O95352 · ATG7_HUMAN
- ProteinUbiquitin-like modifier-activating enzyme ATG7
- GeneATG7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids703 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes (PubMed:34161705).
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. Also plays 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).
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. Also plays 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).
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 572 | Glycyl thioester intermediate | ||||
Sequence: C |
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin-like modifier-activating enzyme ATG7
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO95352
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 31 (SCAR31)
- Note
- DescriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is characterized by global developmental delay, hypotonia, variably impaired intellectual and language development, ataxic gait, tremor, and dysarthria. Most affected individuals have optic atrophy. Additional features may include retinitis pigmentosa, sensorineural deafness, dysmorphic facial features, and possibly endocrine dysfunction.
- See alsoMIM:619422
Natural variants in SCAR31
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085979 | 234 | P>T | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |
VAR_085980 | 261 | Q>R | in SCAR31; uncertain significance | |
VAR_085981 | 511 | G>D | in SCAR31; results in severely decreased LC3-I lipidation to form LC3-II | |
VAR_085982 | 512 | L>P | in SCAR31; in homozygous patient cells it results in diminished autophagic flux | |
VAR_085983 | 576 | R>H | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |
VAR_085984 | 588 | V>M | in SCAR31; results in severely decreased LC3-I lipidation to form LC3-II | |
VAR_085985 | 624 | H>Y | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |
VAR_085986 | 659-703 | missing | in SCAR31 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 15 | Impairs conjugation activity; when associated with D-16 and D-17. | ||||
Sequence: F → D | ||||||
Mutagenesis | 16 | Impairs conjugation activity; when associated with D-15 and D-17. | ||||
Sequence: A → D | ||||||
Mutagenesis | 17 | Impairs conjugation activity; when associated with D-15 and D-16. | ||||
Sequence: P → D | ||||||
Mutagenesis | 45 | Impairs interaction with ATG12. Impairs inrteraction with MAP1LC3B. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_085979 | 234 | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |||
Sequence: P → T | ||||||
Mutagenesis | 243 | Moderately impairs ATG3 binding. Moderately reduces GABARAP-ATG3 thioester bond formation. Moderately reduces GABARAP lipidation. | ||||
Sequence: W → A | ||||||
Mutagenesis | 246 | Almost completely impairs ATG3 binding. Severely reduces GABARAP-ATG3 thioester bond formation. Severely reduces GABARAP lipidation. | ||||
Sequence: R → D | ||||||
Natural variant | VAR_085980 | 261 | in SCAR31; uncertain significance | |||
Sequence: Q → R | ||||||
Natural variant | VAR_053014 | 471 | in dbSNP:rs36117895 | |||
Sequence: V → A | ||||||
Natural variant | VAR_085981 | 511 | in SCAR31; results in severely decreased LC3-I lipidation to form LC3-II | |||
Sequence: G → D | ||||||
Natural variant | VAR_085982 | 512 | in SCAR31; in homozygous patient cells it results in diminished autophagic flux | |||
Sequence: L → P | ||||||
Mutagenesis | 572 | Loss of LC3-I lipidation to form LC3-II. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_085983 | 576 | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |||
Sequence: R → H | ||||||
Natural variant | VAR_085984 | 588 | in SCAR31; results in severely decreased LC3-I lipidation to form LC3-II | |||
Sequence: V → M | ||||||
Natural variant | VAR_085985 | 624 | in SCAR31; results in decreased LC3-I lipidation to form LC3-II | |||
Sequence: H → Y | ||||||
Natural variant | VAR_085986 | 659-703 | in SCAR31 | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 716 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000212806 | 2-703 | Ubiquitin-like modifier-activating enzyme ATG7 | |||
Sequence: AAATGDPGLSKLQFAPFSSALDVGFWHELTQKKLNEYRLDEAPKDIKGYYYNGDSAGLPARLTLEFSAFDMSAPTPARCCPAIGTLYNTNTLESFKTADKKLLLEQAANEIWESIKSGTALENPVLLNKFLLLTFADLKKYHFYYWFCYPALCLPESLPLIQGPVGLDQRFSLKQIEALECAYDNLCQTEGVTALPYFLIKYDENMVLVSLLKHYSDFFQGQRTKITIGVYDPCNLAQYPGWPLRNFLVLAAHRWSSSFQSVEVVCFRDRTMQGARDVAHSIIFEVKLPEMAFSPDCPKAVGWEKNQKGGMGPRMVNLSECMDPKRLAESSVDLNLKLMCWRLVPTLDLDKVVSVKCLLLGAGTLGCNVARTLMGWGVRHITFVDNAKISYSNPVRQPLYEFEDCLGGGKPKALAAADRLQKIFPGVNARGFNMSIPMPGHPVNFSSVTLEQARRDVEQLEQLIESHDVVFLLMDTRESRWLPAVIAASKRKLVINAALGFDTFVVMRHGLKKPKQQGAGDLCPNHPVASADLLGSSLFANIPGYKLGCYFCNDVVAPGDSTRDRTLDQQCTVSRPGLAVIAGALAVELMVSVLQHPEGGYAIASSSDDRMNEPPTSLGLVPHQIRGFLSRFDNVLPVSLAFDKCTACSSKVLDQYEREGFNFLAKVFNSSHSFLEDLTGLTLLHQETQAAEIWDMSDDETI | ||||||
Cross-link | 45 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 698 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Acetylated by EP300.
Polyubiquitinated on Lys-45 via 'Lys-63'-linked ubiquitin by TRIM32; this modification positiely regulates ATG8 and ATG12 activating enzyme activity leading to initiation of autophagy under metabolic stress.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.
Induction
Expression is up-regulated by the transcription factor HSF1.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (PubMed:11096062).
Interacts with ATG3; this interaction is essential for the transfer of ATG8-like proteins's thioester from ATG7 to ATG3 and plays a role in the conjugation of ATG12 to ATG5 (PubMed:11825910, PubMed:26043688).
Interacts with ATG12 (PubMed:11096062, PubMed:11825910).
Forms intermediate conjugates with GABARAPL1 (By similarity).
Forms intermediate conjugates with ATG8-like proteins such as GABARAP, GABARAPL2 or MAP1LC3A (PubMed:11096062, PubMed:16303767).
Interacts with EP300 acetyltransferase (PubMed:19124466).
Interacts with FOXO1 (PubMed:20543840).
Interacts with ATG3; this interaction is essential for the transfer of ATG8-like proteins's thioester from ATG7 to ATG3 and plays a role in the conjugation of ATG12 to ATG5 (PubMed:11825910, PubMed:26043688).
Interacts with ATG12 (PubMed:11096062, PubMed:11825910).
Forms intermediate conjugates with GABARAPL1 (By similarity).
Forms intermediate conjugates with ATG8-like proteins such as GABARAP, GABARAPL2 or MAP1LC3A (PubMed:11096062, PubMed:16303767).
Interacts with EP300 acetyltransferase (PubMed:19124466).
Interacts with FOXO1 (PubMed:20543840).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O95352 | EEF1D P29692 | 2 | EBI-987834, EBI-358607 | |
BINARY | O95352 | GABARAP O95166 | 8 | EBI-987834, EBI-712001 | |
BINARY | O95352 | GABARAPL1 Q9H0R8 | 6 | EBI-987834, EBI-746969 | |
BINARY | O95352 | GABARAPL2 P60520 | 8 | EBI-987834, EBI-720116 | |
BINARY | O95352 | IRF2 P14316 | 2 | EBI-987834, EBI-2866589 | |
BINARY | O95352 | MAP1LC3B Q9GZQ8 | 7 | EBI-987834, EBI-373144 | |
BINARY | O95352 | RWDD2A Q9UIY3 | 3 | EBI-987834, EBI-17677006 | |
BINARY | O95352 | SIRT1 Q96EB6 | 3 | EBI-987834, EBI-1802965 | |
BINARY | O95352-2 | TARDBP Q13148 | 3 | EBI-15980880, EBI-372899 | |
BINARY | O95352-2 | TP53 P04637 | 4 | EBI-15980880, EBI-366083 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 15-17 | FAP motif | ||||
Sequence: FAP |
Domain
The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12.
The N-terminal FAP motif (residues 15 to 17) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates.
Sequence similarities
Belongs to the ATG7 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
O95352-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length703
- Mass (Da)77,960
- Last updated1999-05-01 v1
- ChecksumABBD1A29A6C58356
O95352-2
- Name2
- Differences from canonical
- 626-652: Missing
O95352-3
- Name3
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_045206 | 138-176 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 210 | in Ref. 2; BAG64682 | ||||
Sequence: V → A | ||||||
Sequence conflict | 346 | in Ref. 2; BAG64682 | ||||
Sequence: P → L | ||||||
Alternative sequence | VSP_013205 | 626-652 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_045207 | 653-693 | in isoform 3 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF094516 EMBL· GenBank· DDBJ | AAC69630.1 EMBL· GenBank· DDBJ | mRNA | ||
AK303694 EMBL· GenBank· DDBJ | BAG64682.1 EMBL· GenBank· DDBJ | mRNA | ||
AC020750 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC022001 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC026185 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC083855 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000091 EMBL· GenBank· DDBJ | AAH00091.1 EMBL· GenBank· DDBJ | mRNA | ||
AL122075 EMBL· GenBank· DDBJ | CAB59250.1 EMBL· GenBank· DDBJ | mRNA |