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 27-MAR-2024, entry version 187. DE RecName: Full=Eukaryotic translation initiation factor 5A-1 {ECO:0000305}; 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 {ECO:0000312|HGNC:HGNC:3300}; 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 (MICROBIAL RP INFECTION), 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 RIBOSOME-BINDING. RX PubMed=27115996; DOI=10.1371/journal.pone.0154205; RA Rossi D., Barbosa N.M., Galvao F.C., Boldrin P.E., Hershey J.W., RA Zanelli C.F., Fraser C.S., Valentini S.R.; RT "Evidence for a negative cooperativity between eIF5A and eEF2 on binding to RT the ribosome."; RL PLoS ONE 11:e0154205-e0154205(2016). RN [32] RP FUNCTION. RX PubMed=29712776; DOI=10.15252/embr.201846072; RA Lubas M., Harder L.M., Kumsta C., Tiessen I., Hansen M., Andersen J.S., RA Lund A.H., Frankel L.B.; RT "eIF5A is required for autophagy by mediating ATG3 translation."; RL EMBO Rep. 19:0-0(2018). RN [33] 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 [34] {ECO:0007744|PDB:3CPF} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 15-151. RX PubMed=19280598; DOI=10.1002/prot.22378; RA Tong Y., Park I., Hong B.S., Nedyalkova L., Tempel W., Park H.W.; RT "Crystal structure of human eIF5A1: insight into functional similarity of RT human eIF5A1 and eIF5A2."; RL Proteins 75:1040-1045(2009). RN [35] {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 [36] 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: Translation factor that promotes translation elongation and CC termination, particularly upon ribosome stalling at specific amino acid CC sequence contexts (PubMed:33547280). Binds between the exit (E) and CC peptidyl (P) site of the ribosome and promotes rescue of stalled CC ribosome: specifically required for efficient translation of CC polyproline-containing peptides as well as other motifs that stall the CC ribosome (By similarity). Acts as a ribosome quality control (RQC) CC cofactor by joining the RQC complex to facilitate peptidyl transfer CC during CAT tailing step (By similarity). Also involved in actin CC dynamics and cell cycle progression, mRNA decay and probably in a CC pathway involved in stress response and maintenance of cell wall CC integrity (PubMed:16987817). With syntenin SDCBP, functions as a CC regulator of p53/TP53 and p53/TP53-dependent apoptosis CC (PubMed:15371445). Regulates also TNF-alpha-mediated apoptosis CC (PubMed:15452064, PubMed:17187778). Mediates effects of polyamines on CC neuronal process extension and survival (PubMed:17360499). Is required CC for autophagy by assisting the ribosome in translating the ATG3 protein CC at a specific amino acid sequence, the 'ASP-ASP-Gly' motif, leading to CC the increase of the efficiency of ATG3 translation and facilitation of CC LC3B lipidation and autophagosome formation (PubMed:29712776). CC {ECO:0000250|UniProtKB:P23301, 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:29712776, ECO:0000269|PubMed:33547280}. CC -!- FUNCTION: (Microbial infection) 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. {ECO:0000269|PubMed:8253832}. CC -!- SUBUNIT: Binds to 80S ribosomes (PubMed:27115996). Actively translating CC ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) CC and EEF2/eEF2 (PubMed:27115996). Interacts with DAPL1; interaction CC takes place at the polypeptide exit tunnel of hibernating ribosomes and CC prevents translation (By similarity). Interacts with DHPS CC (PubMed:10229683). Interacts with SDCBP (PubMed:15371445). Interacts CC with DOHH (PubMed:17213197). {ECO:0000250|UniProtKB:Q6NX89, CC ECO:0000269|PubMed:10229683, ECO:0000269|PubMed:15371445, CC ECO:0000269|PubMed:17213197, ECO:0000269|PubMed:27115996}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8A0E; EM; 2.80 A; E=1-154. DR PDBsum; 3CPF; -. DR PDBsum; 5DLQ; -. DR PDBsum; 8A0E; -. DR AlphaFoldDB; P63241; -. DR BMRB; P63241; -. DR EMDB; EMD-29757; -. DR EMDB; EMD-29758; -. DR EMDB; EMD-29760; -. DR SMR; P63241; -. DR BioGRID; 108299; 223. DR IntAct; P63241; 78. DR MINT; P63241; -. DR STRING; 9606.ENSP00000336702; -. DR ChEMBL; CHEMBL4105862; -. DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family. DR GlyCosmos; P63241; 1 site, 1 glycan. 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; 9606-ENSP00000336702; -. DR PeptideAtlas; P63241; -. DR PRIDE; P63241; -. DR ProteomicsDB; 57510; -. [P63241-1] DR ProteomicsDB; 57511; -. [P63241-2] DR Pumba; P63241; -. DR TopDownProteomics; P63241-1; -. [P63241-1] DR TopDownProteomics; P63241-2; -. [P63241-2] DR Antibodypedia; 24021; 367 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 AGR; HGNC:3300; -. DR CTD; 1984; -. DR DisGeNET; 1984; -. DR GeneCards; EIF5A; -. DR HGNC; HGNC:3300; EIF5A. DR HPA; ENSG00000132507; Low tissue specificity. DR MalaCards; EIF5A; -. DR MIM; 600187; gene. DR MIM; 619376; phenotype. DR neXtProt; NX_P63241; -. DR OpenTargets; ENSG00000132507; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA27726; -. DR VEuPathDB; HostDB:ENSG00000132507; -. DR eggNOG; KOG3271; Eukaryota. DR GeneTree; ENSGT00390000003738; -. DR InParanoid; P63241; -. DR OMA; KDDVRMP; -. DR OrthoDB; 5472148at2759; -. 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; 708 hits in 1138 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 98 other cell types or tissues. DR ExpressionAtlas; P63241; baseline and differential. 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: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:0006414; P:translational elongation; IMP:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR CDD; cd04468; S1_eIF5A; 1. DR DisProt; DP02594; -. DR Gene3D; 2.30.30.30; -; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR InterPro; IPR001884; IF5A-like. DR InterPro; IPR048670; IF5A-like_N. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR014722; Rib_uL2_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 NCBIfam; TIGR00037; eIF_5A; 1. DR PANTHER; PTHR11673:SF34; EUKARYOTIC TRANSLATION INITIATION FACTOR 5A-1; 1. DR PANTHER; PTHR11673; TRANSLATION INITIATION FACTOR 5A FAMILY MEMBER; 1. DR Pfam; PF01287; eIF-5a; 1. DR Pfam; PF21485; IF5A-like_N; 1. DR PIRSF; PIRSF003025; eIF5A; 1. DR SMART; SM01376; eIF-5a; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR SUPFAM; SSF50104; Translation proteins SH3-like domain; 1. DR PROSITE; PS00302; IF5A_HYPUSINE; 1. DR Genevisible; P63241; HS. 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 //