ID MCA3_HUMAN Reviewed; 174 AA. AC O43324; C9JLK5; Q5THS2; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 07-NOV-2018, entry version 172. DE RecName: Full=Eukaryotic translation elongation factor 1 epsilon-1; DE AltName: Full=Aminoacyl tRNA synthetase complex-interacting multifunctional protein 3; DE AltName: Full=Elongation factor p18; DE AltName: Full=Multisynthase complex auxiliary component p18 {ECO:0000303|PubMed:19131329}; GN Name=EEF1E1; Synonyms=AIMP3, P18 {ECO:0000303|PubMed:15680327}; 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). RC TISSUE=Testis; RA Motegi H., Noda T., Shiba K.; RT "Cloning of cDNA for human p18 from human testis."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175; RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., RA Wang Y.-X., Chen S.-J., Chen Z.; RT "Identification of genes expressed in human CD34(+) hematopoietic RT stem/progenitor cells by expressed sequence tags and efficient full- RT length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain cortex, and Urinary bladder; 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 [6] RP PROTEIN SEQUENCE OF 2-12 AND 79-88, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma, and Ovarian carcinoma; RA Bienvenut W.V., Calvo F., Lilla S., von Kriegsheim A., Lempens A., RA Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [7] RP INTERACTION WITH ATM, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15680327; DOI=10.1016/j.cell.2004.11.054; RA Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H., RA Choi Y.H., Choi D., Lee K.S., Kim S.; RT "The haploinsufficient tumor suppressor p18 upregulates p53 via RT interactions with ATM/ATR."; RL Cell 120:209-221(2005). RN [8] RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=19131329; DOI=10.1074/jbc.M809636200; RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., RA Le Marechal P., Negrutskii B., Mirande M.; RT "Dissection of the structural organization of the aminoacyl-tRNA RT synthetase complex."; RL J. Biol. Chem. 284:6053-6060(2009). RN [9] RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=19289464; DOI=10.1074/jbc.M900480200; RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., RA Negrutskii B., Mirande M.; RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the RT Cytoplasm of Human Cells."; RL J. Biol. Chem. 284:13746-13754(2009). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-138, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] 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 [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DOMAIN ARCHITECTURE, AND RP COILED-COIL DOMAIN. RX PubMed=18343821; DOI=10.1074/jbc.M800859200; RA Kim K.J., Park M.C., Choi S.J., Oh Y.S., Choi E.C., Cho H.J., RA Kim M.H., Kim S.H., Kim D.W., Kim S., Kang B.S.; RT "Determination of three-dimensional structure and residues of the RT novel tumor suppressor AIMP3/p18 required for the interaction with RT ATM."; RL J. Biol. Chem. 283:14032-14040(2008). RN [13] {ECO:0000244|PDB:4BVX, ECO:0000244|PDB:5BMU} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-169 IN COMPLEX WITH MARS, RP SUBUNIT, INTERACTION WITH MARS AND EPRS, AND MUTAGENESIS OF ALA-69; RP GLN-73 AND ARG-144. RX PubMed=26472928; DOI=10.1074/JBC.M115.690867; RA Cho H.Y., Maeng S.J., Cho H.J., Choi Y.S., Chung J.M., Lee S., RA Kim H.K., Kim J.H., Eom C.Y., Kim Y.G., Guo M., Jung H.S., Kang B.S., RA Kim S.; RT "Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric RT Glutathione Transferase-homology Domains."; RL J. Biol. Chem. 290:29313-29328(2015). CC -!- FUNCTION: Positive modulator of ATM response to DNA damage. CC {ECO:0000250|UniProtKB:Q9D1M4}. CC -!- SUBUNIT: Part of a multisubunit complex that groups tRNA ligases CC for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), CC Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro CC (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and CC EEF1E1/p18 (PubMed:19131329, PubMed:19289464). Can interact CC simultaneously with MARS and EPRS (PubMed:26472928). Forms a CC linear complex that contains MARS, EEF1E1, EPRS and AIMP2 that is CC at the core of the multisubunit complex (PubMed:26472928). CC Interacts with ATM and ATR. The interaction with ATM, which takes CC place independently of TP53, is induced by DNA damage that may CC occur during genotoxic stress or cell growth. The interaction with CC ATR is enhanced by UV irradiation. {ECO:0000269|PubMed:15680327, CC ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464, CC ECO:0000269|PubMed:26472928}. CC -!- INTERACTION: CC Q13137:CALCOCO2; NbExp=3; IntAct=EBI-1048486, EBI-739580; CC P04591:gag (xeno); NbExp=4; IntAct=EBI-1048486, EBI-6179719; CC Q9BTE0:NAT9; NbExp=4; IntAct=EBI-1048486, EBI-711919; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15680327}. CC Cytoplasm, cytosol {ECO:0000269|PubMed:19289464}. Nucleus CC {ECO:0000269|PubMed:15680327}. Note=Cytoplasmic under growth CC arrest conditions. Translocated into the nucleus when growth CC resumes (S phase) and following DNA damage. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43324-1; Sequence=Displayed; CC Name=2; CC IsoId=O43324-2; Sequence=VSP_045088; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Down-regulated in various cancer tissues. CC {ECO:0000269|PubMed:15680327}. CC -!- INDUCTION: By DNA damaging agents such as UV, adriamycin, CC actinomycin-D and cisplatin. 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; AB011079; BAA24926.1; -; mRNA. DR EMBL; AF054186; AAC39916.1; -; mRNA. DR EMBL; BT007306; AAP35970.1; -; mRNA. DR EMBL; AL355499; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL023694; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL451187; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005291; AAH05291.1; -; mRNA. DR EMBL; CK002875; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS4507.1; -. [O43324-1] DR CCDS; CCDS47370.1; -. [O43324-2] DR RefSeq; NP_001129122.1; NM_001135650.1. [O43324-2] DR RefSeq; NP_004271.1; NM_004280.4. [O43324-1] DR UniGene; Hs.602353; -. DR UniGene; Hs.745033; -. DR PDB; 2UZ8; X-ray; 2.00 A; A/B=1-174. DR PDB; 4BL7; X-ray; 1.89 A; B=1-174. DR PDB; 4BVX; X-ray; 1.60 A; B=1-169. DR PDB; 4BVY; X-ray; 1.99 A; B=1-174. DR PDB; 5BMU; X-ray; 2.60 A; A/C/E/G=1-169. DR PDB; 5Y6L; X-ray; 2.90 A; B=1-174. DR PDBsum; 2UZ8; -. DR PDBsum; 4BL7; -. DR PDBsum; 4BVX; -. DR PDBsum; 4BVY; -. DR PDBsum; 5BMU; -. DR PDBsum; 5Y6L; -. DR ProteinModelPortal; O43324; -. DR SMR; O43324; -. DR BioGrid; 114898; 58. DR CORUM; O43324; -. DR DIP; DIP-50581N; -. DR IntAct; O43324; 21. DR MINT; O43324; -. DR STRING; 9606.ENSP00000369038; -. DR iPTMnet; O43324; -. DR PhosphoSitePlus; O43324; -. DR SwissPalm; O43324; -. DR BioMuta; EEF1E1; -. DR EPD; O43324; -. DR MaxQB; O43324; -. DR PaxDb; O43324; -. DR PeptideAtlas; O43324; -. DR PRIDE; O43324; -. DR ProteomicsDB; 48904; -. DR TopDownProteomics; O43324-1; -. [O43324-1] DR TopDownProteomics; O43324-2; -. [O43324-2] DR DNASU; 9521; -. DR Ensembl; ENST00000379715; ENSP00000369038; ENSG00000124802. [O43324-1] DR Ensembl; ENST00000429723; ENSP00000414363; ENSG00000124802. [O43324-2] DR GeneID; 9521; -. DR KEGG; hsa:9521; -. DR UCSC; uc003mxz.4; human. [O43324-1] DR CTD; 9521; -. DR DisGeNET; 9521; -. DR EuPathDB; HostDB:ENSG00000124802.11; -. DR GeneCards; EEF1E1; -. DR HGNC; HGNC:3212; EEF1E1. DR HPA; HPA027901; -. DR HPA; HPA057866; -. DR MIM; 609206; gene. DR neXtProt; NX_O43324; -. DR OpenTargets; ENSG00000124802; -. DR PharmGKB; PA27648; -. DR eggNOG; KOG0867; Eukaryota. DR eggNOG; COG0625; LUCA. DR GeneTree; ENSGT00390000003564; -. DR HOGENOM; HOG000026786; -. DR HOVERGEN; HBG003019; -. DR InParanoid; O43324; -. DR KO; K15439; -. DR OMA; TIACHLV; -. DR OrthoDB; EOG091G0VQB; -. DR PhylomeDB; O43324; -. DR TreeFam; TF326005; -. DR Reactome; R-HSA-2408517; SeMet incorporation into proteins. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR SignaLink; O43324; -. DR ChiTaRS; EEF1E1; human. DR EvolutionaryTrace; O43324; -. DR GeneWiki; EEF1E1; -. DR GenomeRNAi; 9521; -. DR PRO; PR:O43324; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000124802; Expressed in 234 organ(s), highest expression level in material anatomical entity. DR CleanEx; HS_EEF1E1; -. DR ExpressionAtlas; O43324; baseline and differential. DR Genevisible; O43324; HS. DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0008285; P:negative regulation of cell proliferation; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:2000774; P:positive regulation of cellular senescence; IDA:BHF-UCL. DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. DR InterPro; IPR010987; Glutathione-S-Trfase_C-like. DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf. DR InterPro; IPR004046; GST_C. DR Pfam; PF00043; GST_C; 1. DR SUPFAM; SSF47616; SSF47616; 1. DR PROSITE; PS50405; GST_CTER; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Coiled coil; KW Complete proteome; Cytoplasm; Direct protein sequencing; Nucleus; KW Protein biosynthesis; Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000269|Ref.6}. FT CHAIN 2 174 Eukaryotic translation elongation factor FT 1 epsilon-1. FT /FTId=PRO_0000221132. FT DOMAIN 50 173 GST C-terminal. FT REGION 2 56 N-terminal. FT REGION 57 63 Linker. FT REGION 64 152 C-terminal. FT COILED 153 169 {ECO:0000269|PubMed:18343821}. FT MOD_RES 2 2 N-acetylalanine. {ECO:0000269|Ref.6}. FT MOD_RES 138 138 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VAR_SEQ 129 174 VDLTVQEKEKYLNVSRWFCHIQHYPGIRQHLSSVVFIKNRL FT YTNSH -> IRKLRHTEVGN (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_045088. FT MUTAGEN 69 69 A->R: Disrupts interaction with MARS. FT {ECO:0000269|PubMed:26472928}. FT MUTAGEN 73 73 Q->R: Disrupts interaction with MARS. FT {ECO:0000269|PubMed:26472928}. FT MUTAGEN 144 144 R->A: Disrupts interaction with EPRS. FT {ECO:0000269|PubMed:26472928}. FT HELIX 3 14 {ECO:0000244|PDB:4BVX}. FT STRAND 22 25 {ECO:0000244|PDB:4BVX}. FT TURN 26 29 {ECO:0000244|PDB:4BVX}. FT STRAND 30 34 {ECO:0000244|PDB:4BVX}. FT STRAND 36 39 {ECO:0000244|PDB:5BMU}. FT STRAND 40 43 {ECO:0000244|PDB:4BVX}. FT HELIX 44 54 {ECO:0000244|PDB:4BVX}. FT HELIX 58 61 {ECO:0000244|PDB:4BVX}. FT HELIX 65 80 {ECO:0000244|PDB:4BVX}. FT TURN 81 84 {ECO:0000244|PDB:4BVY}. FT HELIX 85 101 {ECO:0000244|PDB:4BVX}. FT HELIX 102 104 {ECO:0000244|PDB:4BVX}. FT STRAND 110 112 {ECO:0000244|PDB:4BVX}. FT HELIX 115 128 {ECO:0000244|PDB:4BVX}. FT HELIX 133 138 {ECO:0000244|PDB:4BVX}. FT HELIX 140 151 {ECO:0000244|PDB:4BVX}. FT TURN 153 155 {ECO:0000244|PDB:4BVX}. SQ SEQUENCE 174 AA; 19811 MW; 58AAE4BD9E1684E2 CRC64; MAAAAELSLL EKSLGLSKGN KYSAQGERQI PVLQTNNGPS LTGLTTIAAH LVKQANKEYL LGSTAEEKAI VQQWLEYRVT QVDGHSSKND IHTLLKDLNS YLEDKVYLTG YNFTLADILL YYGLHRFIVD LTVQEKEKYL NVSRWFCHIQ HYPGIRQHLS SVVFIKNRLY TNSH //