TDR12_MOUSE
ID TDR12_MOUSE Reviewed; 1215 AA.
AC Q9CWU0;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Putative ATP-dependent RNA helicase TDRD12;
DE EC=3.6.4.13;
DE AltName: Full=ES cell-associated transcript 8 protein;
DE AltName: Full=Tudor domain-containing protein 12;
GN Name=Tdrd12; Synonyms=Ecat8, Repro23;
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 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Embryonic stem cell;
RX PubMed=12787504; DOI=10.1016/s0092-8674(03)00393-3;
RA Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K.,
RA Maruyama M., Maeda M., Yamanaka S.;
RT "The homeoprotein Nanog is required for maintenance of pluripotency in
RT mouse epiblast and ES cells.";
RL Cell 113:631-642(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
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 [4]
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND IDENTIFICATION IN A MRNP COMPLEX.
RX PubMed=24067652; DOI=10.1073/pnas.1316316110;
RA Pandey R.R., Tokuzawa Y., Yang Z., Hayashi E., Ichisaka T., Kajita S.,
RA Asano Y., Kunieda T., Sachidanandam R., Chuma S., Yamanaka S., Pillai R.S.;
RT "Tudor domain containing 12 (TDRD12) is essential for secondary PIWI
RT interacting RNA biogenesis in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16492-16497(2013).
RN [6]
RP FUNCTION, AND IDENTIFICATION IN THE PET COMPLEX.
RX PubMed=26669262; DOI=10.1016/j.molcel.2015.11.009;
RA Yang Z., Chen K.M., Pandey R.R., Homolka D., Reuter M., Janeiro B.K.,
RA Sachidanandam R., Fauvarque M.O., McCarthy A.A., Pillai R.S.;
RT "PIWI slicing and EXD1 drive biogenesis of nuclear piRNAs from cytosolic
RT targets of the mouse piRNA pathway.";
RL Mol. Cell 61:138-152(2016).
CC -!- FUNCTION: Probable ATP-binding RNA helicase required during
CC spermatogenesis to repress transposable elements and preventing their
CC mobilization, which is essential for the germline integrity. Acts via
CC the piRNA metabolic process, which mediates the repression of
CC transposable elements during meiosis by forming complexes composed of
CC piRNAs and Piwi proteins and governs the methylation and subsequent
CC repression of transposons (PubMed:24067652). Involved in the secondary
CC piRNAs metabolic process (PubMed:24067652). Acts via the PET complex, a
CC multiprotein complex required during the secondary piRNAs metabolic
CC process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs
CC (PubMed:26669262). {ECO:0000269|PubMed:24067652,
CC ECO:0000269|PubMed:26669262}.
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 -!- SUBUNIT: Component of a mRNP complex containing PIWIL2, TDRD1 and
CC piRNAs (PubMed:24067652). Component of the PET complex, at least
CC composed of EXD1, PIWIL2, TDRD12 and piRNAs (PubMed:26669262).
CC {ECO:0000269|PubMed:24067652, ECO:0000269|PubMed:26669262}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CWU0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CWU0-2; Sequence=VSP_029677, VSP_029678;
CC -!- TISSUE SPECIFICITY: Restricted to the gonads.
CC {ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:24067652}.
CC -!- DEVELOPMENTAL STAGE: Expressed from embryonic to the adult stages in
CC testis. Expressed in embryonic stem (ES) cells.
CC {ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:24067652}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable but show male sterility with
CC chromosome synapsis failure. Male mice display atrophied testes, with
CC seminiferous tubules that are narrow with large vacuolated spaces,
CC devoid of late-stage germ cells. Retrotransposons are derepressed due
CC to DNA demethylation. {ECO:0000269|PubMed:24067652}.
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DR EMBL; AB211061; BAD95488.1; -; mRNA.
DR EMBL; AK010386; BAB26901.1; -; mRNA.
DR EMBL; AC151535; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21151.1; -. [Q9CWU0-2]
DR RefSeq; NP_082310.1; NM_028034.2. [Q9CWU0-2]
DR AlphaFoldDB; Q9CWU0; -.
DR SMR; Q9CWU0; -.
DR BioGRID; 215070; 1.
DR CORUM; Q9CWU0; -.
DR STRING; 10090.ENSMUSP00000032701; -.
DR iPTMnet; Q9CWU0; -.
DR PhosphoSitePlus; Q9CWU0; -.
DR PaxDb; Q9CWU0; -.
DR PRIDE; Q9CWU0; -.
DR ProteomicsDB; 262741; -. [Q9CWU0-1]
DR ProteomicsDB; 262742; -. [Q9CWU0-2]
DR Antibodypedia; 47944; 46 antibodies from 12 providers.
DR DNASU; 71981; -.
DR Ensembl; ENSMUST00000032701; ENSMUSP00000032701; ENSMUSG00000030491. [Q9CWU0-2]
DR GeneID; 71981; -.
DR KEGG; mmu:71981; -.
DR UCSC; uc012fij.1; mouse. [Q9CWU0-2]
DR CTD; 91646; -.
DR MGI; MGI:1919231; Tdrd12.
DR VEuPathDB; HostDB:ENSMUSG00000030491; -.
DR eggNOG; KOG0331; Eukaryota.
DR GeneTree; ENSGT00420000029847; -.
DR InParanoid; Q9CWU0; -.
DR OrthoDB; 231240at2759; -.
DR PhylomeDB; Q9CWU0; -.
DR TreeFam; TF332354; -.
DR BioGRID-ORCS; 71981; 0 hits in 41 CRISPR screens.
DR ChiTaRS; Tdrd12; mouse.
DR PRO; PR:Q9CWU0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9CWU0; protein.
DR Bgee; ENSMUSG00000030491; Expressed in spermatocyte and 54 other tissues.
DR ExpressionAtlas; Q9CWU0; baseline and differential.
DR Genevisible; Q9CWU0; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990923; C:PET complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
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; IMP:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; 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; -; 2.
DR Gene3D; 2.60.40.790; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR007052; CS_dom.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR035437; SNase_OB-fold_sf.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF04969; CS; 1.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00567; TUDOR; 2.
DR SUPFAM; SSF49764; SSF49764; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51203; CS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Developmental protein; Differentiation;
KW Helicase; Hydrolase; Meiosis; Nucleotide-binding; Reference proteome;
KW Repeat; RNA-mediated gene silencing; Spermatogenesis.
FT CHAIN 1..1215
FT /note="Putative ATP-dependent RNA helicase TDRD12"
FT /id="PRO_0000311969"
FT DOMAIN 56..118
FT /note="Tudor 1"
FT DOMAIN 440..628
FT /note="Helicase ATP-binding"
FT DOMAIN 809..909
FT /note="Tudor 2"
FT DOMAIN 1073..1159
FT /note="CS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547"
FT REGION 308..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1027..1071
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 567..570
FT /note="DEAH box"
FT BINDING 453..460
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VAR_SEQ 399..407
FT /note="MALTCLNSD -> VNMFLKPDS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12787504,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_029677"
FT VAR_SEQ 408..1215
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12787504,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_029678"
FT CONFLICT 318
FT /note="S -> SY (in Ref. 3; AC151535)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1215 AA; 137627 MW; 4EF202AFB8B86D8D CRC64;
MFEVLVLKIE DPGCFWVIIK GCSHFLEQEV DYQKLNTAMN DFYNSMCQDV EMKPLMLEEG
QVCVVYCQEL KCWCRALIKS IISSADHYLA ECFLVDFAKY IPVKSKNIRV AVESFMQLPY
RAKKFRLYGT KPVTLHIDFC EDNAEIVPAT KWDSAAIQYF QNLLRATTQV EAKLCAVEED
TFEVYLYATI KNEKVCVNDD LVAKNFAYYV SPMGNKNLNP LEKPRQSLNS VTCSSKLSPS
LTLWPMLLQG KDYHRMENKA LNYKDSLTDS PKMMLEKQQQ SLPLKHTEKC TESSVYWPTK
RGITIYADPD VPSVSGSSQR PNEKPLRLTE KKDCDEKNGC VKLLQFLNPD PLRADGTSDL
HQLQKVKLGT LQPGVVLRNR IEPCLTLEKS PLSADLKKMA LTCLNSDTED MKVAMEEMIP
PEALQRNKFP GPSHTASYSW PPIARGCDMV VISHCGNDPL LYLPPLLTIL QMGGCYKSLP
SRNGPLAVIV CPGWKKAQFI FELLGDYSMS SRPLHPVLLT IGLHKDEAKN MKLPRGCDVI
VTTPHSLLRL LTYRSLLFLR LCHLVLDEVH MLFFEANEQM FAILDNFKKN VEVEERESAP
HQIVAVGVHW NKHIDHLVRE FMKDPCVVIT ALEEAALYGS VQQVVHLCLE CEKTSTLLQV
LDFVPSQAQK TLIFTCSVAE TETVCKGSPA EQGDKKTKSV LLLTERNASH AVGILRYLER
ADAKIPSELY EFTAGVLEAK EDKKARRPLC PYLKAFGFCK DKRICPDRHH INPEMDIPRK
LSNKTLPVFG HIRVIPFYIS NATNYFGRII DKHVDLYETL NAEMNEYFKE SSNKTSAEKV
ENLGLYGLEE KTLFQRVQVL EVSQKEDTWG LGSILVKLID EGRTKLITRD QLLLLPEKFH
TLPPQAVEFI VCRVKPADSE IEWNPKVTRY IHHKIVGKMH DAKVVLALGN TLWIDPMVHV
TKLSNLKTSI IDYNVRAEIL SMGMGIDNSE HLEQLKKLYK EAKLPAFEDL PCQTSIPTTV
EDTVCLQGTQ QGDGGTERGA GSQEDSDNQK PGVLSEDIGS ETISSAPQPH GRSFHPQIKW
FQKDDVVILK IKIRNVKDYK CKFFTDRVIF SAWVGDKFYL ADLELQGDIR KDDCKCIIKD
DEPLITLAKE KQECWCGLLK QRNPNVAFDF DHWEECEEDS PFSKVVNSKN LSCKVAALAE
SSGSSSDTTD GSESE
