Ubiquitin-like-conjugating enzyme ATG3 (ATG3)
The protein contains 314 amino acids for an estimated molecular weight of 35864 Da.
E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Autophagosome assembly
Autophagy of mitochondrion
Autophagy of nucleus
Cellular protein modification process
Macroautophagy
Mitochondrial fragmentation involved in apoptotic process
Negative regulation of phagocytosis
Protein targeting to membrane
Protein ubiquitination
Regulation of cilium assembly
The reference OMIM entry for this protein is 609606
Autophagy 3, s. cerevisiae, homolog of; atg3
Apg3, s. cerevisiae, homolog of; apg3
Apg3-like; apg3l
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by the lysosome or vacuole. Human ATG3 displays the same enzymatic characteristics in vitro as yeast Apg3, a protein-conjugating enzyme essential for autophagy (Tanida et al., 2002).CLONING
By searching an EST database for sequences similar to yeast Apg3, followed by 5-prime RACE of a brain cDNA library, Tanida et al. (2002) cloned ATG3. The deduced 314-amino acid protein has a calculated molecular mass of 35.8 kD. Yeast and human ATG3 share 34.1% amino acid identity, with highest similarity in a region containing the predicted active-site cysteine (cys264 in human). Northern blot analysis detected ATG3 expression in all tissues examined, with highest levels in heart, skeletal muscle, kidney, liver, and placenta. Fluorescence-tagged ATG3 was expressed in the cytosol of transfected human embryonic kidney cells.GENE FUNCTION
Tanida et al. (2002) identified ATG3 as an E2-like protein-conjugating enzyme for 3 homologs of yeast Apg8, MAPLC3 (see 601242), GATE16 (GABARAPL2; 607452), and GABARAP (605125). ATG3 formed an enzyme-substrate intermediate via a thiol ester bond that showed rapid turnover. Replacement of the active-site cysteine of ATG3 with serine (C264S) resulted in the formation of a stable O-ester bond that allowed visualization of stable intermediates. Overexpression of ATG7 (608760) enhanced the formation of stable E2-substrate complexes between ATG3-C264S and each of the Apg8 homologs. MAPLC3 was the preferred substrate, and the reaction with MAPLC3 occurred predominantly in the cytosol. Coimmunoprecipitation of ATG7 with ATG3 indicated that ATG3 forms an E1-E2 complex with ATG7, similar to the yeast Apg3-Apg7 complex. Overexpression of ATG3 facilitated formation of the ATG12 (609608)-ATG5 (604261) conjugate, suggesting that ATG3 cross-talks with the ATG12 conjugation system.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ATG3 gene to chromosome 3 (TMAP RH120928). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609606 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed