ATG18_CAEEL
ID ATG18_CAEEL Reviewed; 412 AA.
AC O16466; H2KYN5;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Autophagy-related protein 18 {ECO:0000305};
GN Name=atg-18 {ECO:0000312|WormBase:F41E6.13a};
GN Synonyms=atgr-18 {ECO:0000312|WormBase:F41E6.13a},
GN tag-283 {ECO:0000312|WormBase:F41E6.13a};
GN ORFNames=F41E6.13 {ECO:0000312|WormBase:F41E6.13a};
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12958363; DOI=10.1126/science.1087782;
RA Melendez A., Talloczy Z., Seaman M., Eskelinen E.L., Hall D.H., Levine B.;
RT "Autophagy genes are essential for dauer development and life-span
RT extension in C. elegans.";
RL Science 301:1387-1391(2003).
RN [3] {ECO:0000305}
RP FUNCTION.
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=21183797; DOI=10.4161/auto.7.4.14391;
RA Ruck A., Attonito J., Garces K.T., Nunez L., Palmisano N.J., Rubel Z.,
RA Bai Z., Nguyen K.C., Sun L., Grant B.D., Hall D.H., Melendez A.;
RT "The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde
RT transport in addition to autophagy in C. elegans.";
RL Autophagy 7:386-400(2011).
RN [5] {ECO:0000305}
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 228-ARG-ARG-229.
RX PubMed=21802374; DOI=10.1016/j.devcel.2011.06.024;
RA Lu Q., Yang P., Huang X., Hu W., Guo B., Wu F., Lin L., Kovacs A.L., Yu L.,
RA Zhang H.;
RT "The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of
RT omegasomes to autophagosomes.";
RL Dev. Cell 21:343-357(2011).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, AND MUTAGENESIS OF
RP 228-ARG-ARG-229.
RX PubMed=22451698; DOI=10.1083/jcb.201111053;
RA Li W., Zou W., Yang Y., Chai Y., Chen B., Cheng S., Tian D., Wang X.,
RA Vale R.D., Ou G.;
RT "Autophagy genes function sequentially to promote apoptotic cell corpse
RT degradation in the engulfing cell.";
RL J. Cell Biol. 197:27-35(2012).
RN [7] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25124690; DOI=10.15252/embr.201438618;
RA Wu Y., Cheng S., Zhao H., Zou W., Yoshina S., Mitani S., Zhang H., Wang X.;
RT "PI3P phosphatase activity is required for autophagosome maturation and
RT autolysosome formation.";
RL EMBO Rep. 15:973-981(2014).
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).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28285998; DOI=10.1016/j.cub.2017.02.015;
RA Ames K., Da Cunha D.S., Gonzalez B., Konta M., Lin F., Shechter G.,
RA Starikov L., Wong S., Buelow H.E., Melendez A.;
RT "A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-
RT Cycle Progression and Stem Cell Proliferation during Germline
RT Development.";
RL Curr. Biol. 27:905-913(2017).
RN [10] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28557996; DOI=10.1371/journal.pgen.1006764;
RA Minnerly J., Zhang J., Parker T., Kaul T., Jia K.;
RT "The cell non-autonomous function of ATG-18 is essential for neuroendocrine
RT regulation of Caenorhabditis elegans lifespan.";
RL PLoS Genet. 13:E1006764-E1006764(2017).
RN [11] {ECO:0000305}
RP FUNCTION.
RX PubMed=30133321; DOI=10.1152/ajpcell.00109.2018;
RA Hibshman J.D., Leuthner T.C., Shoben C., Mello D.F., Sherwood D.R.,
RA Meyer J.N., Baugh L.R.;
RT "Non-selective autophagy reduces mitochondrial content during starvation in
RT Caenorhabditis elegans.";
RL Am. J. Physiol. 2018:C0-C0(2018).
CC -!- FUNCTION: Component of the autophagy machinery that is recruited to
CC phosphatidylinositols on preautophagosomal structures, which are early
CC autophagic structures, to promote autophagosome formation, and the
CC subsequent degradation and clearance of engulfed apoptotic cells and P-
CC granules in somatic cells (PubMed:12958363, PubMed:19167332,
CC PubMed:21183797, PubMed:21802374, PubMed:22451698, PubMed:25124690,
CC PubMed:28557996). In particular, binds with high affinity to
CC phosphatidylinositols including phosphatidylinositol 3-phosphate
CC (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and
CC phosphatidylinositol 5-phosphate (PtdIns(5)P), and more weakly to
CC phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:21802374,
CC PubMed:22451698). Plays a role in mitophagy, which is the autophagic
CC consumption of mitochondria, in response to dietary restriction
CC (PubMed:30133321). Involved in xenophagy, the autophagy-mediated
CC degradation of pathogens and pathogen products, such as toxins
CC (PubMed:27875098). Also plays a role in membrane-pore repair
CC (PubMed:27875098). In a daf-18/PTEN- and daf-16/FOXO-dependent manner,
CC required for the proliferation of germ stem cell progenitors in the
CC gonad during the late phases of larval development (PubMed:28285998).
CC By regulating the release of neurotransmitters and neuropeptides,
CC involved in the control of lifespan in response to dietary restriction
CC and daf-2 signaling (PubMed:28557996). Probably through its involvement
CC in autophagy, required for dauer formation (PubMed:12958363).
CC {ECO:0000269|PubMed:12958363, ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:21183797, ECO:0000269|PubMed:21802374,
CC ECO:0000269|PubMed:22451698, ECO:0000269|PubMed:25124690,
CC ECO:0000269|PubMed:27875098, ECO:0000269|PubMed:28285998,
CC ECO:0000269|PubMed:28557996, ECO:0000269|PubMed:30133321,
CC ECO:0000303|PubMed:22451698}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:22451698}; Peripheral membrane protein
CC {ECO:0000305|PubMed:22451698}; Cytoplasmic side
CC {ECO:0000305|PubMed:22451698}. Cytoplasm {ECO:0000269|PubMed:25124690}.
CC Note=Partially localizes to the phagosome membrane of engulfed
CC apoptotic cells. {ECO:0000269|PubMed:22451698}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F41E6.13a};
CC IsoId=O16466-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F41E6.13b};
CC IsoId=O16466-2; Sequence=VSP_060114, VSP_060115;
CC -!- TISSUE SPECIFICITY: Expressed in neurons and intestinal cells.
CC {ECO:0000269|PubMed:28557996}.
CC -!- DOMAIN: The L/FRRG motif is required for recruitment to
CC phosphatidylinositols including phosphatidylinositol 3-phosphate
CC (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P),
CC phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol
CC 3,5-bisphosphate (PtdIns(3,5)P2). {ECO:0000269|PubMed:21802374,
CC ECO:0000269|PubMed:22451698}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in defective
CC clearance of engulfed apoptotic cells (PubMed:21183797). RNAi-mediated
CC knockdown reduces autophagic degradation of membrane pore-forming toxin
CC Cry5B (PubMed:27875098). RNAi-mediated knockdown results in reduced
CC germ stem cell proliferation during larval development
CC (PubMed:28285998). RNAi-mediated knockdown causes abnormalities in
CC constitutive dauer formation in daf-2 e1370 mutant including a lack of
CC autophagosome formation (PubMed:12958363).
CC {ECO:0000269|PubMed:12958363, ECO:0000269|PubMed:21183797,
CC ECO:0000269|PubMed:27875098, ECO:0000269|PubMed:28285998}.
CC -!- SIMILARITY: Belongs to the WD repeat PROPPIN family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX284605; CCD64090.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD64091.1; -; Genomic_DNA.
DR PIR; T31883; T31883.
DR RefSeq; NP_741576.1; NM_171491.3. [O16466-1]
DR RefSeq; NP_741577.1; NM_171492.4. [O16466-2]
DR AlphaFoldDB; O16466; -.
DR SMR; O16466; -.
DR STRING; 6239.F41E6.13a; -.
DR EPD; O16466; -.
DR PaxDb; O16466; -.
DR EnsemblMetazoa; F41E6.13a.1; F41E6.13a.1; WBGene00018294. [O16466-1]
DR EnsemblMetazoa; F41E6.13b.1; F41E6.13b.1; WBGene00018294. [O16466-2]
DR GeneID; 179246; -.
DR KEGG; cel:CELE_F41E6.13; -.
DR CTD; 179246; -.
DR WormBase; F41E6.13a; CE10268; WBGene00018294; atg-18. [O16466-1]
DR WormBase; F41E6.13b; CE30784; WBGene00018294; atg-18. [O16466-2]
DR eggNOG; KOG2110; Eukaryota.
DR GeneTree; ENSGT00940000167852; -.
DR HOGENOM; CLU_025895_1_1_1; -.
DR InParanoid; O16466; -.
DR OMA; YVHEFPA; -.
DR OrthoDB; 1216824at2759; -.
DR PhylomeDB; O16466; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR PRO; PR:O16466; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00018294; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:WormBase.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034045; C:phagophore assembly site membrane; IBA:GO_Central.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:WormBase.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:WormBase.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:WormBase.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0006914; P:autophagy; IGI:WormBase.
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:0097237; P:cellular response to toxic substance; IMP:UniProtKB.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:0048598; P:embryonic morphogenesis; IGI:WormBase.
DR GO; GO:0036093; P:germ cell proliferation; IMP:UniProtKB.
DR GO; GO:0042078; P:germ-line stem cell division; IMP:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; IMP:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0061365; P:positive regulation of triglyceride lipase activity; IMP:WormBase.
DR GO; GO:0012501; P:programmed cell death; IGI:WormBase.
DR GO; GO:0030163; P:protein catabolic process; IMP:WormBase.
DR GO; GO:0006497; P:protein lipidation; IBA:GO_Central.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IBA:GO_Central.
DR GO; GO:0098792; P:xenophagy; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Cytoplasmic vesicle;
KW Lipid-binding; Membrane; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..412
FT /note="Autophagy-related protein 18"
FT /id="PRO_0000446904"
FT REPEAT 100..139
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 142..183
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 186..226
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 232..271
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REGION 363..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 227..230
FT /note="L/FRRG motif"
FT /evidence="ECO:0000269|PubMed:21802374,
FT ECO:0000269|PubMed:22451698"
FT COMPBIAS 365..398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 392..394
FT /note="NQS -> ISV (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060114"
FT VAR_SEQ 395..412
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060115"
FT MUTAGEN 228..229
FT /note="RR->KK: Abolishes phosphatidylinositol binding.
FT Abolishes recruitment to phagosome membrane. Does not
FT rescue the apoptotic corpse degradation defect of the atg-
FT 18 gk378 mutant."
FT /evidence="ECO:0000269|PubMed:21802374,
FT ECO:0000269|PubMed:22451698"
FT MUTAGEN 228..229
FT /note="RR->TT: Abolishes phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:21802374"
SQ SEQUENCE 412 AA; 45274 MW; D5B99F38FCC3A3D8 CRC64;
MSATTSEENP DSINYIGFNQ DSKVICVGHK DGYMFYKTAD ILENNTLTYE GENLTHLGLN
NCLIIERLFS SALMVVISQK DPRVLHVYHF TSRNIICDHR FNKSVLTVRL NRDRIVVCLE
DCIYIYNLKD MKMMHNIMDT PTNKLGVLDL TSNPGNALIA YPGSTDTGSV HLFDAINLSS
VSTFNAHEGT IACLKFNQEG NMIATASTKG TVIRVYSVPN GHRLFEFRRG VTRCVNIYSL
CFSSDSKYLT SSSNTETVHV FKLEKTEGVD NKPEASTEGG GWFDAINKTF SAYMPSQVLQ
VGELMTTERS FATAKLPGAA RSNQVSLVSH KNQQYVMAAT SDGFVYAYRL DPEGGELDLI
KQHNIGPKSD TSRASPTSTG SGGAAKSAEA SNQSVPNMDD PDDFPPMSHT SG
