Full text data of DDX3X
DDX3X
(DBX, DDX3)
[Confidence: low (only semi-automatic identification from reviews)]
ATP-dependent RNA helicase DDX3X; 3.6.4.13 (DEAD box protein 3, X-chromosomal; DEAD box, X isoform; Helicase-like protein 2; HLP2)
ATP-dependent RNA helicase DDX3X; 3.6.4.13 (DEAD box protein 3, X-chromosomal; DEAD box, X isoform; Helicase-like protein 2; HLP2)
UniProt
O00571
ID DDX3X_HUMAN Reviewed; 662 AA.
AC O00571; A8K538; B4E3E8; O15536;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 160.
DE RecName: Full=ATP-dependent RNA helicase DDX3X;
DE EC=3.6.4.13;
DE AltName: Full=DEAD box protein 3, X-chromosomal;
DE AltName: Full=DEAD box, X isoform;
DE AltName: Full=Helicase-like protein 2;
DE Short=HLP2;
GN Name=DDX3X; Synonyms=DBX, DDX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus, and Liver;
RA Chung J., Lee S.-G., Song K.;
RT "Identification of a human homolog of a putative RNA helicase gene
RT (mDEAD3) expressed in mouse erythroid cells.";
RL Korean J. Biochem. 27:193-197(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH HCV CORE PROTEIN.
RC TISSUE=Liver;
RX PubMed=10329544; DOI=10.1006/viro.1999.9659;
RA Owsianka A.M., Patel A.H.;
RT "Hepatitis C virus core protein interacts with a human DEAD box
RT protein DDX3.";
RL Virology 257:330-340(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9381176; DOI=10.1126/science.278.5338.675;
RA Lahn B.T., Page D.C.;
RT "Functional coherence of the human Y chromosome.";
RL Science 278:675-680(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT SER-2.
RX PubMed=10859333; DOI=10.1084/jem.191.12.2083;
RA Yaguee J., Alvarez I., Rognan D., Ramos M., Vazquez J.,
RA Lopez de Castro J.A.;
RT "An N-acetylated natural ligand of human histocompatibility leukocyte
RT antigen (HLA)-B39. Classical major histocompatibility complex class I
RT proteins bind peptides with a blocked NH(2) terminus in vivo.";
RL J. Exp. Med. 191:2083-2092(2000).
RN [9]
RP FUNCTION IN HIV-1 RNA EXPORT/REPLICATION, IDENTIFICATION IN A COMPLEX
RP WITH XPO1 AND REV, INTERACTION WITH XPO1, MUTAGENESIS OF LYS-230 AND
RP SER-382, AND SUBCELLULAR LOCATION.
RX PubMed=15507209; DOI=10.1016/j.cell.2004.09.029;
RA Yedavalli V.S., Neuveut C., Chi Y.-H., Kleiman L., Jeang K.-T.;
RT "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export
RT function.";
RL Cell 119:381-392(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP FUNCTION, INTERACTION WITH SP1, AND SUBCELLULAR LOCATION.
RX PubMed=16818630; DOI=10.1158/0008-5472.CAN-05-2415;
RA Chao C.H., Chen C.M., Cheng P.L., Shih J.W., Tsou A.P., Lee Y.H.;
RT "DDX3, a DEAD box RNA helicase with tumor growth-suppressive property
RT and transcriptional regulation activity of the p21waf1/cip1 promoter,
RT is a candidate tumor suppressor.";
RL Cancer Res. 66:6579-6588(2006).
RN [12]
RP FUNCTION.
RX PubMed=16301996; DOI=10.1038/sj.onc.1209239;
RA Chang P.C., Chi C.W., Chau G.Y., Li F.Y., Tsai Y.H., Wu J.C.,
RA Wu Lee Y.H.;
RT "DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-
RT associated hepatocellular carcinoma and is involved in cell growth
RT control.";
RL Oncogene 25:1991-2003(2006).
RN [13]
RP FUNCTION.
RX PubMed=17357160; DOI=10.1002/prot.21433;
RA Franca R., Belfiore A., Spadari S., Maga G.;
RT "Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate
RT specificity.";
RL Proteins 67:1128-1137(2007).
RN [14]
RP ASSOCIATION WITH SPLICED MRNAS.
RX PubMed=17095540; DOI=10.1261/rna.336807;
RA Merz C., Urlaub H., Will C.L., Luhrmann R.;
RT "Protein composition of human mRNPs spliced in vitro and differential
RT requirements for mRNP protein recruitment.";
RL RNA 13:116-128(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH GSK3A; GSK3B AND TNFRSF10B.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death
RT receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [16]
RP FUNCTION, PHOSPHORYLATION BY TBK1 AND IKBKE, AND MUTAGENESIS OF
RP SER-181; SER-183; SER-240; SER-269; SER-429; THR-438; SER-442; SER-456
RP AND SER-520.
RX PubMed=18583960; DOI=10.1038/emboj.2008.126;
RA Soulat D., Burckstummer T., Westermayer S., Goncalves A., Bauch A.,
RA Stefanovic A., Hantschel O., Bennett K.L., Decker T.,
RA Superti-Furga G.;
RT "The DEAD-box helicase DDX3X is a critical component of the TANK-
RT binding kinase 1-dependent innate immune response.";
RL EMBO J. 27:2135-2146(2008).
RN [17]
RP FUNCTION, AND INTERACTION WITH VACV PROTEIN K7 AND IKBKE.
RX PubMed=18636090; DOI=10.1038/emboj.2008.143;
RA Schroder M., Baran M., Bowie A.G.;
RT "Viral targeting of DEAD box protein 3 reveals its role in
RT TBK1/IKKepsilon-mediated IRF activation.";
RL EMBO J. 27:2147-2157(2008).
RN [18]
RP INTERACTION WITH TDRD3.
RX PubMed=18632687; DOI=10.1093/hmg/ddn203;
RA Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J.;
RT "TDRD3, a novel Tudor domain-containing protein, localizes to
RT cytoplasmic stress granules.";
RL Hum. Mol. Genet. 17:3055-3074(2008).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NXF1.
RX PubMed=18596238; DOI=10.1091/mbc.E07-12-1264;
RA Lai M.C., Lee Y.H., Tarn W.Y.;
RT "The DEAD-box RNA helicase DDX3 associates with export messenger
RT ribonucleoproteins as well as tip-associated protein and participates
RT in translational control.";
RL Mol. Biol. Cell 19:3847-3858(2008).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND ASSOCIATION WITH THE EIF-3
RP COMPLEX.
RX PubMed=18628297; DOI=10.1093/nar/gkn454;
RA Lee C.S., Dias A.P., Jedrychowski M., Patel A.H., Hsu J.L., Reed R.;
RT "Human DDX3 functions in translation and interacts with the
RT translation initiation factor eIF3.";
RL Nucleic Acids Res. 36:4708-4718(2008).
RN [21]
RP FUNCTION, INTERACTION WITH EIF4E, AND MUTAGENESIS OF TYR-38 AND
RP LEU-43.
RX PubMed=17667941; DOI=10.1038/sj.onc.1210687;
RA Shih J.W., Tsai T.Y., Chao C.H., Wu Lee Y.H.;
RT "Candidate tumor suppressor DDX3 RNA helicase specifically represses
RT cap-dependent translation by acting as an eIF4E inhibitory protein.";
RL Oncogene 27:700-714(2008).
RN [22]
RP FUNCTION.
RX PubMed=18264132; DOI=10.1038/onc.2008.33;
RA Botlagunta M., Vesuna F., Mironchik Y., Raman A., Lisok A.,
RA Winnard P. Jr., Mukadam S., Van Diest P., Chen J.H., Farabaugh P.,
RA Patel A.H., Raman V.;
RT "Oncogenic role of DDX3 in breast cancer biogenesis.";
RL Oncogene 27:3912-3922(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP IDENTIFICATION IN A MRNP COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19029303; DOI=10.1261/rna.1175909;
RA Weidensdorfer D., Stoehr N., Baude A., Lederer M., Koehn M.,
RA Schierhorn A., Buchmeier S., Wahle E., Huettelmaiery S.;
RT "Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic
RT RNPs.";
RL RNA 15:104-115(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [26]
RP FUNCTION, INTERACTION WITH MAVS AND DDX58, AND SUBCELLULAR LOCATION.
RX PubMed=20127681; DOI=10.1002/eji.200940203;
RA Oshiumi H., Sakai K., Matsumoto M., Seya T.;
RT "DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-
RT regulate IFN-beta-inducing potential.";
RL Eur. J. Immunol. 40:940-948(2010).
RN [27]
RP FUNCTION, AND INTERACTION WITH IKBKE AND TBK1.
RX PubMed=20375222; DOI=10.1099/vir.0.020552-0;
RA Yu S., Chen J., Wu M., Chen H., Kato N., Yuan Z.;
RT "Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor
RT 3-mediated beta interferon induction in human hepatocytes through
RT interference with interferon regulatory factor 3 activation and
RT dampening of the interaction between TBK1/IKKepsilon and DDX3.";
RL J. Gen. Virol. 91:2080-2090(2010).
RN [28]
RP FUNCTION.
RX PubMed=20837705; DOI=10.1128/MCB.00560-10;
RA Lai M.C., Chang W.C., Shieh S.Y., Tarn W.Y.;
RT "DDX3 regulates cell growth through translational control of cyclin
RT E1.";
RL Mol. Cell. Biol. 30:5444-5453(2010).
RN [29]
RP FUNCTION, RNA-BINDING, INTERACTION WITH MAVS, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21170385; DOI=10.1371/journal.pone.0014258;
RA Oshiumi H., Ikeda M., Matsumoto M., Watanabe A., Takeuchi O.,
RA Akira S., Kato N., Shimotohno K., Seya T.;
RT "Hepatitis C virus core protein abrogates the DDX3 function that
RT enhances IPS-1-mediated IFN-beta induction.";
RL PLoS ONE 5:E14258-E14258(2010).
RN [30]
RP FUNCTION, AND INTERACTION WITH IKBKE.
RX PubMed=20657822; DOI=10.1371/journal.ppat.1000986;
RA Wang H., Ryu W.S.;
RT "Hepatitis B virus polymerase blocks pattern recognition receptor
RT signaling via interaction with DDX3: implications for immune
RT evasion.";
RL PLoS Pathog. 6:E1000986-E1000986(2010).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [33]
RP FUNCTION.
RX PubMed=21589879; DOI=10.1371/journal.pone.0019810;
RA Garbelli A., Beermann S., Di Cicco G., Dietrich U., Maga G.;
RT "A motif unique to the human DEAD-box protein DDX3 is important for
RT nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1
RT replication.";
RL PLoS ONE 6:E19810-E19810(2011).
RN [34]
RP FUNCTION, AND INTERACTION WITH NCAPH.
RX PubMed=21730191; DOI=10.1073/pnas.1106245108;
RA Pek J.W., Kai T.;
RT "DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway
RT promote mitotic chromosome segregation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:12007-12012(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4E AND PABPC1.
RX PubMed=21883093; DOI=10.1042/BJ20110739;
RA Shih J.W., Wang W.T., Tsai T.Y., Kuo C.Y., Li H.K., Wu Lee Y.H.;
RT "Critical roles of RNA helicase DDX3 and its interactions with
RT eIF4E/PABP1 in stress granule assembly and stress response.";
RL Biochem. J. 441:119-129(2012).
RN [37]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INDUCTION, AND
RP INTERACTION WITH DDX5.
RX PubMed=22034099; DOI=10.1002/jcb.23428;
RA Choi Y.J., Lee S.G.;
RT "The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with
RT it in the cytoplasm during the G2/M phase of the cycle, and affects
RT its shuttling during mRNP export.";
RL J. Cell. Biochem. 113:985-996(2012).
RN [38]
RP FUNCTION, ASSOCIATION WITH THE RIBOSOME SMALL SUBUNIT, INTERACTION
RP WITH EIF3C, AND MUTAGENESIS OF TYR-200; GLN-207; LYS-230; ASP-347 AND
RP GLU-348.
RX PubMed=22323517; DOI=10.1093/nar/gks070;
RA Geissler R., Golbik R.P., Behrens S.E.;
RT "The DEAD-box helicase DDX3 supports the assembly of functional 80S
RT ribosomes.";
RL Nucleic Acids Res. 40:4998-5011(2012).
RN [39]
RP FUNCTION, RNA-BINDING, INTERACTION WITH EIF4G1 AND PABPC1, AND
RP MUTAGENESIS OF TYR-38; LEU-43; GLN-207; LYS-230; GLU-348 AND SER-382.
RX PubMed=22872150; DOI=10.1038/emboj.2012.220;
RA Soto-Rifo R., Rubilar P.S., Limousin T., de Breyne S., Decimo D.,
RA Ohlmann T.;
RT "DEAD-box protein DDX3 associates with eIF4F to promote translation of
RT selected mRNAs.";
RL EMBO J. 31:3745-3756(2012).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 409-580.
RX PubMed=17401195; DOI=10.1107/S1744309107006434;
RA Rodamilans B., Montoya G.;
RT "Expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of the DDX3 RNA helicase domain.";
RL Acta Crystallogr. F 63:283-286(2007).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 168-582 IN COMPLEX WITH AMP.
RX PubMed=17631897; DOI=10.1016/j.jmb.2007.06.050;
RA Hoegbom M., Collins R., van den Berg S., Jenvert R.-M., Karlberg T.,
RA Kotenyova T., Flores A., Karlsson Hedestam G.B., Schiavone L.H.;
RT "Crystal structure of conserved domains 1 and 2 of the human DEAD-box
RT helicase DDX3X in complex with the mononucleotide AMP.";
RL J. Mol. Biol. 372:150-159(2007).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 71-90 IN COMPLEX WITH VACV
RP PROTEIN K7, AND MUTAGENESIS OF 84-PHE-PHE-85.
RX PubMed=19913487; DOI=10.1016/j.str.2009.09.005;
RA Oda S., Schroder M., Khan A.R.;
RT "Structural basis for targeting of human RNA helicase DDX3 by poxvirus
RT protein K7.";
RL Structure 17:1528-1537(2009).
RN [43]
RP VARIANT [LARGE SCALE ANALYSIS] THR-294.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Multifunctional ATP-dependent RNA helicase. The ATPase
CC activity can be stimulated by various ribo- and deoxynucleic acids
CC indicative for a relaxed substrate specificity. In vitro can
CC unwind partially double-stranded DNA with a preference for 5'-
CC single-stranded DNA overhangs. Is involved in several steps of
CC gene expression, such as transcription, mRNA maturation, mRNA
CC export and translation. However, the exact mechanisms are not
CC known and some functions may be specific for a subset of mRNAs.
CC Involved in transcriptional regulation. Can enhance transcription
CC from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found
CC associated with the E-cadherin promoter and can down-regulate
CC transcription from the promoter. Involved in regulation of
CC translation initiation. Proposed to be involved in positive
CC regulation of translation such as of cyclin E1/CCNE1 mRNA and
CC specifically of mRNAs containing complex secondary structures in
CC their 5'UTRs; these functions seem to require RNA helicase
CC activity. Specifically promotes translation of a subset of viral
CC and cellular mRNAs carrying a 5'proximal stem-loop structure in
CC their 5'UTRs and cooperates with the eIF4F complex. Proposed to
CC act prior to 43S ribosomal scanning and to locally destabilize
CC these RNA structures to allow recognition of the mRNA cap or
CC loading onto the 40S subunit. After association with 40S ribosomal
CC subunits seems to be involved in the functional assembly of 80S
CC ribosomes; the function seems to cover translation of mRNAs with
CC structured and non-structured 5'UTRs and is independent of RNA
CC helicase activity. Also proposed to inhibit cap-dependent
CC translation by competetive interaction with EIF4E which can block
CC the EIF4E:EIF4G complex formation. Proposed to be involved in
CC stress response and stress granule assembly; the function is
CC independent of RNA helicase activity and seems to involve
CC association with EIF4E. May be involved in nuclear export of
CC specific mRNAs but not in bulk mRNA export via interactions with
CC XPO1 and NXF1. Also associates with polyadenylated mRNAs
CC independently of NXF1. Associates with spliced mRNAs in an exon
CC junction complex (EJC)-dependent manner and seems not to be
CC directly involved in splicing. May be involved in nuclear mRNA
CC export by association with DDX5 and regulating its nuclear
CC location. Involved in innate immune signaling promoting the
CC production of type I interferon (IFN-alpha and IFN-beta); proposed
CC to act as viral RNA sensor, signaling intermediate and
CC transcriptional coactivator. Involved in TBK1 and IKBKE-dependent
CC IRF3 activation leading to IFN-beta induction. Also found
CC associated with IFN-beta promoters; the function is independent of
CC IRF3. Can bind to viral RNAs and via association with MAVS/IPS1
CC and DDX58/RIG-I is thought to induce signaling in early stages of
CC infection. Involved in regulation of apoptosis. May be required
CC for activation of the intrinsic but inhibit activation of the
CC extrinsic apoptotic pathway. Acts as an antiapoptotic protein
CC through association with GSK3A/B and BIRC2 in an apoptosis
CC antagonizing signaling complex; activation of death receptors
CC promotes caspase-dependent cleavage of BIRC2 and DDX3X and
CC relieves the inhibition. May be involved in mitotic chromosome
CC segregation. Appears to be a prime target for viral manipulations.
CC Hepatitis B virus (HBV) polymerase and possibly vaccinia virus
CC (VACV) protein K7 inhibit IFN-beta induction probably by
CC dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C
CC virus (HCV) replication; the function may involve the association
CC with HCV core protein. HCV core protein inhibits the IPS1-
CC dependent function in viral RNA sensing and may switch the
CC function from a INF-beta inducing to a HCV replication mode.
CC Involved in HIV-1 replication. Acts as a cofactor for XPO1-
CC mediated nuclear export of incompletely spliced HIV-1 Rev RNAs.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- SUBUNIT: Interacts with XPO1, TDRD3, PABPC1, NXF1, EIF3C, MAVS,
CC DDX58 and NCAPH. Interacts with DDX5; the interaction is regulated
CC by the phosphorylation status of both proteins. Interacts with
CC EIF4E; DDX3X competes with EIF4G1/EIF4G3 for interaction with
CC EIF4E. Interacts with IKBKE; the interaction is found to be
CC induced upon virus infection and to be inhibited by HBV
CC polymerase. Interacts with TBK1; the interaction is inhibited by
CC HBV polymerase. Associates with the eukaryotic translation
CC initiation factor 3 (eIF-3) complex. Associates with the 40S
CC ribosome. Identified in a mRNP complex, at least composed of DHX9,
CC DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1,
CC STAU2, SYNCRIP and YBX1. Interacts with HCV core protein.
CC Interacts with vaccinia virus (VACV) protein K7. Found in a
CC complex with HIV-1 Rev and XPO1.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=9; IntAct=EBI-353779, EBI-6674379;
CC O95786:DDX58; NbExp=2; IntAct=EBI-353779, EBI-995350;
CC P05198:EIF2S1; NbExp=3; IntAct=EBI-353779, EBI-1056162;
CC P55884:EIF3B; NbExp=5; IntAct=EBI-353779, EBI-366696;
CC Q99613:EIF3C; NbExp=3; IntAct=EBI-353779, EBI-353741;
CC Q04637:EIF4G1; NbExp=3; IntAct=EBI-353779, EBI-73711;
CC Q14164:IKBKE; NbExp=4; IntAct=EBI-353779, EBI-307369;
CC P68467:K7R (xeno); NbExp=6; IntAct=EBI-353779, EBI-8022707;
CC Q7Z434:MAVS; NbExp=4; IntAct=EBI-353779, EBI-995373;
CC Q15003:NCAPH; NbExp=2; IntAct=EBI-353779, EBI-1046410;
CC Q9UBU9:NXF1; NbExp=5; IntAct=EBI-353779, EBI-398874;
CC P11940:PABPC1; NbExp=10; IntAct=EBI-353779, EBI-81531;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm. Mitochondrion
CC outer membrane. Note=Located predominantly in nuclear speckles
CC and, at low levels, throughout the cytoplasm. Located to the outer
CC side of nuclear pore complexes (NPC). Shuttles between the nucleus
CC and the cytoplasm in a XPO1 and may be also in a NFX1-dependent
CC manner. Associated with polyadenylated mRNAs in the cytoplasm and
CC the nucleus. Predominantly located in nucleus during G(0) phase
CC and in the cytoplasm during G1/S phase.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00571-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00571-2; Sequence=VSP_042830;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: Regulated by the cell cycle. Maximally expressed din
CC the cytoplasm uring G1/S phase and decreased expression during
CC G2/M phase.
CC -!- PTM: Phosphorylated by TBK1; the phosphorylation is required to
CC synergize with TBK1 in IFN-beta induction. Probably also
CC phosphorylated by IKBKE. The cytoplasmic form is highly
CC phosphorylated in the G1/S phase and much lower phosphorylated in
CC G2/M.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1
CC subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
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DR EMBL; U50553; AAB95637.1; -; mRNA.
DR EMBL; AF061337; AAC34298.1; -; mRNA.
DR EMBL; AF000983; AAC51830.1; -; mRNA.
DR EMBL; AF000982; AAC51829.1; -; mRNA.
DR EMBL; AK291153; BAF83842.1; -; mRNA.
DR EMBL; AK304689; BAG65460.1; -; mRNA.
DR EMBL; AL391647; CAI41416.1; -; Genomic_DNA.
DR EMBL; Z93015; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471141; EAW59402.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59403.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59404.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59405.1; -; Genomic_DNA.
DR EMBL; BC011819; AAH11819.1; -; mRNA.
DR RefSeq; NP_001180346.1; NM_001193417.1.
DR RefSeq; NP_001347.3; NM_001356.3.
DR UniGene; Hs.743263; -.
DR PDB; 2I4I; X-ray; 2.20 A; A=168-581.
DR PDB; 2JGN; X-ray; 1.91 A; A/B/C=409-579.
DR PDB; 3JRV; X-ray; 1.60 A; C/D/E=71-90.
DR PDBsum; 2I4I; -.
DR PDBsum; 2JGN; -.
DR PDBsum; 3JRV; -.
DR ProteinModelPortal; O00571; -.
DR SMR; O00571; 139-580.
DR DIP; DIP-27551N; -.
DR IntAct; O00571; 77.
DR MINT; MINT-8395017; -.
DR STRING; 9606.ENSP00000382840; -.
DR BindingDB; O00571; -.
DR ChEMBL; CHEMBL5553; -.
DR PhosphoSite; O00571; -.
DR REPRODUCTION-2DPAGE; IPI00215637; -.
DR SWISS-2DPAGE; O00571; -.
DR PaxDb; O00571; -.
DR PeptideAtlas; O00571; -.
DR PRIDE; O00571; -.
DR Ensembl; ENST00000399959; ENSP00000382840; ENSG00000215301.
DR Ensembl; ENST00000457138; ENSP00000392494; ENSG00000215301.
DR GeneID; 1654; -.
DR KEGG; hsa:1654; -.
DR UCSC; uc004dfe.3; human.
DR CTD; 1654; -.
DR GeneCards; GC0XP041192; -.
DR HGNC; HGNC:2745; DDX3X.
DR HPA; HPA001648; -.
DR HPA; HPA005631; -.
DR MIM; 300160; gene.
DR neXtProt; NX_O00571; -.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR PharmGKB; PA27216; -.
DR eggNOG; COG0513; -.
DR HOVERGEN; HBG015893; -.
DR InParanoid; O00571; -.
DR KO; K11594; -.
DR OMA; GMSHVAV; -.
DR OrthoDB; EOG7B5WV8; -.
DR PhylomeDB; O00571; -.
DR ChiTaRS; DDX3X; human.
DR EvolutionaryTrace; O00571; -.
DR GeneWiki; DDX3X; -.
DR GenomeRNAi; 1654; -.
DR NextBio; 6810; -.
DR PRO; PR:O00571; -.
DR ArrayExpress; O00571; -.
DR Bgee; O00571; -.
DR CleanEx; HS_DDX3X; -.
DR Genevestigator; O00571; -.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; IDA:UniProtKB.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IDA:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:UniProtKB.
DR GO; GO:0008143; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0043024; F:ribosomal small subunit binding; IDA:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; IDA:UniProtKB.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0042256; P:mature ribosome assembly; IMP:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein complex assembly; IDA:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; TAS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; IMP:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0010501; P:RNA secondary structure unwinding; IDA:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS.
DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW ATP-binding; Chromosome partition; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Helicase;
KW Host-virus interaction; Hydrolase; Immunity; Innate immunity;
KW Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Ribosome biogenesis; RNA-binding; Transcription;
KW Transcription regulation; Translation regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 662 ATP-dependent RNA helicase DDX3X.
FT /FTId=PRO_0000055009.
FT DOMAIN 211 403 Helicase ATP-binding.
FT DOMAIN 414 575 Helicase C-terminal.
FT NP_BIND 200 207 ATP.
FT NP_BIND 224 231 ATP.
FT REGION 2 139 Required for TBK1 and IKBKE-dependent
FT IFN-beta activation.
FT REGION 2 100 Interaction with EIF4E.
FT REGION 81 90 Required for interaction with VACV
FT protein K7.
FT REGION 100 662 Interaction with GSK3B.
FT REGION 250 259 Involved in stimulation of ATPase
FT activity by DNA and RNA, nucleic acid
FT binding and unwinding and HIV-1
FT replication.
FT REGION 260 517 Necessary for interaction with XPO1.
FT MOTIF 180 208 Q motif.
FT MOTIF 347 350 DEAD box.
FT COMPBIAS 582 662 Gly/Ser-rich.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 69 69 Phosphotyrosine.
FT MOD_RES 74 74 Phosphoserine.
FT MOD_RES 76 76 Phosphoserine.
FT MOD_RES 78 78 Phosphoserine.
FT MOD_RES 104 104 Phosphotyrosine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 125 125 Phosphoserine.
FT MOD_RES 131 131 Phosphoserine.
FT MOD_RES 343 343 Phosphotyrosine.
FT MOD_RES 590 590 Phosphoserine.
FT MOD_RES 594 594 Phosphoserine.
FT MOD_RES 612 612 Phosphoserine.
FT VAR_SEQ 35 51 KGRYIPPHLRNREATKG -> S (in isoform 2).
FT /FTId=VSP_042830.
FT VARIANT 294 294 R -> T (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035839.
FT MUTAGEN 38 38 Y->A: Impairs interaction with EIF4E. No
FT effect on translation of HIV-1 RNA; when
FT associated with A-43.
FT MUTAGEN 43 43 L->A: Impairs interaction with EIF4E.
FT Fails to induce stress granule assembly
FT and to rescue cell viability after
FT stress. No effect on translation of HIV-1
FT RNA; when associated with A-38.
FT MUTAGEN 84 85 FF->AA: Abolishes interaction with VACV
FT protein K7, IRF3 activation and IFN-beta
FT promoter induction.
FT MUTAGEN 181 181 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-183; A-240 and A-269.
FT MUTAGEN 183 183 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-240 and A-269.
FT MUTAGEN 200 200 Y->A: No effect on general translation;
FT when associated with A-207; A-230; A-347
FT and A-348.
FT MUTAGEN 207 207 Q->A: Inhibits translation of HIV-1 RNA.
FT No effect on general translation; when
FT associated with A-200; A-230: A-347 and
FT A-348.
FT MUTAGEN 230 230 K->A: No effect on general translation;
FT when associated with A-200; A-207; A-347
FT and A-348.
FT MUTAGEN 230 230 K->E: Abolishes ATPase activity and RNA-
FT unwinding activity. Inhibits translation
FT of HIV-1 RNA.
FT MUTAGEN 240 240 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-183 and A-269.
FT MUTAGEN 269 269 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-183 and A-240.
FT MUTAGEN 347 347 D->A: No effect on general translation;
FT when associated with A-200; A-207; A-230
FT and A-348.
FT MUTAGEN 348 348 E->A: No effect on general translation;
FT when associated with A-200; A-207; A-230
FT and A-347.
FT MUTAGEN 348 348 E->Q: Inhibits translation of HIV-1 RNA.
FT MUTAGEN 382 382 S->L: Abolishes ATPase activity and RNA-
FT unwinding activity. No effect on
FT translation of HIV-1 RNA.
FT MUTAGEN 429 429 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-438; A-
FT 442; A-456 and A-520.
FT MUTAGEN 438 438 T->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 442; A-456 and A-520.
FT MUTAGEN 442 442 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-456 and A-520.
FT MUTAGEN 456 456 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-442 and A-520.
FT MUTAGEN 520 520 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-442 and A-456.
FT CONFLICT 50 50 K -> R (in Ref. 3; AAC51830/AAC51829).
FT STRAND 168 172
FT HELIX 182 184
FT HELIX 189 198
FT HELIX 205 215
FT STRAND 220 223
FT HELIX 230 245
FT HELIX 249 256
FT STRAND 268 272
FT HELIX 276 290
FT STRAND 297 300
FT STRAND 302 304
FT HELIX 306 313
FT STRAND 318 322
FT HELIX 324 332
FT STRAND 343 348
FT HELIX 349 354
FT HELIX 358 365
FT STRAND 367 369
FT STRAND 376 383
FT HELIX 387 396
FT STRAND 401 405
FT STRAND 415 421
FT HELIX 424 426
FT HELIX 427 437
FT STRAND 444 449
FT HELIX 451 463
FT STRAND 468 471
FT HELIX 482 488
FT STRAND 491 498
FT HELIX 499 502
FT STRAND 509 517
FT HELIX 522 529
FT STRAND 539 545
FT HELIX 547 552
FT HELIX 553 562
FT HELIX 569 575
SQ SEQUENCE 662 AA; 73243 MW; 7074D2B8A6EBBF09 CRC64;
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW
SSSKDKDAYS SFGSRSDSRG KSSFFSDRGS GSRGRFDDRG RSDYDGIGSR GDRSGFGKFE
RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE
SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS
QIYSDGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV
YGGADIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ
IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV
WVEESDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR
EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL
ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAYEHHY KGSSRGRSKS SRFSGGFGAR
DYRQSSGASS SSFSSSRASS SRSGGGGHGS SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW
GN
//
ID DDX3X_HUMAN Reviewed; 662 AA.
AC O00571; A8K538; B4E3E8; O15536;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 160.
DE RecName: Full=ATP-dependent RNA helicase DDX3X;
DE EC=3.6.4.13;
DE AltName: Full=DEAD box protein 3, X-chromosomal;
DE AltName: Full=DEAD box, X isoform;
DE AltName: Full=Helicase-like protein 2;
DE Short=HLP2;
GN Name=DDX3X; Synonyms=DBX, DDX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus, and Liver;
RA Chung J., Lee S.-G., Song K.;
RT "Identification of a human homolog of a putative RNA helicase gene
RT (mDEAD3) expressed in mouse erythroid cells.";
RL Korean J. Biochem. 27:193-197(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH HCV CORE PROTEIN.
RC TISSUE=Liver;
RX PubMed=10329544; DOI=10.1006/viro.1999.9659;
RA Owsianka A.M., Patel A.H.;
RT "Hepatitis C virus core protein interacts with a human DEAD box
RT protein DDX3.";
RL Virology 257:330-340(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9381176; DOI=10.1126/science.278.5338.675;
RA Lahn B.T., Page D.C.;
RT "Functional coherence of the human Y chromosome.";
RL Science 278:675-680(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT SER-2.
RX PubMed=10859333; DOI=10.1084/jem.191.12.2083;
RA Yaguee J., Alvarez I., Rognan D., Ramos M., Vazquez J.,
RA Lopez de Castro J.A.;
RT "An N-acetylated natural ligand of human histocompatibility leukocyte
RT antigen (HLA)-B39. Classical major histocompatibility complex class I
RT proteins bind peptides with a blocked NH(2) terminus in vivo.";
RL J. Exp. Med. 191:2083-2092(2000).
RN [9]
RP FUNCTION IN HIV-1 RNA EXPORT/REPLICATION, IDENTIFICATION IN A COMPLEX
RP WITH XPO1 AND REV, INTERACTION WITH XPO1, MUTAGENESIS OF LYS-230 AND
RP SER-382, AND SUBCELLULAR LOCATION.
RX PubMed=15507209; DOI=10.1016/j.cell.2004.09.029;
RA Yedavalli V.S., Neuveut C., Chi Y.-H., Kleiman L., Jeang K.-T.;
RT "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export
RT function.";
RL Cell 119:381-392(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP FUNCTION, INTERACTION WITH SP1, AND SUBCELLULAR LOCATION.
RX PubMed=16818630; DOI=10.1158/0008-5472.CAN-05-2415;
RA Chao C.H., Chen C.M., Cheng P.L., Shih J.W., Tsou A.P., Lee Y.H.;
RT "DDX3, a DEAD box RNA helicase with tumor growth-suppressive property
RT and transcriptional regulation activity of the p21waf1/cip1 promoter,
RT is a candidate tumor suppressor.";
RL Cancer Res. 66:6579-6588(2006).
RN [12]
RP FUNCTION.
RX PubMed=16301996; DOI=10.1038/sj.onc.1209239;
RA Chang P.C., Chi C.W., Chau G.Y., Li F.Y., Tsai Y.H., Wu J.C.,
RA Wu Lee Y.H.;
RT "DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-
RT associated hepatocellular carcinoma and is involved in cell growth
RT control.";
RL Oncogene 25:1991-2003(2006).
RN [13]
RP FUNCTION.
RX PubMed=17357160; DOI=10.1002/prot.21433;
RA Franca R., Belfiore A., Spadari S., Maga G.;
RT "Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate
RT specificity.";
RL Proteins 67:1128-1137(2007).
RN [14]
RP ASSOCIATION WITH SPLICED MRNAS.
RX PubMed=17095540; DOI=10.1261/rna.336807;
RA Merz C., Urlaub H., Will C.L., Luhrmann R.;
RT "Protein composition of human mRNPs spliced in vitro and differential
RT requirements for mRNP protein recruitment.";
RL RNA 13:116-128(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH GSK3A; GSK3B AND TNFRSF10B.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death
RT receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [16]
RP FUNCTION, PHOSPHORYLATION BY TBK1 AND IKBKE, AND MUTAGENESIS OF
RP SER-181; SER-183; SER-240; SER-269; SER-429; THR-438; SER-442; SER-456
RP AND SER-520.
RX PubMed=18583960; DOI=10.1038/emboj.2008.126;
RA Soulat D., Burckstummer T., Westermayer S., Goncalves A., Bauch A.,
RA Stefanovic A., Hantschel O., Bennett K.L., Decker T.,
RA Superti-Furga G.;
RT "The DEAD-box helicase DDX3X is a critical component of the TANK-
RT binding kinase 1-dependent innate immune response.";
RL EMBO J. 27:2135-2146(2008).
RN [17]
RP FUNCTION, AND INTERACTION WITH VACV PROTEIN K7 AND IKBKE.
RX PubMed=18636090; DOI=10.1038/emboj.2008.143;
RA Schroder M., Baran M., Bowie A.G.;
RT "Viral targeting of DEAD box protein 3 reveals its role in
RT TBK1/IKKepsilon-mediated IRF activation.";
RL EMBO J. 27:2147-2157(2008).
RN [18]
RP INTERACTION WITH TDRD3.
RX PubMed=18632687; DOI=10.1093/hmg/ddn203;
RA Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J.;
RT "TDRD3, a novel Tudor domain-containing protein, localizes to
RT cytoplasmic stress granules.";
RL Hum. Mol. Genet. 17:3055-3074(2008).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NXF1.
RX PubMed=18596238; DOI=10.1091/mbc.E07-12-1264;
RA Lai M.C., Lee Y.H., Tarn W.Y.;
RT "The DEAD-box RNA helicase DDX3 associates with export messenger
RT ribonucleoproteins as well as tip-associated protein and participates
RT in translational control.";
RL Mol. Biol. Cell 19:3847-3858(2008).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND ASSOCIATION WITH THE EIF-3
RP COMPLEX.
RX PubMed=18628297; DOI=10.1093/nar/gkn454;
RA Lee C.S., Dias A.P., Jedrychowski M., Patel A.H., Hsu J.L., Reed R.;
RT "Human DDX3 functions in translation and interacts with the
RT translation initiation factor eIF3.";
RL Nucleic Acids Res. 36:4708-4718(2008).
RN [21]
RP FUNCTION, INTERACTION WITH EIF4E, AND MUTAGENESIS OF TYR-38 AND
RP LEU-43.
RX PubMed=17667941; DOI=10.1038/sj.onc.1210687;
RA Shih J.W., Tsai T.Y., Chao C.H., Wu Lee Y.H.;
RT "Candidate tumor suppressor DDX3 RNA helicase specifically represses
RT cap-dependent translation by acting as an eIF4E inhibitory protein.";
RL Oncogene 27:700-714(2008).
RN [22]
RP FUNCTION.
RX PubMed=18264132; DOI=10.1038/onc.2008.33;
RA Botlagunta M., Vesuna F., Mironchik Y., Raman A., Lisok A.,
RA Winnard P. Jr., Mukadam S., Van Diest P., Chen J.H., Farabaugh P.,
RA Patel A.H., Raman V.;
RT "Oncogenic role of DDX3 in breast cancer biogenesis.";
RL Oncogene 27:3912-3922(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-612, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP IDENTIFICATION IN A MRNP COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19029303; DOI=10.1261/rna.1175909;
RA Weidensdorfer D., Stoehr N., Baude A., Lederer M., Koehn M.,
RA Schierhorn A., Buchmeier S., Wahle E., Huettelmaiery S.;
RT "Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic
RT RNPs.";
RL RNA 15:104-115(2009).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [26]
RP FUNCTION, INTERACTION WITH MAVS AND DDX58, AND SUBCELLULAR LOCATION.
RX PubMed=20127681; DOI=10.1002/eji.200940203;
RA Oshiumi H., Sakai K., Matsumoto M., Seya T.;
RT "DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-
RT regulate IFN-beta-inducing potential.";
RL Eur. J. Immunol. 40:940-948(2010).
RN [27]
RP FUNCTION, AND INTERACTION WITH IKBKE AND TBK1.
RX PubMed=20375222; DOI=10.1099/vir.0.020552-0;
RA Yu S., Chen J., Wu M., Chen H., Kato N., Yuan Z.;
RT "Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor
RT 3-mediated beta interferon induction in human hepatocytes through
RT interference with interferon regulatory factor 3 activation and
RT dampening of the interaction between TBK1/IKKepsilon and DDX3.";
RL J. Gen. Virol. 91:2080-2090(2010).
RN [28]
RP FUNCTION.
RX PubMed=20837705; DOI=10.1128/MCB.00560-10;
RA Lai M.C., Chang W.C., Shieh S.Y., Tarn W.Y.;
RT "DDX3 regulates cell growth through translational control of cyclin
RT E1.";
RL Mol. Cell. Biol. 30:5444-5453(2010).
RN [29]
RP FUNCTION, RNA-BINDING, INTERACTION WITH MAVS, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21170385; DOI=10.1371/journal.pone.0014258;
RA Oshiumi H., Ikeda M., Matsumoto M., Watanabe A., Takeuchi O.,
RA Akira S., Kato N., Shimotohno K., Seya T.;
RT "Hepatitis C virus core protein abrogates the DDX3 function that
RT enhances IPS-1-mediated IFN-beta induction.";
RL PLoS ONE 5:E14258-E14258(2010).
RN [30]
RP FUNCTION, AND INTERACTION WITH IKBKE.
RX PubMed=20657822; DOI=10.1371/journal.ppat.1000986;
RA Wang H., Ryu W.S.;
RT "Hepatitis B virus polymerase blocks pattern recognition receptor
RT signaling via interaction with DDX3: implications for immune
RT evasion.";
RL PLoS Pathog. 6:E1000986-E1000986(2010).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [33]
RP FUNCTION.
RX PubMed=21589879; DOI=10.1371/journal.pone.0019810;
RA Garbelli A., Beermann S., Di Cicco G., Dietrich U., Maga G.;
RT "A motif unique to the human DEAD-box protein DDX3 is important for
RT nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1
RT replication.";
RL PLoS ONE 6:E19810-E19810(2011).
RN [34]
RP FUNCTION, AND INTERACTION WITH NCAPH.
RX PubMed=21730191; DOI=10.1073/pnas.1106245108;
RA Pek J.W., Kai T.;
RT "DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway
RT promote mitotic chromosome segregation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:12007-12012(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4E AND PABPC1.
RX PubMed=21883093; DOI=10.1042/BJ20110739;
RA Shih J.W., Wang W.T., Tsai T.Y., Kuo C.Y., Li H.K., Wu Lee Y.H.;
RT "Critical roles of RNA helicase DDX3 and its interactions with
RT eIF4E/PABP1 in stress granule assembly and stress response.";
RL Biochem. J. 441:119-129(2012).
RN [37]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INDUCTION, AND
RP INTERACTION WITH DDX5.
RX PubMed=22034099; DOI=10.1002/jcb.23428;
RA Choi Y.J., Lee S.G.;
RT "The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with
RT it in the cytoplasm during the G2/M phase of the cycle, and affects
RT its shuttling during mRNP export.";
RL J. Cell. Biochem. 113:985-996(2012).
RN [38]
RP FUNCTION, ASSOCIATION WITH THE RIBOSOME SMALL SUBUNIT, INTERACTION
RP WITH EIF3C, AND MUTAGENESIS OF TYR-200; GLN-207; LYS-230; ASP-347 AND
RP GLU-348.
RX PubMed=22323517; DOI=10.1093/nar/gks070;
RA Geissler R., Golbik R.P., Behrens S.E.;
RT "The DEAD-box helicase DDX3 supports the assembly of functional 80S
RT ribosomes.";
RL Nucleic Acids Res. 40:4998-5011(2012).
RN [39]
RP FUNCTION, RNA-BINDING, INTERACTION WITH EIF4G1 AND PABPC1, AND
RP MUTAGENESIS OF TYR-38; LEU-43; GLN-207; LYS-230; GLU-348 AND SER-382.
RX PubMed=22872150; DOI=10.1038/emboj.2012.220;
RA Soto-Rifo R., Rubilar P.S., Limousin T., de Breyne S., Decimo D.,
RA Ohlmann T.;
RT "DEAD-box protein DDX3 associates with eIF4F to promote translation of
RT selected mRNAs.";
RL EMBO J. 31:3745-3756(2012).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 409-580.
RX PubMed=17401195; DOI=10.1107/S1744309107006434;
RA Rodamilans B., Montoya G.;
RT "Expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of the DDX3 RNA helicase domain.";
RL Acta Crystallogr. F 63:283-286(2007).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 168-582 IN COMPLEX WITH AMP.
RX PubMed=17631897; DOI=10.1016/j.jmb.2007.06.050;
RA Hoegbom M., Collins R., van den Berg S., Jenvert R.-M., Karlberg T.,
RA Kotenyova T., Flores A., Karlsson Hedestam G.B., Schiavone L.H.;
RT "Crystal structure of conserved domains 1 and 2 of the human DEAD-box
RT helicase DDX3X in complex with the mononucleotide AMP.";
RL J. Mol. Biol. 372:150-159(2007).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 71-90 IN COMPLEX WITH VACV
RP PROTEIN K7, AND MUTAGENESIS OF 84-PHE-PHE-85.
RX PubMed=19913487; DOI=10.1016/j.str.2009.09.005;
RA Oda S., Schroder M., Khan A.R.;
RT "Structural basis for targeting of human RNA helicase DDX3 by poxvirus
RT protein K7.";
RL Structure 17:1528-1537(2009).
RN [43]
RP VARIANT [LARGE SCALE ANALYSIS] THR-294.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Multifunctional ATP-dependent RNA helicase. The ATPase
CC activity can be stimulated by various ribo- and deoxynucleic acids
CC indicative for a relaxed substrate specificity. In vitro can
CC unwind partially double-stranded DNA with a preference for 5'-
CC single-stranded DNA overhangs. Is involved in several steps of
CC gene expression, such as transcription, mRNA maturation, mRNA
CC export and translation. However, the exact mechanisms are not
CC known and some functions may be specific for a subset of mRNAs.
CC Involved in transcriptional regulation. Can enhance transcription
CC from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found
CC associated with the E-cadherin promoter and can down-regulate
CC transcription from the promoter. Involved in regulation of
CC translation initiation. Proposed to be involved in positive
CC regulation of translation such as of cyclin E1/CCNE1 mRNA and
CC specifically of mRNAs containing complex secondary structures in
CC their 5'UTRs; these functions seem to require RNA helicase
CC activity. Specifically promotes translation of a subset of viral
CC and cellular mRNAs carrying a 5'proximal stem-loop structure in
CC their 5'UTRs and cooperates with the eIF4F complex. Proposed to
CC act prior to 43S ribosomal scanning and to locally destabilize
CC these RNA structures to allow recognition of the mRNA cap or
CC loading onto the 40S subunit. After association with 40S ribosomal
CC subunits seems to be involved in the functional assembly of 80S
CC ribosomes; the function seems to cover translation of mRNAs with
CC structured and non-structured 5'UTRs and is independent of RNA
CC helicase activity. Also proposed to inhibit cap-dependent
CC translation by competetive interaction with EIF4E which can block
CC the EIF4E:EIF4G complex formation. Proposed to be involved in
CC stress response and stress granule assembly; the function is
CC independent of RNA helicase activity and seems to involve
CC association with EIF4E. May be involved in nuclear export of
CC specific mRNAs but not in bulk mRNA export via interactions with
CC XPO1 and NXF1. Also associates with polyadenylated mRNAs
CC independently of NXF1. Associates with spliced mRNAs in an exon
CC junction complex (EJC)-dependent manner and seems not to be
CC directly involved in splicing. May be involved in nuclear mRNA
CC export by association with DDX5 and regulating its nuclear
CC location. Involved in innate immune signaling promoting the
CC production of type I interferon (IFN-alpha and IFN-beta); proposed
CC to act as viral RNA sensor, signaling intermediate and
CC transcriptional coactivator. Involved in TBK1 and IKBKE-dependent
CC IRF3 activation leading to IFN-beta induction. Also found
CC associated with IFN-beta promoters; the function is independent of
CC IRF3. Can bind to viral RNAs and via association with MAVS/IPS1
CC and DDX58/RIG-I is thought to induce signaling in early stages of
CC infection. Involved in regulation of apoptosis. May be required
CC for activation of the intrinsic but inhibit activation of the
CC extrinsic apoptotic pathway. Acts as an antiapoptotic protein
CC through association with GSK3A/B and BIRC2 in an apoptosis
CC antagonizing signaling complex; activation of death receptors
CC promotes caspase-dependent cleavage of BIRC2 and DDX3X and
CC relieves the inhibition. May be involved in mitotic chromosome
CC segregation. Appears to be a prime target for viral manipulations.
CC Hepatitis B virus (HBV) polymerase and possibly vaccinia virus
CC (VACV) protein K7 inhibit IFN-beta induction probably by
CC dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C
CC virus (HCV) replication; the function may involve the association
CC with HCV core protein. HCV core protein inhibits the IPS1-
CC dependent function in viral RNA sensing and may switch the
CC function from a INF-beta inducing to a HCV replication mode.
CC Involved in HIV-1 replication. Acts as a cofactor for XPO1-
CC mediated nuclear export of incompletely spliced HIV-1 Rev RNAs.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- SUBUNIT: Interacts with XPO1, TDRD3, PABPC1, NXF1, EIF3C, MAVS,
CC DDX58 and NCAPH. Interacts with DDX5; the interaction is regulated
CC by the phosphorylation status of both proteins. Interacts with
CC EIF4E; DDX3X competes with EIF4G1/EIF4G3 for interaction with
CC EIF4E. Interacts with IKBKE; the interaction is found to be
CC induced upon virus infection and to be inhibited by HBV
CC polymerase. Interacts with TBK1; the interaction is inhibited by
CC HBV polymerase. Associates with the eukaryotic translation
CC initiation factor 3 (eIF-3) complex. Associates with the 40S
CC ribosome. Identified in a mRNP complex, at least composed of DHX9,
CC DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1,
CC STAU2, SYNCRIP and YBX1. Interacts with HCV core protein.
CC Interacts with vaccinia virus (VACV) protein K7. Found in a
CC complex with HIV-1 Rev and XPO1.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=9; IntAct=EBI-353779, EBI-6674379;
CC O95786:DDX58; NbExp=2; IntAct=EBI-353779, EBI-995350;
CC P05198:EIF2S1; NbExp=3; IntAct=EBI-353779, EBI-1056162;
CC P55884:EIF3B; NbExp=5; IntAct=EBI-353779, EBI-366696;
CC Q99613:EIF3C; NbExp=3; IntAct=EBI-353779, EBI-353741;
CC Q04637:EIF4G1; NbExp=3; IntAct=EBI-353779, EBI-73711;
CC Q14164:IKBKE; NbExp=4; IntAct=EBI-353779, EBI-307369;
CC P68467:K7R (xeno); NbExp=6; IntAct=EBI-353779, EBI-8022707;
CC Q7Z434:MAVS; NbExp=4; IntAct=EBI-353779, EBI-995373;
CC Q15003:NCAPH; NbExp=2; IntAct=EBI-353779, EBI-1046410;
CC Q9UBU9:NXF1; NbExp=5; IntAct=EBI-353779, EBI-398874;
CC P11940:PABPC1; NbExp=10; IntAct=EBI-353779, EBI-81531;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm. Mitochondrion
CC outer membrane. Note=Located predominantly in nuclear speckles
CC and, at low levels, throughout the cytoplasm. Located to the outer
CC side of nuclear pore complexes (NPC). Shuttles between the nucleus
CC and the cytoplasm in a XPO1 and may be also in a NFX1-dependent
CC manner. Associated with polyadenylated mRNAs in the cytoplasm and
CC the nucleus. Predominantly located in nucleus during G(0) phase
CC and in the cytoplasm during G1/S phase.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00571-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00571-2; Sequence=VSP_042830;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: Regulated by the cell cycle. Maximally expressed din
CC the cytoplasm uring G1/S phase and decreased expression during
CC G2/M phase.
CC -!- PTM: Phosphorylated by TBK1; the phosphorylation is required to
CC synergize with TBK1 in IFN-beta induction. Probably also
CC phosphorylated by IKBKE. The cytoplasmic form is highly
CC phosphorylated in the G1/S phase and much lower phosphorylated in
CC G2/M.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1
CC subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
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DR EMBL; U50553; AAB95637.1; -; mRNA.
DR EMBL; AF061337; AAC34298.1; -; mRNA.
DR EMBL; AF000983; AAC51830.1; -; mRNA.
DR EMBL; AF000982; AAC51829.1; -; mRNA.
DR EMBL; AK291153; BAF83842.1; -; mRNA.
DR EMBL; AK304689; BAG65460.1; -; mRNA.
DR EMBL; AL391647; CAI41416.1; -; Genomic_DNA.
DR EMBL; Z93015; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471141; EAW59402.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59403.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59404.1; -; Genomic_DNA.
DR EMBL; CH471141; EAW59405.1; -; Genomic_DNA.
DR EMBL; BC011819; AAH11819.1; -; mRNA.
DR RefSeq; NP_001180346.1; NM_001193417.1.
DR RefSeq; NP_001347.3; NM_001356.3.
DR UniGene; Hs.743263; -.
DR PDB; 2I4I; X-ray; 2.20 A; A=168-581.
DR PDB; 2JGN; X-ray; 1.91 A; A/B/C=409-579.
DR PDB; 3JRV; X-ray; 1.60 A; C/D/E=71-90.
DR PDBsum; 2I4I; -.
DR PDBsum; 2JGN; -.
DR PDBsum; 3JRV; -.
DR ProteinModelPortal; O00571; -.
DR SMR; O00571; 139-580.
DR DIP; DIP-27551N; -.
DR IntAct; O00571; 77.
DR MINT; MINT-8395017; -.
DR STRING; 9606.ENSP00000382840; -.
DR BindingDB; O00571; -.
DR ChEMBL; CHEMBL5553; -.
DR PhosphoSite; O00571; -.
DR REPRODUCTION-2DPAGE; IPI00215637; -.
DR SWISS-2DPAGE; O00571; -.
DR PaxDb; O00571; -.
DR PeptideAtlas; O00571; -.
DR PRIDE; O00571; -.
DR Ensembl; ENST00000399959; ENSP00000382840; ENSG00000215301.
DR Ensembl; ENST00000457138; ENSP00000392494; ENSG00000215301.
DR GeneID; 1654; -.
DR KEGG; hsa:1654; -.
DR UCSC; uc004dfe.3; human.
DR CTD; 1654; -.
DR GeneCards; GC0XP041192; -.
DR HGNC; HGNC:2745; DDX3X.
DR HPA; HPA001648; -.
DR HPA; HPA005631; -.
DR MIM; 300160; gene.
DR neXtProt; NX_O00571; -.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR PharmGKB; PA27216; -.
DR eggNOG; COG0513; -.
DR HOVERGEN; HBG015893; -.
DR InParanoid; O00571; -.
DR KO; K11594; -.
DR OMA; GMSHVAV; -.
DR OrthoDB; EOG7B5WV8; -.
DR PhylomeDB; O00571; -.
DR ChiTaRS; DDX3X; human.
DR EvolutionaryTrace; O00571; -.
DR GeneWiki; DDX3X; -.
DR GenomeRNAi; 1654; -.
DR NextBio; 6810; -.
DR PRO; PR:O00571; -.
DR ArrayExpress; O00571; -.
DR Bgee; O00571; -.
DR CleanEx; HS_DDX3X; -.
DR Genevestigator; O00571; -.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; IDA:UniProtKB.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IDA:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:UniProtKB.
DR GO; GO:0008143; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0043024; F:ribosomal small subunit binding; IDA:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; IDA:UniProtKB.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0042256; P:mature ribosome assembly; IMP:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein complex assembly; IDA:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; TAS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; IMP:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0010501; P:RNA secondary structure unwinding; IDA:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS.
DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51195; Q_MOTIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW ATP-binding; Chromosome partition; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Helicase;
KW Host-virus interaction; Hydrolase; Immunity; Innate immunity;
KW Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Ribosome biogenesis; RNA-binding; Transcription;
KW Transcription regulation; Translation regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 662 ATP-dependent RNA helicase DDX3X.
FT /FTId=PRO_0000055009.
FT DOMAIN 211 403 Helicase ATP-binding.
FT DOMAIN 414 575 Helicase C-terminal.
FT NP_BIND 200 207 ATP.
FT NP_BIND 224 231 ATP.
FT REGION 2 139 Required for TBK1 and IKBKE-dependent
FT IFN-beta activation.
FT REGION 2 100 Interaction with EIF4E.
FT REGION 81 90 Required for interaction with VACV
FT protein K7.
FT REGION 100 662 Interaction with GSK3B.
FT REGION 250 259 Involved in stimulation of ATPase
FT activity by DNA and RNA, nucleic acid
FT binding and unwinding and HIV-1
FT replication.
FT REGION 260 517 Necessary for interaction with XPO1.
FT MOTIF 180 208 Q motif.
FT MOTIF 347 350 DEAD box.
FT COMPBIAS 582 662 Gly/Ser-rich.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 69 69 Phosphotyrosine.
FT MOD_RES 74 74 Phosphoserine.
FT MOD_RES 76 76 Phosphoserine.
FT MOD_RES 78 78 Phosphoserine.
FT MOD_RES 104 104 Phosphotyrosine.
FT MOD_RES 118 118 N6-acetyllysine.
FT MOD_RES 125 125 Phosphoserine.
FT MOD_RES 131 131 Phosphoserine.
FT MOD_RES 343 343 Phosphotyrosine.
FT MOD_RES 590 590 Phosphoserine.
FT MOD_RES 594 594 Phosphoserine.
FT MOD_RES 612 612 Phosphoserine.
FT VAR_SEQ 35 51 KGRYIPPHLRNREATKG -> S (in isoform 2).
FT /FTId=VSP_042830.
FT VARIANT 294 294 R -> T (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035839.
FT MUTAGEN 38 38 Y->A: Impairs interaction with EIF4E. No
FT effect on translation of HIV-1 RNA; when
FT associated with A-43.
FT MUTAGEN 43 43 L->A: Impairs interaction with EIF4E.
FT Fails to induce stress granule assembly
FT and to rescue cell viability after
FT stress. No effect on translation of HIV-1
FT RNA; when associated with A-38.
FT MUTAGEN 84 85 FF->AA: Abolishes interaction with VACV
FT protein K7, IRF3 activation and IFN-beta
FT promoter induction.
FT MUTAGEN 181 181 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-183; A-240 and A-269.
FT MUTAGEN 183 183 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-240 and A-269.
FT MUTAGEN 200 200 Y->A: No effect on general translation;
FT when associated with A-207; A-230; A-347
FT and A-348.
FT MUTAGEN 207 207 Q->A: Inhibits translation of HIV-1 RNA.
FT No effect on general translation; when
FT associated with A-200; A-230: A-347 and
FT A-348.
FT MUTAGEN 230 230 K->A: No effect on general translation;
FT when associated with A-200; A-207; A-347
FT and A-348.
FT MUTAGEN 230 230 K->E: Abolishes ATPase activity and RNA-
FT unwinding activity. Inhibits translation
FT of HIV-1 RNA.
FT MUTAGEN 240 240 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-183 and A-269.
FT MUTAGEN 269 269 S->A: Greatly impairs phosphorylation by
FT TBK1 and fails to synergize with TBK1 in
FT IFN-beta induction; when associated with
FT A-181; A-183 and A-240.
FT MUTAGEN 347 347 D->A: No effect on general translation;
FT when associated with A-200; A-207; A-230
FT and A-348.
FT MUTAGEN 348 348 E->A: No effect on general translation;
FT when associated with A-200; A-207; A-230
FT and A-347.
FT MUTAGEN 348 348 E->Q: Inhibits translation of HIV-1 RNA.
FT MUTAGEN 382 382 S->L: Abolishes ATPase activity and RNA-
FT unwinding activity. No effect on
FT translation of HIV-1 RNA.
FT MUTAGEN 429 429 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-438; A-
FT 442; A-456 and A-520.
FT MUTAGEN 438 438 T->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 442; A-456 and A-520.
FT MUTAGEN 442 442 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-456 and A-520.
FT MUTAGEN 456 456 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-442 and A-520.
FT MUTAGEN 520 520 S->A: Impairs phosphorylation by TBK1 and
FT fails to synergize with TBK1 in IFN-beta
FT induction; when associated with A-429; A-
FT 438; A-442 and A-456.
FT CONFLICT 50 50 K -> R (in Ref. 3; AAC51830/AAC51829).
FT STRAND 168 172
FT HELIX 182 184
FT HELIX 189 198
FT HELIX 205 215
FT STRAND 220 223
FT HELIX 230 245
FT HELIX 249 256
FT STRAND 268 272
FT HELIX 276 290
FT STRAND 297 300
FT STRAND 302 304
FT HELIX 306 313
FT STRAND 318 322
FT HELIX 324 332
FT STRAND 343 348
FT HELIX 349 354
FT HELIX 358 365
FT STRAND 367 369
FT STRAND 376 383
FT HELIX 387 396
FT STRAND 401 405
FT STRAND 415 421
FT HELIX 424 426
FT HELIX 427 437
FT STRAND 444 449
FT HELIX 451 463
FT STRAND 468 471
FT HELIX 482 488
FT STRAND 491 498
FT HELIX 499 502
FT STRAND 509 517
FT HELIX 522 529
FT STRAND 539 545
FT HELIX 547 552
FT HELIX 553 562
FT HELIX 569 575
SQ SEQUENCE 662 AA; 73243 MW; 7074D2B8A6EBBF09 CRC64;
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW
SSSKDKDAYS SFGSRSDSRG KSSFFSDRGS GSRGRFDDRG RSDYDGIGSR GDRSGFGKFE
RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE
SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS
QIYSDGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV
YGGADIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ
IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV
WVEESDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR
EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL
ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAYEHHY KGSSRGRSKS SRFSGGFGAR
DYRQSSGASS SSFSSSRASS SRSGGGGHGS SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW
GN
//
MIM
300160
*RECORD*
*FIELD* NO
300160
*FIELD* TI
*300160 DEAD/H BOX 3, X-LINKED; DDX3X
;;DDX3;;
DBX
*FIELD* TX
CLONING
DEAD box proteins are putative RNA helicases that have a characteristic
read moreasp-glu-ala-asp (DEAD) box as 1 of 8 highly conserved sequence motifs.
Chung et al. (1995) cloned cDNAs encoding DDX3, a member of the DEAD box
protein family.
Lahn and Page (1997) identified DDX3, which they called DBX, as 1 of 5
X-linked genes that have homologs located in the nonrecombining region
of the Y chromosome (NRY). They determined that these 5 X-linked genes
escape X inactivation. Lahn and Page (1997) postulated that these 5
genes are cases in which gene expression is maintained at comparable
levels in males and females by preservation of homologous genes on both
the X and the NRY, with male and female cells expressing both copies of
each gene. Sequence analysis revealed that DBX shares 91% protein
sequence identity with DBY (400010), the Y-linked homolog.
GENE FUNCTION
A single transcript in its unspliced and spliced forms directs synthesis
of all human immunodeficiency virus (HIV)-1 proteins. Although nuclear
export of intron-containing cellular transcripts is restricted in
mammalian cells, HIV-1 has evolved the viral Rev protein to overcome
this restriction for viral transcripts. CRM1 (XPO1; 602559) is a
cellular cofactor for Rev-dependent export of intron-containing HIV-1
RNA. Yedavalli et al. (2004) presented evidence that Rev/CRM1 activity
uses the ATP-dependent RNA helicase DDX3. They showed that DDX3 is a
nucleocytoplasmic shuttling protein that binds CRM1 and localizes to
nuclear membrane pores. Knockdown of DDX3 using either antisense vector
or dominant-negative mutants suppressed Rev-RRE (Rev response element)
function in the export of incompletely spliced HIV-1 RNAs. Yedavalli et
al. (2004) concluded that DDX3 is the human RNA helicase that functions
in the CRM1 RNA export pathway analogously to the postulated role for
Dbp5 (605812) in yeast mRNA export.
Cruciat et al. (2013) identified the DEAD box RNA helicase DDX3 as a
regulator of the Wnt (see 164820)-beta-catenin (116806) network, where
it acts as a regulatory subunit of CK1-epsilon (600863): in a
Wnt-dependent manner, DDX3 binds CK1-epsilon and directly stimulates its
kinase activity, and promotes phosphorylation of the scaffold protein
dishevelled (see 601365). DDX3 is required for Wnt-beta-catenin
signaling in mammalian cells and during Xenopus and C. elegans
development. Cruciat et al. (2013) concluded that their results
suggested that the kinase-stimulatory function extends to other DDX and
CK1 members.
MAPPING
By fluorescence in situ hybridization, Park et al. (1998) mapped the
DDX3X gene to Xp11.3-p11.23.
*FIELD* RF
1. Chung, J.; Lee, S.-G.; Song, K.: Identification of a human homolog
of a putative RNA helicase gene (mDEAD3) expressed in mouse erythroid
cells. Korean J. Biochem. 27: 193-197, 1995.
2. Cruciat, C.- M.; Dolde, C.; de Groot, R. E. A.; Ohkawara, B.; Reinhard,
C.; Korswagen, H. C.; Niehrs, C.: RNA helicase DDX3 is a regulatory
subunit of casein kinase 1 in Wnt-beta-catenin signaling. Science 339:
1436-1441, 2013.
3. Lahn, B. T.; Page, D. C.: Functional coherence of the human Y
chromosome. Science 278: 675-680, 1997.
4. Park, S. H.; Lee, S.-G.; Kim, Y.; Song, K.: Assignment of a human
putative RNA helicase gene, DDX3, to human X chromosome bands p11.3-p11.23. Cytogenet.
Cell Genet. 81: 178-179, 1998.
5. Yedavalli, V. S. R. K.; Neuveut, C.; Chi, Y.; Kleiman, L.; Jeang,
K.-T.: Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE
export function. Cell 119: 381-392, 2004.
*FIELD* CN
Ada Hamosh - updated: 05/29/2013
Stylianos E. Antonarakis - updated: 1/19/2005
*FIELD* CD
Rebekah S. Rasooly: 11/19/1998
*FIELD* ED
alopez: 05/29/2013
alopez: 3/4/2009
mgross: 1/19/2005
alopez: 1/5/1999
alopez: 11/20/1998
alopez: 11/19/1998
*RECORD*
*FIELD* NO
300160
*FIELD* TI
*300160 DEAD/H BOX 3, X-LINKED; DDX3X
;;DDX3;;
DBX
*FIELD* TX
CLONING
DEAD box proteins are putative RNA helicases that have a characteristic
read moreasp-glu-ala-asp (DEAD) box as 1 of 8 highly conserved sequence motifs.
Chung et al. (1995) cloned cDNAs encoding DDX3, a member of the DEAD box
protein family.
Lahn and Page (1997) identified DDX3, which they called DBX, as 1 of 5
X-linked genes that have homologs located in the nonrecombining region
of the Y chromosome (NRY). They determined that these 5 X-linked genes
escape X inactivation. Lahn and Page (1997) postulated that these 5
genes are cases in which gene expression is maintained at comparable
levels in males and females by preservation of homologous genes on both
the X and the NRY, with male and female cells expressing both copies of
each gene. Sequence analysis revealed that DBX shares 91% protein
sequence identity with DBY (400010), the Y-linked homolog.
GENE FUNCTION
A single transcript in its unspliced and spliced forms directs synthesis
of all human immunodeficiency virus (HIV)-1 proteins. Although nuclear
export of intron-containing cellular transcripts is restricted in
mammalian cells, HIV-1 has evolved the viral Rev protein to overcome
this restriction for viral transcripts. CRM1 (XPO1; 602559) is a
cellular cofactor for Rev-dependent export of intron-containing HIV-1
RNA. Yedavalli et al. (2004) presented evidence that Rev/CRM1 activity
uses the ATP-dependent RNA helicase DDX3. They showed that DDX3 is a
nucleocytoplasmic shuttling protein that binds CRM1 and localizes to
nuclear membrane pores. Knockdown of DDX3 using either antisense vector
or dominant-negative mutants suppressed Rev-RRE (Rev response element)
function in the export of incompletely spliced HIV-1 RNAs. Yedavalli et
al. (2004) concluded that DDX3 is the human RNA helicase that functions
in the CRM1 RNA export pathway analogously to the postulated role for
Dbp5 (605812) in yeast mRNA export.
Cruciat et al. (2013) identified the DEAD box RNA helicase DDX3 as a
regulator of the Wnt (see 164820)-beta-catenin (116806) network, where
it acts as a regulatory subunit of CK1-epsilon (600863): in a
Wnt-dependent manner, DDX3 binds CK1-epsilon and directly stimulates its
kinase activity, and promotes phosphorylation of the scaffold protein
dishevelled (see 601365). DDX3 is required for Wnt-beta-catenin
signaling in mammalian cells and during Xenopus and C. elegans
development. Cruciat et al. (2013) concluded that their results
suggested that the kinase-stimulatory function extends to other DDX and
CK1 members.
MAPPING
By fluorescence in situ hybridization, Park et al. (1998) mapped the
DDX3X gene to Xp11.3-p11.23.
*FIELD* RF
1. Chung, J.; Lee, S.-G.; Song, K.: Identification of a human homolog
of a putative RNA helicase gene (mDEAD3) expressed in mouse erythroid
cells. Korean J. Biochem. 27: 193-197, 1995.
2. Cruciat, C.- M.; Dolde, C.; de Groot, R. E. A.; Ohkawara, B.; Reinhard,
C.; Korswagen, H. C.; Niehrs, C.: RNA helicase DDX3 is a regulatory
subunit of casein kinase 1 in Wnt-beta-catenin signaling. Science 339:
1436-1441, 2013.
3. Lahn, B. T.; Page, D. C.: Functional coherence of the human Y
chromosome. Science 278: 675-680, 1997.
4. Park, S. H.; Lee, S.-G.; Kim, Y.; Song, K.: Assignment of a human
putative RNA helicase gene, DDX3, to human X chromosome bands p11.3-p11.23. Cytogenet.
Cell Genet. 81: 178-179, 1998.
5. Yedavalli, V. S. R. K.; Neuveut, C.; Chi, Y.; Kleiman, L.; Jeang,
K.-T.: Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE
export function. Cell 119: 381-392, 2004.
*FIELD* CN
Ada Hamosh - updated: 05/29/2013
Stylianos E. Antonarakis - updated: 1/19/2005
*FIELD* CD
Rebekah S. Rasooly: 11/19/1998
*FIELD* ED
alopez: 05/29/2013
alopez: 3/4/2009
mgross: 1/19/2005
alopez: 1/5/1999
alopez: 11/20/1998
alopez: 11/19/1998