ATG5_HUMAN
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 03-AUG-2022, entry version 187.
DE RecName: Full=Autophagy protein 5;
DE AltName: Full=APG5-like;
DE AltName: Full=Apoptosis-specific protein;
GN Name=ATG5; 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 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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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). The ATG5-ATG12
CC conjugate forms a complex with several units of ATG16L1. Forms an 800-
CC 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: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 -!- 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; O95786-1: DDX58; NbExp=4; IntAct=EBI-1047414, EBI-15577823;
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; 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}.
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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 PDBsum; 4GDK; -.
DR PDBsum; 4GDL; -.
DR PDBsum; 4NAW; -.
DR PDBsum; 4TQ0; -.
DR PDBsum; 4TQ1; -.
DR PDBsum; 5D7G; -.
DR PDBsum; 5NPV; -.
DR PDBsum; 5NPW; -.
DR AlphaFoldDB; Q9H1Y0; -.
DR SMR; Q9H1Y0; -.
DR BioGRID; 114859; 122.
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; 55.
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; Q9H1Y0; -.
DR PeptideAtlas; Q9H1Y0; -.
DR PRIDE; Q9H1Y0; -.
DR ProteomicsDB; 80456; -. [Q9H1Y0-1]
DR ProteomicsDB; 80457; -. [Q9H1Y0-2]
DR Antibodypedia; 32129; 1072 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 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; KWHYPLG; -.
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 1090 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 colonic mucosa and 202 other tissues.
DR ExpressionAtlas; Q9H1Y0; baseline and differential.
DR Genevisible; Q9H1Y0; HS.
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; IC:ComplexPortal.
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; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0044804; P:autophagy of nucleus; IBA:GO_Central.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0006501; P:C-terminal protein lipidation; IBA:GO_Central.
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: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:0070254; P:mucus secretion; IEA:Ensembl.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:MGI.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IDA:ComplexPortal.
DR GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; IEA:Ensembl.
DR GO; GO:0045824; P:negative regulation of innate immune response; IEA:Ensembl.
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; IEA:Ensembl.
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: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:0006497; P:protein lipidation; IDA:ComplexPortal.
DR GO; GO:0061739; P:protein lipidation involved in autophagosome assembly; IEA:Ensembl.
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; 1.10.246.190; -; 1.
DR Gene3D; 3.10.20.620; -; 1.
DR InterPro; IPR007239; Atg5.
DR InterPro; IPR042526; Atg5_HR.
DR InterPro; IPR042527; Atg5_UblA_dom.
DR PANTHER; PTHR13040; PTHR13040; 1.
DR Pfam; PF04106; APG5; 1.
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 STRAND 24..26
FT /evidence="ECO:0007829|PDB:5NPV"
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
