LGG2_CAEEL
ID LGG2_CAEEL Reviewed; 130 AA.
AC Q23536;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein lgg-2;
GN Name=lgg-2 {ECO:0000312|WormBase:ZK593.6a};
GN ORFNames=ZK593.6 {ECO:0000312|WormBase:ZK593.6a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20523114; DOI=10.4161/auto.6.5.12252;
RA Alberti A., Michelet X., Djeddi A., Legouis R.;
RT "The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer
RT formation and longevity in C. elegans.";
RL Autophagy 6:622-633(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25126728; DOI=10.4161/auto.29745;
RA Jenzer C., Manil-Segalen M., Lefebvre C., Largeau C., Glatigny A.,
RA Legouis R.;
RT "Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1
RT mutant.";
RL Autophagy 10:1868-1872(2014).
RN [5]
RP FUNCTION, INTERACTION WITH VPS-39, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-130.
RX PubMed=24374177; DOI=10.1016/j.devcel.2013.11.022;
RA Manil-Segalen M., Lefebvre C., Jenzer C., Trichet M., Boulogne C.,
RA Satiat-Jeunemaitre B., Legouis R.;
RT "The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by
RT interacting with the HOPS subunit VPS39.";
RL Dev. Cell 28:43-55(2014).
RN [6]
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 17-130 IN COMPLEX WITH WEEL
RP PEPTIDE, FUNCTION, INTERACTION WITH LGG-3; ATG-16.1; ATG-16.2; SEPA-1;
RP SQST-1; EPG-2; ATG-7 AND ATG-3, SUBCELLULAR LOCATION, LIPIDATION, AND
RP MUTAGENESIS OF 20-ARG-ARG-21; ARG-26 AND ASP-116.
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).
CC -!- FUNCTION: Ubiquitin-like modifier involved in the formation of
CC autophagosomal vacuoles (autophagosomes) (PubMed:26687600). When
CC lipidated mediates tethering between adjacent membranes and stimulates
CC membrane fusion (PubMed:26687600). Less effective at promoting membrane
CC fusion than lgg-1 (PubMed:26687600). Acts upstream of the autophagy
CC protein epg-5 in the aggrephagy pathway, which is the macroautophagic
CC degradation of ubiquitinated protein aggregates, and preferentially
CC interacts with autophagy proteins and substrates containing LIR motifs
CC to mediate autophagosome formation and protein aggregate degradation
CC (PubMed:26687600). In particular binds to components of an atg-5-lgg-3-
CC atg-16 complex to regulate autophagosome formation and cargo
CC sequestration (PubMed:26687600). Required for the degradation of
CC specific sqst-1-containing aggregates during embryogenesis and the
CC early stages of larval development (PubMed:26687600). Involved in
CC allophagy, which is an autophagic process in which paternal
CC mitochondria and organelles are degraded during fertilization, and
CC moreover is required for the degradation of lgg-1-positive allophagic
CC autophagosomes in embryos (PubMed:25126728, PubMed:24374177). 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). Through HOPS complex subunit
CC vps-39, tethers lysosomes with autophagosomes to form autolysosomes
CC (PubMed:24374177). Plays a role in the distribution and clearance of
CC germ cell specific P-granules from somatic cells to ensure exclusive
CC localization of the P-granules in germ cells (PubMed:19167332).
CC Essential for dauer development and life-span extension
CC (PubMed:20523114). {ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:20523114, ECO:0000269|PubMed:24374177,
CC ECO:0000269|PubMed:25126728, ECO:0000269|PubMed:26687600,
CC ECO:0000269|PubMed:27875098}.
CC -!- SUBUNIT: May interact with vps-39 (PubMed:24374177). Interacts with
CC lgg-3; the interaction is direct (PubMed:26687600). Interacts with atg-
CC 16.1 (via WD domain) and atg-16.2 (via WD 5-6 repeats); the
CC interactions are direct (PubMed:26687600). Interacts with sepa-1 (via
CC the LIR motifs); the interaction is direct (PubMed:26687600). Interacts
CC with sqst-1 (via the LIR motifs); the interaction is direct
CC (PubMed:26687600). Interacts with epg-2 (via the LIR motifs); the
CC interaction is weak (PubMed:26687600). Interacts with atg-7; the
CC interaction is direct (PubMed:26687600). Interacts with atg-3
CC (PubMed:26687600). The interaction with atg-7 and atg-3 may be required
CC for the lipidation of lgg-2 (PubMed:26687600).
CC {ECO:0000269|PubMed:24374177, ECO:0000269|PubMed:26687600}.
CC -!- INTERACTION:
CC Q23536; K8ESC5-2: atg-4.1; NbExp=3; IntAct=EBI-331856, EBI-331850;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:20523114, ECO:0000269|PubMed:24374177}. Cytoplasm
CC {ECO:0000269|PubMed:24374177}. Cell membrane
CC {ECO:0000305|PubMed:26687600}; Lipid-anchor
CC {ECO:0000305|PubMed:26687600}. Note=In embryos, diffuse cytoplasmic
CC localization with some areas displaying a more punctate distribution
CC (PubMed:24374177). Specifically, upon fertilization localizes to
CC autophagosomes around the male pronucleus. During the first embryonic
CC divisions and after the 25-cell stage, localizes to a small population
CC of autophagosomes and to another small population of autophagosomes
CC containing both lgg-1 and lgg-2. Localization to autophagosomes is
CC dependent on atg-7. {ECO:0000269|PubMed:24374177}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis.
CC {ECO:0000269|PubMed:24374177, ECO:0000269|PubMed:26687600}.
CC -!- PTM: This protein is subject to lipidation (PubMed:26687600).
CC Lipidation is regulated by lgg-1 (PubMed:26687600).
CC {ECO:0000269|PubMed:26687600}.
CC -!- DISRUPTION PHENOTYPE: Viable with no visible defects in development or
CC fertility (PubMed:24374177). Embryos contain an increased number of
CC endosomes (PubMed:25126728). Lysosomes have a reduced capacity to
CC interact with autophagosomes in embryos and furthermore, there is
CC defective autophagosome degradation with an accumulation of lgg-1-
CC positive autophagosomes in 500-cell embryos (PubMed:24374177). Double
CC knockout with rab-7 partially rescues the defective lgg-1- and lgg-2-
CC positive autophagosome degradation defect in the individual rab-7 and
CC lgg-2 single mutants (PubMed:24374177). RNAi-mediated knockdown results
CC in the accumulation of germ cell specific P-granules in somatic cells
CC as indicated by increased numbers of pgl-1 positive granules in embryos
CC (PubMed:19167332). RNAi-mediated knockdown reduces autophagic
CC degradation of membrane pore-forming toxin Cry5B.
CC {ECO:0000269|PubMed:19167332, ECO:0000269|PubMed:24374177,
CC ECO:0000269|PubMed:25126728, ECO:0000269|PubMed:27875098}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; Z69385; CAA93421.1; -; Genomic_DNA.
DR PIR; T27920; T27920.
DR RefSeq; NP_001255523.2; NM_001268594.2.
DR PDB; 5AZH; X-ray; 2.30 A; A=11-130.
DR PDB; 5E6N; X-ray; 2.10 A; A/B=17-130.
DR PDB; 5E6O; X-ray; 1.80 A; A/B/C/D=17-130.
DR PDBsum; 5AZH; -.
DR PDBsum; 5E6N; -.
DR PDBsum; 5E6O; -.
DR AlphaFoldDB; Q23536; -.
DR SMR; Q23536; -.
DR BioGRID; 43089; 20.
DR DIP; DIP-25399N; -.
DR IntAct; Q23536; 9.
DR STRING; 6239.ZK593.6a; -.
DR EPD; Q23536; -.
DR PaxDb; Q23536; -.
DR PeptideAtlas; Q23536; -.
DR EnsemblMetazoa; ZK593.6a.1; ZK593.6a.1; WBGene00002981.
DR GeneID; 177989; -.
DR KEGG; cel:CELE_ZK593.6; -.
DR UCSC; ZK593.6.1; c. elegans.
DR CTD; 177989; -.
DR WormBase; ZK593.6a; CE50405; WBGene00002981; lgg-2.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000174218; -.
DR HOGENOM; CLU_119276_1_1_1; -.
DR InParanoid; Q23536; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; Q23536; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR Reactome; R-CEL-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-CEL-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-CEL-9664873; Pexophagy.
DR Reactome; R-CEL-9755511; KEAP1-NFE2L2 pathway.
DR SignaLink; Q23536; -.
DR PRO; PR:Q23536; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002981; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q23536; baseline and differential.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0000421; C:autophagosome membrane; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0097352; P:autophagosome maturation; IBA:GO_Central.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0097237; P:cellular response to toxic substance; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEP:WormBase.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0001778; P:plasma membrane repair; IMP:UniProtKB.
DR GO; GO:1901098; P:positive regulation of autophagosome maturation; IMP:UniProtKB.
DR GO; GO:0098792; P:xenophagy; IMP:UniProtKB.
DR InterPro; IPR004241; Atg8-like.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10969; PTHR10969; 1.
DR Pfam; PF02991; ATG8; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Lipoprotein; Membrane; Reference proteome.
FT CHAIN 1..130
FT /note="Protein lgg-2"
FT /id="PRO_0000212378"
FT LIPID 130
FT /note="Phosphatidylethanolamine amidated glycine"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT MUTAGEN 20..21
FT /note="RR->AA: Impairs tethering between adjacent
FT membranes."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 26
FT /note="R->A: Does not rescue the degradation defect in the
FT lgg-2 bp556 mutant."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 26
FT /note="R->C: In bp556; defective degradation of protein
FT aggregates during embryogenesis and early larval stages
FT with an accumulation of sqst-1-containing aggregates in
FT embryos and up until the L1 stage of larval development."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 116
FT /note="D->A: Does not rescue the degradation defect in the
FT lgg-2 bp556 mutant."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 130
FT /note="G->A: Diffuse cytosolic localization in 500-cell
FT embryos with no punctate pattern of distribution which is
FT in contrast to wild-type."
FT /evidence="ECO:0000269|PubMed:24374177"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:5E6O"
FT HELIX 23..36
FT /evidence="ECO:0007829|PDB:5E6O"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:5E6O"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:5E6O"
FT HELIX 70..81
FT /evidence="ECO:0007829|PDB:5E6O"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:5E6O"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:5E6O"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:5E6O"
SQ SEQUENCE 130 AA; 15095 MW; 347518DF8C8D3154 CRC64;
MSGNRGGSYI SGIVPSFKER RPFHERQKDV EEIRSQQPNK VPVIIERFDG ERSLPLMDRC
KFLVPEHITV AELMSIVRRR LQLHPQQAFF LLVNERSMVS NSMSMSNLYS QERDPDGFVY
MVYTSQPAFG
