TDRD9_MOUSE
ID TDRD9_MOUSE Reviewed; 1383 AA.
AC Q14BI7; B1Q3J8; Q14AW6;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 3.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=ATP-dependent RNA helicase TDRD9 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000305|PubMed:28633017};
DE AltName: Full=Tudor domain-containing protein 9 {ECO:0000305};
GN Name=Tdrd9 {ECO:0000312|MGI:MGI:1921941};
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] (ISOFORM 1).
RC TISSUE=Testis;
RA Shoji M., Tanaka T., Kitamura K., Hosokawa M., Kato Y., Kondoh G.,
RA Okawa K., Sasaki H., Chuma S., Nakatsuji N.;
RT "Regulation of retroelement expression and genome dna methylation through
RT conserved TDRD9/SPN-E function in the germline.";
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP AND INTERACTION WITH PIWIL4.
RX PubMed=20059948; DOI=10.1016/j.devcel.2009.10.012;
RA Shoji M., Tanaka T., Hosokawa M., Reuter M., Stark A., Kato Y., Kondoh G.,
RA Okawa K., Chujo T., Suzuki T., Hata K., Martin S.L., Noce T.,
RA Kuramochi-Miyagawa S., Nakano T., Sasaki H., Pillai R.S., Nakatsuji N.,
RA Chuma S.;
RT "The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon
RT silencing in the mouse male germline.";
RL Dev. Cell 17:775-787(2009).
RN [5]
RP INTERACTION WITH PIWIL1 AND PIWIL4.
RX PubMed=19584108; DOI=10.1101/gad.1814809;
RA Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S.,
RA Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.;
RT "Proteomic analysis of murine Piwi proteins reveals a role for arginine
RT methylation in specifying interaction with Tudor family members.";
RL Genes Dev. 23:1749-1762(2009).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=20011505; DOI=10.1371/journal.pgen.1000764;
RA Aravin A.A., van der Heijden G.W., Castaneda J., Vagin V.V., Hannon G.J.,
RA Bortvin A.;
RT "Cytoplasmic compartmentalization of the fetal piRNA pathway in mice.";
RL PLoS Genet. 5:E1000764-E1000764(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-257.
RX PubMed=28633017; DOI=10.1016/j.devcel.2017.05.021;
RA Wenda J.M., Homolka D., Yang Z., Spinelli P., Sachidanandam R.,
RA Pandey R.R., Pillai R.S.;
RT "Distinct roles of RNA helicases MVH and TDRD9 in PIWI slicing-triggered
RT mammalian piRNA biogenesis and function.";
RL Dev. Cell 41:623-637(2017).
CC -!- FUNCTION: ATP-binding RNA helicase which plays a central role during
CC spermatogenesis by repressing transposable elements and preventing
CC their mobilization, which is essential for the germline integrity
CC (PubMed:20059948, PubMed:28633017). Acts via the piRNA metabolic
CC process, which mediates the repression of transposable elements during
CC meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC governs the methylation and subsequent repression of transposons
CC (PubMed:20059948, PubMed:28633017). Acts downstream of piRNA
CC biogenesis: exclusively required for transposon silencing in the
CC nucleus, suggesting that it acts as a nuclear effector in the nucleus
CC together with PIWIL4 (PubMed:28633017). {ECO:0000269|PubMed:20059948,
CC ECO:0000269|PubMed:28633017}.
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:0000305|PubMed:28633017};
CC -!- SUBUNIT: Interacts with piRNA-associated proteins PIWIL1 and PIWIL4.
CC {ECO:0000269|PubMed:19584108, ECO:0000269|PubMed:20059948}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20011505,
CC ECO:0000269|PubMed:20059948, ECO:0000269|PubMed:28633017}. Nucleus
CC {ECO:0000269|PubMed:20059948, ECO:0000269|PubMed:28633017}.
CC Note=Component of the nuage, also named P granule, a germ-cell-specific
CC organelle required to repress transposon activity during meiosis.
CC Specifically localizes to piP-bodies, a subset of the nuage which
CC contains secondary piRNAs. PIWIL2 is required for its localization to
CC piP-bodies. {ECO:0000269|PubMed:20059948}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14BI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14BI7-2; Sequence=VSP_033554;
CC Name=3;
CC IsoId=Q14BI7-3; Sequence=VSP_033553, VSP_033555;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in reproductive organs.
CC Detected in mitotic spermatogonia, meiotic spermatocytes (predominantly
CC at the pachytene stage), haploid spermatids in the testis, and in
CC growing oocytes in the ovary (at protein level).
CC {ECO:0000269|PubMed:20059948}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable but show male sterility with
CC chromosome synapsis failure. In fetal testes, LINE-1 (L1) transposable
CC elements derepression and an aberrant piRNA profile in
CC prospermatogonia, followed by cognate DNA demethylation are observed.
CC {ECO:0000269|PubMed:20059948}.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC {ECO:0000305}.
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DR EMBL; AB362563; BAG15992.1; -; mRNA.
DR EMBL; AC112520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC115831; AAI15832.1; -; mRNA.
DR EMBL; BC116656; AAI16657.1; -; mRNA.
DR CCDS; CCDS49184.1; -. [Q14BI7-1]
DR RefSeq; NP_083332.1; NM_029056.1. [Q14BI7-1]
DR RefSeq; XP_006516384.1; XM_006516321.3. [Q14BI7-2]
DR AlphaFoldDB; Q14BI7; -.
DR SMR; Q14BI7; -.
DR BioGRID; 216946; 1.
DR IntAct; Q14BI7; 1.
DR STRING; 10090.ENSMUSP00000078022; -.
DR iPTMnet; Q14BI7; -.
DR PhosphoSitePlus; Q14BI7; -.
DR PaxDb; Q14BI7; -.
DR PRIDE; Q14BI7; -.
DR ProteomicsDB; 254688; -. [Q14BI7-1]
DR ProteomicsDB; 254689; -. [Q14BI7-2]
DR ProteomicsDB; 254690; -. [Q14BI7-3]
DR Antibodypedia; 47449; 69 antibodies from 14 providers.
DR Ensembl; ENSMUST00000079009; ENSMUSP00000078022; ENSMUSG00000054003. [Q14BI7-1]
DR GeneID; 74691; -.
DR KEGG; mmu:74691; -.
DR UCSC; uc007pei.1; mouse. [Q14BI7-1]
DR UCSC; uc007pej.1; mouse. [Q14BI7-3]
DR CTD; 122402; -.
DR MGI; MGI:1921941; Tdrd9.
DR VEuPathDB; HostDB:ENSMUSG00000054003; -.
DR eggNOG; KOG0920; Eukaryota.
DR GeneTree; ENSGT00940000157035; -.
DR HOGENOM; CLU_002601_1_0_1; -.
DR InParanoid; Q14BI7; -.
DR OMA; DPCRTVY; -.
DR OrthoDB; 278674at2759; -.
DR PhylomeDB; Q14BI7; -.
DR TreeFam; TF324869; -.
DR BioGRID-ORCS; 74691; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Tdrd9; mouse.
DR PRO; PR:Q14BI7; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q14BI7; protein.
DR Bgee; ENSMUSG00000054003; Expressed in spermatocyte and 43 other tissues.
DR ExpressionAtlas; Q14BI7; baseline and differential.
DR Genevisible; Q14BI7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071547; C:piP-body; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB.
DR GO; GO:0009566; P:fertilization; IMP:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0007141; P:male meiosis I; IMP:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; IMP:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR CDD; cd04508; TUDOR; 1.
DR Gene3D; 2.40.50.90; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR007502; Helicase-assoc_dom.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR035437; SNase_OB-fold_sf.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF04408; HA2; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00567; TUDOR; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00847; HA2; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00333; TUDOR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50304; TUDOR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Developmental protein;
KW Differentiation; Helicase; Hydrolase; Meiosis; Nucleotide-binding; Nucleus;
KW Reference proteome; RNA-mediated gene silencing; Spermatogenesis.
FT CHAIN 1..1383
FT /note="ATP-dependent RNA helicase TDRD9"
FT /id="PRO_0000333814"
FT DOMAIN 144..310
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 378..545
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 945..1005
FT /note="Tudor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 35..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 256..259
FT /note="DEAH box"
FT /evidence="ECO:0000269|PubMed:28633017"
FT COMPBIAS 68..82
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 157..164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT VAR_SEQ 1..772
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033553"
FT VAR_SEQ 1..401
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033554"
FT VAR_SEQ 773..813
FT /note="PKTTVVLKHIPPYGFLYYKQLQSLFRQCGQVKSIVFDGAKA -> MDIGTKC
FT TSQVAAGVTAWHLWRRSGPGRLADSEESCGVPRA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033555"
FT MUTAGEN 257
FT /note="E->Q: In Tdrd9(KI); heterozygous and homozygous
FT knockin male mice are infertile due to derepression of
FT transposable elements. PiRNA biogenesis in not affected but
FT piRNAs fail to accumulate in the nucleus."
FT /evidence="ECO:0000269|PubMed:28633017"
SQ SEQUENCE 1383 AA; 155980 MW; 55946F4F639B5777 CRC64;
MLRKLTVDQI NDWFTIGKTV TNVELLGLPP AFPAEAPREE VQRSEEVPNE DPTAQAQVPV
KATAPARPAS TSGRSLSQRS SEMEYINKYR QLEEQELDIY GQDQPPSGPG LRSPLAKLSN
VACIPETTYK YPDLPINRCK EEVISLIESN SVVIIHGATG SGKSTQLPQY VLDHYTQRSA
FCNIVVTQPR KIGASSIARW ISKERSWTLG GLVGYQVGLE KIATEDTRLI YMTTGVLLQK
IVSAKSLMEF THIFIDEVHE RTEEMDFLLL VVRKLLRTNS RFVKVVLMSA TINCKQFADY
FAVPVQNKMN PAYVFEVEGK PHAIEEYYLN DLGHIYHSGL PYRLEEPVIT KDVYEVAVSL
IQMFDDLDMK ESGNKTWSGA QFVSERSSVL VFLPGLGEIN YMHELLTNMI HKRLQVYPLH
SSVTLEEQNN VFLSPVPGYR KIILSTNIAE SSVTVPDVKY VIDFCLTRTL VCDEDTNYQS
LRLSWASKTS CDQRKGRAGR VSKGYCYRLI PRDFWDSAIP DHVVPEMLRC PLGSTILKVK
LLDMGEPRAL LATALSPPSL SDIERTILLL KEVGALAVSG QREDENPHDG ELTFLGRVLA
QLPVSQQLGK LVVLGHVFGC LDECLIIAAA LSLKNFFTMP FRQHLDGYRN KVHFSGSSRS
DCLALVEAFR AWQACRQRGE LRRPKDELDW GRLNYIQIKR IREVAELYEE LKNRISQFNM
FVGPHHPVLD QEYPYKQRFI LQVVLAGAFY PNYFTFGQPD EEMAVRELAG KDPKTTVVLK
HIPPYGFLYY KQLQSLFRQC GQVKSIVFDG AKAFVEFSRN PTERFKTLPA VNLAVKMSQL
KVSLELSVHA AEEIEGKVQG GSVSKLRNTR VNVDFQKQTV DPMQVSFNTL DRPRTVADLL
LTIDVTEVVE VGHFWGYRID ERNAELLKQL TAEINRLELV PLPIHPHPDL VCLAPFTDYN
KESYFRAQIL YVSGNSAEVF FVDYGNRSHV DLDLLREIPC QFLELPFQAL EFKICKMRPS
AKSLICGEHW SGGAHGRFAA LVGGCPLLVK VFSIVHSVLH VDVYRYSGAQ DAVNVRDVLI
REGYAELAEE SYESKQSYEV LKGFFAKSVD TMPDGSVSSP LKDDEKHLLR ILLESFASNR
LGAPNCKAVL HGPFNPYELK CHSLTRISKF RCVWIEKESI NSVVISDSPA DLHQRMLVAA
SLSVNETGST MLLRETSLMP HIPGLPALLS MLFAPVMELR VDREGKCYTG VLCGLGWNSA
TEAPILPEHD IELAFDVRLN VEDIVEINIL RAAINKLVCD GPNGSKYLGP ERIAQLQENA
RQKLLGLFCR LKPREKITPQ WHEKPYEWNQ VDPRLIMEQA EPEGSPGKST SLYQLHTPVV
LSP
