KEGG   PATHWAY: hsa04140Help
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
BRITE hierarchy
Pathway map
Autophagy - animal
hsa04140

All organismsOrtholog table
Disease
H00286  
Crohn's disease
H01227  
Inflammatory bowel disease (IBD)
Drug
D00595  
Buformin (USAN/INN)
D00944  
Metformin hydrochloride (JP17/USP)
D02206  
Buformin hydrochloride (JP17)
D03647  
Dapiclermin (USAN/INN)
D04966  
Metformin (USAN/INN)
D08351  
Phenformin (BAN)
D08352  
Phenformin hydrochloride
Other DBs
BSID: 
GO: 
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:3.1.3.67 3.1.3.48 3.1.3.16]
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; related RAS viral (r-ras) oncogene homolog [KO:K07829]
22800  
RRAS2; related RAS viral (r-ras) oncogene homolog 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 alpha subunit [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 enriched in brain [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 [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]
285973  
ATG9B; autophagy related 9B [KO:K17907]
79065  
ATG9A; autophagy related 9A [KO:K17907]
55578  
SUPT20H; SPT20 homolog, SAGA complex component [KO:K21245]
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:2.7.11.11]
5563  
PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
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; RUN and cysteine rich domain containing beclin 1 interacting protein [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:3.1.26.- 2.7.11.1]
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:3.1.3.95 3.1.3.64 3.1.3.48]
9110  
MTMR4; myotubularin related protein 4 [KO:K18082] [EC:3.1.3.95 3.1.3.64 3.1.3.48]
64419  
MTMR14; myotubularin related protein 14 [KO:K18086] [EC:3.1.3.95 3.1.3.64]
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]
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.-]
3916  
LAMP1; lysosomal associated membrane protein 1 [KO:K06528]
3920  
LAMP2; lysosomal associated membrane protein 2 [KO:K06528]
7879  
RAB7A; RAB7A, member RAS oncogene family [KO:K07897]
338382  
RAB7B; RAB7B, member RAS oncogene family [KO:K07898]
8673  
VAMP8; vesicle associated membrane protein 8 [KO:K08512]
9342  
SNAP29; synaptosome associated protein 29 [KO:K08509]
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
C00350  
Phosphatidylethanolamine
C01194  
1-Phosphatidyl-D-myo-inositol
C04549  
1-Phosphatidyl-1D-myo-inositol 3-phosphate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
KO pathway
 

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