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SID2_CAEEL
ID   SID2_CAEEL              Reviewed;         311 AA.
AC   G5EEV9;
DT   18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 1.
DT   03-AUG-2022, entry version 51.
DE   RecName: Full=Systemic RNA interference defective protein 2 {ECO:0000303|PubMed:17563372};
DE   Flags: Precursor;
GN   Name=sid-2 {ECO:0000312|WormBase:ZK520.2};
GN   ORFNames=ZK520.2 {ECO:0000312|WormBase:ZK520.2};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAS45709.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND MUTAGENESIS OF ASP-34 AND GLY-199.
RX   PubMed=17563372; DOI=10.1073/pnas.0611282104;
RA   Winston W.M., Sutherlin M., Wright A.J., Feinberg E.H., Hunter C.P.;
RT   "Caenorhabditis elegans SID-2 is required for environmental RNA
RT   interference.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:10565-10570(2007).
RN   [2] {ECO:0000312|EMBL:CAB07300.4}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2 {ECO:0000312|EMBL:CAB07300.4};
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   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17381285; DOI=10.1101/sqb.2006.71.060;
RA   Hunter C.P., Winston W.M., Molodowitch C., Feinberg E.H., Shih J.,
RA   Sutherlin M., Wright A.J., Fitzgerald M.C.;
RT   "Systemic RNAi in Caenorhabditis elegans.";
RL   Cold Spring Harb. Symp. Quant. Biol. 71:95-100(2006).
RN   [4] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP   HIS-32; HIS-168 AND HIS-175.
RX   PubMed=22902558; DOI=10.1016/j.molcel.2012.07.014;
RA   McEwan D.L., Weisman A.S., Hunter C.P.;
RT   "Uptake of extracellular double-stranded RNA by SID-2.";
RL   Mol. Cell 47:746-754(2012).
RN   [5]
RP   FUNCTION, AND MUTAGENESIS OF 163-GLN--TRP-311.
RX   PubMed=32908307; DOI=10.1038/s41586-020-2699-5;
RA   Kaletsky R., Moore R.S., Vrla G.D., Parsons L.R., Gitai Z., Murphy C.T.;
RT   "C. elegans interprets bacterial non-coding RNAs to learn pathogenic
RT   avoidance.";
RL   Nature 586:445-451(2020).
CC   -!- FUNCTION: Plays a role in RNA-mediated gene silencing by mediating
CC       endocytic uptake of double-stranded RNA (dsRNA) ingested from the
CC       environment into intestinal cells from the intestinal lumen. Selective
CC       for dsRNAs of at least 50 bp. Required for avoidance behavior induced
CC       by small RNAs derived from pathogenic bacteria such as P.aeruginosa
CC       (PubMed:32908307). {ECO:0000269|PubMed:17381285,
CC       ECO:0000269|PubMed:17563372, ECO:0000269|PubMed:22902558,
CC       ECO:0000269|PubMed:32908307}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:17381285, ECO:0000269|PubMed:17563372,
CC       ECO:0000269|PubMed:22902558}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:17381285, ECO:0000269|PubMed:17563372,
CC       ECO:0000269|PubMed:22902558}. Cytoplasm {ECO:0000269|PubMed:17381285,
CC       ECO:0000269|PubMed:17563372, ECO:0000269|PubMed:22902558}.
CC       Note=Localizes to the apical membrane of intestinal cells and also to
CC       punctate cytoplasmic structures. {ECO:0000269|PubMed:17381285,
CC       ECO:0000269|PubMed:17563372, ECO:0000269|PubMed:22902558}.
CC   -!- TISSUE SPECIFICITY: Expressed in the intestinal lumen. Also present, at
CC       lower levels, in the excretory duct cells.
CC       {ECO:0000269|PubMed:17381285, ECO:0000269|PubMed:17563372,
CC       ECO:0000269|PubMed:22902558}.
CC   -!- DOMAIN: The extracellular domain is necessary for the uptake of dsRNA.
CC       {ECO:0000269|PubMed:22902558}.
CC   -!- MISCELLANEOUS: The avoidance behavior is transgenerationally inherited,
CC       and thus progeny display this same aversion despite never having been
CC       exposed to this pathogenic bacteria. {ECO:0000269|PubMed:32908307}.
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DR   EMBL; AY466439; AAS45709.1; -; mRNA.
DR   EMBL; BX284603; CAB07300.4; -; Genomic_DNA.
DR   PIR; A88618; A88618.
DR   PIR; T27883; T27883.
DR   RefSeq; NP_499823.2; NM_067422.6.
DR   AlphaFoldDB; G5EEV9; -.
DR   STRING; 6239.ZK520.2; -.
DR   EPD; G5EEV9; -.
DR   PaxDb; G5EEV9; -.
DR   PeptideAtlas; G5EEV9; -.
DR   EnsemblMetazoa; ZK520.2.1; ZK520.2.1; WBGene00004796.
DR   GeneID; 176805; -.
DR   KEGG; cel:CELE_ZK520.2; -.
DR   CTD; 176805; -.
DR   WormBase; ZK520.2; CE33908; WBGene00004796; sid-2.
DR   eggNOG; ENOG502TFYD; Eukaryota.
DR   HOGENOM; CLU_967174_0_0_1; -.
DR   InParanoid; G5EEV9; -.
DR   OrthoDB; 1614285at2759; -.
DR   PRO; PR:G5EEV9; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00004796; Expressed in larva and 3 other tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0035194; P:post-transcriptional gene silencing by RNA; IMP:WormBase.
DR   GO; GO:0050658; P:RNA transport; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Cell membrane; Cytoplasm; Endocytosis; Membrane; Reference proteome;
KW   RNA-mediated gene silencing; Signal; Transmembrane; Transmembrane helix;
KW   Transport.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..311
FT                   /note="Systemic RNA interference defective protein 2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000423412"
FT   TOPO_DOM        21..188
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        189..209
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        210..311
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          287..311
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         32
FT                   /note="H->A: Reduced dsRNA uptake but complete rescue of
FT                   gene silencing defect in sid-2 deletion mutant."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         32
FT                   /note="H->E,R: Reduced dsRNA uptake."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         34
FT                   /note="D->Q: In qt13; complete resistance to RNAi following
FT                   soaking in dsRNA solution or ingestion of bacteria
FT                   expressing dsRNA."
FT                   /evidence="ECO:0000269|PubMed:17563372"
FT   MUTAGEN         163..311
FT                   /note="Missing: In qt42; defective avoidance behavior in
FT                   response to P.aeruginosa."
FT                   /evidence="ECO:0000269|PubMed:32908307"
FT   MUTAGEN         168
FT                   /note="H->A: No detectable dsRNA uptake and only partial
FT                   rescue of gene silencing defect in sid-2 deletion mutant."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         168
FT                   /note="H->E,R: Reduced dsRNA uptake."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         175
FT                   /note="H->A: Reduced dsRNA uptake but complete rescue of
FT                   gene silencing defect in sid-2 deletion mutant."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         175
FT                   /note="H->E,R: Reduced dsRNA uptake."
FT                   /evidence="ECO:0000269|PubMed:22902558"
FT   MUTAGEN         199
FT                   /note="G->D: In qt20; complete resistance to RNAi following
FT                   soaking in dsRNA solution or ingestion of bacteria
FT                   expressing dsRNA."
FT                   /evidence="ECO:0000269|PubMed:17563372"
SQ   SEQUENCE   311 AA;  33739 MW;  A3624681315870C2 CRC64;
     MPRFVYFCFA LIALLPISWT MDGILITDVE IHVDVCQISC KASNTASLLI NDAPFTPMCN
     SAGDQIFFTY NGTAAISDLK NVTFILEVTT DTKNCTFTAN YTGYFTPDPK SKPFQLGFAS
     ATLNRDMGKV TKTIMEDSGE MVEQDFSNSS AVPTPASTTP LPQSTVAHLT IAYVHLQYEE
     TKTVVNKNGG AVAVAVIEGI ALIAILAFLG YRTMVNHKLQ NSTRTNGLYG YDNNNSSRIT
     VPDAMRMSDI PPPRDPMYAS PPTPLSQPTP ARNTVMTTQE LVVPTANSSA AQPSTTSNGQ
     FNDPFATLES W
 
 
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