ID LEPA_ECOLI Reviewed; 599 AA. AC P60785; P07682; P76590; Q2MAG1; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 1. DT 10-JUN-2026, entry version 168. DE RecName: Full=Elongation factor 4 {ECO:0000255|HAMAP-Rule:MF_00071}; DE Short=EF-4 {ECO:0000255|HAMAP-Rule:MF_00071}; DE EC=3.6.5.n1 {ECO:0000255|HAMAP-Rule:MF_00071}; DE AltName: Full=Ribosomal back-translocase LepA {ECO:0000255|HAMAP-Rule:MF_00071}; GN Name=lepA {ECO:0000255|HAMAP-Rule:MF_00071}; GN OrderedLocusNames=b2569, JW2553; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=K12; RX PubMed=2987248; DOI=10.1016/s0021-9258(17)39594-7; RA March P.E., Inouye M.; RT "Characterization of the lep operon of Escherichia coli. Identification of RT the promoter and the gene upstream of the signal peptidase I gene."; RL J. Biol. Chem. 260:7206-7213(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=K12; RA Nashimoto H., Saito N.; RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [5] RP SIMILARITY TO GTP-BINDING PROTEINS, AND SUBCELLULAR LOCATION. RX PubMed=2999765; DOI=10.1073/pnas.82.22.7500; RA March P.E., Inouye M.; RT "GTP-binding membrane protein of Escherichia coli with sequence homology to RT initiation factor 2 and elongation factors Tu and G."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7500-7504(1985). RN [6] RP SIMILARITY TO GTP-BINDING PROTEINS. RX PubMed=2826164; DOI=10.1111/j.1432-1033.1987.tb13671.x; RA Kushiro A., Shimizu M., Tomita K.; RT "Molecular cloning and sequence determination of the tuf gene coding for RT the elongation factor Tu of Thermus thermophilus HB8."; RL Eur. J. Biochem. 170:93-98(1987). RN [7] RP FUNCTION. RX PubMed=17110332; DOI=10.1016/j.cell.2006.09.037; RA Qin Y., Polacek N., Vesper O., Staub E., Einfeldt E., Wilson D.N., RA Nierhaus K.H.; RT "The highly conserved LepA is a ribosomal elongation factor that back- RT translocates the ribosome."; RL Cell 127:721-733(2006). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20045415; DOI=10.1016/j.jmb.2009.12.043; RA Liu H., Pan D., Pech M., Cooperman B.S.; RT "Interrupted catalysis: the EF4 (LepA) effect on back-translocation."; RL J. Mol. Biol. 396:1043-1052(2010). RN [9] RP STRUCTURE BY NMR OF 1-545. RX PubMed=19172743; DOI=10.1038/nsmb.1469; RA Connell S.R., Topf M., Qin Y., Wilson D.N., Mielke T., Fucini P., RA Nierhaus K.H., Spahn C.M.; RT "A new tRNA intermediate revealed on the ribosome during EF4-mediated back- RT translocation."; RL Nat. Struct. Mol. Biol. 15:910-915(2008). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). RX PubMed=18362332; DOI=10.1073/pnas.0801308105; RA Evans R.N., Blaha G., Bailey S., Steitz T.A.; RT "The structure of LepA, the ribosomal back translocase."; RL Proc. Natl. Acad. Sci. U.S.A. 105:4673-4678(2008). CC -!- FUNCTION: Required for accurate and efficient protein synthesis under CC certain stress conditions. May act as a fidelity factor of the CC translation reaction, by catalyzing a one-codon backward translocation CC of tRNAs on improperly translocated ribosomes. Back-translocation CC proceeds from a post-translocation (POST) complex to a pre- CC translocation (PRE) complex, thus giving elongation factor G a second CC chance to translocate the tRNAs correctly. Binds to ribosomes in a GTP- CC dependent manner. {ECO:0000255|HAMAP-Rule:MF_00071, CC ECO:0000269|PubMed:17110332, ECO:0000269|PubMed:20045415}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.n1; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00071, CC ECO:0000269|PubMed:20045415}; CC -!- INTERACTION: CC P60785; P60785: lepA; NbExp=2; IntAct=EBI-544544, EBI-544544; CC P60785; P64423: zntB; NbExp=4; IntAct=EBI-544544, EBI-553267; CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:2999765}; CC Peripheral membrane protein {ECO:0000305|PubMed:2999765}; Cytoplasmic CC side {ECO:0000305|PubMed:2999765}. CC -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase CC superfamily. Classic translation factor GTPase family. LepA subfamily. CC {ECO:0000255|HAMAP-Rule:MF_00071}. 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; K00426; AAA24063.1; -; Genomic_DNA. DR EMBL; D64044; BAA10916.1; -; Genomic_DNA. DR EMBL; U00096; AAC75622.1; -; Genomic_DNA. DR EMBL; AP009048; BAE76745.1; -; Genomic_DNA. DR PIR; H65034; BVECLA. DR RefSeq; NP_417064.1; NC_000913.3. DR RefSeq; WP_000790168.1; NZ_CP009789.1. DR PDB; 3CB4; X-ray; 2.80 A; A/B/C/D/E/F=1-599. DR PDB; 3DEG; EM; -; C=1-545. DR PDB; 3JCD; EM; 3.70 A; x=1-599. DR PDB; 3JCE; EM; 3.20 A; x=1-599. DR AlphaFoldDB; P60785; -. DR SMR; P60785; -. DR BioGRID; 4260596; 261. DR BioGRID; 851389; 3. DR DIP; DIP-29868N; -. DR FunCoup; P60785; 893. DR IntAct; P60785; 62. DR STRING; 511145.b2569; -. DR jPOST; P60785; -. DR PaxDb; 511145-b2569; -. DR EnsemblBacteria; AAC75622; AAC75622; b2569. DR GeneID; 93774522; -. DR GeneID; 947051; -. DR KEGG; ecj:JW2553; -. DR KEGG; eco:b2569; -. DR KEGG; ecoc:C3026_14230; -. DR PATRIC; fig|1411691.4.peg.4165; -. DR EchoBASE; EB0524; -. DR eggNOG; COG0481; Bacteria. DR HOGENOM; CLU_009995_3_3_6; -. DR InParanoid; P60785; -. DR OMA; QVKCDEN; -. DR OrthoDB; 9804431at2; -. DR PhylomeDB; P60785; -. DR BioCyc; EcoCyc:EG10529-MONOMER; -. DR BioCyc; MetaCyc:EG10529-MONOMER; -. DR BRENDA; 3.6.5.3; 2026. DR EvolutionaryTrace; P60785; -. DR PRO; PR:P60785; -. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0005829; C:cytosol; IDA:EcoCyc. DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule. DR GO; GO:0003924; F:GTPase activity; IDA:EcoCyc. DR GO; GO:0097216; F:guanosine tetraphosphate binding; IDA:EcoCyc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:EcoCyc. DR GO; GO:0043024; F:ribosomal small subunit binding; IDA:EcoCyc. DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central. DR GO; GO:0003746; F:translation elongation factor activity; IEA:UniProtKB-UniRule. DR GO; GO:0045727; P:positive regulation of translation; IBA:GO_Central. DR GO; GO:0009409; P:response to cold; IMP:EcoCyc. DR GO; GO:0009268; P:response to pH; IMP:EcoCyc. DR GO; GO:0009651; P:response to salt stress; IMP:EcoCyc. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IMP:EcoCyc. DR CDD; cd03699; EF4_II; 1. DR CDD; cd16260; EF4_III; 1. DR CDD; cd01890; LepA; 1. DR CDD; cd03709; lepA_C; 1. DR FunFam; 3.30.70.240:FF:000005; Elongation factor 4; 1. DR FunFam; 3.40.50.300:FF:000078; Elongation factor 4; 1. DR FunFam; 2.40.30.10:FF:000015; Translation factor GUF1, mitochondrial; 1. DR FunFam; 3.30.70.2570:FF:000001; Translation factor GUF1, mitochondrial; 1. DR FunFam; 3.30.70.870:FF:000004; Translation factor GUF1, mitochondrial; 1. DR Gene3D; 3.30.70.240; -; 1. DR Gene3D; 3.30.70.2570; Elongation factor 4, C-terminal domain; 1. DR Gene3D; 3.30.70.870; Elongation Factor G (Translational Gtpase), domain 3; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 2.40.30.10; Translation factors; 1. DR HAMAP; MF_00071; LepA; 1. DR InterPro; IPR006297; EF-4. DR InterPro; IPR035647; EFG_III/V. DR InterPro; IPR000640; EFG_V-like. DR InterPro; IPR004161; EFTu-like_2. DR InterPro; IPR031157; G_TR_CS. DR InterPro; IPR038363; LepA_C_sf. DR InterPro; IPR013842; LepA_CTD. DR InterPro; IPR035654; LepA_IV. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR000795; T_Tr_GTP-bd_dom. DR NCBIfam; TIGR01393; lepA; 1. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR43512:SF4; TRANSLATION FACTOR GUF1 HOMOLOG, CHLOROPLASTIC; 1. DR PANTHER; PTHR43512; TRANSLATION FACTOR GUF1-RELATED; 1. DR Pfam; PF00679; EFG_C; 1. DR Pfam; PF00009; GTP_EFTU; 1. DR Pfam; PF03144; GTP_EFTU_D2; 1. DR Pfam; PF06421; LepA_C; 1. DR PRINTS; PR00315; ELONGATNFCT. DR SUPFAM; SSF54980; EF-G C-terminal domain-like; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00301; G_TR_1; 1. DR PROSITE; PS51722; G_TR_2; 1. DR PDBsum; 3CB4; -. DR PDBsum; 3DEG; -. DR PDBsum; 3JCD; -. DR PDBsum; 3JCE; -. PE 1: Evidence at protein level; KW 3D-structure; Cell inner membrane; Cell membrane; GTP-binding; Hydrolase; KW Membrane; Nucleotide-binding; Protein biosynthesis; Reference proteome. FT CHAIN 1..599 FT /note="Elongation factor 4" FT /id="PRO_0000176271" FT DOMAIN 2..184 FT /note="tr-type G" FT BINDING 14..19 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00071" FT BINDING 131..134 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00071" FT CONFLICT 156..185 FT /note="TDAVRCSAKTGVGVQDVLERLVRDIPPPEG -> HRRGALFSENRRWCAGRS FT RTSGARHSAAGS (in Ref. 1 and 2)" FT /evidence="ECO:0000305" FT CONFLICT 266 FT /note="Missing (in Ref. 1 and 2)" FT /evidence="ECO:0000305" FT STRAND 4..10 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 20..27 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 45..48 FT /evidence="ECO:0007829|PDB:3JCE" FT STRAND 58..64 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 70..77 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 85..94 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 96..103 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 104..106 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 111..121 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 125..131 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 140..146 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 147..151 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 163..165 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 169..179 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 192..201 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 202..204 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 205..215 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 226..228 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 236..246 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 248..250 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 265..267 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 273..279 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 285..288 FT /evidence="ECO:0007829|PDB:3JCE" FT HELIX 291..293 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 295..303 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 304..306 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 307..318 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 325..331 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 332..334 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 335..344 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 345..357 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 366..368 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 372..379 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 381..386 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 390..392 FT /evidence="ECO:0007829|PDB:3JCE" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 396..411 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 412..414 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 415..424 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 428..433 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 438..446 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 447..451 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 452..454 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 455..461 FT /evidence="ECO:0007829|PDB:3CB4" FT TURN 462..464 FT /evidence="ECO:0007829|PDB:3JCE" FT STRAND 467..477 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 480..487 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 490..500 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 501..503 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 504..518 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 522..524 FT /evidence="ECO:0007829|PDB:3JCE" FT STRAND 526..532 FT /evidence="ECO:0007829|PDB:3CB4" FT STRAND 535..542 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 543..546 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 549..551 FT /evidence="ECO:0007829|PDB:3CB4" FT HELIX 559..578 FT /evidence="ECO:0007829|PDB:3JCE" FT TURN 585..592 FT /evidence="ECO:0007829|PDB:3JCE" SQ SEQUENCE 599 AA; 66570 MW; 91E3678557A46D49 CRC64; MKNIRNFSII AHIDHGKSTL SDRIIQICGG LSDREMEAQV LDSMDLERER GITIKAQSVT LDYKASDGET YQLNFIDTPG HVDFSYEVSR SLAACEGALL VVDAGQGVEA QTLANCYTAM EMDLEVVPVL NKIDLPAADP ERVAEEIEDI VGIDATDAVR CSAKTGVGVQ DVLERLVRDI PPPEGDPEGP LQALIIDSWF DNYLGVVSLI RIKNGTLRKG DKVKVMSTGQ TYNADRLGIF TPKQVDRTEL KCGEVGWLVC AIKDIHGAPV GDTLTLARNP AEKALPGFKK VKPQVYAGLF PVSSDDYEAF RDALGKLSLN DASLFYEPES SSALGFGFRC GFLGLLHMEI IQERLEREYD LDLITTAPTV VYEVETTSRE VIYVDSPSKL PAVNNIYELR EPIAECHMLL PQAYLGNVIT LCVEKRGVQT NMVYHGNQVA LTYEIPMAEV VLDFFDRLKS TSRGYASLDY NFKRFQASDM VRVDVLINGE RVDALALITH RDNSQNRGRE LVEKMKDLIP RQQFDIAIQA AIGTHIIARS TVKQLRKNVL AKCYGGDISR KKKLLQKQKE GKKRMKQIGN VELPQEAFLA ILHVGKDNK //