EPG6_CAEEL
ID EPG6_CAEEL Reviewed; 388 AA.
AC Q86MP3; E3CTH5; Q5DTE8; Q9XX21;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Ectopic P granules protein 6 {ECO:0000312|WormBase:Y39A1A.1b};
GN Name=epg-6 {ECO:0000312|WormBase:Y39A1A.1b};
GN ORFNames=Y39A1A.1 {ECO:0000312|WormBase:Y39A1A.1b};
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, INTERACTION WITH ATG-2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DOMAIN, AND MUTAGENESIS OF 161-ARG--GLU-388;
RP 259-ARG-ARG-260 AND 265-ALA--PHE-328.
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 [3]
RP FUNCTION, AND MUTAGENESIS OF 161-ARG--GLU-388.
RX PubMed=30102152; DOI=10.7554/elife.36588;
RA Liu Y., Zou W., Yang P., Wang L., Ma Y., Zhang H., Wang X.;
RT "Autophagy-dependent ribosomal RNA degradation is essential for maintaining
RT nucleotide homeostasis during C. elegans development.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Component of the epg-6/atg-2 complex, which is involved in
CC the generation of autophagosomes from omegasomes and in the
CC distribution of atg-9 and atg-13 during the autophagy-mediated
CC degradation of protein aggregates (PubMed:21802374). Binds to
CC phosphatidylinositols on preautophagosomes, which are early autophagic
CC structures, to promote autophagosome formation (PubMed:21802374). In
CC particular, binds with high affinity to phosphatidylinositols including
CC phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol
CC 5-phosphate (PtdIns(5)P), but more weakly to phosphatidylinositol 4-
CC phosphate (PtdIns(4)P) and phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2) (PubMed:21802374). Involved in autophagy-mediated
CC degradation of ribosomal RNA and ribosomal proteins in lysosomes, which
CC is essential for maintaining nucleotide homeostasis (PubMed:30102152).
CC {ECO:0000269|PubMed:21802374, ECO:0000269|PubMed:30102152}.
CC -!- SUBUNIT: Interacts with atg-2; the interaction is direct.
CC {ECO:0000269|PubMed:21802374}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21802374}.
CC Preautophagosomal structure membrane {ECO:0000305|PubMed:21802374};
CC Peripheral membrane protein {ECO:0000305|PubMed:21802374}.
CC Note=Localizes to the cytoplasm of all cells during embryogenesis.
CC {ECO:0000269|PubMed:21802374}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=b {ECO:0000312|WormBase:Y39A1A.1b};
CC IsoId=Q86MP3-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y39A1A.1a};
CC IsoId=Q86MP3-2; Sequence=VSP_060118;
CC Name=c {ECO:0000312|WormBase:Y39A1A.1c};
CC IsoId=Q86MP3-3; Sequence=VSP_060117, VSP_060118;
CC Name=d {ECO:0000312|WormBase:Y39A1A.1d};
CC IsoId=Q86MP3-4; Sequence=VSP_060116, VSP_060118;
CC -!- TISSUE SPECIFICITY: Widely expressed in tissues including pharyngeal,
CC muscle and neuronal tissues. {ECO:0000269|PubMed:21802374}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:21802374}.
CC -!- DOMAIN: The LRRG motif is required for recruitment to
CC phosphatidylinositols including phosphatidylinositol 3-phosphate
CC (PtdIns(3)P), phosphatidylinositol 5-phosphate (PtdIns(5)P),
CC phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylinositol
CC 3,5-bisphosphate (PtdIns(3,5)P2). {ECO:0000269|PubMed:21802374}.
CC -!- SIMILARITY: Belongs to the WD repeat PROPPIN family. {ECO:0000305}.
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DR EMBL; BX284603; CAA21019.3; -; Genomic_DNA.
DR EMBL; BX284603; CAD60426.1; -; Genomic_DNA.
DR EMBL; BX284603; CAI06057.1; -; Genomic_DNA.
DR EMBL; BX284603; CBX53348.1; -; Genomic_DNA.
DR PIR; T26730; T26730.
DR RefSeq; NP_001022835.1; NM_001027664.3.
DR RefSeq; NP_001255083.1; NM_001268154.1. [Q86MP3-4]
DR RefSeq; NP_499335.2; NM_066934.4. [Q86MP3-2]
DR RefSeq; NP_871659.1; NM_181930.5. [Q86MP3-1]
DR AlphaFoldDB; Q86MP3; -.
DR SMR; Q86MP3; -.
DR ComplexPortal; CPX-3823; epg-6-atg-2 complex.
DR IntAct; Q86MP3; 1.
DR MINT; Q86MP3; -.
DR STRING; 6239.Y39A1A.1b; -.
DR PaxDb; Q86MP3; -.
DR PeptideAtlas; Q86MP3; -.
DR EnsemblMetazoa; Y39A1A.1a.1; Y39A1A.1a.1; WBGene00012641. [Q86MP3-2]
DR EnsemblMetazoa; Y39A1A.1b.1; Y39A1A.1b.1; WBGene00012641. [Q86MP3-1]
DR EnsemblMetazoa; Y39A1A.1c.1; Y39A1A.1c.1; WBGene00012641. [Q86MP3-3]
DR EnsemblMetazoa; Y39A1A.1d.1; Y39A1A.1d.1; WBGene00012641. [Q86MP3-4]
DR GeneID; 189705; -.
DR KEGG; cel:CELE_Y39A1A.1; -.
DR UCSC; Y39A1A.1a; c. elegans.
DR CTD; 189705; -.
DR WormBase; Y39A1A.1a; CE33215; WBGene00012641; epg-6. [Q86MP3-2]
DR WormBase; Y39A1A.1b; CE33216; WBGene00012641; epg-6. [Q86MP3-1]
DR WormBase; Y39A1A.1c; CE37799; WBGene00012641; epg-6. [Q86MP3-3]
DR WormBase; Y39A1A.1d; CE45443; WBGene00012641; epg-6. [Q86MP3-4]
DR eggNOG; KOG2111; Eukaryota.
DR GeneTree; ENSGT00940000155657; -.
DR HOGENOM; CLU_025895_2_0_1; -.
DR InParanoid; Q86MP3; -.
DR OMA; YLNTQTH; -.
DR OrthoDB; 966922at2759; -.
DR PhylomeDB; Q86MP3; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR PRO; PR:Q86MP3; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00012641; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
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:0000045; P:autophagosome assembly; IMP: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:0016236; P:macroautophagy; IC:ComplexPortal.
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 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 SMART; SM00320; WD40; 2.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Lipid-binding; Membrane;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..388
FT /note="Ectopic P granules protein 6"
FT /id="PRO_0000446905"
FT REPEAT 217..257
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 262..301
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..328
FT /note="Required for atg-2 binding"
FT /evidence="ECO:0000269|PubMed:21802374"
FT MOTIF 258..261
FT /note="LRRG motif"
FT /evidence="ECO:0000269|PubMed:21802374"
FT COMPBIAS 1..32
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..107
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060116"
FT VAR_SEQ 1..32
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_060117"
FT VAR_SEQ 331..333
FT /note="IPE -> K (in isoform a, isoform c and isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060118"
FT MUTAGEN 161..388
FT /note="Missing: In bp242; defective degradation of protein
FT aggregates. Suppresses the lysosomal accumulation of
FT ribosomal RNA and ribosomal proteins in a rnst-2 qx245
FT mutant background."
FT /evidence="ECO:0000269|PubMed:21802374,
FT ECO:0000269|PubMed:30102152"
FT MUTAGEN 259..260
FT /note="RR->KK: Reduces, but does not abolish,
FT phosphatidylinositol binding."
FT /evidence="ECO:0000269|PubMed:21802374"
FT MUTAGEN 265..328
FT /note="Missing: Abolishes atg-2 binding."
FT /evidence="ECO:0000269|PubMed:21802374"
SQ SEQUENCE 388 AA; 43678 MW; 7A24C32BF5C6A8B3 CRC64;
MSKKEETIFF RIEKENRPES SKKEEDENST EEMTTLNHAS VTLDHSAFAI ADKDGFKMYQ
LNPLHFRMYK DYVIKVGPVR LVKQDGNSRR IIYVSALAGG RFAQNNLMIF DVARNEEYFE
ITTPSRYGPI TNIHVSPNRL VALNPNRMFV WTYPDDIKQI RSEDIRSNPK GISAMSYDPT
TAACYLAYPG FKTGSVQIMH LNALTARESK SPIVIEAHLT DIAQVALNCQ GTLVATGSTK
GTVIRVFDAR TKGPLYELRR GTVQAHLQCM AFSPCSSYLA VASDKGTLHM FGIRDAEPQK
KKNVLERSRG SSSIVKIQLD RPVMAIGFGK IPETPKNLQS IIAICADATY WRHEFYKDNT
GNFTSHFGSY DELIEVANDS SFFRTPVE
