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-SEP-2016, entry version 152. 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; GN Name=EEF1E1; Synonyms=AIMP3, P18; 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 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 [9] 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 [10] 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). CC -!- FUNCTION: Positive modulator of ATM response to DNA damage. CC -!- SUBUNIT: Component of the multisynthase complex which is comprised CC of a bifunctional glutamyl-prolyl-tRNA synthase, the monospecific CC isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl and CC aspartyl-tRNA synthases, and three auxiliary proteins, EEF1E1/p18, CC AIMP2/p38 and AIMP1/p43. Interacts with ATM and ATR. The CC interaction with ATM, which takes place independently of TP53, is CC induced by DNA damage that may occur during genotoxic stress or CC cell growth. The interaction with ATR is enhanced by UV CC irradiation. {ECO:0000269|PubMed:15680327}. 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 Nucleus {ECO:0000269|PubMed:15680327}. Note=Cytoplasmic under CC growth arrest conditions. Translocated into the nucleus when CC growth 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 -!- SIMILARITY: Contains 1 GST C-terminal domain. {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; AB011079; BAA24926.1; -; mRNA. DR EMBL; AF054186; AAC39916.1; -; mRNA. DR EMBL; BT007306; AAP35970.1; -; mRNA. DR EMBL; AL355499; CAH72539.1; -; Genomic_DNA. DR EMBL; AL023694; CAH72539.1; JOINED; Genomic_DNA. DR EMBL; AL451187; CAH72539.1; JOINED; Genomic_DNA. DR EMBL; AL023694; CAI21644.1; -; Genomic_DNA. DR EMBL; AL355499; CAI21644.1; JOINED; Genomic_DNA. DR EMBL; AL451187; CAI21644.1; JOINED; Genomic_DNA. DR EMBL; AL451187; CAI14747.1; -; Genomic_DNA. DR EMBL; AL023694; CAI14747.1; JOINED; Genomic_DNA. DR EMBL; AL355499; CAI14747.1; JOINED; 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 PDBsum; 2UZ8; -. DR PDBsum; 4BL7; -. DR PDBsum; 4BVX; -. DR PDBsum; 4BVY; -. DR PDBsum; 5BMU; -. DR ProteinModelPortal; O43324; -. DR SMR; O43324; 1-166. DR BioGrid; 114898; 51. DR DIP; DIP-50581N; -. DR IntAct; O43324; 14. DR STRING; 9606.ENSP00000369038; -. DR iPTMnet; O43324; -. DR PhosphoSite; O43324; -. DR SwissPalm; O43324; -. DR BioMuta; EEF1E1; -. DR EPD; O43324; -. DR MaxQB; O43324; -. DR PaxDb; O43324; -. DR PeptideAtlas; O43324; -. DR PRIDE; O43324; -. 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 GeneCards; EEF1E1; -. DR HGNC; HGNC:3212; EEF1E1. DR HPA; HPA027901; -. DR HPA; HPA057866; -. DR MIM; 609206; gene. DR neXtProt; NX_O43324; -. 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; -. DR CleanEx; HS_EEF1E1; -. DR ExpressionAtlas; O43324; baseline and differential. DR Genevisible; O43324; HS. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0004364; F:glutathione transferase activity; IBA:GO_Central. DR GO; GO:0003746; F:translation elongation factor activity; IBA:GO_Central. DR GO; GO:0006749; P:glutathione metabolic process; IBA:GO_Central. 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 Gene3D; 1.20.1050.10; -; 1. DR InterPro; IPR010987; Glutathione-S-Trfase_C-like. 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 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 //