TDRD6_MOUSE
ID TDRD6_MOUSE Reviewed; 2134 AA.
AC P61407;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Tudor domain-containing protein 6 {ECO:0000303|PubMed:27149095};
GN Name=Tdrd6 {ECO:0000303|PubMed:27149095, ECO:0000312|MGI:MGI:2679727};
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], IDENTIFICATION IN A MRNP COMPLEX, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=17141210; DOI=10.1016/j.ydbio.2006.10.046;
RA Hosokawa M., Shoji M., Kitamura K., Tanaka T., Noce T., Chuma S.,
RA Nakatsuji N.;
RT "Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain
RT composition, intracellular localization, and function in male germ cells in
RT mice.";
RL Dev. Biol. 301:38-52(2007).
RN [2]
RP FUNCTION, INTERACTION WITH DDX4, IDENTIFICATION IN A COMPLEX WITH PIWIL1
RP AND PIWIL2, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19345099; DOI=10.1016/j.cub.2009.02.047;
RA Vasileva A., Tiedau D., Firooznia A., Muller-Reichert T., Jessberger R.;
RT "Tdrd6 is required for spermiogenesis, chromatoid body architecture, and
RT regulation of miRNA expression.";
RL Curr. Biol. 19:630-639(2009).
RN [3]
RP INTERACTION WITH PIWIL1.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-292; SER-1723; SER-1726;
RP SER-1925; SER-1980; SER-2063 AND SER-2115, AND IDENTIFICATION BY MASS
RP 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 IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH PIWIL1, AND TISSUE
RP SPECIFICITY.
RX PubMed=19926723; DOI=10.1261/rna.1869710;
RA Kirino Y., Vourekas A., Sayed N., de Lima Alves F., Thomson T., Lasko P.,
RA Rappsilber J., Jongens T.A., Mourelatos Z.;
RT "Arginine methylation of Aubergine mediates Tudor binding and germ plasm
RT localization.";
RL RNA 16:70-78(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27149095; DOI=10.1371/journal.pgen.1005857;
RA Fanourgakis G., Lesche M., Akpinar M., Dahl A., Jessberger R.;
RT "Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense
RT Mediated mRNA Decay.";
RL PLoS Genet. 12:E1005857-E1005857(2016).
RN [7]
RP FUNCTION, INTERACTION WITH PRMT5, AND INTERACTION WITH SNRPB.
RX PubMed=28263986; DOI=10.1371/journal.pgen.1006660;
RA Akpinar M., Lesche M., Fanourgakis G., Fu J., Anastassiadis K., Dahl A.,
RA Jessberger R.;
RT "TDRD6 mediates early steps of spliceosome maturation in primary
RT spermatocytes.";
RL PLoS Genet. 13:E1006660-E1006660(2017).
RN [8]
RP INTERACTION WITH TEX19.1.
RX PubMed=28254886; DOI=10.1242/jcs.188763;
RA Tarabay Y., Achour M., Teletin M., Ye T., Teissandier A., Mark M.,
RA Bourc'his D., Viville S.;
RT "Tex19 paralogs are new members of the piRNA pathway controlling
RT retrotransposon suppression.";
RL J. Cell Sci. 130:1463-1474(2017).
CC -!- FUNCTION: Tudor domain-containing protein involved in germ cell
CC development, more specifically the formation of chromatoid body (during
CC spermiogenesis), Balbiani body (during oogenesis), germ plasm (upon
CC fertilization), and for proper miRNA expression and spliceosome
CC maturation (PubMed:19345099, PubMed:27149095, PubMed:28263986) (By
CC similarity). Essential for RNA-dependent helicase UPF1 localization to
CC chromatoid body, for UPF1-UPF2 and UPF1-DDX4 interactions which are
CC required for mRNA degradation, using the extended 3' UTR-triggered
CC nonsense-mediated mRNA decay (NMD) pathway (PubMed:27149095). Involved
CC in spliceosome maturation and mRNA splicing in prophase I spermatocytes
CC through interaction with arginine N-methyltransferase PRMT5 and
CC symmetrically arginine dimethylated SNRPB (small nuclear
CC ribonucleoprotein-associated protein) (PubMed:28263986).
CC {ECO:0000250|UniProtKB:F1R237, ECO:0000269|PubMed:19345099,
CC ECO:0000269|PubMed:27149095, ECO:0000269|PubMed:28263986}.
CC -!- SUBUNIT: Found in a mRNP complex (i.e. messenger ribonucleoproteins
CC which correspond to mRNA with bound proteins), at least composed of
CC TDRD1, TDRD6, TDRD7 and DDX4 (PubMed:17141210). Found in a complex, at
CC least composed of PIWIL1, PIWIL2, DDX4 and TDRD6 (PubMed:19345099,
CC PubMed:19584108, PubMed:19926723). Interacts with Tex19.1 and probably
CC Tex19.2 (PubMed:28254886). Interacts with PRMT5 (PubMed:28263986).
CC Interacts with SNRPB (when methylated); to trigger spliceosome
CC formation (PubMed:28263986). {ECO:0000269|PubMed:17141210,
CC ECO:0000269|PubMed:19345099, ECO:0000269|PubMed:19584108,
CC ECO:0000269|PubMed:19926723, ECO:0000269|PubMed:28254886,
CC ECO:0000269|PubMed:28263986}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17141210,
CC ECO:0000269|PubMed:19345099, ECO:0000269|PubMed:27149095,
CC ECO:0000269|PubMed:28263986}. Note=Present in chromatoid body (CB) of
CC spermatids, also named processing bodies (P-bodies) in somatic cells
CC (PubMed:17141210, PubMed:19345099, PubMed:27149095). Detected in the
CC multilobular cytoplasmic CBs (also called intermitochondrial cementin)
CC in pachytene spermatocytes and as a single perinuclear CB in haploid
CC round spermatids (PubMed:17141210, PubMed:19345099). Colocalizes in CB
CC with DDX4, PIWIL1, PIWIL2, TDRD1 and TDRD7 (PubMed:17141210,
CC PubMed:19345099). {ECO:0000269|PubMed:17141210,
CC ECO:0000269|PubMed:19345099, ECO:0000269|PubMed:27149095}.
CC -!- TISSUE SPECIFICITY: Testis specific. Expressed in primary spermatocytes
CC at post natal (PN) day 17.5. Expressed in midpachytene stage of primary
CC spermatocytes at PN16 and in round spermatids at PN22 (at protein
CC level). {ECO:0000269|PubMed:17141210, ECO:0000269|PubMed:19345099,
CC ECO:0000269|PubMed:19926723}.
CC -!- DOMAIN: The tudor domains recognize and bind to proteins with
CC dimethylated arginine residues. {ECO:0000305|PubMed:28263986}.
CC -!- PTM: Undergoes proteolytic cleavage near the C-terminal by an unknown
CC protease during the transition from meiosis I to meiosis II in primary
CC spermatocytes.
CC -!- DISRUPTION PHENOTYPE: Males are sterile (elongated spermatids are
CC almost completely lacking), but viable (PubMed:19345099). Chromatoid
CC body (CB) components mislocalize and CB architecture is distorted in
CC round spermatids (PubMed:19345099). miRNA expression is altered
CC (PubMed:19345099). Knockout spermatids are accompanied by distortion of
CC chromatoid body structure, preventing UPF1-DDX4 and UPF1-UPF2
CC interactions, as well as disturbed association of several mRNAs with
CC UPF1 and UPF2, and impaired long 3' UTR-triggered NMD
CC (PubMed:27149095). Knockout diplotene spermatocytes display a reduction
CC of PRMT5 association with SNRPB (also named SmB) and a reduction in
CC arginine dimethylation of SNRPB, leading to an impairment in the
CC assembly of spliceosomes (PubMed:28263986).
CC {ECO:0000269|PubMed:19345099, ECO:0000269|PubMed:27149095,
CC ECO:0000269|PubMed:28263986}.
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DR EMBL; AB097085; BAD01486.1; -; mRNA.
DR CCDS; CCDS28797.1; -.
DR RefSeq; NP_940810.2; NM_198418.2.
DR AlphaFoldDB; P61407; -.
DR SMR; P61407; -.
DR BioGRID; 229157; 7.
DR STRING; 10090.ENSMUSP00000035338; -.
DR iPTMnet; P61407; -.
DR PhosphoSitePlus; P61407; -.
DR PaxDb; P61407; -.
DR PRIDE; P61407; -.
DR ProteomicsDB; 262747; -.
DR GeneID; 210510; -.
DR KEGG; mmu:210510; -.
DR CTD; 221400; -.
DR MGI; MGI:2679727; Tdrd6.
DR eggNOG; KOG2039; Eukaryota.
DR InParanoid; P61407; -.
DR PhylomeDB; P61407; -.
DR BioGRID-ORCS; 210510; 4 hits in 73 CRISPR screens.
DR PRO; PR:P61407; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P61407; protein.
DR GO; GO:0033391; C:chromatoid body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0043186; C:P granule; IDA:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0007281; P:germ cell development; IDA:MGI.
DR GO; GO:0030719; P:P granule organization; IBA:GO_Central.
DR GO; GO:0034587; P:piRNA metabolic process; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; IMP:CACAO.
DR CDD; cd04508; TUDOR; 6.
DR Gene3D; 2.40.50.90; -; 7.
DR InterPro; IPR035437; SNase_OB-fold_sf.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF00567; TUDOR; 7.
DR SMART; SM00333; TUDOR; 7.
DR PROSITE; PS50304; TUDOR; 6.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Differentiation; Oogenesis;
KW Phosphoprotein; Reference proteome; Repeat; Spermatogenesis.
FT CHAIN 1..2134
FT /note="Tudor domain-containing protein 6"
FT /id="PRO_0000183168"
FT DOMAIN 309..368
FT /note="Tudor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT DOMAIN 542..599
FT /note="Tudor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT DOMAIN 820..879
FT /note="Tudor 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT DOMAIN 1038..1092
FT /note="Tudor 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT DOMAIN 1358..1417
FT /note="Tudor 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT DOMAIN 1570..1630
FT /note="Tudor 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 287..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1271..1296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1699..1733
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1860..1885
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1930..1987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1699..1722
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1860..1874
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1938..1962
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 292
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1726
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1925
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1980
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2063
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2115
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 2134 AA; 237914 MW; 0862BA0B2F183C91 CRC64;
MSSTPGLPTP GASLALRVSF VDVHPEVIPV QLWGLVGQRR EEYVRLSREI QEAAATRGPW
ALGGASASPG ELCLVQVGLM WHRCRVVSRQ AQDSRVFLLD EGRTITAGAG SLAPGRSEFF
HLPSEVLGCV LAGLVPAGGG GTGGGEPQQW SPRAVDFLSN LQGKEVHGRV LDVLLLHRLV
LLEVPVVSQQ MEELGLARQV PDSLFCSLLK RYLTAAGQGS SGAPVLPRAA PKQEHPGLDY
FYPQLQLGVT EPVVVTQVCH PHRIHCQLRS LSQEIHRLSE SMAQVYRAPV GTDDEDSGSA
TWEEREESPD KPGSPCASCG LDGQWYRALL LETFRPQRCA QVLHVDYGRK ELVSCSSLRY
LLPEYFRMPV VTYPCALYGL WDCGRGWSRS QVGDLKALIL GQAVNAKIEF YCSFEHMYYV
TLYGEDGINL NSAFGVQSCC LADWFLQSQG IEEEEEEDED EVEAAFQSQS PAEEMEAEVS
LPSLRSIRLK MNTFYDAQVE FVKSPSEFWI RLRKHKNTFS KLTKRMCSFY SSASKLDGVI
LRPEPDDLCC VKWKENGYYR ATVTRLDSKS VDVFLVDRGN SENVDWCDVR MLLPQFRQLP
ILALKCTLAD IWPLGKTWSQ EATSFFKKTV LHKELVVHVL DKQDHQYVIE ILDESRMGEE
NISKVIAQAG FAKFQEFETK ENIRLSAHSP GHVSGHFMAE PSKITSAKKA EGDQRAKKDN
KTLSVSEALA DTVSLSNLST AQDTEKVTSD PSLLMLNFLK TKPDCCGKGE LEVGSTVEVK
VSHIENPGSF WCQLMRNAQG FRTLMCDIED YCKSSEPSPY EGDTRVCLAK RTASGRWSRA
LISGAHSLEH VRVVFVDYGD RDVVSTKDIL SVSDVFFQVR AQAFRCSLYN LIQPMGENPF
VWDEKAVQAF SGFIDSARQN NLELKCTVFA LASRHEEEWF NVVDLLTPFQ SACRFLVEKR
LARPVKHQKP LEPSVQLHSY YYSTHDLKIG SEELVYVTHA DDPWTFYCQL ARNINVLEQL
SYNIMQLSKA LLNLKASTLA PGTLCLARYT DGNWYRGIII EKEPSKVFFV DFGNTYIAVD
HLLPIPRDAH DVLLLPMQAL KCSLSDIPHH IPEEVTAWFQ ETVLDKSLKA LVVAKDPDGR
LIIELYDDSV QINASINEKL GLLGYKNRTR RKEKENEIIL HETKALEDKK ESVKPSLADY
LGKPGESKAH SIEIMGESCK PKMGPACKEL RYLQGSAKAN LVPPYQDSVG NKNDGGFPLT
REKKEDIFAS SPMSGTKLDS ALPERRMGEP SGRDLPPKFC EFPQKTIAPG FKTSVYVSHI
NDLSDFYIQL IEDEAEINNL SERLNDVRTR PQYHTGPQWQ SGDVICAVFP EDNLWYRALV
MEQQPNGLLS VQFIDYGNMS VVHTNRTGRL GPVDAVLPAL CLHCSLWGLS VPVCKEMVSY
FSQRTDEAQI RCEFVKFQGT WEVILADEHG VIAEDMISRF PCNGNSQAGL TTQTMKGDCL
KIANKPNTDT SVLLNWYNPK AKLIKAYATV IDGPEYFWCQ FADSEKLQYL ETEVQSAGKQ
LSDRRSCTQC PQIGDPCIVR YREDGHYYRA LITNICDGEL ASVRLVDFGN AEDCVDAKEL
WSIPSELLLV PMQAFPCCLA GFSVSGGVCP QEGNDYFYDI VTEDVLDITI LEIKRDVCNI
PLAIVELRSK GENINEKMKK YAKTGVPKND LSSEKRGPER KGSLASPDLG LKKPSHKIAQ
DKTFYGEARA SELSERLEKD LNIETKTSKF YERSTRSIFN AFENSCKGKM GSERLEGSMD
YHFVDRAKFD NNYLITGFNP ILAHASEPKE LLELSSLEVP LSADNDDECK EFLELESIEL
QHSPAGEEEK EELGLGSPMA PLSPGCQAGA TLESFMMQLP LDCEAEKQLE LKLPTPQLSL
EDSISPLSAA VSQDIQGSRC SEDERKAGYM GSSDDDHSRS PLLQHGKGGN SPAHDGRNLS
EEEFPQFESR DSAALLAPLF SEEEAREGRK CGSMVPAQLQ STYTLKGFSV GSKCVVWSSL
RNTWSKCEIL ELAEEGTRVL NLSNGVEETV SPENVWNGIP KVDKRPSEAV FQTVGKDLPF
MPSDDATTKG FSSVSEEEAC GGDADSLSTA KLNI
