TDRKH_MOUSE
ID TDRKH_MOUSE Reviewed; 560 AA.
AC Q80VL1;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Tudor and KH domain-containing protein;
DE AltName: Full=Tudor domain-containing protein 2;
GN Name=Tdrkh; Synonyms=Tdrd2;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 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 [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP INTERACTION WITH PIWIL1 AND PIWIL2.
RX PubMed=19918066; DOI=10.1073/pnas.0911640106;
RA Chen C., Jin J., James D.A., Adams-Cioaba M.A., Park J.G., Guo Y.,
RA Tenaglia E., Xu C., Gish G., Min J., Pawson T.;
RT "Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain
RT to arginine methylated Miwi.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20336-20341(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Pancreas, 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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE,
RP AND INTERACTION WITH PIWIL1 AND PIWIL4.
RX PubMed=23714778; DOI=10.1038/emboj.2013.121;
RA Saxe J.P., Chen M., Zhao H., Lin H.;
RT "Tdrkh is essential for spermatogenesis and participates in primary piRNA
RT biogenesis in the germline.";
RL EMBO J. 32:1869-1885(2013).
RN [7]
RP STRUCTURE BY NMR OF 118-208.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of KH domain in protein BAB28342.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Participates in the primary piRNA biogenesis pathway and is
CC required during spermatogenesis to repress transposable elements and
CC prevent their mobilization, which is essential for the germline
CC integrity. The piRNA metabolic process mediates the repression of
CC transposable elements during meiosis by forming complexes composed of
CC piRNAs and Piwi proteins and govern the methylation and subsequent
CC repression of transposons. Required for the final steps of primary
CC piRNA biogenesis by participating in the processing of 31-37 nt
CC intermediates into mature piRNAs. May act in pi-bodies and piP-bodies
CC by transferring piRNA precursors or intermediates to or between these
CC granules. {ECO:0000269|PubMed:23714778}.
CC -!- SUBUNIT: Interacts with (symmetrically methylated) PIWIL1, PIWIL2 and
CC PIWIL4. {ECO:0000269|PubMed:19584108, ECO:0000269|PubMed:19918066,
CC ECO:0000269|PubMed:23714778}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Note=Probable component
CC of the meiotic nuage, also named P granule, a germ-cell-specific
CC organelle required to repress transposon activity during meiosis.
CC Colocalizes with pi- and piP-bodies, a subset of the nuage which
CC contains secondary piRNAs. Associated with mitochondria in the
CC germline.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, present at lower level
CC in brain. Weakly or not expressed in other tissues (at protein level).
CC {ECO:0000269|PubMed:19918066}.
CC -!- DEVELOPMENTAL STAGE: Present at low level in male gonads in postnatal
CC day 7 (P7) Expressed at higher level in P14, P21 and adult testes,
CC correlating with the onset of meiosis (at protein level). Expressed in
CC spermatogonia, spermatocytes and round spermatids, but not in
CC elongating spermatids. {ECO:0000269|PubMed:19918066,
CC ECO:0000269|PubMed:23714778}.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000250|UniProtKB:Q9Y2W6}.
CC -!- DISRUPTION PHENOTYPE: Male mice are sterile due to defects in male
CC meiosis, piRNA production defects, DNA demethylation of LINE-1 (L1)
CC transposable elements and an increase in L1 expression in the adult
CC testis. Mutants have severely reduced levels of mature piRNAs and
CC accumulate 1'U-containing, 2'O-methylated 31-37 nt RNAs that complement
CC the missing mature piRNAs. {ECO:0000269|PubMed:23714778}.
CC -!- SIMILARITY: Belongs to the Tdrkh family. {ECO:0000305}.
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DR EMBL; GL456099; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049363; AAH49363.1; -; mRNA.
DR CCDS; CCDS38534.1; -.
DR RefSeq; NP_082583.1; NM_028307.1.
DR RefSeq; XP_006502201.1; XM_006502138.3.
DR RefSeq; XP_017175235.1; XM_017319746.1.
DR PDB; 1WE8; NMR; -; A=118-208.
DR PDBsum; 1WE8; -.
DR AlphaFoldDB; Q80VL1; -.
DR SMR; Q80VL1; -.
DR IntAct; Q80VL1; 1.
DR MINT; Q80VL1; -.
DR STRING; 10090.ENSMUSP00000129635; -.
DR iPTMnet; Q80VL1; -.
DR PhosphoSitePlus; Q80VL1; -.
DR SwissPalm; Q80VL1; -.
DR EPD; Q80VL1; -.
DR MaxQB; Q80VL1; -.
DR PaxDb; Q80VL1; -.
DR PRIDE; Q80VL1; -.
DR ProteomicsDB; 262850; -.
DR Antibodypedia; 10583; 84 antibodies from 25 providers.
DR Ensembl; ENSMUST00000045245; ENSMUSP00000041002; ENSMUSG00000041912.
DR Ensembl; ENSMUST00000166032; ENSMUSP00000129635; ENSMUSG00000041912.
DR Ensembl; ENSMUST00000197901; ENSMUSP00000142561; ENSMUSG00000041912.
DR GeneID; 72634; -.
DR KEGG; mmu:72634; -.
DR UCSC; uc008qge.1; mouse.
DR CTD; 11022; -.
DR MGI; MGI:1919884; Tdrkh.
DR VEuPathDB; HostDB:ENSMUSG00000041912; -.
DR eggNOG; KOG2279; Eukaryota.
DR GeneTree; ENSGT00940000159364; -.
DR HOGENOM; CLU_023629_1_0_1; -.
DR InParanoid; Q80VL1; -.
DR OMA; MEVYVSA; -.
DR OrthoDB; 971207at2759; -.
DR PhylomeDB; Q80VL1; -.
DR TreeFam; TF318292; -.
DR BioGRID-ORCS; 72634; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Tdrkh; mouse.
DR EvolutionaryTrace; Q80VL1; -.
DR PRO; PR:Q80VL1; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q80VL1; protein.
DR Bgee; ENSMUSG00000041912; Expressed in embryonic brain and 181 other tissues.
DR ExpressionAtlas; Q80VL1; baseline and differential.
DR Genevisible; Q80VL1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043186; C:P granule; IBA:GO_Central.
DR GO; GO:0071546; C:pi-body; IDA:UniProtKB.
DR GO; GO:0071547; C:piP-body; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; 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:0007140; P:male meiotic nuclear division; IMP:UniProtKB.
DR GO; GO:0030719; P:P granule organization; IBA:GO_Central.
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; 3.30.1370.10; -; 2.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR035437; SNase_OB-fold_sf.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF00013; KH_1; 2.
DR Pfam; PF00567; TUDOR; 1.
DR SMART; SM00322; KH; 2.
DR SMART; SM00333; TUDOR; 1.
DR SUPFAM; SSF54791; SSF54791; 2.
DR PROSITE; PS50084; KH_TYPE_1; 2.
DR PROSITE; PS50304; TUDOR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Differentiation; Isopeptide bond; Mitochondrion;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW RNA-mediated gene silencing; Spermatogenesis; Ubl conjugation.
FT CHAIN 1..560
FT /note="Tudor and KH domain-containing protein"
FT /id="PRO_0000050142"
FT DOMAIN 52..115
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 124..190
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 353..412
FT /note="Tudor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 211..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 65
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 76
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 152
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 181
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 187
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 193
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 256
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 267
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 479
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 510
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT CROSSLNK 529
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2W6"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1WE8"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:1WE8"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1WE8"
FT HELIX 136..140
FT /evidence="ECO:0007829|PDB:1WE8"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1WE8"
FT HELIX 145..154
FT /evidence="ECO:0007829|PDB:1WE8"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:1WE8"
FT STRAND 167..179
FT /evidence="ECO:0007829|PDB:1WE8"
FT HELIX 180..205
FT /evidence="ECO:0007829|PDB:1WE8"
SQ SEQUENCE 560 AA; 62134 MW; 57AB7B6F56D33128 CRC64;
MSTERTSWTN LSTIQKIALG LGIPASATVA YILYRRYRES REERLTFVGE DDIEIEMRVP
QEAVKLIIGR QGANIKQLRK QTGARIDVDT EDVGDERVLL ISGFPVQVCK AKAAIHQILT
ENTPVFEQLS VPQRSVGRII GRGGETIRSI CKASGAKITC DKESEGTLLL SRLIKISGTQ
KEVAAAKHLI LEKVSEDEEL RKRIAHSAET RVPRKQPISV RREEVTEPGG AGEAALWKNT
NSSMGPATPL EVPLRKGGGD MVVVGPKEGS WEKPNDDSFQ NSGAQSSPET SMFEIPSPDF
SFHADEYLEV YVSASEHPNH FWIQIIGSRS LQLDKLVSEM TQHYENSLPE DLTVHVGDIV
AAPLSTNGSW YRARVLGTLE NGNLDLYFVD FGDNGDCALK DLRALRSDFL SLPFQAIECS
LARIAPTGEE WEEEALDEFD RLTHCADWKP LVAKISSYVQ TGISTWPKIY LYDTSDEKKL
DIGLELVRKG YAVELPEDME ENRTVPNMLK DMATETDDSL ASILTETKKS PEEMPHTLSC
LSLSEAASMS GDDNLEDDLF
