ATG4B explained

Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.^[1]

Function

Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[1] One main function of Atg4 is to cleave the pre-protein of Atg8, leading to the non-lipidated soluble (-I) form which can be processed further by Atg3, Atg7, Atg5-12 into the lipidated form (-II) anchored to the autophagic membrane.

Interactions

ATG4B has been shown to interact with GABARAPL2.^{[2] [3]}

Further reading

• Kraft LJ, Kenworthy AK . Imaging protein complex formation in the autophagy pathway: analysis of the interaction of LC3 and Atg4B(C74A) in live cells using Förster resonance energy transfer and fluorescence recovery after photobleaching . Journal of Biomedical Optics . 17 . 1 . 011008–011008–13 . Jan 2012 . 22352642 . 3380812 . 10.1117/1.JBO.17.1.011008 . 2012JBO....17a1008K .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 1 . 63–70 . Feb 1999 . 10231032 . 10.1093/dnares/6.1.63 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T . LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation . Journal of Cell Science . 117 . Pt 13 . 2805–12 . Jun 2004 . 15169837 . 10.1242/jcs.01131 . free .
• Tanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E . HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates . The Journal of Biological Chemistry . 279 . 35 . 36268–76 . Aug 2004 . 15187094 . 10.1074/jbc.M401461200 . free .
• Tanida I, Ueno T, Kominami E . Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes . The Journal of Biological Chemistry . 279 . 46 . 47704–10 . Nov 2004 . 15355958 . 10.1074/jbc.M407016200 . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . Sep 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F . Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy . The Journal of Biological Chemistry . 280 . 48 . 40058–65 . Dec 2005 . 16183633 . 10.1074/jbc.M509158200 . free .
• Kumanomidou T, Mizushima T, Komatsu M, Suzuki A, Tanida I, Sou YS, Ueno T, Kominami E, Tanaka K, Yamane T . The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers . Journal of Molecular Biology . 355 . 4 . 612–8 . Jan 2006 . 16325851 . 10.1016/j.jmb.2005.11.018 .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415-8 . Jan 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .
• Tanida I, Sou YS, Minematsu-Ikeguchi N, Ueno T, Kominami E . Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3 . The FEBS Journal . 273 . 11 . 2553–62 . Jun 2006 . 16704426 . 10.1111/j.1742-4658.2006.05260.x . 11899126 . free .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . Nov 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Web site: Entrez Gene: ATG4B ATG4 autophagy related 4 homolog B (S. cerevisiae).
2. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
3. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . Sep 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .