ATG12_MOUSE
ID ATG12_MOUSE Reviewed; 141 AA.
AC Q9CQY1; Q3TKE5; Q9D7Y5;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ubiquitin-like protein ATG12;
DE AltName: Full=Autophagy-related protein 12;
DE Short=APG12-like;
GN Name=Atg12; Synonyms=Apg12, Apg12l;
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], CONJUGATION TO ATG5, FUNCTION OF THE ATG12/ATG5
RP CONJUGATE, AND SUBCELLULAR LOCATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Blastocyst, Placenta, Stomach, and Testis;
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=C57BL/6J; TISSUE=Brain;
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 ATG10, AND CONJUGATION TO ATG5.
RX PubMed=12482611; DOI=10.1016/s0014-5793(02)03739-0;
RA Mizushima N., Yoshimori T., Ohsumi Y.;
RT "Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-
RT mediated yeast two-hybrid method.";
RL FEBS Lett. 532:450-454(2002).
RN [5]
RP CONJUGATION TO ATG5 BY ATG10, AND FUNCTION.
RX PubMed=12890687; DOI=10.1074/jbc.m300550200;
RA Nemoto T., Tanida I., Tanida-Miyake E., Minematsu-Ikeguchi N., Yokota M.,
RA Ohsumi M., Ueno T., Kominami E.;
RT "The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation,
RT facilitates MAP-LC3 modification.";
RL J. Biol. Chem. 278:39517-39526(2003).
RN [6]
RP IDENTIFICATION IN A COMPLEX WITH ATG5 AND ATG16L1.
RX PubMed=12665549; DOI=10.1242/jcs.00381;
RA Mizushima N., Kuma A., Kobayashi Y., Yamamoto A., Matsubae M., Takao T.,
RA Natsume T., Ohsumi Y., Yoshimori T.;
RT "Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic
RT isolation membrane with the Apg12-Apg5 conjugate.";
RL J. Cell Sci. 116:1679-1688(2003).
RN [7]
RP FUNCTION IN VIRAL INFECTION.
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 [8]
RP DOMAIN.
RX PubMed=18704115; DOI=10.1038/embor.2008.163;
RA Geng J., Klionsky D.J.;
RT "The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy.
RT 'Protein modifications: beyond the usual suspects' review series.";
RL EMBO Rep. 9:859-864(2008).
RN [9]
RP CONJUGATION TO ATG5.
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 [10]
RP CONJUGATION TO ATG5.
RX PubMed=19417210; DOI=10.1182/blood-2008-04-151639;
RA Zhang J., Randall M.S., Loyd M.R., Dorsey F.C., Kundu M., Cleveland J.L.,
RA Ney P.A.;
RT "Mitochondrial clearance is regulated by Atg7-dependent and -independent
RT mechanisms during reticulocyte maturation.";
RL Blood 114:157-164(2009).
RN [11]
RP FUNCTION.
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 [12]
RP IDENTIFICATION IN A COMPLEX WITH ATG5 AND ATG16L2.
RX PubMed=22082872; DOI=10.4161/auto.7.12.18025;
RA Ishibashi K., Fujita N., Kanno E., Omori H., Yoshimori T., Itoh T.,
RA Fukuda M.;
RT "Atg16L2, a novel isoform of mammalian Atg16L that is not essential for
RT canonical autophagy despite forming an Atg12-5-16L2 complex.";
RL Autophagy 7:1500-1513(2011).
CC -!- FUNCTION: Ubiquitin-like protein involved in autophagy vesicles
CC formation. Conjugation with ATG5 through a ubiquitin-like conjugating
CC system involving also ATG7 as an E1-like activating enzyme and ATG10 as
CC an E2-like conjugating enzyme, is essential for its function. The
CC ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for
CC lipidation of ATG8 family proteins and their association to the vesicle
CC membranes. {ECO:0000269|PubMed:11266458, ECO:0000269|PubMed:12890687,
CC ECO:0000269|PubMed:20723759}.
CC -!- FUNCTION: (Microbial infection) May act as a proviral factor. In
CC association with ATG5, negatively regulates the innate antiviral immune
CC response by impairing the type I IFN production pathway upon vesicular
CC stomatitis virus (VSV) infection. {ECO:0000269|PubMed:17709747}.
CC -!- SUBUNIT: Forms a conjugate with ATG5 (PubMed:11266458, PubMed:12482611,
CC PubMed:12890687, PubMed:12665549, PubMed:18768753, PubMed:19417210).
CC The ATG12-ATG5 conjugate forms a complex with several units of ATG16L1
CC (PubMed:12665549). Forms an 800-kDa complex composed of ATG12-ATG5 and
CC ATG16L2 (PubMed:22082872). Interacts with DHX58/RIG-1, IFIH1/MDA5 and
CC MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate. The
CC interaction with MAVS is further enhanced upon vesicular stomatitis
CC virus (VSV) infection. Interacts with ATG3 and ATG7 (By similarity).
CC Interacts with ATG10 (PubMed:12482611). Interacts with TECPR1 (By
CC similarity). {ECO:0000250|UniProtKB:O94817,
CC ECO:0000269|PubMed:11266458, ECO:0000269|PubMed:12482611,
CC ECO:0000269|PubMed:12665549, ECO:0000269|PubMed:12890687,
CC ECO:0000269|PubMed:18768753, ECO:0000269|PubMed:19417210,
CC ECO:0000269|PubMed:22082872}.
CC -!- INTERACTION:
CC Q9CQY1; Q9CPX6: Atg3; NbExp=5; IntAct=EBI-2911788, EBI-2911810;
CC Q9CQY1; Q99J83: Atg5; NbExp=4; IntAct=EBI-2911788, EBI-2911848;
CC Q9CQY1; Q9WU78-1: Pdcd6ip; NbExp=3; IntAct=EBI-2911788, EBI-15788421;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Preautophagosomal
CC structure membrane {ECO:0000250|UniProtKB:O94817}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:O94817}. Note=TECPR1 recruits the ATG12-
CC ATG5 conjugate to the autolysosomal membrane.
CC {ECO:0000250|UniProtKB:O94817}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: Shares weak sequence similarity with ubiquitin family, but
CC contains an 'ubiquitin superfold' and the C-terminal Gly is required
CC for isopeptide linkage. {ECO:0000269|PubMed:18704115}.
CC -!- PTM: Acetylated by EP300. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ATG12 family. {ECO:0000305}.
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DR EMBL; AB066216; BAB62092.1; -; mRNA.
DR EMBL; AK008698; BAB25839.1; -; mRNA.
DR EMBL; AK016474; BAB30256.1; -; mRNA.
DR EMBL; AK005405; BAB24005.1; -; mRNA.
DR EMBL; AK167027; BAE39200.1; -; mRNA.
DR EMBL; BC070470; AAH70470.1; -; mRNA.
DR CCDS; CCDS37811.1; -.
DR RefSeq; NP_080493.2; NM_026217.3.
DR AlphaFoldDB; Q9CQY1; -.
DR SMR; Q9CQY1; -.
DR BioGRID; 212249; 239.
DR ComplexPortal; CPX-328; Atg12-Atg5-Atg16l1 complex.
DR ComplexPortal; CPX-355; Atg12-Atg5-Atg16l2 complex.
DR ComplexPortal; CPX-357; Atg5-Atg12 complex.
DR ComplexPortal; CPX-360; ATG5-ATG12-TECPR1 complex.
DR CORUM; Q9CQY1; -.
DR DIP; DIP-57729N; -.
DR IntAct; Q9CQY1; 10.
DR MINT; Q9CQY1; -.
DR STRING; 10090.ENSMUSP00000038489; -.
DR iPTMnet; Q9CQY1; -.
DR PhosphoSitePlus; Q9CQY1; -.
DR MaxQB; Q9CQY1; -.
DR PaxDb; Q9CQY1; -.
DR PeptideAtlas; Q9CQY1; -.
DR PRIDE; Q9CQY1; -.
DR ProteomicsDB; 265146; -.
DR Antibodypedia; 4593; 801 antibodies from 40 providers.
DR Ensembl; ENSMUST00000035648; ENSMUSP00000038489; ENSMUSG00000032905.
DR GeneID; 67526; -.
DR KEGG; mmu:67526; -.
DR UCSC; uc008evu.1; mouse.
DR CTD; 9140; -.
DR MGI; MGI:1914776; Atg12.
DR VEuPathDB; HostDB:ENSMUSG00000032905; -.
DR eggNOG; KOG3439; Eukaryota.
DR GeneTree; ENSGT00390000016654; -.
DR HOGENOM; CLU_106795_3_0_1; -.
DR InParanoid; Q9CQY1; -.
DR OMA; LFIYVHQ; -.
DR OrthoDB; 1525971at2759; -.
DR PhylomeDB; Q9CQY1; -.
DR TreeFam; TF325131; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-MMU-8934903; Receptor Mediated Mitophagy.
DR BioGRID-ORCS; 67526; 26 hits in 76 CRISPR screens.
DR ChiTaRS; Atg12; mouse.
DR PRO; PR:Q9CQY1; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9CQY1; protein.
DR Bgee; ENSMUSG00000032905; Expressed in blood and 262 other tissues.
DR Genevisible; Q9CQY1; MM.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IDA:ComplexPortal.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0034045; C:phagophore assembly site membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:1990234; C:transferase complex; IDA:ComplexPortal.
DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
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:0006501; P:C-terminal protein lipidation; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IMP:ComplexPortal.
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; IDA:ComplexPortal.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IDA:ComplexPortal.
DR GO; GO:1904973; P:positive regulation of viral translation; ISO:MGI.
DR GO; GO:0006497; P:protein lipidation; ISO:MGI.
DR GO; GO:1901096; P:regulation of autophagosome maturation; ISO:MGI.
DR InterPro; IPR007242; Atg12.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR13385; PTHR13385; 1.
DR Pfam; PF04110; APG12; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Cytoplasm; Isopeptide bond; Membrane;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..141
FT /note="Ubiquitin-like protein ATG12"
FT /id="PRO_0000212472"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor protein)"
FT CONFLICT 44..48
FT /note="GTEEP -> ERGT (in Ref. 2; BAB25839)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 141 AA; 15207 MW; 440F9A625624A78B CRC64;
MSEDSEVVLQ LPSAPVGAGG ESLPELSPET ATPEPPSSAA VSPGTEEPPG DTKKKIDILL
KAVGDTPIMK TKKWAVERTR TIQGLIDFIK KFLKLVASEQ LFIYVNQSFA PSPDQEVGTL
YECFGSDGKL VLHYCKSQAW G
