MCA3_HUMAN
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 03-AUG-2022, entry version 195.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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-length
RT 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 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., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., 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., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA 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 project:
RT 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., Le Marechal P.,
RA Negrutskii B., Mirande M.;
RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase
RT 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., Negrutskii B.,
RA 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 MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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., 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 [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DOMAIN ARCHITECTURE, AND COILED-COIL
RP 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., Kim M.H.,
RA Kim S.H., Kim D.W., Kim S., Kang B.S.;
RT "Determination of three-dimensional structure and residues of the novel
RT tumor suppressor AIMP3/p18 required for the interaction with ATM.";
RL J. Biol. Chem. 283:14032-14040(2008).
RN [13] {ECO:0007744|PDB:4BVX, ECO:0007744|PDB:5BMU}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-169 IN COMPLEX WITH MARS1,
RP SUBUNIT, INTERACTION WITH MARS1 AND EPRS1, 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., Kim H.K.,
RA Kim J.H., Eom C.Y., Kim Y.G., Guo M., Jung H.S., Kang B.S., Kim S.;
RT "Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione
RT 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 for
CC Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys
CC (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1)
CC and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18
CC (PubMed:19131329, PubMed:19289464). Can interact simultaneously with
CC MARS1 and EPRS1 (PubMed:26472928). Forms a linear complex that contains
CC MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit
CC complex (PubMed:26472928). Interacts with ATM and ATR. The interaction
CC with ATM, which takes place independently of TP53, is induced by DNA
CC damage that may occur during genotoxic stress or cell growth. The
CC interaction with ATR is enhanced by UV irradiation.
CC {ECO:0000269|PubMed:15680327, ECO:0000269|PubMed:19131329,
CC ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:26472928}.
CC -!- INTERACTION:
CC O43324; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-1048486, EBI-739580;
CC O43324; Q9BTE0: NAT9; NbExp=4; IntAct=EBI-1048486, EBI-711919;
CC O43324; PRO_0000038593 [P04591]: gag; Xeno; NbExp=4; IntAct=EBI-1048486, EBI-6179719;
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 arrest
CC conditions. Translocated into the nucleus when growth resumes (S phase)
CC 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 -!- TISSUE SPECIFICITY: Down-regulated in various cancer tissues.
CC {ECO:0000269|PubMed:15680327}.
CC -!- INDUCTION: By DNA damaging agents such as UV, adriamycin, actinomycin-D
CC and cisplatin.
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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 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 AlphaFoldDB; O43324; -.
DR SMR; O43324; -.
DR BioGRID; 114898; 99.
DR CORUM; O43324; -.
DR DIP; DIP-50581N; -.
DR IntAct; O43324; 40.
DR MINT; O43324; -.
DR STRING; 9606.ENSP00000369038; -.
DR iPTMnet; O43324; -.
DR PhosphoSitePlus; O43324; -.
DR SwissPalm; O43324; -.
DR BioMuta; EEF1E1; -.
DR EPD; O43324; -.
DR jPOST; O43324; -.
DR MassIVE; O43324; -.
DR MaxQB; O43324; -.
DR PaxDb; O43324; -.
DR PeptideAtlas; O43324; -.
DR PRIDE; O43324; -.
DR ProteomicsDB; 10721; -.
DR ProteomicsDB; 48904; -. [O43324-1]
DR TopDownProteomics; O43324-1; -. [O43324-1]
DR TopDownProteomics; O43324-2; -. [O43324-2]
DR Antibodypedia; 24724; 203 antibodies from 31 providers.
DR DNASU; 9521; -.
DR Ensembl; ENST00000379715.10; ENSP00000369038.5; ENSG00000124802.12. [O43324-1]
DR Ensembl; ENST00000429723.6; ENSP00000414363.2; ENSG00000124802.12. [O43324-2]
DR GeneID; 9521; -.
DR KEGG; hsa:9521; -.
DR MANE-Select; ENST00000379715.10; ENSP00000369038.5; NM_004280.5; NP_004271.1.
DR UCSC; uc003mxz.4; human. [O43324-1]
DR CTD; 9521; -.
DR DisGeNET; 9521; -.
DR GeneCards; EEF1E1; -.
DR HGNC; HGNC:3212; EEF1E1.
DR HPA; ENSG00000124802; Low tissue specificity.
DR MIM; 609206; gene.
DR neXtProt; NX_O43324; -.
DR OpenTargets; ENSG00000124802; -.
DR PharmGKB; PA27648; -.
DR VEuPathDB; HostDB:ENSG00000124802; -.
DR eggNOG; KOG0867; Eukaryota.
DR GeneTree; ENSGT00390000003564; -.
DR HOGENOM; CLU_098079_0_0_1; -.
DR InParanoid; O43324; -.
DR OMA; FIVDLTF; -.
DR OrthoDB; 1422931at2759; -.
DR PhylomeDB; O43324; -.
DR TreeFam; TF326005; -.
DR PathwayCommons; O43324; -.
DR Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; O43324; -.
DR BioGRID-ORCS; 9521; 72 hits in 1074 CRISPR screens.
DR EvolutionaryTrace; O43324; -.
DR GeneWiki; EEF1E1; -.
DR GenomeRNAi; 9521; -.
DR Pharos; O43324; Tbio.
DR PRO; PR:O43324; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O43324; protein.
DR Bgee; ENSG00000124802; Expressed in pons and 206 other tissues.
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; ISS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
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:0006412; P:translation; IEA:UniProtKB-KW.
DR InterPro; IPR042450; EEF1E1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR004046; GST_C.
DR PANTHER; PTHR44490; PTHR44490; 1.
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; Cytoplasm;
KW Direct protein sequencing; Nucleus; Protein biosynthesis;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6"
FT CHAIN 2..174
FT /note="Eukaryotic translation elongation factor 1 epsilon-
FT 1"
FT /id="PRO_0000221132"
FT DOMAIN 50..173
FT /note="GST C-terminal"
FT REGION 2..56
FT /note="N-terminal"
FT REGION 57..63
FT /note="Linker"
FT REGION 64..152
FT /note="C-terminal"
FT COILED 153..169
FT /evidence="ECO:0000269|PubMed:18343821"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6"
FT MOD_RES 138
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 129..174
FT /note="VDLTVQEKEKYLNVSRWFCHIQHYPGIRQHLSSVVFIKNRLYTNSH -> IR
FT KLRHTEVGN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045088"
FT MUTAGEN 69
FT /note="A->R: Disrupts interaction with MARS1."
FT /evidence="ECO:0000269|PubMed:26472928"
FT MUTAGEN 73
FT /note="Q->R: Disrupts interaction with MARS1."
FT /evidence="ECO:0000269|PubMed:26472928"
FT MUTAGEN 144
FT /note="R->A: Disrupts interaction with EPRS1."
FT /evidence="ECO:0000269|PubMed:26472928"
FT HELIX 3..14
FT /evidence="ECO:0007829|PDB:4BVX"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:4BVX"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:4BVX"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:4BVX"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:5BMU"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 44..54
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 58..61
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 65..80
FT /evidence="ECO:0007829|PDB:4BVX"
FT TURN 81..84
FT /evidence="ECO:0007829|PDB:4BVY"
FT HELIX 85..101
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:4BVX"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 115..128
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:4BVX"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:4BVX"
FT TURN 153..155
FT /evidence="ECO:0007829|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
