ATG4B

Autophagy related 4B, cysteine peptidase
PDB rendering based on 2cy7.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2CY7​, 2D1I​, 2Z0D​, 2Z0E​, 2ZZP​
Identifiers
Symbols	ATG4B ; APG4B; AUTL1
External IDs	OMIM: 611338 HomoloGene: 100868 IUPHAR: 2329 ChEMBL: 1741221 GeneCards: ATG4B Gene
Gene ontology Molecular function • endopeptidase activity • cysteine-type endopeptidase activity • protein binding • cysteine-type peptidase activity Cellular component • cytoplasm • cytosol Biological process • autophagosome assembly • mitophagy • C-terminal protein lipidation • proteolysis • protein targeting to membrane • autophagy • cellular response to nitrogen starvation • positive regulation of autophagy • protein processing • nucleophagy • positive regulation of protein catabolic process • protein delipidation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23192	66615
Ensembl	ENSG00000168397	ENSMUSG00000026280
UniProt	Q9Y4P1	Q8BGE6
RefSeq (mRNA)	NM_013325	NM_174874
RefSeq (protein)	NP_037457	NP_777363
Location (UCSC)	Chr 2: 241.64 – 241.67 Mb	Chr 1: 93.75 – 93.79 Mb
PubMed search

Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.^[1][2]

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.^[2] One main function of Atg4 is to cleave the pre-protein of Atg8, leading to the non-lapidated 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.^[3][4]

References

1. Mariño G, Uría JA, Puente XS, Quesada V, Bordallo J, López-Otín C (Feb 2003). "Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy". The Journal of Biological Chemistry 278 (6): 3671–8. doi:10.1074/jbc.M208247200. PMID 12446702.
2. "Entrez Gene: ATG4B ATG4 autophagy related 4 homolog B (S. cerevisiae)".
3. 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
4. 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 (Sep 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.

Further reading

• Kraft LJ, Kenworthy AK (Jan 2012). "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. doi:10.1117/1.JBO.17.1.011008. PMC 3380812. PMID 22352642.
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Feb 1999). "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. doi:10.1093/dnares/6.1.63. PMID 10231032.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• 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 (Mar 2001). "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. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T (Jun 2004). "LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation". Journal of Cell Science 117 (Pt 13): 2805–12. doi:10.1242/jcs.01131. PMID 15169837.
• Tanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E (Aug 2004). "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. doi:10.1074/jbc.M401461200. PMID 15187094.
• Tanida I, Ueno T, Kominami E (Nov 2004). "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. doi:10.1074/jbc.M407016200. PMID 15355958.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• 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 (Sep 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
• Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F (Dec 2005). "Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy". The Journal of Biological Chemistry 280 (48): 40058–65. doi:10.1074/jbc.M509158200. PMID 16183633.
• Kumanomidou T, Mizushima T, Komatsu M, Suzuki A, Tanida I, Sou YS, Ueno T, Kominami E, Tanaka K, Yamane T (Jan 2006). "The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers". Journal of Molecular Biology 355 (4): 612–8. doi:10.1016/j.jmb.2005.11.018. PMID 16325851.
• 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 (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Tanida I, Sou YS, Minematsu-Ikeguchi N, Ueno T, Kominami E (Jun 2006). "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. doi:10.1111/j.1742-4658.2006.05260.x. PMID 16704426.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.