KEGG   PATHWAY: btax04613
Entry
btax04613                   Pathway                                
Name
Neutrophil extracellular trap formation - Budorcas taxicolor (takin)
Description
Neutrophils play a central role in innate immune defense. One of the mechanisms of neutrophil action is the formation of neutrophil extracellular traps (NETs), the extracellular structures composed of chromatin coated with histones, proteases and granular and cytosolic proteins that help catch and kill microorganisms. NETs are formed by a process known as "NETosis" that can be triggered by microorganisms and endogenous stimuli, such as damage-associated molecular patterns and immune complexes, and involves activation in most cases of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, which produces reactive oxygen species (ROS). Recent study has reported that there are two different mechanisms of NETosis, including a lytic NETosis and a vital NETosis. Lytic NETosis begins with nuclear delobulation and the disassembly of the nuclear envelope and continues with loss of cellular polarization, chromatin decondensation and plasma membrane rupture. Vital NETosis can occur independently of cell death and involves the secreted expulsion of nuclear chromatin that is accompanied by the release of granule proteins through degranulation.
Class
Organismal Systems; Immune system
Pathway map
btax04613  Neutrophil extracellular trap formation
btax04613

Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128043242  PADI4; protein-arginine deiminase type-4 [KO:K24669]
128043285  ATG7; ubiquitin-like modifier-activating enzyme ATG7 isoform X1 [KO:K08337]
128043343  HAT1; histone acetyltransferase type B catalytic subunit [KO:K11303] [EC:2.3.1.48]
128043403  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128043471  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
128043504  [KO:K11253]
128043956  ACTB; actin, cytoplasmic 1 [KO:K05692]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128044328  HDAC4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
128044336  [KO:K11252]
128044360  [KO:K11252]
128044372  [KO:K06472]
128044373  [KO:K06463]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128044782  [KO:K11253]
128044805  [KO:K11253]
128044872  [KO:K13916]
128044882  [KO:K13916]
128044892  [KO:K13916]
128044948  [KO:K11254]
128045052  [KO:K11251]
128045053  [KO:K11251]
128045090  [KO:K11251]
128045092  [KO:K11253]
128045223  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
128045433  [KO:K11251]
128045443  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128046489  [KO:K11251]
128046885  [KO:K11252]
128046991  HDAC9; histone deacetylase 9 [KO:K11409] [EC:3.5.1.98]
128047159  ITGB2; integrin beta-2 [KO:K06464]
128047278  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
128047318  [KO:K13916]
128047426  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
128047431  [KO:K13916]
128047519  [KO:K13916]
128047614  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial [KO:K09565] [EC:5.2.1.8]
128047628  [KO:K13916]
128047644  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
128047881  [KO:K11251]
128047902  [KO:K11251]
128047918  [KO:K11254]
128047922  [KO:K13916]
128048390  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
128048391  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
128048587  VWF; von Willebrand factor [KO:K03900]
128048638  NCF4; neutrophil cytosol factor 4 [KO:K08012]
128048691  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
128048700  CLEC7A; C-type lectin domain family 7 member A [KO:K10074]
128049417  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128049643  [KO:K11251]
128050332  [KO:K03990]
128050333  [KO:K03990]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128050576  [KO:K11251]
128050619  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
128050636  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
128050659  [KO:K11252]
128050664  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128050946  [KO:K11251]
128051418  [KO:K11253]
128051477  H3-4; histone H3.1t [KO:K11253]
128051781  ELANE; neutrophil elastase [KO:K01327] [EC:3.4.21.37]
128051783  AZU1; azurocidin [KO:K24665]
128052008  CLCN3; H(+)/Cl(-) exchange transporter 3 isoform X1 [KO:K05012]
128052350  [KO:K11251]
128052376  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
128052396  TLR4; toll-like receptor 4 [KO:K10160]
128052536  C5; complement C5 [KO:K03994]
128052563  [KO:K11253]
128053221  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
128053252  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128054050  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
128054233  [KO:K13916]
128054554  AQP9; aquaporin-9 [KO:K09877]
128055097  [KO:K11251]
128055173  [KO:K11254]
128055175  [KO:K11253]
128055176  [KO:K11254]
128055179  [KO:K11251]
128055181  [KO:K11251]
128055189  [KO:K11253]
128055192  [KO:K11251]
128055193  [KO:K11251]
128055194  [KO:K11251]
128055195  [KO:K11251]
128055196  [KO:K11251]
128055197  [KO:K11251]
128055201  [KO:K11251]
128055202  [KO:K11252]
128055203  [KO:K11252]
128055204  [KO:K11252]
128055205  [KO:K11252]
128055207  [KO:K11252]
128055208  [KO:K11252]
128055209  [KO:K11252]
128055210  [KO:K11254]
128055212  [KO:K11253]
128055213  [KO:K11253]
128055214  [KO:K11253]
128055215  [KO:K11252]
128055216  [KO:K11254]
128055218  [KO:K11254]
128055294  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
128055379  [KO:K11252]
128055518  [KO:K11253]
128055537  [KO:K11254]
128055547  [KO:K11254]
128055548  [KO:K11253]
128055801  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
128055916  [KO:K11251]
128055917  [KO:K11251]
128055918  [KO:K11252]
128055919  [KO:K11252]
128056099  [KO:K11252]
128056116  [KO:K11253]
128056192  [KO:K11252]
128056470  AGER; advanced glycosylation end product-specific receptor [KO:K19722]
128056795  [KO:K11251]
128057499  HMGB1; high mobility group protein B1 [KO:K10802]
128057830  [KO:K11253]
128058011  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
128058174  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
128058189  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
128058303  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
128058611  [KO:K11253]
128058634  [KO:K05862]
128059118  [KO:K15040]
128059276  [KO:K11253]
128059451  GSDMD; gasdermin-D isoform X1 [KO:K20917]
128060434  [KO:K11251]
128060592  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
128060611  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061557  SELP; P-selectin [KO:K06496]
128061580  [KO:K11253]
128061687  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
128061705  [KO:K11253]
128061783  NCF2; neutrophil cytosol factor 2 [KO:K08010]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128062008  SELPLG; P-selectin glycoprotein ligand 1 isoform X1 [KO:K06544]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128062323  NCF1; neutrophil cytosol factor 1 [KO:K08011]
128062410  TLR2; toll-like receptor 2 [KO:K10159]
128062424  FGB; fibrinogen beta chain [KO:K03904]
128062431  SLC25A31; ADP/ATP translocase 4 [KO:K05863]
128062535  FGG; fibrinogen gamma chain [KO:K03905]
128062599  FGA; fibrinogen alpha chain [KO:K03903]
128063096  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
128063111  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
128063588  C5AR1; C5a anaphylatoxin chemotactic receptor 1 [KO:K04010]
128063662  [KO:K08009]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128064385  ACTG1; actin, cytoplasmic 2 [KO:K05692]
128064875  ITGB3; integrin beta-3 [KO:K06493]
128065174  MPO; myeloperoxidase [KO:K10789] [EC:1.11.2.2]
128065180  [KO:K11253]
128065261  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
128065265  ITGA2B; integrin alpha-IIb [KO:K06476]
128065393  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128065686  GP1BA; platelet glycoprotein Ib alpha chain [KO:K06261]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128066252  [KO:K11252]
128066359  [KO:K06461]
128066420  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
128066557  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
128066749  [KO:K01319] [EC:3.4.21.20]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128068182  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
128068228  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
128068545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
128068546  RELA; transcription factor p65 [KO:K04735]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128069371  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
128069697  CLCN4; H(+)/Cl(-) exchange transporter 4 isoform X1 [KO:K05012]
128069760  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
128069880  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
128069952  CLCN5; H(+)/Cl(-) exchange transporter 5 [KO:K05012]
128069970  [KO:K11252]
128069971  [KO:K11252]
128070027  [KO:K10802]
128070075  [KO:K21421] [EC:1.-.-.-]
128070124  [KO:K11252]
128070125  [KO:K11252]
128070126  [KO:K11252]
128070130  [KO:K11252]
128070131  [KO:K11252]
128070133  [KO:K11252]
128070134  [KO:K11252]
128070136  [KO:K11252]
128070137  [KO:K11252]
128070138  [KO:K11252]
128070139  [KO:K11252]
128070286  TLR8; toll-like receptor 8 [KO:K10170]
128070301  TLR7; toll-like receptor 7 [KO:K05404]
128070308  [KO:K11252]
128070318  [KO:K11252]
128070319  [KO:K11252]
128070342  [KO:K11252]
128070343  [KO:K11252]
128070377  [KO:K11252]
128070378  [KO:K11252]
128070379  [KO:K11252]
128070481  [KO:K11252]
128070536  [KO:K11251]
128070565  [KO:K11251]
128070620  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
128070817  ITGAL; integrin alpha-L [KO:K05718]
Compound
C00027  Hydrogen peroxide
C00039  DNA
C00076  Calcium cation
C00165  Diacylglycerol
C00338  Lipopolysaccharide
C00464  Mannan
C00518  Hyaluronate
C00551  beta-D-Glucan
C00704  Superoxide
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05151  12-O-Tetradecanoylphorbol 13-acetate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C11221  Formylmethionyl-leucyl-phenylalanine methyl ester
Reference
  Authors
Van Avondt K, Hartl D
  Title
Mechanisms and disease relevance of neutrophil extracellular trap formation.
  Journal
Eur J Clin Invest 48 Suppl 2:e12919 (2018)
DOI:10.1111/eci.12919
Reference
  Authors
Sorvillo N, Cherpokova D, Martinod K, Wagner DD
  Title
Extracellular DNA NET-Works With Dire Consequences for Health.
  Journal
Circ Res 125:470-488 (2019)
DOI:10.1161/CIRCRESAHA.119.314581
Reference
  Authors
Papayannopoulos V
  Title
Neutrophil extracellular traps in immunity and disease.
  Journal
Nat Rev Immunol 18:134-147 (2018)
DOI:10.1038/nri.2017.105
Reference
  Authors
Liu FC, Chuang YH, Tsai YF, Yu HP
  Title
Role of neutrophil extracellular traps following injury.
  Journal
Shock 41:491-8 (2014)
DOI:10.1097/SHK.0000000000000146
Reference
  Authors
Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y, Herrmann M
  Title
New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation.
  Journal
Front Immunol 7:302 (2016)
DOI:10.3389/fimmu.2016.00302
Reference
  Authors
Zawrotniak M, Bochenska O, Karkowska-Kuleta J, Seweryn-Ozog K, Aoki W, Ueda M, Kozik A, Rapala-Kozik M
  Title
Aspartic Proteases and Major Cell Wall Components in Candida albicans Trigger the Release of Neutrophil Extracellular Traps.
  Journal
Front Cell Infect Microbiol 7:414 (2017)
DOI:10.3389/fcimb.2017.00414
Reference
  Authors
Honda M, Kubes P
  Title
Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system.
  Journal
Nat Rev Gastroenterol Hepatol 15:206-221 (2018)
DOI:10.1038/nrgastro.2017.183
Reference
  Authors
Hamam HJ, Palaniyar N
  Title
Post-Translational Modifications in NETosis and NETs-Mediated Diseases.
  Journal
Biomolecules 9:E369 (2019)
DOI:10.3390/biom9080369
Reference
  Authors
Burgener SS, Schroder K
  Title
Neutrophil Extracellular Traps in Host Defense.
  Journal
Cold Spring Harb Perspect Biol 12:a037028 (2020)
DOI:10.1101/cshperspect.a037028
Reference
  Authors
Vorobjeva NV, Chernyak BV
  Title
NETosis: Molecular Mechanisms, Role in Physiology and Pathology.
  Journal
Biochemistry (Mosc) 85:1178-1190 (2020)
DOI:10.1134/S0006297920100065
Reference
  Authors
Ravindran M, Khan MA, Palaniyar N
  Title
Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology.
  Journal
Biomolecules 9:E365 (2019)
DOI:10.3390/biom9080365
Reference
  Authors
Jorch SK, Kubes P
  Title
An emerging role for neutrophil extracellular traps in noninfectious disease.
  Journal
Nat Med 23:279-287 (2017)
DOI:10.1038/nm.4294
Reference
  Authors
Goggs R, Jeffery U, LeVine DN, Li RHL
  Title
Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review.
  Journal
Vet Pathol 57:6-23 (2020)
DOI:10.1177/0300985819861721
Reference
  Authors
Kim SJ, Jenne CN
  Title
Role of platelets in neutrophil extracellular trap (NET) production and tissue injury.
  Journal
Semin Immunol 28:546-554 (2016)
DOI:10.1016/j.smim.2016.10.013
Reference
  Authors
de Bont CM, Boelens WC, Pruijn GJM
  Title
NETosis, complement, and coagulation: a triangular relationship.
  Journal
Cell Mol Immunol 16:19-27 (2019)
DOI:10.1038/s41423-018-0024-0
Reference
  Authors
Zawrotniak M, Bartnicka D, Rapala-Kozik M
  Title
UVA and UVB radiation induce the formation of neutrophil extracellular traps by human polymorphonuclear cells.
  Journal
J Photochem Photobiol B 196:111511 (2019)
DOI:10.1016/j.jphotobiol.2019.111511
Reference
  Authors
Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T
  Title
Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality.
  Journal
Cell Death Differ 18:581-8 (2011)
DOI:10.1038/cdd.2011.1
Reference
  Authors
Zawrotniak M, Rapala-Kozik M
  Title
Neutrophil extracellular traps (NETs) - formation and implications.
  Journal
Acta Biochim Pol 60:277-84 (2013)
Reference
  Authors
Rosales C
  Title
Fcgamma Receptor Heterogeneity in Leukocyte Functional Responses.
  Journal
Front Immunol 8:280 (2017)
DOI:10.3389/fimmu.2017.00280
Reference
  Authors
Vorobjeva NV, Pinegin BV
  Title
Neutrophil extracellular traps: mechanisms of formation and role in health and disease.
  Journal
Biochemistry (Mosc) 79:1286-96 (2014)
DOI:10.1134/S0006297914120025
Reference
  Authors
Delgado-Rizo V, Martinez-Guzman MA, Iniguez-Gutierrez L, Garcia-Orozco A, Alvarado-Navarro A, Fafutis-Morris M
  Title
Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview.
  Journal
Front Immunol 8:81 (2017)
DOI:10.3389/fimmu.2017.00081
Reference
  Authors
Fonseca Z, Diaz-Godinez C, Mora N, Aleman OR, Uribe-Querol E, Carrero JC, Rosales C
  Title
Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation.
  Journal
Front Cell Infect Microbiol 8:226 (2018)
DOI:10.3389/fcimb.2018.00226
Reference
  Authors
Agraz-Cibrian JM, Giraldo DM, Mary FM, Urcuqui-Inchima S
  Title
Understanding the molecular mechanisms of NETs and their role in antiviral innate immunity.
  Journal
Virus Res 228:124-133 (2017)
DOI:10.1016/j.virusres.2016.11.033
Reference
  Authors
Schonrich G, Raftery MJ
  Title
Neutrophil Extracellular Traps Go Viral.
  Journal
Front Immunol 7:366 (2016)
DOI:10.3389/fimmu.2016.00366
Reference
  Authors
Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T, Uehata T, Iwasaki H, Omori H, Yamaoka S, Yamamoto N, Akira S
  Title
Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1.
  Journal
Cell Host Microbe 12:109-16 (2012)
DOI:10.1016/j.chom.2012.05.015
Reference
  Authors
Kumar S, Gupta E, Kaushik S, Jyoti A
  Title
Neutrophil Extracellular Traps: Formation and Involvement in Disease Progression.
  Journal
Iran J Allergy Asthma Immunol 17:208-220 (2018)
Related
pathway
btax04010  MAPK signaling pathway
btax04020  Calcium signaling pathway
btax04140  Autophagy - animal
btax04151  PI3K-Akt signaling pathway
btax04610  Complement and coagulation cascades
btax04611  Platelet activation
btax04620  Toll-like receptor signaling pathway
btax04621  NOD-like receptor signaling pathway
btax04666  Fc gamma R-mediated phagocytosis
KO pathway
ko04613   

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