KEGG   PATHWAY: ko04140
Entry
ko04140                     Pathway                                
Name
Autophagy - animal
Description
Autophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily conserved among eukaryotes and exquisitely regulated. This progress initiates with production of the autophagosome, a double-membrane intracellular structure of reticular origin that engulfs cytoplasmic contents and ultimately fuses with lysosomes for cargo degradation. Autophagy is regulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation and ER stress. Constitutive level of autophagy plays an important role in cellular homeostasis and maintains quality control of essential cellular components.
Class
Cellular Processes; Transport and catabolism
Pathway map
ko04140  Autophagy - animal
ko04140

Other DBs
GO: 0006914
Orthology
K00914  PIK3C3, VPS34; phosphatidylinositol 3-kinase [EC:2.7.1.137]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01110  PTEN; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K01363  CTSB; cathepsin B [EC:3.4.22.1]
K01365  CTSL; cathepsin L [EC:3.4.22.15]
K01379  CTSD; cathepsin D [EC:3.4.23.5]
K02158  BAD; Bcl-2-antagonist of cell death
K02161  BCL2; apoptosis regulator Bcl-2
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02833  HRAS; GTPase HRas
K02927  RP-L40e, RPL40, UBA52; ubiquitin-large subunit ribosomal protein L40e
K02977  RP-S27Ae, RPS27A, UBA80; ubiquitin-small subunit ribosomal protein S27Ae
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03237  EIF2S1; translation initiation factor 2 subunit 1
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04382  PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K04427  MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04526  INS; insulin
K04551  UBB; ubiquitin B
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K04724  CFLAR, FLIP; CASP8 and FADD-like apoptosis regulator
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K06068  PRKCD; novel protein kinase C delta type [EC:2.7.11.13]
K06276  PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K06528  LAMP1_2, CD107; lysosomal-associated membrane protein 1/2
K07187  IRS2; insulin receptor substrate 2
K07198  PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31]
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07204  RAPTOR; regulatory associated protein of mTOR
K07206  TSC1; tuberous sclerosis 1
K07207  TSC2; tuberous sclerosis 2
K07208  RHEB; Ras homolog enriched in brain
K07298  STK11, LKB1; serine/threonine-protein kinase 11 [EC:2.7.11.1]
K07359  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 [EC:2.7.11.17]
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07829  RRAS; Ras-related protein R-Ras
K07830  RRAS2, TC21; Ras-related protein R-Ras2
K07831  MRAS; Ras-related protein M-Ras
K07874  RAB1A; Ras-related protein Rab-1A
K07897  RAB7A; Ras-related protein Rab-7A
K07898  RAB7B; Ras-related protein Rab-7B
K07901  RAB8A, MEL; Ras-related protein Rab-8A
K07920  RAB33B; Ras-related protein Rab-33B
K07925  RAB39B; Ras-related protein Rab-39B
K08266  MLST8, GBL; target of rapamycin complex subunit LST8
K08268  HIF1A; hypoxia-inducible factor 1 alpha
K08269  ULK2, ATG1; serine/threonine-protein kinase ULK2 [EC:2.7.11.1]
K08270  DDIT4, REDD1; DNA-damage-inducible transcript 4
K08331  ATG13; autophagy-related protein 13
K08333  PIK3R4, VPS15; phosphoinositide-3-kinase, regulatory subunit 4 [EC:2.7.11.1]
K08334  BECN, VPS30, ATG6; beclin
K08336  ATG12; ubiquitin-like protein ATG12
K08337  ATG7; ubiquitin-like modifier-activating enzyme ATG7
K08339  ATG5; autophagy-related protein 5
K08341  GABARAP, ATG8, LC3; GABA(A) receptor-associated protein
K08342  ATG4; cysteine protease ATG4 [EC:3.4.22.-]
K08343  ATG3; ubiquitin-like-conjugating enzyme ATG3
K08488  STX7; syntaxin 7
K08491  STX17; syntaxin 17
K08509  SNAP29; synaptosomal-associated protein 29
K08512  VAMP8; vesicle-associated membrane protein 8
K08516  YKT6; synaptobrevin homolog YKT6
K08770  UBC; ubiquitin C
K08803  DAPK; death-associated protein kinase [EC:2.7.11.1]
K08852  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 [EC:2.7.11.1 3.1.26.-]
K08860  EIF2AK3, PERK; eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]
K10435  MAP1LC; microtubule-associated protein 1 light chain
K10586  BIRC6, BRUCE; baculoviral IAP repeat-containing protein 6 (apollon) [EC:2.3.2.23]
K10802  HMGB1; high mobility group protein B1
K11248  SH3GLB1; endophilin-B1
K12650  TANK; TRAF family member-associated NF-kappa-B activator
K14381  SQSTM1; sequestosome 1
K15464  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
K16172  IRS1; insulin receptor substrate 1
K16184  AKT1S1, PRAS40; proline-rich AKT1 substrate 1
K16185  RRAGA_B; Ras-related GTP-binding protein A/B
K16186  RRAGC_D; Ras-related GTP-binding protein C/D
K16196  EIF2AK4; eukaryotic translation initiation factor 2-alpha kinase 4 [EC:2.7.11.1]
K17445  IRS3; insulin receptor substrate 3
K17446  IRS4; insulin receptor substrate 4
K17589  RB1CC1; RB1-inducible coiled-coil protein 1
K17603  ZFYVE1; zinc finger FYVE domain-containing protein 1
K17606  IGBP1, TAP42; immunoglobulin-binding protein 1
K17888  ATG10L, ATG10; ubiquitin-like-conjugating enzyme ATG10
K17889  ATG14L, ATG14; beclin 1-associated autophagy-related key regulator
K17890  ATG16L1; autophagy-related protein 16-1
K17906  ATG2; autophagy-related protein 2
K17907  ATG9; autophagy-related protein 9
K17908  WIPI1_2, ATG18; autophagy-related protein 18
K17985  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1
K17987  NBR1; next to BRCA1 gene 1 protein
K18052  PRKCQ; novel protein kinase C theta type [EC:2.7.11.13]
K18082  MTMR3_4, ZFYVE10_11; myotubularin-related protein 3/4 [EC:3.1.3.48 3.1.3.64 3.1.3.95]
K18086  MTMR14; myotubularin-related protein 14 [EC:3.1.3.64 3.1.3.95]
K19330  RUBCN; run domain Beclin-1 interacting and cysteine-rich containing protein
K19730  ATG101; autophagy-related protein 101
K19946  OPTN, FIP2; optineurin
K20179  VPS11, PEP5; vacuolar protein sorting-associated protein 11
K20180  VPS16; vacuolar protein sorting-associated protein 16
K20181  VPS18, PEP3; vacuolar protein sorting-associated protein 18
K20182  VPS33A; vacuolar protein sorting-associated protein 33A
K20183  VPS39, VAM6; Vam6/Vps39-like protein vacuolar protein sorting-associated protein 39
K20184  VPS41; vacuolar protein sorting-associated protein 41
K20402  DEPTOR; DEP domain-containing mTOR-interacting protein
K20868  ATG16L2; autophagy-related protein 16-2
K21245  SUPT20H; transcription factor SPT20 homolog
K21246  NRBF2; nuclear receptor-binding factor 2
K21247  TP53INP2; tumor protein p53-inducible nuclear protein 2
K21248  VMP1; vacuole membrane protein 1
K21249  UVRAG; UV radiation resistance-associated gene protein
K21250  PRAP1; proline-rich acidic protein 1
K21347  TAX1BP1; Tax1-binding protein 1
K21348  CALCOCO2, NDP52; calcium-binding and coiled-coil domain-containing protein 2
K21357  ULK1; serine/threonine-protein kinase ULK1 [EC:2.7.11.1]
K22262  WDFY3, ALFY; WD repeat and FYVE domain-containing protein 3
K22991  WDR45, WIPI4, WIPI3; WD repeat-containing protein 45
K23282  PLEKHM1; pleckstrin homology domain-containing family M member 1
K23609  C9ORF72; guanine nucleotide exchange protein C9orf72
K23610  WDR41; WD repeat-containing protein 41
K23611  SMCR8; guanine nucleotide exchange protein SMCR8
K23883  EPG5; ectopic P granules protein 5
K26797  GORASP, GRASP65_55; golgi reassembly-stacking protein
Compound
C00035  GDP
C00044  GTP
C00350  Phosphatidylethanolamine
C01194  1-Phosphatidyl-D-myo-inositol
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15325584
  Authors
Meijer AJ, Codogno P.
  Title
Regulation and role of autophagy in mammalian cells.
  Journal
Int J Biochem Cell Biol 36:2445-62 (2004)
DOI:10.1016/j.biocel.2004.02.002
Reference
PMID:16099218
  Authors
Deretic V.
  Title
Autophagy in innate and adaptive immunity.
  Journal
Trends Immunol 26:523-8 (2005)
DOI:10.1016/j.it.2005.08.003
Reference
PMID:16200202
  Authors
Levine B, Yuan J.
  Title
Autophagy in cell death: an innocent convict?
  Journal
J Clin Invest 115:2679-88 (2005)
DOI:10.1172/JCI26390
Reference
PMID:15325588
  Authors
Tanida I, Ueno T, Kominami E.
  Title
LC3 conjugation system in mammalian autophagy.
  Journal
Int J Biochem Cell Biol 36:2503-18 (2004)
DOI:10.1016/j.biocel.2004.05.009
Reference
PMID:15928708
  Authors
Lum JJ, DeBerardinis RJ, Thompson CB.
  Title
Autophagy in metazoans: cell survival in the land of plenty.
  Journal
Nat Rev Mol Cell Biol 6:439-48 (2005)
DOI:10.1038/nrm1660
Reference
PMID:15978794
  Authors
Reggiori F, Klionsky DJ.
  Title
Autophagosomes: biogenesis from scratch?
  Journal
Curr Opin Cell Biol 17:415-22 (2005)
DOI:10.1016/j.ceb.2005.06.007
Reference
PMID:11099404
  Authors
Klionsky DJ, Emr SD.
  Title
Autophagy as a regulated pathway of cellular degradation.
  Journal
Science 290:1717-21 (2000)
DOI:10.1126/science.290.5497.1717
Reference
PMID:16125113
  Authors
Bechet D, Tassa A, Taillandier D, Combaret L, Attaix D.
  Title
Lysosomal proteolysis in skeletal muscle.
  Journal
Int J Biochem Cell Biol 37:2098-114 (2005)
DOI:10.1016/j.biocel.2005.02.029
Reference
PMID:19653858
  Authors
He C, Klionsky DJ
  Title
Regulation mechanisms and signaling pathways of autophagy.
  Journal
Annu Rev Genet 43:67-93 (2009)
DOI:10.1146/annurev-genet-102808-114910
Reference
PMID:19802558
  Authors
Yang Z, Klionsky DJ
  Title
An overview of the molecular mechanism of autophagy.
  Journal
Curr Top Microbiol Immunol 335:1-32 (2009)
DOI:10.1007/978-3-642-00302-8_1
Reference
PMID:20034776
  Authors
Yang Z, Klionsky DJ
  Title
Mammalian autophagy: core molecular machinery and signaling regulation.
  Journal
Curr Opin Cell Biol 22:124-31 (2010)
DOI:10.1016/j.ceb.2009.11.014
Reference
PMID:21187343
  Authors
Chen Y, Klionsky DJ
  Title
The regulation of autophagy - unanswered questions.
  Journal
J Cell Sci 124:161-70 (2011)
DOI:10.1242/jcs.064576
Reference
PMID:21801009
  Authors
Mizushima N, Yoshimori T, Ohsumi Y
  Title
The role of Atg proteins in autophagosome formation.
  Journal
Annu Rev Cell Dev Biol 27:107-32 (2011)
DOI:10.1146/annurev-cellbio-092910-154005
Reference
PMID:24343578
  Authors
Russell RC, Yuan HX, Guan KL
  Title
Autophagy regulation by nutrient signaling.
  Journal
Cell Res 24:42-57 (2014)
DOI:10.1038/cr.2013.166
Reference
PMID:25948417
  Authors
Noda NN, Fujioka Y
  Title
Atg1 family kinases in autophagy initiation.
  Journal
Cell Mol Life Sci 72:3083-96 (2015)
DOI:10.1007/s00018-015-1917-z
Related
pathway
ko04010  MAPK signaling pathway
ko04141  Protein processing in endoplasmic reticulum
ko04142  Lysosome
ko04150  mTOR signaling pathway
ko04152  AMPK signaling pathway
ko04910  Insulin signaling pathway

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