TDRKH_DROME
ID TDRKH_DROME Reviewed; 576 AA.
AC Q9VQ91;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Tudor and KH domain-containing protein homolog {ECO:0000305};
DE AltName: Full=Partner of PIWIs protein {ECO:0000303|PubMed:21447556};
GN Name=papi {ECO:0000303|PubMed:21447556, ECO:0000312|FlyBase:FBgn0031401};
GN Synonyms=Tdrd2 {ECO:0000303|PubMed:29531043};
GN ORFNames=CG7082 {ECO:0000312|FlyBase:FBgn0031401};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, INTERACTION WITH AGO3; PIWI; TRAL AND ME31B, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21447556; DOI=10.1242/dev.059287;
RA Liu L., Qi H., Wang J., Lin H.;
RT "PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in
RT the nuage to silence transposition.";
RL Development 138:1863-1873(2011).
RN [5] {ECO:0007744|PDB:5YGB, ECO:0007744|PDB:5YGC, ECO:0007744|PDB:5YGD, ECO:0007744|PDB:5YGF}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 259-479, FUNCTION, INTERACTION
RP WITH PIWI, DOMAIN, AND MUTAGENESIS OF ASP-287; PHE-323; TYR-328; ASP-348;
RP TYR-354; ASP-356; GLU-358; TYR-359 AND GLU-407.
RX PubMed=29531043; DOI=10.1073/pnas.1717116115;
RA Zhang Y.H., Liu W.W., Li R.H., Gu J.Q., Wu P., Peng C., Ma J.B., Wu L.G.,
RA Yu Y., Huang Y.;
RT "Structural insights into the sequence-specific recognition of Piwi by
RT Drosophila Papi.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:3374-3379(2018).
CC -!- FUNCTION: Involved in the piwi-interacting RNA (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 which
CC is essential for germline integrity (PubMed:21447556, PubMed:29531043).
CC Likely to act by recruiting Piwi proteins such as AGO3 and piwi to the
CC piRNA biogenesis machinery in the nuage (PubMed:21447556,
CC PubMed:29531043). Required for the final steps of primary piRNA
CC biogenesis by participating in the 3' end-trimming of piwi-bound
CC intermediates into mature piRNAs (PubMed:29531043).
CC {ECO:0000269|PubMed:21447556, ECO:0000269|PubMed:29531043}.
CC -!- SUBUNIT: Interacts (via C-terminus) with AGO3 (via the N-terminal
CC region when symmetrically methylated on arginine residues); this
CC interaction is RNA-independent and may be required for AGO3
CC localization to the nuage (PubMed:21447556). Interacts (via Tudor
CC domain) with piwi (via N-terminus) (PubMed:21447556, PubMed:29531043).
CC Interacts with tral and me31B (PubMed:21447556).
CC {ECO:0000269|PubMed:21447556, ECO:0000269|PubMed:29531043}.
CC -!- INTERACTION:
CC Q9VQ91; Q7PLK0: AGO3; NbExp=6; IntAct=EBI-6915287, EBI-3431981;
CC Q9VQ91; Q9VKM1: piwi; NbExp=3; IntAct=EBI-6915287, EBI-3406276;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21447556}. Nucleus
CC {ECO:0000269|PubMed:21447556}. Cytoplasm, P-body
CC {ECO:0000269|PubMed:21447556}. Note=Component of the meiotic nuage,
CC also named P granule, a germ-cell-specific organelle required to
CC repress transposon activity during meiosis. Expressed in the cytoplasm
CC of germline stem cells, cyst cells, nurse cells and oocytes, with
CC strong accumulation in region IIb germline cysts in the germarium. In
CC post-germarium egg chambers accumulates in the perinuclear loci that
CC appear to be the nuage. {ECO:0000269|PubMed:21447556}.
CC -!- TISSUE SPECIFICITY: Ovaries (at protein level). Expressed in the ovary
CC and testis. {ECO:0000269|PubMed:21447556}.
CC -!- DEVELOPMENTAL STAGE: Embryo (at protein level) (PubMed:21447556).
CC Expressed throughout development with highest levels of expression in
CC 3rd-instar larvae and adults (PubMed:21447556). Expressed throughout
CC the whole early embryo including the pole cells (PubMed:21447556).
CC {ECO:0000269|PubMed:21447556}.
CC -!- DOMAIN: The Tudor domain is sufficient for binding to the N-terminus
CC (1-14) of both unmethylated piwi or piwi symmetrically dimethylated at
CC 'Arg-10' (PubMed:29531043). However, it may not be sufficient for
CC binding to symmetrically dimethylated AGO3, instead this interaction
CC may require a larger region of the C-terminus which includes the Tudor
CC domain (257-576) (PubMed:21447556, PubMed:29531043).
CC {ECO:0000269|PubMed:21447556, ECO:0000269|PubMed:29531043}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown does not produce a
CC visible phenotype. However, fertility is reduced with egg-laying
CC decreased by 30%. AGO3 protein levels are decreased and AGO3 is
CC delocalized from the nuage. No effect on nuage morphology and no
CC mislocalization of piwi and aub. RNAi-mediated knockdown in germline
CC tissues results in delocalization of AGO3 from the nuage.
CC {ECO:0000269|PubMed:21447556}.
CC -!- SIMILARITY: Belongs to the Tdrkh family. {ECO:0000305}.
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DR EMBL; AE014134; AAF51286.1; -; Genomic_DNA.
DR EMBL; AY058408; AAL13637.1; -; mRNA.
DR EMBL; AE014134; AAN10448.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10449.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10450.1; -; Genomic_DNA.
DR RefSeq; NP_608657.1; NM_134813.3.
DR RefSeq; NP_722773.1; NM_164461.2.
DR RefSeq; NP_722774.1; NM_164462.2.
DR RefSeq; NP_722775.1; NM_164463.2.
DR PDB; 5YGB; X-ray; 1.40 A; A=259-479.
DR PDB; 5YGC; X-ray; 2.00 A; A=259-479.
DR PDB; 5YGD; X-ray; 1.55 A; A=259-479.
DR PDB; 5YGF; X-ray; 1.70 A; A=259-479.
DR PDBsum; 5YGB; -.
DR PDBsum; 5YGC; -.
DR PDBsum; 5YGD; -.
DR PDBsum; 5YGF; -.
DR AlphaFoldDB; Q9VQ91; -.
DR SMR; Q9VQ91; -.
DR IntAct; Q9VQ91; 7.
DR STRING; 7227.FBpp0077508; -.
DR PaxDb; Q9VQ91; -.
DR PRIDE; Q9VQ91; -.
DR DNASU; 33401; -.
DR EnsemblMetazoa; FBtr0077836; FBpp0077508; FBgn0031401.
DR EnsemblMetazoa; FBtr0077837; FBpp0077509; FBgn0031401.
DR EnsemblMetazoa; FBtr0077838; FBpp0077510; FBgn0031401.
DR EnsemblMetazoa; FBtr0077839; FBpp0077511; FBgn0031401.
DR GeneID; 33401; -.
DR KEGG; dme:Dmel_CG7082; -.
DR UCSC; CG7082-RA; d. melanogaster.
DR CTD; 33401; -.
DR FlyBase; FBgn0031401; papi.
DR VEuPathDB; VectorBase:FBgn0031401; -.
DR eggNOG; KOG2279; Eukaryota.
DR GeneTree; ENSGT00940000166206; -.
DR HOGENOM; CLU_023629_0_1_1; -.
DR InParanoid; Q9VQ91; -.
DR OMA; MEVYVSA; -.
DR OrthoDB; 971207at2759; -.
DR PhylomeDB; Q9VQ91; -.
DR Reactome; R-DME-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 33401; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33401; -.
DR PRO; PR:Q9VQ91; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031401; Expressed in crop (Drosophila) and 37 other tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043186; C:P granule; IDA:FlyBase.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0070895; P:negative regulation of transposon integration; IMP:UniProtKB.
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:1903829; P:positive regulation of protein localization; 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; Nucleus; Reference proteome.
FT CHAIN 1..576
FT /note="Tudor and KH domain-containing protein homolog"
FT /id="PRO_0000445617"
FT DOMAIN 65..127
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 136..199
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 310..375
FT /note="Tudor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 40..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 287
FT /note="D->A: No effect on binding to piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 323
FT /note="F->A: Decreased binding to piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 328
FT /note="Y->A: Significant decrease in binding to
FT unmethylated piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 328
FT /note="Y->A: Unable to rescue fertility and transposon
FT activation defects in mutants. Abolishes binding to piwi;
FT when associated with R-348."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 348
FT /note="D->R: Decreased binding to piwi and unable to rescue
FT fertility and transposon activation defects in mutants.
FT Abolishes binding to piwi; when associated with A-328."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 354
FT /note="Y->A: Decreased binding to unmethylated piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 356
FT /note="D->A: Decreased binding to unmethylated piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 358
FT /note="E->A: Decreased binding to piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 359
FT /note="Y->A: Decreased binding to unmethylated piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 359
FT /note="Y->R: Decreased binding to piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT MUTAGEN 407
FT /note="E->A: Decreased binding to piwi."
FT /evidence="ECO:0000269|PubMed:29531043"
FT STRAND 261..270
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 281..297
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 300..304
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 316..320
FT /evidence="ECO:0007829|PDB:5YGB"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 327..337
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:5YGB"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 357..360
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 370..373
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:5YGC"
FT HELIX 400..410
FT /evidence="ECO:0007829|PDB:5YGB"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:5YGB"
FT STRAND 418..427
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:5YGF"
FT STRAND 443..451
FT /evidence="ECO:0007829|PDB:5YGB"
FT HELIX 461..467
FT /evidence="ECO:0007829|PDB:5YGB"
SQ SEQUENCE 576 AA; 63823 MW; AF7FBC9A62FF8622 CRC64;
MLRNTPFGAT PTYKLLLGFG LCSLGGAMLY AYFKTRNDEE EADSGGQRPA SGIRGQTEEQ
KPQKEVCLKI VVDNEHVPLI MGRGGSNIKL IEEKTLAKIR LRDKDSGHKF CDISGVPDAV
KAARALLIKE IERAPVVKVE LQVPQRLASK INGRGGELLQ EIRSSSLAKL NIDLNGRNGK
AKITIIGNQK QVNIARKMLD DQIEEDEELV RSMEEVEQRR EPRRSPTNSI ASSMYSSQTS
LSSHTQPRDK LMASKGEGKP MEVYVSAVAS PTKFWVQLIG PQSKKLDSMV QEMTSYYSSA
ENRAKHVLTA PYVGQIVAAV FKFDEKWYRA EIVDIMPNQY NPKEQVIDLY FVDYGDSEYI
SPADICELRT DFLTLRFQAV ECFLANVKST IQTEPITWPK SSIAKFEELT EVAHWRKLIA
RVVTYKERPR ATTAVSAAAK EGTPLPGVEL FDPADNSELN IADLMITQGF ALPLDDSYPV
RSRSSTPSSN SDSTIEELCV SNPVTPLTPH SPMSMSIDVD SITQAENEHL AQQLQHLQHK
LNGNDIKNIN PAKLTATDLE NGNNNNASTT NGASAH
