Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)
The protein contains 703 amino acids for an estimated molecular weight of 77960 Da.
E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for 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. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Plays also a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (By similarity). (updated: Dec. 5, 2018)
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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| Variant | Description |
|---|---|
| dbSNP:rs36117895 |
Biological Process
Adult walking behavior
Aging
Autophagosome assembly
Autophagy
Autophagy of mitochondrion
C-terminal protein lipidation
Cardiac muscle cell development
Cellular amino acid metabolic process
Cellular protein modification process
Cellular response to hyperoxia
Cellular response to morphine
Cellular response to nitrogen starvation
Cellular response to starvation
Central nervous system neuron axonogenesis
Cerebellar Purkinje cell layer development
Cerebral cortex development
Chaperone-mediated autophagy
Defense response to virus
Late nucleophagy
Liver development
Macroautophagy
Membrane fusion
Negative regulation of apoptotic process
Negative regulation of histone H4-K16 acetylation
Negative regulation of mitochondrial DNA replication
Negative regulation of oxidative stress-induced neuron death
Negative stranded viral RNA replication
Nervous system process
Neutrophil degranulation
Piecemeal microautophagy of the nucleus
Positive regulation by symbiont of host autophagy
Positive regulation of apoptotic process
Positive regulation of autophagy
Positive regulation of macroautophagy
Positive regulation of mucus secretion
Positive regulation of protein catabolic process
Positive regulation of protein modification process
Post-embryonic development
Protein catabolic process
Protein lipidation
Protein modification by small protein conjugation
Protein transport
Pyramidal neuron development
Regulation of autophagy of mitochondrion
Regulation of circadian rhythm
Regulation of protein ubiquitination
Response to fluoride
Response to glucose
Rhythmic process
Suppression by virus of host autophagy
The reference OMIM entry for this protein is 608760
Autophagy 7, s. cerevisiae, homolog of; atg7
Apg7, s. cerevisiae, homolog of, apg7
Apg7-like; apg7l
Gsa7
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by the lysosomal/vacuolar system. ATG7 is a ubiquitin-activating enzyme E1 (see 314370)-like protein essential for the Apg12 (ATG12; 609608) conjugation system that mediates membrane fusion in autophagy (Tanida et al., 2001).CLONING
Yuan et al. (1999) identified several APG7L ESTs by searching a database for sequences similar to P. pastoris Apg7, and they sequenced an APG7L cDNA from an infant brain cDNA library. The deduced 703-amino acid protein contains a central putative E1-like ATP-binding site (GxGxxG), conserved charged amino acids flanking the GxGxxG motif, and a putative E1 active site with a conserved catalytic cysteine. APG7L shares similarity with the E1 enzymes UBA2 and UBA3 (UBE1C; 603172), and it shares 38% identity with yeast Apg7. EST database analysis indicated that APG7L is expressed by many diverse tissues. Tanida et al. (2001) found that APG7L expressed by transfected human embryonic kidney cells had an apparent molecular mass of about 80 kD.MAPPING
Gross (2012) mapped the ATG7 gene to chromosome 3p25.3 based on an alignment of the ATG7 sequence (GenBank GENBANK BC000091) with the genomic sequence (GRCh37).GENE FUNCTION
Using yeast 2-hybrid analysis, Tanida et al. (2001) found that APG7L interacts with APG12L. Site-directed mutagenesis revealed that cys572 of APG7L is an active site cysteine essential for formation of the APG7L-APG12L intermediate. Overexpression of APG7L enhanced the formation of the APG5L (ATG5; 604261)-APG12L conjugate, indicating that APG7L is an E1-like enzyme essential for the APG12 conjugation system. Cross-linking experiments and glycerol-gradient centrifugation analysis showed that APG7L forms homodimers. Coimmunoprecipitation studies indicated that 3 human Apg8 counterparts, GATE16 (GABARAPL2; 607452), GABARAP (605125), and MAP1ALC3 (601242), also form conjugates with APG7L. Like E1 enzymes, APG7L carrying a mutation of the active site cysteine (cys572 to ser) formed a stable intermediate via an O-ester bond instead of a thioester bond. Tanida et al. (2002) found that ATG7 coimmunoprecipitated with ATG3 (609606), indicating that ATG3 forms an E1-E2 complex with ATG7, similar to the yeast Apg3-Apg7 complex. Yu et al. (2004) defined a novel molecular pathway in which activation of the receptor-interacting protein (RIP; 603453), a serine-threonine kinase, and Jun amino-terminal kinase (601158) induced cell death with the morphology of autophagy. Autophagic death required the genes ATG7 (GSA7) and beclin-1 (604378) and was induced by caspase-8 (601763) inhibition. Yu et al. (2004) cautioned that clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death. Sanjuan et al. (2007) demonstrated that a particle that engages Toll-like receptors on a murine macrophage while it is phagocytosed triggers the autophagosome marker LC3 (601242) to be rapidly recruited to the phagosome in a manner that depends on the autophagy pathway proteins ATG5 and ATG7; this process is preceded by recruitment of beclin-1 and phosphoinositide-3-OH kinase activity. Translocation of beclin-1 and LC3 to the phagosome was not associated with observable double-membrane structures characteristic of conventional autophagosomes, but was associated with phagosome fusion with lysosomes, leading to rapid acidification and en ... More on the omim web site
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 608760 was added.