SEPA1_CAEEL
ID SEPA1_CAEEL Reviewed; 702 AA.
AC G5EC37;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Protein sepa-1 {ECO:0000305};
DE AltName: Full=Suppressor of ectopic P granules in autophagy {ECO:0000312|WormBase:M01E5.6};
GN Name=sepa-1 {ECO:0000303|PubMed:19167332, ECO:0000312|WormBase:M01E5.6};
GN ORFNames=M01E5.6 {ECO:0000312|WormBase:M01E5.6};
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 DEVELOPMENTAL STAGE.
RX PubMed=19377305; DOI=10.4161/auto.5.5.8624;
RA Tian E., Wang F., Han J., Zhang H.;
RT "epg-1 functions in autophagy-regulated processes and may encode a highly
RT divergent Atg13 homolog in C. elegans.";
RL Autophagy 5:608-615(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19372764; DOI=10.4161/auto.5.5.8552;
RA Zhao Y., Tian E., Zhang H.;
RT "Selective autophagic degradation of maternally-loaded germline P granule
RT components in somatic cells during C. elegans embryogenesis.";
RL Autophagy 5:717-719(2009).
RN [4] {ECO:0000305}
RP FUNCTION, SUBUNIT, INTERACTION WITH LGG-1 AND PGL-3, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, PROTEOLYTIC DEGRADATION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF CYS-255 AND GLU-275.
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 [5] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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, INTERACTION WITH EPG-2 AND PGL-3, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=24140420; DOI=10.1016/j.molcel.2013.09.014;
RA Li S., Yang P., Tian E., Zhang H.;
RT "Arginine methylation modulates autophagic degradation of PGL granules in
RT C. elegans.";
RL Mol. Cell 52:421-433(2013).
RN [7]
RP INTERACTION WITH LGG-1 AND LGG-2, DOMAIN LIR MOTIF, AND MUTAGENESIS OF
RP ASP-105; PHE-107; GLU-109; VAL-110; 246-ASP--ILE-250; PHE-298 AND
RP 469-TYR--LEU-472.
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 [8]
RP FUNCTION, AND INTERACTION WITH EPG-2.
RX PubMed=28806108; DOI=10.1080/15548627.2017.1339843;
RA Zhang G., Lin L., Qi D., Zhang H.;
RT "The composition of a protein aggregate modulates the specificity and
RT efficiency of its autophagic degradation.";
RL Autophagy 13:1487-1495(2017).
CC -!- FUNCTION: Adapter protein that connects P-granules in somatic cells
CC with the autophagic machinery (PubMed:19377305, PubMed:19372764,
CC PubMed:19167332, PubMed:24140420). Association with other adapters such
CC as epg-2 and P-granule components such as pgl-3 is required for the
CC accumulation and degradation of P-granules by autophagy in somatic
CC cells (PubMed:19372764, PubMed:19167332, PubMed:24140420,
CC PubMed:28806108). This ensures exclusive localization of the P-granules
CC in germ cells (PubMed:19372764, PubMed:19167332, PubMed:24140420,
CC PubMed:28806108). {ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:19372764, ECO:0000269|PubMed:19377305,
CC ECO:0000269|PubMed:24140420, ECO:0000269|PubMed:28806108}.
CC -!- SUBUNIT: Self-associates (PubMed:19167332). Interacts (via the LIR
CC motifs) with lgg-1; the interaction is direct (PubMed:19167332,
CC PubMed:26687600). Interacts (via the LIR motifs) with lgg-2; the
CC interaction is direct (PubMed:26687600). Interacts with pgl-3;
CC interaction is enhanced in the presence of RNA (PubMed:19167332,
CC PubMed:24140420). Interacts with epg-2; may be modulated by prmt-1
CC (PubMed:24140420, PubMed:28806108). {ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:24140420, ECO:0000269|PubMed:26687600,
CC ECO:0000269|PubMed:28806108}.
CC -!- INTERACTION:
CC G5EC37; Q09490: lgg-1; NbExp=3; IntAct=EBI-2256317, EBI-325374;
CC G5EC37; G5EBV6: pgl-3; NbExp=5; IntAct=EBI-2256317, EBI-328338;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00311}.
CC Cytoplasm {ECO:0000269|PubMed:19167332, ECO:0000269|PubMed:19372764,
CC ECO:0000269|PubMed:21802374, ECO:0000269|PubMed:24140420}. Cytoplasmic
CC granule {ECO:0000305|PubMed:19167332}. Note=Diffuse cytoplasmic
CC localization, but also localized to cytoplasmic aggregates throughout
CC development (PubMed:19167332, PubMed:21802374). Co-localizes with epg-2
CC and lgg-1 in cytoplasmic aggregates (PubMed:19167332, PubMed:24140420).
CC {ECO:0000269|PubMed:19167332, ECO:0000269|PubMed:21802374,
CC ECO:0000269|PubMed:24140420}.
CC -!- DEVELOPMENTAL STAGE: First expressed in 16-cell stage embryos
CC (PubMed:19167332). Temporal expression during embryogenesis with high
CC expression as embryos develop into 100-stage embryos, but with low
CC expression in most cells at the comma stage and almost diminished
CC expression at the 2-fold stage of embryogenesis (PubMed:19377305,
CC PubMed:19167332, PubMed:21802374, PubMed:24140420). Expressed in the
CC head, tail and intestine, especially in the anterior and posterior
CC intestinal cells, of larvae (PubMed:19167332).
CC {ECO:0000269|PubMed:19167332, ECO:0000269|PubMed:19377305,
CC ECO:0000269|PubMed:21802374, ECO:0000269|PubMed:24140420}.
CC -!- DOMAIN: The LIR motifs (LC3-interacting region) are required for its
CC interaction with lgg-1 and lgg-2. {ECO:0000269|PubMed:26687600}.
CC -!- PTM: Degraded by autophagy. {ECO:0000269|PubMed:19167332}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in the
CC accumulation of cytoplasmic aggregates containing the P-granule
CC component pgl-3 (PubMed:24140420). RNAi-mediated knockdown results in
CC the disrupted formation of P-granules in an atg-18 autophagy mutant
CC background (PubMed:19167332). {ECO:0000269|PubMed:19167332,
CC ECO:0000269|PubMed:24140420}.
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DR EMBL; BX284601; CAB07643.1; -; Genomic_DNA.
DR PIR; T23651; T23651.
DR RefSeq; NP_493339.1; NM_060938.3.
DR AlphaFoldDB; G5EC37; -.
DR SMR; G5EC37; -.
DR ELM; G5EC37; -.
DR IntAct; G5EC37; 2.
DR STRING; 6239.M01E5.6; -.
DR EPD; G5EC37; -.
DR PaxDb; G5EC37; -.
DR PeptideAtlas; G5EC37; -.
DR EnsemblMetazoa; M01E5.6.1; M01E5.6.1; WBGene00010808.
DR GeneID; 173196; -.
DR KEGG; cel:CELE_M01E5.6; -.
DR CTD; 173196; -.
DR WormBase; M01E5.6; CE12286; WBGene00010808; sepa-1.
DR eggNOG; KOG1778; Eukaryota.
DR GeneTree; ENSGT00970000195870; -.
DR HOGENOM; CLU_392902_0_0_1; -.
DR InParanoid; G5EC37; -.
DR OMA; NTSKEWI; -.
DR OrthoDB; 1790598at2759; -.
DR PhylomeDB; G5EC37; -.
DR PRO; PR:G5EC37; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00010808; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043621; F:protein self-association; IPI:WormBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:WormBase.
DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; IMP:WormBase.
DR Gene3D; 1.10.246.20; -; 1.
DR InterPro; IPR003101; KIX_dom.
DR InterPro; IPR036529; KIX_dom_sf.
DR InterPro; IPR039908; Sepa-1.
DR PANTHER; PTHR21504; PTHR21504; 1.
DR Pfam; PF02172; KIX; 1.
DR SUPFAM; SSF47040; SSF47040; 1.
DR PROSITE; PS50952; KIX; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..702
FT /note="Protein sepa-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000440173"
FT DOMAIN 597..674
FT /note="KIX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00311"
FT REGION 39..160
FT /note="Required for self-association and interaction with
FT pgl-3"
FT /evidence="ECO:0000269|PubMed:19167332"
FT REGION 450..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 545..564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 508..543
FT /evidence="ECO:0000255"
FT MOTIF 107..110
FT /note="LIR 1"
FT /evidence="ECO:0000269|PubMed:26687600"
FT MOTIF 247..250
FT /note="LIR 2"
FT /evidence="ECO:0000269|PubMed:26687600,
FT ECO:0000305|PubMed:19167332"
FT MOTIF 298..301
FT /note="LIR 3"
FT /evidence="ECO:0000269|PubMed:26687600,
FT ECO:0000305|PubMed:19167332"
FT MOTIF 469..472
FT /note="LIR 4"
FT /evidence="ECO:0000269|PubMed:26687600,
FT ECO:0000305|PubMed:19167332"
FT SITE 105
FT /note="Required for interaction with lgg-1 and lgg-2"
FT /evidence="ECO:0000269|PubMed:26687600"
FT SITE 246
FT /note="Required for interaction with lgg-1 and lgg-2"
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 105
FT /note="D->K: Impairs interaction with lgg-1 and lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 107
FT /note="F->A: Impairs interaction with lgg-1 and lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 109
FT /note="E->K: Impairs interaction with lgg-1 and lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 110
FT /note="V->A: Impairs interaction with lgg-1 and lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 246..250
FT /note="DFQKI->KAQKA,DAQKI,DFQKA,KFQKI: Abolishes the
FT interaction with lgg-1 and lgg-2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 255
FT /note="C->Y: In bp400; mutant protein does not form
FT aggregates, but cytoplasmic localization is diffuse
FT throughout embryogenesis."
FT /evidence="ECO:0000269|PubMed:19167332"
FT MUTAGEN 275
FT /note="E->K: In bp401; temperature sensitive with the
FT mutant protein forming 'speckles' at 15 degrees Celsius and
FT diffusely localized at 25 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:19167332"
FT MUTAGEN 298
FT /note="F->A: Abolishes the interaction with lgg-1 and lgg-
FT 2."
FT /evidence="ECO:0000269|PubMed:26687600"
FT MUTAGEN 469..472
FT /note="YQEL->AQRA: Abolishes the interaction with lgg-1."
FT /evidence="ECO:0000269|PubMed:26687600"
SQ SEQUENCE 702 AA; 80262 MW; 209253AF6164BB88 CRC64;
MTPLSALTSN PAPSPPPKFA LGKCPATAIH VVSVLRPNRQ RFCYEKTDAG DLIPHKCLIC
QPILTEKHIS PYYAVYSDLL EDFVLFGYNT MTGKMEQFIY AFKTDCFVEV NRPEIKYNPA
FLVKGNVVVA LNGPEGELVV IERDCRGLLS KESTSYGQFR TLPTAALRTL TLQDLERDRW
DRAANSDEVK ISSGNESFDR LYAEYQKNLP RFQVRQCLHL NKEFLCVYSK TSGDYTRLEY
IDETGDFQKI SCTLCTCEVT ESNLIPLYVE RNASELVIHV HNTENNQIEQ YIYDVRTFGF
VQVKRNLVYD PKKITSGLNL FMAENIDNRK VYMIMRGRDG RLQKETSGSG GFEKMQPVAV
KTFQVQWVEM KTEFEKKKAS TERVEPQHPV QTEGEDIMET VLAMVESFNC DLRKELGLTQ
DQEIPRKAPR VESAETEENI VKNLEKLQIA KDPEEPTTAA SEGGNTYGYQ ELDDTMSEGL
LEKEAESKHQ DANEPEPVKN VTYEPDVAAM DKKKKRRELK SRLNKINAQI DELEKRRMER
AGKKQVVSSS VPSEEAAQVE APASPALAEN TNQISNEETP KIDIFEGYNG SFLFGTNTSK
EWIVEDIRNH MVGKLLKAFW PRIQNVEEMN GELFKKLIAN ARKCETEILE ASNDRDEYYR
LMQLTVDQIL KKTLKKDQRA TEHNHQQPTQ SSDELAKNHE KN
