ATG12_CAEEL
ID ATG12_CAEEL Reviewed; 118 AA.
AC Q10931;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Ubiquitin-like protein atg-12 {ECO:0000250|UniProtKB:O94817};
DE AltName: Full=Autophagy-related protein 12 {ECO:0000250|UniProtKB:O94817};
GN Name=lgg-3 {ECO:0000312|WormBase:B0336.8};
GN Synonyms=atg-12 {ECO:0000312|WormBase:B0336.8};
GN ORFNames=B0336.8 {ECO:0000312|WormBase:B0336.8};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=17204841; DOI=10.4161/auto.3636;
RA Hars E.S., Qi H., Ryazanov A.G., Jin S., Cai L., Hu C., Liu L.F.;
RT "Autophagy regulates ageing in C. elegans.";
RL Autophagy 3:93-95(2007).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19167332; DOI=10.1016/j.cell.2008.12.022;
RA Zhang Y., Yan L., Zhou Z., Yang P., Tian E., Zhang K., Zhao Y., Li Z.,
RA Song B., Han J., Miao L., Zhang H.;
RT "SEPA-1 mediates the specific recognition and degradation of P granule
RT components by autophagy in C. elegans.";
RL Cell 136:308-321(2009).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22105480; DOI=10.1038/cr.2011.182;
RA Zhou Q., Li H., Xue D.;
RT "Elimination of paternal mitochondria through the lysosomal degradation
RT pathway in C. elegans.";
RL Cell Res. 21:1662-1669(2011).
RN [5] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=24185444; DOI=10.4161/auto.26095;
RA Zhang H., Wu F., Wang X., Du H., Wang X., Zhang H.;
RT "The two C. elegans ATG-16 homologs have partially redundant functions in
RT the basal autophagy pathway.";
RL Autophagy 9:1965-1974(2013).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH LGG-2, DEVELOPMENTAL STAGE, DOMAIN, AND
RP MUTAGENESIS OF ASP-87; 90-PHE--LEU-93 AND GLU-91.
RX PubMed=26687600; DOI=10.1016/j.molcel.2015.11.019;
RA Wu F., Watanabe Y., Guo X.Y., Qi X., Wang P., Zhao H.Y., Wang Z.,
RA Fujioka Y., Zhang H., Ren J.Q., Fang T.C., Shen Y.X., Feng W., Hu J.J.,
RA Noda N.N., Zhang H.;
RT "Structural Basis of the Differential Function of the Two C. elegans Atg8
RT Homologs, LGG-1 and LGG-2, in Autophagy.";
RL Mol. Cell 60:914-929(2015).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28758895; DOI=10.18632/aging.101267;
RA Shamalnasab M., Dhaoui M., Thondamal M., Harvald E.B., Faergeman N.J.,
RA Aguilaniu H., Fabrizio P.;
RT "HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the
RT acyl-CoA-binding protein MAA-1.";
RL Aging (Albany NY) 9:1745-1769(2017).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27875098; DOI=10.1080/15548627.2016.1256933;
RA Chen H.D., Kao C.Y., Liu B.Y., Huang S.W., Kuo C.J., Ruan J.W., Lin Y.H.,
RA Huang C.R., Chen Y.H., Wang H.D., Aroian R.V., Chen C.S.;
RT "HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for
RT epithelium intrinsic cellular defense against bacterial pore-forming toxin
RT in C. elegans.";
RL Autophagy 13:371-385(2017).
CC -!- FUNCTION: Ubiquitin-like protein involved in autophagy vesicles
CC formation (By similarity). Conjugation with atg-5 through a ubiquitin-
CC like conjugating system involving also atg-7 as an E1-like activating
CC enzyme and atg-10 as an E2-like conjugating enzyme, is essential for
CC its function (By similarity). Most likely a component of an atg-5-lgg-
CC 3-atg-16 complex that promotes autophagosome formation by associating
CC with lgg-2, but not lgg-1, at the preautophagosomal membrane
CC (PubMed:26687600, PubMed:28758895). Probably, as part of an atg-5-lgg-
CC 3-atg-16 complex, required for lgg-1 lipidation; the complex acts as an
CC E3-like enzyme promoting atg-3-mediated lgg-1 lipidation (Probable).
CC Involved in the degradation of P-granules by autophagy in somatic cells
CC (PubMed:19167332). This ensures exclusive localization of the P-
CC granules in germ cells (PubMed:19167332). Involved in the elimination
CC of paternal mitochondria in fertilized eggs (PubMed:22105480). Involved
CC in xenophagy, the autophagy-mediated degradation of pathogens and
CC pathogen products, such as toxins (PubMed:27875098). Also plays a role
CC in membrane-pore repair (PubMed:27875098).
CC {ECO:0000250|UniProtKB:O94817, ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:22105480, ECO:0000269|PubMed:26687600,
CC ECO:0000269|PubMed:27875098, ECO:0000269|PubMed:28758895,
CC ECO:0000305|PubMed:24185444}.
CC -!- SUBUNIT: Most likely a component of a complex at least containing atg-
CC 5, lgg-3/ATG12, atg-16.1 and/or atg-16.2 (Probable). Interacts with
CC atg-5 (By similarity). Interacts (via the LIR motif) with lgg-2; the
CC interaction is direct (PubMed:26687600).
CC {ECO:0000255|RuleBase:RU361201, ECO:0000269|PubMed:26687600,
CC ECO:0000305|PubMed:24185444}.
CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane
CC {ECO:0000269|PubMed:24185444}; Peripheral membrane protein
CC {ECO:0000269|PubMed:24185444}. Note=Recruited to the membrane of
CC autophagic vesicles. {ECO:0000269|PubMed:24185444}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low levels in embryos.
CC {ECO:0000269|PubMed:24185444, ECO:0000269|PubMed:26687600}.
CC -!- DOMAIN: The LIR motif (LC3-interacting region) is required for its
CC interaction with lgg-2. {ECO:0000269|PubMed:26687600}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes no visible
CC phenotype, but animals have a reduced lifespan (PubMed:17204841).
CC Accumulation of pgl-1-positive P granules in somatic cells
CC (PubMed:19167332). Reduced lgg-1-positive autophagosomes in seam cells
CC (PubMed:28758895). Delayed removal of paternal mitochondria in
CC fertilized eggs (PubMed:22105480). RNAi-mediated knockdown reduces
CC autophagic degradation of membrane pore-forming toxin Cry5B.
CC {ECO:0000269|PubMed:17204841, ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:22105480, ECO:0000269|PubMed:27875098,
CC ECO:0000269|PubMed:28758895}.
CC -!- SIMILARITY: Belongs to the ATG12 family.
CC {ECO:0000255|RuleBase:RU361201}.
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DR EMBL; BX284603; CCD61524.1; -; Genomic_DNA.
DR PIR; T15334; T15334.
DR RefSeq; NP_498228.1; NM_065827.1.
DR AlphaFoldDB; Q10931; -.
DR SMR; Q10931; -.
DR ComplexPortal; CPX-3863; atg-5-atg-12-atg-16.1-atg-16.2 complex.
DR ComplexPortal; CPX-3864; ATG12-ATG5 complex.
DR ComplexPortal; CPX-3865; atg-5-atg-12-atg-16.1 complex.
DR ComplexPortal; CPX-3866; atg-5-atg-12-atg-16.2 complex.
DR STRING; 6239.B0336.8; -.
DR EPD; Q10931; -.
DR PaxDb; Q10931; -.
DR PeptideAtlas; Q10931; -.
DR EnsemblMetazoa; B0336.8.1; B0336.8.1; WBGene00002982.
DR GeneID; 175793; -.
DR KEGG; cel:CELE_B0336.8; -.
DR UCSC; B0336.8; c. elegans.
DR CTD; 175793; -.
DR WormBase; B0336.8; CE00776; WBGene00002982; lgg-3.
DR eggNOG; KOG3439; Eukaryota.
DR GeneTree; ENSGT00390000016654; -.
DR HOGENOM; CLU_106795_2_0_1; -.
DR InParanoid; Q10931; -.
DR OMA; FASANCK; -.
DR OrthoDB; 1525971at2759; -.
DR PhylomeDB; Q10931; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR Reactome; R-CEL-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-CEL-8934903; Receptor Mediated Mitophagy.
DR PRO; PR:Q10931; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00002982; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IBA:GO_Central.
DR GO; GO:0000421; C:autophagosome membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IC:ComplexPortal.
DR GO; GO:0034045; C:phagophore assembly site membrane; IBA:GO_Central.
DR GO; GO:1990234; C:transferase complex; IC:ComplexPortal.
DR GO; GO:0000045; P:autophagosome assembly; IMP:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IC:ComplexPortal.
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:0097237; P:cellular response to toxic substance; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0016236; P:macroautophagy; IC:ComplexPortal.
DR GO; GO:0001778; P:plasma membrane repair; IMP:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; IC:ComplexPortal.
DR GO; GO:0098792; P:xenophagy; IMP:UniProtKB.
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 Autophagy; Isopeptide bond; Membrane; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..118
FT /note="Ubiquitin-like protein atg-12"
FT /id="PRO_0000447608"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 90..93
FT /note="LIR"
FT /evidence="ECO:0000269|PubMed:26687600"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 87
FT /note="Required for interaction with lgg-2"
FT /evidence="ECO:0000269|PubMed:26687600"
FT CROSSLNK 118
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-129 in atg-5)"
FT /evidence="ECO:0000250|UniProtKB:O94817"
FT MUTAGEN 87
FT /note="D->K: Abolishes the interaction with lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 90..93
FT /note="FETL->AAAA,AETL: Abolishes the interaction with lgg-
FT 2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 91
FT /note="E->K: Abolishes the interaction with lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
SQ SEQUENCE 118 AA; 12982 MW; 6201B9F1AEAFACE4 CRC64;
METETATTPT GNTEPTAAAS AEPPKSDKVT VRLRNIADAP VLKNKKMVVN PTDTVASFIL
KLRKLLNIQA NNSLFLYIDN TFAPSPDTTF ETLSRCYSVK ITDKEILELQ YSITPAYG
