | (13) PubMed: 22908298 | |
| 14 | CagA (15611562) | TNF receptor-associated factor 1 and 4-1BB (TRAF1 and 4-1BB) | human | CagA facilitates the proliferation and represses the apoptosis of GES-1 cells by upregulated TRAF1/4-1BB. | (14) PubMed: 28627614 | |
| 15 | CagA (15611562) | Adapter molecule crk | human | The 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: 16275761 | |
| 16 | CagA (15611562) | SHP-1 | human | CagA interacts with SHP1 to enhance the phosphatase activity of SHP1 so that it dampens the oncogenic action of CagA. | (16) PubMed: 27572445 | |
| 17 | CagA (15611562) | Transforming growth factor-beta-activated kinase 1 (TAK1) | human | CagA interacts with TAK1 and improves its activity to activate NF-kappaB through the ubiquitination of TAK1. | (17) PubMed: 19820695 | |
| 18 | CagA (15611562) | Myeloid cell leukemia sequence-1 (MCL1) | mongolian gerbil | CagA 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: 18005743 | |
| 19 | CagL (15611554) | integrin α5β1 receptor | human | CagL, 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: 17943123 | |
| 20 | CagL (15611554) | integrin αvβ3 | human | Host cell docking of T4SS. | (20) PubMed: 21915696 | |
| 21 | CagL (15611554) | integrin αvβ5 | human | CagL/integrin β5 signalling complex is important for gastrin expression induced by H. pylori. | (21) PubMed: 22287591 | |
| 22 | CagL (15611554) | integrin αvβ6 | human | αvβ6 is a specific, high affinity receptor for CagL. | (22) PubMed: 31197920 | |
This T4SE is mentioned in the literature.
This T4SE is highly identical with the protein mentioned in the literature.
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(12) Amieva MR et al. (2003). Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 300(5624):1430-4. [PudMed:12775840]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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(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]
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T4SS ID
Genes in the 5-Kb flanking regions if available, or non-essential genes in the T4SS gene cluster if any.