ID DDX3_CAEEL Reviewed; 708 AA.
AC D0PV95; Q4W5R4;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 1.
DT 27-MAR-2024, entry version 105.
DE RecName: Full=ATP-dependent RNA helicase laf-1 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000269|PubMed:27546789};
DE AltName: Full=DEAD-box RNA helicase laf-1 {ECO:0000303|PubMed:19361491};
GN Name=laf-1 {ECO:0000303|PubMed:19361491, ECO:0000312|WormBase:Y71H2AM.19b};
GN ORFNames=Y71H2AM.19 {ECO:0000312|WormBase:Y71H2AM.19b};
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:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ARG-426; MET-430 AND THR-434.
RX PubMed=19361491; DOI=10.1016/j.ydbio.2009.04.003;
RA Hubert A., Anderson P.;
RT "The C. elegans sex determination gene laf-1 encodes a putative DEAD-box
RT RNA helicase.";
RL Dev. Biol. 330:358-367(2009).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9043090; DOI=10.1242/dev.124.3.749;
RA Goodwin E.B., Hofstra K., Hurney C.A., Mango S., Kimble J.;
RT "A genetic pathway for regulation of tra-2 translation.";
RL Development 124:749-758(1997).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=9321409; DOI=10.1093/emboj/16.20.6301;
RA Jan E., Yoon J.W., Walterhouse D., Iannaccone P., Goodwin E.B.;
RT "Conservation of the C.elegans tra-2 3'UTR translational control.";
RL EMBO J. 16:6301-6313(1997).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24844228; DOI=10.1371/journal.pone.0097924;
RA Paz-Gomez D., Villanueva-Chimal E., Navarro R.E.;
RT "The DEAD Box RNA helicase VBH-1 is a new player in the stress response in
RT C. elegans.";
RL PLoS ONE 9:E97924-E97924(2014).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=26015579; DOI=10.1073/pnas.1504822112;
RA Elbaum-Garfinkle S., Kim Y., Szczepaniak K., Chen C.C., Eckmann C.R.,
RA Myong S., Brangwynne C.P.;
RT "The disordered P granule protein LAF-1 drives phase separation into
RT droplets with tunable viscosity and dynamics.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:7189-7194(2015).
RN [7] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP DOMAIN.
RX PubMed=27546789; DOI=10.1016/j.molcel.2016.07.010;
RA Kim Y., Myong S.;
RT "RNA remodeling activity of DEAD box proteins tuned by protein
RT concentration, RNA length, and ATP.";
RL Mol. Cell 63:865-876(2016).
CC -!- FUNCTION: Multifunctional ATP-dependent RNA helicase (PubMed:27546789).
CC Plays a role in RNA remodeling, but is not required for RNA unwinding
CC (PubMed:27546789). Binds to RNA in a concentration-dependent manner to
CC stimulate annealing between two complementary strands of RNA
CC (PubMed:26015579, PubMed:27546789). This process is also dependent upon
CC ATP; ATP reduces binding to RNA and subsequently diminishes RNA
CC annealing (PubMed:27546789). Involved in many cellular processes, which
CC do not necessarily require its ATPase/helicase catalytic activities.
CC Involved in the regulation of transcription and translation initiation.
CC Involved in innate immunity (By similarity). Involved in both stress
CC and inflammatory responses (By similarity). Promotes liquid-liquid
CC phase separation of P granules, which is a process important for
CC intracellular organization and stress granule assembly
CC (PubMed:26015579). Required for embryonic development (PubMed:19361491,
CC PubMed:26015579). Plays a role in sexual cell fate determination by
CC negatively regulating the translation of the sex determining protein
CC tra-2 (PubMed:9043090, PubMed:9321409, PubMed:26015579). May play a
CC protective role in the response to heat and oxidative stress
CC (PubMed:24844228). May negatively regulate extrinsic apoptotic
CC signaling pathway via death domain receptors. May be involved in
CC mitotic chromosome segregation (By similarity).
CC {ECO:0000250|UniProtKB:O00571, ECO:0000250|UniProtKB:Q62167,
CC ECO:0000269|PubMed:19361491, ECO:0000269|PubMed:24844228,
CC ECO:0000269|PubMed:26015579, ECO:0000269|PubMed:27546789,
CC ECO:0000269|PubMed:9043090, ECO:0000269|PubMed:9321409}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:27546789};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.3156 mM for ATP {ECO:0000269|PubMed:27546789};
CC -!- SUBUNIT: Binds RNA as a monomer at low laf-1 concentrations and as a
CC dimer at high laf-1 concentrations. {ECO:0000269|PubMed:27546789}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19361491,
CC ECO:0000269|PubMed:26015579}. Cytoplasmic granule
CC {ECO:0000269|PubMed:19361491, ECO:0000269|PubMed:26015579}. Nucleus
CC {ECO:0000250|UniProtKB:O00571}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:O00571}. Inflammasome
CC {ECO:0000250|UniProtKB:Q62167}. Cell membrane
CC {ECO:0000250|UniProtKB:O00571}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O00571}. Note=Localizes to P granules in
CC germline precursor cells. Shuttles between the nucleus and the cytosol
CC (By similarity). {ECO:0000250|UniProtKB:O00571,
CC ECO:0000269|PubMed:19361491}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:Y71H2AM.19b};
CC IsoId=D0PV95-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y71H2AM.19a};
CC IsoId=D0PV95-2; Sequence=VSP_058672;
CC -!- TISSUE SPECIFICITY: Expressed in the germline and soma of young adult
CC hermaphrodites. {ECO:0000269|PubMed:19361491}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all developmental stages. Highly
CC expressed in embryos with levels decreasing during larval development
CC and increasing as animals reach adulthood.
CC {ECO:0000269|PubMed:19361491}.
CC -!- DOMAIN: The N-terminal domain is required for the multimeric binding of
CC laf-1 to RNA. {ECO:0000269|PubMed:26015579,
CC ECO:0000269|PubMed:27546789}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal or lethal at the first larval
CC stage of development (PubMed:9043090). Embryos exhibit severe
CC morphological defects (PubMed:9043090). RNAi-mediated knockdown results
CC in embryonic lethality in 88% of animals (PubMed:19361491,
CC PubMed:26015579). Knockdown also results in disrupted P granule
CC organization and assembly in the early embryo (PubMed:26015579).
CC Reduced survival in response to heat and oxidative stress
CC (PubMed:24844228). Double RNAi knockdown with vbh-1 results in a high
CC number of female offspring (PubMed:19361491).
CC {ECO:0000269|PubMed:19361491, ECO:0000269|PubMed:24844228,
CC ECO:0000269|PubMed:26015579, ECO:0000269|PubMed:9043090}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1
CC subfamily. {ECO:0000305}.
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DR EMBL; FJ348231; ACO56244.1; -; mRNA.
DR EMBL; BX284603; CCD73871.1; -; Genomic_DNA.
DR EMBL; BX284603; CCG28150.1; -; Genomic_DNA.
DR RefSeq; NP_001254858.1; NM_001267929.1.
DR RefSeq; NP_001254859.1; NM_001267930.1. [D0PV95-1]
DR AlphaFoldDB; D0PV95; -.
DR SMR; D0PV95; -.
DR STRING; 6239.Y71H2AM.19b.1; -.
DR EPD; D0PV95; -.
DR PaxDb; 6239-Y71H2AM-19b; -.
DR PeptideAtlas; D0PV95; -.
DR EnsemblMetazoa; Y71H2AM.19.1; Y71H2AM.19.1; WBGene00002244. [D0PV95-1]
DR GeneID; 190611; -.
DR KEGG; cel:CELE_Y71H2AM.19; -.
DR AGR; WB:WBGene00002244; -.
DR WormBase; Y71H2AM.19a; CE38657; WBGene00002244; laf-1. [D0PV95-2]
DR WormBase; Y71H2AM.19b; CE47305; WBGene00002244; laf-1. [D0PV95-1]
DR eggNOG; KOG0335; Eukaryota.
DR GeneTree; ENSGT00940000168275; -.
DR InParanoid; D0PV95; -.
DR OMA; FEEHQNT; -.
DR OrthoDB; 5480645at2759; -.
DR PhylomeDB; D0PV95; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR PRO; PR:D0PV95; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00002244; Expressed in pharyngeal muscle cell (C elegans) and 3 other cell types or tissues.
DR GO; GO:0061702; C:canonical inflammasome complex; IEA:UniProtKB-SubCell.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043186; C:P granule; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:DisProt.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0003724; F:RNA helicase activity; IBA:GO_Central.
DR GO; GO:0033592; F:RNA strand annealing activity; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007276; P:gamete generation; IBA:GO_Central.
DR GO; GO:0042006; P:masculinization of hermaphroditic germ-line; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR CDD; cd17967; DEADc_DDX3_DDX4; 1.
DR CDD; cd18787; SF2_C_DEAD; 1.
DR DisProt; DP01113; -.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR IDEAL; IID50296; -.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR044763; Ded1/Dbp1_DEADc.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS.
DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif.
DR PANTHER; PTHR47958; ATP-DEPENDENT RNA HELICASE DBP3; 1.
DR PANTHER; PTHR47958:SF32; RNA HELICASE; 1.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasm; Helicase; Hydrolase; Inflammasome; Membrane; Nucleotide-binding;
KW Nucleus; Reference proteome; RNA-binding; Transcription;
KW Transcription regulation; Translation regulation.
FT CHAIN 1..708
FT /note="ATP-dependent RNA helicase laf-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438522"
FT DOMAIN 262..453
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 465..626
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 231..259
FT /note="Q motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00552"
FT MOTIF 397..400
FT /note="DEAD box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT COMPBIAS 72..98
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..167
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 168..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 275..282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT VAR_SEQ 41..105
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058672"
FT MUTAGEN 426
FT /note="R->C: In q80; embryonic lethal."
FT /evidence="ECO:0000269|PubMed:19361491"
FT MUTAGEN 430
FT /note="M->I: In q217; embryonic lethal."
FT /evidence="ECO:0000269|PubMed:19361491"
FT MUTAGEN 434
FT /note="T->I: In q267; embryonic lethal."
FT /evidence="ECO:0000269|PubMed:19361491"
SQ SEQUENCE 708 AA; 76343 MW; 13644AD830B03888 CRC64;
MESNQSNNGG SGNAALNRGG RYVPPHLRGG DGGAAAAASA GGDDRRGGAG GGGYRRGGGN
SGGGGGGGYD RGYNDNRDDR DNRGGSGGYG RDRNYEDRGY NGGGGGGGNR GYNNNRGGGG
GGYNRQDRGD GGSSNFSRGG YNNRDEGSDN RGSGRSYNND RRDNGGDGQN TRWNNLDAPP
SRGTSKWENR GARDERIEQE LFSGQLSGIN FDKYEEIPVE ATGDDVPQPI SLFSDLSLHE
WIEENIKTAG YDRPTPVQKY SIPALQGGRD LMSCAQTGSG KTAAFLVPLV NAILQDGPDA
VHRSVTSSGG RKKQYPSALV LSPTRELSLQ IFNESRKFAY RTPITSALLY GGRENYKDQI
HKLRLGCHIL IATPGRLIDV MDQGLIGMEG CRYLVLDEAD RMLDMGFEPQ IRQIVECNRM
PSKEERITAM FSATFPKEIQ LLAQDFLKEN YVFLAVGRVG STSENIMQKI VWVEEDEKRS
YLMDLLDATG DSSLTLVFVE TKRGASDLAY YLNRQNYEVV TIHGDLKQFE REKHLDLFRT
GTAPILVATA VAARGLDIPN VKHVINYDLP SDVDEYVHRI GRTGRVGNVG LATSFFNDKN
RNIARELMDL IVEANQELPD WLEGMSGDMR SGGGYRGRGG RGNGQRFGGR DHRYQGGSGN
GGGGNGGGGG FGGGGQRSGG GGGFQSGGGG GRQQQQQQRA QPQQDWWS
//
