IF4A1_HUMAN
ID IF4A1_HUMAN Reviewed; 406 AA.
AC P60842; B2R6L8; D3DTP9; J3QLC4; P04765; Q5U018; Q61516;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Eukaryotic initiation factor 4A-I;
DE Short=eIF-4A-I;
DE Short=eIF4A-I;
DE EC=3.6.4.13;
DE AltName: Full=ATP-dependent RNA helicase eIF4A-1;
GN Name=EIF4A1; Synonyms=DDX2A, EIF4A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8493113; DOI=10.1093/nar/21.8.2012;
RA Kim N.-S., Kato T., Abe N., Kato S.;
RT "Nucleotide sequence of human cDNA encoding eukaryotic initiation factor
RT 4AI.";
RL Nucleic Acids Res. 21:2012-2012(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE 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., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., 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 the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Bone marrow, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH PAIP1.
RX PubMed=9548260; DOI=10.1038/33198;
RA Craig A.W.B., Haghighat A., Yu A.T.K., Sonenberg N.;
RT "Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP
RT enhances translation.";
RL Nature 392:520-523(1998).
RN [8]
RP INTERACTION WITH UPF2.
RX PubMed=11073994; DOI=10.1128/mcb.20.23.8944-8957.2000;
RA Mendell J.T., Medghalchi S.M., Lake R.G., Noensie E.N., Dietz H.C.;
RT "Novel Upf2p orthologues suggest a functional link between translation
RT initiation and nonsense surveillance complexes.";
RL Mol. Cell. Biol. 20:8944-8957(2000).
RN [9]
RP INTERACTION WITH EIF4E.
RX PubMed=11408474; DOI=10.1074/jbc.c100284200;
RA Li W., Belsham G.J., Proud C.G.;
RT "Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact
RT in a 1:1 ratio in vivo.";
RL J. Biol. Chem. 276:29111-29115(2001).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; VPS26A; VPS29; VPS35 AND
RP SFN.
RX PubMed=15282546; DOI=10.1038/sj.emboj.7600338;
RA Mingot J.-M., Bohnsack M.T., Jaekle U., Goerlich D.;
RT "Exportin 7 defines a novel general nuclear export pathway.";
RL EMBO J. 23:3227-3236(2004).
RN [12]
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 within
RT the chromosome 7q36 breakpoint region targeted in cases of pediatric acute
RT myeloid leukemia.";
RL Gene 347:137-145(2005).
RN [13]
RP INTERACTION WITH RBM4.
RX PubMed=17284590; DOI=10.1073/pnas.0611015104;
RA Lin J.C., Hsu M., Tarn W.Y.;
RT "Cell stress modulates the function of splicing regulatory protein RBM4 in
RT translation control.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2235-2240(2007).
RN [14]
RP INTERACTION WITH DDX3X.
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 in
RT translational control.";
RL Mol. Biol. Cell 19:3847-3858(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118 AND LYS-174, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [17]
RP INTERACTION WITH HHV-5 PROTEIN UL69 (MICROBIAL INFECTION).
RX PubMed=20133758; DOI=10.1073/pnas.0914856107;
RA Aoyagi M., Gaspar M., Shenk T.E.;
RT "Human cytomegalovirus UL69 protein facilitates translation by associating
RT with the mRNA cap-binding complex and excluding 4EBP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2640-2645(2010).
RN [18]
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., Buerckstuemmer T.,
RA 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 [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-4, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-146; LYS-225; LYS-238; LYS-309;
RP LYS-369 AND LYS-381, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) IN COMPLEX WITH PDCD4, FUNCTION,
RP SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=19153607; DOI=10.1038/emboj.2008.278;
RA Loh P.G., Yang H.S., Walsh M.A., Wang Q., Wang X., Cheng Z., Liu D.,
RA Song H.;
RT "Structural basis for translational inhibition by the tumour suppressor
RT Pdcd4.";
RL EMBO J. 28:274-285(2009).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 20-406 IN COMPLEX WITH PDCD4,
RP FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=19204291; DOI=10.1073/pnas.0808275106;
RA Chang J.H., Cho Y.H., Sohn S.Y., Choi J.M., Kim A., Kim Y.C., Jang S.K.,
RA Cho Y.;
RT "Crystal structure of the eIF4A-PDCD4 complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3148-3153(2009).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 20-236.
RX PubMed=20941364; DOI=10.1371/journal.pone.0012791;
RA Schutz P., Karlberg T., van den Berg S., Collins R., Lehtio L., Hogbom M.,
RA Holmberg-Schiavone L., Tempel W., Park H.W., Hammarstrom M., Moche M.,
RA Thorsell A.G., Schuler H.;
RT "Comparative structural analysis of human DEAD-box RNA helicases.";
RL PLoS ONE 5:E12791-E12791(2010).
CC -!- FUNCTION: ATP-dependent RNA helicase which is a subunit of the eIF4F
CC complex involved in cap recognition and is required for mRNA binding to
CC ribosome. In the current model of translation initiation, eIF4A unwinds
CC RNA secondary structures in the 5'-UTR of mRNAs which is necessary to
CC allow efficient binding of the small ribosomal subunit, and subsequent
CC scanning for the initiator codon. {ECO:0000269|PubMed:19153607,
CC ECO:0000269|PubMed:19204291}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC -!- ACTIVITY REGULATION: Helicase activity and function in translation are
CC inhibited by interaction with PDCD4. {ECO:0000269|PubMed:19153607,
CC ECO:0000269|PubMed:19204291}.
CC -!- SUBUNIT: eIF4F is a multi-subunit complex, the composition of which
CC varies with external and internal environmental conditions. It is
CC composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Interacts with
CC PAIP1, EIF4E and UPF2. Found in a complex with XPO7, EIF4A1, ARHGAP1,
CC VPS26A, VPS29, VPS35 and SFN. May interact with NOM1. Interacts with
CC PDCD4; this interferes with the interaction between EIF4A and EIF4G.
CC Interacts with RBM4. Interacts with DDX3X in an RNA-independent manner
CC (PubMed:18596238). {ECO:0000269|PubMed:11073994,
CC ECO:0000269|PubMed:11408474, ECO:0000269|PubMed:15282546,
CC ECO:0000269|PubMed:17284590, ECO:0000269|PubMed:18596238,
CC ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291,
CC ECO:0000269|PubMed:9548260}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human
CC cytomegalovirus/HHV-5 protein UL69. {ECO:0000269|PubMed:20133758}.
CC -!- INTERACTION:
CC P60842; Q04637: EIF4G1; NbExp=11; IntAct=EBI-73449, EBI-73711;
CC P60842; Q04637-1: EIF4G1; NbExp=2; IntAct=EBI-73449, EBI-5456295;
CC P60842; P78344: EIF4G2; NbExp=3; IntAct=EBI-73449, EBI-296519;
CC P60842; P78344-1: EIF4G2; NbExp=3; IntAct=EBI-73449, EBI-16040248;
CC P60842; Q15056: EIF4H; NbExp=2; IntAct=EBI-73449, EBI-748492;
CC P60842; Q53EL6: PDCD4; NbExp=9; IntAct=EBI-73449, EBI-935824;
CC P60842; Q9BWF3-1: RBM4; NbExp=3; IntAct=EBI-73449, EBI-15621561;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P60842-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P60842-2; Sequence=VSP_046032;
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. eIF4A subfamily.
CC {ECO:0000305}.
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DR EMBL; D13748; BAA02897.1; -; mRNA.
DR EMBL; BT019880; AAV38683.1; -; mRNA.
DR EMBL; BT019881; AAV38684.1; -; mRNA.
DR EMBL; AK312630; BAG35515.1; -; mRNA.
DR EMBL; AC016876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90167.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90168.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90169.1; -; Genomic_DNA.
DR EMBL; BC006210; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC009585; AAH09585.1; -; mRNA.
DR EMBL; BC073752; AAH73752.1; -; mRNA.
DR CCDS; CCDS11113.1; -. [P60842-1]
DR CCDS; CCDS58511.1; -. [P60842-2]
DR PIR; S33681; S33681.
DR RefSeq; NP_001191439.1; NM_001204510.1. [P60842-2]
DR RefSeq; NP_001407.1; NM_001416.3. [P60842-1]
DR PDB; 2G9N; X-ray; 2.25 A; A/B=20-238.
DR PDB; 2ZU6; X-ray; 2.80 A; A/C/D/F=20-406.
DR PDB; 3EIQ; X-ray; 3.50 A; A/D=1-406.
DR PDB; 5ZBZ; X-ray; 1.31 A; A=20-238.
DR PDB; 5ZC9; X-ray; 2.00 A; A=19-406.
DR PDB; 6ZMW; EM; 3.70 A; j=1-406.
DR PDB; 7PPZ; X-ray; 2.52 A; B=20-406.
DR PDB; 7PQ0; X-ray; 3.00 A; B=20-406.
DR PDBsum; 2G9N; -.
DR PDBsum; 2ZU6; -.
DR PDBsum; 3EIQ; -.
DR PDBsum; 5ZBZ; -.
DR PDBsum; 5ZC9; -.
DR PDBsum; 6ZMW; -.
DR PDBsum; 7PPZ; -.
DR PDBsum; 7PQ0; -.
DR AlphaFoldDB; P60842; -.
DR SMR; P60842; -.
DR BioGRID; 108289; 242.
DR ComplexPortal; CPX-2666; Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G1 variant.
DR ComplexPortal; CPX-5635; Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G3 variant.
DR CORUM; P60842; -.
DR DIP; DIP-29755N; -.
DR IntAct; P60842; 96.
DR MINT; P60842; -.
DR STRING; 9606.ENSP00000293831; -.
DR BindingDB; P60842; -.
DR ChEMBL; CHEMBL2052028; -.
DR DrugBank; DB09130; Copper.
DR SwissLipids; SLP:000001628; -.
DR GlyGen; P60842; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P60842; -.
DR MetOSite; P60842; -.
DR PhosphoSitePlus; P60842; -.
DR SwissPalm; P60842; -.
DR BioMuta; EIF4A1; -.
DR DMDM; 46397463; -.
DR EPD; P60842; -.
DR jPOST; P60842; -.
DR MassIVE; P60842; -.
DR MaxQB; P60842; -.
DR PaxDb; P60842; -.
DR PeptideAtlas; P60842; -.
DR PRIDE; P60842; -.
DR ProteomicsDB; 57227; -. [P60842-1]
DR TopDownProteomics; P60842-1; -. [P60842-1]
DR Antibodypedia; 24168; 231 antibodies from 27 providers.
DR DNASU; 1973; -.
DR Ensembl; ENST00000293831.13; ENSP00000293831.8; ENSG00000161960.16. [P60842-1]
DR Ensembl; ENST00000577269.5; ENSP00000463486.1; ENSG00000161960.16. [P60842-2]
DR GeneID; 1973; -.
DR KEGG; hsa:1973; -.
DR MANE-Select; ENST00000293831.13; ENSP00000293831.8; NM_001416.4; NP_001407.1.
DR UCSC; uc002ghr.2; human. [P60842-1]
DR CTD; 1973; -.
DR DisGeNET; 1973; -.
DR GeneCards; EIF4A1; -.
DR HGNC; HGNC:3282; EIF4A1.
DR HPA; ENSG00000161960; Low tissue specificity.
DR MIM; 602641; gene.
DR neXtProt; NX_P60842; -.
DR OpenTargets; ENSG00000161960; -.
DR PharmGKB; PA27710; -.
DR VEuPathDB; HostDB:ENSG00000161960; -.
DR eggNOG; KOG0327; Eukaryota.
DR GeneTree; ENSGT00940000153889; -.
DR HOGENOM; CLU_003041_1_0_1; -.
DR InParanoid; P60842; -.
DR OMA; HLGDYMN; -.
DR OrthoDB; 726081at2759; -.
DR PhylomeDB; P60842; -.
DR TreeFam; TF101524; -.
DR PathwayCommons; P60842; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-HSA-429947; Deadenylation of mRNA.
DR Reactome; R-HSA-72649; Translation initiation complex formation.
DR Reactome; R-HSA-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR SignaLink; P60842; -.
DR SIGNOR; P60842; -.
DR BioGRID-ORCS; 1973; 732 hits in 1096 CRISPR screens.
DR EvolutionaryTrace; P60842; -.
DR GeneWiki; EIF4A1; -.
DR GenomeRNAi; 1973; -.
DR Pharos; P60842; Tchem.
DR PRO; PR:P60842; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P60842; protein.
DR Bgee; ENSG00000161960; Expressed in colonic epithelium and 102 other tissues.
DR ExpressionAtlas; P60842; baseline and differential.
DR Genevisible; P60842; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016281; C:eukaryotic translation initiation factor 4F complex; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0004386; F:helicase activity; TAS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; TAS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000339; F:RNA cap binding; TAS:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0008135; F:translation factor activity, RNA binding; TAS:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central.
DR GO; GO:0002183; P:cytoplasmic translational initiation; IBA:GO_Central.
DR GO; GO:0006413; P:translational initiation; IC:ComplexPortal.
DR CDD; cd18046; DEADc_EIF4AII_EIF4AI_DDX2; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR044728; EIF4A_DEADc.
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; ATP-binding; Helicase;
KW Host-virus interaction; Hydrolase; Initiation factor; Isopeptide bond;
KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; RNA-binding; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CHAIN 2..406
FT /note="Eukaryotic initiation factor 4A-I"
FT /id="PRO_0000054933"
FT DOMAIN 63..234
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 245..406
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 32..60
FT /note="Q motif"
FT MOTIF 182..185
FT /note="DEAD box"
FT BINDING 76..83
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 118
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 158
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 174
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 193
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P60843"
FT MOD_RES 238
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P60843"
FT CROSSLNK 146
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 225
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 369
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 381
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 333..406
FT /note="ARGIDVQQVSLVINYDLPTNRENYIHRIGRGGRFGRKGVAINMVTEEDKRTL
FT RDIETFYNTSIEEMPLNVADLI -> GKLYPQNRSRWTVWP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046032"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:2ZU6"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:3EIQ"
FT HELIX 84..93
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 110..117
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT TURN 124..128
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 140..145
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:3EIQ"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 159..167
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 178..183
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 184..189
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 195..201
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 218..224
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:3EIQ"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:5ZBZ"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:2ZU6"
FT STRAND 246..255
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 259..265
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 282..294
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:2ZU6"
FT HELIX 308..319
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:2ZU6"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:3EIQ"
FT STRAND 341..348
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 353..360
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:5ZC9"
FT STRAND 370..377
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 378..391
FT /evidence="ECO:0007829|PDB:5ZC9"
FT HELIX 400..404
FT /evidence="ECO:0007829|PDB:5ZC9"
SQ SEQUENCE 406 AA; 46154 MW; 6EF89939F3045420 CRC64;
MSASQDSRSR DNGPDGMEPE GVIESNWNEI VDSFDDMNLS ESLLRGIYAY GFEKPSAIQQ
RAILPCIKGY DVIAQAQSGT GKTATFAISI LQQIELDLKA TQALVLAPTR ELAQQIQKVV
MALGDYMGAS CHACIGGTNV RAEVQKLQME APHIIVGTPG RVFDMLNRRY LSPKYIKMFV
LDEADEMLSR GFKDQIYDIF QKLNSNTQVV LLSATMPSDV LEVTKKFMRD PIRILVKKEE
LTLEGIRQFY INVEREEWKL DTLCDLYETL TITQAVIFIN TRRKVDWLTE KMHARDFTVS
AMHGDMDQKE RDVIMREFRS GSSRVLITTD LLARGIDVQQ VSLVINYDLP TNRENYIHRI
GRGGRFGRKG VAINMVTEED KRTLRDIETF YNTSIEEMPL NVADLI
