ID SYEP_HUMAN Reviewed; 1512 AA.
AC P07814; A0AVA9; B9EGH3; Q05BP6; Q05DF8; Q5DSM1; Q5H9S5; Q6PD57;
AC Q86X73;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 5.
DT 01-MAY-2013, entry version 162.
DE RecName: Full=Bifunctional glutamate/proline--tRNA ligase;
DE AltName: Full=Bifunctional aminoacyl-tRNA synthetase;
DE AltName: Full=Cell proliferation-inducing gene 32 protein;
DE AltName: Full=Glutamatyl-prolyl-tRNA synthetase;
DE Includes:
DE RecName: Full=Glutamate--tRNA ligase;
DE EC=6.1.1.17;
DE AltName: Full=Glutamyl-tRNA synthetase;
DE Short=GluRS;
DE Includes:
DE RecName: Full=Proline--tRNA ligase;
DE EC=6.1.1.15;
DE AltName: Full=Prolyl-tRNA synthetase;
GN Name=EPRS; Synonyms=GLNS, PARS, QARS, QPRS; ORFNames=PIG32;
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 [LARGE SCALE MRNA], AND VARIANTS GLU-308 AND
RP VAL-1043.
RC TISSUE=Bone marrow;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-308.
RC TISSUE=Brain, Duodenum, Eye, Lung, Placenta, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 54-1512, AND VARIANTS GLU-308 AND
RP HIS-334.
RX PubMed=1988429;
RA Fett R., Knippers R.;
RT "The primary structure of human glutaminyl-tRNA synthetase. A highly
RT conserved core, amino acid repeat regions, and homologies with
RT translation elongation factors.";
RL J. Biol. Chem. 266:1448-1455(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 62-1512, AND VARIANTS
RP GLU-308 AND HIS-334.
RA Kim J.W.;
RT "Identification of a proliferation inducing gene.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 168-959, AND VARIANTS
RP GLU-308 AND HIS-334.
RC TISSUE=Cervix carcinoma;
RX PubMed=3290852; DOI=10.1093/nar/16.12.5391;
RA Thoemmes P., Fett R., Schray B., Kunze N., Knippers R.;
RT "The core region of human glutaminyl-tRNA synthetase homologies with
RT the Escherichia coli and yeast enzymes.";
RL Nucleic Acids Res. 16:5391-5406(1988).
RN [7]
RP FUNCTION.
RX PubMed=1756734;
RA Cerini C., Kerjan P., Astier M., Gratecos D., Mirande M., Semeriva M.;
RT "A component of the multisynthetase complex is a multifunctional
RT aminoacyl-tRNA synthetase.";
RL EMBO J. 10:4267-4277(1991).
RN [8]
RP GENE STRUCTURE.
RX PubMed=1556743; DOI=10.1007/BF00163851;
RA Kaiser E., Eberhard D., Knippers R.;
RT "Exons encoding the highly conserved part of human glutaminyl-tRNA
RT synthetase.";
RL J. Mol. Evol. 34:45-53(1992).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN THE GAIT COMPLEX.
RX PubMed=15479637; DOI=10.1016/j.cell.2004.09.030;
RA Sampath P., Mazumder B., Seshadri V., Gerber C.A., Chavatte L.,
RA Kinter M., Ting S.M., Dignam J.D., Kim S., Driscoll D.M., Fox P.L.;
RT "Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-
RT specific silencing of translation.";
RL Cell 119:195-208(2004).
RN [10]
RP INTERACTION WITH DUS2L.
RX PubMed=15994936; DOI=10.1158/0008-5472.CAN-05-0600;
RA Kato T., Daigo Y., Hayama S., Ishikawa N., Yamabuki T., Ito T.,
RA Miyamoto M., Kondo S., Nakamura Y.;
RT "A novel human tRNA-dihydrouridine synthase involved in pulmonary
RT carcinogenesis.";
RL Cancer Res. 65:5638-5646(2005).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-898, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-872; SER-882; SER-885;
RP SER-886 AND THR-898, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP PHOSPHORYLATION AT SER-886 AND SER-999, AND INTERACTION WITH SYNCRIP.
RX PubMed=19647514; DOI=10.1016/j.molcel.2009.05.028;
RA Arif A., Jia J., Mukhopadhyay R., Willard B., Kinter M., Fox P.L.;
RT "Two-site phosphorylation of EPRS coordinates multimodal regulation of
RT noncanonical translational control activity.";
RL Mol. Cell 35:164-180(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-882; SER-886 AND
RP SER-891, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-300; LYS-417; LYS-498;
RP LYS-535; LYS-542; LYS-637; LYS-788 AND LYS-1503, AND MASS
RP SPECTROMETRY.
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
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 [21]
RP MALONYLATION AT LYS-300.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [22]
RP PHOSPHORYLATION AT SER-886.
RX PubMed=21220307; DOI=10.1073/pnas.1011275108;
RA Arif A., Jia J., Moodt R.A., DiCorleto P.E., Fox P.L.;
RT "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-
RT dependent kinase 5 dictates transcript-selective translational
RT control.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1415-1420(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP FUNCTION, RECONSTITUTION OF THE GAIT COMPLEX, AND MUTAGENESIS OF
RP SER-886 AND SER-999.
RX PubMed=23071094; DOI=10.1128/MCB.01168-12;
RA Arif A., Chatterjee P., Moodt R.A., Fox P.L.;
RT "Heterotrimeric GAIT complex drives transcript-selective translation
RT inhibition in murine macrophages.";
RL Mol. Cell. Biol. 32:5046-5055(2012).
RN [25]
RP STRUCTURE BY NMR OF 749-805, AND RNA-BINDING.
RX PubMed=11123902; DOI=10.1021/bi001393h;
RA Jeong E.-J., Hwang G.-S., Kim K.H., Kim M.J., Kim S., Kim K.-S.;
RT "Structural analysis of multifunctional peptide motifs in human
RT bifunctional tRNA synthetase: identification of RNA-binding residues
RT and functional implications for tandem repeats.";
RL Biochemistry 39:15775-15782(2000).
CC -!- FUNCTION: Catalyzes the attachment of the cognate amino acid to
CC the corresponding tRNA in a two-step reaction: the amino acid is
CC first activated by ATP to form a covalent intermediate with AMP
CC and is then transferred to the acceptor end of the cognate tRNA.
CC Component of the GAIT (gamma interferon-activated inhibitor of
CC translation) complex which mediates interferon-gamma-induced
CC transcript-selective translation inhibition in inflammation
CC processes. Upon interferon-gamma activation and subsequent
CC phosphorylation dissociates from the multisynthetase complex and
CC assembles into the GAIT complex which binds to stem loop-
CC containing GAIT elements in the 3'-UTR of diverse inflammatory
CC mRNAs (such as ceruplasmin) and suppresses their translation.
CC -!- CATALYTIC ACTIVITY: ATP + L-glutamate + tRNA(Glu) = AMP +
CC diphosphate + L-glutamyl-tRNA(Glu).
CC -!- CATALYTIC ACTIVITY: ATP + L-proline + tRNA(Pro) = AMP +
CC diphosphate + L-prolyl-tRNA(Pro).
CC -!- SUBUNIT: Component of the multisynthetase complex which is
CC comprised of a bifunctional glutamyl-prolyl-tRNA synthetase, the
CC monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl,
CC arginyl, and aspartyl-tRNA synthetases as well as three auxiliary
CC proteins, p18, p48 and p43. Interacts with DUS2L. Component of the
CC GAIT complex; in humans the complex assembly seems to be a two-
CC step process in which EPRS first associates with SYNCRIP to form a
CC pre-GAIT complex which is deficient in GAIT element binding.
CC -!- INTERACTION:
CC P41252:IARS; NbExp=4; IntAct=EBI-355315, EBI-355303;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Probable).
CC -!- DOMAIN: The WHEP-TRS domain is involved in RNA binding.
CC -!- PTM: Phosphorylated at Ser-886 by CDK5 and at Ser-999 by an
CC unknown kinase in a IFN-gamma-dependent manner in monocytes; these
CC sequential phosphorylations are causing release from the
CC multisynthetase complex, association with the GAIT complex and
CC subsequent involvement in transcript-selective translation
CC inhibition. Phosphorylation at Ser-999 is specifically required
CC for the interaction of GAIT complex-associated RPL13A with eIF4G.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class-I
CC aminoacyl-tRNA synthetase family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the class-II
CC aminoacyl-tRNA synthetase family.
CC -!- SIMILARITY: Contains 3 WHEP-TRS domains.
CC -!- CAUTION: Was originally thought to be a glutaminyl-tRNA
CC synthetase.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15494.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=AAH34797.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=AAH46156.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=AAH58921.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
CC Sequence=AAS72877.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA30354.1; Type=Miscellaneous discrepancy; Note=Sequencing errors;
CC Sequence=CAA38224.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; CR933648; CAI45949.1; -; mRNA.
DR EMBL; AC103590; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015494; AAH15494.1; ALT_SEQ; mRNA.
DR EMBL; BC034797; AAH34797.1; ALT_SEQ; mRNA.
DR EMBL; BC046156; AAH46156.1; ALT_SEQ; mRNA.
DR EMBL; BC058921; AAH58921.1; ALT_SEQ; mRNA.
DR EMBL; BC126275; AAI26276.1; -; mRNA.
DR EMBL; BC136465; AAI36466.1; -; mRNA.
DR EMBL; X54326; CAA38224.1; ALT_INIT; mRNA.
DR EMBL; AY493416; AAS72877.1; ALT_INIT; mRNA.
DR EMBL; X07466; CAA30354.1; ALT_SEQ; mRNA.
DR IPI; IPI00013452; -.
DR PIR; A38663; SYHUQT.
DR RefSeq; NP_004437.2; NM_004446.2.
DR UniGene; Hs.497788; -.
DR PDB; 1FYJ; NMR; -; A=749-805.
DR PDB; 4HVC; X-ray; 2.00 A; A/B=1003-1512.
DR PDBsum; 1FYJ; -.
DR PDBsum; 4HVC; -.
DR ProteinModelPortal; P07814; -.
DR SMR; P07814; 189-689, 749-805, 826-875, 903-952, 1015-1512.
DR DIP; DIP-40825N; -.
DR IntAct; P07814; 15.
DR MINT; MINT-141120; -.
DR PhosphoSite; P07814; -.
DR DMDM; 288558855; -.
DR PaxDb; P07814; -.
DR PRIDE; P07814; -.
DR Ensembl; ENST00000366923; ENSP00000355890; ENSG00000136628.
DR GeneID; 2058; -.
DR KEGG; hsa:2058; -.
DR UCSC; uc001hly.1; human.
DR CTD; 2058; -.
DR GeneCards; GC01M220141; -.
DR HGNC; HGNC:3418; EPRS.
DR HPA; HPA026490; -.
DR HPA; HPA030052; -.
DR MIM; 138295; gene.
DR neXtProt; NX_P07814; -.
DR PharmGKB; PA27837; -.
DR eggNOG; COG0442; -.
DR HOVERGEN; HBG017875; -.
DR InParanoid; P07814; -.
DR KO; K14163; -.
DR OMA; KAQYKEK; -.
DR OrthoDB; EOG4001HD; -.
DR Reactome; REACT_71; Gene Expression.
DR ChEMBL; CHEMBL3873; -.
DR DrugBank; DB00142; L-Glutamic Acid.
DR DrugBank; DB00172; L-Proline.
DR EvolutionaryTrace; P07814; -.
DR GenomeRNAi; 2058; -.
DR NextBio; 8369; -.
DR Bgee; P07814; -.
DR CleanEx; HS_EPRS; -.
DR CleanEx; HS_QARS; -.
DR Genevestigator; P07814; -.
DR GermOnline; ENSG00000136628; Homo sapiens.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004818; F:glutamate-tRNA ligase activity; TAS:Reactome.
DR GO; GO:0004827; F:proline-tRNA ligase activity; TAS:Reactome.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0006424; P:glutamyl-tRNA aminoacylation; IEA:InterPro.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0006433; P:prolyl-tRNA aminoacylation; IEA:InterPro.
DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 1.10.1160.10; -; 1.
DR Gene3D; 1.10.287.10; -; 3.
DR Gene3D; 1.20.1050.10; -; 1.
DR Gene3D; 2.40.240.10; -; 2.
DR Gene3D; 3.30.110.30; -; 1.
DR Gene3D; 3.40.50.620; -; 2.
DR Gene3D; 3.40.50.800; -; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb_cons-dom.
DR InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR004526; Glu-tRNA-synth_Ib_arc/euk.
DR InterPro; IPR000924; Glu/Gln-tRNA-synth_Ib.
DR InterPro; IPR020061; Glu/Gln-tRNA-synth_Ib_a-bdl.
DR InterPro; IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom.
DR InterPro; IPR020059; Glu/Gln-tRNA-synth_Ib_codon-bd.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR004499; Pro-tRNA-ligase_IIa_arc-type.
DR InterPro; IPR016061; Pro-tRNA_ligase_II_C.
DR InterPro; IPR017449; Pro-tRNA_synth_II.
DR InterPro; IPR020056; Rbsml_L25/Gln-tRNA_synth_b-brl.
DR InterPro; IPR011035; Ribosomal_L25/Gln-tRNA_synth.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009068; S15_NS1_RNA-bd.
DR InterPro; IPR000738; WHEP-TRS.
DR PANTHER; PTHR10119; PTHR10119; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF09180; ProRS-C_1; 1.
DR Pfam; PF00749; tRNA-synt_1c; 1.
DR Pfam; PF03950; tRNA-synt_1c_C; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR Pfam; PF00458; WHEP-TRS; 3.
DR PRINTS; PR00987; TRNASYNTHGLU.
DR SMART; SM00946; ProRS-C_1; 1.
DR SMART; SM00991; WHEP-TRS; 3.
DR SUPFAM; SSF52954; Anticodon_bd; 1.
DR SUPFAM; SSF47616; GST_C_like; 1.
DR SUPFAM; SSF64586; Pro-tRNA_synth_II_C; 1.
DR SUPFAM; SSF50715; Ribosomal_L25rel; 1.
DR SUPFAM; SSF47060; S15/NS1_bind; 3.
DR TIGRFAMs; TIGR00463; gltX_arch; 1.
DR TIGRFAMs; TIGR00408; proS_fam_I; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR PROSITE; PS00762; WHEP_TRS_1; 3.
DR PROSITE; PS51185; WHEP_TRS_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding;
KW Complete proteome; Cytoplasm; Ligase; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Protein biosynthesis; Reference proteome; Repeat; RNA-binding;
KW Translation regulation.
FT CHAIN 1 1512 Bifunctional glutamate/proline--tRNA
FT ligase.
FT /FTId=PRO_0000119743.
FT DOMAIN 749 805 WHEP-TRS 1.
FT DOMAIN 822 878 WHEP-TRS 2.
FT DOMAIN 900 956 WHEP-TRS 3.
FT NP_BIND 432 436 ATP (By similarity).
FT REGION 164 759 Glutamate--tRNA ligase.
FT REGION 760 956 3 X 57 AA approximate repeats.
FT REGION 959 991 Charged.
FT REGION 1007 1512 Proline--tRNA ligase.
FT MOTIF 204 214 "HIGH" region.
FT MOTIF 432 436 "KMSKS" region.
FT BINDING 211 211 ATP (By similarity).
FT BINDING 398 398 ATP (By similarity).
FT MOD_RES 300 300 N6-acetyllysine; alternate.
FT MOD_RES 300 300 N6-malonyllysine; alternate.
FT MOD_RES 417 417 N6-acetyllysine.
FT MOD_RES 498 498 N6-acetyllysine.
FT MOD_RES 535 535 N6-acetyllysine.
FT MOD_RES 542 542 N6-acetyllysine.
FT MOD_RES 637 637 N6-acetyllysine.
FT MOD_RES 788 788 N6-acetyllysine.
FT MOD_RES 872 872 Phosphotyrosine.
FT MOD_RES 882 882 Phosphoserine.
FT MOD_RES 885 885 Phosphoserine.
FT MOD_RES 886 886 Phosphoserine; by CDK5.
FT MOD_RES 891 891 Phosphoserine.
FT MOD_RES 898 898 Phosphothreonine.
FT MOD_RES 999 999 Phosphoserine.
FT MOD_RES 1000 1000 Phosphoserine.
FT MOD_RES 1503 1503 N6-acetyllysine.
FT VARIANT 296 296 A -> P (in dbSNP:rs35999099).
FT /FTId=VAR_037288.
FT VARIANT 308 308 D -> E (in dbSNP:rs2230301).
FT /FTId=VAR_037289.
FT VARIANT 334 334 Q -> H (in dbSNP:rs1063236).
FT /FTId=VAR_037290.
FT VARIANT 893 893 P -> H (in dbSNP:rs5030751).
FT /FTId=VAR_037291.
FT VARIANT 913 913 E -> G (in dbSNP:rs2230302).
FT /FTId=VAR_057358.
FT VARIANT 1043 1043 I -> V (in dbSNP:rs5030752).
FT /FTId=VAR_037292.
FT VARIANT 1107 1107 S -> F (in dbSNP:rs12144752).
FT /FTId=VAR_037293.
FT VARIANT 1399 1399 T -> N (in dbSNP:rs34559775).
FT /FTId=VAR_037294.
FT MUTAGEN 886 886 S->A: Abolishes release from
FT multisynthetase complex and association
FT with GAIT complex assembly upon
FT interferon-gamma treatment. Abolishes
FT interaction with SYNCRIP.
FT MUTAGEN 886 886 S->D: Not active in translation
FT inhibition (phosphomimetic) and abolishes
FT GAIT complex association with eiF4G. No
FT effect on interaction with SYNCRIP.
FT MUTAGEN 999 999 S->A: Not active in translation
FT inhibition, and abolishes release from
FT multisynthetase complex and association
FT with GAIT complex assembly upon
FT interferon-gamma treatment.
FT MUTAGEN 999 999 S->D: Active in translation inhibition
FT (phosphomimetic). No effect on GAIT
FT complex association with eiF4G.
FT CONFLICT 532 532 K -> R (in Ref. 1; CAI45949).
FT CONFLICT 594 594 L -> F (in Ref. 4; CAA38224 and 5;
FT AAS72877).
FT CONFLICT 943 943 K -> E (in Ref. 1; CAI45949).
FT CONFLICT 1177 1179 ATM -> VTV (in Ref. 1; CAI45949).
FT CONFLICT 1441 1441 K -> R (in Ref. 1; CAI45949).
FT HELIX 750 769
FT HELIX 774 795
FT TURN 1020 1022
FT HELIX 1024 1034
FT STRAND 1038 1040
FT STRAND 1047 1049
FT HELIX 1051 1070
FT STRAND 1080 1083
FT HELIX 1084 1087
FT HELIX 1095 1100
FT STRAND 1102 1107
FT STRAND 1110 1118
FT STRAND 1120 1122
FT HELIX 1123 1133
FT HELIX 1137 1139
FT STRAND 1142 1151
FT TURN 1160 1162
FT STRAND 1165 1178
FT HELIX 1179 1198
FT STRAND 1206 1209
FT TURN 1212 1214
FT STRAND 1219 1229
FT TURN 1230 1233
FT STRAND 1234 1245
FT HELIX 1247 1252
FT STRAND 1255 1257
FT STRAND 1265 1267
FT STRAND 1269 1276
FT HELIX 1278 1287
FT TURN 1297 1299
FT STRAND 1303 1308
FT HELIX 1317 1336
FT STRAND 1341 1343
FT STRAND 1347 1349
FT HELIX 1351 1360
FT STRAND 1364 1369
FT HELIX 1371 1376
FT STRAND 1378 1383
FT TURN 1384 1386
FT STRAND 1389 1393
FT HELIX 1394 1396
FT HELIX 1397 1423
FT STRAND 1424 1426
FT HELIX 1430 1438
FT STRAND 1442 1447
FT HELIX 1451 1462
FT STRAND 1477 1484
FT STRAND 1504 1509
SQ SEQUENCE 1512 AA; 170591 MW; 2CE4311076719403 CRC64;
MATLSLTVNS GDPPLGALLA VEHVKDDVSI SVEEGKENIL HVSENVIFTD VNSILRYLAR
VATTAGLYGS NLMEHTEIDH WLEFSATKLS SCDSFTSTIN ELNHCLSLRT YLVGNSLSLA
DLCVWATLKG NAAWQEQLKQ KKAPVHVKRW FGFLEAQQAF QSVGTKWDVS TTKARVAPEK
KQDVGKFVEL PGAEMGKVTV RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN
PEKEKEDFEK VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK
AEREQRIDSK HRKNPIEKNL QMWEEMKKGS QFGQSCCLRA KIDMSSNNGC MRDPTLYRCK
IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH DRDEQFYWII EALGIRKPYI
WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS
SRSVVNMEWD KIWAFNKKVI DPVAPRYVAL LKKEVIPVNV PEAQEEMKEV AKHPKNPEVG
LKPVWYSPKV FIEGADAETF SEGEMVTFIN WGNLNITKIH KNADGKIISL DAKLNLENKD
YKKTTKVTWL AETTHALPIP VICVTYEHLI TKPVLGKDED FKQYVNKNSK HEELMLGDPC
LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCKEAPCVLI YIPDGHTKEM PTSGSKEKTK
VEATKNETSA PFKERPTPSL NNNCTTSEDS LVLYNRVAVQ GDVVRELKAK KAPKEDVDAA
VKQLLSLKAE YKEKTGQEYK PGNPPAEIGQ NISSNSSASI LESKSLYDEV AAQGEVVRKL
KAEKSPKAKI NEAVECLLSL KAQYKEKTGK EYIPGQPPLS QSSDSSPTRN SEPAGLETPE
AKVLFDKVAS QGEVVRKLKT EKAPKDQVDI AVQELLQLKA QYKSLIGVEY KPVSATGAED
KDKKKKEKEN KSEKQNKPQK QNDGQRKDPS KNQGGGLSSS GAGEGQGPKK QTRLGLEAKK
EENLADWYSQ VITKSEMIEY HDISGCYILR PWAYAIWEAI KDFFDAEIKK LGVENCYFPM
FVSQSALEKE KTHVADFAPE VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL
PIKLNQWCNV VRWEFKHPQP FLRTREFLWQ EGHSAFATME EAAEEVLQIL DLYAQVYEEL
LAIPVVKGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGGT SHHLGQNFSK MFEIVFEDPK
IPGEKQFAYQ NSWGLTTRTI GVMTMVHGDN MGLVLPPRVA CVQVVIIPCG ITNALSEEDK
EALIAKCNDY RRRLLSVNIR VRADLRDNYS PGWKFNHWEL KGVPIRLEVG PRDMKSCQFV
AVRRDTGEKL TVAENEAETK LQAILEDIQV TLFTRASEDL KTHMVVANTM EDFQKILDSG
KIVQIPFCGE IDCEDWIKKT TARDQDLEPG APSMGAKSLC IPFKPLCELQ PGAKCVCGKN
PAKYYTLFGR SY
//
