Full text data of EIF5A
EIF5A
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Eukaryotic translation initiation factor 5A-1; eIF-5A-1; eIF-5A1 (Eukaryotic initiation factor 5A isoform 1; eIF-5A; Rev-binding factor; eIF-4D)
Eukaryotic translation initiation factor 5A-1; eIF-5A-1; eIF-5A1 (Eukaryotic initiation factor 5A isoform 1; eIF-5A; Rev-binding factor; eIF-4D)
UniProt
P63241
ID IF5A1_HUMAN Reviewed; 154 AA.
AC P63241; A8K9A0; D3DTP2; P10159; Q16182; Q7L7L3; Q7Z4L1; Q9D0G2;
read moreDT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Eukaryotic translation initiation factor 5A-1;
DE Short=eIF-5A-1;
DE Short=eIF-5A1;
DE AltName: Full=Eukaryotic initiation factor 5A isoform 1;
DE Short=eIF-5A;
DE AltName: Full=Rev-binding factor;
DE AltName: Full=eIF-4D;
GN Name=EIF5A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2492279;
RA Smit-Mcbride Z., Dever T.E., Hershey J.W.B., Merrick W.C.;
RT "Sequence determination and cDNA cloning of eukaryotic initiation
RT factor 4D, the hypusine-containing protein.";
RL J. Biol. Chem. 264:1578-1583(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-154, INTERACTION
RP WITH HIV-1 REV, AND SUBCELLULAR LOCATION.
RX PubMed=8253832; DOI=10.1083/jcb.123.6.1309;
RA Ruhl M., Himmelspach M., Bahr G.M., Hammerschmid F., Jaksche H.,
RA Wolff B., Aschauer H., Farrington G.K., Probst H., Bevec D.,
RA Hauber J.;
RT "Eukaryotic initiation factor 5A is a cellular target of the human
RT immunodeficiency virus type 1 Rev activation domain mediating trans-
RT activation.";
RL J. Cell Biol. 123:1309-1320(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7545941; DOI=10.1016/0378-1119(94)90385-9;
RA Koettnitz K., Kappel B., Baumruker T., Hauber J., Bevec D.;
RT "The genomic structure encoding human initiation factor eIF-5A.";
RL Gene 144:249-252(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7622067; DOI=10.1016/0378-1119(95)00136-T;
RA Koettnitz K., Woehl T., Kappel B., Lottspeich F., Hauber J., Bevec D.;
RT "Identification of a new member of the human eIF-5A gene family.";
RL Gene 159:283-284(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Johansson H.E., Jenkins Z.A.;
RT "Differential expression of eIF5AI-mRNAs.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, Prostate, and Uterus;
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 [9]
RP PROTEIN SEQUENCE OF 2-6, AND INTERACTION WITH DHPS.
RX PubMed=10229683; DOI=10.1042/0264-6021:3400273;
RA Lee Y.B., Joe Y.A., Wolff E.C., Dimitriadis E.K., Park M.H.;
RT "Complex formation between deoxyhypusine synthase and its protein
RT substrate, the eukaryotic translation initiation factor 5A (eIF5A)
RT precursor.";
RL Biochem. J. 340:273-281(1999).
RN [10]
RP PROTEIN SEQUENCE OF 2-26; 56-67; 69-85 AND 110-121, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 48-55, AND HYPUSINE AT LYS-50.
RX PubMed=3095320;
RA Park M.H., Liu T.-Y., Neece S.H., Swiggard W.J.;
RT "Eukaryotic initiation factor 4D. Purification from human red blood
RT cells and the sequence of amino acids around its single hypusine
RT residue.";
RL J. Biol. Chem. 261:14515-14519(1986).
RN [12]
RP PROTEIN SEQUENCE OF 56-121, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 68-84 AND 114-121.
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=8660923; DOI=10.1006/excr.1996.0185;
RA Shi X.-P., Yin K.-C., Zimolo Z.A., Stern A.M., Waxman L.;
RT "The subcellular distribution of eukaryotic translation initiation
RT factor, eIF-5A, in cultured cells.";
RL Exp. Cell Res. 225:348-356(1996).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4.
RX PubMed=10944119; DOI=10.1093/emboj/19.16.4362;
RA Lipowsky G., Bischoff F.R., Schwarzmaier P., Kraft R., Kostka S.,
RA Hartmann E., Kutay U., Goerlich D.;
RT "Exportin 4: a mediator of a novel nuclear export pathway in higher
RT eukaryotes.";
RL EMBO J. 19:4362-4371(2000).
RN [16]
RP MRNA-BINDING.
RX PubMed=15303967; DOI=10.1042/BJ20041232;
RA Xu A., Jao D.L., Chen K.Y.;
RT "Identification of mRNA that binds to eukaryotic initiation factor 5A
RT by affinity co-purification and differential display.";
RL Biochem. J. 384:585-590(2004).
RN [17]
RP BIOTECHNOLOGY.
RX PubMed=15262146; DOI=10.1016/j.ygyno.2004.03.018;
RA Cracchiolo B.M., Heller D.S., Clement P.M.J., Wolff E.C., Park M.H.,
RA Hanauske-Abel H.M.;
RT "Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker
RT for aberrant proliferation in intraepithelial neoplasia of the
RT vulva.";
RL Gynecol. Oncol. 94:217-222(2004).
RN [18]
RP FUNCTION, AND INTERACTION WITH SDCBP.
RX PubMed=15371445; DOI=10.1074/jbc.M407165200;
RA Li A.-L., Li H.-Y., Jin B.-F., Ye Q.-N., Zhou T., Yu X.-D., Pan X.,
RA Man J.-H., He K., Yu M., Hu M.-R., Wang J., Yang S.-C., Shen B.-F.,
RA Zhang X.-M.;
RT "A novel eIF5A complex functions as a regulator of p53 and p53-
RT dependent apoptosis.";
RL J. Biol. Chem. 279:49251-49258(2004).
RN [19]
RP FUNCTION.
RX PubMed=15452064; DOI=10.1167/iovs.03-1367;
RA Taylor C.A., Senchyna M., Flanagan J., Joyce E.M., Cliche D.O.,
RA Boone A.N., Culp-Stewart S., Thompson J.E.;
RT "Role of eIF5A in TNF-alpha-mediated apoptosis of lamina cribrosa
RT cells.";
RL Invest. Ophthalmol. Vis. Sci. 45:3568-3576(2004).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16519677; DOI=10.1111/j.1742-4658.2006.05135.x;
RA Clement P.M.J., Johansson H.E., Wolff E.C., Park M.H.;
RT "Differential expression of eIF5A-1 and eIF5A-2 in human cancer
RT cells.";
RL FEBS J. 273:1102-1114(2006).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF VAL-81.
RX PubMed=16987817; DOI=10.1074/jbc.M601460200;
RA Schrader R., Young C., Kozian D., Hoffmann R., Lottspeich F.;
RT "Temperature-sensitive eIF5A mutant accumulates transcripts targeted
RT to the nonsense-mediated decay pathway.";
RL J. Biol. Chem. 281:35336-35346(2006).
RN [22]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF LYS-50.
RX PubMed=17187778; DOI=10.1016/j.yexcr.2006.09.030;
RA Taylor C.A., Sun Z., Cliche D.O., Ming H., Eshaque B., Jin S.,
RA Hopkins M.T., Thai B., Thompson J.E.;
RT "Eukaryotic translation initiation factor 5A induces apoptosis in
RT colon cancer cells and associates with the nucleus in response to
RT tumour necrosis factor alpha signalling.";
RL Exp. Cell Res. 313:437-449(2007).
RN [23]
RP INTERACTION WITH DOHH.
RX PubMed=17213197; DOI=10.1074/jbc.M607495200;
RA Kang K.R., Kim Y.S., Wolff E.C., Park M.H.;
RT "Specificity of the deoxyhypusine hydroxylase-eukaryotic translation
RT initiation factor (eIF5A) interaction: identification of amino acid
RT residues of the enzyme required for binding of its substrate,
RT deoxyhypusine-containing eIF5A.";
RL J. Biol. Chem. 282:8300-8308(2007).
RN [24]
RP FUNCTION.
RX PubMed=17360499; DOI=10.1073/pnas.0611609104;
RA Huang Y., Higginson D.S., Hester L., Park M.H., Snyder S.H.;
RT "Neuronal growth and survival mediated by eIF5A, a polyamine-modified
RT translation initiation factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4194-4199(2007).
RN [25]
RP MUTAGENESIS OF LYS-47; GLY-49; LYS-50; GLY-52 AND LYS-55.
RX PubMed=18067580; DOI=10.1111/j.1742-4658.2007.06172.x;
RA Cano V.S.P., Jeon G.A., Johansson H.E., Henderson C.A., Park J.-H.,
RA Valentini S.R., Hershey J.W.B., Park M.H.;
RT "Mutational analyses of human eIF5A-1: identification of amino acid
RT residues critical for eIF5A activity and hypusine modification.";
RL FEBS J. 275:44-58(2008).
RN [26]
RP ACETYLATION AT LYS-47, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-47
RP AND LYS-50.
RX PubMed=19379712; DOI=10.1016/j.bbrc.2009.04.049;
RA Lee S.B., Park J.-H., Kaevel J., Sramkova M., Weigert R., Park M.H.;
RT "The effect of hypusine modification on the intracellular localization
RT of eIF5A.";
RL Biochem. Biophys. Res. Commun. 383:497-502(2009).
RN [27]
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 [28]
RP 3D-STRUCTURE MODELING.
RX PubMed=11742107; DOI=10.1093/protein/14.11.881;
RA Facchiano A.M., Stiuso P., Chiusano M.L., Caraglia M., Giuberti G.,
RA Marra M., Abbruzzese A., Colonna G.;
RT "Homology modelling of the human eukaryotic initiation factor 5A (eIF-
RT 5A).";
RL Protein Eng. 14:881-890(2001).
CC -!- FUNCTION: mRNA-binding protein involved in translation elongation.
CC Has an important function at the level of mRNA turnover, probably
CC acting downstream of decapping. Involved in actin dynamics and
CC cell cycle progression, mRNA decay and probably in a pathway
CC involved in stress response and maintenance of cell wall
CC integrity. With syntenin SDCBP, functions as a regulator of
CC p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF-
CC alpha-mediated apoptosis. Mediates effects of polyamines on
CC neuronal process extension and survival. May play an important
CC role in brain development and function, and in skeletal muscle
CC stem cell differentiation. Also described as a cellular cofactor
CC of human T-cell leukemia virus type I (HTLV-1) Rex protein and of
CC human immunodeficiency virus type 1 (HIV-1) Rev protein, essential
CC for mRNA export of retroviral transcripts.
CC -!- SUBUNIT: Interacts with DHPS, with SDCBP and DOHH. Interacts with
CC HIV-1 protein Rev. Found in a complex with Ran and XPO4. The
CC hypusine modification increases the interaction with XPO4.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endoplasmic reticulum
CC membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus,
CC nuclear pore complex. Note=Hypusine modification promotes the
CC nuclear export and cytoplasmic localization and there was a
CC dynamic shift in the localization from predominantly cytoplasmic
CC to primarily nuclear under apoptotic inducing conditions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=B, C, D;
CC IsoId=P63241-1; Sequence=Displayed;
CC Name=2; Synonyms=A;
CC IsoId=P63241-2; Sequence=VSP_022020;
CC -!- TISSUE SPECIFICITY: Expressed in umbilical vein endothelial cells
CC and several cancer cell lines (at protein level).
CC -!- PTM: eIF-5A seems to be the only eukaryotic protein to have a
CC hypusine residue which is a post-translational modification of a
CC lysine by the addition of a butylamino group (from spermidine).
CC -!- BIOTECHNOLOGY: Mature eIF5A-1 may be used as an in situ diagnostic
CC marker for aberrant proliferation in intraepithelial neoplasia of
CC the vulva.
CC -!- SIMILARITY: Belongs to the eIF-5A family.
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DR EMBL; M23419; AAA58453.1; -; mRNA.
DR EMBL; S72024; AAD14095.1; -; Genomic_DNA.
DR EMBL; U17969; AAA86989.1; -; Genomic_DNA.
DR EMBL; AY129319; AAN17514.1; -; mRNA.
DR EMBL; AY129320; AAN17515.1; -; mRNA.
DR EMBL; AY129321; AAN17516.1; -; mRNA.
DR EMBL; AY129322; AAN17518.1; -; mRNA.
DR EMBL; AK292615; BAF85304.1; -; mRNA.
DR EMBL; CH471108; EAW90219.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90220.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90221.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90222.1; -; Genomic_DNA.
DR EMBL; BC000751; AAH00751.1; -; mRNA.
DR EMBL; BC001832; AAH01832.1; -; mRNA.
DR EMBL; BC030160; AAH30160.1; -; mRNA.
DR EMBL; BC080196; AAH80196.1; -; mRNA.
DR EMBL; BC085015; AAH85015.1; -; mRNA.
DR EMBL; BC107779; AAI07780.1; -; mRNA.
DR PIR; B31486; FIHUA.
DR RefSeq; NP_001137232.1; NM_001143760.1.
DR RefSeq; NP_001137233.1; NM_001143761.1.
DR RefSeq; NP_001137234.1; NM_001143762.1.
DR RefSeq; NP_001961.1; NM_001970.4.
DR RefSeq; XP_005256566.1; XM_005256509.1.
DR UniGene; Hs.104825; -.
DR UniGene; Hs.534314; -.
DR PDB; 1FH4; Model; -; A=1-154.
DR PDB; 3CPF; X-ray; 2.50 A; A/B=15-151.
DR PDBsum; 1FH4; -.
DR PDBsum; 3CPF; -.
DR ProteinModelPortal; P63241; -.
DR SMR; P63241; 15-150.
DR IntAct; P63241; 11.
DR MINT; MINT-1829069; -.
DR STRING; 9606.ENSP00000336702; -.
DR PhosphoSite; P63241; -.
DR DMDM; 54037409; -.
DR DOSAC-COBS-2DPAGE; P63241; -.
DR OGP; P63241; -.
DR PaxDb; P63241; -.
DR PRIDE; P63241; -.
DR DNASU; 1984; -.
DR Ensembl; ENST00000336452; ENSP00000336702; ENSG00000132507.
DR Ensembl; ENST00000336458; ENSP00000336776; ENSG00000132507.
DR Ensembl; ENST00000416016; ENSP00000396073; ENSG00000132507.
DR Ensembl; ENST00000419711; ENSP00000390677; ENSG00000132507.
DR Ensembl; ENST00000571955; ENSP00000458269; ENSG00000132507.
DR Ensembl; ENST00000573542; ENSP00000459611; ENSG00000132507.
DR Ensembl; ENST00000576930; ENSP00000459196; ENSG00000132507.
DR GeneID; 1984; -.
DR KEGG; hsa:1984; -.
DR UCSC; uc002gft.3; human.
DR CTD; 1984; -.
DR GeneCards; GC17P007210; -.
DR HGNC; HGNC:3300; EIF5A.
DR HPA; CAB005042; -.
DR MIM; 600187; gene.
DR neXtProt; NX_P63241; -.
DR PharmGKB; PA27726; -.
DR eggNOG; COG0231; -.
DR HOVERGEN; HBG001104; -.
DR InParanoid; P63241; -.
DR KO; K03263; -.
DR OMA; IPDGDLG; -.
DR OrthoDB; EOG7KSXB7; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; EIF5A; human.
DR EvolutionaryTrace; P63241; -.
DR GeneWiki; EIF5A; -.
DR GenomeRNAi; 1984; -.
DR NextBio; 8037; -.
DR PMAP-CutDB; P63241; -.
DR PRO; PR:P63241; -.
DR ArrayExpress; P63241; -.
DR Bgee; P63241; -.
DR CleanEx; HS_EIF5A; -.
DR Genevestigator; P63241; -.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IEA:InterPro.
DR GO; GO:0003746; F:translation elongation factor activity; ISS:UniProtKB.
DR GO; GO:0017070; F:U6 snRNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0006406; P:mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0008612; P:peptidyl-lysine modification to hypusine; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IGI:UniProtKB.
DR GO; GO:0045901; P:positive regulation of translational elongation; ISS:UniProtKB.
DR GO; GO:0045905; P:positive regulation of translational termination; IEA:InterPro.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006611; P:protein export from nucleus; IMP:UniProtKB.
DR GO; GO:0006452; P:translational frameshifting; IEA:InterPro.
DR Gene3D; 2.30.30.30; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR014722; Rib_L2_dom2.
DR InterPro; IPR019769; Trans_elong_IF5A_hypusine_site.
DR InterPro; IPR001884; Transl_elong_IF5A.
DR InterPro; IPR020189; Transl_elong_IF5A_C.
DR InterPro; IPR008991; Translation_prot_SH3-like.
DR PANTHER; PTHR11673; PTHR11673; 1.
DR Pfam; PF01287; eIF-5a; 1.
DR PIRSF; PIRSF003025; eIF5A; 1.
DR SUPFAM; SSF50104; SSF50104; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR TIGRFAMs; TIGR00037; eIF_5A; 1.
DR PROSITE; PS00302; IF5A_HYPUSINE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Elongation factor;
KW Endoplasmic reticulum; Hypusine; Membrane; mRNA transport;
KW Nuclear pore complex; Nucleus; Protein biosynthesis;
KW Protein transport; Reference proteome; RNA-binding; Translocation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 154 Eukaryotic translation initiation factor
FT 5A-1.
FT /FTId=PRO_0000142451.
FT REGION 20 90 DOHH-binding.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 47 47 N6-acetyllysine.
FT MOD_RES 50 50 Hypusine.
FT VAR_SEQ 1 2 MA -> MCGTGGTDSKTRRPPHRASFLKRLESKPLKMA
FT (in isoform 2).
FT /FTId=VSP_022020.
FT MUTAGEN 47 47 K->A,R: Abolishes acetylation.
FT MUTAGEN 47 47 K->D: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 49 49 G->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 50 50 K->A: Decreases significantly the
FT acetylation at position K-47 and causes
FT total inactivation of eIF5A in supporting
FT yeast growth.
FT MUTAGEN 50 50 K->I,D,R: Causes total inactivation of
FT eIF5A in supporting yeast growth.
FT MUTAGEN 52 52 G->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 55 55 K->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 81 81 V->G: Leads to temperature sensitivity
FT when expressed in yeast cells.
FT CONFLICT 36 36 R -> W (in Ref. 3; AAD14095).
FT CONFLICT 45 45 T -> A (in Ref. 3; AAD14095).
FT CONFLICT 85 85 K -> R (in Ref. 3; AAD14095).
FT CONFLICT 109 109 R -> P (in Ref. 3; AAD14095).
FT STRAND 17 21
FT HELIX 22 24
FT STRAND 29 33
FT STRAND 36 46
FT STRAND 55 62
FT TURN 63 65
FT STRAND 68 74
FT STRAND 77 82
FT STRAND 85 95
FT STRAND 98 102
FT HELIX 117 129
FT STRAND 134 140
FT STRAND 143 150
SQ SEQUENCE 154 AA; 16832 MW; 07EF043C7DEA3091 CRC64;
MADDLDFETG DAGASATFPM QCSALRKNGF VVLKGRPCKI VEMSTSKTGK HGHAKVHLVG
IDIFTGKKYE DICPSTHNMD VPNIKRNDFQ LIGIQDGYLS LLQDSGEVRE DLRLPEGDLG
KEIEQKYDCG EEILITVLSA MTEEAAVAIK AMAK
//
ID IF5A1_HUMAN Reviewed; 154 AA.
AC P63241; A8K9A0; D3DTP2; P10159; Q16182; Q7L7L3; Q7Z4L1; Q9D0G2;
read moreDT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Eukaryotic translation initiation factor 5A-1;
DE Short=eIF-5A-1;
DE Short=eIF-5A1;
DE AltName: Full=Eukaryotic initiation factor 5A isoform 1;
DE Short=eIF-5A;
DE AltName: Full=Rev-binding factor;
DE AltName: Full=eIF-4D;
GN Name=EIF5A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2492279;
RA Smit-Mcbride Z., Dever T.E., Hershey J.W.B., Merrick W.C.;
RT "Sequence determination and cDNA cloning of eukaryotic initiation
RT factor 4D, the hypusine-containing protein.";
RL J. Biol. Chem. 264:1578-1583(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-154, INTERACTION
RP WITH HIV-1 REV, AND SUBCELLULAR LOCATION.
RX PubMed=8253832; DOI=10.1083/jcb.123.6.1309;
RA Ruhl M., Himmelspach M., Bahr G.M., Hammerschmid F., Jaksche H.,
RA Wolff B., Aschauer H., Farrington G.K., Probst H., Bevec D.,
RA Hauber J.;
RT "Eukaryotic initiation factor 5A is a cellular target of the human
RT immunodeficiency virus type 1 Rev activation domain mediating trans-
RT activation.";
RL J. Cell Biol. 123:1309-1320(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7545941; DOI=10.1016/0378-1119(94)90385-9;
RA Koettnitz K., Kappel B., Baumruker T., Hauber J., Bevec D.;
RT "The genomic structure encoding human initiation factor eIF-5A.";
RL Gene 144:249-252(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7622067; DOI=10.1016/0378-1119(95)00136-T;
RA Koettnitz K., Woehl T., Kappel B., Lottspeich F., Hauber J., Bevec D.;
RT "Identification of a new member of the human eIF-5A gene family.";
RL Gene 159:283-284(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Johansson H.E., Jenkins Z.A.;
RT "Differential expression of eIF5AI-mRNAs.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, Prostate, and Uterus;
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 [9]
RP PROTEIN SEQUENCE OF 2-6, AND INTERACTION WITH DHPS.
RX PubMed=10229683; DOI=10.1042/0264-6021:3400273;
RA Lee Y.B., Joe Y.A., Wolff E.C., Dimitriadis E.K., Park M.H.;
RT "Complex formation between deoxyhypusine synthase and its protein
RT substrate, the eukaryotic translation initiation factor 5A (eIF5A)
RT precursor.";
RL Biochem. J. 340:273-281(1999).
RN [10]
RP PROTEIN SEQUENCE OF 2-26; 56-67; 69-85 AND 110-121, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 48-55, AND HYPUSINE AT LYS-50.
RX PubMed=3095320;
RA Park M.H., Liu T.-Y., Neece S.H., Swiggard W.J.;
RT "Eukaryotic initiation factor 4D. Purification from human red blood
RT cells and the sequence of amino acids around its single hypusine
RT residue.";
RL J. Biol. Chem. 261:14515-14519(1986).
RN [12]
RP PROTEIN SEQUENCE OF 56-121, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 68-84 AND 114-121.
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=8660923; DOI=10.1006/excr.1996.0185;
RA Shi X.-P., Yin K.-C., Zimolo Z.A., Stern A.M., Waxman L.;
RT "The subcellular distribution of eukaryotic translation initiation
RT factor, eIF-5A, in cultured cells.";
RL Exp. Cell Res. 225:348-356(1996).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4.
RX PubMed=10944119; DOI=10.1093/emboj/19.16.4362;
RA Lipowsky G., Bischoff F.R., Schwarzmaier P., Kraft R., Kostka S.,
RA Hartmann E., Kutay U., Goerlich D.;
RT "Exportin 4: a mediator of a novel nuclear export pathway in higher
RT eukaryotes.";
RL EMBO J. 19:4362-4371(2000).
RN [16]
RP MRNA-BINDING.
RX PubMed=15303967; DOI=10.1042/BJ20041232;
RA Xu A., Jao D.L., Chen K.Y.;
RT "Identification of mRNA that binds to eukaryotic initiation factor 5A
RT by affinity co-purification and differential display.";
RL Biochem. J. 384:585-590(2004).
RN [17]
RP BIOTECHNOLOGY.
RX PubMed=15262146; DOI=10.1016/j.ygyno.2004.03.018;
RA Cracchiolo B.M., Heller D.S., Clement P.M.J., Wolff E.C., Park M.H.,
RA Hanauske-Abel H.M.;
RT "Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker
RT for aberrant proliferation in intraepithelial neoplasia of the
RT vulva.";
RL Gynecol. Oncol. 94:217-222(2004).
RN [18]
RP FUNCTION, AND INTERACTION WITH SDCBP.
RX PubMed=15371445; DOI=10.1074/jbc.M407165200;
RA Li A.-L., Li H.-Y., Jin B.-F., Ye Q.-N., Zhou T., Yu X.-D., Pan X.,
RA Man J.-H., He K., Yu M., Hu M.-R., Wang J., Yang S.-C., Shen B.-F.,
RA Zhang X.-M.;
RT "A novel eIF5A complex functions as a regulator of p53 and p53-
RT dependent apoptosis.";
RL J. Biol. Chem. 279:49251-49258(2004).
RN [19]
RP FUNCTION.
RX PubMed=15452064; DOI=10.1167/iovs.03-1367;
RA Taylor C.A., Senchyna M., Flanagan J., Joyce E.M., Cliche D.O.,
RA Boone A.N., Culp-Stewart S., Thompson J.E.;
RT "Role of eIF5A in TNF-alpha-mediated apoptosis of lamina cribrosa
RT cells.";
RL Invest. Ophthalmol. Vis. Sci. 45:3568-3576(2004).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16519677; DOI=10.1111/j.1742-4658.2006.05135.x;
RA Clement P.M.J., Johansson H.E., Wolff E.C., Park M.H.;
RT "Differential expression of eIF5A-1 and eIF5A-2 in human cancer
RT cells.";
RL FEBS J. 273:1102-1114(2006).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF VAL-81.
RX PubMed=16987817; DOI=10.1074/jbc.M601460200;
RA Schrader R., Young C., Kozian D., Hoffmann R., Lottspeich F.;
RT "Temperature-sensitive eIF5A mutant accumulates transcripts targeted
RT to the nonsense-mediated decay pathway.";
RL J. Biol. Chem. 281:35336-35346(2006).
RN [22]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF LYS-50.
RX PubMed=17187778; DOI=10.1016/j.yexcr.2006.09.030;
RA Taylor C.A., Sun Z., Cliche D.O., Ming H., Eshaque B., Jin S.,
RA Hopkins M.T., Thai B., Thompson J.E.;
RT "Eukaryotic translation initiation factor 5A induces apoptosis in
RT colon cancer cells and associates with the nucleus in response to
RT tumour necrosis factor alpha signalling.";
RL Exp. Cell Res. 313:437-449(2007).
RN [23]
RP INTERACTION WITH DOHH.
RX PubMed=17213197; DOI=10.1074/jbc.M607495200;
RA Kang K.R., Kim Y.S., Wolff E.C., Park M.H.;
RT "Specificity of the deoxyhypusine hydroxylase-eukaryotic translation
RT initiation factor (eIF5A) interaction: identification of amino acid
RT residues of the enzyme required for binding of its substrate,
RT deoxyhypusine-containing eIF5A.";
RL J. Biol. Chem. 282:8300-8308(2007).
RN [24]
RP FUNCTION.
RX PubMed=17360499; DOI=10.1073/pnas.0611609104;
RA Huang Y., Higginson D.S., Hester L., Park M.H., Snyder S.H.;
RT "Neuronal growth and survival mediated by eIF5A, a polyamine-modified
RT translation initiation factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:4194-4199(2007).
RN [25]
RP MUTAGENESIS OF LYS-47; GLY-49; LYS-50; GLY-52 AND LYS-55.
RX PubMed=18067580; DOI=10.1111/j.1742-4658.2007.06172.x;
RA Cano V.S.P., Jeon G.A., Johansson H.E., Henderson C.A., Park J.-H.,
RA Valentini S.R., Hershey J.W.B., Park M.H.;
RT "Mutational analyses of human eIF5A-1: identification of amino acid
RT residues critical for eIF5A activity and hypusine modification.";
RL FEBS J. 275:44-58(2008).
RN [26]
RP ACETYLATION AT LYS-47, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-47
RP AND LYS-50.
RX PubMed=19379712; DOI=10.1016/j.bbrc.2009.04.049;
RA Lee S.B., Park J.-H., Kaevel J., Sramkova M., Weigert R., Park M.H.;
RT "The effect of hypusine modification on the intracellular localization
RT of eIF5A.";
RL Biochem. Biophys. Res. Commun. 383:497-502(2009).
RN [27]
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 [28]
RP 3D-STRUCTURE MODELING.
RX PubMed=11742107; DOI=10.1093/protein/14.11.881;
RA Facchiano A.M., Stiuso P., Chiusano M.L., Caraglia M., Giuberti G.,
RA Marra M., Abbruzzese A., Colonna G.;
RT "Homology modelling of the human eukaryotic initiation factor 5A (eIF-
RT 5A).";
RL Protein Eng. 14:881-890(2001).
CC -!- FUNCTION: mRNA-binding protein involved in translation elongation.
CC Has an important function at the level of mRNA turnover, probably
CC acting downstream of decapping. Involved in actin dynamics and
CC cell cycle progression, mRNA decay and probably in a pathway
CC involved in stress response and maintenance of cell wall
CC integrity. With syntenin SDCBP, functions as a regulator of
CC p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF-
CC alpha-mediated apoptosis. Mediates effects of polyamines on
CC neuronal process extension and survival. May play an important
CC role in brain development and function, and in skeletal muscle
CC stem cell differentiation. Also described as a cellular cofactor
CC of human T-cell leukemia virus type I (HTLV-1) Rex protein and of
CC human immunodeficiency virus type 1 (HIV-1) Rev protein, essential
CC for mRNA export of retroviral transcripts.
CC -!- SUBUNIT: Interacts with DHPS, with SDCBP and DOHH. Interacts with
CC HIV-1 protein Rev. Found in a complex with Ran and XPO4. The
CC hypusine modification increases the interaction with XPO4.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endoplasmic reticulum
CC membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus,
CC nuclear pore complex. Note=Hypusine modification promotes the
CC nuclear export and cytoplasmic localization and there was a
CC dynamic shift in the localization from predominantly cytoplasmic
CC to primarily nuclear under apoptotic inducing conditions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=B, C, D;
CC IsoId=P63241-1; Sequence=Displayed;
CC Name=2; Synonyms=A;
CC IsoId=P63241-2; Sequence=VSP_022020;
CC -!- TISSUE SPECIFICITY: Expressed in umbilical vein endothelial cells
CC and several cancer cell lines (at protein level).
CC -!- PTM: eIF-5A seems to be the only eukaryotic protein to have a
CC hypusine residue which is a post-translational modification of a
CC lysine by the addition of a butylamino group (from spermidine).
CC -!- BIOTECHNOLOGY: Mature eIF5A-1 may be used as an in situ diagnostic
CC marker for aberrant proliferation in intraepithelial neoplasia of
CC the vulva.
CC -!- SIMILARITY: Belongs to the eIF-5A family.
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DR EMBL; M23419; AAA58453.1; -; mRNA.
DR EMBL; S72024; AAD14095.1; -; Genomic_DNA.
DR EMBL; U17969; AAA86989.1; -; Genomic_DNA.
DR EMBL; AY129319; AAN17514.1; -; mRNA.
DR EMBL; AY129320; AAN17515.1; -; mRNA.
DR EMBL; AY129321; AAN17516.1; -; mRNA.
DR EMBL; AY129322; AAN17518.1; -; mRNA.
DR EMBL; AK292615; BAF85304.1; -; mRNA.
DR EMBL; CH471108; EAW90219.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90220.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90221.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90222.1; -; Genomic_DNA.
DR EMBL; BC000751; AAH00751.1; -; mRNA.
DR EMBL; BC001832; AAH01832.1; -; mRNA.
DR EMBL; BC030160; AAH30160.1; -; mRNA.
DR EMBL; BC080196; AAH80196.1; -; mRNA.
DR EMBL; BC085015; AAH85015.1; -; mRNA.
DR EMBL; BC107779; AAI07780.1; -; mRNA.
DR PIR; B31486; FIHUA.
DR RefSeq; NP_001137232.1; NM_001143760.1.
DR RefSeq; NP_001137233.1; NM_001143761.1.
DR RefSeq; NP_001137234.1; NM_001143762.1.
DR RefSeq; NP_001961.1; NM_001970.4.
DR RefSeq; XP_005256566.1; XM_005256509.1.
DR UniGene; Hs.104825; -.
DR UniGene; Hs.534314; -.
DR PDB; 1FH4; Model; -; A=1-154.
DR PDB; 3CPF; X-ray; 2.50 A; A/B=15-151.
DR PDBsum; 1FH4; -.
DR PDBsum; 3CPF; -.
DR ProteinModelPortal; P63241; -.
DR SMR; P63241; 15-150.
DR IntAct; P63241; 11.
DR MINT; MINT-1829069; -.
DR STRING; 9606.ENSP00000336702; -.
DR PhosphoSite; P63241; -.
DR DMDM; 54037409; -.
DR DOSAC-COBS-2DPAGE; P63241; -.
DR OGP; P63241; -.
DR PaxDb; P63241; -.
DR PRIDE; P63241; -.
DR DNASU; 1984; -.
DR Ensembl; ENST00000336452; ENSP00000336702; ENSG00000132507.
DR Ensembl; ENST00000336458; ENSP00000336776; ENSG00000132507.
DR Ensembl; ENST00000416016; ENSP00000396073; ENSG00000132507.
DR Ensembl; ENST00000419711; ENSP00000390677; ENSG00000132507.
DR Ensembl; ENST00000571955; ENSP00000458269; ENSG00000132507.
DR Ensembl; ENST00000573542; ENSP00000459611; ENSG00000132507.
DR Ensembl; ENST00000576930; ENSP00000459196; ENSG00000132507.
DR GeneID; 1984; -.
DR KEGG; hsa:1984; -.
DR UCSC; uc002gft.3; human.
DR CTD; 1984; -.
DR GeneCards; GC17P007210; -.
DR HGNC; HGNC:3300; EIF5A.
DR HPA; CAB005042; -.
DR MIM; 600187; gene.
DR neXtProt; NX_P63241; -.
DR PharmGKB; PA27726; -.
DR eggNOG; COG0231; -.
DR HOVERGEN; HBG001104; -.
DR InParanoid; P63241; -.
DR KO; K03263; -.
DR OMA; IPDGDLG; -.
DR OrthoDB; EOG7KSXB7; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; EIF5A; human.
DR EvolutionaryTrace; P63241; -.
DR GeneWiki; EIF5A; -.
DR GenomeRNAi; 1984; -.
DR NextBio; 8037; -.
DR PMAP-CutDB; P63241; -.
DR PRO; PR:P63241; -.
DR ArrayExpress; P63241; -.
DR Bgee; P63241; -.
DR CleanEx; HS_EIF5A; -.
DR Genevestigator; P63241; -.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IEA:InterPro.
DR GO; GO:0003746; F:translation elongation factor activity; ISS:UniProtKB.
DR GO; GO:0017070; F:U6 snRNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0006406; P:mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:0008612; P:peptidyl-lysine modification to hypusine; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IGI:UniProtKB.
DR GO; GO:0045901; P:positive regulation of translational elongation; ISS:UniProtKB.
DR GO; GO:0045905; P:positive regulation of translational termination; IEA:InterPro.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006611; P:protein export from nucleus; IMP:UniProtKB.
DR GO; GO:0006452; P:translational frameshifting; IEA:InterPro.
DR Gene3D; 2.30.30.30; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR014722; Rib_L2_dom2.
DR InterPro; IPR019769; Trans_elong_IF5A_hypusine_site.
DR InterPro; IPR001884; Transl_elong_IF5A.
DR InterPro; IPR020189; Transl_elong_IF5A_C.
DR InterPro; IPR008991; Translation_prot_SH3-like.
DR PANTHER; PTHR11673; PTHR11673; 1.
DR Pfam; PF01287; eIF-5a; 1.
DR PIRSF; PIRSF003025; eIF5A; 1.
DR SUPFAM; SSF50104; SSF50104; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR TIGRFAMs; TIGR00037; eIF_5A; 1.
DR PROSITE; PS00302; IF5A_HYPUSINE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Elongation factor;
KW Endoplasmic reticulum; Hypusine; Membrane; mRNA transport;
KW Nuclear pore complex; Nucleus; Protein biosynthesis;
KW Protein transport; Reference proteome; RNA-binding; Translocation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 154 Eukaryotic translation initiation factor
FT 5A-1.
FT /FTId=PRO_0000142451.
FT REGION 20 90 DOHH-binding.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 47 47 N6-acetyllysine.
FT MOD_RES 50 50 Hypusine.
FT VAR_SEQ 1 2 MA -> MCGTGGTDSKTRRPPHRASFLKRLESKPLKMA
FT (in isoform 2).
FT /FTId=VSP_022020.
FT MUTAGEN 47 47 K->A,R: Abolishes acetylation.
FT MUTAGEN 47 47 K->D: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 49 49 G->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 50 50 K->A: Decreases significantly the
FT acetylation at position K-47 and causes
FT total inactivation of eIF5A in supporting
FT yeast growth.
FT MUTAGEN 50 50 K->I,D,R: Causes total inactivation of
FT eIF5A in supporting yeast growth.
FT MUTAGEN 52 52 G->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 55 55 K->A: Causes total inactivation of eIF5A
FT in supporting yeast growth.
FT MUTAGEN 81 81 V->G: Leads to temperature sensitivity
FT when expressed in yeast cells.
FT CONFLICT 36 36 R -> W (in Ref. 3; AAD14095).
FT CONFLICT 45 45 T -> A (in Ref. 3; AAD14095).
FT CONFLICT 85 85 K -> R (in Ref. 3; AAD14095).
FT CONFLICT 109 109 R -> P (in Ref. 3; AAD14095).
FT STRAND 17 21
FT HELIX 22 24
FT STRAND 29 33
FT STRAND 36 46
FT STRAND 55 62
FT TURN 63 65
FT STRAND 68 74
FT STRAND 77 82
FT STRAND 85 95
FT STRAND 98 102
FT HELIX 117 129
FT STRAND 134 140
FT STRAND 143 150
SQ SEQUENCE 154 AA; 16832 MW; 07EF043C7DEA3091 CRC64;
MADDLDFETG DAGASATFPM QCSALRKNGF VVLKGRPCKI VEMSTSKTGK HGHAKVHLVG
IDIFTGKKYE DICPSTHNMD VPNIKRNDFQ LIGIQDGYLS LLQDSGEVRE DLRLPEGDLG
KEIEQKYDCG EEILITVLSA MTEEAAVAIK AMAK
//
MIM
600187
*RECORD*
*FIELD* NO
600187
*FIELD* TI
*600187 EUKARYOTIC TRANSLATION INITIATION FACTOR 5A; EIF5A
;;EIF5A1
*FIELD* TX
CLONING
read more
The eukaryotic initiation factor 5A is an 18-kD protein composed of 154
amino acids. It contains a unique amino acid residue, hypusine, that is
formed posttranslationally via the transfer and hydroxylation of the
butylamino-group from the polyamine spermidine to a lys50 within the
EIF5A protein. Koettnitz et al. (1994) isolated and characterized the
human EIF5A pseudogene. Subsequently, Koettnitz et al. (1995) identified
a genomic clone encoding a functional EIF5A. The authors showed that
this sequence could successfully complement yeast carrying the HYP2
mutation (the homolog of EIF5A), whereas the pseudogenes could not.
GENE STRUCTURE
Koettnitz et al. (1995) found that the human EIF5A gene contains at
least 4 exons and spans at least 4.8 kb.
GENE FUNCTION
Saini et al. (2009) used molecular genetic and biochemical studies to
show that EIF5A promotes translation elongation. Depletion or
inactivation of EIF5A in the yeast S. cerevisiae resulted in the
accumulation of polysomes and an increase in ribosomal transit times.
Addition of recombinant EIF5A from yeast, but not a derivative lacking
hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover,
inactivation of EIF5A mimicked the effects of the EEF2 (130610)
inhibitor sordarin, indicating that EIF5A might function together with
EEF2 to promote ribosomal translocation. Because EIF5A is a structural
homolog of the bacterial protein EF-P, Saini et al. (2009) proposed that
EIF5A/EF-P is a universally conserved translation elongation factor.
To identify tumor suppressor genes in lymphoma (605027), Scuoppo et al.
(2012) screened a short hairpin RNA library targeting genes deleted in
human lymphomas and functionally confirmed those in a mouse lymphoma
model. Of the 9 tumor suppressors identified, 8 corresponded to genes
occurring in 3 physically linked 'clusters,' suggesting that the common
occurrence of large chromosomal deletions in human tumors reflects
selective pressure to attenuate multiple genes. Among the newly
identified tumor suppressors were adenosylmethionine decarboxylase-1
(AMD1; 180980) and eukaryotic translation initiation factor 5A (eIF5A),
2 genes associated with hypusine, a unique amino acid produced as a
product of polyamine metabolism through a highly conserved pathway.
Through a secondary screen surveying the impact of all polyamine enzymes
on tumorigenesis, Scuoppo et al. (2012) established the
polyamine-hypusine axis as a new tumor suppressor network regulating
apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and
eIF5A often occur together in human lymphomas, and cosuppression of both
genes promotes lymphomagenesis in mice. Thus, Scuoppo et al. (2012)
concluded that some tumor suppressor functions can be disabled through a
2-step process targeting different genes acting in the same pathway.
Translation elongation factor P (EF-P) is critical for virulence in
bacteria. EF-P is present in all bacteria and orthologous to archaeal
and eukaryotic initiation factor 5A (a/eIF5A). Ude et al. (2013)
demonstrated that EF-P is an elongation factor that enhances translation
of polyproline-containing proteins: in the absence of EF-P, ribosomes
stall at polyproline stretches, whereas the presence of EF-P alleviates
the translational stalling. Moreover, Ude et al. (2013) demonstrated the
physiologic relevance of EF-P to fine-tune the expression of the
polyproline-containing pH receptor CadC to levels necessary for an
appropriate stress response. Bacterial, archaeal, and eukaryotic cells
have hundreds to thousands of polyproline-containing proteins of diverse
function, suggesting that EF-P and a/elF5A are critical for copy number
adjustment of multiple pathways across all kingdoms of life.
Doerfel et al. (2013) showed that EF-P prevents the ribosome from
stalling during synthesis of proteins containing consecutive prolines,
such as PPG, PPP, or longer proline strings, in natural and engineered
model proteins. EF-P promotes peptide-bond formation and stabilizes the
peptidyl-transfer RNA in the catalytic center of the ribosome. EF-P is
posttranslationally modified by a hydroxylated beta-lysine attached to a
lysine residue. The modification enhances the catalytic proficiency of
the factor mainly by increasing its affinity to the ribosome. Doerfel et
al. (2013) proposed that EF-P and its eukaryotic homolog, elF5A, are
essential for the synthesis of a subset of proteins containing proline
stretches in all cells.
MAPPING
Steinkasserer et al. (1995) mapped the EIF5A gene to 17p13-p12 by
fluorescence in situ hybridization. Three pseudogenes were mapped to
10q23.3, 17q25, and 19q13.2.
*FIELD* RF
1. Doerfel, L. K.; Wohlgemuth, I.; Kothe, C.; Peske, F.; Urlaub, H.;
Rodnina, M. V.: EF-P is essential for rapid synthesis of proteins
containing consecutive proline residues. Science 339: 85-88, 2013.
2. Koettnitz, K.; Kappel, B.; Baumruker, T.; Hauber, J.; Bevec, D.
: The genomic structure encoding human initiation factor eIF-5A. Gene 144:
249-252, 1994.
3. Koettnitz, K.; Wohl, T.; Kappel, B.; Lottspeich, F.; Hauber, J.;
Bevec, D.: Identification of a new member of the human eIF-5A gene
family. Gene 159: 283-284, 1995.
4. Saini, P.; Eyler, D. E.; Green, R.; Dever, T. E.: Hypusine-containing
protein eIF5A promotes translation elongation. Nature 459: 118-121,
2009.
5. Scuoppo, C.; Miething, C.; Lindqvist, L.; Reyes, J.; Ruse, C.;
Appelmann, I.; Yoon, S.; Krasnitz, A.; Teruya-Feldstein, J.; Pappin,
D.; Pelletier, J.; Lowe, S. W.: A tumour suppressor network relying
on the polyamine-hypusine axis. Nature 487: 244-248, 2012.
6. Steinkasserer, A.; Jones, T.; Sheer, D.; Koettnitz, K.; Hauber,
J.; Bevec, D.: The eukaryotic cofactor for the human immunodeficiency
virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12-p13:
three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2. Genomics 25:
749-752, 1995.
7. Ude, S.; Lassak, J.; Starosta, A. L.; Kraxenberger, T.; Wilson,
D. N.; Jung, K.: Translation elongation factor EF-P alleviates ribosome
stalling at polyproline stretches. Science 339: 82-85, 2013.
*FIELD* CN
Ada Hamosh - updated: 1/29/2013
Ada Hamosh - updated: 8/29/2012
Ada Hamosh - updated: 5/19/2009
Alan F. Scott - updated: 9/17/1995
*FIELD* CD
Victor A. McKusick: 11/11/1994
*FIELD* ED
alopez: 01/29/2013
terry: 1/29/2013
alopez: 9/4/2012
terry: 8/29/2012
alopez: 6/4/2009
terry: 5/19/2009
mgross: 3/27/2001
joanna: 5/8/1998
terry: 3/20/1997
jamie: 1/17/1997
mark: 9/17/1995
mark: 4/19/1995
terry: 11/11/1994
*RECORD*
*FIELD* NO
600187
*FIELD* TI
*600187 EUKARYOTIC TRANSLATION INITIATION FACTOR 5A; EIF5A
;;EIF5A1
*FIELD* TX
CLONING
read more
The eukaryotic initiation factor 5A is an 18-kD protein composed of 154
amino acids. It contains a unique amino acid residue, hypusine, that is
formed posttranslationally via the transfer and hydroxylation of the
butylamino-group from the polyamine spermidine to a lys50 within the
EIF5A protein. Koettnitz et al. (1994) isolated and characterized the
human EIF5A pseudogene. Subsequently, Koettnitz et al. (1995) identified
a genomic clone encoding a functional EIF5A. The authors showed that
this sequence could successfully complement yeast carrying the HYP2
mutation (the homolog of EIF5A), whereas the pseudogenes could not.
GENE STRUCTURE
Koettnitz et al. (1995) found that the human EIF5A gene contains at
least 4 exons and spans at least 4.8 kb.
GENE FUNCTION
Saini et al. (2009) used molecular genetic and biochemical studies to
show that EIF5A promotes translation elongation. Depletion or
inactivation of EIF5A in the yeast S. cerevisiae resulted in the
accumulation of polysomes and an increase in ribosomal transit times.
Addition of recombinant EIF5A from yeast, but not a derivative lacking
hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover,
inactivation of EIF5A mimicked the effects of the EEF2 (130610)
inhibitor sordarin, indicating that EIF5A might function together with
EEF2 to promote ribosomal translocation. Because EIF5A is a structural
homolog of the bacterial protein EF-P, Saini et al. (2009) proposed that
EIF5A/EF-P is a universally conserved translation elongation factor.
To identify tumor suppressor genes in lymphoma (605027), Scuoppo et al.
(2012) screened a short hairpin RNA library targeting genes deleted in
human lymphomas and functionally confirmed those in a mouse lymphoma
model. Of the 9 tumor suppressors identified, 8 corresponded to genes
occurring in 3 physically linked 'clusters,' suggesting that the common
occurrence of large chromosomal deletions in human tumors reflects
selective pressure to attenuate multiple genes. Among the newly
identified tumor suppressors were adenosylmethionine decarboxylase-1
(AMD1; 180980) and eukaryotic translation initiation factor 5A (eIF5A),
2 genes associated with hypusine, a unique amino acid produced as a
product of polyamine metabolism through a highly conserved pathway.
Through a secondary screen surveying the impact of all polyamine enzymes
on tumorigenesis, Scuoppo et al. (2012) established the
polyamine-hypusine axis as a new tumor suppressor network regulating
apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and
eIF5A often occur together in human lymphomas, and cosuppression of both
genes promotes lymphomagenesis in mice. Thus, Scuoppo et al. (2012)
concluded that some tumor suppressor functions can be disabled through a
2-step process targeting different genes acting in the same pathway.
Translation elongation factor P (EF-P) is critical for virulence in
bacteria. EF-P is present in all bacteria and orthologous to archaeal
and eukaryotic initiation factor 5A (a/eIF5A). Ude et al. (2013)
demonstrated that EF-P is an elongation factor that enhances translation
of polyproline-containing proteins: in the absence of EF-P, ribosomes
stall at polyproline stretches, whereas the presence of EF-P alleviates
the translational stalling. Moreover, Ude et al. (2013) demonstrated the
physiologic relevance of EF-P to fine-tune the expression of the
polyproline-containing pH receptor CadC to levels necessary for an
appropriate stress response. Bacterial, archaeal, and eukaryotic cells
have hundreds to thousands of polyproline-containing proteins of diverse
function, suggesting that EF-P and a/elF5A are critical for copy number
adjustment of multiple pathways across all kingdoms of life.
Doerfel et al. (2013) showed that EF-P prevents the ribosome from
stalling during synthesis of proteins containing consecutive prolines,
such as PPG, PPP, or longer proline strings, in natural and engineered
model proteins. EF-P promotes peptide-bond formation and stabilizes the
peptidyl-transfer RNA in the catalytic center of the ribosome. EF-P is
posttranslationally modified by a hydroxylated beta-lysine attached to a
lysine residue. The modification enhances the catalytic proficiency of
the factor mainly by increasing its affinity to the ribosome. Doerfel et
al. (2013) proposed that EF-P and its eukaryotic homolog, elF5A, are
essential for the synthesis of a subset of proteins containing proline
stretches in all cells.
MAPPING
Steinkasserer et al. (1995) mapped the EIF5A gene to 17p13-p12 by
fluorescence in situ hybridization. Three pseudogenes were mapped to
10q23.3, 17q25, and 19q13.2.
*FIELD* RF
1. Doerfel, L. K.; Wohlgemuth, I.; Kothe, C.; Peske, F.; Urlaub, H.;
Rodnina, M. V.: EF-P is essential for rapid synthesis of proteins
containing consecutive proline residues. Science 339: 85-88, 2013.
2. Koettnitz, K.; Kappel, B.; Baumruker, T.; Hauber, J.; Bevec, D.
: The genomic structure encoding human initiation factor eIF-5A. Gene 144:
249-252, 1994.
3. Koettnitz, K.; Wohl, T.; Kappel, B.; Lottspeich, F.; Hauber, J.;
Bevec, D.: Identification of a new member of the human eIF-5A gene
family. Gene 159: 283-284, 1995.
4. Saini, P.; Eyler, D. E.; Green, R.; Dever, T. E.: Hypusine-containing
protein eIF5A promotes translation elongation. Nature 459: 118-121,
2009.
5. Scuoppo, C.; Miething, C.; Lindqvist, L.; Reyes, J.; Ruse, C.;
Appelmann, I.; Yoon, S.; Krasnitz, A.; Teruya-Feldstein, J.; Pappin,
D.; Pelletier, J.; Lowe, S. W.: A tumour suppressor network relying
on the polyamine-hypusine axis. Nature 487: 244-248, 2012.
6. Steinkasserer, A.; Jones, T.; Sheer, D.; Koettnitz, K.; Hauber,
J.; Bevec, D.: The eukaryotic cofactor for the human immunodeficiency
virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12-p13:
three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2. Genomics 25:
749-752, 1995.
7. Ude, S.; Lassak, J.; Starosta, A. L.; Kraxenberger, T.; Wilson,
D. N.; Jung, K.: Translation elongation factor EF-P alleviates ribosome
stalling at polyproline stretches. Science 339: 82-85, 2013.
*FIELD* CN
Ada Hamosh - updated: 1/29/2013
Ada Hamosh - updated: 8/29/2012
Ada Hamosh - updated: 5/19/2009
Alan F. Scott - updated: 9/17/1995
*FIELD* CD
Victor A. McKusick: 11/11/1994
*FIELD* ED
alopez: 01/29/2013
terry: 1/29/2013
alopez: 9/4/2012
terry: 8/29/2012
alopez: 6/4/2009
terry: 5/19/2009
mgross: 3/27/2001
joanna: 5/8/1998
terry: 3/20/1997
jamie: 1/17/1997
mark: 9/17/1995
mark: 4/19/1995
terry: 11/11/1994