IED ID | IndEnz0002019030 |
Enzyme Type ID | protease019030 |
Protein Name |
Gamma-aminobutyric acid receptor-associated protein-like 2 GABA A receptor-associated protein-like 2 Ganglioside expression factor 2 GEF-2 General protein transport factor p16 Golgi-associated ATPase enhancer of 16 kDa GATE-16 MAP1 light chain 3-related protein |
Gene Name | GABARAPL2 FLC3A GEF2 |
Organism | Homo sapiens (Human) |
Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
Enzyme Sequence | MKWMFKEDHSLEHRCVESAKIRAKYPDRVPVIVEKVSGSQIVDIDKRKYLVPSDITVAQFMWIIRKRIQLPSEKAIFLFVDKTVPQSSLTMGQLYEKEKDEDGFLYVAYSGENTFGF |
Enzyme Length | 117 |
Uniprot Accession Number | P60520 |
Absorption | |
Active Site | |
Activity Regulation | |
Binding Site | |
Calcium Binding | |
catalytic Activity | |
DNA Binding | |
EC Number | |
Enzyme Function | FUNCTION: Ubiquitin-like modifier involved in intra-Golgi traffic (By similarity). Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation (By similarity). It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy (PubMed:20418806, PubMed:23209295). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (PubMed:20418806, PubMed:23209295). Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:20418806, PubMed:23209295). {ECO:0000250|UniProtKB:P60519, ECO:0000269|PubMed:20418806, ECO:0000269|PubMed:23209295}. |
Temperature Dependency | |
PH Dependency | |
Pathway | |
nucleotide Binding | |
Features | Beta strand (5); Chain (1); Helix (4); Lipidation (2); Modified residue (4); Mutagenesis (5); Natural variant (1); Propeptide (1); Sequence conflict (1); Site (1) |
Keywords | 3D-structure;Acetylation;Autophagy;Cytoplasmic vesicle;Endoplasmic reticulum;Golgi apparatus;Lipoprotein;Membrane;Phosphoprotein;Protein transport;Reference proteome;Transport |
Interact With | Q6RW13; Q8IVF2-2; Q9P2R3; Q8N6T3; Q8N6T3-2; O75143; Q676U5; Q2TAZ0; Q9NT62; Q9Y4P1; O95352; Q9BXK5; O60238; Q9NW68; Q9P1Z2; Q13137; Q8WXU2; P63167; Q96FJ2; P00533; Q8IVP5; Q9BQS8; P40939; P54257; Q2T9L4; O00410; Q8N6L0; Q86V97; Q8WVZ9; Q8N8K9; Q96L93-6; P60409; P60411; Q8N653; Q9UH92; Q9UH92-3; Q14596; P46934; P46934-3; Q8TD19; O75323; Q9NV35; Q9H4L5; Q15154; Q9NS23; Q8WWW0; Q14257; Q9H6L5-1; Q9H6L5-2; Q86VR2; Q8IZE3-2; Q9H0K1; Q13501; O95210; Q13188; Q13043; Q86VP1; Q8TC07; Q3MII6; Q9UPU7; B9A6K1; Q92609; Q66K14-2; O15040; Q9Y6I9; Q15025; Q96A56; Q9H8W5-2; Q969E8; Q9GZZ9; O75385; Q8IZQ1; Q8N680; Q6NX45; Q9Z2F7 |
Induction | |
Subcellular Location | SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:12507496, ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19056683, ECO:0000269|PubMed:22311637, ECO:0000269|PubMed:31709703}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:30990354}. Golgi apparatus {ECO:0000250|UniProtKB:P60519}. |
Modified Residue | MOD_RES 24; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 39; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:17525332; MOD_RES 87; /note=Phosphoserine; by TBK1; /evidence=ECO:0000269|PubMed:31709703; MOD_RES 88; /note=Phosphoserine; by TBK1; /evidence=ECO:0000269|PubMed:31709703 |
Post Translational Modification | PTM: The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, GABARAPL2-I (PubMed:15169837, PubMed:20818167, PubMed:30661429, PubMed:31709703). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, GABARAPL2-II (PubMed:15169837, PubMed:31709703). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (PubMed:33909989). ATG4 proteins also mediate the delipidation of PE-conjugated forms required for GABARAPL2 recycling when autophagosomes fuse with lysosomes (PubMed:29458288, PubMed:31709703, PubMed:33909989). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (PubMed:33909989). ATG4B constitutes the major protein for proteolytic activation (PubMed:30661429). ATG4D is the main enzyme for delipidation activity (By similarity). {ECO:0000250|UniProtKB:P60521, ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:20818167, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:30661429, ECO:0000269|PubMed:31709703, ECO:0000269|PubMed:33909989}.; PTM: (Microbial infection) The Legionella effector RavZ is a deconjugating enzyme that hydrolyzes the amide bond between the C-terminal glycine residue and an adjacent aromatic residue in ATG8 proteins conjugated to phosphatidylethanolamine (PE), producing an ATG8 protein that is resistant to reconjugation by the host machinery due to the cleavage of the reactive C-terminal glycine (PubMed:31722778). RavZ is also able to mediate delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (PubMed:33909989). {ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:33909989}.; PTM: Phosphorylation at Ser-87 and Ser-88 by TBK1 prevents interaction with ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) (PubMed:31709703). Phosphorylation by TBK1 on autophagosomes prevents their delipidation by ATG4 and premature removal from nascent autophagosomes (PubMed:31709703). {ECO:0000269|PubMed:31709703}. |
Signal Peptide | |
Structure 3D | NMR spectroscopy (1); X-ray crystallography (2) |
Cross Reference PDB | 4CO7; 6H8C; 7LK3; |
Mapped Pubmed ID | 15187094; 16169070; 16189514; 16303767; 17353931; 18321988; 18768753; 18776740; 19250911; 19322194; 19533740; 19549727; 19844255; 20010802; 20010805; 20029029; 20468064; 21177865; 21497758; 21669198; 21684337; 21900206; 21988832; 22170151; 22885598; 22959883; 23112293; 23891751; 24269818; 24747438; 25181299; 25416956; 25568151; 25609649; 26284781; 27764541; 27879200; 28512061; 28729737; 29038162; 29230017; 29496607; 29544880; 30218067; 30282803; 31006537; 31960529; 32094251; 32437499; 32685442; 33374830; 33845085; 33949974; |
Motif | |
Gene Encoded By | |
Mass | 13,667 |
Kinetics | |
Metal Binding | |
Rhea ID | |
Cross Reference Brenda |