ID   SYEP_MOUSE              Reviewed;        1512 AA.
AC   Q8CGC7; E9QKC4; Q3UFJ2; Q4VC16;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Bifunctional glutamate/proline--tRNA ligase {ECO:0000305};
DE   AltName: Full=Bifunctional aminoacyl-tRNA synthetase;
DE   Includes:
DE     RecName: Full=Glutamate--tRNA ligase {ECO:0000250|UniProtKB:P07814};
DE              EC=6.1.1.17 {ECO:0000250|UniProtKB:P07814};
DE     AltName: Full=Glutamyl-tRNA synthetase {ECO:0000250|UniProtKB:P07814};
DE              Short=GluRS {ECO:0000250|UniProtKB:P07814};
DE   Includes:
DE     RecName: Full=Proline--tRNA ligase {ECO:0000250|UniProtKB:P07814};
DE              EC=6.1.1.15 {ECO:0000250|UniProtKB:P07814};
DE     AltName: Full=Prolyl-tRNA synthetase;
DE              Short=ProRS;
GN   Name=Eprs1 {ECO:0000312|MGI:MGI:97838};
GN   Synonyms=Eprs {ECO:0000303|PubMed:28178239}, Qprs;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and FVB/N; TISSUE=Eye, and Mammary tumor;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-962.
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 406-1512.
RA   Knippers R.;
RT   "M.musculus mRNA for glutamyl-tRNA synthetase.";
RL   Submitted (JUL-1990) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   SUBUNIT.
RX   PubMed=12060739; DOI=10.1073/pnas.122110199;
RA   Kim J.Y., Kang Y.-S., Lee J.-W., Kim H.J., Ahn Y.H., Park H., Ko Y.-G.,
RA   Kim S.;
RT   "p38 is essential for the assembly and stability of macromolecular tRNA
RT   synthetase complex: implications for its physiological significance.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7912-7916(2002).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=15592455; DOI=10.1038/nbt1046;
RA   Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA   Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT   "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL   Nat. Biotechnol. 23:94-101(2005).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [8]
RP   FUNCTION, PHOSPHORYLATION AT SER-999, SUBUNIT, RECONSTITUTION OF THE GAIT
RP   COMPLEX, AND MUTAGENESIS OF 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   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-300; LYS-788 AND LYS-861, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [10]
RP   FUNCTION, INTERACTION WITH SLC27A1, SUBCELLULAR LOCATION, TOPOLOGY,
RP   PHOSPHORYLATION AT SER-999 BY RPS6KB1, AND MUTAGENESIS OF SER-999.
RX   PubMed=28178239; DOI=10.1038/nature21380;
RA   Arif A., Terenzi F., Potdar A.A., Jia J., Sacks J., China A., Halawani D.,
RA   Vasu K., Li X., Brown J.M., Chen J., Kozma S.C., Thomas G., Fox P.L.;
RT   "EPRS is a critical mTORC1-S6K1 effector that influences adiposity in
RT   mice.";
RL   Nature 542:357-361(2017).
CC   -!- FUNCTION: Multifunctional protein which primarily functions within the
CC       aminoacyl-tRNA synthetase multienzyme complex, also known as
CC       multisynthetase complex. Within the complex it catalyzes the attachment
CC       of both L-glutamate and L-proline to their cognate tRNAs in a two-step
CC       reaction where the amino acid is first activated by ATP to form a
CC       covalent intermediate with AMP. Subsequently, the activated amino acid
CC       is transferred to the acceptor end of the cognate tRNA to form L-
CC       glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (By similarity). Upon
CC       interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing
CC       its dissociation from the aminoacyl-tRNA synthetase multienzyme
CC       complex. It is recruited to form the GAIT complex, which binds to stem
CC       loop-containing GAIT elements found in the 3'-UTR of various
CC       inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits
CC       the translation of these mRNAs, allowing interferon-gamma to redirect
CC       the function of EPRS1 from protein synthesis to translation inhibition
CC       in specific cell contexts (PubMed:23071094). Furthermore, it can
CC       function as a downstream effector in the mTORC1 signaling pathway, by
CC       promoting the translocation of SLC27A1 from the cytoplasm to the plasma
CC       membrane where it mediates the uptake of long-chain fatty acid by
CC       adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more
CC       indirectly influences lifespan (PubMed:28178239).
CC       {ECO:0000250|UniProtKB:P07814, ECO:0000269|PubMed:23071094,
CC       ECO:0000269|PubMed:28178239}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-
CC         glutamyl-tRNA(Glu); Xref=Rhea:RHEA:23540, Rhea:RHEA-COMP:9663,
CC         Rhea:RHEA-COMP:9680, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78520,
CC         ChEBI:CHEBI:456215; EC=6.1.1.17;
CC         Evidence={ECO:0000250|UniProtKB:P07814};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23541;
CC         Evidence={ECO:0000250|UniProtKB:P07814};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-
CC         tRNA(Pro); Xref=Rhea:RHEA:14305, Rhea:RHEA-COMP:9700, Rhea:RHEA-
CC         COMP:9702, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC         ChEBI:CHEBI:78442, ChEBI:CHEBI:78532, ChEBI:CHEBI:456215;
CC         EC=6.1.1.15; Evidence={ECO:0000250|UniProtKB:P07814};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14306;
CC         Evidence={ECO:0000250|UniProtKB:P07814};
CC   -!- SUBUNIT: Homodimer. Part of the aminoacyl-tRNA synthetase multienzyme
CC       complex, also know as multisynthetase complex, that is composed of the
CC       tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1),
CC       Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu
CC       and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and
CC       EEF1E1/p18. Forms a linear complex that contains MARS1, EEF1E1, EPRS1
CC       and AIMP2 that is at the core of the multisubunit complex
CC       (PubMed:12060739). Interacts with TARS3 (By similarity). Interacts with
CC       DUS2L (By similarity). Component of the GAIT complex which is composed
CC       of EPRS1, RPL13A and GAPDH (PubMed:23071094). Interacts (phosphorylated
CC       at Ser-999) with SLC27A1; mediates the translocation of SLC27A1 from
CC       the cytoplasm to the plasma membrane thereby increasing the uptake of
CC       long-chain fatty acids (PubMed:28178239).
CC       {ECO:0000250|UniProtKB:P07814, ECO:0000269|PubMed:12060739,
CC       ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:28178239}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P07814}. Membrane {ECO:0000269|PubMed:28178239};
CC       Peripheral membrane protein {ECO:0000305|PubMed:28178239}.
CC       Note=Translocates from cytosol to membranes upon phosphorylation at
CC       Ser-999. {ECO:0000305|PubMed:28178239}.
CC   -!- DOMAIN: The WHEP-TRS domains are involved in RNA binding.
CC       {ECO:0000250|UniProtKB:Q7SIA2}.
CC   -!- PTM: Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS1 release from
CC       the aminoacyl-tRNA synthetase multienzyme complex. In monocytes, the
CC       IFN-gamma-induced phosphorylation at Ser-999 releases EPRS1 from the
CC       aminoacyl-tRNA synthetase multienzyme complex, allowing its association
CC       with the GAIT complex. Phosphorylation at Ser-999 is specifically
CC       required for the RPL13A-mediated interaction of the GAIT complex with
CC       eIF4G (By similarity). Phosphorylation at Ser-999 by RPS6KB1, is also
CC       induced by insulin through activation of the mTORC1 signaling pathway
CC       and promotes the interaction of EPRS1 with SLC27A1 (PubMed:28178239).
CC       {ECO:0000250|UniProtKB:P07814, ECO:0000269|PubMed:28178239}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the class-I
CC       aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 2
CC       subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the class-II
CC       aminoacyl-tRNA synthetase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH40802.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR   EMBL; AC129195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC131980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC040802; AAH40802.1; ALT_SEQ; mRNA.
DR   EMBL; BC094679; AAH94679.1; -; mRNA.
DR   EMBL; AK148463; BAE28568.1; -; mRNA.
DR   EMBL; X54327; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS35818.1; -.
DR   RefSeq; NP_084011.1; NM_029735.1.
DR   AlphaFoldDB; Q8CGC7; -.
DR   SMR; Q8CGC7; -.
DR   BioGRID; 223350; 60.
DR   IntAct; Q8CGC7; 7.
DR   MINT; Q8CGC7; -.
DR   STRING; 10090.ENSMUSP00000045841; -.
DR   GlyGen; Q8CGC7; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8CGC7; -.
DR   PhosphoSitePlus; Q8CGC7; -.
DR   SwissPalm; Q8CGC7; -.
DR   EPD; Q8CGC7; -.
DR   jPOST; Q8CGC7; -.
DR   MaxQB; Q8CGC7; -.
DR   PaxDb; 10090-ENSMUSP00000045841; -.
DR   PeptideAtlas; Q8CGC7; -.
DR   ProteomicsDB; 254505; -.
DR   Pumba; Q8CGC7; -.
DR   Antibodypedia; 20734; 240 antibodies from 30 providers.
DR   DNASU; 107508; -.
DR   Ensembl; ENSMUST00000046514.13; ENSMUSP00000045841.8; ENSMUSG00000026615.15.
DR   GeneID; 107508; -.
DR   KEGG; mmu:107508; -.
DR   UCSC; uc007dze.1; mouse.
DR   AGR; MGI:97838; -.
DR   CTD; 2058; -.
DR   MGI; MGI:97838; Eprs1.
DR   VEuPathDB; HostDB:ENSMUSG00000026615; -.
DR   eggNOG; KOG1147; Eukaryota.
DR   eggNOG; KOG4163; Eukaryota.
DR   GeneTree; ENSGT00550000074815; -.
DR   HOGENOM; CLU_001882_0_2_1; -.
DR   InParanoid; Q8CGC7; -.
DR   OMA; WDPKGNN; -.
DR   OrthoDB; 2733051at2759; -.
DR   PhylomeDB; Q8CGC7; -.
DR   TreeFam; TF300380; -.
DR   BRENDA; 6.1.1.15; 3474.
DR   BRENDA; 6.1.1.17; 3474.
DR   BioGRID-ORCS; 107508; 27 hits in 82 CRISPR screens.
DR   ChiTaRS; Eprs; mouse.
DR   PRO; PR:Q8CGC7; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q8CGC7; Protein.
DR   Bgee; ENSMUSG00000026615; Expressed in otic placode and 261 other cell types or tissues.
DR   ExpressionAtlas; Q8CGC7; baseline and differential.
DR   GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0097452; C:GAIT complex; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004818; F:glutamate-tRNA ligase activity; ISS:UniProtKB.
DR   GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0004827; F:proline-tRNA ligase activity; IMP:CAFA.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IMP:UniProtKB.
DR   GO; GO:0071346; P:cellular response to type II interferon; IDA:UniProtKB.
DR   GO; GO:0006424; P:glutamyl-tRNA aminoacylation; ISS:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR   GO; GO:0006433; P:prolyl-tRNA aminoacylation; IDA:CAFA.
DR   GO; GO:0140212; P:regulation of long-chain fatty acid import into cell; IMP:UniProtKB.
DR   CDD; cd00807; GlnRS_core; 1.
DR   CDD; cd10309; GST_C_GluProRS_N; 1.
DR   CDD; cd00862; ProRS_anticodon_zinc; 1.
DR   CDD; cd00778; ProRS_core_arch_euk; 1.
DR   CDD; cd00936; WEPRS_RNA; 3.
DR   Gene3D; 1.20.1050.130; -; 1.
DR   Gene3D; 3.40.50.800; Anticodon-binding domain; 1.
DR   Gene3D; 3.30.110.30; C-terminal domain of ProRS; 1.
DR   Gene3D; 3.40.50.620; HUPs; 1.
DR   Gene3D; 1.10.287.10; S15/NS1, RNA-binding; 3.
DR   HAMAP; MF_02076; Glu_tRNA_synth_type2; 1.
DR   HAMAP; MF_01571; Pro_tRNA_synth_type3; 1.
DR   InterPro; IPR002314; aa-tRNA-synt_IIb.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR006195; aa-tRNA-synth_II.
DR   InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR   InterPro; IPR004154; Anticodon-bd.
DR   InterPro; IPR036621; Anticodon-bd_dom_sf.
DR   InterPro; IPR004526; Glu-tRNA-synth_arc/euk.
DR   InterPro; IPR000924; Glu/Gln-tRNA-synth.
DR   InterPro; IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom.
DR   InterPro; IPR020059; Glu/Gln-tRNA-synth_Ib_codon-bd.
DR   InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
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; IPR033721; ProRS_core_arch_euk.
DR   InterPro; IPR020056; Rbsml_bL25/Gln-tRNA_synth_N.
DR   InterPro; IPR011035; Ribosomal_bL25/Gln-tRNA_synth.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   InterPro; IPR049437; tRNA-synt_1c_C2.
DR   InterPro; IPR009068; uS15_NS1_RNA-bd_sf.
DR   InterPro; IPR000738; WHEP-TRS_dom.
DR   NCBIfam; TIGR00463; gltX_arch; 1.
DR   NCBIfam; TIGR00408; proS_fam_I; 1.
DR   PANTHER; PTHR43382:SF2; BIFUNCTIONAL GLUTAMATE_PROLINE--TRNA LIGASE; 1.
DR   PANTHER; PTHR43382; PROLYL-TRNA SYNTHETASE; 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; PF20974; tRNA-synt_1c_C2; 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; SSF64586; C-terminal domain of ProRS; 1.
DR   SUPFAM; SSF52954; Class II aaRS ABD-related; 1.
DR   SUPFAM; SSF55681; Class II aaRS and biotin synthetases; 1.
DR   SUPFAM; SSF47616; GST C-terminal domain-like; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF50715; Ribosomal protein L25-like; 1.
DR   SUPFAM; SSF47060; S15/NS1 RNA-binding domain; 3.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
DR   PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR   PROSITE; PS00762; WHEP_TRS_1; 2.
DR   PROSITE; PS51185; WHEP_TRS_2; 3.
DR   Genevisible; Q8CGC7; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW   Magnesium; Membrane; Metal-binding; Methylation; Multifunctional enzyme;
KW   Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW   Reference proteome; Repeat; RNA-binding; Translation regulation; Zinc.
FT   CHAIN           1..1512
FT                   /note="Bifunctional glutamate/proline--tRNA ligase"
FT                   /id="PRO_0000119744"
FT   DOMAIN          749..805
FT                   /note="WHEP-TRS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00531"
FT   DOMAIN          822..878
FT                   /note="WHEP-TRS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00531"
FT   DOMAIN          900..956
FT                   /note="WHEP-TRS 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00531"
FT   REGION          164..759
FT                   /note="Glutamate--tRNA ligase"
FT                   /evidence="ECO:0000250|UniProtKB:P28668"
FT   REGION          294..315
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          709..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          760..956
FT                   /note="3 X 57 AA approximate repeats"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   REGION          795..819
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          869..898
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          956..1011
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1007..1512
FT                   /note="Proline--tRNA ligase"
FT                   /evidence="ECO:0000250|UniProtKB:P28668"
FT   MOTIF           204..214
FT                   /note="'HIGH' region"
FT                   /evidence="ECO:0000250|UniProtKB:P28668"
FT   MOTIF           432..436
FT                   /note="'KMSKS' region"
FT                   /evidence="ECO:0000250|UniProtKB:P28668"
FT   COMPBIAS        710..732
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        804..819
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        875..892
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        956..981
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        982..1000
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         1121..1123
FT                   /ligand="L-proline"
FT                   /ligand_id="ChEBI:CHEBI:60039"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1152
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1152
FT                   /ligand="L-proline"
FT                   /ligand_id="ChEBI:CHEBI:60039"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1154
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1163
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1164
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1237
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1237
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1240
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1242
FT                   /ligand="L-proline"
FT                   /ligand_id="ChEBI:CHEBI:60039"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1276
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1278
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1448
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1453
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1495
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   BINDING         1497
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         300
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         300
FT                   /note="N6-malonyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         355
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         417
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         434
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         498
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         535
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         542
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         637
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         788
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         861
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         872
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         885
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         998
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         999
FT                   /note="Phosphoserine; by RPS6KB1"
FT                   /evidence="ECO:0000269|PubMed:23071094"
FT   MOD_RES         1152
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         1350
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MOD_RES         1503
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P07814"
FT   MUTAGEN         999
FT                   /note="S->A: Loss of function in translation inhibition.
FT                   Loss of interaction with SLC27A1. Mutant mice have no
FT                   apparent developmental defect but display reduced adiposity
FT                   associated with decreased insulin levels and adipocytes
FT                   size. They also display increased lipolysis and fatty acid
FT                   beta-oxidation and an extended lifespan. Adipocytes display
FT                   decreased insulin-stimulated long-chain fatty acid uptake."
FT                   /evidence="ECO:0000269|PubMed:23071094,
FT                   ECO:0000269|PubMed:28178239"
FT   MUTAGEN         999
FT                   /note="S->D: Constitutively active in translation
FT                   inhibition (phosphomimetic). Mutant mice have no apparent
FT                   developmental defect and do not display overt phenotype
FT                   related to adiposity or lifespan."
FT                   /evidence="ECO:0000269|PubMed:23071094,
FT                   ECO:0000269|PubMed:28178239"
FT   CONFLICT        94
FT                   /note="R -> G (in Ref. 2; AAH40802)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        172
FT                   /note="N -> S (in Ref. 2; AAH40802)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        618
FT                   /note="S -> P (in Ref. 2; AAH40802)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        986
FT                   /note="G -> R (in Ref. 4; X54327)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1290
FT                   /note="N -> S (in Ref. 2; AAH94679)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1512 AA;  170079 MW;  D14F6EA015B1BB6A CRC64;
     MAALCLTVNA GNPPLEALLA VEHVKGDVSI SVEEGKENLL RVSETVAFTD VNSILRYLAR
     IATTSGLYGT NLMEHTEIDH WLEFSATKLS SCDRLTSAIN ELNHCLSLRT YLVGNSLTLA
     DLCVWATLKG SAAWQEHLKQ NKTLVHVKRW FGFLEAQQAF RSVGTKWDVS GNRATVAPDK
     KQDVGKFVEL PGAEMGKVTV RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN
     PEKEKEDFEK VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK
     AEREQRTESK HRKNSVEKNL QMWEEMKKGS QFGQSCCLRA KIDMSSNNGC MRDPTLYRCK
     IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH DRDEQFYWII EALGIRKPYI
     WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS
     SRSVVNMEWD KIWAFNKKVI DPVAPRYVAL LKKEVVPVNV LDAQEEMKEV ARHPKNPDVG
     LKPVWYSPKV FIEGADAETF SEGEMVTFIN WGNINITKIH KNADGKITSL DAKLNLENKD
     YKKTTKITWL AESTHALSIP AVCVTYEHLI TKPVLGKDED FKQYINKDSK HEELMLGDPC
     LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCREAPCILI YIPDGHTKEM PTSGSKEKTK
     VEISKKETSS APKERPAPAV SSTCATAEDS SVLYSRVAVQ GDVVRELKAK KAPKEDIDAA
     VKQLLTLKAE YKEKTGQEYK PGNPSAAAVQ TVSTKSSSNT VESTSLYNKV AAQGEVVRKL
     KAEKAPKAKV TEAVECLLSL KAEYKEKTGK DYVPGQPPAS QNSHSNPVSN AQPAGAEKPE
     AKVLFDRVAC QGEVVRKLKA EKASKDQVDS AVQELLQLKA QYKSLTGIEY KPVSATGAED
     KDKKKKEKEN KSEKQNKPQK QNDGQGKDSS KSQGSGLSSG GAGEGQGPKK QTRLGLEAKK
     EENLAEWYSQ VITKSEMIEY YDVSGCYILR PWSYSIWESI KDFFDAEIKK LGVENCYFPI
     FVSQAALEKE KNHIEDFAPE VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL
     PVRLNQWCNV VRWEFKHPQP FLRTREFLWQ EGHSAFATFE EAADEVLQIL ELYARVYEEL
     LAIPVVRGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGAT SHHLGQNFSK MCEIVFEDPK
     TPGEKQFAYQ CSWGLTTRTI GVMVMVHGDN MGLVLPPRVA SVQVVVIPCG ITNALSEEDR
     EALMAKCNEY RRRLLGANIR VRVDLRDNYS PGWKFNHWEL KGVPVRLEVG PRDMKSCQFV
     AVRRDTGEKL TIAEKEAEAK LEKVLEDIQL NLFTRASEDL KTHMVVSNTL EDFQKVLDAG
     KVAQIPFCGE IDCEDWIKKM TARDQDVEPG APSMGAKSLC IPFNPLCELQ PGAMCVCGKN
     PAKFYTLFGR SY
//