ATG3_MOUSE
ID ATG3_MOUSE Reviewed; 314 AA.
AC Q9CPX6; Q3TXJ9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Ubiquitin-like-conjugating enzyme ATG3;
DE EC=2.3.2.-;
DE AltName: Full=Autophagy-related protein 3;
DE Short=APG3-like;
GN Name=Atg3; Synonyms=Apg3l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Cerebellum, and Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [4]
RP INTERACTION WITH ATG12.
RX PubMed=18321988; DOI=10.1091/mbc.e07-12-1257;
RA Fujita N., Itoh T., Omori H., Fukuda M., Noda T., Yoshimori T.;
RT "The Atg16L complex specifies the site of LC3 lipidation for membrane
RT biogenesis in autophagy.";
RL Mol. Biol. Cell 19:2092-2100(2008).
RN [5]
RP FUNCTION.
RX PubMed=18768753; DOI=10.1091/mbc.e08-03-0309;
RA Sou Y.S., Waguri S., Iwata J., Ueno T., Fujimura T., Hara T., Sawada N.,
RA Yamada A., Mizushima N., Uchiyama Y., Kominami E., Tanaka K., Komatsu M.;
RT "The Atg8 conjugation system is indispensable for proper development of
RT autophagic isolation membranes in mice.";
RL Mol. Biol. Cell 19:4762-4775(2008).
RN [6]
RP FUNCTION, CONJUGATION TO ATG12 AT LYS-243, AND MUTAGENESIS OF LYS-71;
RP LYS-83; LYS-243; CYS-264; LYS-271 AND LYS-295.
RX PubMed=20723759; DOI=10.1016/j.cell.2010.07.018;
RA Radoshevich L., Murrow L., Chen N., Fernandez E., Roy S., Fung C.,
RA Debnath J.;
RT "ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell
RT death.";
RL Cell 142:590-600(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP CONJUGATION TO ATG12.
RX PubMed=22024753; DOI=10.4161/auto.7.12.17793;
RA Moloughney J.G., Monken C.E., Tao H., Zhang H., Thomas J.D., Lattime E.C.,
RA Jin S.;
RT "Vaccinia virus leads to ATG12-ATG3 conjugation and deficiency in
RT autophagosome formation.";
RL Autophagy 7:1434-1447(2011).
RN [9]
RP FUNCTION.
RX PubMed=24089205; DOI=10.1038/nature12606;
RA Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B.,
RA Zhong Q.;
RT "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar
RT satellites.";
RL Nature 502:254-257(2013).
CC -!- FUNCTION: E2 conjugating enzyme required for the cytoplasm to vacuole
CC transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible
CC for the E2-like covalent binding of phosphatidylethanolamine to the C-
CC terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or
CC MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes
CC the transfer of ATG8-like proteins from ATG3 to
CC phosphatidylethanolamine (PE). This step is required for the membrane
CC association of ATG8-like proteins. The formation of the ATG8-
CC phosphatidylethanolamine conjugates is essential for autophagy and for
CC the cytoplasm to vacuole transport (Cvt). Preferred substrate is
CC MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the
CC conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a
CC role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like
CC enzyme) facilitates this reaction by forming an E1-E2 complex with
CC ATG3. ATG12-ATG3 conjugate is also formed upon viccina virus infection,
CC leading to the disruption the cellular autophagy which is not necessary
CC for vaccinia survival and proliferation. Promotes primary ciliogenesis
CC by removing OFD1 from centriolar satellites via the autophagic pathway.
CC {ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:18768753,
CC ECO:0000269|PubMed:20723759, ECO:0000269|PubMed:24089205}.
CC -!- SUBUNIT: Interacts with ATG7 and ATG12. The complex composed of ATG3
CC and ATG7 plays a role in the conjugation of ATG12 to ATG5. Interacts
CC with FNBP1L (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9CPX6; Q9CQY1: Atg12; NbExp=5; IntAct=EBI-2911810, EBI-2911788;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in
CC regulation of mitochondrial homeostasis and cell death, while it is not
CC involved in PE-conjugation to ATG8-like proteins and autophagy.
CC -!- PTM: Cleaved by CASP8 upon death ligand binding such as tumor necrosis
CC factor-alpha. CASP8 cleavage blocks survival-related autophagy and
CC favors apoptosis (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ATG3 family. {ECO:0000305}.
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DR EMBL; AB079386; BAC57452.1; -; mRNA.
DR EMBL; AK005266; BAB23918.1; -; mRNA.
DR EMBL; AK011409; BAB27600.1; -; mRNA.
DR EMBL; AK078877; BAC37437.1; -; mRNA.
DR EMBL; AK150914; BAE29952.1; -; mRNA.
DR EMBL; AK159231; BAE34917.1; -; mRNA.
DR EMBL; BC010809; AAH10809.1; -; mRNA.
DR CCDS; CCDS28194.1; -.
DR RefSeq; NP_080678.1; NM_026402.3.
DR AlphaFoldDB; Q9CPX6; -.
DR SMR; Q9CPX6; -.
DR BioGRID; 212471; 19.
DR DIP; DIP-60109N; -.
DR IntAct; Q9CPX6; 4.
DR MINT; Q9CPX6; -.
DR STRING; 10090.ENSMUSP00000023343; -.
DR iPTMnet; Q9CPX6; -.
DR PhosphoSitePlus; Q9CPX6; -.
DR SwissPalm; Q9CPX6; -.
DR EPD; Q9CPX6; -.
DR jPOST; Q9CPX6; -.
DR MaxQB; Q9CPX6; -.
DR PaxDb; Q9CPX6; -.
DR PeptideAtlas; Q9CPX6; -.
DR PRIDE; Q9CPX6; -.
DR ProteomicsDB; 265163; -.
DR Antibodypedia; 32502; 751 antibodies from 39 providers.
DR Ensembl; ENSMUST00000023343; ENSMUSP00000023343; ENSMUSG00000022663.
DR GeneID; 67841; -.
DR KEGG; mmu:67841; -.
DR UCSC; uc007zii.1; mouse.
DR CTD; 64422; -.
DR MGI; MGI:1915091; Atg3.
DR VEuPathDB; HostDB:ENSMUSG00000022663; -.
DR eggNOG; KOG2981; Eukaryota.
DR GeneTree; ENSGT00390000010308; -.
DR HOGENOM; CLU_027518_0_0_1; -.
DR InParanoid; Q9CPX6; -.
DR OMA; YDKYYQV; -.
DR OrthoDB; 1432328at2759; -.
DR PhylomeDB; Q9CPX6; -.
DR TreeFam; TF105903; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR BioGRID-ORCS; 67841; 22 hits in 75 CRISPR screens.
DR ChiTaRS; Atg3; mouse.
DR PRO; PR:Q9CPX6; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9CPX6; protein.
DR Bgee; ENSMUSG00000022663; Expressed in parotid gland and 242 other tissues.
DR Genevisible; Q9CPX6; MM.
DR GO; GO:0000153; C:cytoplasmic ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0019777; F:Atg12 transferase activity; IDA:UniProtKB.
DR GO; GO:0019776; F:Atg8 ligase activity; IMP:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; 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:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:MGI.
DR GO; GO:0036211; P:protein modification process; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:1902017; P:regulation of cilium assembly; IMP:UniProtKB.
DR InterPro; IPR007135; Atg3/Atg10.
DR PANTHER; PTHR12866; PTHR12866; 1.
DR Pfam; PF03987; Autophagy_act_C; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Cytoplasm; Isopeptide bond; Protein transport;
KW Reference proteome; Transferase; Transport; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..314
FT /note="Ubiquitin-like-conjugating enzyme ATG3"
FT /id="PRO_0000213570"
FT REGION 143..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 264
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000305"
FT SITE 169..170
FT /note="Cleavage; by CASP8"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9NT62"
FT CROSSLNK 243
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ATG12)"
FT MUTAGEN 71
FT /note="K->R: Does not affect ATG12 conjugation."
FT /evidence="ECO:0000269|PubMed:20723759"
FT MUTAGEN 83
FT /note="K->R: Does not affect ATG12 conjugation."
FT /evidence="ECO:0000269|PubMed:20723759"
FT MUTAGEN 243
FT /note="K->R: Abolishes ATG12 conjugation, leading to an
FT expansion in mitochondrial mass and fragmented
FT mitochondrial morphology. Does not affect PE-conjugation to
FT ATG8-like proteins."
FT /evidence="ECO:0000269|PubMed:20723759"
FT MUTAGEN 264
FT /note="C->A: Abolishes E2-like activity."
FT /evidence="ECO:0000269|PubMed:20723759"
FT MUTAGEN 271
FT /note="K->R: Does not affect ATG12 conjugation."
FT /evidence="ECO:0000269|PubMed:20723759"
FT MUTAGEN 295
FT /note="K->R: Does not affect ATG12 conjugation."
FT /evidence="ECO:0000269|PubMed:20723759"
SQ SEQUENCE 314 AA; 35796 MW; EC5ECACD3247ED66 CRC64;
MQNVINTVKG KALEVAEYLT PVLKESKFKE TGVITPEEFV AAGDHLVHHC PTWQWATGEE
LKVKAYLPTD KQFLVTKNVP CYKRCKQMEY SDELEAIIEE DDGDGGWVDT YHNTGITGIT
EAVKEITLES KDSIKLQDCS ALCDEEDEED EGEAADMEEY EESGLLETDE ATLDTRKIVE
ACKAKADAGG EDAILQTRTY DLYITYDKYY QTPRLWLFGY DEQRQPLTVE HMYEDISQDH
VKKTVTIENH PHLPPPPMCS VHPCRHAEVM KKIIETVAEG GGELGVHMYL LIFLKFVQAV
IPTIEYDYTR HFTM
