DHX15_MOUSE
ID DHX15_MOUSE Reviewed; 795 AA.
AC O35286; Q99L91;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=ATP-dependent RNA helicase DHX15 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:O43143};
DE AltName: Full=DEAH box protein 15 {ECO:0000303|PubMed:9342318};
GN Name=Dhx15 {ECO:0000303|PubMed:26494172, ECO:0000312|MGI:MGI:1099786};
GN Synonyms=Ddx15, Deah9 {ECO:0000303|PubMed:9342318};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9342318; DOI=10.1073/pnas.94.22.11803;
RA Gee S., Krauss S.W., Miller E., Aoyagi K., Arenas J., Conboy J.G.;
RT "Cloning of mDEAH9, a putative RNA helicase and mammalian homologue of
RT Saccharomyces cerevisiae splicing factor Prp43.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11803-11807(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND INTERACTION WITH NLRP6.
RX PubMed=26494172; DOI=10.1126/science.aab3145;
RA Wang P., Zhu S., Yang L., Cui S., Pan W., Jackson R., Zheng Y.,
RA Rongvaux A., Sun Q., Yang G., Gao S., Lin R., You F., Flavell R.,
RA Fikrig E.;
RT "Nlrp6 regulates intestinal antiviral innate immunity.";
RL Science 350:826-830(2015).
RN [5]
RP FUNCTION.
RX PubMed=34678144; DOI=10.1016/j.cell.2021.09.032;
RA Shen C., Li R., Negro R., Cheng J., Vora S.M., Fu T.M., Wang A., He K.,
RA Andreeva L., Gao P., Tian Z., Flavell R.A., Zhu S., Wu H.;
RT "Phase separation drives RNA virus-induced activation of the NLRP6
RT inflammasome.";
RL Cell 184:5759-5774(2021).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=34161762; DOI=10.1016/j.celrep.2021.109205;
RA Xing J., Zhou X., Fang M., Zhang E., Minze L.J., Zhang Z.;
RT "DHX15 is required to control RNA virus-induced intestinal inflammation.";
RL Cell Rep. 35:109205-109205(2021).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33483420; DOI=10.1073/pnas.2017432118;
RA Wang Y., He K., Sheng B., Lei X., Tao W., Zhu X., Wei Z., Fu R., Wang A.,
RA Bai S., Zhang Z., Hong N., Ye C., Tian Y., Wang J., Li M., Zhang K., Li L.,
RA Yang H., Li H.B., Flavell R.A., Zhu S.;
RT "The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein
RT expression in Paneth cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: RNA helicase involved in mRNA processing and antiviral innate
CC immunity (PubMed:26494172, PubMed:34161762). Pre-mRNA processing factor
CC involved in disassembly of spliceosomes after the release of mature
CC mRNA (By similarity). In cooperation with TFIP11 seem to be involved in
CC the transition of the U2, U5 and U6 snRNP-containing IL complex to the
CC snRNP-free IS complex leading to efficient debranching and turnover of
CC excised introns (By similarity). Plays a key role in antiviral innate
CC immunity by promoting both MAVS-dependent signaling and NLRP6
CC inflammasome (PubMed:26494172). Acts as an RNA virus sensor: recognizes
CC and binds viral double stranded RNA (dsRNA) and activates the MAVS-
CC dependent signaling to produce interferon-beta and interferon lambda-3
CC (IFNL3) (By similarity). Involved in intestinal antiviral innate
CC immunity together with NLRP6: recognizes and binds viral dsRNA and
CC promotes activation of the NLRP6 inflammasome in intestinal epithelial
CC cells to restrict infection by enteric viruses (PubMed:26494172,
CC PubMed:34678144, PubMed:34161762). The NLRP6 inflammasome acts by
CC promoting maturation and secretion of IL18 in the extracellular milieu
CC (PubMed:34161762). Also involved in antibacterial innate immunity by
CC promoting Wnt-induced antimicrobial protein expression in Paneth cells
CC (PubMed:33483420). {ECO:0000250|UniProtKB:O43143,
CC ECO:0000269|PubMed:26494172, ECO:0000269|PubMed:33483420,
CC ECO:0000269|PubMed:34161762, ECO:0000269|PubMed:34678144}.
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:0000250|UniProtKB:O43143};
CC -!- ACTIVITY REGULATION: ATPase activity is enhanced upon binding to G-
CC patch domain-containing proteins. G-patch domain-containing proteins
CC act like a brace that tethers mobile sections of DHX15 together,
CC stabilizing a functional conformation with high RNA affinity, thereby
CC promoting the ATPase activity. {ECO:0000250|UniProtKB:O43143}.
CC -!- SUBUNIT: Component of the U11/U12 snRNPs that are part of the U12-type
CC spliceosome (By similarity). Identified in the Intron Large spliceosome
CC complex (IL, also named intron lariat spliceosome), a post-mRNA release
CC spliceosomal complex containing the excised intron, U2, U5 and U6
CC snRNPs, and splicing factors; the association may be transient (By
CC similarity). The IL complex exists in two distinct conformations, one
CC with the DHX15 (ILS2) and one without (ILS1) (By similarity). Interacts
CC with TFIP11 (via G-patch domain); indicative for a recruitment to the
CC IL complex (By similarity). Interacts with SSB/La (By similarity).
CC Interacts with GPATCH2 (via G-patch domain); promoting the RNA helicase
CC activity (By similarity). Interacts with NKRF (via G-patch domain);
CC promoting the RNA helicase activity (By similarity). Interacts with
CC NLRP6 (PubMed:26494172). {ECO:0000250|UniProtKB:O43143,
CC ECO:0000269|PubMed:26494172}.
CC -!- INTERACTION:
CC O35286; Q91WS2: Nlrp6; NbExp=2; IntAct=EBI-8322087, EBI-16182145;
CC O35286; Q9ERA6: Tfip11; NbExp=3; IntAct=EBI-8322087, EBI-8338752;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9342318}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:9342318}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9342318}.
CC -!- DISRUPTION PHENOTYPE: Conditional deletion in intestinal epithelial
CC cells leads to impaired antiviral innate immunity, leading to lethality
CC following infection by an RNA virus (PubMed:34161762). Conditional
CC deletion in intestinal epithelial cells leads to impaired antibacterial
CC immunity, characterized by susceptibility to infection by enteric
CC bacteria C.rodentium (PubMed:33483420). Conditional deletion in Paneth
CC cells leads to reduced expression of alpha-defensins and severe DSS
CC (dextran sodium sulfate)-induced colitis (PubMed:33483420).
CC {ECO:0000269|PubMed:33483420, ECO:0000269|PubMed:34161762}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC DDX15/PRP43 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC003745; Type=Frameshift; Evidence={ECO:0000305};
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; AF017153; AAC36129.1; -; mRNA.
DR EMBL; BC003745; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS39085.1; -.
DR RefSeq; NP_031865.2; NM_007839.3.
DR AlphaFoldDB; O35286; -.
DR SMR; O35286; -.
DR BioGRID; 199083; 57.
DR CORUM; O35286; -.
DR DIP; DIP-61875N; -.
DR IntAct; O35286; 6.
DR MINT; O35286; -.
DR STRING; 10090.ENSMUSP00000031061; -.
DR iPTMnet; O35286; -.
DR PhosphoSitePlus; O35286; -.
DR SwissPalm; O35286; -.
DR EPD; O35286; -.
DR jPOST; O35286; -.
DR PaxDb; O35286; -.
DR PeptideAtlas; O35286; -.
DR PRIDE; O35286; -.
DR ProteomicsDB; 279649; -.
DR Antibodypedia; 10152; 180 antibodies from 22 providers.
DR DNASU; 13204; -.
DR Ensembl; ENSMUST00000031061; ENSMUSP00000031061; ENSMUSG00000029169.
DR GeneID; 13204; -.
DR KEGG; mmu:13204; -.
DR UCSC; uc008xkf.2; mouse.
DR CTD; 1665; -.
DR MGI; MGI:1099786; Dhx15.
DR VEuPathDB; HostDB:ENSMUSG00000029169; -.
DR eggNOG; KOG0925; Eukaryota.
DR GeneTree; ENSGT00940000155800; -.
DR InParanoid; O35286; -.
DR OMA; DHDLKRY; -.
DR OrthoDB; 354219at2759; -.
DR PhylomeDB; O35286; -.
DR TreeFam; TF105735; -.
DR Reactome; R-MMU-72163; mRNA Splicing - Major Pathway.
DR BioGRID-ORCS; 13204; 26 hits in 71 CRISPR screens.
DR ChiTaRS; Dhx15; mouse.
DR PRO; PR:O35286; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O35286; protein.
DR Bgee; ENSMUSG00000029169; Expressed in primitive streak and 241 other tissues.
DR ExpressionAtlas; O35286; baseline and differential.
DR Genevisible; O35286; MM.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005681; C:spliceosomal complex; IBA:GO_Central.
DR GO; GO:0005689; C:U12-type spliceosomal complex; ISS:HGNC-UCL.
DR GO; GO:0071008; C:U2-type post-mRNA release spliceosomal complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR CDD; cd17973; DEXHc_DHX15; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011709; DEAD-box_helicase_OB_fold.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR044756; DHX15_DEXHc.
DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS.
DR InterPro; IPR007502; Helicase-assoc_dom.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF04408; HA2; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF07717; OB_NTP_bind; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00847; HA2; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Helicase; Hydrolase; Immunity; Innate immunity;
KW Isopeptide bond; mRNA processing; mRNA splicing; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding; Ubl conjugation.
FT CHAIN 1..795
FT /note="ATP-dependent RNA helicase DHX15"
FT /id="PRO_0000055140"
FT DOMAIN 147..313
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 338..518
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 260..263
FT /note="DEAH box"
FT COMPBIAS 1..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..111
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 160..167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43143"
FT MOD_RES 488
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43143"
FT CROSSLNK 786
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43143"
FT CONFLICT 388..389
FT /note="LY -> FS (in Ref. 1; AAC36129)"
FT /evidence="ECO:0000305"
FT CONFLICT 391..393
FT /note="TLP -> YTS (in Ref. 1; AAC36129)"
FT /evidence="ECO:0000305"
FT CONFLICT 757..758
FT /note="WL -> CW (in Ref. 1; AAC36129)"
FT /evidence="ECO:0000305"
FT CONFLICT 759..795
FT /note="Missing (in Ref. 1; AAC36129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 91007 MW; 25A97254318E497A CRC64;
MSKRHRLDLG EDYPSGKKRA GTDGKDRERD RDREDRSKDR DRERDRGDRE REREKEKEKE
LRASTNAMLI SAGLPPLKAS HSAHSTHSAH STHSTHSAHS THTGHTGHTS LPQCINPFTN
LPHTPRYYDI LKKRLQLPVW EYKDRFTDIL VRHQSFVLVG ETGSGKTTQI PQWCVEYMRS
LPGPKRGVAC TQPRRVAAMS VAQRVADEMD VMLGQEVGYS IRFEDCSSAK TILKYMTDGM
LLREAMNDPL LERYGVIILD EAHERTLATD ILMGVLKEVV RQRSDLKVIV MSATLDAGKF
QIYFDNCPLL TIPGRTHPVE IFYTPEPERD YLEAAIRTVI QIHMCEEEEG DLLLFLTGQE
EIDEACKRIK REVDDLGPEV GDIKIIPLYS TLPPQQQQRI FEPPPPKKQN GAIGRKVVVS
TNIAETSLTI DGVVFVIDPG FAKQKVYNPR IRVESLLVTA ISKASAQQRA GRAGRTRPGK
CFRLYTEKAY KTEMQDNTYP EILRSNLGSV VLQLKKLGID DLVHFDFMDP PAPETLMRAL
ELLNYLAALN DDGDLTELGS MMAEFPLDPQ LAKMVIASCD YNCSNEVLSI TAMLSVPQCF
VRPTEAKKAA DEAKMRFAHI DGDHLTLLNV YHAFKQNHES VQWCYDNFIN YRSLMSADNV
RQQLSRIMDR FNLPRRSTDF TSRDYYINIR KALVTGYFMQ VAHLERTGHY LTVKDNQVVQ
LHPSTVLDHK PEWVLYNEFV LTTKNYIRTC TDIKPEWLVK IAPQYYDMSN FPQCEAKRQL
DRIIAKLQSK EYSQY
