Full text data of EIF4A3
EIF4A3
(DDX48, KIAA0111)
[Confidence: low (only semi-automatic identification from reviews)]
Eukaryotic initiation factor 4A-III; eIF-4A-III; eIF4A-III; 3.6.4.13 (ATP-dependent RNA helicase DDX48; ATP-dependent RNA helicase eIF4A-3; DEAD box protein 48; Eukaryotic initiation factor 4A-like NUK-34; Eukaryotic translation initiation factor 4A isoform 3; Nuclear matrix protein 265; NMP 265; hNMP 265; Eukaryotic initiation factor 4A-III, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Eukaryotic initiation factor 4A-III; eIF-4A-III; eIF4A-III; 3.6.4.13 (ATP-dependent RNA helicase DDX48; ATP-dependent RNA helicase eIF4A-3; DEAD box protein 48; Eukaryotic initiation factor 4A-like NUK-34; Eukaryotic translation initiation factor 4A isoform 3; Nuclear matrix protein 265; NMP 265; hNMP 265; Eukaryotic initiation factor 4A-III, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P38919
ID IF4A3_HUMAN Reviewed; 411 AA.
AC P38919; Q15033; Q6IBQ2; Q96A18;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 162.
DE RecName: Full=Eukaryotic initiation factor 4A-III;
DE Short=eIF-4A-III;
DE Short=eIF4A-III;
DE EC=3.6.4.13;
DE AltName: Full=ATP-dependent RNA helicase DDX48;
DE AltName: Full=ATP-dependent RNA helicase eIF4A-3;
DE AltName: Full=DEAD box protein 48;
DE AltName: Full=Eukaryotic initiation factor 4A-like NUK-34;
DE AltName: Full=Eukaryotic translation initiation factor 4A isoform 3;
DE AltName: Full=Nuclear matrix protein 265;
DE Short=NMP 265;
DE Short=hNMP 265;
DE Contains:
DE RecName: Full=Eukaryotic initiation factor 4A-III, N-terminally processed;
GN Name=EIF4A3; Synonyms=DDX48, KIAA0111;
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].
RC TISSUE=Skin;
RA Leffers H., Wiemann S., Ansorge W.;
RT "Cloning and sequencing of a putative human translation initiation
RT factor with similarity to initiation factor 4AII.";
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III.
RT The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, Placenta, and 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 2-14, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 340-358, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [10]
RP PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Leukocyte;
RX PubMed=10623621; DOI=10.1006/bbrc.1999.1973;
RA Holzmann K., Gerner C., Poeltl A., Schaefer R., Obrist P.,
RA Ensinger C., Grimm R., Sauermann G.;
RT "A human common nuclear matrix protein homologous to eukaryotic
RT translation initiation factor 4A.";
RL Biochem. Biophys. Res. Commun. 267:339-344(2000).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [12]
RP FUNCTION IN MRNA SPLICING AND NONSENSE-MEDIATED MRNA DECAY,
RP INTERACTION WITH MAGOH AND RBM8A, AND RNA-BINDING.
RX PubMed=15034551; DOI=10.1038/nsmb750;
RA Shibuya T., Tange T.O., Sonenberg N., Moore M.J.;
RT "eIF4AIII binds spliced mRNA in the exon junction complex and is
RT essential for nonsense-mediated decay.";
RL Nat. Struct. Mol. Biol. 11:346-351(2004).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE EXON
RP JUNCTION COMPLEX, INTERACTION WITH NXF1 AND ALYREF/THOC4, RNA-BINDING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=14730019; DOI=10.1261/rna.5230104;
RA Chan C.C., Dostie J., Diem M.D., Feng W., Mann M., Rappsilber J.,
RA Dreyfuss G.;
RT "eIF4A3 is a novel component of the exon junction complex.";
RL RNA 10:200-209(2004).
RN [14]
RP POSSIBLE INTERACTION WITH NOM1.
RX PubMed=15715967; DOI=10.1016/j.gene.2004.12.027;
RA Simmons H.M., Ruis B.L., Kapoor M., Hudacek A.W., Conklin K.F.;
RT "Identification of NOM1, a nucleolar, eIF4A binding protein encoded
RT within the chromosome 7q36 breakpoint region targeted in cases of
RT pediatric acute myeloid leukemia.";
RL Gene 347:137-145(2005).
RN [15]
RP FUNCTION.
RX PubMed=16209946; DOI=10.1016/j.molcel.2005.08.012;
RA Gehring N.H., Kunz J.B., Neu-Yilik G., Breit S., Viegas M.H.,
RA Hentze M.W., Kulozik A.E.;
RT "Exon-junction complex components specify distinct routes of nonsense-
RT mediated mRNA decay with differential cofactor requirements.";
RL Mol. Cell 20:65-75(2005).
RN [16]
RP FUNCTION, IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX,
RP INTERACTION WITH CASC3, MUTAGENESIS OF LYS-88, AND RNA-BINDING.
RX PubMed=16170325; DOI=10.1038/nsmb990;
RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B.,
RA Le Hir H.;
RT "The exon junction core complex is locked onto RNA by inhibition of
RT eIF4AIII ATPase activity.";
RL Nat. Struct. Mol. Biol. 12:861-869(2005).
RN [17]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A
RP MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP INTERACTION WITH CASC3 AND MAGOH, AND MUTAGENESIS.
RX PubMed=16495234; DOI=10.1261/rna.2190706;
RA Shibuya T., Tange T.O., Stroupe M.E., Moore M.J.;
RT "Mutational analysis of human eIF4AIII identifies regions necessary
RT for exon junction complex formation and nonsense-mediated mRNA
RT decay.";
RL RNA 12:360-374(2006).
RN [20]
RP FUNCTION IN ATPASE AND RNA-HELICASE ACTIVITY.
RX PubMed=17375189; DOI=10.1371/journal.pone.0000303;
RA Noble C.G., Song H.;
RT "MLN51 stimulates the RNA-helicase activity of eIF4AIII.";
RL PLoS ONE 2:E303-E303(2007).
RN [21]
RP INTERACTION WITH POLDIP3.
RX PubMed=18423201; DOI=10.1016/j.cell.2008.02.031;
RA Ma X.M., Yoon S.O., Richardson C.J., Julich K., Blenis J.;
RT "SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced
RT translation efficiency of spliced mRNAs.";
RL Cell 133:303-313(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-163, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP FUNCTION IN MRNA TRANSLATION.
RX PubMed=19409878; DOI=10.1016/j.bbrc.2009.04.123;
RA Lee H.C., Choe J., Chi S.G., Kim Y.K.;
RT "Exon junction complex enhances translation of spliced mRNAs at
RT multiple steps.";
RL Biochem. Biophys. Res. Commun. 384:334-340(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-296 AND LYS-321, AND MASS
RP 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 [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ALA-2, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-12 AND THR-163, 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 [29]
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 [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ALA-2, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-12, AND MASS 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 [31]
RP INTERACTION WITH CWC22, AND MUTAGENESIS OF ASP-270; ASP-273;
RP 276-THR-ILE-277 AND 301-ASN--THR-303.
RX PubMed=22959432; DOI=10.1016/j.celrep.2012.08.017;
RA Steckelberg A.L., Boehm V., Gromadzka A.M., Gehring N.H.;
RT "CWC22 connects pre-mRNA splicing and exon junction complex
RT assembly.";
RL Cell Rep. 2:454-461(2012).
RN [32]
RP FUNCTION.
RX PubMed=22203037; DOI=10.1128/MCB.06130-11;
RA Michelle L., Cloutier A., Toutant J., Shkreta L., Thibault P.,
RA Durand M., Garneau D., Gendron D., Lapointe E., Couture S., Le Hir H.,
RA Klinck R., Elela S.A., Prinos P., Chabot B.;
RT "Proteins associated with the exon junction complex also control the
RT alternative splicing of apoptotic regulators.";
RL Mol. Cell. Biol. 32:954-967(2012).
RN [33]
RP ENZYME REGULATION, INTERACTION WITH CASC3; CWC22; MAGOH; PRPF19 AND
RP RBM8A, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-401 AND GLU-402.
RX PubMed=22961380; DOI=10.1038/nsmb.2380;
RA Barbosa I., Haque N., Fiorini F., Barrandon C., Tomasetto C.,
RA Blanchette M., Le Hir H.;
RT "Human CWC22 escorts the helicase eIF4AIII to spliceosomes and
RT promotes exon junction complex assembly.";
RL Nat. Struct. Mol. Biol. 19:983-990(2012).
RN [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP INTERACTION WITH CWC22, AND MUTAGENESIS OF THR-334.
RX PubMed=23236153; DOI=10.1073/pnas.1219725110;
RA Alexandrov A., Colognori D., Shu M.D., Steitz J.A.;
RT "Human spliceosomal protein CWC22 plays a role in coupling splicing to
RT exon junction complex deposition and nonsense-mediated decay.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:21313-21318(2012).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 2-411 IN THE EJC COMPLEX
RP WITH CASC3; MAGOH; RBM8A; AMP-PNP AND POLY URACIL.
RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006;
RA Bono F., Ebert J., Lorentzen E., Conti E.;
RT "The crystal structure of the exon junction complex reveals how it
RT maintains a stable grip on mRNA.";
RL Cell 126:713-725(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN THE EJC COMPLEX WITH CASC3;
RP MAGOH; RBM8A; ADP-NP AND POLY URACIL.
RX PubMed=16931718; DOI=10.1126/science.1131981;
RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H.,
RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.;
RT "Structure of the exon junction core complex with a trapped DEAD-box
RT ATPase bound to RNA.";
RL Science 313:1968-1972(2006).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN THE EJC COMPLEX WITH CASC3;
RP MAGOH; RBM8A; TRANSITION STATE ANALOG ADP-ALF3 AND POLY URACIL.
RX PubMed=19033377; DOI=10.1261/rna.1283109;
RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K.,
RA Le Hir H., Andersen G.R.;
RT "Mechanism of ATP turnover inhibition in the EJC.";
RL RNA 15:67-75(2009).
CC -!- FUNCTION: ATP-dependent RNA helicase. Core component of the
CC splicing-dependent multiprotein exon junction complex (EJC)
CC deposited at splice junctions on mRNAs. The EJC is a dynamic
CC structure consisting of core proteins and several peripheral
CC nuclear and cytoplasmic associated factors that join the complex
CC only transiently either during EJC assembly or during subsequent
CC mRNA metabolism. The EJC marks the position of the exon-exon
CC junction in the mature mRNA for the gene expression machinery and
CC the core components remain bound to spliced mRNAs throughout all
CC stages of mRNA metabolism thereby influencing downstream processes
CC including nuclear mRNA export, subcellular mRNA localization,
CC translation efficiency and nonsense-mediated mRNA decay (NMD). Its
CC RNA-dependent ATPase and RNA-helicase activities are induced by
CC CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer,
CC thereby trapping the ATP-bound EJC core onto spliced mRNA in a
CC stable conformation. The inhibition of ATPase activity by the
CC MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the
CC EJC. Involved in translational enhancement of spliced mRNAs after
CC formation of the 80S ribosome complex. Binds spliced mRNA in
CC sequence-independent manner, 20-24 nucleotides upstream of mRNA
CC exon-exon junctions. Shows higher affinity for single-stranded RNA
CC in an ATP-bound core EJC complex than after the ATP is hydrolyzed.
CC Involved in the splicing modulation of BCL2L1/Bcl-X (and probably
CC other apoptotic genes); specifically inhibits formation of
CC proapoptotic isoforms such as Bcl-X(S); the function is different
CC from the established EJC assembly.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- ENZYME REGULATION: The ATPase activity is increased some 4-fold in
CC the presence of RNA.
CC -!- SUBUNIT: Part of the mRNA splicing-dependent exon junction complex
CC (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH and
CC RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4.
CC Identified in the spliceosome C complex. May interact with NOM1.
CC Interacts with POLDIP3. Interacts with CWC22 and PRPF19 in an RNA-
CC independent manner. Direct interaction with CWC22 is mediated by
CC the helicase C-terminal domain. Full interaction with CWC22 occurs
CC only when EIF4A3 is not part of the EJC and prevents EIF4A3
CC binding to RNA.
CC -!- INTERACTION:
CC O15234:CASC3; NbExp=7; IntAct=EBI-299104, EBI-299118;
CC Q9HCG8:CWC22; NbExp=3; IntAct=EBI-299104, EBI-373289;
CC P61326:MAGOH; NbExp=20; IntAct=EBI-299104, EBI-299134;
CC Q9Y5S9:RBM8A; NbExp=21; IntAct=EBI-299104, EBI-447231;
CC Q9Y2W1:THRAP3; NbExp=2; IntAct=EBI-299104, EBI-352039;
CC Q9BZI7:UPF3B; NbExp=7; IntAct=EBI-299104, EBI-372780;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Cytoplasm.
CC Note=Nucleocytoplasmic shuttling protein. Travels to the cytoplasm
CC as part of the exon junction complex (EJC) bound to mRNA. Detected
CC in dendritic layer as well as the nuclear and cytoplasmic
CC (somatic) compartments of neurons. Colocalizes with STAU1 and FMR1
CC in dendrites (By similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. eIF4A
CC subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04879.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; X79538; CAA56074.1; -; mRNA.
DR EMBL; D21853; BAA04879.2; ALT_INIT; mRNA.
DR EMBL; AK290608; BAF83297.1; -; mRNA.
DR EMBL; CR456750; CAG33031.1; -; mRNA.
DR EMBL; AC087741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89584.1; -; Genomic_DNA.
DR EMBL; BC003662; AAH03662.1; -; mRNA.
DR EMBL; BC004386; AAH04386.1; -; mRNA.
DR EMBL; BC011151; AAH11151.1; -; mRNA.
DR PIR; S45142; S45142.
DR RefSeq; NP_055555.1; NM_014740.3.
DR UniGene; Hs.389649; -.
DR PDB; 2HXY; X-ray; 3.30 A; A/B/C/D=23-410.
DR PDB; 2HYI; X-ray; 2.30 A; C/I=1-411.
DR PDB; 2J0Q; X-ray; 3.20 A; A/B=2-411.
DR PDB; 2J0S; X-ray; 2.21 A; A=2-411.
DR PDB; 2J0U; X-ray; 3.00 A; A/B=38-411.
DR PDB; 2XB2; X-ray; 3.40 A; A/X=1-411.
DR PDB; 3EX7; X-ray; 2.30 A; C/H=1-411.
DR PDB; 4C9B; X-ray; 2.00 A; A=1-411.
DR PDBsum; 2HXY; -.
DR PDBsum; 2HYI; -.
DR PDBsum; 2J0Q; -.
DR PDBsum; 2J0S; -.
DR PDBsum; 2J0U; -.
DR PDBsum; 2XB2; -.
DR PDBsum; 3EX7; -.
DR PDBsum; 4C9B; -.
DR ProteinModelPortal; P38919; -.
DR SMR; P38919; 21-411.
DR DIP; DIP-33218N; -.
DR IntAct; P38919; 134.
DR MINT; MINT-1460615; -.
DR STRING; 9606.ENSP00000269349; -.
DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR PhosphoSite; P38919; -.
DR DMDM; 20532400; -.
DR REPRODUCTION-2DPAGE; IPI00009328; -.
DR PaxDb; P38919; -.
DR PeptideAtlas; P38919; -.
DR PRIDE; P38919; -.
DR DNASU; 9775; -.
DR Ensembl; ENST00000269349; ENSP00000269349; ENSG00000141543.
DR GeneID; 9775; -.
DR KEGG; hsa:9775; -.
DR UCSC; uc002jxs.3; human.
DR CTD; 9775; -.
DR GeneCards; GC17M078109; -.
DR HGNC; HGNC:18683; EIF4A3.
DR HPA; HPA021878; -.
DR MIM; 608546; gene.
DR neXtProt; NX_P38919; -.
DR PharmGKB; PA162384945; -.
DR eggNOG; COG0513; -.
DR HOGENOM; HOG000268797; -.
DR HOVERGEN; HBG107989; -.
DR InParanoid; P38919; -.
DR KO; K13025; -.
DR OMA; TQIQKVI; -.
DR PhylomeDB; P38919; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; EIF4A3; human.
DR EvolutionaryTrace; P38919; -.
DR GeneWiki; EIF4A3; -.
DR GenomeRNAi; 9775; -.
DR NextBio; 36802; -.
DR PRO; PR:P38919; -.
DR ArrayExpress; P38919; -.
DR Bgee; P38919; -.
DR CleanEx; HS_EIF4A3; -.
DR Genevestigator; P38919; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; IDA:HGNC.
DR GO; GO:0008143; F:poly(A) RNA binding; IDA:HGNC.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IDA:HGNC.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; 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; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Helicase; Hydrolase; mRNA processing;
KW mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; rRNA processing; Spliceosome; Translation regulation;
KW Transport.
FT CHAIN 1 411 Eukaryotic initiation factor 4A-III.
FT /FTId=PRO_0000423267.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 411 Eukaryotic initiation factor 4A-III, N-
FT terminally processed.
FT /FTId=PRO_0000054942.
FT DOMAIN 69 239 Helicase ATP-binding.
FT DOMAIN 250 411 Helicase C-terminal.
FT NP_BIND 85 90 ATP.
FT NP_BIND 367 371 ATP.
FT MOTIF 38 66 Q motif.
FT MOTIF 187 190 DEAD box.
FT BINDING 60 60 ATP; via carbonyl oxygen.
FT BINDING 65 65 ATP.
FT BINDING 342 342 ATP.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylalanine; in Eukaryotic initiation
FT factor 4A-III, N-terminally processed.
FT MOD_RES 12 12 Phosphoserine.
FT MOD_RES 163 163 Phosphothreonine.
FT MOD_RES 296 296 N6-acetyllysine.
FT MOD_RES 321 321 N6-acetyllysine.
FT MUTAGEN 88 88 K->A: ATPase activity is not induced in
FT presence of CASC3. Does not prevent EJC
FT formation. Prevents the EJC disassembly.
FT MUTAGEN 270 270 D->K: Loss of CWC22-binding and loss of
FT incorporation into EJCs; when associated
FT with K-273.
FT MUTAGEN 273 273 D->K: Loss of CWC22-binding and loss of
FT incorporation into EJCs; when associated
FT with K-270.
FT MUTAGEN 276 277 TI->GD: Loss of CWC22-binding and loss of
FT incorporation into EJCs.
FT MUTAGEN 301 303 NFT->LAG: Loss of CWC22-binding and loss
FT of incorporation into EJCs.
FT MUTAGEN 334 334 T->V: Reduced incorporation into EJCs.
FT MUTAGEN 401 401 D->K: Loss of incorporation into EJCs;
FT when associated with R-402.
FT MUTAGEN 402 402 E->R: Loss of incorporation into EJCs;
FT when associated with K-401.
FT CONFLICT 210 210 P -> S (in Ref. 1; CAA56074).
FT CONFLICT 370 370 R -> Q (in Ref. 1; CAA56074).
FT STRAND 23 25
FT HELIX 40 43
FT HELIX 47 56
FT HELIX 63 73
FT STRAND 78 81
FT STRAND 84 86
FT HELIX 88 98
FT STRAND 102 104
FT STRAND 109 112
FT HELIX 116 129
FT TURN 130 134
FT STRAND 137 140
FT STRAND 143 145
FT HELIX 146 155
FT STRAND 158 162
FT HELIX 164 172
FT STRAND 183 187
FT HELIX 189 192
FT TURN 195 197
FT HELIX 198 205
FT STRAND 213 219
FT HELIX 223 226
FT HELIX 229 231
FT STRAND 237 239
FT HELIX 243 245
FT STRAND 251 260
FT HELIX 263 275
FT STRAND 277 283
FT HELIX 287 299
FT STRAND 305 307
FT STRAND 309 311
FT HELIX 313 324
FT STRAND 330 333
FT HELIX 335 337
FT STRAND 338 340
FT STRAND 346 353
FT HELIX 358 365
FT HELIX 370 372
FT STRAND 375 382
FT HELIX 383 385
FT HELIX 386 395
FT STRAND 400 402
FT HELIX 408 411
SQ SEQUENCE 411 AA; 46871 MW; 3A21888CA96CA5EA CRC64;
MATTATMATS GSARKRLLKE EDMTKVEFET SEEVDVTPTF DTMGLREDLL RGIYAYGFEK
PSAIQQRAIK QIIKGRDVIA QSQSGTGKTA TFSISVLQCL DIQVRETQAL ILAPTRELAV
QIQKGLLALG DYMNVQCHAC IGGTNVGEDI RKLDYGQHVV AGTPGRVFDM IRRRSLRTRA
IKMLVLDEAD EMLNKGFKEQ IYDVYRYLPP ATQVVLISAT LPHEILEMTN KFMTDPIRIL
VKRDELTLEG IKQFFVAVER EEWKFDTLCD LYDTLTITQA VIFCNTKRKV DWLTEKMREA
NFTVSSMHGD MPQKERESIM KEFRSGASRV LISTDVWARG LDVPQVSLII NYDLPNNREL
YIHRIGRSGR YGRKGVAINF VKNDDIRILR DIEQYYSTQI DEMPMNVADL I
//
ID IF4A3_HUMAN Reviewed; 411 AA.
AC P38919; Q15033; Q6IBQ2; Q96A18;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 162.
DE RecName: Full=Eukaryotic initiation factor 4A-III;
DE Short=eIF-4A-III;
DE Short=eIF4A-III;
DE EC=3.6.4.13;
DE AltName: Full=ATP-dependent RNA helicase DDX48;
DE AltName: Full=ATP-dependent RNA helicase eIF4A-3;
DE AltName: Full=DEAD box protein 48;
DE AltName: Full=Eukaryotic initiation factor 4A-like NUK-34;
DE AltName: Full=Eukaryotic translation initiation factor 4A isoform 3;
DE AltName: Full=Nuclear matrix protein 265;
DE Short=NMP 265;
DE Short=hNMP 265;
DE Contains:
DE RecName: Full=Eukaryotic initiation factor 4A-III, N-terminally processed;
GN Name=EIF4A3; Synonyms=DDX48, KIAA0111;
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].
RC TISSUE=Skin;
RA Leffers H., Wiemann S., Ansorge W.;
RT "Cloning and sequencing of a putative human translation initiation
RT factor with similarity to initiation factor 4AII.";
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III.
RT The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, Placenta, and 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 2-14, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 340-358, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [10]
RP PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Leukocyte;
RX PubMed=10623621; DOI=10.1006/bbrc.1999.1973;
RA Holzmann K., Gerner C., Poeltl A., Schaefer R., Obrist P.,
RA Ensinger C., Grimm R., Sauermann G.;
RT "A human common nuclear matrix protein homologous to eukaryotic
RT translation initiation factor 4A.";
RL Biochem. Biophys. Res. Commun. 267:339-344(2000).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [12]
RP FUNCTION IN MRNA SPLICING AND NONSENSE-MEDIATED MRNA DECAY,
RP INTERACTION WITH MAGOH AND RBM8A, AND RNA-BINDING.
RX PubMed=15034551; DOI=10.1038/nsmb750;
RA Shibuya T., Tange T.O., Sonenberg N., Moore M.J.;
RT "eIF4AIII binds spliced mRNA in the exon junction complex and is
RT essential for nonsense-mediated decay.";
RL Nat. Struct. Mol. Biol. 11:346-351(2004).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE EXON
RP JUNCTION COMPLEX, INTERACTION WITH NXF1 AND ALYREF/THOC4, RNA-BINDING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=14730019; DOI=10.1261/rna.5230104;
RA Chan C.C., Dostie J., Diem M.D., Feng W., Mann M., Rappsilber J.,
RA Dreyfuss G.;
RT "eIF4A3 is a novel component of the exon junction complex.";
RL RNA 10:200-209(2004).
RN [14]
RP POSSIBLE INTERACTION WITH NOM1.
RX PubMed=15715967; DOI=10.1016/j.gene.2004.12.027;
RA Simmons H.M., Ruis B.L., Kapoor M., Hudacek A.W., Conklin K.F.;
RT "Identification of NOM1, a nucleolar, eIF4A binding protein encoded
RT within the chromosome 7q36 breakpoint region targeted in cases of
RT pediatric acute myeloid leukemia.";
RL Gene 347:137-145(2005).
RN [15]
RP FUNCTION.
RX PubMed=16209946; DOI=10.1016/j.molcel.2005.08.012;
RA Gehring N.H., Kunz J.B., Neu-Yilik G., Breit S., Viegas M.H.,
RA Hentze M.W., Kulozik A.E.;
RT "Exon-junction complex components specify distinct routes of nonsense-
RT mediated mRNA decay with differential cofactor requirements.";
RL Mol. Cell 20:65-75(2005).
RN [16]
RP FUNCTION, IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX,
RP INTERACTION WITH CASC3, MUTAGENESIS OF LYS-88, AND RNA-BINDING.
RX PubMed=16170325; DOI=10.1038/nsmb990;
RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B.,
RA Le Hir H.;
RT "The exon junction core complex is locked onto RNA by inhibition of
RT eIF4AIII ATPase activity.";
RL Nat. Struct. Mol. Biol. 12:861-869(2005).
RN [17]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A
RP MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP INTERACTION WITH CASC3 AND MAGOH, AND MUTAGENESIS.
RX PubMed=16495234; DOI=10.1261/rna.2190706;
RA Shibuya T., Tange T.O., Stroupe M.E., Moore M.J.;
RT "Mutational analysis of human eIF4AIII identifies regions necessary
RT for exon junction complex formation and nonsense-mediated mRNA
RT decay.";
RL RNA 12:360-374(2006).
RN [20]
RP FUNCTION IN ATPASE AND RNA-HELICASE ACTIVITY.
RX PubMed=17375189; DOI=10.1371/journal.pone.0000303;
RA Noble C.G., Song H.;
RT "MLN51 stimulates the RNA-helicase activity of eIF4AIII.";
RL PLoS ONE 2:E303-E303(2007).
RN [21]
RP INTERACTION WITH POLDIP3.
RX PubMed=18423201; DOI=10.1016/j.cell.2008.02.031;
RA Ma X.M., Yoon S.O., Richardson C.J., Julich K., Blenis J.;
RT "SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced
RT translation efficiency of spliced mRNAs.";
RL Cell 133:303-313(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-163, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP FUNCTION IN MRNA TRANSLATION.
RX PubMed=19409878; DOI=10.1016/j.bbrc.2009.04.123;
RA Lee H.C., Choe J., Chi S.G., Kim Y.K.;
RT "Exon junction complex enhances translation of spliced mRNAs at
RT multiple steps.";
RL Biochem. Biophys. Res. Commun. 384:334-340(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-296 AND LYS-321, AND MASS
RP 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 [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ALA-2, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-12 AND THR-163, 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 [29]
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 [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ALA-2, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-12, AND MASS 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 [31]
RP INTERACTION WITH CWC22, AND MUTAGENESIS OF ASP-270; ASP-273;
RP 276-THR-ILE-277 AND 301-ASN--THR-303.
RX PubMed=22959432; DOI=10.1016/j.celrep.2012.08.017;
RA Steckelberg A.L., Boehm V., Gromadzka A.M., Gehring N.H.;
RT "CWC22 connects pre-mRNA splicing and exon junction complex
RT assembly.";
RL Cell Rep. 2:454-461(2012).
RN [32]
RP FUNCTION.
RX PubMed=22203037; DOI=10.1128/MCB.06130-11;
RA Michelle L., Cloutier A., Toutant J., Shkreta L., Thibault P.,
RA Durand M., Garneau D., Gendron D., Lapointe E., Couture S., Le Hir H.,
RA Klinck R., Elela S.A., Prinos P., Chabot B.;
RT "Proteins associated with the exon junction complex also control the
RT alternative splicing of apoptotic regulators.";
RL Mol. Cell. Biol. 32:954-967(2012).
RN [33]
RP ENZYME REGULATION, INTERACTION WITH CASC3; CWC22; MAGOH; PRPF19 AND
RP RBM8A, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-401 AND GLU-402.
RX PubMed=22961380; DOI=10.1038/nsmb.2380;
RA Barbosa I., Haque N., Fiorini F., Barrandon C., Tomasetto C.,
RA Blanchette M., Le Hir H.;
RT "Human CWC22 escorts the helicase eIF4AIII to spliceosomes and
RT promotes exon junction complex assembly.";
RL Nat. Struct. Mol. Biol. 19:983-990(2012).
RN [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP INTERACTION WITH CWC22, AND MUTAGENESIS OF THR-334.
RX PubMed=23236153; DOI=10.1073/pnas.1219725110;
RA Alexandrov A., Colognori D., Shu M.D., Steitz J.A.;
RT "Human spliceosomal protein CWC22 plays a role in coupling splicing to
RT exon junction complex deposition and nonsense-mediated decay.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:21313-21318(2012).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 2-411 IN THE EJC COMPLEX
RP WITH CASC3; MAGOH; RBM8A; AMP-PNP AND POLY URACIL.
RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006;
RA Bono F., Ebert J., Lorentzen E., Conti E.;
RT "The crystal structure of the exon junction complex reveals how it
RT maintains a stable grip on mRNA.";
RL Cell 126:713-725(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN THE EJC COMPLEX WITH CASC3;
RP MAGOH; RBM8A; ADP-NP AND POLY URACIL.
RX PubMed=16931718; DOI=10.1126/science.1131981;
RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H.,
RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.;
RT "Structure of the exon junction core complex with a trapped DEAD-box
RT ATPase bound to RNA.";
RL Science 313:1968-1972(2006).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN THE EJC COMPLEX WITH CASC3;
RP MAGOH; RBM8A; TRANSITION STATE ANALOG ADP-ALF3 AND POLY URACIL.
RX PubMed=19033377; DOI=10.1261/rna.1283109;
RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K.,
RA Le Hir H., Andersen G.R.;
RT "Mechanism of ATP turnover inhibition in the EJC.";
RL RNA 15:67-75(2009).
CC -!- FUNCTION: ATP-dependent RNA helicase. Core component of the
CC splicing-dependent multiprotein exon junction complex (EJC)
CC deposited at splice junctions on mRNAs. The EJC is a dynamic
CC structure consisting of core proteins and several peripheral
CC nuclear and cytoplasmic associated factors that join the complex
CC only transiently either during EJC assembly or during subsequent
CC mRNA metabolism. The EJC marks the position of the exon-exon
CC junction in the mature mRNA for the gene expression machinery and
CC the core components remain bound to spliced mRNAs throughout all
CC stages of mRNA metabolism thereby influencing downstream processes
CC including nuclear mRNA export, subcellular mRNA localization,
CC translation efficiency and nonsense-mediated mRNA decay (NMD). Its
CC RNA-dependent ATPase and RNA-helicase activities are induced by
CC CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer,
CC thereby trapping the ATP-bound EJC core onto spliced mRNA in a
CC stable conformation. The inhibition of ATPase activity by the
CC MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the
CC EJC. Involved in translational enhancement of spliced mRNAs after
CC formation of the 80S ribosome complex. Binds spliced mRNA in
CC sequence-independent manner, 20-24 nucleotides upstream of mRNA
CC exon-exon junctions. Shows higher affinity for single-stranded RNA
CC in an ATP-bound core EJC complex than after the ATP is hydrolyzed.
CC Involved in the splicing modulation of BCL2L1/Bcl-X (and probably
CC other apoptotic genes); specifically inhibits formation of
CC proapoptotic isoforms such as Bcl-X(S); the function is different
CC from the established EJC assembly.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- ENZYME REGULATION: The ATPase activity is increased some 4-fold in
CC the presence of RNA.
CC -!- SUBUNIT: Part of the mRNA splicing-dependent exon junction complex
CC (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH and
CC RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4.
CC Identified in the spliceosome C complex. May interact with NOM1.
CC Interacts with POLDIP3. Interacts with CWC22 and PRPF19 in an RNA-
CC independent manner. Direct interaction with CWC22 is mediated by
CC the helicase C-terminal domain. Full interaction with CWC22 occurs
CC only when EIF4A3 is not part of the EJC and prevents EIF4A3
CC binding to RNA.
CC -!- INTERACTION:
CC O15234:CASC3; NbExp=7; IntAct=EBI-299104, EBI-299118;
CC Q9HCG8:CWC22; NbExp=3; IntAct=EBI-299104, EBI-373289;
CC P61326:MAGOH; NbExp=20; IntAct=EBI-299104, EBI-299134;
CC Q9Y5S9:RBM8A; NbExp=21; IntAct=EBI-299104, EBI-447231;
CC Q9Y2W1:THRAP3; NbExp=2; IntAct=EBI-299104, EBI-352039;
CC Q9BZI7:UPF3B; NbExp=7; IntAct=EBI-299104, EBI-372780;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Cytoplasm.
CC Note=Nucleocytoplasmic shuttling protein. Travels to the cytoplasm
CC as part of the exon junction complex (EJC) bound to mRNA. Detected
CC in dendritic layer as well as the nuclear and cytoplasmic
CC (somatic) compartments of neurons. Colocalizes with STAU1 and FMR1
CC in dendrites (By similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. eIF4A
CC subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04879.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; X79538; CAA56074.1; -; mRNA.
DR EMBL; D21853; BAA04879.2; ALT_INIT; mRNA.
DR EMBL; AK290608; BAF83297.1; -; mRNA.
DR EMBL; CR456750; CAG33031.1; -; mRNA.
DR EMBL; AC087741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89584.1; -; Genomic_DNA.
DR EMBL; BC003662; AAH03662.1; -; mRNA.
DR EMBL; BC004386; AAH04386.1; -; mRNA.
DR EMBL; BC011151; AAH11151.1; -; mRNA.
DR PIR; S45142; S45142.
DR RefSeq; NP_055555.1; NM_014740.3.
DR UniGene; Hs.389649; -.
DR PDB; 2HXY; X-ray; 3.30 A; A/B/C/D=23-410.
DR PDB; 2HYI; X-ray; 2.30 A; C/I=1-411.
DR PDB; 2J0Q; X-ray; 3.20 A; A/B=2-411.
DR PDB; 2J0S; X-ray; 2.21 A; A=2-411.
DR PDB; 2J0U; X-ray; 3.00 A; A/B=38-411.
DR PDB; 2XB2; X-ray; 3.40 A; A/X=1-411.
DR PDB; 3EX7; X-ray; 2.30 A; C/H=1-411.
DR PDB; 4C9B; X-ray; 2.00 A; A=1-411.
DR PDBsum; 2HXY; -.
DR PDBsum; 2HYI; -.
DR PDBsum; 2J0Q; -.
DR PDBsum; 2J0S; -.
DR PDBsum; 2J0U; -.
DR PDBsum; 2XB2; -.
DR PDBsum; 3EX7; -.
DR PDBsum; 4C9B; -.
DR ProteinModelPortal; P38919; -.
DR SMR; P38919; 21-411.
DR DIP; DIP-33218N; -.
DR IntAct; P38919; 134.
DR MINT; MINT-1460615; -.
DR STRING; 9606.ENSP00000269349; -.
DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR PhosphoSite; P38919; -.
DR DMDM; 20532400; -.
DR REPRODUCTION-2DPAGE; IPI00009328; -.
DR PaxDb; P38919; -.
DR PeptideAtlas; P38919; -.
DR PRIDE; P38919; -.
DR DNASU; 9775; -.
DR Ensembl; ENST00000269349; ENSP00000269349; ENSG00000141543.
DR GeneID; 9775; -.
DR KEGG; hsa:9775; -.
DR UCSC; uc002jxs.3; human.
DR CTD; 9775; -.
DR GeneCards; GC17M078109; -.
DR HGNC; HGNC:18683; EIF4A3.
DR HPA; HPA021878; -.
DR MIM; 608546; gene.
DR neXtProt; NX_P38919; -.
DR PharmGKB; PA162384945; -.
DR eggNOG; COG0513; -.
DR HOGENOM; HOG000268797; -.
DR HOVERGEN; HBG107989; -.
DR InParanoid; P38919; -.
DR KO; K13025; -.
DR OMA; TQIQKVI; -.
DR PhylomeDB; P38919; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; EIF4A3; human.
DR EvolutionaryTrace; P38919; -.
DR GeneWiki; EIF4A3; -.
DR GenomeRNAi; 9775; -.
DR NextBio; 36802; -.
DR PRO; PR:P38919; -.
DR ArrayExpress; P38919; -.
DR Bgee; P38919; -.
DR CleanEx; HS_EIF4A3; -.
DR Genevestigator; P38919; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; IDA:HGNC.
DR GO; GO:0008143; F:poly(A) RNA binding; IDA:HGNC.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IDA:HGNC.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; 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; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Helicase; Hydrolase; mRNA processing;
KW mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; rRNA processing; Spliceosome; Translation regulation;
KW Transport.
FT CHAIN 1 411 Eukaryotic initiation factor 4A-III.
FT /FTId=PRO_0000423267.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 411 Eukaryotic initiation factor 4A-III, N-
FT terminally processed.
FT /FTId=PRO_0000054942.
FT DOMAIN 69 239 Helicase ATP-binding.
FT DOMAIN 250 411 Helicase C-terminal.
FT NP_BIND 85 90 ATP.
FT NP_BIND 367 371 ATP.
FT MOTIF 38 66 Q motif.
FT MOTIF 187 190 DEAD box.
FT BINDING 60 60 ATP; via carbonyl oxygen.
FT BINDING 65 65 ATP.
FT BINDING 342 342 ATP.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylalanine; in Eukaryotic initiation
FT factor 4A-III, N-terminally processed.
FT MOD_RES 12 12 Phosphoserine.
FT MOD_RES 163 163 Phosphothreonine.
FT MOD_RES 296 296 N6-acetyllysine.
FT MOD_RES 321 321 N6-acetyllysine.
FT MUTAGEN 88 88 K->A: ATPase activity is not induced in
FT presence of CASC3. Does not prevent EJC
FT formation. Prevents the EJC disassembly.
FT MUTAGEN 270 270 D->K: Loss of CWC22-binding and loss of
FT incorporation into EJCs; when associated
FT with K-273.
FT MUTAGEN 273 273 D->K: Loss of CWC22-binding and loss of
FT incorporation into EJCs; when associated
FT with K-270.
FT MUTAGEN 276 277 TI->GD: Loss of CWC22-binding and loss of
FT incorporation into EJCs.
FT MUTAGEN 301 303 NFT->LAG: Loss of CWC22-binding and loss
FT of incorporation into EJCs.
FT MUTAGEN 334 334 T->V: Reduced incorporation into EJCs.
FT MUTAGEN 401 401 D->K: Loss of incorporation into EJCs;
FT when associated with R-402.
FT MUTAGEN 402 402 E->R: Loss of incorporation into EJCs;
FT when associated with K-401.
FT CONFLICT 210 210 P -> S (in Ref. 1; CAA56074).
FT CONFLICT 370 370 R -> Q (in Ref. 1; CAA56074).
FT STRAND 23 25
FT HELIX 40 43
FT HELIX 47 56
FT HELIX 63 73
FT STRAND 78 81
FT STRAND 84 86
FT HELIX 88 98
FT STRAND 102 104
FT STRAND 109 112
FT HELIX 116 129
FT TURN 130 134
FT STRAND 137 140
FT STRAND 143 145
FT HELIX 146 155
FT STRAND 158 162
FT HELIX 164 172
FT STRAND 183 187
FT HELIX 189 192
FT TURN 195 197
FT HELIX 198 205
FT STRAND 213 219
FT HELIX 223 226
FT HELIX 229 231
FT STRAND 237 239
FT HELIX 243 245
FT STRAND 251 260
FT HELIX 263 275
FT STRAND 277 283
FT HELIX 287 299
FT STRAND 305 307
FT STRAND 309 311
FT HELIX 313 324
FT STRAND 330 333
FT HELIX 335 337
FT STRAND 338 340
FT STRAND 346 353
FT HELIX 358 365
FT HELIX 370 372
FT STRAND 375 382
FT HELIX 383 385
FT HELIX 386 395
FT STRAND 400 402
FT HELIX 408 411
SQ SEQUENCE 411 AA; 46871 MW; 3A21888CA96CA5EA CRC64;
MATTATMATS GSARKRLLKE EDMTKVEFET SEEVDVTPTF DTMGLREDLL RGIYAYGFEK
PSAIQQRAIK QIIKGRDVIA QSQSGTGKTA TFSISVLQCL DIQVRETQAL ILAPTRELAV
QIQKGLLALG DYMNVQCHAC IGGTNVGEDI RKLDYGQHVV AGTPGRVFDM IRRRSLRTRA
IKMLVLDEAD EMLNKGFKEQ IYDVYRYLPP ATQVVLISAT LPHEILEMTN KFMTDPIRIL
VKRDELTLEG IKQFFVAVER EEWKFDTLCD LYDTLTITQA VIFCNTKRKV DWLTEKMREA
NFTVSSMHGD MPQKERESIM KEFRSGASRV LISTDVWARG LDVPQVSLII NYDLPNNREL
YIHRIGRSGR YGRKGVAINF VKNDDIRILR DIEQYYSTQI DEMPMNVADL I
//
MIM
608546
*RECORD*
*FIELD* NO
608546
*FIELD* TI
*608546 DEAD/H BOX 48; DDX48
;;EUKARYOTIC TRANSLATION INITIATION FACTOR 4A, ISOFORM 3; EIF4A3;;
read moreNUK34;;
NUCLEAR MATRIX PROTEIN 265; NMP265;;
KIAA0111
*FIELD* TX
DESCRIPTION
DDX48 is a component of the exon junction complex (EJC), which assembles
near exon-exon junctions of mRNAs as a result of splicing. EJC proteins
play roles in postsplicing events, including mRNA export, cytoplasmic
localization, and nonsense-mediated decay (Chan et al., 2004).
CLONING
By sequencing clones obtained from a size-fractionated immature myeloid
cell line cDNA library, Nagase et al. (1995) cloned DDX48, which they
designated KIAA0111. The deduced protein contains 411 amino acids.
Northern blot analysis detected DDX48 expression in all tissues and cell
lines examined. Highest expression was in heart, brain, placenta, lung,
liver, skeletal muscle, kidney, and thymus, and lowest expression was in
peripheral blood leukocytes.
Holzmann et al. (2000) purified DDX48, which they called NMP265, from
nuclear matrix proteins isolated from various human tissues and cells.
The protein had an apparent molecular mass of 47 kD by 2-dimensional
electrophoresis. The deduced protein contains 8 DEAD-box motifs that
correspond to those of ATP-dependent RNA helicases. DDX48 shares 66%
amino acid identity with EIF4A1 (602641) and 71% identity with EIF4A2
(601102), although the N termini differ between the 3 proteins. DDX48
shares 61 to 96% amino acid identity with its rodent, frog, nematode,
and yeast homologs. Northern blot analysis detected an mRNA of about 1.7
kb in 3 human cell lines. RNA dot blot analysis detected expression in
all adult and fetal tissues examined. Immunofluorescence and confocal
microscopy detected fluorescence-tagged DDX48 in a punctate nuclear
staining pattern preferentially at perinucleolar sites. Mutation
analysis indicated that the N-terminal 23 amino acids of DDX48 were
involved in nuclear localization.
GENE FUNCTION
Chan et al. (2004) showed that EIF4A3 is a component of the EJC. EIF4A3
preferentially associated with the nuclear EJC complex proteins MAGOH
(602603) and Y14 (605313), and it interacted with these components
indirectly through interactions with TAP (602647) and ALY (604171).
Furthermore, EIF4A3, but not EIF4A1 or EIF4A2, preferentially associated
with spliced mRNA. EIF4A3 did not bind intronless mRNA. In vitro
splicing and mapping experiments demonstrated that EIF4A3 bound mRNAs at
the EJC. Chan et al. (2004) concluded that EIF4A3 provides a
splicing-dependent influence on the translation of mRNAs.
Using a library of endoribonuclease-prepared short interfering RNAs
(esiRNAs), Kittler et al. (2004) identified 37 genes required for cell
division, one of which was DDX48. These 37 genes included several
splicing factors for which knockdown generates mitotic spindle defects.
In addition, a putative nuclear-export terminator was found to speed up
cell proliferation and mitotic progression after knockdown.
MAPPING
By examining human-rodent hybrid cell lines, Nagase et al. (1995) mapped
the DDX48 gene to chromosome 17.
*FIELD* RF
1. Chan, C. C.; Dostie, J.; Diem, M. D.; Feng, W.; Mann, M.; Rappsilber,
J.; Dreyfuss, G.: eIF4A3 is a novel component of the exon junction
complex. RNA 10: 200-209, 2004.
2. Holzmann, K.; Gerner, C.; Poltl, A.; Schafer, R.; Obrist, P.; Ensinger,
C.; Grimm, R.; Sauermann, G.: A human common nuclear matrix protein
homologous to eukaryotic translation initiation factor 4A. Biochem.
Biophys. Res. Commun. 267: 339-344, 2000.
3. Kittler, R.; Putz, G.; Pelletier, L.; Poser, I.; Heninger, A.-K.;
Drechsel, D.; Fischer, S.; Konstantinova, I.; Habermann, B.; Grabner,
H.; Yaspo, M.-L.; Himmelbauer, H.; Korn, B.; Neugebauer, K.; Pisabarro,
M. T.; Buchholz, F.: An endoribonuclease-prepared siRNA screen in
human cells identifies genes essential for cell division. Nature 432:
1036-1040, 2004.
4. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
*FIELD* CN
Ada Hamosh - updated: 03/08/2005
*FIELD* CD
Patricia A. Hartz: 3/23/2004
*FIELD* ED
alopez: 03/08/2005
mgross: 3/23/2004
*RECORD*
*FIELD* NO
608546
*FIELD* TI
*608546 DEAD/H BOX 48; DDX48
;;EUKARYOTIC TRANSLATION INITIATION FACTOR 4A, ISOFORM 3; EIF4A3;;
read moreNUK34;;
NUCLEAR MATRIX PROTEIN 265; NMP265;;
KIAA0111
*FIELD* TX
DESCRIPTION
DDX48 is a component of the exon junction complex (EJC), which assembles
near exon-exon junctions of mRNAs as a result of splicing. EJC proteins
play roles in postsplicing events, including mRNA export, cytoplasmic
localization, and nonsense-mediated decay (Chan et al., 2004).
CLONING
By sequencing clones obtained from a size-fractionated immature myeloid
cell line cDNA library, Nagase et al. (1995) cloned DDX48, which they
designated KIAA0111. The deduced protein contains 411 amino acids.
Northern blot analysis detected DDX48 expression in all tissues and cell
lines examined. Highest expression was in heart, brain, placenta, lung,
liver, skeletal muscle, kidney, and thymus, and lowest expression was in
peripheral blood leukocytes.
Holzmann et al. (2000) purified DDX48, which they called NMP265, from
nuclear matrix proteins isolated from various human tissues and cells.
The protein had an apparent molecular mass of 47 kD by 2-dimensional
electrophoresis. The deduced protein contains 8 DEAD-box motifs that
correspond to those of ATP-dependent RNA helicases. DDX48 shares 66%
amino acid identity with EIF4A1 (602641) and 71% identity with EIF4A2
(601102), although the N termini differ between the 3 proteins. DDX48
shares 61 to 96% amino acid identity with its rodent, frog, nematode,
and yeast homologs. Northern blot analysis detected an mRNA of about 1.7
kb in 3 human cell lines. RNA dot blot analysis detected expression in
all adult and fetal tissues examined. Immunofluorescence and confocal
microscopy detected fluorescence-tagged DDX48 in a punctate nuclear
staining pattern preferentially at perinucleolar sites. Mutation
analysis indicated that the N-terminal 23 amino acids of DDX48 were
involved in nuclear localization.
GENE FUNCTION
Chan et al. (2004) showed that EIF4A3 is a component of the EJC. EIF4A3
preferentially associated with the nuclear EJC complex proteins MAGOH
(602603) and Y14 (605313), and it interacted with these components
indirectly through interactions with TAP (602647) and ALY (604171).
Furthermore, EIF4A3, but not EIF4A1 or EIF4A2, preferentially associated
with spliced mRNA. EIF4A3 did not bind intronless mRNA. In vitro
splicing and mapping experiments demonstrated that EIF4A3 bound mRNAs at
the EJC. Chan et al. (2004) concluded that EIF4A3 provides a
splicing-dependent influence on the translation of mRNAs.
Using a library of endoribonuclease-prepared short interfering RNAs
(esiRNAs), Kittler et al. (2004) identified 37 genes required for cell
division, one of which was DDX48. These 37 genes included several
splicing factors for which knockdown generates mitotic spindle defects.
In addition, a putative nuclear-export terminator was found to speed up
cell proliferation and mitotic progression after knockdown.
MAPPING
By examining human-rodent hybrid cell lines, Nagase et al. (1995) mapped
the DDX48 gene to chromosome 17.
*FIELD* RF
1. Chan, C. C.; Dostie, J.; Diem, M. D.; Feng, W.; Mann, M.; Rappsilber,
J.; Dreyfuss, G.: eIF4A3 is a novel component of the exon junction
complex. RNA 10: 200-209, 2004.
2. Holzmann, K.; Gerner, C.; Poltl, A.; Schafer, R.; Obrist, P.; Ensinger,
C.; Grimm, R.; Sauermann, G.: A human common nuclear matrix protein
homologous to eukaryotic translation initiation factor 4A. Biochem.
Biophys. Res. Commun. 267: 339-344, 2000.
3. Kittler, R.; Putz, G.; Pelletier, L.; Poser, I.; Heninger, A.-K.;
Drechsel, D.; Fischer, S.; Konstantinova, I.; Habermann, B.; Grabner,
H.; Yaspo, M.-L.; Himmelbauer, H.; Korn, B.; Neugebauer, K.; Pisabarro,
M. T.; Buchholz, F.: An endoribonuclease-prepared siRNA screen in
human cells identifies genes essential for cell division. Nature 432:
1036-1040, 2004.
4. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
*FIELD* CN
Ada Hamosh - updated: 03/08/2005
*FIELD* CD
Patricia A. Hartz: 3/23/2004
*FIELD* ED
alopez: 03/08/2005
mgross: 3/23/2004