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Protein

Bifunctional glutamate/proline--tRNA ligase

Gene

EPRS

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
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. 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. 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.By similarity

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 sitei1151L-prolineBy similarity1
Binding sitei1241L-prolineBy similarity1
Binding sitei1275ATPBy similarity1
Metal bindingi1447ZincBy similarity1
Metal bindingi1452ZincBy similarity1
Metal bindingi1494ZincBy similarity1
Metal bindingi1496ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi432 – 436ATPBy similarity5
Nucleotide bindingi1151 – 1153ATPBy similarity3
Nucleotide bindingi1162 – 1163ATPBy similarity2
Nucleotide bindingi1236 – 1239ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

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
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaCricetidaeCricetinaeCricetulus

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197421 – 1511Bifunctional glutamate/proline--tRNA ligaseAdd BLAST1511

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei300N6-acetyllysine; alternateBy similarity1
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 residuei746PhosphoserineBy similarity1
Modified residuei787N6-acetyllysineBy similarity1
Modified residuei860N6-acetyllysineBy similarity1
Modified residuei871PhosphotyrosineBy similarity1
Modified residuei885Phosphoserine; by CDK5By similarity1
Modified residuei897PhosphothreonineBy similarity1
Modified residuei997PhosphoserineBy similarity1
Modified residuei998Phosphoserine; by RPS6KB1By similarity1
Modified residuei999PhosphoserineBy similarity1
Modified residuei1151Omega-N-methylarginineBy similarity1
Modified residuei1349PhosphoserineBy similarity1
Modified residuei1502N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-998 by RPS6KB1; triggers EPRS release from the aminoacyl-tRNA synthetase multienzyme complex. In monocytes, the IFN-gamma-induced phosphorylation at Ser-998 releases EPRS from the aminoacyl-tRNA synthetase multienzyme complex, allowing its association with the GAIT complex. Phosphorylation at Ser-998 is specifically required for the RPL13A-mediated interaction of the GAIT complex with eIF4G. Phosphorylation at Ser-998 by RPS6KB1, is also induced by insulin through activation of the mTORC1 signaling pathway and promotes the interaction of EPRS with SLC27A1.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PRIDEiQ7SIA2

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. Interacts with DUS2L. Component of the GAIT complex which is composed of EPRS, RPL13A and GAPDH. Interacts (phosphorylated at Ser-998) with SLC27A1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids.By similarity

Structurei

Secondary structure

11511
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi827 – 841Combined sources15
Helixi846 – 863Combined sources18
Beta strandi865 – 870Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D2DNMR-A826-874[»]
1R1BNMR-A826-874[»]
ProteinModelPortaliQ7SIA2
SMRiQ7SIA2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7SIA2

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini748 – 804WHEP-TRS 1PROSITE-ProRule annotationAdd BLAST57
Domaini821 – 877WHEP-TRS 2PROSITE-ProRule annotationAdd BLAST57
Domaini899 – 955WHEP-TRS 3PROSITE-ProRule annotationAdd BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni164 – 758Glutamate--tRNA ligaseBy similarityAdd BLAST595
Regioni759 – 9553 X 57 AA approximate repeatsBy similarityAdd BLAST197
Regioni958 – 990ChargedBy similarityAdd BLAST33
Regioni1006 – 1511Proline--tRNA ligaseBy similarityAdd BLAST506
Regioni1120 – 1122L-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 biasi960 – 990Lys-richPROSITE-ProRule annotationAdd BLAST31

Domaini

The WHEP-TRS domains are involved in RNA binding.1 Publication

Sequence similaritiesi

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

Family and domain databases

InterProiView protein in InterPro
IPR009068 S15_NS1_RNA-bd
IPR000738 WHEP-TRS_dom
PfamiView protein in Pfam
PF00458 WHEP-TRS, 1 hit
SMARTiView protein in SMART
SM00991 WHEP-TRS, 1 hit
SUPFAMiSSF47060 SSF47060, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
PS50862 AA_TRNA_LIGASE_II, 1 hit
PS00762 WHEP_TRS_1, 3 hits
PS51185 WHEP_TRS_2, 3 hits

Sequencei

Sequence statusi: Complete.

Q7SIA2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAALCLTVNA GDPPLDALLA VEHVKGDVSV SVEEGKENLL RVSEDVVFTD
60 70 80 90 100
INSILRYLAR VATTSGLYGT NLMEHTEIDH WLEFSATKLS SCAALTSALT
110 120 130 140 150
ELNHCLSLRT YLVGNSLTLA DLCVWATLKG NAAWQEQLEQ NKTLVHVKRW
160 170 180 190 200
FGFLEAQQAF RSVGTKWDVS ENKARVVPDK 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
AEREQRAESK HRQNSVEKNL QMWEEMKKGS PFGQSCCLRA 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 PEAQEEMKEV ARHPKNPDVG LKPVWYSPKV
560 570 580 590 600
FIEGADAETF SEGEMVTFIN WGNINITKIH KNADGKITSL DAKLNLENKD
610 620 630 640 650
YKKTTKITWL AETTHALPIP AICVTYEHLI TKPVLGKDED FKQYVNKDSK
660 670 680 690 700
HEELMLGDPC LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCKEAPCILI
710 720 730 740 750
YIPDGHTKEM PTSGSKEKTK AEPLKKETSS APKEGPVPAV SPCAASEESS
760 770 780 790 800
VLYNRVAAQG DVVRELKAKK AAKEDVDAAV KQLLALKAEY KQKTGQEYKP
810 820 830 840 850
GNPPSAAAQS ASTKSLPSAG EDRSLYDKIA AQGEVVRKLK AEKAPKAKVT
860 870 880 890 900
EAVECLLSLK AEYKEKTGKE YVPGQPPASQ KSQPSPASKA EPAGPETTEA
910 920 930 940 950
KALFDRVACQ GEVVRKLKAE KASKDQVDPA VQELLQLKAQ YKSLTGIEYK
960 970 980 990 1000
PVSATGSEDK DKKKKEKENK SEKQNKPQKQ NDGPGKDSSK SQGGGLSSSG
1010 1020 1030 1040 1050
AGEGQGPKKQ TRLGLEAKKE ENLAEWYSQV ITKSEMIEYY DVSGCYILRP
1060 1070 1080 1090 1100
WSYSIWESIK DFFDTEIKKL GVENCYFPIF VSQAALEKEK SHIEDFAPEV
1110 1120 1130 1140 1150
AWVTRSGKTE LAEPIAIRPT SETVMYPAYA KWVQSHRDLP IRLNQWCNVV
1160 1170 1180 1190 1200
RWEFKHPQPF LRTREFLWQE GHSAFATFEE AADEVMQILE LYARVYEELL
1210 1220 1230 1240 1250
AIPVVRGRKT EKEKFAGGDY TTTVEAFISA SGRAIQGATS HHLGQNFSKM
1260 1270 1280 1290 1300
CEIVFEDPKT PGEKQFAFQC SWGLTTRTIG VMIMVHGDNM GLVLPPRVAC
1310 1320 1330 1340 1350
VQVVVIPCGI TNALSEEDRE ALMAKCNEYR KRLLGVNIRV RVDLRDNYSP
1360 1370 1380 1390 1400
GWKFNHWELK GVPVRLEVGP RDMKSCQFVA VRRDTGEKLT IAEKEAESKL
1410 1420 1430 1440 1450
QEILEDIQLN LFTRASEDLK THMVVSNTLE DFQKVLDSGK IAQIPFCGEI
1460 1470 1480 1490 1500
DCEDWIKKTT ARDQDVEPGA PSMGAKSLCI PFTPLCELQP GAMCVCGKNP
1510
AKFYTLFGRS Y
Length:1,511
Mass (Da):169,781
Last modified:May 23, 2018 - v3
Checksum:i58CC131EAD375785
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AMDS01047676 Genomic DNA No translation available.
AMDS01047677 Genomic DNA No translation available.
AMDS01047678 Genomic DNA No translation available.
AMDS01047679 Genomic DNA No translation available.
AMDS01047680 Genomic DNA No translation available.

Similar proteinsi

Entry informationi

Entry nameiSYEP_CRIGR
AccessioniPrimary (citable) accession number: Q7SIA2
Secondary accession number(s): Q7SIG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 23, 2018
Last modified: May 23, 2018
This is version 66 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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