TDRD9_HUMAN
ID TDRD9_HUMAN Reviewed; 1382 AA.
AC Q8NDG6; A1A4S7; Q6ZU54; Q8N7T3; Q8N827; Q8N9V5; Q96AS9;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=ATP-dependent RNA helicase TDRD9 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q14BI7};
DE AltName: Full=Tudor domain-containing protein 9 {ECO:0000305};
GN Name=TDRD9 {ECO:0000312|HGNC:HGNC:20122};
GN Synonyms=C14orf75 {ECO:0000312|HGNC:HGNC:20122};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-1382 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-1382 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 635-1382 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 278-1382 (ISOFORM 1).
RC TISSUE=Bone marrow;
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 [5]
RP INVOLVEMENT IN SPGF30, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=28536242; DOI=10.1136/jmedgenet-2017-104514;
RA Arafat M., Har-Vardi I., Harlev A., Levitas E., Zeadna A., Abofoul-Azab M.,
RA Dyomin V., Sheffield V.C., Lunenfeld E., Huleihel M., Parvari R.;
RT "Mutation in TDRD9 causes non-obstructive azoospermia in infertile men.";
RL J. Med. Genet. 54:633-639(2017).
CC -!- FUNCTION: ATP-binding RNA helicase required during spermatogenesis
CC (PubMed:28536242). Required to repress transposable elements and
CC prevent their mobilization, which is essential for the germline
CC integrity. Acts via the piRNA metabolic process, which mediates the
CC repression of transposable elements during meiosis by forming complexes
CC composed of piRNAs and Piwi proteins and governs the methylation and
CC subsequent repression of transposons. 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. {ECO:0000250|UniProtKB:Q14BI7,
CC ECO:0000269|PubMed:28536242}.
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:0000250|UniProtKB:Q14BI7};
CC -!- SUBUNIT: Interacts with piRNA-associated proteins PIWIL1 and PIWIL4.
CC {ECO:0000269|PubMed:28536242}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28536242}. Nucleus
CC {ECO:0000250|UniProtKB:Q14BI7}. Note=Component of the nuage, also named
CC P granule, a germ-cell-specific organelle required to repress
CC transposon activity during meiosis. Specifically localizes to piP-
CC bodies, a subset of the nuage which contains secondary piRNAs. PIWIL2
CC is required for its localization to piP-bodies.
CC {ECO:0000250|UniProtKB:Q14BI7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NDG6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NDG6-2; Sequence=VSP_033552;
CC -!- DISEASE: Spermatogenic failure 30 (SPGF30) [MIM:618110]: An autosomal
CC recessive infertility disorder caused by spermatogenesis defects that
CC result in non-obstructive azoospermia or cryptozoospermia.
CC {ECO:0000269|PubMed:28536242}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI28058.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI28058.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC04182.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC05047.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC05144.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC86372.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL132712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL833915; CAD38771.1; -; mRNA.
DR EMBL; AK093483; BAC04182.1; ALT_INIT; mRNA.
DR EMBL; AK097429; BAC05047.1; ALT_INIT; mRNA.
DR EMBL; AK097699; BAC05144.1; ALT_INIT; mRNA.
DR EMBL; AK125978; BAC86372.1; ALT_INIT; mRNA.
DR EMBL; BC016796; AAH16796.1; -; mRNA.
DR EMBL; BC128057; AAI28058.1; ALT_SEQ; mRNA.
DR CCDS; CCDS9987.2; -. [Q8NDG6-1]
DR PIR; G02632; G02632.
DR RefSeq; NP_694591.2; NM_153046.2. [Q8NDG6-1]
DR AlphaFoldDB; Q8NDG6; -.
DR SMR; Q8NDG6; -.
DR BioGRID; 125766; 8.
DR IntAct; Q8NDG6; 2.
DR STRING; 9606.ENSP00000387303; -.
DR iPTMnet; Q8NDG6; -.
DR PhosphoSitePlus; Q8NDG6; -.
DR BioMuta; TDRD9; -.
DR EPD; Q8NDG6; -.
DR MassIVE; Q8NDG6; -.
DR PaxDb; Q8NDG6; -.
DR PeptideAtlas; Q8NDG6; -.
DR PRIDE; Q8NDG6; -.
DR ProteomicsDB; 73024; -. [Q8NDG6-1]
DR ProteomicsDB; 73025; -. [Q8NDG6-2]
DR Antibodypedia; 47449; 69 antibodies from 14 providers.
DR DNASU; 122402; -.
DR Ensembl; ENST00000409874.9; ENSP00000387303.4; ENSG00000156414.20. [Q8NDG6-1]
DR GeneID; 122402; -.
DR KEGG; hsa:122402; -.
DR MANE-Select; ENST00000409874.9; ENSP00000387303.4; NM_153046.3; NP_694591.2.
DR UCSC; uc001yom.5; human. [Q8NDG6-1]
DR CTD; 122402; -.
DR DisGeNET; 122402; -.
DR GeneCards; TDRD9; -.
DR HGNC; HGNC:20122; TDRD9.
DR HPA; ENSG00000156414; Group enriched (parathyroid gland, testis).
DR MalaCards; TDRD9; -.
DR MIM; 617963; gene.
DR MIM; 618110; phenotype.
DR neXtProt; NX_Q8NDG6; -.
DR OpenTargets; ENSG00000156414; -.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA134890186; -.
DR VEuPathDB; HostDB:ENSG00000156414; -.
DR eggNOG; KOG0920; Eukaryota.
DR GeneTree; ENSGT00940000157035; -.
DR HOGENOM; CLU_002601_1_0_1; -.
DR InParanoid; Q8NDG6; -.
DR OMA; DPCRTVY; -.
DR PhylomeDB; Q8NDG6; -.
DR TreeFam; TF324869; -.
DR PathwayCommons; Q8NDG6; -.
DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis.
DR SignaLink; Q8NDG6; -.
DR BioGRID-ORCS; 122402; 7 hits in 1072 CRISPR screens.
DR ChiTaRS; TDRD9; human.
DR GenomeRNAi; 122402; -.
DR Pharos; Q8NDG6; Tbio.
DR PRO; PR:Q8NDG6; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8NDG6; protein.
DR Bgee; ENSG00000156414; Expressed in right testis and 124 other tissues.
DR ExpressionAtlas; Q8NDG6; baseline and differential.
DR Genevisible; Q8NDG6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071547; C:piP-body; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0009566; P:fertilization; ISS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0007141; P:male meiosis I; ISS:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; ISS: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 2: Evidence at transcript 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..1382
FT /note="ATP-dependent RNA helicase TDRD9"
FT /id="PRO_0000333813"
FT DOMAIN 142..308
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 377..544
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 944..1004
FT /note="Tudor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 36..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 254..257
FT /note="DEAH box"
FT /evidence="ECO:0000250|UniProtKB:Q14BI7"
FT BINDING 155..162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT VAR_SEQ 1095..1285
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033552"
FT CONFLICT 758
FT /note="P -> L (in Ref. 3; BAC05047)"
FT /evidence="ECO:0000305"
FT CONFLICT 1260
FT /note="T -> G (in Ref. 4; AAH16796)"
FT /evidence="ECO:0000305"
FT CONFLICT 1276
FT /note="V -> F (in Ref. 3; BAC05144)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1382 AA; 155683 MW; 8A48E71E4A12041F CRC64;
MLRKLTIEQI NDWFTIGKTV TNVELLGAPP AFPAGAAREE VQRQDVAPGA GPAAQAPALA
QAPARPAAAF ERSLSQRSSE VEYINKYRQL EAQELDVCRS VQPTSGPGPR PSLAKLSSVT
CIPGTTYKYP DLPISRYKEE VVSLIESNSV VIIHGATGSG KSTQLPQYIL DHYVQRSAYC
SIVVTQPRKI GASSIARWIS KERAWTLGGV VGYQVGLEKI ATEDTRLIYM TTGVLLQKIV
SAKSLMEFTH IIIDEVHERT EEMDFLLLVV RKLLRTNSRF VKVVLMSATI SCKEFADYFA
VPVQNKMNPA YIFEVEGKPH SVEEYYLNDL EHIHHSKLSP HLLEEPVITK DIYEVAVSLI
QMFDDLDMKE SGNKAWSGAQ FVLERSSVLV FLPGLGEINY MHELLTSLVH KRLQVYPLHS
SVALEEQNNV FLSPVPGYRK IILSTNIAES SVTVPDVKYV IDFCLTRTLV CDEDTNYQSL
RLSWASKTSC NQRKGRAGRV SRGYCYRLVH KDFWDNSIPD HVVPEMLRCP LGSTILKVKL
LDMGEPRALL ATALSPPGLS DIERTILLLK EVGALAVSGQ REDENPHDGE LTFLGRVLAQ
LPVNQQLGKL IVLGHVFGCL DECLIIAAAL SLKNFFAMPF RQHLDGYRNK VNFSGSSKSD
CIALVEAFKT WKACRQTGEL RYPKDELNWG RLNYIQIKRI REVAELYEEL KTRISQFNMH
VDSRRPVMDQ EYIYKQRFIL QVVLAGAFYP NYFTFGQPDE EMAVRELAGK DPKTTVVLKH
IPPYGFLYYK QLQSLFRQCG QVKSIVFDGA KAFVEFSRNP TERFKTLPAV YMAIKMSQLK
VSLELSVHSA EEIEGKVQGM NVSKLRNTRV NVDFQKQTVD PMQVSFNTSD RSQTVTDLLL
TIDVTEVVEV GHFWGYRIDE NNSEILKKLT AEINQLTLVP LPTHPHPDLV CLAPFADFDK
QRYFRAQVLY VSGNSAEVFF VDYGNKSHVD LHLLMEIPCQ FLELPFQALE FKICKMRPSA
KSLVCGKHWS DGASQWFASL VSGCTLLVKV FSVVHSVLHV DVYQYSGVQD AINIRDVLIQ
QGYAELTEES YESKQSHEVL KGLFSKSVEN MTDGSVPFPM KDDEKYLIRI LLESFSTNKL
GTPNCKAELH GPFNPYELKC HSLTRISKFR CVWIEKESIN SVIISDAPED LHQRMLVAAS
LSINATGSTM LLRETSLMPH IPGLPALLSM LFAPVIELRI DQNGKYYTGV LCGLGWNPAT
GASILPEHDM ELAFDVQFSV EDVVEVNILR AAINKLVCDG PNGCKCLGPE RVAQLQDIAR
QKLLGLFCQS KPREKIVPKW HEKPYEWNQV DPKLVMEQAD RESSRGKNTF LYQLHKLVVL
GT
