SYEP_MOUSE
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 03-AUG-2022, entry version 159.
DE RecName: Full=Bifunctional glutamate/proline--tRNA ligase;
DE AltName: Full=Bifunctional aminoacyl-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 {ECO:0000250|UniProtKB:P07814};
DE AltName: Full=Prolyl-tRNA synthetase;
DE Short=ProRS;
GN Name=Eprs1; Synonyms=Eprs, 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, Pancreas,
RC 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 is primarily part of the
CC aminoacyl-tRNA synthetase multienzyme complex, also know as
CC multisynthetase complex, that catalyzes the attachment of the cognate
CC amino acid to the corresponding tRNA in a two-step reaction: the amino
CC acid is first activated by ATP to form a covalent intermediate with AMP
CC and is then transferred to the acceptor end of the cognate tRNA (By
CC similarity). The phosphorylation of EPRS1, induced by interferon-gamma,
CC dissociates the protein from the aminoacyl-tRNA synthetase multienzyme
CC complex and recruits it to the GAIT complex that binds to stem loop-
CC containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs
CC (such as ceruplasmin), suppressing their translation. Interferon-gamma
CC can therefore redirect, in specific cells, the EPRS1 function from
CC protein synthesis to translation inhibition (PubMed:23071094). Also
CC functions as an effector of the mTORC1 signaling pathway by promoting,
CC through SLC27A1, the uptake of long-chain fatty acid by adipocytes.
CC Thereby, it also plays a role in fat metabolism and more indirectly
CC influences lifespan (PubMed:28178239). {ECO:0000250|UniProtKB:P07814,
CC ECO:0000269|PubMed:23071094, 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 -!- 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 -!- 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; 52.
DR IntAct; Q8CGC7; 7.
DR MINT; Q8CGC7; -.
DR STRING; 10090.ENSMUSP00000045841; -.
DR iPTMnet; Q8CGC7; -.
DR PhosphoSitePlus; Q8CGC7; -.
DR SwissPalm; Q8CGC7; -.
DR EPD; Q8CGC7; -.
DR jPOST; Q8CGC7; -.
DR MaxQB; Q8CGC7; -.
DR PaxDb; Q8CGC7; -.
DR PeptideAtlas; Q8CGC7; -.
DR PRIDE; Q8CGC7; -.
DR ProteomicsDB; 254505; -.
DR Antibodypedia; 20734; 204 antibodies from 30 providers.
DR DNASU; 107508; -.
DR Ensembl; ENSMUST00000046514; ENSMUSP00000045841; ENSMUSG00000026615.
DR GeneID; 107508; -.
DR KEGG; mmu:107508; -.
DR UCSC; uc007dze.1; mouse.
DR CTD; 107508; -.
DR MGI; MGI:97838; Eprs.
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; 809861at2759; -.
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 77 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 257 other tissues.
DR ExpressionAtlas; Q8CGC7; baseline and differential.
DR Genevisible; Q8CGC7; MM.
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; ISO:MGI.
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; IEA:UniProtKB-EC.
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 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; IDA:CAFA.
DR GO; GO:0140212; P:regulation of long-chain fatty acid import into cell; IMP:UniProtKB.
DR CDD; cd00778; ProRS_core_arch_euk; 1.
DR Gene3D; 2.40.240.10; -; 2.
DR Gene3D; 3.30.110.30; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
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; IPR004046; GST_C.
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_L25/Gln-tRNA_synth_N.
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_dom.
DR PANTHER; PTHR43382; PTHR43382; 1.
DR Pfam; PF00043; GST_C; 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; SSF47060; SSF47060; 3.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF50715; SSF50715; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF64586; SSF64586; 1.
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; 2.
DR PROSITE; PS51185; WHEP_TRS_2; 3.
PE 1: Evidence at protein level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW 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 DOMAIN 822..878
FT /note="WHEP-TRS 2"
FT DOMAIN 900..956
FT /note="WHEP-TRS 3"
FT REGION 164..759
FT /note="Glutamate--tRNA ligase"
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 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 MOTIF 204..214
FT /note="'HIGH' region"
FT MOTIF 432..436
FT /note="'KMSKS' region"
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 211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 432..436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1121..1123
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000250|UniProtKB:P07814"
FT BINDING 1152..1154
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 1163..1164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07814"
FT BINDING 1237..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 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
