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| | ==Cysteine protease ATG4A== | | ==Cysteine protease ATG4A== |
| - | <StructureSection load='2p82' size='340' side='right' caption='[[2p82]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2p82' size='340' side='right'caption='[[2p82]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2p82]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P82 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2p82]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P82 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATG4A, APG4A, AUTL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATG4A, APG4A, AUTL2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p82 OCA], [http://pdbe.org/2p82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p82 RCSB], [http://www.ebi.ac.uk/pdbsum/2p82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p82 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p82 OCA], [https://pdbe.org/2p82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p82 RCSB], [https://www.ebi.ac.uk/pdbsum/2p82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p82 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ATG4A_HUMAN ATG4A_HUMAN]] Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP.<ref>PMID:15169837</ref> <ref>PMID:12473658</ref> | + | [[https://www.uniprot.org/uniprot/ATG4A_HUMAN ATG4A_HUMAN]] Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP.<ref>PMID:15169837</ref> <ref>PMID:12473658</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Autophagy-related protein|Autophagy-related protein]] | + | *[[Autophagy-related protein 3D structures|Autophagy-related protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Arrowsmith, C H]] | | [[Category: Arrowsmith, C H]] |
| | [[Category: Bochkarev, A]] | | [[Category: Bochkarev, A]] |
| Structural highlights
Function
[ATG4A_HUMAN] Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We have cloned four human cDNAs encoding putative cysteine proteinases that have been tentatively called autophagins. These proteins are similar to Apg4/Aut2, a yeast enzyme involved in the activation of Apg8/Aut7 during the process of autophagy. The identified proteins ranging in length from 393 to 474 amino acids also contain several structural features characteristic of cysteine proteinases including a conserved cysteine residue that is essential for the catalytic properties of these enzymes. Northern blot analysis demonstrated that autophagins are broadly distributed in human tissues, being especially abundant in skeletal muscle. Functional and morphological analysis in autophagy-defective yeast strains lacking Apg4/Aut2 revealed that human autophagins-1 and -3 were able to complement the deficiency in the yeast protease, restoring the phenotypic and biochemical characteristics of autophagic cells. Enzymatic studies performed with autophagin-3, the most widely expressed human autophagin, revealed that the recombinant protein hydrolyzed the synthetic substrate Mca-Thr-Phe-Gly-Met-Dpa-NH(2) whose sequence derives from that present around the Apg4 cleavage site in yeast Apg8/Aut7. This proteolytic activity was diminished by N-ethylmaleimide, an inhibitor of cysteine proteases including yeast Apg4/Aut2. These results provide additional evidence that the autophagic process widely studied in yeast can also be fully reconstituted in human tissues and open the possibility to explore the relevance of the autophagin-based proteolytic system in the induction, regulation, and execution of autophagy.
Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy.,Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C J Biol Chem. 2003 Feb 7;278(6):3671-8. Epub 2002 Nov 21. PMID:12446702[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12. PMID:15169837 doi:10.1242/jcs.01131
- ↑ Scherz-Shouval R, Sagiv Y, Shorer H, Elazar Z. The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A. J Biol Chem. 2003 Apr 18;278(16):14053-8. Epub 2002 Dec 7. PMID:12473658 doi:10.1074/jbc.M212108200
- ↑ Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem. 2003 Feb 7;278(6):3671-8. Epub 2002 Nov 21. PMID:12446702 doi:http://dx.doi.org/10.1074/jbc.M208247200
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