ID ATG5_HUMAN Reviewed; 275 AA. AC Q9H1Y0; O60875; Q5JVR2; Q68DI4; Q9H2B8; Q9HCZ7; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 16-NOV-2001, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=Autophagy protein 5 {ECO:0000305}; DE AltName: Full=APG5-like; DE AltName: Full=Apoptosis-specific protein; GN Name=ATG5 {ECO:0000312|HGNC:HGNC:589}; Synonyms=APG5L, ASP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC TISSUE=Fetal liver; RX PubMed=9563500; DOI=10.1016/s0014-5793(98)00266-x; RA Hammond E.M., Brunet C.L., Johnson G.D., Parkhill J., Milner A.E., RA Brady G., Gregory C.D., Grand R.J.A.; RT "Homology between a human apoptosis specific protein and the product of RT APG5, a gene involved in autophagy in yeast."; RL FEBS Lett. 425:391-395(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RA Chen Y., Piao Y.J., Jiang Y.; RT "A novel splicing isoform of human APG5."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). RC TISSUE=Fetal brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Endometrium, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION IN APOPTOSIS. RX PubMed=7796880; DOI=10.1006/excr.1995.1177; RA Grand R.J.A., Milner A.E., Mustoe T., Johnson G.D., Owen D., Grant M.L., RA Gregory C.D.; RT "A novel protein expressed in mammalian cells undergoing apoptosis."; RL Exp. Cell Res. 218:439-451(1995). RN [7] RP CONJUGATION TO ATG12 AT LYS-130, AND MUTAGENESIS OF LYS-130. RX PubMed=9852036; DOI=10.1074/jbc.273.51.33889; RA Mizushima N., Sugita H., Yoshimori T., Ohsumi Y.; RT "A new protein conjugation system in human. The counterpart of the yeast RT Apg12p conjugation system essential for autophagy."; RL J. Biol. Chem. 273:33889-33892(1998). RN [8] RP CONJUGATION TO ATG12. RX PubMed=11096062; DOI=10.1074/jbc.c000752200; RA Tanida I., Tanida-Miyake E., Ueno T., Kominami E.; RT "The human homolog of Saccharomyces cerevisiae Apg7p is a Protein- RT activating enzyme for multiple substrates including human Apg12p, GATE-16, RT GABARAP, and MAP-LC3."; RL J. Biol. Chem. 276:1701-1706(2001). RN [9] RP CONJUGATION TO ATG12, AND SUBCELLULAR LOCATION. RC TISSUE=Embryonic stem cell; RX PubMed=11266458; DOI=10.1083/jcb.152.4.657; RA Mizushima N., Yamamoto A., Hatano M., Kobayashi Y., Kabeya Y., Suzuki K., RA Tokuhisa T., Ohsumi Y., Yoshimori T.; RT "Dissection of autophagosome formation using Apg5-deficient mouse embryonic RT stem cells."; RL J. Cell Biol. 152:657-668(2001). RN [10] RP INTERACTION WITH ATG3, CONJUGATION TO ATG12, AND FUNCTION. RX PubMed=12207896; DOI=10.1016/s0006-291x(02)02057-0; RA Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.; RT "Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 RT processing."; RL Biochem. Biophys. Res. Commun. 296:1164-1170(2002). RN [11] RP INTERACTION WITH ATG3, AND CONJUGATION TO ATG12. RX PubMed=11825910; DOI=10.1074/jbc.m200385200; RA Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.; RT "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple RT substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation RT of hApg12p to hApg5p."; RL J. Biol. Chem. 277:13739-13744(2002). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FADD. RX PubMed=15778222; DOI=10.1074/jbc.m413934200; RA Pyo J.O., Jang M.H., Kwon Y.K., Lee H.J., Jun J.I., Woo H.N., Cho D.H., RA Choi B., Lee H., Kim J.H., Mizushima N., Oshumi Y., Jung Y.K.; RT "Essential roles of Atg5 and FADD in autophagic cell death: dissection of RT autophagic cell death into vacuole formation and cell death."; RL J. Biol. Chem. 280:20722-20729(2005). RN [13] RP INTERACTION WITH S.FLEXNERI ICSA (MICROBIAL INFECTION). RX PubMed=15576571; DOI=10.1126/science.1106036; RA Ogawa M., Yoshimori T., Suzuki T., Sagara H., Mizushima N., Sasakawa C.; RT "Escape of intracellular Shigella from autophagy."; RL Science 307:727-731(2005). RN [14] RP CONJUGATION TO ATG12. RX PubMed=16963840; DOI=10.4161/auto.3270; RA Shao Y., Gao Z., Feldman T., Jiang X.; RT "Stimulation of ATG12-ATG5 conjugation by ribonucleic acid."; RL Autophagy 3:10-16(2007). RN [15] RP FUNCTION IN VIRAL INFECTION, INTERACTION WITH ATG12; DHX58; IFIH1 AND MAVS, RP MUTAGENESIS OF LYS-130, AND SUBCELLULAR LOCATION. RX PubMed=17709747; DOI=10.1073/pnas.0704014104; RA Jounai N., Takeshita F., Kobiyama K., Sawano A., Miyawaki A., Xin K.Q., RA Ishii K.J., Kawai T., Akira S., Suzuki K., Okuda K.; RT "The Atg5-Atg12 conjugate associates with innate antiviral immune RT responses."; RL Proc. Natl. Acad. Sci. U.S.A. 104:14050-14055(2007). RN [16] RP ACETYLATION BY EP300. RX PubMed=19124466; DOI=10.1074/jbc.m807135200; RA Lee I.H., Finkel T.; RT "Regulation of autophagy by the p300 acetyltransferase."; RL J. Biol. Chem. 284:6322-6328(2009). RN [17] RP FUNCTION IN VIRAL REPLICATION. RX PubMed=19666601; DOI=10.1073/pnas.0907344106; RA Dreux M., Gastaminza P., Wieland S.F., Chisari F.V.; RT "The autophagy machinery is required to initiate hepatitis C virus RT replication."; RL Proc. Natl. Acad. Sci. U.S.A. 106:14046-14051(2009). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HEPATITIS C VIRUS RP PROTEIN NS5B. RX PubMed=20580051; DOI=10.1016/j.virol.2010.05.032; RA Guevin C., Manna D., Belanger C., Konan K.V., Mak P., Labonte P.; RT "Autophagy protein ATG5 interacts transiently with the hepatitis C virus RT RNA polymerase (NS5B) early during infection."; RL Virology 405:1-7(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP INTERACTION WITH TECPR1. RX PubMed=21575909; DOI=10.1016/j.chom.2011.04.010; RA Ogawa M., Yoshikawa Y., Kobayashi T., Mimuro H., Fukumatsu M., Kiga K., RA Piao Z., Ashida H., Yoshida M., Kakuta S., Koyama T., Goto Y., Nagatake T., RA Nagai S., Kiyono H., Kawalec M., Reichhart J.M., Sasakawa C.; RT "A Tecpr1-dependent selective autophagy pathway targets bacterial RT pathogens."; RL Cell Host Microbe 9:376-389(2011). RN [21] RP FUNCTION. RX PubMed=22170153; DOI=10.4161/auto.8.1.18174; RA Mai S., Muster B., Bereiter-Hahn J., Jendrach M.; RT "Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control RT after mitochondrial damage and influence lifespan."; RL Autophagy 8:47-62(2012). RN [22] RP INTERACTION WITH TECPR1. RX PubMed=22342342; DOI=10.1016/j.molcel.2011.12.036; RA Chen D., Fan W., Lu Y., Ding X., Chen S., Zhong Q.; RT "A mammalian autophagosome maturation mechanism mediated by TECPR1 and the RT Atg12-Atg5 conjugate."; RL Mol. Cell 45:629-641(2012). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN CONJUGATION WITH ATG12. RX PubMed=23202584; DOI=10.1038/nsmb.2431; RA Otomo C., Metlagel Z., Takaesu G., Otomo T.; RT "Structure of the human ATG12-ATG5 conjugate required for LC3 lipidation in RT autophagy."; RL Nat. Struct. Mol. Biol. 20:59-66(2013). RN [25] {ECO:0007744|PDB:4NAW} RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) IN COMPLEX WITH ATG12; ATG3 AND RP ATG16L1, AND SUBUNIT. RX PubMed=24191030; DOI=10.1073/pnas.1314755110; RA Metlagel Z., Otomo C., Takaesu G., Otomo T.; RT "Structural basis of ATG3 recognition by the autophagic ubiquitin-like RT protein ATG12."; RL Proc. Natl. Acad. Sci. U.S.A. 110:18844-18849(2013). RN [26] RP VARIANT [LARGE SCALE ANALYSIS] MET-58. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [27] RP VARIANT SCAR25 ASP-122, CHARACTERIZATION OF VARIANT SCAR25 ASP-122, RP FUNCTION, AND CONJUGATION TO ATG12. RX PubMed=26812546; DOI=10.7554/elife.12245; RA Kim M., Sandford E., Gatica D., Qiu Y., Liu X., Zheng Y., Schulman B.A., RA Xu J., Semple I., Ro S.H., Kim B., Mavioglu R.N., Tolun A., Jipa A., RA Takats S., Karpati M., Li J.Z., Yapici Z., Juhasz G., Lee J.H., RA Klionsky D.J., Burmeister M.; RT "Mutation in ATG5 reduces autophagy and leads to ataxia with developmental RT delay."; RL Elife 5:0-0(2016). CC -!- FUNCTION: Involved in autophagic vesicle formation. Conjugation with CC ATG12, through a ubiquitin-like conjugating system involving ATG7 as an CC E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, CC is essential for its function. The ATG12-ATG5 conjugate acts as an E3- CC like enzyme which is required for lipidation of ATG8 family proteins CC and their association to the vesicle membranes. Involved in CC mitochondrial quality control after oxidative damage, and in subsequent CC cellular longevity. Plays a critical role in multiple aspects of CC lymphocyte development and is essential for both B and T lymphocyte CC survival and proliferation. Required for optimal processing and CC presentation of antigens for MHC II. Involved in the maintenance of CC axon morphology and membrane structures, as well as in normal adipocyte CC differentiation. Promotes primary ciliogenesis through removal of OFD1 CC from centriolar satellites and degradation of IFT20 via the autophagic CC pathway. {ECO:0000250|UniProtKB:Q99J83, ECO:0000269|PubMed:12207896, CC ECO:0000269|PubMed:20580051, ECO:0000269|PubMed:22170153, CC ECO:0000269|PubMed:26812546}. CC -!- FUNCTION: May play an important role in the apoptotic process, possibly CC within the modified cytoskeleton. Its expression is a relatively late CC event in the apoptotic process, occurring downstream of caspase CC activity. Plays a crucial role in IFN-gamma-induced autophagic cell CC death by interacting with FADD. {ECO:0000269|PubMed:15778222, CC ECO:0000269|PubMed:7796880}. CC -!- FUNCTION: (Microbial infection) May act as a proviral factor. In CC association with ATG12, negatively regulates the innate antiviral CC immune response by impairing the type I IFN production pathway upon CC vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required CC for the translation of incoming hepatitis C virus (HCV) RNA and, CC thereby, for initiation of HCV replication, but not required once CC infection is established (PubMed:19666601). CC {ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19666601}. CC -!- SUBUNIT: Forms a conjugate with ATG12 (PubMed:12207896, CC PubMed:11825910, PubMed:17709747, PubMed:26812546). Part of the minor CC complex composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this CC complex interacts with ATG3 leading to disruption of ATG7 interaction CC and promotion of ATG8-like proteins lipidation (PubMed:24191030). Forms CC an 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (By similarity). CC Interacts with TECPR1; the interaction is direct and does not take CC place when ATG16L1 is associated with the ATG5-ATG12 conjugate CC (PubMed:21575909, PubMed:22342342). Interacts with DHX58/RIG-1, CC IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 CC conjugate form. The interaction with MAVS is further enhanced upon CC vesicular stomatitis virus (VSV) infection (PubMed:17709747). Interacts CC with ATG3 (PubMed:12207896, PubMed:11825910). Interacts with ATG7 and CC ATG10 (By similarity). Interacts with FADD (PubMed:15778222). Interacts CC with Bassoon/BSN; this interaction is important for the regulation of CC presynaptic autophagy (By similarity). Interacts with ATG16L2 (By CC similarity). {ECO:0000250|UniProtKB:Q99J83, CC ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:12207896, CC ECO:0000269|PubMed:15778222, ECO:0000269|PubMed:17709747, CC ECO:0000269|PubMed:21575909, ECO:0000269|PubMed:22342342, CC ECO:0000269|PubMed:24191030, ECO:0000269|PubMed:26812546}. CC -!- SUBUNIT: (Microbial infection) Interacts transiently interacts with CC hepatitis C virus (HCV) protein NS5B during HCV infection. CC {ECO:0000269|PubMed:20580051}. CC -!- SUBUNIT: (Microbial infection) Interacts with S.flexneri IcsA; CC bacterial IcsB inhibits this interaction. CC {ECO:0000305|PubMed:15576571}. CC -!- INTERACTION: CC Q9H1Y0; Q9H0Y0: ATG10; NbExp=5; IntAct=EBI-1047414, EBI-1048913; CC Q9H1Y0; Q676U5: ATG16L1; NbExp=7; IntAct=EBI-1047414, EBI-535909; CC Q9H1Y0; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-1047414, EBI-12811889; CC Q9H1Y0; Q8WUD4: CCDC12; NbExp=4; IntAct=EBI-1047414, EBI-2557572; CC Q9H1Y0; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-1047414, EBI-10175300; CC Q9H1Y0; Q8IXW7: FMR1; NbExp=3; IntAct=EBI-1047414, EBI-11976595; CC Q9H1Y0; O95166: GABARAP; NbExp=2; IntAct=EBI-1047414, EBI-712001; CC Q9H1Y0; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-1047414, EBI-717919; CC Q9H1Y0; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-1047414, EBI-10961706; CC Q9H1Y0; Q0VD86: INCA1; NbExp=3; IntAct=EBI-1047414, EBI-6509505; CC Q9H1Y0; Q14145: KEAP1; NbExp=3; IntAct=EBI-1047414, EBI-751001; CC Q9H1Y0; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-1047414, EBI-3437878; CC Q9H1Y0; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-1047414, EBI-742610; CC Q9H1Y0; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-1047414, EBI-373144; CC Q9H1Y0; Q7Z434-1: MAVS; NbExp=4; IntAct=EBI-1047414, EBI-15577799; CC Q9H1Y0; A5LHX3: PSMB11; NbExp=3; IntAct=EBI-1047414, EBI-19951687; CC Q9H1Y0; Q8TDY2: RB1CC1; NbExp=3; IntAct=EBI-1047414, EBI-1047793; CC Q9H1Y0; O95786-1: RIGI; NbExp=4; IntAct=EBI-1047414, EBI-15577823; CC Q9H1Y0; Q7Z6L1: TECPR1; NbExp=9; IntAct=EBI-1047414, EBI-2946676; CC Q9H1Y0; Q8WW24: TEKT4; NbExp=6; IntAct=EBI-1047414, EBI-750487; CC Q9H1Y0; P09936: UCHL1; NbExp=3; IntAct=EBI-1047414, EBI-714860; CC Q9H1Y0; Q8IZQ1: WDFY3; NbExp=7; IntAct=EBI-1047414, EBI-1569256; CC Q9H1Y0; Q8C0J2-3: Atg16l1; Xeno; NbExp=2; IntAct=EBI-1047414, EBI-16029274; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17709747}. CC Preautophagosomal structure membrane; Peripheral membrane protein. CC Note=Colocalizes with nonmuscle actin. The conjugate detaches from the CC membrane immediately before or after autophagosome formation is CC completed (By similarity). Localizes also to discrete punctae along the CC ciliary axoneme and to the base of the ciliary axoneme. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q9H1Y0-1; Sequence=Displayed; CC Name=Short; Synonyms=APG5beta; CC IsoId=Q9H1Y0-2; Sequence=VSP_003791; CC -!- TISSUE SPECIFICITY: Ubiquitous. The mRNA is present at similar levels CC in viable and apoptotic cells, whereas the protein is dramatically CC highly expressed in apoptotic cells. CC -!- INDUCTION: By apoptotic stimuli. CC -!- PTM: Conjugated to ATG12; which is essential for autophagy, but is not CC required for association with isolation membrane. CC -!- PTM: Acetylated by EP300. {ECO:0000269|PubMed:19124466}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 25 (SCAR25) CC [MIM:617584]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR25 patients manifest delayed psychomotor CC development with delayed walking, truncal ataxia, dysmetria, and CC nystagmus, Cerebellar hypoplasia is seen on brain imaging. CC {ECO:0000269|PubMed:26812546}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ATG5 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y11588; CAA72327.1; -; mRNA. DR EMBL; AF293841; AAG44955.1; -; mRNA. DR EMBL; CR749386; CAH18236.1; -; mRNA. DR EMBL; AL022067; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133509; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL138917; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002699; AAH02699.1; -; mRNA. DR EMBL; BC093011; AAH93011.1; -; mRNA. DR CCDS; CCDS5055.1; -. [Q9H1Y0-1] DR CCDS; CCDS69159.1; -. [Q9H1Y0-2] DR RefSeq; NP_001273035.1; NM_001286106.1. [Q9H1Y0-1] DR RefSeq; NP_001273036.1; NM_001286107.1. [Q9H1Y0-2] DR RefSeq; NP_001273037.1; NM_001286108.1. DR RefSeq; NP_001273040.1; NM_001286111.1. DR RefSeq; NP_004840.1; NM_004849.3. [Q9H1Y0-1] DR PDB; 4GDK; X-ray; 2.70 A; B/E=1-275. DR PDB; 4GDL; X-ray; 2.88 A; B=1-275. DR PDB; 4NAW; X-ray; 2.20 A; B/F/J/N=1-275. DR PDB; 4TQ0; X-ray; 2.70 A; A/C/E=1-275. DR PDB; 4TQ1; X-ray; 1.80 A; A=1-275. DR PDB; 5D7G; X-ray; 3.00 A; A/C/E/G=1-275. DR PDB; 5NPV; X-ray; 3.10 A; A/C=1-275. DR PDB; 5NPW; X-ray; 3.10 A; A/C/E/G=1-275. DR PDB; 7W36; X-ray; 3.00 A; A=1-275. DR PDBsum; 4GDK; -. DR PDBsum; 4GDL; -. DR PDBsum; 4NAW; -. DR PDBsum; 4TQ0; -. DR PDBsum; 4TQ1; -. DR PDBsum; 5D7G; -. DR PDBsum; 5NPV; -. DR PDBsum; 5NPW; -. DR PDBsum; 7W36; -. DR AlphaFoldDB; Q9H1Y0; -. DR SMR; Q9H1Y0; -. DR BioGRID; 114859; 131. DR ComplexPortal; CPX-200; ATG12-ATG5-ATG16L1 complex. DR ComplexPortal; CPX-354; ATG12-ATG5-ATG16L2 complex. DR ComplexPortal; CPX-356; ATG5-ATG12 complex. DR ComplexPortal; CPX-358; ATG5-ATG12-TECPR1 complex. DR DIP; DIP-29758N; -. DR IntAct; Q9H1Y0; 56. DR MINT; Q9H1Y0; -. DR STRING; 9606.ENSP00000358072; -. DR GlyGen; Q9H1Y0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H1Y0; -. DR PhosphoSitePlus; Q9H1Y0; -. DR BioMuta; ATG5; -. DR DMDM; 17366828; -. DR EPD; Q9H1Y0; -. DR jPOST; Q9H1Y0; -. DR MassIVE; Q9H1Y0; -. DR MaxQB; Q9H1Y0; -. DR PaxDb; 9606-ENSP00000358072; -. DR PeptideAtlas; Q9H1Y0; -. DR ProteomicsDB; 80456; -. [Q9H1Y0-1] DR ProteomicsDB; 80457; -. [Q9H1Y0-2] DR Pumba; Q9H1Y0; -. DR Antibodypedia; 32129; 1231 antibodies from 43 providers. DR DNASU; 9474; -. DR Ensembl; ENST00000343245.7; ENSP00000343313.3; ENSG00000057663.16. [Q9H1Y0-1] DR Ensembl; ENST00000369076.8; ENSP00000358072.3; ENSG00000057663.16. [Q9H1Y0-1] DR Ensembl; ENST00000635758.2; ENSP00000490493.1; ENSG00000057663.16. [Q9H1Y0-2] DR GeneID; 9474; -. DR KEGG; hsa:9474; -. DR MANE-Select; ENST00000369076.8; ENSP00000358072.3; NM_004849.4; NP_004840.1. DR UCSC; uc003prf.4; human. [Q9H1Y0-1] DR AGR; HGNC:589; -. DR CTD; 9474; -. DR DisGeNET; 9474; -. DR GeneCards; ATG5; -. DR HGNC; HGNC:589; ATG5. DR HPA; ENSG00000057663; Low tissue specificity. DR MalaCards; ATG5; -. DR MIM; 604261; gene. DR MIM; 617584; phenotype. DR neXtProt; NX_Q9H1Y0; -. DR OpenTargets; ENSG00000057663; -. DR PharmGKB; PA24880; -. DR VEuPathDB; HostDB:ENSG00000057663; -. DR eggNOG; KOG2976; Eukaryota. DR GeneTree; ENSGT00390000004766; -. DR HOGENOM; CLU_051894_1_0_1; -. DR InParanoid; Q9H1Y0; -. DR OMA; SIQKAVW; -. DR OrthoDB; 8084at2759; -. DR PhylomeDB; Q9H1Y0; -. DR TreeFam; TF314415; -. DR PathwayCommons; Q9H1Y0; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-HSA-8934903; Receptor Mediated Mitophagy. DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling. DR SignaLink; Q9H1Y0; -. DR SIGNOR; Q9H1Y0; -. DR BioGRID-ORCS; 9474; 25 hits in 1168 CRISPR screens. DR ChiTaRS; ATG5; human. DR GeneWiki; ATG5; -. DR GenomeRNAi; 9474; -. DR Pharos; Q9H1Y0; Tbio. DR PRO; PR:Q9H1Y0; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9H1Y0; Protein. DR Bgee; ENSG00000057663; Expressed in primordial germ cell in gonad and 204 other cell types or tissues. DR ExpressionAtlas; Q9H1Y0; baseline and differential. DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IPI:ComplexPortal. DR GO; GO:0005776; C:autophagosome; IDA:MGI. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0005930; C:axoneme; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome. DR GO; GO:0034045; C:phagophore assembly site membrane; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; NAS:ComplexPortal. DR GO; GO:1990234; C:transferase complex; ISO:ComplexPortal. DR GO; GO:0019776; F:Atg8-family ligase activity; IDA:UniProt. DR GO; GO:0035973; P:aggrephagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0019883; P:antigen processing and presentation of endogenous antigen; IEA:Ensembl. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProt. DR GO; GO:0006914; P:autophagy; IMP:UniProtKB. DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central. DR GO; GO:0071500; P:cellular response to nitrosative stress; IEA:Ensembl. DR GO; GO:0061684; P:chaperone-mediated autophagy; IEA:Ensembl. DR GO; GO:0006325; P:chromatin organization; IEA:Ensembl. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0060047; P:heart contraction; IEA:Ensembl. DR GO; GO:0016236; P:macroautophagy; IMP:ComplexPortal. DR GO; GO:0000423; P:mitophagy; IEA:Ensembl. DR GO; GO:0070254; P:mucus secretion; IEA:Ensembl. DR GO; GO:1904093; P:negative regulation of autophagic cell death; IMP:MGI. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0050687; P:negative regulation of defense response to virus; IDA:ComplexPortal. DR GO; GO:0045824; P:negative regulation of innate immune response; ISO:ComplexPortal. DR GO; GO:0050765; P:negative regulation of phagocytosis; IEA:Ensembl. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IEA:Ensembl. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0032480; P:negative regulation of type I interferon production; ISO:ComplexPortal. DR GO; GO:0039689; P:negative stranded viral RNA replication; IEA:Ensembl. DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl. DR GO; GO:0044804; P:nucleophagy; IBA:GO_Central. DR GO; GO:0048840; P:otolith development; IEA:Ensembl. DR GO; GO:0070257; P:positive regulation of mucus secretion; IEA:Ensembl. DR GO; GO:1904973; P:positive regulation of viral translation; IDA:ComplexPortal. DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl. DR GO; GO:1901096; P:regulation of autophagosome maturation; IMP:ComplexPortal. DR GO; GO:1902017; P:regulation of cilium assembly; ISS:UniProtKB. DR GO; GO:0002718; P:regulation of cytokine production involved in immune response; IEA:Ensembl. DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl. DR GO; GO:1902617; P:response to fluoride; IEA:Ensembl. DR GO; GO:0009620; P:response to fungus; IEA:Ensembl. DR GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0042311; P:vasodilation; IEA:Ensembl. DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEA:Ensembl. DR Gene3D; 3.10.20.620; -; 1. DR Gene3D; 1.10.246.190; Autophagy protein Apg5, helix rich domain; 1. DR InterPro; IPR007239; Atg5. DR InterPro; IPR048940; ATG5_HBR. DR InterPro; IPR042526; Atg5_HR. DR InterPro; IPR048939; ATG5_UblA. DR InterPro; IPR042527; Atg5_UblA_dom_sf. DR InterPro; IPR048318; ATG5_UblB. DR PANTHER; PTHR13040; AUTOPHAGY PROTEIN 5; 1. DR PANTHER; PTHR13040:SF2; AUTOPHAGY PROTEIN 5; 1. DR Pfam; PF20637; ATG5_HBR; 1. DR Pfam; PF20638; ATG5_UblA; 1. DR Pfam; PF04106; ATG5_UblB; 1. DR Genevisible; Q9H1Y0; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Autophagy; KW Cytoplasm; Disease variant; Host-virus interaction; Immunity; KW Isopeptide bond; Membrane; Neurodegeneration; Reference proteome; KW Ubl conjugation. FT CHAIN 1..275 FT /note="Autophagy protein 5" FT /id="PRO_0000218994" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT CROSSLNK 130 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ATG12)" FT /evidence="ECO:0000305" FT VAR_SEQ 1..79 FT /note="MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKV FT KKHFQKVMRQEDISEIWFEYEGTPLKW -> M (in isoform Short)" FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.2" FT /id="VSP_003791" FT VARIANT 58 FT /note="K -> M (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036243" FT VARIANT 122 FT /note="E -> D (in SCAR25; reduced conjugation to ATG12; FT decrease in autophagy activity; dbSNP:rs1131692265)" FT /evidence="ECO:0000269|PubMed:26812546" FT /id="VAR_079274" FT MUTAGEN 130 FT /note="K->R: Loss of conjugaction with ATG12. Does affect FT interaction with DHX58, nor with MAVS." FT /evidence="ECO:0000269|PubMed:17709747, FT ECO:0000269|PubMed:9852036" FT HELIX 4..12 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 15..22 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 23..27 FT /evidence="ECO:0007829|PDB:7W36" FT STRAND 28..30 FT /evidence="ECO:0007829|PDB:4GDL" FT STRAND 35..40 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 45..48 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 50..57 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:4NAW" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 83..91 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:5D7G" FT STRAND 96..103 FT /evidence="ECO:0007829|PDB:4TQ1" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:5NPV" FT HELIX 118..137 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 140..144 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 147..158 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 162..172 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:4TQ0" FT STRAND 187..192 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:4GDL" FT HELIX 215..222 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:4TQ1" FT TURN 229..231 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 232..240 FT /evidence="ECO:0007829|PDB:4TQ1" FT HELIX 251..257 FT /evidence="ECO:0007829|PDB:4TQ1" FT STRAND 265..270 FT /evidence="ECO:0007829|PDB:4TQ1" SQ SEQUENCE 275 AA; 32447 MW; C33A1E0B3C1DBE5C CRC64; MTDDKDVLRD VWFGRIPTCF TLYQDEITER EAEPYYLLLP RVSYLTLVTD KVKKHFQKVM RQEDISEIWF EYEGTPLKWH YPIGLLFDLL ASSSALPWNI TVHFKSFPEK DLLHCPSKDA IEAHFMSCMK EADALKHKSQ VINEMQKKDH KQLWMGLQND RFDQFWAINR KLMEYPAEEN GFRYIPFRIY QTTTERPFIQ KLFRPVAADG QLHTLGDLLK EVCPSAIDPE DGEKKNQVMI HGIEPMLETP LQWLSEHLSY PDNFLHISII PQPTD //