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   27-MAR-2024, entry version 169.
DE   RecName: Full=Ubiquitin-like protein ATG12 {ECO:0000305};
DE   AltName: Full=Autophagy-related protein 12;
DE            Short=APG12-like;
GN   Name=Atg12 {ECO:0000312|MGI:MGI:1914776}; 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).
RN   [13]
RP   INTERACTION WITH PDCD6IP.
RX   PubMed=25686249; DOI=10.1038/ncb3112;
RA   Murrow L., Malhotra R., Debnath J.;
RT   "ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late
RT   endosome function.";
RL   Nat. Cell Biol. 17:300-310(2015).
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       Part of the minor complex composed of 4 sets of ATG12-ATG5 and ATG16L1
CC       (400 kDa); this complex interacts with ATG3 leading to disruption of
CC       ATG7 interaction and promotion of ATG8-like proteins lipidation
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; this interaction is
CC       essential for phosphatidylethanolamine (PE)-conjugated ATG8-like
CC       proteins formation (By similarity). Interacts with ATG7 (By
CC       similarity). Interacts with ATG10 (PubMed:12482611). Interacts with
CC       TECPR1 (By similarity). Interacts with SH3BGRL (By similarity). The
CC       ATG12-ATG5 conjugate interacts with PDCD6IP (via the BRO1 domain); this
CC       interaction is bridged by ATG12 and promotes multiple PDCD6IP-mediated
CC       functions such as endolysosomal trafficking, macroautophagy and exosome
CC       biogenesis (PubMed:25686249). {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, ECO:0000269|PubMed:25686249}.
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; 10090-ENSMUSP00000038489; -.
DR   PeptideAtlas; Q9CQY1; -.
DR   ProteomicsDB; 265146; -.
DR   Antibodypedia; 4593; 860 antibodies from 40 providers.
DR   Ensembl; ENSMUST00000035648.6; ENSMUSP00000038489.5; ENSMUSG00000032905.6.
DR   GeneID; 67526; -.
DR   KEGG; mmu:67526; -.
DR   UCSC; uc008evu.1; mouse.
DR   AGR; MGI:1914776; -.
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; 101981at2759; -.
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 81 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 266 other cell types or tissues.
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: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:0044804; P:nucleophagy; IBA:GO_Central.
DR   GO; GO:1904973; P:positive regulation of viral translation; ISO:MGI.
DR   GO; GO:1901096; P:regulation of autophagosome maturation; ISO:MGI.
DR   CDD; cd01612; Ubl_ATG12; 1.
DR   InterPro; IPR007242; Atg12.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR13385; AUTOPHAGY PROTEIN 12; 1.
DR   PANTHER; PTHR13385:SF0; UBIQUITIN-LIKE PROTEIN ATG12; 1.
DR   Pfam; PF04110; APG12; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   Genevisible; Q9CQY1; MM.
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
//