KEGG   PATHWAY: hsa04140
Entry
hsa04140                    Pathway                                
Name
Autophagy - animal - Homo sapiens (human)
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
hsa04140  Autophagy - animal
hsa04140

Network
  Element
N00155  Autophagy-vesicle nucleation/elongation/maturation, mTORC1-PI3KC3-C1
N00156  Autophagy-vesicle nucleation/elongation/maturation, LC3-II formation
N01142  C9orf72-mediated autophagy initiation
N01715  Autophagy-vesicle nucleation/elongation/maturation, PI3P synthesis by PI3KC3-C1
N01716  Autophagy-vesicle nucleation/elongation/maturation, sequestosome-1-like receptor
N01718  Autophagy-vesicle nucleation/elongation/maturation, PACER-RUBCN-PI3KC3-C2
N01720  Autophagosome and lysosome fusion, trans-SNARE
N01721  Autophagosome and lysosome fusion, tethering factor
N01722  Autophagosome and lysosome fusion, tethering factor, GRASP55
Drug
D12777  Olgotrelvir (USAN)
D12778  Olgotrelvir sodium (USAN)
Other DBs
GO: 0006914
Organism
Homo sapiens (human) [GN:hsa]
Gene
3630  INS; insulin [KO:K04526]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
3667  IRS1; insulin receptor substrate 1 [KO:K16172]
8660  IRS2; insulin receptor substrate 2 [KO:K07187]
8471  IRS4; insulin receptor substrate 4 [KO:K17446]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
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]
5170  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
5728  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
22808  MRAS; muscle RAS oncogene homolog [KO:K07831]
6237  RRAS; RAS related [KO:K07829]
22800  RRAS2; RAS related 2 [KO:K07830]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
3091  HIF1A; hypoxia inducible factor 1 subunit alpha [KO:K08268]
54541  DDIT4; DNA damage inducible transcript 4 [KO:K08270]
7249  TSC2; TSC complex subunit 2 [KO:K07207]
7248  TSC1; TSC complex subunit 1 [KO:K07206]
664  BNIP3; BCL2 interacting protein 3 [KO:K15464]
6009  RHEB; Ras homolog, mTORC1 binding [KO:K07208]
57521  RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204]
64798  DEPTOR; DEP domain containing MTOR interacting protein [KO:K20402]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
84335  AKT1S1; AKT1 substrate 1 [KO:K16184]
64223  MLST8; MTOR associated protein, LST8 homolog [KO:K08266]
6198  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
6199  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
3476  IGBP1; immunoglobulin binding protein 1 [KO:K17606]
5515  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
5516  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
8408  ULK1; unc-51 like autophagy activating kinase 1 [KO:K21357] [EC:2.7.11.1]
9706  ULK2; unc-51 like autophagy activating kinase 2 [KO:K08269] [EC:2.7.11.1]
9776  ATG13; autophagy related 13 [KO:K08331]
60673  ATG101; autophagy related 101 [KO:K19730]
9821  RB1CC1; RB1 inducible coiled-coil 1 [KO:K17589]
23130  ATG2A; autophagy related 2A [KO:K17906]
55102  ATG2B; autophagy related 2B [KO:K17906]
26100  WIPI2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908]
55062  WIPI1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908]
56270  WDR45B; WD repeat domain 45B [KO:K22991]
11152  WDR45; WD repeat domain 45 [KO:K22991]
285973  ATG9B; autophagy related 9B [KO:K17907]
79065  ATG9A; autophagy related 9A [KO:K17907]
55578  SUPT20H; SPT20 homolog, SAGA complex component [KO:K21245]
100130302  SUPT20HL1; SUPT20H like 1 [KO:K21245]
170067  SUPT20HL2; SUPT20H like 2 [KO:K21245]
140775  SMCR8; SMCR8-C9orf72 complex subunit [KO:K23611]
55255  WDR41; WD repeat domain 41 [KO:K23610]
203228  C9orf72; C9orf72-SMCR8 complex subunit [KO:K23609]
4218  RAB8A; RAB8A, member RAS oncogene family [KO:K07901]
116442  RAB39B; RAB39B, member RAS oncogene family [KO:K07925]
8878  SQSTM1; sequestosome 1 [KO:K14381]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
10010  TANK; TRAF family member associated NFKB activator [KO:K12650]
5861  RAB1A; RAB1A, member RAS oncogene family [KO:K07874]
10670  RRAGA; Ras related GTP binding A [KO:K16185]
10325  RRAGB; Ras related GTP binding B [KO:K16185]
64121  RRAGC; Ras related GTP binding C [KO:K16186]
58528  RRAGD; Ras related GTP binding D [KO:K16186]
6794  STK11; serine/threonine kinase 11 [KO:K07298] [EC:2.7.11.1]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5580  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
598  BCL2L1; BCL2 like 1 [KO:K04570]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
8678  BECN1; beclin 1 [KO:K08334]
441925  BECN2; beclin 2 [KO:K08334]
29982  NRBF2; nuclear receptor binding factor 2 [KO:K21246]
30849  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
5289  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
22863  ATG14; autophagy related 14 [KO:K17889]
55626  AMBRA1; autophagy and beclin 1 regulator 1 [KO:K17985]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
58476  TP53INP2; tumor protein p53 inducible nuclear protein 2 [KO:K21247]
81671  VMP1; vacuole membrane protein 1 [KO:K21248]
55014  STX17; syntaxin 17 [KO:K08491]
7405  UVRAG; UV radiation resistance associated [KO:K21249]
51100  SH3GLB1; SH3 domain containing GRB2 like, endophilin B1 [KO:K11248]
9711  RUBCN; rubicon autophagy regulator [KO:K19330]
10645  CAMKK2; calcium/calmodulin dependent protein kinase kinase 2 [KO:K07359] [EC:2.7.11.17]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
2081  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
1612  DAPK1; death associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
1613  DAPK3; death associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
23604  DAPK2; death associated protein kinase 2 [KO:K08803] [EC:2.7.11.1]
3146  HMGB1; high mobility group box 1 [KO:K10802]
118471  PRAP1; proline rich acidic protein 1 [KO:K21250]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
440275  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
8897  MTMR3; myotubularin related protein 3 [KO:K18082] [EC:3.1.3.48 3.1.3.64 3.1.3.95]
9110  MTMR4; myotubularin related protein 4 [KO:K18082] [EC:3.1.3.48 3.1.3.64 3.1.3.95]
64419  MTMR14; myotubularin related protein 14 [KO:K18086] [EC:3.1.3.64 3.1.3.95]
53349  ZFYVE1; zinc finger FYVE-type containing 1 [KO:K17603]
9140  ATG12; autophagy related 12 [KO:K08336]
9474  ATG5; autophagy related 5 [KO:K08339]
55054  ATG16L1; autophagy related 16 like 1 [KO:K17890]
89849  ATG16L2; autophagy related 16 like 2 [KO:K20868]
10533  ATG7; autophagy related 7 [KO:K08337]
83734  ATG10; autophagy related 10 [KO:K17888]
64422  ATG3; autophagy related 3 [KO:K08343]
8837  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
83452  RAB33B; RAB33B, member RAS oncogene family [KO:K07920]
5588  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
11337  GABARAP; GABA type A receptor-associated protein [KO:K08341]
23710  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
11345  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
440738  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
81631  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
84557  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
643246  MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435]
115201  ATG4A; autophagy related 4A cysteine peptidase [KO:K08342] [EC:3.4.22.-]
23192  ATG4B; autophagy related 4B cysteine peptidase [KO:K08342] [EC:3.4.22.-]
84938  ATG4C; autophagy related 4C cysteine peptidase [KO:K08342] [EC:3.4.22.-]
84971  ATG4D; autophagy related 4D cysteine peptidase [KO:K08342] [EC:3.4.22.-]
4077  NBR1; NBR1 autophagy cargo receptor [KO:K17987]
10133  OPTN; optineurin [KO:K19946]
10241  CALCOCO2; calcium binding and coiled-coil domain 2 [KO:K21348]
8887  TAX1BP1; Tax1 binding protein 1 [KO:K21347]
23001  WDFY3; WD repeat and FYVE domain containing 3 [KO:K22262]
7311  UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927]
6233  RPS27A; ribosomal protein S27a [KO:K02977]
7314  UBB; ubiquitin B [KO:K04551]
7316  UBC; ubiquitin C [KO:K08770]
9342  SNAP29; synaptosome associated protein 29 [KO:K08509]
8673  VAMP8; vesicle associated membrane protein 8 [KO:K08512]
10652  YKT6; YKT6 v-SNARE homolog [KO:K08516]
8417  STX7; syntaxin 7 [KO:K08488]
57724  EPG5; ectopic P-granules 5 autophagy tethering factor [KO:K23883]
9842  PLEKHM1; pleckstrin homology and RUN domain containing M1 [KO:K23282]
55823  VPS11; VPS11 core subunit of CORVET and HOPS complexes [KO:K20179]
64601  VPS16; VPS16 core subunit of CORVET and HOPS complexes [KO:K20180]
57617  VPS18; VPS18 core subunit of CORVET and HOPS complexes [KO:K20181]
65082  VPS33A; VPS33A core subunit of CORVET and HOPS complexes [KO:K20182]
23339  VPS39; VPS39 subunit of HOPS complex [KO:K20183]
27072  VPS41; VPS41 subunit of HOPS complex [KO:K20184]
57448  BIRC6; baculoviral IAP repeat containing 6 [KO:K10586] [EC:2.3.2.23]
26003  GORASP2; golgi reassembly stacking protein 2 [KO:K26797]
64689  GORASP1; golgi reassembly stacking protein 1 [KO:K26797]
7879  RAB7A; RAB7A, member RAS oncogene family [KO:K07897]
338382  RAB7B; RAB7B, member RAS oncogene family [KO:K07898]
3916  LAMP1; lysosomal associated membrane protein 1 [KO:K06528]
3920  LAMP2; lysosomal associated membrane protein 2 [KO:K06528]
1509  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
1514  CTSL; cathepsin L [KO:K01365] [EC:3.4.22.15]
1508  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
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
hsa04010  MAPK signaling pathway
hsa04141  Protein processing in endoplasmic reticulum
hsa04142  Lysosome
hsa04150  mTOR signaling pathway
hsa04152  AMPK signaling pathway
hsa04910  Insulin signaling pathway
KO pathway
ko04140   
LinkDB

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