ID   ATG12_RAT               Reviewed;         141 AA.
AC   Q2TBJ5; Q5M9F9;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 1.
DT   27-MAR-2024, entry version 121.
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|RGD:1306306}; Synonyms=Apg12l;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney, 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   [2]
RP   INDUCTION BY OPTIC NERVE TRANSECTION.
RX   PubMed=18521932; DOI=10.1002/jnr.21738;
RA   Kim S.H., Munemasa Y., Kwong J.M., Ahn J.H., Mareninov S., Gordon L.K.,
RA   Caprioli J., Piri N.;
RT   "Activation of autophagy in retinal ganglion cells.";
RL   J. Neurosci. Res. 86:2943-2951(2008).
RN   [3]
RP   INDUCTION BY STARVATION.
RX   PubMed=19696026; DOI=10.1074/jbc.m109.024406;
RA   Sengupta A., Molkentin J.D., Yutzey K.E.;
RT   "FoxO transcription factors promote autophagy in cardiomyocytes.";
RL   J. Biol. Chem. 284:28319-28331(2009).
RN   [4]
RP   INDUCTION BY STARVATION.
RX   PubMed=24187137; DOI=10.1074/jbc.m113.500736;
RA   Seldin M.M., Lei X., Tan S.Y., Stanson K.P., Wei Z., Wong G.W.;
RT   "Skeletal muscle-derived myonectin activates the mammalian target of
RT   rapamycin (mTOR) pathway to suppress autophagy in liver.";
RL   J. Biol. Chem. 288:36073-36082(2013).
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. The ATG12-ATG5 conjugate also negatively regulates the
CC       innate antiviral immune response by blocking the type I IFN production
CC       pathway through direct association with RARRES3 and MAVS. Also plays a
CC       role in translation or delivery of incoming viral RNA to the
CC       translation apparatus (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Forms a conjugate with ATG5. Part of the minor complex
CC       composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this complex
CC       interacts with ATG3 leading to disruption of ATG7 interaction and
CC       promotion of ATG8-like proteins lipidation (By similarity). Forms an
CC       800-kDa complex composed of ATG12-ATG5 and ATG16L2 (By similarity).
CC       Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form
CC       as well as in ATG12-ATG5 conjugate. The interaction with MAVS is
CC       further enhanced upon vesicular stomatitis virus (VSV) infection.
CC       Interacts with ATG3; this interaction is essential for
CC       phosphatidylethanolamine (PE)-conjugated ATG8-like proteins formation
CC       (By similarity). Interacts with ATG7 (By similarity). Interacts with
CC       ATG10 (By similarity). Interacts with TECPR1. Interacts with SH3BGRL
CC       (By similarity). The ATG12-ATG5 conjugate interacts with PDCD6IP (via
CC       the BRO1 domain); this interaction is bridged by ATG12 and promotes
CC       multiple PDCD6IP-mediated functions such as endolysosomal trafficking,
CC       macroautophagy and exosome biogenesis (By similarity).
CC       {ECO:0000250|UniProtKB:O94817, ECO:0000250|UniProtKB:Q9CQY1}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Preautophagosomal
CC       structure membrane {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}. Note=TECPR1 recruits the ATG12-ATG5 conjugate to the
CC       autolysosomal membrane. {ECO:0000250}.
CC   -!- INDUCTION: Activated in retinal ganglion cells (RGCs) following optic
CC       nerve transection (PubMed:18521932). Induced under starvation
CC       conditions, through the action of the Foxo1 and Foxo3 transcription
CC       factors (PubMed:19696026, PubMed:24187137).
CC       {ECO:0000269|PubMed:18521932, ECO:0000269|PubMed:19696026,
CC       ECO:0000269|PubMed:24187137}.
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:0000250}.
CC   -!- PTM: Acetylated by EP300. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ATG12 family. {ECO:0000305}.
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DR   EMBL; BC087139; AAH87139.1; -; mRNA.
DR   EMBL; BC110056; AAI10057.1; -; mRNA.
DR   RefSeq; NP_001033584.1; NM_001038495.1.
DR   AlphaFoldDB; Q2TBJ5; -.
DR   SMR; Q2TBJ5; -.
DR   BioGRID; 262598; 1.
DR   STRING; 10116.ENSRNOP00000000170; -.
DR   PhosphoSitePlus; Q2TBJ5; -.
DR   jPOST; Q2TBJ5; -.
DR   PaxDb; 10116-ENSRNOP00000000170; -.
DR   Ensembl; ENSRNOT00000000170.6; ENSRNOP00000000170.4; ENSRNOG00000000157.6.
DR   GeneID; 361321; -.
DR   KEGG; rno:361321; -.
DR   UCSC; RGD:1306306; rat.
DR   AGR; RGD:1306306; -.
DR   CTD; 9140; -.
DR   RGD; 1306306; Atg12.
DR   eggNOG; KOG3439; Eukaryota.
DR   GeneTree; ENSGT00390000016654; -.
DR   HOGENOM; CLU_106795_3_0_1; -.
DR   InParanoid; Q2TBJ5; -.
DR   OMA; LFIYVHQ; -.
DR   OrthoDB; 101981at2759; -.
DR   PhylomeDB; Q2TBJ5; -.
DR   TreeFam; TF325131; -.
DR   Reactome; R-RNO-1632852; Macroautophagy.
DR   Reactome; R-RNO-5205685; PINK1-PRKN Mediated Mitophagy.
DR   Reactome; R-RNO-8934903; Receptor Mediated Mitophagy.
DR   PRO; PR:Q2TBJ5; -.
DR   Proteomes; UP000002494; Chromosome 18.
DR   Bgee; ENSRNOG00000000157; Expressed in thymus and 20 other cell types or tissues.
DR   GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; ISO:RGD.
DR   GO; GO:0005776; C:autophagosome; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0034045; C:phagophore assembly site membrane; ISO:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:1990234; C:transferase complex; ISO:RGD.
DR   GO; GO:0000045; P:autophagosome assembly; ISO:RGD.
DR   GO; GO:0006914; P:autophagy; IMP:RGD.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0016236; P:macroautophagy; ISO:RGD.
DR   GO; GO:0050687; P:negative regulation of defense response to virus; ISO:RGD.
DR   GO; GO:0045824; P:negative regulation of innate immune response; ISO:RGD.
DR   GO; GO:0032480; P:negative regulation of type I interferon production; ISO:RGD.
DR   GO; GO:0044804; P:nucleophagy; IBA:GO_Central.
DR   GO; GO:1904973; P:positive regulation of viral translation; ISO:RGD.
DR   GO; GO:1901096; P:regulation of autophagosome maturation; ISO:RGD.
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; Q2TBJ5; RN.
PE   2: Evidence at transcript level;
KW   Acetylation; Autophagy; Cytoplasm; Immunity; Innate immunity;
KW   Isopeptide bond; Membrane; Reference proteome; Ubl conjugation pathway.
FT   CHAIN           1..141
FT                   /note="Ubiquitin-like protein ATG12"
FT                   /id="PRO_0000233273"
FT   REGION          24..54
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                   /evidence="ECO:0000250"
SQ   SEQUENCE   141 AA;  15284 MW;  938B3F50F6454CB6 CRC64;
     MAEDPEAVLQ LPAAPAAAAG ESLLELSPET AIPEPPSSVA VSPGTEEPPG DTKKKIDILL
     KAVGDTPIMK TKKWAVERTR TVQALIDFIR KFLRLLASEQ LFIYVNQSFA PSPDQEVGTL
     YECFGSDGKL VLHYCKSQAW G
//