{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9H1Y0","secondaryAccessions":["O60875","Q5JVR2","Q68DI4","Q9H2B8","Q9HCZ7"],"uniProtkbId":"ATG5_HUMAN","entryAudit":{"firstPublicDate":"2001-11-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-11-16","entryVersion":205,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Autophagy protein 5"}},"alternativeNames":[{"fullName":{"value":"APG5-like"}},{"fullName":{"value":"Apoptosis-specific protein"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:589"}],"value":"ATG5"},"synonyms":[{"value":"APG5L"},{"value":"ASP"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q99J83"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12207896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20580051"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22170153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26812546"}],"value":"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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15778222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7796880"}],"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17709747"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19666601"}],"value":"(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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q99J83"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11825910"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12207896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15778222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17709747"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21575909"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22342342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24191030"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26812546"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32960676"}],"value":"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). The ATG12-ATG5 conjugate interacts with RAB33A; this interaction is bridged by ATG16L1 and promotes ATG12-ATG5-ATG16L1 complex recruitment to phagophores (PubMed:32960676). 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)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20580051"}],"value":"(Microbial infection) Interacts transiently interacts with hepatitis C virus (HCV) protein NS5B during HCV infection"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15576571"}],"value":"(Microbial infection) Interacts with S.flexneri IcsA; bacterial IcsB inhibits this 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The conjugate detaches from the membrane immediately before or after autophagosome formation is completed (By similarity). Also localizes to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme. Under starved conditions, the ATG12-ATG5-ATG16L1 complex is translocated to phagophores driven by RAB33B (PubMed:32960676)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17709747"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32960676"}],"value":"Preautophagosomal structure membrane","id":"SL-0221"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"Long"},"isoformIds":["Q9H1Y0-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"Short"},"synonyms":[{"value":"APG5beta"}],"isoformIds":["Q9H1Y0-2"],"sequenceIds":["VSP_003791"],"isoformSequenceStatus":"Described"}]},{"texts":[{"value":"Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"value":"By apoptotic stimuli"}],"commentType":"INDUCTION"},{"texts":[{"value":"Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19124466"}],"value":"Acetylated by EP300"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Spinocerebellar ataxia, autosomal recessive, 25","diseaseAccession":"DI-05044","acronym":"SCAR25","description":"A 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.","diseaseCrossReference":{"database":"MIM","id":"617584"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26812546"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the ATG5 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":275,"modifier":"EXACT"}},"description":"Autophagy protein 5","featureId":"PRO_0000218994"},{"type":"Modified residue","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"N-acetylmethionine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"22814378"}]},{"type":"Cross-link","location":{"start":{"value":130,"modifier":"EXACT"},"end":{"value":130,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)","evidences":[{"evidenceCode":"ECO:0000305"}]},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":79,"modifier":"EXACT"}},"description":"in isoform Short","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17974005"},{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.2"}],"featureId":"VSP_003791","alternativeSequence":{"originalSequence":"MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVMRQEDISEIWFEYEGTPLKW","alternativeSequences":["M"]}},{"type":"Natural variant","location":{"start":{"value":58,"modifier":"EXACT"},"end":{"value":58,"modifier":"EXACT"}},"description":"in a colorectal cancer sample; somatic mutation","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16959974"}],"featureId":"VAR_036243","alternativeSequence":{"originalSequence":"K","alternativeSequences":["M"]}},{"type":"Natural variant","location":{"start":{"value":122,"modifier":"EXACT"},"end":{"value":122,"modifier":"EXACT"}},"description":"in SCAR25; reduced conjugation to ATG12; decrease in autophagy activity; dbSNP:rs1131692265","featureCrossReferences":[{"database":"dbSNP","id":"rs1131692265"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26812546"}],"featureId":"VAR_079274","alternativeSequence":{"originalSequence":"E","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":130,"modifier":"EXACT"},"end":{"value":130,"modifier":"EXACT"}},"description":"Loss of conjugaction with ATG12. 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