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Protein

Bifunctional glutamate/proline--tRNA ligase

Gene

Eprs

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (By similarity). The phosphorylation of EPRS, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS function from protein synthesis to translation inhibition (PubMed:23071094). Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239).By similarity2 Publications

Catalytic activityi

ATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-glutamyl-tRNA(Glu).
ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-tRNA(Pro).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei211ATPBy similarity1
Binding sitei398ATPBy similarity1
Binding sitei1152L-prolineBy similarity1
Binding sitei1242L-prolineBy similarity1
Binding sitei1276ATPBy similarity1
Metal bindingi1448ZincBy similarity1
Metal bindingi1453ZincBy similarity1
Metal bindingi1495ZincBy similarity1
Metal bindingi1497ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi432 – 436ATPBy similarity5
Nucleotide bindingi1152 – 1154ATPBy similarity3
Nucleotide bindingi1163 – 1164ATPBy similarity2
Nucleotide bindingi1237 – 1240ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

  • cellular response to insulin stimulus Source: UniProtKB
  • cellular response to interferon-gamma Source: UniProtKB
  • glutamyl-tRNA aminoacylation Source: GO_Central
  • long-chain fatty acid import Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • prolyl-tRNA aminoacylation Source: CAFA

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, Ligase, Multifunctional enzyme, RNA-binding
Biological processProtein biosynthesis, Translation regulation
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional glutamate/proline--tRNA ligase
Alternative name(s):
Bifunctional aminoacyl-tRNA synthetase
Including the following 2 domains:
Glutamate--tRNA ligase (EC:6.1.1.17)
Alternative name(s):
Glutamyl-tRNA synthetase
Short name:
GluRS
Proline--tRNA ligase (EC:6.1.1.15By similarity)
Alternative name(s):
Prolyl-tRNA synthetase
Short name:
ProRS
Gene namesi
Name:Eprs
Synonyms:Qprs
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:97838 Eprs

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi999S → A: Loss of function in translation inhibition. Loss of interaction with SLC27A1. Mutant mice have no apparent developmental defect but display reduced adiposity associated with decreased insulin levels and adipocytes size. They also display increased lipolysis and fatty acid beta-oxidation and an extended lifespan. Adipocytes display decreased insulin-stimulated long-chain fatty acid uptake. 2 Publications1
Mutagenesisi999S → D: Constitutively active in translation inhibition (phosphomimetic). Mutant mice have no apparent developmental defect and do not display overt phenotype related to adiposity or lifespan. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197441 – 1512Bifunctional glutamate/proline--tRNA ligaseAdd BLAST1512

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei300N6-acetyllysine; alternateCombined sources1
Modified residuei300N6-malonyllysine; alternateBy similarity1
Modified residuei355PhosphothreonineBy similarity1
Modified residuei417N6-acetyllysineBy similarity1
Modified residuei434PhosphoserineBy similarity1
Modified residuei498N6-acetyllysineBy similarity1
Modified residuei535N6-acetyllysineBy similarity1
Modified residuei542N6-acetyllysineBy similarity1
Modified residuei637N6-acetyllysineBy similarity1
Modified residuei788N6-acetyllysineCombined sources1
Modified residuei861N6-acetyllysineCombined sources1
Modified residuei872PhosphotyrosineBy similarity1
Modified residuei885PhosphoserineBy similarity1
Modified residuei998PhosphoserineBy similarity1
Modified residuei999Phosphoserine; by RPS6KB11 Publication1
Modified residuei1152Omega-N-methylarginineBy similarity1
Modified residuei1350PhosphoserineBy similarity1
Modified residuei1503N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS release from the aminoacyl-tRNA synthetase multienzyme complex. In monocytes, the IFN-gamma-induced phosphorylation at Ser-999 releases EPRS from the aminoacyl-tRNA synthetase multienzyme complex, allowing its association with the GAIT complex. Phosphorylation at Ser-999 is specifically required for the RPL13A-mediated interaction of the GAIT complex with eIF4G (By similarity). Phosphorylation at Ser-999 by RPS6KB1, is also induced by insulin through activation of the mTORC1 signaling pathway and promotes the interaction of EPRS with SLC27A1 (PubMed:28178239).By similarity1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ8CGC7
MaxQBiQ8CGC7
PaxDbiQ8CGC7
PeptideAtlasiQ8CGC7
PRIDEiQ8CGC7

PTM databases

iPTMnetiQ8CGC7
PhosphoSitePlusiQ8CGC7
SwissPalmiQ8CGC7

Expressioni

Gene expression databases

BgeeiENSMUSG00000026615
CleanExiMM_EPRS
ExpressionAtlasiQ8CGC7 baseline and differential
GenevisibleiQ8CGC7 MM

Interactioni

Subunit structurei

Homodimer. Part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that is composed of the tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18. Forms a linear complex that contains MARS, EEF1E1, EPRS and AIMP2 that is at the core of the multisubunit complex (PubMed:12060739). Interacts with DUS2L (By similarity). Component of the GAIT complex which is composed of EPRS, RPL13A and GAPDH (PubMed:23071094). Interacts (phosphorylated at Ser-999) with SLC27A1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids (PubMed:28178239).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi223350, 4 interactors
IntActiQ8CGC7, 7 interactors
MINTiQ8CGC7
STRINGi10090.ENSMUSP00000045841

Structurei

3D structure databases

ProteinModelPortaliQ8CGC7
SMRiQ8CGC7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini749 – 805WHEP-TRS 1Add BLAST57
Domaini822 – 878WHEP-TRS 2Add BLAST57
Domaini900 – 956WHEP-TRS 3Add BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni164 – 759Glutamate--tRNA ligaseAdd BLAST596
Regioni760 – 9563 X 57 AA approximate repeatsAdd BLAST197
Regioni1007 – 1512Proline--tRNA ligaseAdd BLAST506
Regioni1121 – 1123L-proline bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi204 – 214"HIGH" regionAdd BLAST11
Motifi432 – 436"KMSKS" region5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi961 – 991Lys-richPROSITE-ProRule annotationAdd BLAST31

Domaini

The WHEP-TRS domains are involved in RNA binding.By similarity

Sequence similaritiesi

In the C-terminal section; belongs to the class-II aminoacyl-tRNA synthetase family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1147 Eukaryota
KOG4163 Eukaryota
COG0008 LUCA
COG0442 LUCA
GeneTreeiENSGT00550000074815
HOGENOMiHOG000022047
HOVERGENiHBG017875
InParanoidiQ8CGC7
KOiK14163
OMAiVAMLHIK
OrthoDBiEOG091G04TK
TreeFamiTF300380

Family and domain databases

CDDicd00778 ProRS_core_arch_euk, 1 hit
Gene3Di2.40.240.10, 3 hits
3.30.110.30, 1 hit
3.40.50.620, 1 hit
3.40.50.800, 1 hit
HAMAPiMF_02076 Glu_tRNA_synth_type2, 1 hit
MF_01571 Pro_tRNA_synth_type3, 1 hit
InterProiView protein in InterPro
IPR002314 aa-tRNA-synt_IIb
IPR001412 aa-tRNA-synth_I_CS
IPR006195 aa-tRNA-synth_II
IPR004154 Anticodon-bd
IPR036621 Anticodon-bd_dom_sf
IPR004526 Glu-tRNA-synth_arc/euk
IPR000924 Glu/Gln-tRNA-synth
IPR020058 Glu/Gln-tRNA-synth_Ib_cat-dom
IPR020059 Glu/Gln-tRNA-synth_Ib_codon-bd
IPR036282 Glutathione-S-Trfase_C_sf
IPR004046 GST_C
IPR004499 Pro-tRNA-ligase_IIa_arc-type
IPR016061 Pro-tRNA_ligase_II_C
IPR017449 Pro-tRNA_synth_II
IPR033721 ProRS_core_arch_euk
IPR020056 Rbsml_L25/Gln-tRNA_synth_N
IPR011035 Ribosomal_L25/Gln-tRNA_synth
IPR014729 Rossmann-like_a/b/a_fold
IPR009068 S15_NS1_RNA-bd
IPR000738 WHEP-TRS_dom
PfamiView protein in Pfam
PF00043 GST_C, 1 hit
PF03129 HGTP_anticodon, 1 hit
PF09180 ProRS-C_1, 1 hit
PF00749 tRNA-synt_1c, 1 hit
PF03950 tRNA-synt_1c_C, 1 hit
PF00587 tRNA-synt_2b, 1 hit
PF00458 WHEP-TRS, 3 hits
PRINTSiPR00987 TRNASYNTHGLU
SMARTiView protein in SMART
SM00946 ProRS-C_1, 1 hit
SM00991 WHEP-TRS, 3 hits
SUPFAMiSSF47060 SSF47060, 3 hits
SSF47616 SSF47616, 1 hit
SSF50715 SSF50715, 1 hit
SSF64586 SSF64586, 1 hit
TIGRFAMsiTIGR00463 gltX_arch, 1 hit
TIGR00408 proS_fam_I, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS50862 AA_TRNA_LIGASE_II, 1 hit
PS00762 WHEP_TRS_1, 2 hits
PS51185 WHEP_TRS_2, 3 hits

Sequencei

Sequence statusi: Complete.

Q8CGC7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAALCLTVNA GNPPLEALLA VEHVKGDVSI SVEEGKENLL RVSETVAFTD
60 70 80 90 100
VNSILRYLAR IATTSGLYGT NLMEHTEIDH WLEFSATKLS SCDRLTSAIN
110 120 130 140 150
ELNHCLSLRT YLVGNSLTLA DLCVWATLKG SAAWQEHLKQ NKTLVHVKRW
160 170 180 190 200
FGFLEAQQAF RSVGTKWDVS GNRATVAPDK KQDVGKFVEL PGAEMGKVTV
210 220 230 240 250
RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN PEKEKEDFEK
260 270 280 290 300
VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK
310 320 330 340 350
AEREQRTESK HRKNSVEKNL QMWEEMKKGS QFGQSCCLRA KIDMSSNNGC
360 370 380 390 400
MRDPTLYRCK IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH
410 420 430 440 450
DRDEQFYWII EALGIRKPYI WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW
460 470 480 490 500
DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS SRSVVNMEWD KIWAFNKKVI
510 520 530 540 550
DPVAPRYVAL LKKEVVPVNV LDAQEEMKEV ARHPKNPDVG LKPVWYSPKV
560 570 580 590 600
FIEGADAETF SEGEMVTFIN WGNINITKIH KNADGKITSL DAKLNLENKD
610 620 630 640 650
YKKTTKITWL AESTHALSIP AVCVTYEHLI TKPVLGKDED FKQYINKDSK
660 670 680 690 700
HEELMLGDPC LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCREAPCILI
710 720 730 740 750
YIPDGHTKEM PTSGSKEKTK VEISKKETSS APKERPAPAV SSTCATAEDS
760 770 780 790 800
SVLYSRVAVQ GDVVRELKAK KAPKEDIDAA VKQLLTLKAE YKEKTGQEYK
810 820 830 840 850
PGNPSAAAVQ TVSTKSSSNT VESTSLYNKV AAQGEVVRKL KAEKAPKAKV
860 870 880 890 900
TEAVECLLSL KAEYKEKTGK DYVPGQPPAS QNSHSNPVSN AQPAGAEKPE
910 920 930 940 950
AKVLFDRVAC QGEVVRKLKA EKASKDQVDS AVQELLQLKA QYKSLTGIEY
960 970 980 990 1000
KPVSATGAED KDKKKKEKEN KSEKQNKPQK QNDGQGKDSS KSQGSGLSSG
1010 1020 1030 1040 1050
GAGEGQGPKK QTRLGLEAKK EENLAEWYSQ VITKSEMIEY YDVSGCYILR
1060 1070 1080 1090 1100
PWSYSIWESI KDFFDAEIKK LGVENCYFPI FVSQAALEKE KNHIEDFAPE
1110 1120 1130 1140 1150
VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL PVRLNQWCNV
1160 1170 1180 1190 1200
VRWEFKHPQP FLRTREFLWQ EGHSAFATFE EAADEVLQIL ELYARVYEEL
1210 1220 1230 1240 1250
LAIPVVRGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGAT SHHLGQNFSK
1260 1270 1280 1290 1300
MCEIVFEDPK TPGEKQFAYQ CSWGLTTRTI GVMVMVHGDN MGLVLPPRVA
1310 1320 1330 1340 1350
SVQVVVIPCG ITNALSEEDR EALMAKCNEY RRRLLGANIR VRVDLRDNYS
1360 1370 1380 1390 1400
PGWKFNHWEL KGVPVRLEVG PRDMKSCQFV AVRRDTGEKL TIAEKEAEAK
1410 1420 1430 1440 1450
LEKVLEDIQL NLFTRASEDL KTHMVVSNTL EDFQKVLDAG KVAQIPFCGE
1460 1470 1480 1490 1500
IDCEDWIKKM TARDQDVEPG APSMGAKSLC IPFNPLCELQ PGAMCVCGKN
1510
PAKFYTLFGR SY
Length:1,512
Mass (Da):170,079
Last modified:July 27, 2011 - v4
Checksum:iD14F6EA015B1BB6A
GO

Sequence cautioni

The sequence AAH40802 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti94R → G in AAH40802 (PubMed:15489334).Curated1
Sequence conflicti172N → S in AAH40802 (PubMed:15489334).Curated1
Sequence conflicti618S → P in AAH40802 (PubMed:15489334).Curated1
Sequence conflicti986G → R in X54327 (Ref. 4) Curated1
Sequence conflicti1290N → S in AAH94679 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129195 Genomic DNA No translation available.
AC131980 Genomic DNA No translation available.
BC040802 mRNA Translation: AAH40802.1 Sequence problems.
BC094679 mRNA Translation: AAH94679.1
AK148463 mRNA Translation: BAE28568.1
X54327 mRNA No translation available.
CCDSiCCDS35818.1
RefSeqiNP_084011.1, NM_029735.1
UniGeneiMm.154511
Mm.490980

Genome annotation databases

EnsembliENSMUST00000046514; ENSMUSP00000045841; ENSMUSG00000026615
GeneIDi107508
KEGGimmu:107508
UCSCiuc007dze.1 mouse

Similar proteinsi

Entry informationi

Entry nameiSYEP_MOUSE
AccessioniPrimary (citable) accession number: Q8CGC7
Secondary accession number(s): E9QKC4, Q3UFJ2, Q4VC16
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 136 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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