Entry Name Yersinia infection - Neomonachus schauinslandi (Hawaiian monk seal)
Description 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.
Class Human Diseases; Infectious disease: bacterialBRITE hierarchy
Pathway map Ortholog table Organism Neomonachus schauinslandi (Hawaiian monk seal) [GN:
nsu ]
Gene 110591950 BCAR1; breast cancer anti-estrogen resistance protein 1 [KO:K05726 ]
110589050 ELMO1; engulfment and cell motility protein 1 isoform X2 [KO:K12366 ]
110579610 ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985 ]
110572663 LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1-like [KO:K04392 ]
110571993 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
110588896 WASL; LOW QUALITY PROTEIN: neural Wiskott-Aldrich syndrome protein [KO:K23612 ]
110571984 ARPC1A; actin-related protein 2/3 complex subunit 1A isoform X2 [KO:K05757 ]
110571914 LOW QUALITY PROTEIN: actin-related protein 2/3 complex subunit 2-like [KO:K05758 ]
110588290 ARPC3; actin-related protein 2/3 complex subunit 3 isoform X2 [KO:K05756 ]
110581890 ARPC5L; actin-related protein 2/3 complex subunit 5-like protein isoform X2 [KO:K05754 ]
110573958 ARPC5; actin-related protein 2/3 complex subunit 5 isoform X1 [KO:K05754 ]
110572564 BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627 ]
110575196 WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748 ]
110585793 ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X1 [KO:K13710 ]
110575167 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
110579709 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
110586254 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
110582277 ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330 ]
110580236 NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800 ]
110587476 NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805 ]
110589905 apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799 ]
110569660 MYD88; myeloid differentiation primary response protein MyD88 isoform X2 [KO:K04729 ]
110577941 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
110583336 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
110572155 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
110593848 TICAM1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842 ]
110575119 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110582352 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
110570825 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
110574558 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
110575009 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
110591287 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110587368 CD8A; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD8 alpha chain [KO:K06458 ]
110589908 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
110579324 PLCG1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116 ] [EC:3.1.4.11 ]
110576910 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
110576691 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
110594240 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Pha K, Navarro L
Title Yersinia type III effectors perturb host innate immune responses.
Journal Reference Authors Pinaud L, Sansonetti PJ, Phalipon A
Title Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
Journal Reference Authors Huveneers S, Danen EH
Title Adhesion signaling - crosstalk between integrins, Src and Rho.
Journal Reference Authors Angot A, Vergunst A, Genin S, Peeters N
Title Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
Journal Reference Authors Bliska JB
Title Yop effectors of Yersinia spp. and actin rearrangements.
Journal Reference Authors Gustavsson A, Yuan M, Fallman M
Title Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.
Journal Reference Authors Bruce-Staskal PJ, Weidow CL, Gibson JJ, Bouton AH
Title Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake.
Journal J Cell Sci 115:2689-700 (2002)
Reference Authors McGee K, Zettl M, Way M, Fallman M
Title A role for N-WASP in invasin-promoted internalisation.
Journal Reference Authors Pizarro-Cerda J, Cossart P
Title Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
Journal Reference Authors Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, Chae JJ, Bliska JB
Title The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
Journal Reference Authors Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R
Title Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta.
Journal Reference Authors Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE
Title Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
Journal Reference Authors Zhou H, Monack DM, Kayagaki N, Wertz I, Yin J, Wolf B, Dixit VM
Title Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B activation.
Journal Reference Authors Haase R, Richter K, Pfaffinger G, Courtois G, Ruckdeschel K
Title Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cells.
Journal Reference Authors Thiefes A, Wolf A, Doerrie A, Grassl GA, Matsumoto K, Autenrieth I, Bohn E, Sakurai H, Niedenthal R, Resch K, Kracht M
Title The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
Journal Reference Authors Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC
Title A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4.
Journal Reference Authors Rolan HG, Durand EA, Mecsas J
Title Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.
Journal Reference Authors Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, Mustelin T
Title Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
Journal Related nsu04620 Toll-like receptor signaling pathway
nsu04621 NOD-like receptor signaling pathway
nsu04660 T cell receptor signaling pathway
nsu04666 Fc gamma R-mediated phagocytosis
nsu04810 Regulation of actin cytoskeleton
KO pathway LinkDB All DBs
