Yersinia infection - Homo sapiens (human)
Pathogenic Yersinia injects virulent Yersinia outer proteins (Yops) into the host cell through a type three secretion system (T3SS) to express its pathogenicity. Through inactivation of small GTPases by YopT protease, YopE GTPase-activating protein, and YpkA/YopO sequestration of GDP-bound small GTPases, Yersinia prevents its uptake by phagocytic cells and disrupts the actin cytoskeleton. YopH phosphatase shuts down phagocytosis by dephosphorylating key host proteins as well as suppresses T cell activation. Yersinia induces macrophage pyroptosis via YopB/YopD activation of canonical and noncanonical inflammasomes and YopT/YopE-mediated activation of pyrin. These effects are counteracted by YopK and YopM. YopP/J is a member of an ubiquitin-like protein cysteine protease family and simultaneously targets signaling components of the MAPK and NF-kappaB signaling pathways following activation of Toll-like receptor4 to inhibit production of proinflammatory cytokines.
Human Diseases; Infectious disease: bacterial
Pathway map Ortholog table
Calcium signaling (viruses and bacteria)
Cytoskeletal regulation (viruses and bacteria)
N00859 Yersinia YopP/J to TLR2/4-NFKB signaling pathway
N00862 Yersinia YopP/J to TLR2/4-MAPK signaling pathway
N00863 Yersinia YopM to NLRP3 Inflammasome signaling pathway
N00864 Yersinia YopK to NLRP3 Inflammasome signaling pathway
N00865 Yersinia YopK to NLRC4 Inflammasome signaling pathway
N00866 Yersinia YopM to Pyrin Inflammasome signaling pathway
N01098 Yersinia YopT to ITGA/B-RhoGEF-RhoA signaling pathway
N01099 Yersinia YopE to RhoA signaling pathway
N01100 Yersinia YopE to ITGA/B-RHOG-RAC signaling pathway
N01101 Yersinia YopT to ITGA/B-RHOG-RAC signaling pathway
N01102 Yersinia YopE to ITGA/B-RHOG-RAC signaling pathway
N01103 Yersinia YpkA to IGG-FCGR-RAC signaling pathway
N01105 Yersinia YpkA to LPA-GNAQ-RhoA signaling pathway
N01107 Yersinia YopH to TCR-NFAT signaling pathway
N01108 Yersinia YopH to TCR-NFAT signaling pathway
N01109 Yersinia YopH to ITGA/B-FAK-RAC signaling pathway
N01110 Yersinia YopH to ITGA/B-FAK-RAC signaling pathway
N01111 Yersinia YopH to ITGA/B-FAK-RAC signaling pathway
Homo sapiens (human) [GN:
391 RHOG; ras homolog family member G [KO: K07863]
1398 CRK; CRK proto-oncogene, adaptor protein [KO: K04438]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO: K04438]
9564 BCAR1; BCAR1 scaffold protein, Cas family member [KO: K05726]
9844 ELMO1; engulfment and cell motility 1 [KO: K12366]
63916 ELMO2; engulfment and cell motility 2 [KO: K18985]
1793 DOCK1; dedicator of cytokinesis 1 [KO: K13708]
23396 PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO: K00889] [EC: 220.127.116.11]
8394 PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO: K00889] [EC: 18.104.22.168]
8395 PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO: K00889] [EC: 22.214.171.124]
382 ARF6; ADP ribosylation factor 6 [KO: K07941]
8976 WASL; WASP like actin nucleation promoting factor [KO: K23612]
10095 ARPC1B; actin related protein 2/3 complex subunit 1B [KO: K05757]
10552 ARPC1A; actin related protein 2/3 complex subunit 1A [KO: K05757]
10109 ARPC2; actin related protein 2/3 complex subunit 2 [KO: K05758]
10094 ARPC3; actin related protein 2/3 complex subunit 3 [KO: K05756]
10093 ARPC4; actin related protein 2/3 complex subunit 4 [KO: K05755]
10092 ARPC5; actin related protein 2/3 complex subunit 5 [KO: K05754]
81873 ARPC5L; actin related protein 2/3 complex subunit 5 like [KO: K05754]
147179 WIPF2; WAS/WASL interacting protein family member 2 [KO: K19475]
7456 WIPF1; WAS/WASL interacting protein family member 1 [KO: K19475]
644150 WIPF3; WAS/WASL interacting protein family member 3 [KO: K19475]
10458 BAIAP2; BAR/IMD domain containing adaptor protein 2 [KO: K05627]
8874 ARHGEF7; Rho guanine nucleotide exchange factor 7 [KO: K13710]
998 CDC42; cell division cycle 42 [KO: K04393]
7454 WAS; WASP actin nucleation promoting factor [KO: K05747]
23365 ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO: K07532]
9138 ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO: K12330]
64283 ARHGEF28; Rho guanine nucleotide exchange factor 28 [KO: K21072]
387 RHOA; ras homolog family member A [KO: K04513]
6093 ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO: K04514] [EC: 126.96.36.199]
9475 ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO: K17388] [EC: 188.8.131.52]
8935 SKAP2; src kinase associated phosphoprotein 2 [KO: K23471]
114548 NLRP3; NLR family pyrin domain containing 3 [KO: K12800]
58484 NLRC4; NLR family CARD domain containing 4 [KO: K12805]
4210 MEFV; MEFV innate immunity regulator, pyrin [KO: K12803]
29108 PYCARD; PYD and CARD domain containing [KO: K12799]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO: K04729]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO: K04403]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO: K04404]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO: K07210]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO: K04467] [EC: 184.108.40.206]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO: K02580]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO: K04735]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO: K04379]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO: K04448]
148022 TICAM1; TIR domain containing adaptor molecule 1 [KO: K05842]
3661 IRF3; interferon regulatory factor 3 [KO: K05411]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO: K10030]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO: K00922] [EC: 220.127.116.11]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 18.104.22.168]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 22.214.171.124]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO: K02649]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO: K02649]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO: K02649]
6347 CCL2; C-C motif chemokine ligand 2 [KO: K14624]
7535 ZAP70; zeta chain of T cell receptor associated protein kinase 70 [KO: K07360] [EC: 126.96.36.199]
27040 LAT; linker for activation of T cells [KO: K07362]
3937 LCP2; lymphocyte cytosolic protein 2 [KO: K07361]
10451 VAV3; vav guanine nucleotide exchange factor 3 [KO: K05730]
7409 VAV1; vav guanine nucleotide exchange factor 1 [KO: K05730]
7410 VAV2; vav guanine nucleotide exchange factor 2 [KO: K05730]
4772 NFATC1; nuclear factor of activated T cells 1 [KO: K04446]
4773 NFATC2; nuclear factor of activated T cells 2 [KO: K17332]
4775 NFATC3; nuclear factor of activated T cells 3 [KO: K17333]
C01245 D-myo-Inositol 1,4,5-trisphosphate
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Pha K, Navarro L
Yersinia type III effectors perturb host innate immune responses.
Pinaud L, Sansonetti PJ, Phalipon A
Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
Huveneers S, Danen EH
Adhesion signaling - crosstalk between integrins, Src and Rho.
Angot A, Vergunst A, Genin S, Peeters N
Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
Yop effectors of Yersinia spp. and actin rearrangements.
Gustavsson A, Yuan M, Fallman M
Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.
Bruce-Staskal PJ, Weidow CL, Gibson JJ, Bouton AH
Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake.
J Cell Sci 115:2689-700 (2002)
McGee K, Zettl M, Way M, Fallman M
A role for N-WASP in invasin-promoted internalisation.
Pizarro-Cerda J, Cossart P
Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, Chae JJ, Bliska JB
The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R
Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta.
Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE
Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
Zhou H, Monack DM, Kayagaki N, Wertz I, Yin J, Wolf B, Dixit VM
Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B activation.
Haase R, Richter K, Pfaffinger G, Courtois G, Ruckdeschel K
Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cells.
Thiefes A, Wolf A, Doerrie A, Grassl GA, Matsumoto K, Autenrieth I, Bohn E, Sakurai H, Niedenthal R, Resch K, Kracht M
The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC
A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4.
Rolan HG, Durand EA, Mecsas J
Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.
Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, Mustelin T
Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis
hsa04810 Regulation of actin cytoskeleton
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