KEGG   PATHWAY: tros04148
Entry
tros04148                   Pathway                                
Name
Efferocytosis - Triplophysa rosa
Class
Cellular Processes; Transport and catabolism
Pathway map
tros04148  Efferocytosis
tros04148

Organism
Triplophysa rosa [GN:tros]
Gene
130563511  casp3b; caspase-3b [KO:K02187] [EC:3.4.22.56]
130552814  casp3a; caspase-3a isoform X1 [KO:K02187] [EC:3.4.22.56]
130569476  casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
130569772  casp21; caspase 21, apoptosis-related cysteine peptidase [KO:K04397] [EC:3.4.22.60]
130557700  caspa; caspase a [KO:K01370] [EC:3.4.22.36]
130565283  panx1a; pannexin-1a [KO:K03443]
130549533  panx1b; pannexin-1b isoform X1 [KO:K03443]
130562869  P2Y purinoceptor 2-like [KO:K04269]
130562931  P2Y purinoceptor 2-like [KO:K04269]
130562473  P2Y purinoceptor 3 [KO:K04272]
130564989  p2ry12; P2Y purinoceptor 12 [KO:K04298]
130561107  sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
130557577  sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
130549023  s1pr1; sphingosine 1-phosphate receptor 1 [KO:K04288]
130549101  pla2g6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
130563554  abca1b; phospholipid-transporting ATPase ABCA1b [KO:K05641]
130552732  abca1a; phospholipid-transporting ATPase ABCA1a isoform X1 [KO:K05641]
130570970  abca7; phospholipid-transporting ATPase ABCA1 isoform X1 [KO:K05641]
130566026  gpr132b; probable G-protein coupled receptor 132b [KO:K08426]
130560598  si:dkey-165a24.9; probable G-protein coupled receptor 132 [KO:K08426]
130565599  adam17b; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
130560624  adam17a; disintegrin and metalloproteinase domain-containing protein 17a isoform X1 [KO:K06059] [EC:3.4.24.86]
130551632  disintegrin and metalloproteinase domain-containing protein 10-like [KO:K06704] [EC:3.4.24.81]
130554878  adam10a; disintegrin and metalloproteinase domain-containing protein 10 isoform X1 [KO:K06704] [EC:3.4.24.81]
130548346  si:ch1073-396h14.1; disintegrin and metalloproteinase domain-containing protein 10 isoform X1 [KO:K06704] [EC:3.4.24.81]
130545405  nfatc2a; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
130556728  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
130567005  nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
130559482  nfatc3a; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
130551287  nfatc3b; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
130554157  nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
130565346  hif1al; hypoxia inducible factor 1 subunit alpha, like isoform X1 [KO:K08268]
130559367  hif1aa; hypoxia inducible factor 1 subunit alpha a isoform X1 [KO:K08268]
130565527  hif1ab; hypoxia inducible factor 1 subunit alpha b isoform X1 [KO:K08268]
130557541  arnt; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
130558505  epoa; erythropoietin isoform X1 [KO:K05437]
130546324  epob; erythropoietin b isoform X1 [KO:K05437]
130561942  epor; erythropoietin receptor [KO:K05079]
130566863  jak2b; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
130550198  jak2a; tyrosine-protein kinase JAK2a isoform X1 [KO:K04447] [EC:2.7.10.2]
130564406  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
130561543  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
130568011  cebpb; CCAAT/enhancer-binding protein beta [KO:K10048]
130571051  pparg; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
130570047  rxraa; retinoic acid receptor RXR-alpha-A isoform X1 [KO:K08524]
130554856  rxrga; retinoic acid receptor RXR-gamma-A [KO:K08524]
130567758  rxrab; retinoic acid receptor RXR-alpha-B isoform X1 [KO:K08524]
130551963  mfge8b; milk fat globule EGF and factor V/VIII domain containing b isoform X1 [KO:K17253]
130558438  mfge8a; milk fat globule EGF and factor V/VIII domain containing a [KO:K17253]
130553441  gas6; growth arrest-specific protein 6 [KO:K05464]
130559295  mertka; tyrosine-protein kinase Mer [KO:K05117] [EC:2.7.10.1]
130547867  cd36; platelet glycoprotein 4 [KO:K06259]
130559911  thrombospondin-1-like isoform X1 [KO:K16857]
130565978  thbs1b; thrombospondin-1 [KO:K16857]
130562953  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
130553870  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
130549161  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
130553772  ptgs2a; LOW QUALITY PROTEIN: prostaglandin G/H synthase 2a [KO:K11987] [EC:1.14.99.1]
130560646  ptger2a; prostaglandin E receptor 2a (subtype EP2) [KO:K04259]
130554653  ptger4c; prostaglandin E receptor 4 (subtype EP4) c [KO:K04261]
130566917  ptger4b; prostaglandin E receptor 4 (subtype EP4) b [KO:K04261]
130568263  ptger4a; prostaglandin E receptor 4 (subtype EP4) a [KO:K04261]
130560157  dnmt3ab; DNA (cytosine-5)-methyltransferase 3A isoform X1 [KO:K17398] [EC:2.1.1.37]
130566394  dnmt3aa; DNA (cytosine-5-)-methyltransferase 3 alpha a [KO:K17398] [EC:2.1.1.37]
130552390  creb1a; cyclic AMP-responsive element-binding protein 1a isoform X1 [KO:K05870]
130555518  creb1b; cyclic AMP-responsive element-binding protein 1b [KO:K05870]
130564574  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
130570154  tgfb1b; transforming growth factor beta-1 proprotein [KO:K13375]
130570169  atp2a2b; sarcoplasmic/endoplasmic reticulum calcium ATPase 2b [KO:K05853] [EC:7.2.2.10]
130552730  si:dkey-28b4.8; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
130561480  atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
130567771  atp2a2a; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
130567907  atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
130569146  atp2a1l; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1, like isoform X1 [KO:K05853] [EC:7.2.2.10]
130551882  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain [KO:K04515] [EC:2.7.11.17]
130545748  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
130552663  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
130559418  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
130549675  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
130550120  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
130569278  camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
130571729  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
130571846  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
130547809  mapk12b; mitogen-activated protein kinase 12b isoform X1 [KO:K04441] [EC:2.7.11.24]
130547810  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
130567647  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
130567679  mapk13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
130563235  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
130571246  mapkapk2a; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
130568382  mapkapk2b; MAP kinase-activated protein kinase 2b [KO:K04443] [EC:2.7.11.1]
130565158  polyunsaturated fatty acid 5-lipoxygenase-like [KO:K00461] [EC:1.13.11.34]
130559644  alox5a; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
130551653  dusp8a; dual specificity protein phosphatase 8 isoform X1 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130570153  dusp4; dual specificity protein phosphatase 4 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130571142  dusp7; dual specificity protein phosphatase 7 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130547773  dusp16; dual specificity protein phosphatase 16 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130549148  dusp5; dual specificity protein phosphatase 5 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130568534  dusp2; dual specificity protein phosphatase 2 [KO:K04459] [EC:3.1.3.16 3.1.3.48]
130548128  ano6; anoctamin-6 isoform X1 [KO:K19500]
130551959  ano3; anoctamin-3 isoform X1 [KO:K19498]
130567857  ano5b; anoctamin-5b isoform X1 [KO:K19480]
130549749  ano5a; anoctamin-5 isoform X1 [KO:K19480]
130545562  ano11; anoctamin-7 [KO:K19501]
130564811  ano7; anoctamin-7 isoform X1 [KO:K19501]
130567967  ano9b; anoctamin-9 isoform X1 [KO:K19503]
130549713  anoctamin-9 isoform X1 [KO:K19503]
130548454  bsg; basigin isoform X1 [KO:K06535]
130567032  xkr8.3; XK-related protein 8.3 [KO:K26813]
130567212  XK-related protein 8-like [KO:K26813]
130547462  xkr9; XK-related protein 9 [KO:K26814]
130545085  xkr7a; XK-related protein 7 [KO:K26811]
130571825  xkr7b; XK-related protein 7 [KO:K26811]
130554323  xkr4; XK-related protein 4 [KO:K26811]
130560309  xkr6a; XK-related protein 6 [KO:K26811]
130565839  xkr6b; XK-related protein 6b [KO:K26811]
130563849  atp8a1; phospholipid-transporting ATPase IA isoform X1 [KO:K14802] [EC:7.6.2.1]
130547002  atp8a2; phospholipid-transporting ATPase IB isoform X1 [KO:K14802] [EC:7.6.2.1]
130549092  atp11b; phospholipid-transporting ATPase IF isoform X1 [KO:K26934] [EC:7.6.2.1]
130563401  atp11c; phospholipid-transporting ATPase 11C isoform X1 [KO:K26934] [EC:7.6.2.1]
130552623  atp11a; phospholipid-transporting ATPase IH isoform X1 [KO:K26934] [EC:7.6.2.1]
130560514  tmem30aa; transmembrane protein 30Aa [KO:K26935]
130565916  tmem30ab; transmembrane protein 30Ab [KO:K26935]
130552778  pros1; vitamin K-dependent protein S [KO:K03908]
130555555  itgav; integrin alpha-V [KO:K06487]
130562007  itgb3a; LOW QUALITY PROTEIN: integrin beta-3a [KO:K06493]
130568975  itgb3b; integrin beta-3b [KO:K06493]
130555447  itgb5; integrin beta-5 [KO:K06588]
130564422  tyrosine-protein kinase receptor UFO [KO:K05115] [EC:2.7.10.1]
130559887  tyro3; tyrosine-protein kinase receptor TYRO3 isoform X1 [KO:K05116] [EC:2.7.10.1]
130566673  adhesion G protein-coupled receptor B1-like [KO:K04596]
130557551  adgrb1a; adhesion G protein-coupled receptor B1 isoform X1 [KO:K04596]
130570620  havcr1; hepatitis A virus cellular receptor 1 [KO:K20413]
130548806  stab1; stabilin-1 [KO:K19020]
130547784  stab2; stabilin-2 isoform X1 [KO:K19013]
130558020  ptk2ab; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
130566708  ptk2aa; protein tyrosine kinase 2aa isoform X1 [KO:K05725] [EC:2.7.10.2]
130562897  bcar1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
130564632  crk; adapter molecule crk [KO:K04438]
130570638  crkl; crk-like protein [KO:K04438]
130566651  elmo1; engulfment and cell motility protein 1 isoform X1 [KO:K12366]
130569437  dock1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
130561532  rac1b; ras-related C3 botulinum toxin substrate 1b [KO:K04392]
130569042  rac1a; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
130569598  zgc:174164; disintegrin and metalloproteinase domain-containing protein 9 isoform X1 [KO:K06834] [EC:3.4.24.-]
130567649  adam9; disintegrin and metalloproteinase domain-containing protein 9 isoform X1 [KO:K06834] [EC:3.4.24.-]
130554944  calr3b; calreticulin 3b [KO:K08057]
130548706  calr3a; calreticulin 3a [KO:K08057]
130567975  calr; calreticulin [KO:K08057]
130570391  complement C1q subcomponent subunit C-like [KO:K03988]
130544988  lrp1ab; low-density lipoprotein receptor-related protein 1 [KO:K04550]
130571620  low-density lipoprotein receptor-related protein 1-like [KO:K04550]
130545760  megf10; multiple epidermal growth factor-like domains protein 10 isoform X1 [KO:K24068]
130562523  megf11; multiple epidermal growth factor-like domains protein 11 isoform X1 [KO:K24068]
130564757  scarf1; scavenger receptor class F member 1 [KO:K24318]
130571776  PTB domain-containing engulfment adapter protein 1-like [KO:K23285]
130556068  gulp1a; PTB domain-containing engulfment adapter protein 1 isoform X1 [KO:K23285]
130556450  gulp1b; PTB domain-containing engulfment adapter protein 1 isoform X1 [KO:K23285]
130557618  rab5ab; RAB5A, member RAS oncogene family, b [KO:K07887]
130566701  rab5aa; RAB5A, member RAS oncogene family, a [KO:K07887]
130555885  rab5b; ras-related protein Rab-5B [KO:K07888]
130561680  rab5c; ras-related protein Rab-5C [KO:K07889]
130559822  si:ch211-266g18.9; LOW QUALITY PROTEIN: transforming growth factor-beta receptor-associated protein 1 [KO:K20177]
130557016  tgfbrap1; transforming growth factor-beta receptor-associated protein 1 homolog [KO:K20177]
130552577  vacuolar protein sorting-associated protein 8 homolog [KO:K20178]
130545982  vps11; vacuolar protein sorting-associated protein 11 homolog [KO:K20179]
130556525  vps16; vacuolar protein sorting-associated protein 16 homolog [KO:K20180]
130565722  vps18; vacuolar protein sorting-associated protein 18 homolog [KO:K20181]
130568807  vps33a; vacuolar protein sorting-associated protein 33A [KO:K20182]
130545944  rab14; ras-related protein Rab-14 [KO:K07881]
130565303  rab14l; RAB14, member RAS oncogene family, like [KO:K07881]
130560565  vps39; vam6/Vps39-like protein isoform X1 [KO:K20183]
130546924  vps41; LOW QUALITY PROTEIN: vacuolar protein sorting-associated protein 41 homolog [KO:K20184]
130545652  zgc:100918; ras-related protein rab7-like [KO:K07897]
130570869  si:dkey-13a21.4; ras-related protein Rab-7a [KO:K07897]
130571349  rab7a; ras-related protein Rab-7a [KO:K07897]
130568270  ras-related protein rab7-like [KO:K07897]
130568524  slc66a1; lysosomal amino acid transporter 1 homolog [KO:K23678]
130558824  arg2; arginase-2, mitochondrial [KO:K01476] [EC:3.5.3.1]
130569105  arg1; arginase-1 isoform X1 [KO:K01476] [EC:3.5.3.1]
130560730  odc1; ornithine decarboxylase isoform X1 [KO:K01581] [EC:4.1.1.17]
130570758  ch25hl2; cholesterol 25-hydroxylase-like protein 2 [KO:K10223] [EC:1.14.99.38]
130562559  cholesterol 25-hydroxylase-like protein 1, member 2 [KO:K10223] [EC:1.14.99.38]
130551017  ch25hl3; cholesterol 25-hydroxylase-like protein [KO:K10223] [EC:1.14.99.38]
130569197  cholesterol 25-hydroxylase-like protein [KO:K10223] [EC:1.14.99.38]
130569202  cholesterol 25-hydroxylase-like protein [KO:K10223] [EC:1.14.99.38]
130551539  cpt1ab; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
130551648  cpt1aa; carnitine palmitoyltransferase 1Aa (liver) isoform X1 [KO:K08765] [EC:2.3.1.21]
130546818  carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
130561431  cpt1a2b; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
130562617  cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
130559638  cytochrome b-c1 complex subunit Rieske, mitochondrial [KO:K00411] [EC:7.1.1.8]
130562571  cytochrome b-c1 complex subunit Rieske, mitochondrial-like [KO:K00411] [EC:7.1.1.8]
130558770  sirt1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
130554695  pbx1a; pre-B-cell leukemia homeobox 1a isoform X1 [KO:K09355]
130557131  pbx1b; pre-B-cell leukemia transcription factor 1b isoform X1 [KO:K09355]
130571262  il10; interleukin-10 [KO:K05443]
130569142  lipf; gastric triacylglycerol lipase [KO:K01052] [EC:3.1.1.13]
130551487  pla2g15; group XV phospholipase A2 [KO:K06129] [EC:3.1.1.5]
130548894  pparda; peroxisome proliferator-activated receptor delta isoform X1 [KO:K04504]
130567968  ppardb; peroxisome proliferator-activated receptor delta b [KO:K04504]
130545431  solute carrier family 2, facilitated glucose transporter member 1-like [KO:K07299]
130560346  solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
130556523  slc2a1b; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
130567852  slc16a1b; monocarboxylate transporter 1b [KO:K08179]
130557318  slc16a1a; monocarboxylate transporter 1a [KO:K08179]
130557985  sgk2b; serine/threonine-protein kinase Sgk2b [KO:K13302] [EC:2.7.11.1]
130572051  sgk1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
130567197  si:ch211-195b13.1; STKc_SGK domain-containing protein isoform X1 [KO:K13302] [EC:2.7.11.1]
130562248  pecam1a; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471]
130549771  pecam1b; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471]
130557522  ptpn6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
130545936  ptpn11a; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
130571983  ptpn11b; tyrosine-protein phosphatase non-receptor type 11b isoform X1 [KO:K07293] [EC:3.1.3.48]
Compound
C00002  ATP
C00003  NAD+
C00019  S-Adenosyl-L-methionine
C00031  D-Glucose
C00062  L-Arginine
C00073  L-Methionine
C00075  UTP
C00077  L-Ornithine
C00134  Putrescine
C00162  Fatty acid
C00186  (S)-Lactate
C00187  Cholesterol
C00584  Prostaglandin E2
C02530  Cholesterol ester
C02737  Phosphatidylserine
C04230  1-Acyl-sn-glycero-3-phosphocholine
C06124  Sphingosine 1-phosphate
C06314  Lipoxin A4
C15519  25-Hydroxycholesterol
C15610  Cholest-5-ene-3beta,26-diol
C18178  Resolvin D1
Reference
PMID:31822793
  Authors
Doran AC, Yurdagul A Jr, Tabas I
  Title
Efferocytosis in health and disease.
  Journal
Nat Rev Immunol 20:254-267 (2020)
DOI:10.1038/s41577-019-0240-6
Reference
PMID:36028471
  Authors
Zhang J, Ding W, Zhao M, Liu J, Xu Y, Wan J, Wang M
  Title
Mechanisms of efferocytosis in determining inflammation resolution: Therapeutic potential and the association with cardiovascular disease.
  Journal
Br J Pharmacol 179:5151-5171 (2022)
DOI:10.1111/bph.15939
Reference
PMID:30165442
  Authors
Kawano M, Nagata S
  Title
Efferocytosis and autoimmune disease.
  Journal
Int Immunol 30:551-558 (2018)
DOI:10.1093/intimm/dxy055
Reference
PMID:35650427
  Authors
Mehrotra P, Ravichandran KS
  Title
Drugging the efferocytosis process: concepts and opportunities.
  Journal
Nat Rev Drug Discov 21:601-620 (2022)
DOI:10.1038/s41573-022-00470-y
Reference
PMID:28496201
  Authors
Park SY, Kim IS
  Title
Engulfment signals and the phagocytic machinery for apoptotic cell clearance.
  Journal
Exp Mol Med 49:e331 (2017)
DOI:10.1038/emm.2017.52
Reference
PMID:28137963
  Authors
Kojima Y, Weissman IL, Leeper NJ
  Title
The Role of Efferocytosis in Atherosclerosis.
  Journal
Circulation 135:476-489 (2017)
DOI:10.1161/CIRCULATIONAHA.116.025684
Related
pathway
tros00010  Glycolysis / Gluconeogenesis
tros04140  Autophagy - animal
tros04145  Phagosome
KO pathway
ko04148   
LinkDB

DBGET integrated database retrieval system