| Structural highlights
Function
ATG5_HUMAN Involved in autophagy vesicles formation. Conjugation with ATG12 through an ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus. HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures; as well as in normal adipocyte differentiation.[1] [2] [3] [4] [5] [6] May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.[7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health.
Mutation in reduces autophagy and leads to ataxia with developmental delay.,Kim M, Sandford E, Gatica D, Qiu Y, Liu X, Zheng Y, Schulman BA, Xu J, Semple I, Ro SH, Kim B, Mavioglu RN, Tolun A, Jipa A, Takats S, Karpati M, Li JZ, Yapici Z, Juhasz G, Lee JH, Klionsky DJ, Burmeister M Elife. 2016 Jan 26;5. pii: e12245. doi: 10.7554/eLife.12245. PMID:26812546[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grand RJ, Milner AE, Mustoe T, Johnson GD, Owen D, Grant ML, Gregory CD. A novel protein expressed in mammalian cells undergoing apoptosis. Exp Cell Res. 1995 Jun;218(2):439-51. PMID:7796880 doi:http://dx.doi.org/S0014-4827(85)71177-9
- ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
- ↑ Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem. 2005 May 27;280(21):20722-9. Epub 2005 Mar 18. PMID:15778222 doi:http://dx.doi.org/10.1074/jbc.M413934200
- ↑ Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5. Epub 2007 Aug 20. PMID:17709747 doi:http://dx.doi.org/10.1073/pnas.0704014104
- ↑ Guevin C, Manna D, Belanger C, Konan KV, Mak P, Labonte P. Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection. Virology. 2010 Sep 15;405(1):1-7. doi: 10.1016/j.virol.2010.05.032. Epub 2010 Jun, 26. PMID:20580051 doi:http://dx.doi.org/10.1016/j.virol.2010.05.032
- ↑ Mai S, Muster B, Bereiter-Hahn J, Jendrach M. Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy. 2012 Jan;8(1):47-62. doi: 10.4161/auto.8.1.18174. Epub 2012 Jan 1. PMID:22170153 doi:http://dx.doi.org/10.4161/auto.8.1.18174
- ↑ Grand RJ, Milner AE, Mustoe T, Johnson GD, Owen D, Grant ML, Gregory CD. A novel protein expressed in mammalian cells undergoing apoptosis. Exp Cell Res. 1995 Jun;218(2):439-51. PMID:7796880 doi:http://dx.doi.org/S0014-4827(85)71177-9
- ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
- ↑ Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem. 2005 May 27;280(21):20722-9. Epub 2005 Mar 18. PMID:15778222 doi:http://dx.doi.org/10.1074/jbc.M413934200
- ↑ Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5. Epub 2007 Aug 20. PMID:17709747 doi:http://dx.doi.org/10.1073/pnas.0704014104
- ↑ Guevin C, Manna D, Belanger C, Konan KV, Mak P, Labonte P. Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection. Virology. 2010 Sep 15;405(1):1-7. doi: 10.1016/j.virol.2010.05.032. Epub 2010 Jun, 26. PMID:20580051 doi:http://dx.doi.org/10.1016/j.virol.2010.05.032
- ↑ Mai S, Muster B, Bereiter-Hahn J, Jendrach M. Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy. 2012 Jan;8(1):47-62. doi: 10.4161/auto.8.1.18174. Epub 2012 Jan 1. PMID:22170153 doi:http://dx.doi.org/10.4161/auto.8.1.18174
- ↑ Kim M, Sandford E, Gatica D, Qiu Y, Liu X, Zheng Y, Schulman BA, Xu J, Semple I, Ro SH, Kim B, Mavioglu RN, Tolun A, Jipa A, Takats S, Karpati M, Li JZ, Yapici Z, Juhasz G, Lee JH, Klionsky DJ, Burmeister M. Mutation in reduces autophagy and leads to ataxia with developmental delay. Elife. 2016 Jan 26;5. pii: e12245. doi: 10.7554/eLife.12245. PMID:26812546 doi:http://dx.doi.org/10.7554/eLife.12245
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