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}.
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; 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