IF5A1_HUMAN
ID IF5A1_HUMAN Reviewed; 154 AA.
AC P63241; A8K9A0; D3DTP2; P10159; Q16182; Q7L7L3; Q7Z4L1; Q9D0G2;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND HYPUSINE AT LYS-50.
RX PubMed=2492279; DOI=10.1016/s0021-9258(18)94226-2;
RA Smit-Mcbride Z., Dever T.E., Hershey J.W.B., Merrick W.C.;
RT "Sequence determination and cDNA cloning of eukaryotic initiation factor
RT 4D, the hypusine-containing protein.";
RL J. Biol. Chem. 264:1578-1583(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-154, FUNCTION,
RP INTERACTION 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., Wolff B.,
RA Aschauer H., Farrington G.K., Probst H., Bevec D., 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., 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 [7]
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 [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 project:
RT 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/bj3400273;
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 INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY 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; DOI=10.1016/s0021-9258(18)66899-1;
RA Park M.H., Liu T.-Y., Neece S.H., Swiggard W.J.;
RT "Eukaryotic initiation factor 4D. Purification from human red blood cells
RT and the sequence of amino acids around its single hypusine residue.";
RL J. Biol. Chem. 261:14515-14519(1986).
RN [12]
RP PROTEIN SEQUENCE OF 56-121, AND IDENTIFICATION BY 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 protein
RT 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 factor,
RT eIF-5A, in cultured cells.";
RL Exp. Cell Res. 225:348-356(1996).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, AND SUBCELLULAR LOCATION.
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 by
RT 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 for
RT aberrant proliferation in intraepithelial neoplasia of the 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-dependent
RT 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., Boone A.N.,
RA Culp-Stewart S., Thompson J.E.;
RT "Role of eIF5A in TNF-alpha-mediated apoptosis of lamina cribrosa 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 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 to the
RT 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 colon
RT cancer cells and associates with the nucleus in response to tumour necrosis
RT 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 AND
RP 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 of
RT 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., 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 [28]
RP ACETYLATION, AND DEACETYLATION BY SIRT2.
RX PubMed=22771473; DOI=10.1016/j.febslet.2012.06.042;
RA Ishfaq M., Maeta K., Maeda S., Natsume T., Ito A., Yoshida M.;
RT "Acetylation regulates subcellular localization of eukaryotic translation
RT initiation factor 5A (eIF5A).";
RL FEBS Lett. 586:3236-3241(2012).
RN [29]
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 [30]
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 [31]
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).
RN [32] {ECO:0007744|PDB:5DLQ}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 15-154 IN COMPLEX WITH XPO4 AND
RP RAN, SUBCELLULAR LOCATION, AND HYPUSINE AT LYS-50.
RX PubMed=27306458; DOI=10.1038/ncomms11952;
RA Aksu M., Trakhanov S., Goerlich D.;
RT "Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-
RT containing translation factor eIF5A.";
RL Nat. Commun. 7:11952-11952(2016).
RN [33]
RP INVOLVEMENT IN FABAS, VARIANTS FABAS ASN-48; ARG-106; 109-ARG--LYS-154 DEL;
RP GLY-109; SER-115 AND LYS-122, CHARACTERIZATION OF VARIANTS FABAS ASN-48;
RP ARG-106 AND ARG-106, AND FUNCTION.
RX PubMed=33547280; DOI=10.1038/s41467-021-21053-2;
RA Faundes V., Jennings M.D., Crilly S., Legraie S., Withers S.E.,
RA Cuvertino S., Davies S.J., Douglas A.G.L., Fry A.E., Harrison V., Amiel J.,
RA Lehalle D., Newman W.G., Newkirk P., Ranells J., Splitt M., Cross L.A.,
RA Saunders C.J., Sullivan B.R., Granadillo J.L., Gordon C.T., Kasher P.R.,
RA Pavitt G.D., Banka S.;
RT "Impaired eIF5A function causes a Mendelian disorder that is partially
RT rescued in model systems by spermidine.";
RL Nat. Commun. 12:833-833(2021).
CC -!- FUNCTION: mRNA-binding protein involved in translation elongation
CC (PubMed:16987817, PubMed:17187778, PubMed:33547280). Has an important
CC function at the level of mRNA turnover, probably acting downstream of
CC decapping (PubMed:16987817, PubMed:17187778, PubMed:33547280). Critical
CC for the efficient synthesis of peptide bonds between consecutive
CC proline residues (PubMed:16987817, PubMed:17187778, PubMed:33547280).
CC Can resolve ribosomal stalling caused by consecutive prolines during
CC translation (PubMed:16987817, PubMed:17187778, PubMed:33547280).
CC Involved in actin dynamics and cell cycle progression, mRNA decay and
CC probably in a pathway involved in stress response and maintenance of
CC cell wall integrity (PubMed:16987817, PubMed:17187778,
CC PubMed:33547280). With syntenin SDCBP, functions as a regulator of
CC p53/TP53 and p53/TP53-dependent apoptosis (PubMed:15371445). Regulates
CC also TNF-alpha-mediated apoptosis (PubMed:15452064). Mediates effects
CC of polyamines on neuronal process extension and survival
CC (PubMed:17360499). May play an important role in brain development and
CC function, and in skeletal muscle stem cell differentiation (By
CC similarity). Also described as a cellular cofactor of human T-cell
CC leukemia virus type I (HTLV-1) Rex protein and of human
CC immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA
CC export of retroviral transcripts (PubMed:8253832).
CC {ECO:0000250|UniProtKB:Q3T1J1, ECO:0000269|PubMed:15371445,
CC ECO:0000269|PubMed:15452064, ECO:0000269|PubMed:16987817,
CC ECO:0000269|PubMed:17187778, ECO:0000269|PubMed:17360499,
CC ECO:0000269|PubMed:33547280, ECO:0000269|PubMed:8253832}.
CC -!- SUBUNIT: Interacts with DHPS, with SDCBP and DOHH.
CC {ECO:0000269|PubMed:10229683, ECO:0000269|PubMed:15371445,
CC ECO:0000269|PubMed:17213197}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 protein Rev.
CC {ECO:0000269|PubMed:8253832}.
CC -!- INTERACTION:
CC P63241; O43186: CRX; NbExp=3; IntAct=EBI-373150, EBI-748171;
CC P63241; P49366: DHPS; NbExp=6; IntAct=EBI-373150, EBI-741925;
CC P63241; O15499: GSC2; NbExp=3; IntAct=EBI-373150, EBI-19954058;
CC P63241; P52954: LBX1; NbExp=3; IntAct=EBI-373150, EBI-20141748;
CC P63241; A8MW99: MEI4; NbExp=3; IntAct=EBI-373150, EBI-19944212;
CC P63241; P50222: MEOX2; NbExp=3; IntAct=EBI-373150, EBI-748397;
CC P63241; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-373150, EBI-16439278;
CC P63241; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-373150, EBI-79165;
CC P63241; Q04864: REL; NbExp=3; IntAct=EBI-373150, EBI-307352;
CC P63241; Q04864-2: REL; NbExp=3; IntAct=EBI-373150, EBI-10829018;
CC P63241; O00560: SDCBP; NbExp=3; IntAct=EBI-373150, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10944119,
CC ECO:0000269|PubMed:17187778, ECO:0000269|PubMed:19379712,
CC ECO:0000269|PubMed:27306458, ECO:0000269|PubMed:8660923}. Nucleus
CC {ECO:0000269|PubMed:10944119, ECO:0000269|PubMed:17187778,
CC ECO:0000269|PubMed:19379712, ECO:0000269|PubMed:27306458,
CC ECO:0000269|PubMed:8253832}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8660923}; Peripheral membrane protein
CC {ECO:0000269|PubMed:8660923}; Cytoplasmic side
CC {ECO:0000269|PubMed:8660923}. Note=Hypusine modification promotes the
CC nuclear export and cytoplasmic localization and there was a dynamic
CC shift in the localization from predominantly cytoplasmic to primarily
CC nuclear under apoptotic inducing conditions (PubMed:19379712,
CC PubMed:27306458). Nuclear export of hypusinated protein is mediated by
CC XPO4 (PubMed:10944119, PubMed:27306458). {ECO:0000269|PubMed:10944119,
CC ECO:0000269|PubMed:19379712, ECO:0000269|PubMed:27306458}.
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 and
CC several cancer cell lines (at protein level).
CC {ECO:0000269|PubMed:16519677}.
CC -!- PTM: Acetylated by PCAF/KAT2B, regulating its subcellular localization
CC (PubMed:19379712, PubMed:22771473). Deacetylated by SIRT2
CC (PubMed:22771473). {ECO:0000269|PubMed:19379712,
CC ECO:0000269|PubMed:22771473}.
CC -!- PTM: Lys-50 undergoes hypusination, a unique post-translational
CC modification that consists in the addition of a butylamino group from
CC spermidine to lysine side chain, leading to the formation of the
CC unusual amino acid hypusine. eIF-5As are the only known proteins to
CC undergo this modification, which is essential for their function.
CC {ECO:0000269|PubMed:10229683, ECO:0000269|PubMed:17213197,
CC ECO:0000269|PubMed:18067580, ECO:0000269|PubMed:2492279,
CC ECO:0000269|PubMed:27306458, ECO:0000269|PubMed:3095320}.
CC -!- DISEASE: Faundes-Banka syndrome (FABAS) [MIM:619376]: An autosomal
CC dominant disorder characterized by variable combinations of
CC developmental delay, microcephaly, micrognathia and dysmorphic
CC features. {ECO:0000269|PubMed:33547280}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- BIOTECHNOLOGY: Mature eIF5A-1 may be used as an in situ diagnostic
CC marker for aberrant proliferation in intraepithelial neoplasia of the
CC vulva. {ECO:0000269|PubMed:15262146}.
CC -!- SIMILARITY: Belongs to the eIF-5A family. {ECO:0000305}.
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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 CCDS; CCDS11099.1; -. [P63241-1]
DR CCDS; CCDS45601.1; -. [P63241-2]
DR PIR; B31486; FIHUA.
DR RefSeq; NP_001137232.1; NM_001143760.1. [P63241-2]
DR RefSeq; NP_001137233.1; NM_001143761.1. [P63241-1]
DR RefSeq; NP_001137234.1; NM_001143762.1. [P63241-1]
DR RefSeq; NP_001961.1; NM_001970.4. [P63241-1]
DR RefSeq; XP_005256566.1; XM_005256509.2.
DR PDB; 3CPF; X-ray; 2.50 A; A/B=15-151.
DR PDB; 5DLQ; X-ray; 3.20 A; E/F=15-154.
DR PDBsum; 3CPF; -.
DR PDBsum; 5DLQ; -.
DR AlphaFoldDB; P63241; -.
DR BMRB; P63241; -.
DR SMR; P63241; -.
DR BioGRID; 108299; 157.
DR IntAct; P63241; 74.
DR MINT; P63241; -.
DR STRING; 9606.ENSP00000336702; -.
DR ChEMBL; CHEMBL4105862; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; P63241; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P63241; -.
DR MetOSite; P63241; -.
DR PhosphoSitePlus; P63241; -.
DR SwissPalm; P63241; -.
DR BioMuta; EIF5A; -.
DR DMDM; 54037409; -.
DR DOSAC-COBS-2DPAGE; P63241; -.
DR OGP; P63241; -.
DR EPD; P63241; -.
DR jPOST; P63241; -.
DR MassIVE; P63241; -.
DR MaxQB; P63241; -.
DR PaxDb; P63241; -.
DR PeptideAtlas; P63241; -.
DR PRIDE; P63241; -.
DR ProteomicsDB; 57510; -. [P63241-1]
DR ProteomicsDB; 57511; -. [P63241-2]
DR TopDownProteomics; P63241-1; -. [P63241-1]
DR TopDownProteomics; P63241-2; -. [P63241-2]
DR Antibodypedia; 24021; 336 antibodies from 39 providers.
DR DNASU; 1984; -.
DR Ensembl; ENST00000336452.11; ENSP00000336702.7; ENSG00000132507.18. [P63241-2]
DR Ensembl; ENST00000336458.13; ENSP00000336776.8; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000416016.2; ENSP00000396073.2; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000419711.6; ENSP00000390677.2; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000571955.5; ENSP00000458269.1; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000573542.5; ENSP00000459611.1; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000576930.5; ENSP00000459196.1; ENSG00000132507.18. [P63241-1]
DR Ensembl; ENST00000672250.1; ENSP00000500717.1; ENSG00000288145.1. [P63241-1]
DR Ensembl; ENST00000672755.1; ENSP00000500847.1; ENSG00000288145.1. [P63241-1]
DR Ensembl; ENST00000672765.1; ENSP00000500669.1; ENSG00000288145.1. [P63241-2]
DR Ensembl; ENST00000673099.1; ENSP00000499855.1; ENSG00000288145.1. [P63241-1]
DR Ensembl; ENST00000673210.1; ENSP00000500414.1; ENSG00000288145.1. [P63241-1]
DR Ensembl; ENST00000673259.1; ENSP00000500624.1; ENSG00000288145.1. [P63241-1]
DR Ensembl; ENST00000673304.1; ENSP00000499995.1; ENSG00000288145.1. [P63241-1]
DR GeneID; 1984; -.
DR KEGG; hsa:1984; -.
DR MANE-Select; ENST00000336458.13; ENSP00000336776.8; NM_001970.5; NP_001961.1.
DR UCSC; uc002gfr.3; human. [P63241-1]
DR CTD; 1984; -.
DR DisGeNET; 1984; -.
DR GeneCards; EIF5A; -.
DR HGNC; HGNC:3300; EIF5A.
DR HPA; ENSG00000132507; Low tissue specificity.
DR MIM; 600187; gene.
DR MIM; 619376; phenotype.
DR neXtProt; NX_P63241; -.
DR OpenTargets; ENSG00000132507; -.
DR PharmGKB; PA27726; -.
DR VEuPathDB; HostDB:ENSG00000132507; -.
DR eggNOG; KOG3271; Eukaryota.
DR GeneTree; ENSGT00390000003738; -.
DR InParanoid; P63241; -.
DR OMA; VFRNEYQ; -.
DR OrthoDB; 1370513at2759; -.
DR PhylomeDB; P63241; -.
DR TreeFam; TF101534; -.
DR PathwayCommons; P63241; -.
DR Reactome; R-HSA-204626; Hypusine synthesis from eIF5A-lysine.
DR SignaLink; P63241; -.
DR SIGNOR; P63241; -.
DR BioGRID-ORCS; 1984; 680 hits in 1052 CRISPR screens.
DR ChiTaRS; EIF5A; human.
DR EvolutionaryTrace; P63241; -.
DR GeneWiki; EIF5A; -.
DR GenomeRNAi; 1984; -.
DR Pharos; P63241; Tbio.
DR PRO; PR:P63241; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P63241; protein.
DR Bgee; ENSG00000132507; Expressed in lower esophagus mucosa and 96 other tissues.
DR ExpressionAtlas; P63241; baseline and differential.
DR Genevisible; P63241; HS.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005643; C:nuclear pore; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0003746; F:translation elongation factor activity; ISS:UniProtKB.
DR GO; GO:0017070; F:U6 snRNA binding; IDA:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:1902255; P:positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP: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:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR DisProt; DP02594; -.
DR Gene3D; 2.30.30.30; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR001884; IF5A-like.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR014722; Rib_L2_dom2.
DR InterPro; IPR019769; Trans_elong_IF5A_hypusine_site.
DR InterPro; IPR020189; Transl_elong_IF5A_C.
DR InterPro; IPR008991; Translation_prot_SH3-like_sf.
DR PANTHER; PTHR11673; PTHR11673; 1.
DR Pfam; PF01287; eIF-5a; 1.
DR PIRSF; PIRSF003025; eIF5A; 1.
DR SMART; SM01376; eIF-5a; 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; Cytoplasm;
KW Direct protein sequencing; Disease variant; Elongation factor;
KW Endoplasmic reticulum; Hypusine; Membrane; Nucleus; Protein biosynthesis;
KW Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:10229683, ECO:0000269|Ref.10"
FT CHAIN 2..154
FT /note="Eukaryotic translation initiation factor 5A-1"
FT /id="PRO_0000142451"
FT REGION 20..90
FT /note="Interaction with DOHH"
FT /evidence="ECO:0000269|PubMed:17213197"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.10"
FT MOD_RES 47
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:19379712"
FT MOD_RES 50
FT /note="Hypusine"
FT /evidence="ECO:0000269|PubMed:27306458,
FT ECO:0000269|PubMed:3095320"
FT MOD_RES 121
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63242"
FT VAR_SEQ 1..2
FT /note="MA -> MCGTGGTDSKTRRPPHRASFLKRLESKPLKMA (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_022020"
FT VARIANT 48
FT /note="T -> N (in FABAS; in yeast, exhibits reduced
FT ribosome binding, reduced levels of hypusination and
FT transfected cells show impaired synthesis of proteins
FT containing poly-proline tracts)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085973"
FT VARIANT 106
FT /note="G -> R (in FABAS; in yeast, exhibits reduced
FT ribosome binding and cells show impaired synthesis of
FT proteins containing poly-proline tracts)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085974"
FT VARIANT 109..154
FT /note="Missing (in FABAS)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085975"
FT VARIANT 109
FT /note="R -> G (in FABAS)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085976"
FT VARIANT 115
FT /note="P -> S (in FABAS)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085977"
FT VARIANT 122
FT /note="E -> K (in FABAS; in yeast, exhibits reduced
FT ribosome binding and cells show impaired synthesis of
FT proteins containing poly-proline tracts)"
FT /evidence="ECO:0000269|PubMed:33547280"
FT /id="VAR_085978"
FT MUTAGEN 47
FT /note="K->A,R: Abolishes acetylation."
FT /evidence="ECO:0000269|PubMed:18067580,
FT ECO:0000269|PubMed:19379712"
FT MUTAGEN 47
FT /note="K->D: Causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:18067580,
FT ECO:0000269|PubMed:19379712"
FT MUTAGEN 49
FT /note="G->A: Causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:18067580"
FT MUTAGEN 50
FT /note="K->A: Decreases significantly the acetylation at
FT position K-47 and causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:17187778,
FT ECO:0000269|PubMed:18067580, ECO:0000269|PubMed:19379712"
FT MUTAGEN 50
FT /note="K->I,D,R: Causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:17187778,
FT ECO:0000269|PubMed:18067580, ECO:0000269|PubMed:19379712"
FT MUTAGEN 52
FT /note="G->A: Causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:18067580"
FT MUTAGEN 55
FT /note="K->A: Causes total inactivation of eIF5A in
FT supporting yeast growth."
FT /evidence="ECO:0000269|PubMed:18067580"
FT MUTAGEN 81
FT /note="V->G: Leads to temperature sensitivity when
FT expressed in yeast cells."
FT /evidence="ECO:0000269|PubMed:16987817"
FT CONFLICT 36
FT /note="R -> W (in Ref. 3; AAD14095)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="T -> A (in Ref. 3; AAD14095)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="K -> R (in Ref. 3; AAD14095)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="R -> P (in Ref. 3; AAD14095)"
FT /evidence="ECO:0000305"
FT STRAND 17..21
FT /evidence="ECO:0007829|PDB:3CPF"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 36..46
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:3CPF"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 85..95
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:3CPF"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:3CPF"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:3CPF"
SQ SEQUENCE 154 AA; 16832 MW; 07EF043C7DEA3091 CRC64;
MADDLDFETG DAGASATFPM QCSALRKNGF VVLKGRPCKI VEMSTSKTGK HGHAKVHLVG
IDIFTGKKYE DICPSTHNMD VPNIKRNDFQ LIGIQDGYLS LLQDSGEVRE DLRLPEGDLG
KEIEQKYDCG EEILITVLSA MTEEAAVAIK AMAK
