ATG4B

ATG4B
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2CY7, 2D1I, 2Z0D, 2Z0E, 2ZZP
Identifiers
Aliases	ATG4B , APG4B, AUTL1, autophagy related 4B cysteine peptidase, HsAPG4B
External IDs	OMIM: 611338; MGI: 1913865; HomoloGene: 100868; GeneCards: ATG4B; OMA:ATG4B - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	241,673,857 bp
RNA expression pattern
	Top expressed in
	anterior pituitary; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; canal of the cervix; ; gallbladder; ; gastric mucosa; ; stromal cell of endometrium; ; right uterine tube; ; tibial nerve; ; body of stomach;
	n/a
	More reference expression data
	n/a
Gene ontology
Molecular function	peptidase activity ; cysteine-type peptidase activity ; endopeptidase activity ; protein binding ; hydrolase activity ; cysteine-type endopeptidase activity ;
Cellular component	cytoplasm ; cytosol ;
Biological process	autophagy ; protein transport ; autophagy of nucleus ; C-terminal protein lipidation ; positive regulation of protein catabolic process ; autophagy of mitochondrion ; autophagosome assembly ; macroautophagy ; proteolysis ; protein targeting to membrane ; protein delipidation ;
	Sources:Amigo / QuickGO
Orthologs
	23192
	66615
	ENSG00000168397
	n/a
	Q9Y4P1
	Q8BGE6
	NM_013325 ; NM_178326
	NM_174874 ; NM_001368266
	NP_037457 ; NP_847896
	NP_777363 ; NP_001355195
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated May 26, 2024

Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.^[4]

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.^[4] 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.^[5]^[6]

Related Research Articles

Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16.

Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.

Autophagy protein 5 (ATG5) is a protein that, in humans, is encoded by the ATG5 gene located on chromosome 6. It is an E3 ubi autophagic cell death. ATG5 is a key protein involved in the extension of the phagophoric membrane in autophagic vesicles. It is activated by ATG7 and forms a complex with ATG12 and ATG16L1. This complex is necessary for LC3-I conjugation to PE (phosphatidylethanolamine) to form LC3-II. ATG5 can also act as a pro-apoptotic molecule targeted to the mitochondria. Under low levels of DNA damage, ATG5 can translocate to the nucleus and interact with survivin.

Microtubule-associated proteins 1A/1B light chain 3B is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.

Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene. Two transcript variants encoding different isoforms have been found for this gene.

Tax1-binding protein 1 is a protein that in humans is encoded by the TAX1BP1 gene.

Actin-binding LIM protein 3 is a protein that in humans is encoded by the ABLIM3 gene.

Polyadenylate-binding protein-interacting protein 2 is a protein that in humans is encoded by the PAIP2 gene.

Myotubularin-related protein 6 is a protein that in humans is encoded by the MTMR6 gene.

Gamma-aminobutyric acid receptor-associated protein-like 2 is a protein that in humans is encoded by the GABARAPL2 gene.

Autophagy-related protein 10 is a protein that in humans is encoded by the ATG10 gene.

Autophagy related 12 is a protein that in humans is encoded by the ATG12 gene.

Uncharacterized protein KIAA1267 is a protein that in humans is encoded by the KIAA1267 gene.

Ubiquitin-like modifier-activating enzyme 5 is a protein that in humans is encoded by the UBA5 gene.

LisH domain-containing protein ARMC9 is a protein that in humans is encoded by the ARMC9 gene.

RNA-binding protein MEX3B is a protein that in humans is encoded by the MEX3B gene.

Autophagy related 7 is a protein in humans encoded by ATG7 gene. Related to GSA7; APG7L; APG7-LIKE.

Zinc finger protein 34 is a protein that in humans is encoded by the ZNF34 gene.

Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals, this article mainly focuses on its role in lower eukaryotes such as Saccharomyces cerevisiae.

In molecular biology, autophagy related 3 (Atg3) is the E2 enzyme for the LC3 lipidation process. It is essential for autophagy. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000168397 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: ATG4B ATG4 autophagy related 4 homolog B (S. cerevisiae)".
↑ 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.
↑ 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. hdl: 11858/00-001M-0000-0010-8592-0 . PMID 16169070. S2CID 8235923.

External links

Human ATG4B genome location and ATG4B gene details page in the UCSC Genome Browser .

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): 011008–011008–13. Bibcode:2012JBO....17a1008K. 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. hdl: 11858/00-001M-0000-0010-8592-0 . PMID 16169070. S2CID 8235923.
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. S2CID 11899126.
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. S2CID 7827573.
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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000168397 – Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-4] 1 2 "Entrez Gene: ATG4B ATG4 autophagy related 4 homolog B (S. cerevisiae)".

[pmid17353931-5] 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.

[pmid16169070-6] 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. hdl: 11858/00-001M-0000-0010-8592-0 . PMID 16169070. S2CID 8235923.

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