Q9H1Y0 · ATG5_HUMAN
- ProteinAutophagy protein 5
- GeneATG5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids275 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. As part of the ATG8 conjugation system with ATG12 and ATG16L1, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity).
May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.
(Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747).
Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601).
Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601).
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAutophagy protein 5
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H1Y0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Preautophagosomal structure membrane ; Peripheral membrane protein
Note: Colocalizes with nonmuscle actin. The conjugate detaches from the membrane immediately before or after autophagosome formation is completed (By similarity).
Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme
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, 25 (SCAR25)
- 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. SCAR25 patients manifest delayed psychomotor development with delayed walking, truncal ataxia, dysmetria, and nystagmus, Cerebellar hypoplasia is seen on brain imaging.
- See alsoMIM:617584
Natural variants in SCAR25
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_079274 | 122 | E>D | in SCAR25; reduced conjugation to ATG12; decrease in autophagy activity; dbSNP:rs1131692265 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_036243 | 58 | in a colorectal cancer sample; somatic mutation | |||
Sequence: K → M | ||||||
Natural variant | VAR_079274 | 122 | in SCAR25; reduced conjugation to ATG12; decrease in autophagy activity; dbSNP:rs1131692265 | |||
Sequence: E → D | ||||||
Mutagenesis | 130 | Loss of conjugaction with ATG12. Does affect interaction with DHX58, nor with MAVS. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 266 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000218994 | 1-275 | Autophagy protein 5 | |||
Sequence: MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVMRQEDISEIWFEYEGTPLKWHYPIGLLFDLLASSSALPWNITVHFKSFPEKDLLHCPSKDAIEAHFMSCMKEADALKHKSQVINEMQKKDHKQLWMGLQNDRFDQFWAINRKLMEYPAEENGFRYIPFRIYQTTTERPFIQKLFRPVAADGQLHTLGDLLKEVCPSAIDPEDGEKKNQVMIHGIEPMLETPLQWLSEHLSYPDNFLHISIIPQPTD | ||||||
Cross-link | 130 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12) | ||||
Sequence: K |
Post-translational modification
Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.
Acetylated by EP300.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells.
Induction
By apoptotic stimuli.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms a conjugate with ATG12 (PubMed:11825910, PubMed:12207896, PubMed:17709747, PubMed:26812546).
Part of the minor complex composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this complex interacts with ATG3 leading to disruption of ATG7 interaction and promotion of ATG8-like proteins lipidation (PubMed:24191030).
Forms an 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (By similarity).
Interacts with TECPR1; the interaction is direct and does not take place when ATG16L1 is associated with the ATG5-ATG12 conjugate (PubMed:21575909, PubMed:22342342).
Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate form. The interaction with MAVS is further enhanced upon vesicular stomatitis virus (VSV) infection (PubMed:17709747).
Interacts with ATG3 (PubMed:11825910, PubMed:12207896).
Interacts with ATG7 and ATG10 (By similarity).
Interacts with FADD (PubMed:15778222).
Interacts with Bassoon/BSN; this interaction is important for the regulation of presynaptic autophagy (By similarity).
Interacts with ATG16L2 (By similarity).
Part of the minor complex composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this complex interacts with ATG3 leading to disruption of ATG7 interaction and promotion of ATG8-like proteins lipidation (PubMed:24191030).
Forms an 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (By similarity).
Interacts with TECPR1; the interaction is direct and does not take place when ATG16L1 is associated with the ATG5-ATG12 conjugate (PubMed:21575909, PubMed:22342342).
Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate form. The interaction with MAVS is further enhanced upon vesicular stomatitis virus (VSV) infection (PubMed:17709747).
Interacts with ATG3 (PubMed:11825910, PubMed:12207896).
Interacts with ATG7 and ATG10 (By similarity).
Interacts with FADD (PubMed:15778222).
Interacts with Bassoon/BSN; this interaction is important for the regulation of presynaptic autophagy (By similarity).
Interacts with ATG16L2 (By similarity).
(Microbial infection) Interacts transiently interacts with hepatitis C virus (HCV) protein NS5B during HCV infection.
(Microbial infection) Interacts with S.flexneri IcsA; bacterial IcsB inhibits this interaction.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9H1Y0-1
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.
- NameLong
- Length275
- Mass (Da)32,447
- Last updated2001-11-16 v2
- ChecksumC33A1E0B3C1DBE5C
Q9H1Y0-2
- NameShort
- SynonymsAPG5beta
- Differences from canonical
- 1-79: MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVMRQEDISEIWFEYEGTPLKW → M
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8Y718 | A0A2R8Y718_HUMAN | ATG5 | 233 | ||
A0A1B0GV54 | A0A1B0GV54_HUMAN | ATG5 | 153 | ||
A0A1B0GUS1 | A0A1B0GUS1_HUMAN | ATG5 | 159 | ||
L7UMD8 | L7UMD8_HUMAN | ATG5 | 44 | ||
L7UQJ2 | L7UQJ2_HUMAN | ATG5 | 162 | ||
Q7Z3H3 | Q7Z3H3_HUMAN | ATG5 | 91 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_003791 | 1-79 | in isoform Short | |||
Sequence: MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVMRQEDISEIWFEYEGTPLKW → M |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y11588 EMBL· GenBank· DDBJ | CAA72327.1 EMBL· GenBank· DDBJ | mRNA | ||
AF293841 EMBL· GenBank· DDBJ | AAG44955.1 EMBL· GenBank· DDBJ | mRNA | ||
CR749386 EMBL· GenBank· DDBJ | CAH18236.1 EMBL· GenBank· DDBJ | mRNA | ||
AL022067 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL133509 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL138917 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002699 EMBL· GenBank· DDBJ | AAH02699.1 EMBL· GenBank· DDBJ | mRNA | ||
BC093011 EMBL· GenBank· DDBJ | AAH93011.1 EMBL· GenBank· DDBJ | mRNA |